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Treating female pattern hair loss – Harvard Health

Noticeable hair loss in women can be deeply distressing. Here are some medical treatments that may help.

About one-third of women experience hair loss (alopecia) at some time in their lives; among postmenopausal women, as many as two-thirds suffer hair thinning or bald spots. Hair loss in women often has a greater impact than hair loss does on men w, because it's less socially acceptable for them. Alopecia can severely affect a woman's emotional well-being and quality of life.

The main type of hair loss in women is the same as it is men. It's called androgenetic alopecia, or female (or male) pattern hair loss. In men, hair loss usually begins above the temples, and the receding hairline eventually forms a characteristic "M" shape; hair at the top of the head also thins, often progressing to baldness. In women, androgenetic alopecia begins with gradual thinning at the part line, followed by increasing diffuse hair loss radiating from the top of the head. A woman's hairline rarely recedes, and women rarely become bald.

There are many potential causes of hair loss in women , including medical conditions, medications, and physical or emotional stress. If you notice unusual hair loss of any kind, it's important to see your primary care provider or a dermatologist, to determine the cause and appropriate treatment. You may also want to ask your clinician for a referral to a therapist or support group to address emotional difficulties. Hair loss in women can be frustrating, but recent years have seen an increase in resources for coping with the problem.

Clinicians use the Ludwig Classification to describe female pattern hair loss. Type I is minimal thinning that can be camouflaged with hair styling techniques. Type II is characterized by decreased volume and noticeable widening of the mid-line part. Type III describes diffuse thinning, with a see-through appearance on the top of the scalp.

Almost every woman eventually develops some degree of female pattern hair loss. It can start any time after the onset of puberty, but women tend to first notice it around menopause, when hair loss typically increases. The risk rises with age, and it's higher for women with a history of hair loss on either side of the family.

As the name suggests, androgenetic alopecia involves the action of the hormones called androgens, which are essential for normal male sexual development and have other important functions in both sexes, including sex drive and regulation of hair growth. The condition may be inherited and involve several different genes. It can also result from an underlying endocrine condition, such as overproduction of androgen or an androgen-secreting tumor on the ovary, pituitary, or adrenal gland. In either case, the alopecia is likely related to increased androgen activity. But unlike androgenetic alopecia in men, in women the precise role of androgens is harder to determine. On the chance that an androgen-secreting tumor is involved, it's important to measure androgen levels in women with clear female pattern hair loss.

In either sex, hair loss from androgenetic alopecia occurs because of a genetically determined shortening of anagen, a hair's growing phase, and a lengthening of the time between the shedding of a hair and the start of a new anagen phase. (See "Life cycle of a hair.") That means it takes longer for hair to start growing back after it is shed in the course of the normal growth cycle. The hair follicle itself also changes, shrinking and producing a shorter, thinner hair shaft a process called "follicular miniaturization." As a result, thicker, pigmented, longer-lived "terminal" hairs are replaced by shorter, thinner, non-pigmented hairs called "vellus."

Each hair develops from a follicle a narrow pocket in the skin and goes through three phases of growth. Anagen (A), the active growth phase, lasts two to seven years. Catagen (B), the transition phase, lasts about two weeks. During this phase, the hair shaft moves upward toward the skin's surface, and the dermal papilla (the structure that nourishes cells that give rise to hair) begins to separate from the follicle. Telogen (C), the resting phase, lasts around three months and culminates in the shedding of the hair shaft.

A clinician diagnoses female pattern hair loss by taking a medical history and examining the scalp. She or he will observe the pattern of hair loss, check for signs of inflammation or infection, and possibly order blood tests to investigate other possible causes of hair loss, including hyperthyroidism, hypothyroidism, and iron deficiency. Unless there are signs of excess androgen activity (such as menstrual irregularities, acne, and unwanted hair growth), a hormonal evaluation is usually unnecessary.

Medications are the most common treatment for hair loss in women. They include the following:

Minoxidil (Rogaine, generic versions). This drug was initially introduced as a treatment for high blood pressure, but people who took it noticed that they were growing hair in places where they had lost it. Research studies confirmed that minoxidil applied directly to the scalp could stimulate hair growth. As a result of the studies, the FDA originally approved over-the-counter 2% minoxidil to treat hair loss in women. Since then a 5% solution has also become available when a stronger solution is need for a woman's hair loss.

Clearly, minoxidil is not a miracle drug. While it can produce some new growth of fine hair in some not all women, it can't restore the full density of the lost hair. It's not a quick fix, either for hair loss in women . You won't see results until you use the drug for at least two months. The effect often peaks at around four months, but it could take longer, so plan on a trial of six to 12 months. If minoxidil works for you, you'll need to keep using it to maintain those results. If you stop, you'll start to lose hair again.

How to use minoxidil: Be sure that your hair and scalp are dry. Using the dropper or spray pump that's provided with the over-the-counter solution, apply it twice daily to every area where your hair is thinning. Gently massage it into the scalp with your fingers so it can reach the hair follicles. Then air-dry your hair, wash your hands thoroughly, and wash off any solution that has dripped onto your forehead or face. Don't shampoo for at least four hours afterwards.

Some women find that the minoxidil solution leaves a deposit that dries and irritates their scalp. This irritation, called contact dermatitis, is probably caused not by the minoxidil itself, but rather by the alcohol that is included to facilitate drying.

Side effects and concerns: Minoxidil is safe, but it can have unpleasant side effects even apart from the alcohol-related skin irritation. Sometimes the new hair differs in color and texture from surrounding hair. Another risk is hypertrichosis excessive hair growth in the wrong places, such as the cheeks or forehead. (This problem is more likely with the stronger 5% solution.)

Because the patent on Rogaine (the brand-name version of minoxidil) has expired, many generic products are available. They all contain the same amount of minoxidil, but some include additional ingredients, such as herbal extracts, which might trigger allergic reactions.

Anti-androgens. Androgens include testosterone and other "male" hormones, which can accelerate hair loss in women. Some women who don't respond to minoxidil may benefit from the addition of the anti-androgen drug spironolactone (Aldactone) for treatment of androgenic alopecia. This is especially true for women with polycystic ovary syndrome (PCOS) because they tend to make excess androgens. Doctors will usually prescribe spironolactone together with an oral contraceptive for women of reproductive age. (A woman taking one of these drugs should not become pregnant because they can cause genital abnormalities in a male fetus.) Possible side effects include weight gain, loss of libido, depression, and fatigue.

Iron supplements. Iron deficiency could be a cause of hair loss in some women . Your doctor may test your blood iron level, particularly if you're a vegetarian, have a history of anemia, or have heavy menstrual bleeding. If you do have iron deficiency, you will need to take a supplement and it may stop your hair loss. However, if your iron level is normal, taking extra iron will only cause side effects, such as stomach upset and constipation.

Hair transplantation, a procedure used in the United States since the 1950s to treat androgenic alopecia, involves removing a strip of scalp from the back of the head and using it to fill in a bald patch. Today, 90% of hair-transplant surgeons use a technique called follicular unit transplantation, which was introduced in the mid-1990s.

During this procedure, surgeons remove a narrow strip of scalp and divide it into hundreds of tiny grafts, each containing just a few hairs. Each graft is planted in a slit in the scalp created by a blade or needle in the area of missing hair. Hair grows naturally this way, in small clusters of one to four follicles, called follicular units. As a result, the graft looks better than the larger "plugs" associated with hair transplants of yesteryear.


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Whole Bone Marrow –

Bone Marrow (BM) contains hematopoietic stem/progenitor cells, which have the potential to self-renew, proliferate, and differentiate into multi-lineage blood cells. Multipotent, non-hematopoietic stem cells, such as mesenchymal stem cells, can be isolated from human BM as well. These non-hematopoietic, mesenchymal stem cells are capable of both self-renewal and differentiation into bone, cartilage, muscle, tendons, and fat. BM is drawn into a 60cc syringe containing heparin (80 U/mL of BM) from the posterior iliac crest, 25 mL/site, from a maximum of four sites.CustomizationLet us know how we can customize your product today Custom InquiryDonor CriteriaAge18-65 years oldWeight>= 130 lbsScreened before donationHIV (HIV 1 & 2 Ab)HBV (Surface Antigen HbsAg)HCV (HCVAb)Donation FrequencyMinimum 10 weeks between donationsDonors with any of the following will be excluded from donatingPregnancyHistory of heart, lung, liver, or kidney diseaseHistory of asthmaBlood and bleeding disorders including sickle cell diseaseNeurologic disordersAutoimmune disordersCancerDiabetesOther CriteriaMust be in general good healthMust have accessible hipsComplete Blood Count lab test must meet protocol specsRequired to sign procedure-specific consent form

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Pellet Hormone Therapy | Hormone Replacement Clinic


Estrogen and testosterone therapy by hormone pellet implantation is a safe and effective method of hormone therapy for both men and women. Hormone pellets deliver consistent, healthy levels of hormones for 3-4 months in women and 4-5 months in men. They avoid the fluctuations, or ups and downs, of hormone levels seen with every other method of delivery. Estrogen delivered by subcutaneous pellets, maintains the normal ratio of estradiol to estrone. This is important for optimal health and disease prevention. Hormone pellet therapy does not increase the risk of blood clots like conventional or synthetic hormone replacement therapy.

Pellet implantation has consistently proven more effective than oral, intramuscular, and topical hormone therapy with regard to bone density, sexual function, mood and cognitive function, urinary and vaginal complaints, breast health, lipid profiles, hormone ratios and metabolites. Pellet hormone therapy has been shown to be superior for relief of menopausal symptoms, maintenance of bone density, restoration of sleep patterns, and improvement in sex drive, libido, sexual response and performance.

To learn more, visit one of our hormone replacement clinics or please download our comprehensive brochure:

Blue Sky MD Pellets FAQ

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If you’ve had a stem cell treatment, how was your …

Have you had astem cell treatment and if so, what was your experience like? (Update, please also take our poll on stem cell therapy cost).

I really value the diversity of readers on this blog from all over the world. I know we have a lot of readerswho are patients and have had stem cell treatments. Every week I get emails from people asking about stem cell treatments and clinics.

I encourage you to weigh in here in the comments if you or a loved have had a stem cell treatment. What was itlike? If it was positive, why did you feel that way? Same if it was negative.

How much did you have to pay and did you think it was reasonable?

What condition were you hoping to improve?

How did you find out about the clinic and would you refer someone else to them?

Anything else youd like to share?Feel free to remain anonymous if you prefer.


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Too Much Growth Hormone in a Child: Causes and Effects …

The pituitary gland produces growth hormones and releases them in bursts every three to five hours. The body normally regulates the amount which is produced and released. However, its possible for too much to be produced. Growth hormones are essential to promoting proper development in children, but what happens when there is too much growth hormone in a child?

Growth hormones are important influences on a childs height and development. While many children are shorter or taller than others due to genetics, some children may have a growth disorder.

Growth disorders affect the speed at which a child develops. Height, weight, and sexual development are just a few features which can be affected. Diseases or problems with the pituitary gland are the leading causes of growth disorders.

The pituitary gland is responsible for producing growth hormones. Too few can lead to poor growth in children, while too many can lead to a condition called gigantism.

