Science Weekly: Philosopher AC Grayling defends human free will

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Philosopher AC Grayling discusses free will, the LHC, those climate change emails and the meaning of ‘identity’

Science Weekly Extra: EO Wilson on biodiversity

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Professor EO Wilson warns that the crisis in biodiversity has been pushed from centre stage by the climate change debate

Target Health Closed Between December 25 and January 3

Continuing our tradition of giving our loyal and dedicated staff more time with their families over the holiday season, Target Health will again be closed between December 25, 2009 and January 1, 2010, with all back to work on January 4, 2010.  Since we always have ongoing business, even during holidays all key employees will be available via email or cell phone for all urgent matters. The EDC Help Desk will still be operating 24/7.

For more information about Target Health and our software tools for paperless clinical trials, please contact Dr. Jules T. Mitchel (212-681-2100 ext 0) or Ms. Joyce Hays. Target Health’s software tools are designed to partner with both CROs and Sponsors. Please visit the Target Health Website at: www.targethealth.com

Taste Develops in Utero

Most of us assume that the womb is like Grandma’s off-limits closet: dark and mysterious. But the truth is that there is some connection to the outside 1) ___ while a baby is in utero, and that many people develop preferences based on experiences during those 9 months. Here’s what developed when you first started to smell and 2) ___. Scientists used to believe that fetuses had no sense of 3) ___. We now know that, before birth, amniotic fluid moves through the nasal and oral cavities, and that develops sense of smell — an ability that starts at about 30 weeks. Taste buds start to develop in utero by week 8, and they begin communicating with the 4) ___ about 5 weeks later. Located around the perimeter of the tongue, each of the 4,500 taste buds has about 40 receptor cells, which bind with food and send information to the brain. A 5) ___ can taste some flavors by 8 weeks, and by 15 to 17 weeks, the amniotic fluid can taste of curry, cumin, onion, or other foods from the mother’s diet. The taste of the 6) ___ ___ changes all the time, depending on what mother is eating, which may strongly influence what the baby will prefer later in life. Abstracted from Mehmet Oz, MD and, Michael Roizen, MD

ANSWERS: 1) world; 2) taste; 3) smell; 4) brain; 5) fetus; 6) amniotic fluid 

Diabetes

Ancient Hindu writings, many thousands of years old, document how black ants and flies were attracted to the urine of diabetics. The Indian physician Sushruta in 400 BCE described the sweet taste of urine from affected individuals, and for many centuries to come, the sweet taste of urine was key to the diagnosis of diabetes. Around 250 BCE, the name “diabetes” was first used. It is a Greek word that means “to syphon”, reflecting how diabetes seemed to rapidly drain fluid from the affected individual. The Greek physician Aretaeus noted that as affected individuals wasted away, they passed increasing amounts of urine as if there was “liquefaction of flesh and bones into urine”. The complete term “diabetes mellitus” was coined in 1674 by Thomas Willis, personal physician to King Charles II. Mellitus is Latin for honey, which is how Willis described the urine of diabetics (“as if imbued with honey and sugar”). Up until the mid-1800s, the treatments offered for diabetes varied tremendously. Various “fad” diets were prescribed, and the use of opium was suggested, as were bleeding and other therapies. The most successful treatments were starvation diets in which calorie intake was severely restricted. Naturally, this was intolerable for the patient and at best extended life expectancy for a few years. A breakthrough in the puzzle of diabetes came in 1889 when German physicians Joseph von Mering and Oskar Minkowski surgically removed the pancreas from dogs. The dogs immediately developed diabetes. As the link was established between the pancreas gland and diabetes, research focused on isolating the pancreatic extract that could treat diabetes. When Dr. Frederick Banting took up the challenge of isolating a pancreatic extract, he was met with much skepticism. But Banting, a surgeon, persisted and in May 1921, he began work in the laboratory of Professor John Macloed in Toronto, Canada. Charles Best, a medical student at the time, worked as his assistant. To concentrate what we now know as insulin, Banting tied the pancreatic ducts of dogs. The pancreatic cells that released digestive enzymes (and could also destroy insulin) degenerated, but the cells that secreted insulin were spared. Over several weeks the pancreas degenerated into a residue from which insulin could be extracted. In July 1921, a dog that had had its pancreas surgically removed was injected with an extract collected from a duct-tied dog. In the two hours that followed the injection, the blood sugar level of the dog fell, and its condition improved. Another de-pancreatized (diabetic-like) dog was kept alive for eight days by regular injections until supplies of the extract, at that time called “isletin”, were exhausted. Further experiments on dogs showed that extracts from the pancreas caused a drop in blood sugar, caused glucose in the urine to disappear, and produced a marked improvement in clinical condition. So long as the extract was being given, the dogs were kept alive. The supply of the extract was improved: the pancreas of different animals were used until that of the cow was settled upon. This extract kept a de-pancreatized dog alive for 70 days. Dr. James B. Collip, a biochemist, was drafted to continue improving the purity of the pancreas extract, and later, Best carried on this work. A young boy, Leonard Thompson, was the first patient to receive insulin treatment. On January 11, 1922, aged 14 and weighing only 64 pounds, he was extremely ill. The first injections of insulin only produced a slight lowering of blood sugar level. The extract still was not pure enough, and abscesses developed at the injection site. Collip continued to refine the extract. Several weeks later, Leonard was treated again and showed a remarkable recovery. His blood sugar levels fell, he gained weight and lived for another 13 years. He died from pneumonia at the age of 27. During the spring of 1922, Best increased the production of insulin to enable the treatment of diabetic patients coming to the Toronto clinic. Over the next 60 years, insulin was further refined and purified, and long-acting and intermediate types were developed to provide more flexibility. A revolution came with the production of recombinant human DNA insulin in 1978. Instead of collecting insulin from animals, new human insulin could be synthesized. In 1923, Banting and Macloed were awarded the Nobel Prize for the discovery of insulin. Banting split his prize with Best, and Macloed split his prize with Collip. In his Nobel Lecture, Banting concluded the following about their discovery: “Insulin is not a cure for diabetes; it is a treatment. It enables the diabetic to burn sufficient carbohydrates, so that proteins and fats may be added to the diet in sufficient quantities to provide energy for the economic burdens of life.”