Gigantism is a rare condition that usually occurs when a tumor grows on the pituitary gland, affecting the amount of growth hormones in a child. As a result, the childs body and organs grow extremely large for their age.

Excessive growth hormone symptoms are usually slow to form. Symptoms can be difficult to notice because children can develop in spurts or at different rates than their peers.

Symptoms of too much growth hormone in a child include:

Its important to treat gigantism because a child may experience delayed puberty, or their genitals may not fully develop.

Your doctor will be able to confirm whether a growth disorder is present through a combination of blood tests, CT or MRI, and study of serial photographs (photographs taken over the course of several years).

Treatment can stop or slow growth hormones from causing your child to grow larger than normal.

Stopping or slowing the production of growth hormones is not easy. Your doctor may need to use a combination of techniques to effectively treat your child.

Treating excess growth hormones in children is essential to ensuring that they live a long and healthy life.

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Bone Marrow – Boston Stem Cell Center

The problem with the embryonic stem cells are the many complications associated with them. Besides the ethical considerations, from a practical point of view, we are still a long way from being able to utilize these cells in a safe and consistent manner.

When using embryonic stem cells, you are inheriting any potential diseases that the baby may have. For instance, the baby may have a gene that increases susceptibility to cancer. In fact, the embryonic cells themselves may act as a tumor since there is no natural check on these cells. Furthermore, these cells are foreign materials to the body, and the body will react and attack these cells in an immune response. This can sometimes cause a serious medical condition called graft versus host disease. In that case, the patient may have to be placed on immunosuppressant drugslike an organ transplant patient. With our present technology, embryonic stem cells are not the answer. For those reasons, the FDA has put significant restrictions on the use of this type of cell in humans.

Bone Marrow - Boston Stem Cell Center

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Genetic Causes of Male Infertility | Common male fertility …

The human genome is the complete set of instructions for building a human.

It is made up of 23 pair of chromosomes which each have somewhere between 500 5,000 individual genes, each of which are responsible for a particular trait hair color, eye color, etc. 22 of the chromosome pairs are the same in men and women, but the last set is the sex chromosome. Women have 2 X chromosomes (XX), while Men have an X and a Y (XY).When a baby is conceived the babys DNA comes from both the father and the mother. The egg contains a single set of 23 chromosomes and the sperm contains the other 23. When the sperm fertilizes the egg, the two sets of chromosomes combine to form a full set of DNA for the new little person. Interestingly, the gender of the baby is determined by the man. Sperm can carry either an X or a Y chromosome which will determine whether the baby will be a boy or a girl.

Genetic disorders can be divided into a few different categories. Numerical chromosomal abnormalities occur when a person receives an extra chromosome, which can cause various disorders such as Downs or Turners syndrome. Another thing that can happen is pieces of a gene can get deleted during duplication. Most of the time, large deletions cause severe enough disorders that dont enable an embryo to develop. However, some very small deletions, known as micro-deletions can lead to a variety of congenital defects including infertility. Microdeletions in the Y chromosome have a profound impact on sperm production and is a fairly common cause of infertility in men. Finally, mutations or trans-locations are disorders where parts of a gene form abnormally or get mixed up with other genes causing it to malfunction. This can cause disorders such as cystic fibrosis or sickle cell anemia. Sometimes these mutations can impact fertility.

As mentioned above, the most well-known of the numeric abnormalities is trisomy 21 or Downs Syndrome. This occurs when someone receives an extra copy of the 21st chromosome and happens in about 1 in every 700 births. It is also fairly common to have extra copies of either the X or the Y chromosome. Some women may have a an extra X resulting in a condition known as triple X. Men can receive either an extra X or an extra Y chromosome, resulting in XXY or XYY. Rarely, babies are born that are genetically female with two X chromosomes but present as males.

The most common genetic cause of male infertility is a condition known as Klinefelter Syndrome. About 1 in every 500 boys are born with an extra X chromosome in their genetic makeup XXY. This condition is known as Klinefelter Syndrome, and it has been shown to drastically reduce the mans fertility.

Microdeletions make up another large portion of the genetic causes of male infertility. Most of the time deletions occur on the Y chromosome.

The Y chromosome is by far the smallest chromosome and is primarily responsible for the creation of sperm and the development of tissue in the testicle. Because it is only passed from man to man via sperm, and sperm are continually being made by the body, it has a higher risk of mutating from one generation to the next when compared to the other genes. When a man has Y microdeletions, it is kind of like having a few bad sectors on a hard drive, it really doesnt affect anything EXCEPT trying to make sperm. Its estimated that somewhere around 10% of azoospermic men have these micro-deletions but the number could be bigger as it has been traditionally difficult and expensive to diagnose.

Another genetic disorder caused by microdeletions is Prader-Willi Syndrome. This syndrome is incredibly rare occurring once in every 25,000 births. It is caused by microdeletions on the 15th chromosome and is commonly diagnosed via genetic testing at birth. Like autism, Prader-Willi is a spectral disorder with a range of symptoms from mild to severe. The most common symptoms include hypgonadism, infertility, small hands and feet, and obesity stemming from an uncontrollable appetite.

Scientists estimate that there are around 2,300 genes involved in male reproduction. Each gene has several possible mutations, making it nearly impossible to isolate all genetic causes of infertility. The rise in genetic sequencing and other genetic testing techniques has dramatically increased our understanding of how genes impact our health and fertility. Here are some of the more common genetic mutations that can impact fertility.

Cystic Fibrosis is one of the most well known genetic mutation disorders. It occurs when there is a mutation in the CFTR gene (located on the 7th chromosome). This gene is responsible for helping your body regulate use of salt and over 1,200 mutations of the gene have been identified by scientists. Full blown CF occurs when an individual has two copies of a mutated gene, which happens about once in every 2,500 births. Thanks to modern medicine, CF patients are living longer, healthier lives and many are able to start families of their own. However, a hidden side-effect of CF is that it can often cause a natural vasectomy by preventing the formation of the vas deferens. Skilled urologists specialized in fertility are able to help men with CF become fathers.A lesser known fact about CF is 1 in 25 people carry one copy of the mutated gene. Some mutations specifically impact the formation of the vas deferens, so even men who dont have full blown CF may be genetic carriers with unexplained obstructive azoospermia. A skilled urologist should be able to detect the absence of the vas deferens during a physical evaluation and recommend genetic testing if a CF mutation is suspected.

Mutations in key genes involved with fetal development can prevent the testicles from descending. Other mutations can cause abnormal development of the ducts that connect the testicles to the body. Since sperm production is regulated by hormones, genetic problems with the endocrine system may also create conditions that are unfavorable for or preclude sperm production. Some of the known syndromes stemming from genetic mutations that affect male fertility include: Noonan Syndrome, Androgen Insensitivity Syndrome, Kallman Syndrome, Myotonic Dystrophy, and Kartageners Syndrome.

Genetic Causes of Male Infertility | Common male fertility ...

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What is CAR-T Cell Therapy | CAR-T Definition | Bioinformant

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Genetics May Explain Why Birth Control Doesn’t Always Work …

Some women release an enzyme that canbreak down the hormones from birth control, which may makethese contraceptive methods less effective in preventing pregnancy. (Credit: Image Point Fr/Shutterstock)

No form of birth control is 100 percent effective. Now, a new study provides an explanation for why a small number of women who use hormonalcontraceptive methods still become pregnant, even if they use them correctly.

A new study published in Obstetrics & Gynecologyexplains that somewomen have an uncommon genetic difference that makes hormonal contraception less effective for them.

In the paper, researchers at the University of Colorado School of Medicinesay that around5 percent of women carry a gene that makes their bodies produce an enzyme that breaks down the hormones in birth control faster than usual. The researchers think that the enzyme leaves women with hormone levels that may be too low to prevent pregnancy, particularly among users of low-dose contraceptives.

Hormonal contraceptive methods like the pill, implant or injection work by releasing synthetic versions of female hormones, usually estrogen and progestin, thatoverrides awomans monthly cycle andprevents ovulation. Receiving these hormones, ironically, tricks a womans body into thinking its pregnant, which stops the release of an egg each month. Thehormones also work to prevent pregnancy by thickening the mucus near the cervix, which preventssperm from reaching the egg.

To learn how a womans genetic makeup influences birth control hormones,the researchers examined 350 healthy women with a median age of 22.5 years old who had received a contraceptive implant. This long-lasting birth control device sits under the skin and delivers the hormones necessary toprevent ovulation.

The researchers found that around 5percent of women tested positive for agenetic variant, called CYP3A7*1C. And among these women, the researchers observed lower levels of birth control hormones in their system. Its thought thattheenzyme somehow interferes with the ovulation-suppressing effects of hormonal birth control.

Lead study author Aaron Lazorwitz said that the CYP3A7*1C gene normally shuts off during gestation, before a woman is ever born. But in some women that never happens and evidently impacts how they process steroid hormone-based drugs, like birth control.Better understanding genetic differences in medication effectiveness could be a game-changer in womens healthcare, Lazorwitz said.

The field of pharmacogenomics, looking at how genetics affects drugs, has been a hot topic in multiple areas of medicine [but] womens health research has unfortunately not focused much on this field to this point, he said. As we use the same types of hormonal medications for so many different treatments in womens health, the impact of genetics on these medications has huge potential to change how we take care of women.

According to the Centers for Disease Control and Prevention, 24 percent of women use a hormonal form of contraception like the pill or the implant. Lazorwitz said that many cases of birth control failure come down to user error such as missing a few pills. But, as this study shows, there arefactors outside of a womans controlthat can impact birth control effectiveness, and there are probably more to find, according to Lazorwitz.

We think that genetics is part of the equation, but there likely are other things we havent even considered yet, he said. This is just the first step in our work to try and figure out this complicated issue. Thankfully, we have extremely efficacious birth control methods like intrauterine devices and the [contraceptive] implant that we know work very well for the vast majority of women.

Lazorwitz said the findings likely apply to all forms of hormonal birth control such as the pill, implant or injection because the hormones used in these methods are similar and are processed similarly in the body. But future studies are needed to prove this.

The unintended pregnancy risk for women carrying this genetic variant cannot be quantified yet because its too early. Because the implant releases more than enough hormones needed to prevent pregnancy, Lazorwitz said the variant probably does not impact efficacy of the contraceptive implant. The researchers are more concerned that the genetic variant could affect the effectiveness of lower-dose hormonal methods, like the pill.

For now, Lazorwitz saidwomen should continue to work with their doctorsin finding the best birth control method for them.

We want to reassure women taking hormonal birth control that they dont need to go get genetic screening or anything like that at this time We hope that this kind of research will one day lead to enough information that we can develop some tools or screenings to help guide women on their individualized decision-making process in choosing a birth control method, he said.

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Bone Marrow Transplantation: Autologous and Allogeneic …

Hematopoietic stem cell transplantation (HSCT) is the new name for bone marrow transplantation.

The bone marrow is home to hematopoietic stem cells (HSCs), also called pluripotent stem cells because they can give rise to any cell your body requires at any given moment. These specialized cells play an essential role in replenishing our blood supply on a daily basis to maintain blood counts in a healthy host. These cells can be collected either by performing repeated bone marrow aspirations or by mobilizing HSCs into the circulation using special medications called cytokines (like GCSF, also called neupogen), and filtering them out of your blood using a highly specialized process called apheresis. After they are collected from your body, these stem cells can be preserved by storing them in a chemical called DMSO, and placing them in a freezer. Stem cell transplantation refers to a process whereby the patients HSCs are replaced by new cells (either from yourself [autologous] or someone else [allogeneic] that grow into a healthy hematopoietic system.

There are many types of HSCTs depending on the source of stem cells as described below:

Autologous Stem Cell Transplantation:

Autologous stem cell transplants are predicated on a simple concept: if a little chemotherapy has the potential to cure, than a lot could be even better. For lymphoma that has come back after conventional chemotherapy, this disease is not usually sensitive to lower doses of chemotherapy, so there is a need to consider higher doses. The challenge of course, is that higher doses of chemotherapy, while effective at treating the lymphoma, can also destroy all your bodys normal blood cells. Hence, after receiving high dose chemotherapy, there is a need to re-infuse your own normal stem cells, collected before you get the high dose therapy.

The use of your own stem cells, collected and frozen prior to the high dose therapy, is referred to as an autologous stem cell transplant. The most common indications for this kind of stem cell transplant are recurrent non-Hodgkin lymphoma and Hodgkin lymphoma. Typically, the patient undergoes chemotherapy to put their cancer into remission. At some point during their treatment they are assessed for HSCT that includes evaluation of the marrow to ensure healthy stem cells as well as adequate heart, lung and liver function. If they qualify then the stem cells are collected usually by apheresis.

In this process, stem cells that have been stimulated to divide and mobilized by medications (ex: GCSF or Neupogen) are filtered out of the circulation through an IV and stored for future use. Once the stem cells are collected, the patient undergoes further conditioning chemotherapy to destroy all cancer cells in their body. This kind of treatment can be toxic to stem cells and may result in long term inability to produce blood. The previously collected stem cells are infused back into the patient and after 7 to 10 days the blood counts recover and the patient can go home. Since these are the patients own cells there is no danger of graft rejection or graft versus host disease. The immune system may take up to a year to fully recover.

Allogeneic Stem Cell Transplantation:

Unlike autologous stem cell transplants, allogeneic stem cell transplants are predicated on the idea that if your immune system could not detect and destroy your lymphoma before it became obvious, then maybe an immune system from someone else (a sibling or an unrelated but matched person), can identify your lymphoma as foreign, and mount an immune response against it. The problem of course is that while the donor immune system, now transplanted and growing in a new host (that is the patient), can recognize the lymphoma as foreign (graft versus lymphoma effect, or GVL), it can also recognize the normal organs of the host as foreign, and mount a graft versus host (GVHD) response against your skin, lung, liver, and gastrointestinal tract. Drugs to suppress the immune system, called immunosuppressants, are often used to help control GVHD, but can obviously compromise some of the GVL effect as well. It is a double edge sword you want GVL without the GVHD, but unfortunately the two go and-in-hand. Indications for allogeneic stem cell transplant typically include acute myeloid leukemia, aggressive lymphomas, and stem cell disorders. A donor for a patient is defined by HLA typing of blood and tissues.

HLA stands for Human Leukocyte Antigen, and describes a series of proteins that exist on the surface of all cells in your body, and which is defined genetically. The degree of relatedness between individuals can be described by the similarities or differences in these genes that code for the HLA proteins, and are used to determine who might be a suitable donor for any given patient. The more closely related the individuals (say identical twins), the lower the risk of GVHD, but the lower the risk of GVL. The greater the difference in the HLA, the greater the risk of GVHD, but consequently, the greater the GVL benefit. Of course, if the toxicity of the GVHD is so great, producing increased mortality, then the GVL benefit becomes inconsequential. Thus, allogeneic transplanters walk a very fine line in assessing each patients individual risk and benefit with this type of transplant.

An HLA matched donor is needed for the host to allow the donor blood cells to engraft in the marrow, otherwise they will be rejected by the bodys immune system. The best donor, usually meaning the least degree of graft versus host disease (GVHD), is usually a sibling. Each person has about a 25% chance of having an HLA matched sibling donor. HLA matching is different from blood typing and can be done by a simple blood test or obtaining a swab from the inside of a persons mouth. Should no siblings be identified as a match, than a search is initiated to find an unrelated HLA match through the National Marrow Donor Program (NMDP). Once a match is identified, the patient is admitted to the hospital to receive conditioning chemotherapy and / or radiation therapy. At the end of this treatment, stem cells from the donor are infused into the patient and allowed to engraft. Even with an HLA matched donor there is a considerable risk of GVHD where the new grafted donor cells will attack the patients organs.

After the transplant, the patient is given immunosuppressive medications to prevent this condition, and is required to be on these for a considerable period of time.

Cord blood transplants:

Umbilical cord blood is an excellent source of stem cells and can be used as a source of stem cells in cases where an unrelated donor cannot be found. This has saved the lives of many patients. HSCT is a complicated process that requires a commitment from the patient and their families for the best outcome .You will be referred to a specialized center for HSCT where you will receive further details and education about the process.

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Bone Marrow Stem Cell Transplant HSCT : National …

In January 2019, an international team of researchers led by Richard K. Burt, MD (Northwestern University, Chicago, IL) published results of the first randomized, control trial of bone marrow stem cell transplant (HSCT) in people with aggressive relapsing-remitting MS. They enrolled 110 people whose MS was not controlled by available disease-modifying therapies. Half received immunosuppressant therapy followed by hematopoietic (blood cell-producing) stem transplant. The other half were switched to a different disease-modifying therapy. Significantly fewer people experienced MS progression in the group that underwent HSCT, compared with the group who were switched to a different MS disease-modifying therapy. There were no deaths or life-threatening adverse events in either group. The investigators consider this study to be preliminary and recommend that further research is needed to confirm these findings and to determine longer-term outcomes and safety. Read the summary or read the abstract in JAMA.

In December 2018, Drs. John Moore, David Ma (St. Vincents Hospital, Darlinghurst, NSW, Australia) and colleagues reported results of a small clinical trial of HSCT conducted at a single medical center in Australia. This trial enrolled 35 people with relapsing-remitting MS or secondary progressive MS whose disease had not responded well to disease-modifying medications. There was no control group or blinding; all participants underwent the HSCT procedure. The team reported on results after following participants from 12 to 66 months after transplantation. After 12 months, 82% remained free of relapses, MRI-detected new or enlarging lesions, and progression (called Event-Free Survival or EFS). At two years after transplant, 65% of the group had EFS, and at three years 60%. EFS was better in those who had relapsing MS. Of 8 who experienced MS progression after transplantation, 2 had relapsing-remitting MS and 6 had secondary progressive MS. Twelve of thirteen whose disability scores improved after transplantation had relapsing-remitting MS.At this center, which has a long experience with bone marrow transplants, there were no transplant-related deaths. Many experienced complications expected from the chemotherapy cocktail (called BEAMS) used to deplete their bone marrow cells in preparation for the transplant. Read a summary or read the abstract in the JNNP.

In April 2017, researchers in Italy combined and analyzed results from 15 previously published studies of HSCT (Hematopoietic Stem Cell Transplantation) involving 764 people with various forms of MS. They found that overall, the procedure showed a significant benefit against disease activity and progression. Two years after transplantation, about 83% of all participants had not progressed; overall, studies involving more people with relapsing-remitting MS had lower progression rates. The pooled results showed an overall transplant-related mortality rate of 2.1%.There were fewer deaths in later studies as researchers gained more experience with the procedure. Read a summary of more details here or the abstract in Neurology

In February 2017, results of an international study were published. The study evaluated long-term outcomes from HSCT in 261 people with different forms of MS. The transplants took place between 1995 and 2006, with a follow-up period of up to 16 years. Several different transplant protocols were followed. After 5 years, 46% still had not experienced any progression or worsening of symptoms, including 73% of those with relapsing MS and 33% of those with secondary progressive MS. Eight deaths (2.8%) occurred within 100 days of the transplant. Most of these occurred during the early development of the procedure; improvements in patient selection and transplant techniques have significantly reduced the mortality. Those with the best outcomes tended to be younger, had relapsing MS, lower accumulation of disability and had used fewer MS therapies prior to the transplant procedure. Additional research is needed to better understand who might benefit from this procedure and how it compares to the benefits of powerful immune-modulating therapies now available. A phase 3 trial of HSCT is now in planning stages. The Society is engaged with the team planning the trial and is encouraging quick action to design and launch the trial.Read a summary of the results or the paper in JAMA Neurology

In February 2017, results were published from a multi-center, 5-year trial called theHALT MS Study. It tested HSCT in 24 people with MS and active relapsing-remitting disease that was not controlled by disease-modifying medications. Results suggest that after five years, 69.2% of participants experienced no new disease activity after the procedure and did not need disease-modifying therapies to control their disease. All participants experienced severe and/or life threatening adverse events. Most of these occurred within the first 30 days after transplant and were related to low white blood cell counts and infections. This trial, which was funded by the National Institutes of Health, is an important addition to research needed to determine whether this approach to stem cell transplantation is safe and effective in people with MS. A larger, phase 3 trial is in planning stages.Read a summary of the results or the paper in Neurology

In June 2016 researchers in Canada published results of a long-term HSCT trial involving 24 people with aggressive relapsing-remitting MS whose disease was not controlled with available therapies. Three years after the procedure, 70% remained free of disease activity, with no relapses, no new MRI-detected inflammatory brain lesions, and no signs of progression. None of the surviving participants experienced clinical relapses or required MS disease-modifying therapies to control their disease, and 40% experienced reductions in disability. One participant died and another required intensive hospital care for liver complications. All participants developed fevers, which were frequently associated with infections, and other toxicities.Read more about this study

In October 2015, researchers at the University of Genoa and other institutions in Italy reported on a small trial of HSCT in seven people with very active relapsing-remitting MS that was not controlled with MS disease-modifying therapy. They underwent a low-intensity lympho-ablative regimen in which the immune system was suppressed but not completely depleted before the stem cell transplant as an approach to reducing toxicity. The investigators did MRI scans (for 3 years) and clinical evaluations (for 5 years). They found dramatic reductions of MRI-detected inflammation after the procedure, but did not achieve complete absence of inflammation. After 5 years, two participants remained stable, one significantly improved, and four had mild disease progression. One experienced a relapse after treatment. No severe side effects occurred. The authors conclude that the low-intensity regimen they used was not sufficient to treat aggressive MS.Read an abstract from the paper(Multiple Sclerosis 2015 Oct;21(11):1423-30) In January 2015, doctors at Northwestern University published their10-year experience of treating people with HSCT. The report included 123 people with relapsing-remitting MS and 28 with secondary-progressive MS. Their method is nonmyeloblative HSCT, in which the immune system is suppressed but not completely depleted before the stem cell transplant. Individuals were followed from 6 months to 5 years, or an average of 2.5 years. The EDSS disability scores improved, compared to pretreatment, by one point or more in 64% of those followed out to year 4. Relapses and MRI-detected disease activity were also reduced. In evaluating which type of individuals benefited from the therapy, the doctors suggested that people with relapsing-remitting MS who had had MS for ten years or less showed improvements in their disability scores, whereas those with secondary-progressive MS or disease duration greater than ten years did not show improvements on their disability scores. They reported no treatment-related deaths or serious infections. ITP (immune-mediated thrombocytopenia), a potentially serious bleeding disorder, developed in 7 people, and thyroid disorders developed in 7 people.Read a summary of their resultsor thepaper in JAMA (Published onlineJanuary 20, 2015).

Ongoing Research in HSCTAdditional research is focusing on figuring out who might benefit from this procedure and how to reduce its risks. HSCTis being investigated in Canada, the United States, Europe and elsewhere. For example:

Dr. Richard Burt of Northwestern University in Chicago has recently begun a new phase 3 clinical trial at Northwestern to try to determine the optimal protocol for safety and benefit. Read more about this trial on A clinical trial is getting underway at medical centers in Denmark, Netherlands, Norway and Sweden. The trial is testing treatment with HSCT compared with alemtuzumab in people with active relapsing-remitting MS. Read more about this trial on

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Bone Marrow Stem Cell Transplant HSCT : National ...

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Thyroid Hormone Treatment | American Thyroid Association

Thyroid hormone is easy to take. Because it stays in your system for a long time, it can be taken just once a day, and this results in very stable levels of thyroid hormone in the blood stream. When thyroid hormone is used to treat hypothyroidism, the goal of treatment is to keep thyroid function within the same range as people without thyroid problems. Keeping the TSH level in the normal range does this. The best time to take thyroid hormone is probably first thing in the morning on an empty stomach. This is because food in the stomach can affect the absorption of thyroid hormone. However, the most important thing is to be consistent, and take your thyroid hormone at the same time, and in the same way, every day. If you are taking several other medications, you should discuss the timing of your thyroid hormone dose with your physician. Sometimes taking your thyroid hormone at night can make it simpler to prevent your thyroid hormone from interacting with food or other medications.

Do not stop your thyroid hormone without discussing this with your physician. Most thyroid problems are permanent, and therefore most patients require thyroid hormone for life. If you miss a dose of thyroid hormone, it is usually best to take the missed dose as soon as you remember. It is also safe to take two pills the next day; one in the morning and one in the evening. It is very important that your thyroid hormone and TSH levels are checked periodically, even if you are feeling fine, so that your dose of thyroid hormone can be adjusted if needed.

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Thyroid Hormone Treatment | American Thyroid Association

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What is Gene Therapy? | Pfizer: One of the world’s premier …

Gene therapy is a technology aimed at correcting or fixing a gene that may be defective. This exciting and potentially transformative area of research is focused on the development of potential treatments for monogenic diseases, or diseases that are caused by a defect in one gene.

The technology involves the introduction of genetic material (DNA or RNA) into the body, often through delivering a corrected copy of a gene to a patients cells to compensate for a defective one, using a viral vector.

The technology involves the introduction of genetic material (DNA or RNA) into the body, often through delivering a corrected copy of a gene to a patients cells to compensate for a defective one, using a viral vector.

Viral vectors can be developed using adeno-associated virus (AAV), a naturally occurring virus which has been adapted for gene therapy use. Its ability to deliver genetic material to a wide range of tissues makes AAV vectors useful for transferring therapeutic genes into target cells. Gene therapy research holds tremendous promise in leading to the possible development of highly-specialized, potentially one-time delivery treatments for patients suffering from rare, monogenic diseases.

Pfizer aims to build an industry-leading gene therapy platform with a strategy focused on establishing a transformational portfolio through in-house capabilities, and enhancing those capabilities through strategic collaborations, as well as potential licensing and M&A activities.

We're working to access the most effective vector designs available to build a robust clinical stage portfolio, and employing a scalable manufacturing approach, proprietary cell lines and sophisticated analytics to support clinical development.

In addition, we're collaborating with some of the foremost experts in this field, through collaborations with Spark Therapeutics, Inc., on a potentially transformative gene therapy treatment for hemophilia B, which received Breakthrough Therapy designation from the US Food and Drug Administration, and 4D Molecular Therapeutics to discover and develop targeted next-generation AAV vectors for cardiac disease.

Gene therapy holds the promise of bringing true disease modification for patients suffering from devastating diseases, a promise were working to seeing become a reality in the years to come.

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What is Gene Therapy? | Pfizer: One of the world's premier ...

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STAR Gene Therapy | Charcot-Marie-Tooth Association

The CMTA Is Accelerating Research Through Gene Therapy

The CMTA looks forward to a time when doctors are able to use genetic therapies to treat the root cause of CMT rather than prescribing medications or recommending surgery. We are already envisioning the possibilities that gene therapy holds for our community of 2.8 million people worldwide living with CMT. In fact, were leading the pursuit to explore gene therapy in CMT by expanding our Strategy to Accelerate Research (STAR) program and our STAR Advisory Board.

At the CMTA, we are already envisioning the possibilities that gene therapy holds for our community of 2.8 million people worldwide living with CMT. John Svaren, PhD, Chair, CMTA Scientific Advisory Board

Given the increased feasibility and applicability of gene therapy to CMT, the CMTA hosted a Gene Therapy Workshop in 2018. In response to invitations from CMTA board member Dr. Steven Scherer, more than 20 of the top gene therapy experts gathered for the inaugural CMT-centered workshop on gene therapy. This meeting included experts who have worked in related genetic and neuromuscular disease areas, as well as clinicians and scientists spearheading efforts toward gene therapy for CMT2D and CMT4J.

Building on this meeting, the CMTA is assembling the best experts to formulate gene therapy strategies for CMT2 and CMT1 subtypes. Four gene therapy experts, Beverly Davidson, PhD, at the University of Pennsylvania, Kleopas Kleopa, MD, at the Cyprus Institute of Neurology & Genetics, Scott Harper, PhD, at the Ohio State University School of Medicine, and Steven Gray, PhD, at the University of Texas Southwestern Medical Center have now joined the Scientific Advisory Board of the CMTA. Dr. Davidson is an acknowledged leader in the gene therapy field, and her extensive experience includes both academic research and commercial translation gene therapy approaches. Dr. Kleopa has shown proof of concept that gene therapy works in two mouse models of CMT: CMT1X and CMT4C. This strategy can capitalize on the CMT animal models that have been developed and characterized with CMTA support. Dr. Harper is collaborating with Robert Burgess, PhD, at the Jackson Laboratory to develop a gene therapy vector to be used in a treatment for CMT2D. Dr. Grays core expertise is in Adeno-Associated Virus (AAV) gene therapy vector engineering, followed by optimizing approaches to deliver a gene to the nervous system, with application to CMT4J.

Our genes dictate many of our personal characteristics; however, mutations in genes cause genetic diseases, such as CMT. Scientists have been working for decades to modify or replace faulty genes with healthy ones to treat, cure or prevent disease. Fortunately, we are seeing significant progress on these efforts to provide gene therapy options for CMT. In fact, recent studies have provided an effective gene therapy for spinal muscular atrophy (SMA), a devastating disorder that affects the same motor neurons that are affected by CMT.

Sometimes the whole gene is duplicated, as in CMT1A, where a chromosome segment around the PMP22 gene is present in three copies instead of two. Alternatively, a part of a gene is defective or missing from birth, causing many of the other known forms of CMT. Any of these variations can disrupt the structure of the protein that is encoded by the affected gene, causing cellular problems that ultimately lead to disease.

In gene therapy, scientists can do one of several things depending on the problem with the gene. The simplest form of gene therapy is to simply provide a correct copy of the gene, which is the basis of the gene therapy for SMA. In variations of this approach, genes that are causing problems can be suppressed. One example of this was the recent demonstration that antisense oligonucleotides can be used to improve the neuropathy in rodent models of CMT1A. In addition, the exciting new field of genome editing using CRISPR technology has now made it possible to correct disease-causing mutations, and collaborative projects have already been initiated with leaders in this field

In order to insert new genes directly into cells, scientists use a vehicle called a vector that is genetically engineered to deliver the correct version of the gene. For example, viruses have a natural ability to deliver genetic material into cells, and therefore, can be used as vectors. While some viruses cause disease, virus vectors are highly modified to remove their ability to cause disease so that they can be safely used to carry therapeutic genes into human cells.

Gene therapy can be used to modify cells inside or outside the body. When its done inside the body, a doctor will inject the vector carrying the gene directly into the part of the body that has defective cells.

Before a company can market a gene therapy product for use in humans, the gene therapy product has to be tested for safety and effectiveness so that the Food and Drug Administration (FDA) can evaluate whether the risks of the therapy are acceptable in light of its potential benefits. Gene therapies have begun to receive FDA approval, and many gene therapies are in clinical trials.

At the CMTA, we believe gene therapy holds the promise to provide effective therapies for people living with CMT. As we continue to make great strides in this area, the CMTA is committed to helping speed the development of gene therapy approaches by investing in the most promising and groundbreaking gene therapy treatments that have the potential to benefit our community.

We are members of the National Organization for Rare Disorders (NORD), and they have put together a six-minute video to help answer questions frequently asked about gene therapy. We think this video will help you better understand the basics of gene therapy.

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STAR Gene Therapy | Charcot-Marie-Tooth Association

Recommendation and review posted by Bethany Smith

Testosterone Replacement Therapy For Men – Renue Health

Testosterone is a hormone that is present in both men and women. Testosterone is the androgenic hormone primarily responsible for normal growth and development of male sex and reproductive organs, including the penis, testicles, scrotum, prostate, and seminal vesicles. It facilitates the development of secondary male sex characteristics such as musculature, bone mass, fat distribution, hair patterns, laryngeal enlargement, and vocal chord thickening. Additionally, normal testosterone levels maintain energy level, healthy mood, fertility, and sexual desire.

The number of men diagnosed with hypogonadism, commonly referred to as Low T has grown dramatically in recent years due to an increasing awareness of the importance of hormones in a mans health and well being. Research shows that about 1 out of 4 men over the age of 30 may have low testosterone. Circulating testosterone levels decline progressively with age, starting in the second and third decade of life. Testing for testosterone deficiency requires a comprehensive understanding of the intricacies of hormone balance before one makes a commitment to what may be lifelong therapy.

Low Libido

Gaining fat around the middle

If you have any of these common symptoms, it is recommended you have a proper and thorough set of labs drawnto help determine if you havehypogonadism.

Testosterone replacement therapy is essential for men with hypogonadism. In these men, full replacement of testosterone is necessary. The amount of total testosterone in men can range from 300 to 1100 ng/ml, while the range for free testosterone is 50 to 250 ng/ml. It is more accurate to utilize free testosterone levels instead of total T levels.

Because the range is so broad, testosterone optimization must be individualized. In general, Dr. Rob aims to provide the lowest dose of testosterone that relieves symptoms and causes the man to be in the optimized zone. All while monitoring testosterone and its by-products for any potential unwanted side effects. There are several delivery method options and Dr. Rob presents the pros and cons of each before a mutually agreed upon delivery method is instituted.

It is also important to note that men should not be started on testosterone replacement without a careful endocrine evaluation to determine the cause of the low testosterone. Serious conditions including pituitary tumors can present with low testosterone.

Women have testosterone too

Men have 10 to 20 times higher levels of testosterone than women. Nonetheless, even this small amount of testosterone in women is important for maintaining sexual function, and healthy bladder and vaginal function.

When used in small physiologic doses with monitoring of testosterone blood levels, testosterone in women is well tolerated. High doses must be avoided as they can cause facial hair, loss of scalp hair, deepening of voice, and acne. Just like men, womenshould not be started on testosterone replacement without a careful endocrine evaluation to determine if it will provide a health benefit.

ReNue Healthis located conveniently in Springboro, Ohio with easy access from Dayton International Airport, Cincinnati International Airport or the adjacent Wright Brothers Private Airport (MGY) for those travelling by private aviation.Click here for directions and contact information.

Only one visit is necessary to perform a comprehensive history, interview, and education. Follow up evaluations, adjustments and balancing of hormones are done by phone or written communications and a return visit to Dr. Rob is not necessary. Ongoing testing and adjustment is mandatory and performed through a laboratory convenient to your home.

Its that nagging feeling that something does not feel quite right and you cant put your finger on it. Youre a busy person and your own health is the last thing you have time to think about, but think again!

To learn how the ReNue Health Opportunity may help restore your youth and vitality, simply call937-350-5527or visit us online

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Testosterone Replacement Therapy For Men - Renue Health

Recommendation and review posted by Bethany Smith

Gene Therapy to Treat Macular Degeneration – AMDF

In Boston, scientists are working at the frontier of genetic research in an attempt to cure Macular Degeneration, the leading cause of blindness in the U.S., an enormous task.

Rajendra Kumar-Singh: There are about 3 billion nucleotides in the human genome and just 1 small mistake is sufficient to cause a problem. And when that problem occurs it can lead to inherited retinal degeneration.

Dean Bok: The promises of gene therapy at this point in time are tremendous. In principal, one can replace a bad gene with a good one. Its easier to replace a gene thats recessive, where you need two bad ones in order to produce the disease, and thats where weve had success. The challenge is for genes that are dominant. You need to get rid of the bad guys before the good guys can do their work.

Rajendra Kumar-Singh: Because the source of inherited retinal degeneration is DNA, it makes sense to be able to deliver normal DNA to correct the defect and hence gene therapy is going to be a key player in trying to develop novel therapies for these inherited retinal degeneration.

Narrator: (Animation) An imbalance in the complement system, which helps to fight many diseases, can cause holes or, macs, to form in the macula. A protein called cd59 normally helps prevent this from occurring. At Tufts University they are seeking a way to increase this protein in people with macular degeneration.

Rajendra Kumar-Singh: We plan to express the same protein but at higher levels on the cells that are normally getting damaged in AMD and theoretically we hope to be able to prevent the formation of these macs on these cells. When we use gene therapy we are in fact putting back in a normal version of the gene, such as the protein that is produced from that is now normal and allows the cell to revert to a normal, healthy looking or healthy functioning cell. We can potentially inject just once directly into the eye and that may serve as a therapeutic for the lifetime of the patient whether it be dry AMD or wet AMD. Science is all about solving problems and I would love to be the one to be able to solve this problem and provide some sort of therapies to people who otherwise might potentially go blind. And I think Ill have fulfilled my role as a scientist if I can achieve that.

Rajendra Kumar-Singh, PhD, Professor of Ophthalmology and NeuroscienceTufts University

Dean Bok, Phd, Distinguished Professor of Neurobiology and OphthalmologyUCLA

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Gene Therapy to Treat Macular Degeneration - AMDF

Recommendation and review posted by Bethany Smith

Crude versus defined CAR T-cell therapy product

In the race for the most potent CAR T-cell therapy, there is a big interest to the issue of purity and composition of the final cell product. In this post, Ill try to summarize the current knowledge about defined CAR T-cell products, based on two clinical studies, published this week.

What is defined product and why it is important?We can roughly divide CAR T-cell products on bulk T-cell or crude and defined composition. Crude CART products are not purified and contain: different ratios of CD4/CD8 T-cells and their subsets, other than T- contaminating cells and non-CAR cells. Defined composition products could be the following:

There are few good reasons for development of defined CART products:

The later is single most important reason, which begs the question Will defined CAR T-cell products deliver superior therapeutic benefit? As of today, vast majority of CART developers manufacture crude cell products. Manufacturing process usually does not include sorting of T-cells on day 0 or purification of T-cells/ CAR+ cells in-process or on a harvest day. Most of developers release final CAR T-cell product with CD3+ cells >80-90%, highly variable CD4/CD8 ratio and % of CAR+ cells.

Preclinical dataAt least one group of researchers have done a lot of experimental and clinical work on defined composition of CAR T-cell products. Defined product/ process development has been done by Michael Jensen lab, initially at City of Hope and then further adapted and modified at Fred Hutchinson Cancer Center and Seattle Childrens Hospital. Stanly Riddells lab from Hutch did a lot of experimental work to demonstrate potential value of defined CAR T-cell product. All together they have tried all versions of defined composition CAR T-cell products, mentioned above. One of recent and the most comprehensive studies by Riddells lab, showed that (1) combination of both CD4 and CD8 T-cells has superior therapeutic potency and (2) naive CD4 cells and central memory (T-CM) CD8 T-cell subsets were the most potent in vivo. Long-term persistence of human memory T-cells was demonstrated by Riddell and Jensen earlier in mouse and primate models. Importance of CD4+CD8 combo rather than use of potent cytotoxic CD8+ cells alone was also demonstrated in numerous studies (check here, here and here). Therefore, experimental studies created a strong rational for favoring T-CM, naive T-cells (T-N) and CD4+CD8 combo in adoptive cell therapy trials.

Feasibility of manufacturing defined T-CM CAR T-cell productBefore I get to the first clinical results, Id like to look at manufacturing process of defined CAR T-cell product. Jensen started with purified CD8 T-CM or CD4 + CD8 T-CM manufacturing process, which described in details here. It includes sequential 2-step CliniMACS procedure for negative selection of CD14/CD45RA/CD4 or CD14/CD45RA-negative cells, positive selection for CD62L (marker of T-CM) and culture with IL2/IL15 for up to 30 days in bags. After two CliniMACS procedures, cell recovery was as low as 0.4% (in contrast to expected 1.4%). If input cell number was usually 5 billions PBMCs, average output cell number before starting a culture was ~19 millions. T-CM recovery efficiency was 26%. Even though, they typically started culture from 7-15 millions of CD8 T-CM cells, generation of ~3 billions of cells in 3-6 weeks was feasible. This manufacturing process was used in 2 clinical trials: NHL1 and NHL2.

In the modified manufacturing process, designed for NCT01865617 trial, included CliniMACS selection of CD4+ bulk population and 2-step CD8 T-CM (see above) or CD8 bulk selection with 2 parallel 15-20 days cultures and mixing CD4:CD8 as 1:1 before infusion. Importantly, CAR+ cells were selected before infusion by a marker (EGFRt). Interestingly, either CD8 T-CM purified on day 0 or CD8 bulk cells yielded only ~40-50% of CD8+/CAR+ cells with T-CM phenotype (CD45RA-CD62L+).Now, feasibility of manufacturing in NCT01865617. 16/30 (53%) patients have passed threshold of 20 T-CM cells/ ul in screening assay for feasibility of manufacturing. From selected products, T-CM were successfully manufactured in all, but 1 cases. 3 out of 30 infused products were not formulated as 1:1 (10%), due to lack of expansion.Id summarize some of my thoughts of defined CAR T-cell product manufacturing feasibility as the following:

Clinical outcomes of using defined CAR T-cell productsResults of 3 clinical trials (NCT01318317, NCT01815749, NCT01318317), using defined CAR T-cell products have been published so far (here and here). However, the therapeutic benefit of using defined versus crude CAR T-cell product remains unclear. Ideally, defined CAR T-cells should be compared with crude product within one trial settings, because even for the same conditions, clinical protocols are very very different between sites. Also, ideally, CD8 bulk vs. CD T-CM or CD8 alone vs. CD8+CD4 combo should be compared within one trial in exactly the same settings. Unfortunately, none of these ideal comparison conditions were met in 3 published trials, mentioned above.

Even though, it seem like CD4 + CD8 T-CM combo performed better in NHL2 trial (75% progression-free survival at 1-year) than CD8 T-CM alone in NHL1 (50% progression-free survival at 1-year), the difference is not significant, due to low number of patients (n=8 in each trial). On top of it, different CAR vectors were used between these trials, culture duration was shorter and CD25+ T-regs were depleted in NHL2 trial manufacturing protocol. So, data cannot be compared. If we look at results of other CAR T-cell lymphoma trials (narrowing to DLBCL), City of Hope results are not much better than reported from other centers (for example, from Penn). CD8 T-CM persistence was not beneficial, compare to data from other centers. Two excerpts from the study, which demonstrate that assessment of defined CAR T-cell product benefit is impossible:

CD19-CAR T cell activity is difficult to assess by disease response, since 9/16 patients were in CR at start of study, and HSCT can also produce CRs.Thus, a T cell product derived from central-memory enrichment as described in these studies, does not persist longer than what is observed in trials with conventional bulk T cells transduced with CARs bearing CD28 co-stimulatory domains.

Now, moving to B-ALL study, published this week in JCI. First of all, B-ALL is not the best condition to assess a difference by clinical outcome between crude and defined CAR T-cell products, because response rate is too high (close to 90%) across the centers no matter what. The authors about outcome:

The 93% remission rate by flow cytometry and 86% MRD-negative CR rate in our study compares very favorably to that reported by others in which CART cells of undefined composition were manufactured using CD19 CARs that incorporate either a 4-1BB costimulatory domain (children and young adults, 79%) or a CD28 costimulatory domain (adults, 75%; children and young adults, 60%) (1-4)

What about persistence? Theoretically, based on experimental work, CD8 T-CM should have superior long-term persistence. But it was not the case. The study showed persistence only at 1 month time point. What about relapses? Maybe application of T-CM will reduce the rate of relapses? No, 9/30 patients in the study relapsed, half of them (5/9) received CD8 T-CM product. Clinical outcome was significantly improved in the study after implementation of different conditioning regiment (with fludarabine). This change significantly complicates and even make impossible data comparison between CD8 bulk and CD8 T-CM groups:

The high overall rate of BM remission of 93% by flow cytometry in this study and differences in lymphodepletion regimens and infused cell doses do not allow comparison of the efficacy of CART cell products manufactured from CD8+ TCM cells or from bulk CD8+ T cells. Analysis of differences in long-term persistence of cell products that were selected for CD8+ TCM or bulk CD8+ T cells in our study was further complicated by our findings that immune-mediated rejection of CART cells occurs in some patients, which may provide an explanation for the loss of CART cells observed in a subset of patients in other studies

To conclude: Despite the strong experimental evidence and very attractive idea behind of defined CAR T-cell products, it is too early to conclude about their therapeutic benefit and superior potency. With greater number of patients and technical improvements in manufacturing (more efficient clinical cell sorting, IL7+IL15 in culture and other), potential benefit of defined CAR T-cell product may become more obvious. Such benefits as dropping a therapeutic dose, better correlation between dose and in vivo expansion dynamics, decreasing donor variability in manufacturing, we can see today already.

Tagged as:CART, cell product, manufacturing

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Crude versus defined CAR T-cell therapy product

Recommendation and review posted by Bethany Smith

Lick Your Rats – Genetics

In our society, we think of anxious behavior as being a disadvantage. But that's because, for the most part, we live in a nutrient-rich, low-danger environment. In the rat equivalent to our world, the relaxed rat lives a comfortable life. It is likely to reach a high social standing, and it doesn't have to worry about where its next meal is coming from. An anxious rat, on the other hand, doesn't do so well. It is more likely to have a low social standing and suffer from diabetes and heart disease.

In another environment, however, the tables turn. The anxious, guarded behavior of the low-nurtured rat is an advantage in an environment where food is scarce and danger is high. The low nurtured rat is more likely to keep a low profile and respond quickly to stress. In the same environment, a relaxed rat might be a little too relaxed. It may be more likely to let down its guard and be eaten by a predator.

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Lick Your Rats - Genetics

Recommendation and review posted by Bethany Smith

Life Extension Mix, 360 capsules | Life Extension

Studies show that people who eat the most fruits and vegetables enjoy healthier and longer lives, but getting the recommended five servings a day is difficult for even the healthiest diets. That's why we created Life Extension Mix, a daily supplement that provides all the high-potency vitamins and minerals needed to form the cornerstone of a comprehensive health maintenance program.

Benefits at a Glance:

Our formula saves time and money by combining the most important nutrients including unique vegetable, fruit, and botanical extracts into one product, eliminating the need to take dozens of separate supplements.

More facts about Life Extension Mix

Life Extension Mix is a state-of-the-art multi-nutrient formula jam-packed with the purest and most potent forms of vitamins, minerals, amino acids, and unique vegetable, fruit, and botanical extracts. In every daily dose of Life Extension Mix, you'll get an extensive array of nutrients:

Bioactive quercetin phytosome

Life Extension Mix contains 5 mg of quercetin that has been integrated into a phytosome. A phytosome is a phospholipid sphere that encases a botanical compound, aiding in its absorption and making it more bioavailable: this quercetin is up to 50 times more bioavailable than standard quercetin. Quercetin supports cellular health, endothelial health, and healthy immune function.


Found in dark red fruits, delphinidins are potent anthocyanin compounds that activate the production of nitric oxide, promoting vascular relaxation and blood pressure support.14 They can also help inhibit inflammatory factors58 and glycation,9 support immune health, and help maintain healthy blood sugar levels within normal range.

Pyridoxal 5'-phosphate

Glycation is a normal part of the aging process that can affect your health.1014 To help inhibit glycation, each daily dose of Life Extension Mix provides 100 mg of pyridoxal 5'-phosphate a metabolically active B6 that has been shown to help inhibit glycation reactions.15-17

Standardized pomegranate extract

Pomegranate supports healthy cardiovascular function32-37 and DNA structure in prostate cells.18-23 Our pomegranate extract is standardized to provide the biologically active punicalagins that are so unique to this fruit. These punicalagins are 100% water-soluble, have a remarkable 95% absorption rate,24 and are highly potent at inhibiting free radicals.25

Blueberry extracts

Blueberry anthocyanin compounds help inhibit free radicals, while blueberry's other active constituents promote healthy lipid and glucose levels for those already within normal range.26-29 Even more exciting: these blueberry constituents may help protect DNA structure.30-34 Life Extension Mix features the wild blueberry extract packed with active blueberry constituents.

Standardized green tea extract

In recent years, the active polyphenol compounds in green tea have been found to help inhibit LDL oxidation, neuronal peroxidation, and help maintain healthy DNA structure.35-44 Life Extension Mix's daily dose contains 325 mg of a decaffeinated green tea extract standardized to provide 98% of the active polyphenols that scientists attribute to green tea's multiple health benefits.

Standardized vegetable extracts

Life Extension Mix offers a wide array of vegetable extracts, including 8 mg of luteolin, a flavonoid found in parsley, basil, celery, and other foods. Luteolin has been shown to inhibit DNA oxidation45 and to inhibit excess levels of cytokines such as interleukin-4 and interleukin-13.46

Our formula features a concentrated broccoli mixture with standardized extracts of sulforaphane and glucosinolates, compounds attributed to broccoli's detoxification, DNA,47-50 and other health benefits,51-71 as well as chlorophyll.72-83A daily dose also provides 200 mg of calcium D-glucarate (supplying 175 mg of D-glucarate), a phytonutrient found in grapefruit, apples, oranges, broccoli, and Brussels sprouts. D-glucarate supports detoxification processes.84-86

Life Extension Mix also contains lutein and lycopene. Lutein, an extract found in in leafy greens such as kale and spinach, has been shown to help maintain critical pigments in the eye macula.87 Lycopene from tomatoes helps to maintain DNA structure and protect against LDL oxidation.88-98

Standardized fruit extracts

In addition to our standardized pomegranate and wild blueberry extracts, Life Extension Mix also features fruit extracts such as bilberry, grape seed, and citrus bioflavonoids to promote healthy circulation help maintain healthy DNA.

Our unique formula is fortified with maqui berry and tart cherry for their antioxidant benefits for heart health as well as muscle and joint function support.99-118 It also includes a customized blend of blackberry, cranberry, plum, elderberry, persimmon, cherry, and other fruits that studies indicate provide multiple favorable effects on the body.

Numerous studies have pointed toward the many benefits of olive polyphenols, and Life Extension Mix contains an olive extract standardized to provide polyphenols like hydroxytyrosol that have been shown to help inhibit LDL oxidation, free radicals, and promote healthy cell membranes.119-131

Sesame seed lignan extract

Sesame lignans promote healthy levels of gamma tocopherol,132,133 enhance the beneficial effects of fish oils, and helping to maintain already-normal cholesterol/LDL levels.134-143 Life Extension Mix provides 10 mg of a sesame lignan extract to supply the direct benefits of the lignans and to augment the effects of vitamin E174 and other nutrients such as gamma-linolenic acid (GLA).

Nutrients to maintain healthy blood glucose levels

Chromium, magnesium, and biotin help maintain healthy blood sugar for those already within normal range.145-156 In addition to highly absorbable forms of magnesium and biotin, Life Extension Mix contains 500 mcg of Crominex 3+, a biologically active chromium complex. Studies on the benefits of chromium supplementation show that doses exceeding 200 mcg a day are required for optimal effects.157-159

High-potency vitamin D3

Researchers today are concerned that many people are not supplementing with enough vitamin D, a critical nutrient for maintaining bone density and healthy cell division.160-167 Currently, most experts in the field believe that intakes of between 1,000 and 10,000 IU for adults will lead to a more healthy level of serum 25(OH)D, at approximately 50-80 ng/mL.168-170

Each daily dose of Life Extension Mix provides 2,000 IU of vitamin D3. What's more, this formula contains only 500 IU of preformed vitamin A. Preformed (not beta-carotene) vitamin A may interfere with the benefits of vitamin D, yet most multivitamins contain between 5,000 and 25,000 IU of preformed vitamin A.171

Cyanidin-3-glucoside (C3G)

Life Extension Mix contains 1.25 mg of C3G to support eye health. Found in blackberries and black currants, this potent compound promotes healthy levels of rhodopsin a compound that absorbs light in the retina and enhance night vision.172-176

In one study, just 50 mg of a berry extract concentrate containing C3G helped aging individuals see better in the darkness after 30 minutes.177 Bioavailable C3G also supports other body functions,178-191 has potent antioxidant properties,192,193 and supports endothelial cell health.194,195

5-MTHF (5-methyltetrahydrofolate)

Folate helps maintain homocysteine levels within the normal range. One dose of our formula contains 400 mcg of the bioactive 5-MTHF form of folate, which is up to 7 times more bioavailable than ordinary folic acid.

Selenium and Apigenin

Life Extension Mix contains three potent forms of selenium (SelenoExcell, Se-methyl-selenocysteine, and sodium selenite). Also newly included is apigenin, a powerful bioflavonoid found in many vegetables and fruits which boosts cell protection.

Why choose Life Extension Mix?

The ingredients in Life Extension Mix are based on over 35 years of clinical research, and we've selected the purest and most potent forms of plant extracts, vitamins, minerals, and other nutrients for maximum absorption. Discover the extensive benefits of Life Extension Mix!

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Life Extension Mix, 360 capsules | Life Extension

Recommendation and review posted by Bethany Smith

Pluripotent Stem Cells 101 Boston Children’s Hospital

Pluripotent stem cells are master cells. Theyre able to make cells from all three basic body layers, so they can potentially produce any cell or tissue the body needs to repair itself. This master property is called pluripotency. Like all stem cells, pluripotent stem cells are also able to self-renew, meaning they can perpetually create more copies of themselves.

There are several types of pluripotent stem cells, including embryonic stem cells. At Childrens Hospital Boston, we use the broader term because pluripotent stem cells can come from different sources, and each method creates a cell with slightly different properties.

But all of them are able to differentiate, or mature, into the three primary groups of cells that form a human being:

Right now, its not clear which type or types of pluripotent stem cells will ultimately be used to create cells for treatment, but all of them are valuable for research purposes, and each type has unique lessons to teach scientists. Scientists are just beginning to understand the subtle differences between the different kinds of pluripotent stem cells, and studying all of them offers the greatest chance of success in using them to help patients.

Types of pluripotent stem cells:

All four types of pluripotent stem cells are being actively studied at Childrens.

Induced pluripotent cells (iPS cells):Scientists have discovered ways to take an ordinary cell, such as a skin cell, and reprogram it by introducing several genes that convert it into a pluripotent cell. These genetically reprogrammed cells are known as induced pluripotent cells, or iPS cells. The Stem Cell Program at Childrens Hospital Boston was one of the first three labs to do this in human cells, an accomplishment cited as the Breakthrough of the Year in 2008 by the journal Science.

iPS cells offer great therapeutic potential. Because they come from a patients own cells, they are genetically matched to that patient, so they can eliminate tissue matching and tissue rejection problems that currently hinder successful cell and tissue transplantation. iPS cells are also a valuable research tool for understanding how different diseases develop.

Because iPS cells are derived from skin or other body cells, some people feel that genetic reprogramming is more ethical than deriving embryonic stem cells from embryos or eggs. However, this process must be carefully controlled and tested for safety before its used to create treatments. In animal studies, some of the genes and the viruses used to introduce them have been observed to cause cancer. More research is also needed to make the process of creating iPS cells more efficient.

iPS cells are of great interest at Childrens, and the lab of George Q. Daley, MD, PhD, Director of Stem Cell Transplantation Program, reported creating 10 disease-specific iPS lines, the start of a growing repository of iPS cell lines.

Embryonic stem cells:Scientists use embryonic stem cell as a general term for pluripotent stem cells that are made using embryos or eggs, rather than for cells genetically reprogrammed from the body. There are several types of embryonic stem cells:

1. True embryonic stem cell (ES cells)These are perhaps the best-known type of pluripotent stem cell, made from unused embryos that are donated by couples who have undergone in vitro fertilization (IVF). The IVF process, in which the egg and sperm are brought together in a lab dish, frequently generates more embryos than a couple needs to achieve a pregnancy.

These unused embryos are sometimes frozen for future use, sometimes made available to other couples undergoing fertility treatment, and sometimes simply discarded, but some couples choose to donate them to science. For details on how theyre turned into stem cells, visit our page How do we get pluripotent stem cells?

Pluripotent stem cells made from embryos are generic and arent genetically matched to a particular patient, so are unlikely to be used to create cells for treatment. Instead, they are used to advance our knowledge of how stem cells behave and differentiate.

2. Stem cells made by somatic cell nuclear transfer (ntES cells)The term somatic cell nuclear transfer (SCNT) means, literally, transferring the nucleus (which contains all of a cells genetic instructions) from a somatic cellany cell of the bodyto another cell, in this case an egg cell. This type of pluripotent stem cell, sometimes called an ntES cell, has only been made successfully in lower animals. To make ntES cells in human patients, an egg donor would be needed, as well as a cell from the patient (typically a skin cell).

The process of transferring a different nucleus into the egg reprograms it to a pluripotent state, reactivating the full set of genes for making all the tissues of the body. The egg is then allowed to develop in the lab for several days, and pluripotent stem cells are derived from it. (Read more in How do we get pluripotent stem cells?)

Like iPS cells, ntES cells match the patient genetically. If created successfully in humans, and if proven safe, ntES cells could completely eliminate tissue matching and tissue rejection problems. For this reason, they are actively being researched at Childrens.

3. Stem cells from unfertilized eggs (parthenogenetic embryonic stem cells)Through chemical treatments, unfertilized eggs can be tricked into developing into embryos without being fertilized by sperm, a process called parthenogenesis. The embryos are allowed to develop in the lab for several days, and then pluripotent stem cells can be derived from them (for more, see How do we get pluripotent stem cells?)

If this technique is proven safe, a woman might be able to donate her own eggs to create pluripotent stem cells matching her genetically that in turn could be used to make cells that wouldnt be rejected by her immune system.

Through careful genetic typing, it might also be possible to use pES cells to create treatments for patients beyond the egg donor herself, by creating master banks of cells matched to different tissue types. In 2006, working with mice, Childrens researchers were the first to demonstrate the potential feasibility of this approach. (For details, see Turning pluripotent stem cells into treatment).

Because pES cells can be made more easily and more efficiently than ntES cells, they could potentially be ready for clinical use sooner. However, more needs to be known about their safety. Concerns have been raised that tissues derived from them might not function normally.

Read more about pluripotent stem cells by following these links:

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Pluripotent Stem Cells 101 Boston Children's Hospital

Recommendation and review posted by Bethany Smith

Louisville hormone clinic 25 Again sued over diet drug

A popular hormone clinic that was accused in a lawsuit in September of causing a patients death by giving him too much testosterone has been accused in another complaint of prescribing a diet drug banned by the federal government.

In a suit filed Friday in Jefferson Circuit Court, Cindy Kinder-Benge and her husband Mark allege that a nurse at 25 Again gave her human chorionic gonadotropin, or HCG, for weight loss, without disclosing that it is ineffective for that purpose.

In a consumer update headlined HCG Diet Products Are Illegal, the U.S. Food & Drug Administration saidthe hormone is not approved and there is no evidence that it produces weight loss.

The latest suit alleges that a nurse at 25 Agains New Albany clinic provided HCG in conjunction with a 700-calorie-a-day diet, which the FDA says can be dangerous and potentially fatal.

The suitsays "multiple peer-reviewed, prospective, randomized, clinical trials dating back to 1976 have concluded that HCG is ineffective for weight loss and should not be prescribed for that purpose. This information was not shared with the plaintiff."

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Ted Ennenbach, who owns 25 Again, also known as Body Shapes Medical, said in an email that the company "promotes health" anddoes not "endorse or use" either homeopathic HCG or 700-calorie diets. He said he was out of town and hadn't seen the suit and couldn't confirm whetherKinder-Benge was a patient.

The lawsuit follows other legal trouble for the clinic. In the suit filed in September, MelanieLester said the clinic repeatedly administered testosterone to her husband David, even thoughhis levels of it were normal, eventually causing his death from a heart attack.

Two other widows have sued nurse practitioner Karla King, who previously worked in Owensboro, alleging she also gave excessive testosterone to their husbands, who had normal levels of the male hormone, resulting in their deaths.King has denied negligence.

In her complaint Friday, Kinder-Bengesaid she saw ads on TV in which the clinic said its hormone treatments could resolve symptoms of menopause, such as hot flashes, and cause weight loss. She signed up for treatment at an annual rate of $2,388 plus an additional $209 for HCG.

She said blood work showed she had normal thyroid levels but a nurse nonetheless gave her additionalthyroid that caused her to experience severe chest pain and weakness due to her heart racing.

The clinic allegedly continued to tell her she needed extra thyroid, which she took for 22 months.

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From August: Why are nurses fleeing a controversial Louisville hormone treatment clinic 25 Again?

The lawsuit alleges a co-worker had to take her to BaptistHealth Floyd, where she was diagnosed as suffering from atrial fibrillation, an irregular heartbeat that can lead to blood clots, stroke, heart failure and other heart-related complications

Last September, despite being on medication to control her irregular heartbeat, she had chest pains again and hadto be returned by ambulance to the hospital, where she was intubated, placed on a ventilator and spent several days in the intensive care unit, according to the suit.

It asks for unspecified damages for negligence, fraud, lack of informed consent and violations of consumer-protection laws.

The suit,Lesters and the Owensboro complaints werefiled by attorney Ronald Johnson, who says 25 Again prescribes and administers hormones to patients when they are not clinically indicated, do not provide any benefit, and expose patients to risk of harm and death.

The Kentucky Board of Medical Licensure in June prohibited 25 Agains then-medical director, Elizabeth Bates, from practicing hormone medicine after finding her practice violated acceptable and prevailing standards of medicine.

But the agency did not ban others from the practice.

Ennenbach has said the clinic provides safe care to thousands of satisfied patients.

It is a sponsor of University of Louisville mens basketball and advertises heavily on sports talk radio, promising that patients will look younger, feel healthier and feel 25 again.

Andrew Wolfson: 502-582-7189;; Twitter: @adwolfson. Support strong local journalism by subscribing today:

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Louisville hormone clinic 25 Again sued over diet drug

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Hypogonadism Causes + 6 Ways to Help Balance … – Dr. Axe

If you or a loved one is struggling with hypogonadism, you may already know that it can be a devastating condition that reduces your quality of life and livelihood. People with hypogonadism can experience muscle loss, low libido, infertility and depressed mood. In fact, these symptoms can make talking about hypogonadism difficult. (1)

Thankfully, research shows that there are ways to balance your hormones, either using hormone replacement therapy, which is the conventional form of treatment for this condition, or natural estrogen and testosterone boosters like exercise, dietary and lifestyle changes, adaptogen herbs and essential oils. But if youve been struggling with the symptoms of hypogonadism, rest assured that there are natural remedies to help support your treatment and improve your quality of life.

Hypogonadism is a condition that occurs when the bodys sex glands, the testes for males and ovaries for females, produce little or no hormones. For males with hypogonadism, low testosterone can affect the development and maintenance of male reproductive organs, including the testes, penis and prostate. In fact, low testosterone levels can lead to issues like reduced muscle strength, hair loss and impotence.

For females, hypogonadism occurs when the ovaries arent producing enough estrogen. Estrogen is responsible for maintaining sex organs like the uterus, vagina, fallopian tubes and mammary glands. But low or little estrogen in the body can lead to infertility, loss of libido, mood swings, loss of menstruation and osteoporosis. (2)

There are two types of hypogonadism, primary or central, or secondary. The definition of these types of hypogonadism depends on the cause of the condition.

Primary hypogonadism: Primary hypothyroidism occurs when theres a problem in a persons testes or ovaries, which are the gonads. The gonads are receiving messages from the brain to produce hormones, but they arent functioning properly.

The symptoms of hypogonadism vary depending on the patients age, sex and type of condition.

Symptoms in Females: Women with hypogonadism may experience the following symptoms:

If a young girl has hypogonadism, she may not menstruate. Plus the condition can affect her height and breast development.

Boys with low testosterone may have growth problems, with a delay in muscle growth and beard development, impaired testicle and penis growth, and enlarged male breasts. Also, low testosterone levels may result in failure of normal pubertal progression.

The cause of hypogonadism depends on the type of condition, either primary or central.

Primary hypogonadism can be caused by any of the following health conditions or factors (5):

Central hypogonadism (also known as hypogonadotropic hypogonadism) occurs when theres an issue with the centers of the brain that control hormone production. The following issues can cause it:

Androgen deficiency of the aging male (known as ADAM) is a cause of secondary hypogonadism. ADAM occurs when a mans testosterone levels decline progressively after age 40, leading to sexual dysfunction and altered body composition, cognition and metabolism. (6) In fact, research published by the International Journal of Clinical Practice indicates that older men are more likely to have low testosterone levels, with the prevalence being 34 percent in men between the ages of 45 and 54, and 50 percent in men over 85 years. (7)

According to research published in the International Journal of Clinical Practice, hypogonadism is significantly associated with various health issues, including Type 2 diabetes, hypertension, obesity, osteoporosis and metabolic syndrome. (8)

Treatment for hypogonadism depends on the cause of the condition. But the most common form of treatment is hormone replacement therapy, which is used to restore hormone levels to the normal range.

For Females: Women with hypogonadism are usually given a combination of estrogen and progesterone. However, research shows that estrogen therapy can increase the risk of heart disease, blood clots and cancer. Progesterone is added to estrogen therapy because it may reduce the risk of endometrial cancer.

1. Reduce Stress

A study conducted at the University of Massachusetts Medical School investigated the association between testosterone levels and stress. Researchers measured the stress levels of participants by taking into account daily hassles, major life events and perceived stress. They found that testosterone levels were significantly associated with stress in both males and females. This study suggests that testosterone levels are reflective of a persons ability to respond to stressors and his or her emotional coping mechanisms. (14)

To support your treatment for hypogonadism, practice some simple stress relievers, like spending time outdoors, meditating, exercising, being social and keeping a journal. Pursuing some form of therapeutic practice, like cognitive behavioral therapy, may also be beneficial because it helps you to better react to stressful situations. Plus, vocalizing your fears and emotions about coping with hypogonadism can be extremely helpful.

2. Address your Weight and Diet

Being overweight and being underweight can both contribute to low sex hormone levels. For the majority of people, before they can maintain a normal body weight to help regulate their hormone levels, they need to change the way they eat. This may be the most important natural remedy to help treat hypogonadism. (15)

In fact, a 2014 study published in the Journal of Neuroinflammation found that low testosterone and diet-induced obesity can contribute to impairments in neural health, increasing the risk of serious disorders like type 2 diabetes and Alzheimers disease. (16) Theres also a childhood obesity epidemic that is causing serious health issues among children, including problems with growth and development.

So if you have low testosterone and youre struggling with weight loss, now is the time to make some serious changes to your diet in order to get well.

First, cut out all of the junk food, the processed, packaged and fast food, the refined carbohydrates and the artificial sweeteners. Focus on eating whole, real foods, including the following:

If you are having trouble staying on track with your diet and eating healthy, consider working with a health coach who can serve as a mentor and help you to reach your weight and health-related goals.

3. Exercise Regularly

Theres plenty of research that proves exercise can regulate or boost low testosterone levels. In fact, one study published in the Indian Journal of Physiology and Pharmacology found that even short-term exercise produces an elevation in serum testosterone levels in adults. (17)

Some of the best forms of exercise to boost testosterone and human growth hormone levels are weight training and high intensity interval training (HIIT workouts). Research shows that even moderate and light weightlifting can increase serum testosterone levels when compared to not doing any exercise at all. (18)

Try lifting weights for at least 30 minutes, three times a week. Doing this in combination with burst training can be even more beneficial in helping to elevate your testosterone levels. Burst training means that you are exercising at 90100 percent of your maximum effort for short, bursts of time (about 30 to 60 seconds), followed by a period of low impact exercise for recovery.

Exercise can also be helpful for women with hypogonadism because it helps to reduce stress and helps you to get to a normal weight. Weighing too little or being overweight are both factors that may cause low estrogen levels. Low-impact exercises like yoga and pilates can be very beneficial in helping to relieve symptoms and reduce some causes of hypogonadism.

4. Supplement with L-arginine

L-arginine is a type of amino acid that we obtain from our diets. It has multiple benefits, including its ability to stimulate the production of growth hormones, correct impotence, and improve erectile dysfunction and male infertility. A study published in The Journal of Endocrinology found that dietary arginine is actually required for the anabolic action of androgens, like testosterone. (19)

Research also shows that L-arginine ingestion enhances growth hormone response, increasing resting human growth hormone (HGH) levels by at least 100 percent. This is beneficial for men with hypogonadism because HGH is a natural testosterone booster. (20)

The best way to help your body make and use more L-arginine is by eating a diet based on whole, real foods, including organic grass-fed beef, wild-caught salmon, cage-free eggs, cultured yogurt, nuts and seeds, sea vegetables and coconut meat.

To supplement with L-arginine in order to improve hypogonadism symptoms, I recommend you take 36 grams per day, divided into two doses.

5. Try Ashwagandha

According to research published in Evidence-Based Complementary and Alternative Medicine, ashwagandha has been used in Ayurvedic medicine as an aphrodisiac that can treat male sexual dysfunction and infertility. Researchers involved in a pilot study found that patients with a low sperm count who were using ashwagandha had a 167 percent increase in sperm count, 53 percent increase in sperm volume and 57 percent increase in sperm motility. The ashwagandha group also showed improved serum hormone levels compared to the placebo group. (21)

To use ashwagandha to boost your libido, improve your hormone levels, increase your endurance and improve your mood, I recommend supplementing with 500 milligrams, one to two times daily. But do this in combination with eating a diet filled with healthy fats, fiber and clean protein.

6. Use Essential Oils

Two essential oils that can help to regulate hormone levels and improve hypogonadism symptoms are clary sage and sandalwood.

Clary sage contains natural phytoestrogens, so it helps to balance estrogen levels. According to a 2017 study published in Neuro Endocrinology Letters, clary sage can be used to alleviate menopausal symptoms caused by declining levels of estrogen secretion. In fact, researchers found that some essential oils, including clary sage, were able to increase estrogen concentration. (22) To use clary sage oil to support your hypogonadism treatment, combine 5 drops with a teaspoon of coconut oil and massage the mixture into your abdomen, wrists and bottoms of your feet.

Sandalwood essential oil can be used to relieve hypogonadism symptoms, like low sex drive, moodiness, stress and cognitive issues. A 2015 study conducted at South Dakota State University shows that sandalwood also has anticancer mechanisms because of its antioxidant and anti-inflammatory properties. Researchers found that sandalwood has anticancer effects against both breast and prostate cancer. (23) You can diffuse 5 drops of sandalwood at home, inhale it directly from the bottle or apply 23 drops to the bottoms of your feet.

Talk to your doctor about the risks and benefits of hormone replacement therapy. There are studies supporting the benefits of hormone replacement therapy, and evidence opposing its use for hypogonadism.

Use the natural remedies discussed in this article to support your treatment for hypogonadism or to naturally boost your low estrogen or testosterone levels. However, make sure that you discuss any supplements that you choose to take with your doctor.

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Hypogonadism Causes + 6 Ways to Help Balance ... - Dr. Axe

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Hypopituitarism Symptoms & Causes | Boston Children’s Hospital

We understand that you may have a lot of questions when your child is diagnosed with hypopituitarism. Is it dangerous? Will it affect my child long term? What do we do next? Weve tried to provide some answers to those questions on this site, and our experts can explain your childs condition fully.

Growth hormone is a protein produced by the pituitary gland, which is located near the base of the brain and attached to the hypothalamus (a part of the brain that helps to regulate the pituitary gland). If the pituitary gland or the hypothalamus is malformed or damaged, it may mean that the pituitary gland cant produce some or all of its hormones.

Hypopituitarism in children may be caused by:

Hypopituitarism can also be idiopathic, meaning that no exact cause can be determined.

The symptoms of hypopituitarism will vary depending on two things: which hormones are lacking, and your childs age. Symptoms that newborn babies may have include:

Older infants and children may have these symptoms:

Because the symptoms of hypopituitarism may resemble other conditions or medical problems, you should always consult your child's physician for a diagnosis.

Q: What is hypopituitarism?

A: Hypopituitarism occurs when the anterior (front) lobe of the pituitary gland loses its ability to make hormones, resulting in multiple pituitary hormone deficiencies. Physical symptoms depend on which hormones are no longer being produced by the gland.

Q: What causes hypopituitarism?

A: Hypopituitarism may be caused by many different conditions, including:

Hypopituitarism can also be idiopathic, meaning that no exact cause can be determined.

Q: Is hypopituitarism treatable?

A: Treating hypopituitarism depends both on its cause and on which hormones are missing. The goal of treatment is to restore normal levels of hormones. Treating the underlying condition thats causing your childs hypopituitarism often leads to a full recovery.

Since your childs body is unable to make some or all of these missing hormones, life-long hormone replacement therapy is necessary. Replacement therapy needs to be monitored and adjusted, but the extent of your childs pituitary deficiency will determine how often he will need to see his doctor.

Q: How safe is treatment?

A: While there are many potential side effects, researchers generally agree that hormone replacement therapy is safe and effective.

You and your family are key players in your childs medical care. Its important that you share your observations and ideas with your childs health care provider and that you understand your providers recommendations.

If your child is experiencing symptoms of hypopituitarism and youve set up an appointment, you probably already have some ideas and questions on your mind. But at the appointment, it can be easy to forget the questions you wanted to ask. Its often helpful to jot them down ahead of time so that you can leave the appointment feeling like you have the information you need.

If your child is old enough, you may want to suggest that she write down what she wants to ask her health care provider, too.

Some of the questions you may want to ask include:

Hypopituitarism Symptoms & Causes | Boston Children's Hospital

Recommendation and review posted by Bethany Smith

Thyroid Disorders | Hormone Health Network

The thyroid is a small butterfly-shaped gland inside the neck, located in front of the trachea (windpipe) and below the larynx (voicebox). It produces two thyroid hormonestriiodothyronine (T3) and thyroxine (T4)that travel through the blood to all tissues of the body.

Thyroid hormones regulate how the body breaks down food and either uses that energy immediately or stores it for the future. In other words, our thyroid hormones regulate our body's metabolism.

Another gland, called the pituitary gland, controls how well the thyroid works. The pituitary gland is located at the base of the brain and produces thyroid-stimulating hormone (TSH). The bloodstream carries TSH to the thyroid gland, where it tells the thyroid to produce more thyroid hormones, as needed.

Thyroid hormones influence virtually every organ system in the body. They tell organs how fast or slow they should work. Thyroid hormones also regulate the consumption of oxygen and the production of heat.

Endocrinologistsphysicians and scientists who study and care for patients with endocrine gland and hormone problemsstudy and treat several major disorders of the thyroid gland. The following is a list of some common thyroid disorders.

Too much thyroid hormone from an overactive thyroid gland is called hyperthyroidism, because it speeds up the body's metabolism. This hormone imbalance occurs in about 1 percent of all women, who get hyperthyroidism more often than men. One of the most common forms of hyperthyroidism is known as Graves' disease. This autoimmune disorder (when your bodys defense system attacks your own cells) tends to run in families. Because the thyroid gland is producing too much hormone in hyperthyroidism, the body develops an increased metabolic state, with many body systems developing abnormal function.

Too little thyroid hormone from an underactive thyroid gland is called hypothyroidism. In hypothyroidism, the body's metabolism is slowed. Several causes for this condition exist, most of which affect the thyroid gland directly, impairing its ability to make enough hormone. More rarely, there may be a pituitary gland tumor, which blocks the pituitary from producing TSH. Whether the problem is caused by the thyroid or by the pituitary gland, the result is that the thyroid is producing too few hormones, causing many physical and mental processes to become sluggish. The body consumes less oxygen and produces less body heat.

A thyroid nodule is a small lump in the thyroid gland. Thyroid nodules are common. These nodules can be either a growth of thyroid tissue or a fluid-filled cyst, which forms a lump in the thyroid gland. Almost half of the population will have tiny thyroid nodules at some point in their lives but, typically, these are not noticeable until they become large and affect normal thyroid size. About 5% of people develop large nodules, more than a half inch across (about 1 centimeter).

Although most nodules are not cancerous, people who have them should seek medical attention to rule out cancer. Also, some thyroid nodules may produce too much thyroid hormone and cause hyperthyroidism, or become too large, interfering with breathing or swallowing or causing neck discomfort.

Other thyroid problems include cancer, thyroiditis (swelling of the thyroid gland), or a goiter, which is an enlargement of the thyroid gland.

July 2018


Bryan Haugen, MD

Leonard Wartofsky, MD, MACP

Ramon Martinez, MD

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Thyroid Disorders | Hormone Health Network

Recommendation and review posted by Bethany Smith

Life Extension | SNC-Lavalin

CANDU reactors can operate economically and reliably for up to 60 years. After about 30 years of operation, reactor components are replaced and refurbished, extending the life of a reactor for another 30 years. This process is called life extension.

During life extension, the reactors pressure tubes, calandria tubes and end fitters are removed and replaced. Our experts have designed and delivered multi-tonne, remotely controlled tooling systems to accomplish this in a safe and effective manner. The outage also allows operators to refurbish other key reactor components, and make system upgrades.

All utilities that operate CANDU reactors are currently undergoing or will at some point consider life extension work on their reactors.

One of the worlds top-performing CANDU stations, the Darlington Nuclear Generating Station supplies 20% of Ontarios energy needs. Its refurbishment is crucial to deliver the power required to serve the provinces residents. Refurbishment operations began in the fall of 2016; it is the largest clean energy project in Canada.

This life extension project will allow Argentinas Embalse Nuclear Station to continue producing safe, reliable, low-carbon power for up to another 30 years. The Embalse CANDU 6 reactor began commercial operation in January 1984 and the single-unit has a gross output of 648 Mwe. The station shut down for this project in December 2015; the outage is expected to last until December 2017.

Bruce Power is Ontarios lowest cost source of nuclear, currently generating over 30% of the provinces electricity. Extending the operational life of the Bruce Power Units 3-8 will ensure long-term price stability. We are currently working with Bruce Power to solidify our scope for the Bruce Power major component replacement(MCR) project and look forward to concluding negotiations in late 2016.

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Life Extension | SNC-Lavalin

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