Novel Antibody Associated with Autoimmune Pancreatitis

Autoimmune pancreatitis is characterized by an inflammatory process that leads to organ dysfunction. The cause of the disease is unknown, and while its autoimmune origin has been suggested it has never been proved. In addition, little is known about the pathogenesis of this condition. As a result, a study published in the New England Journal of Medicine (2009;361:2135-2142), was performed to identify pathogenetically relevant autoantigen targets from a random peptide library with pooled IgG obtained from 20 patients with autoimmune pancreatitis. Results showed that peptide-specific antibodies were detected in serum specimens obtained from the patients. Among the detected peptides, peptide AIP1-7 was recognized by the serum specimens from 18 of 20 patients with autoimmune pancreatitis and by serum specimens from 4 of 40 patients with pancreatic cancer, but not by serum specimens from healthy controls. The peptide showed homology with an amino acid sequence of plasminogen-binding protein (PBP) of Helicobacter pylori and with ubiquitin-protein ligase E3 component n-recognin 2 (UBR2), an enzyme highly expressed in acinar cells of the pancreas. Antibodies against the PBP peptide were detected in 19 of 20 patients with autoimmune pancreatitis (95%) and in 4 of 40 patients with pancreatic cancer (10%). Such reactivity was not detected in patients with alcohol-induced chronic pancreatitis or intraductal papillary mucinous neoplasm. The results were validated in another series of patients with autoimmune pancreatitis or pancreatic cancer: 14 of 15 patients with autoimmune pancreatitis (93%) and 1 of 70 patients with pancreatic cancer (1%) had a positive test for anti-PBP peptide antibodies. When the training and validation groups were combined, the test was positive in 33 of 35 patients with autoimmune pancreatitis (94%) and in 5 of 110 patients with pancreatic cancer (5%).

Can Association Between Preterm Birth and Autism be Explained by Maternal or Neonatal Morbidity?

A study reported in Pediatrics (2009;124: e817-e825) was performed to examine whether an association between preterm birth and risk of autistic disorders could be explained by pregnancy complications or neonatal morbidity. This Swedish, population-based, case-control study included 1,216 case subjects with autistic disorders who were born between 1987 and 2002 and 6,080 control subjects who were matched with respect to gender, birth year, and birth hospital. Associations were assessed between gestational age and autistic disorders and adjusted for maternal, birth, and neonatal characteristics. Conditional logistic regression was used to estimate odds ratios (ORs) and 95% confidence intervals (CIs). Results showed that compared with infants born at term, the unadjusted ORs for autistic disorders among very and moderately preterm infants were 2.05 and 1.55, respectively. When maternal, pregnancy and birth characteristics were controlled for, ORs were reduced to 1.48 and 1.33, respectively. When neonatal complications were controlled for, ORs were 0.98 and 1.25, respectively. Reductions in risks of autistic disorders related to preterm birth were primarily attributable to preeclampsia, small-for-gestational age birth, congenital malformations, low Apgar scores at 5 minutes, and intracranial bleeding, cerebral edema, or seizures in the neonatal period. Neonatal hypoglycemia, respiratory distress, and neonatal jaundice were associated with increased risk of autistic disorders for term but not preterm infants. According to the authors, the increased risk of autistic disorders related to preterm birth is mediated primarily by prenatal and neonatal complications that occur more commonly among preterm infants.

Complete Local Elimination of Infectious Trachoma from Severely Affected Communities after Six Biannual Mass Azithromycin Distributions

Trachoma is the result of infection of the eye with Chlamydia trachomatis. Infection spreads from person to person, and is frequently passed from child to child and from child to mother, especially where there are shortages of water, numerous flies, and crowded living conditions. Infection often begins during infancy or childhood and can become chronic. If left untreated, the infection eventually causes the eyelid to turn inwards, which in turn causes the eyelashes to rub on the eyeball, resulting in intense pain and scarring of the front of the eye. This ultimately leads to irreversible blindness, typically between 30 and 40 years of age. A study published in the journal Ophthalmology (2009; 116:2047-2050), was performed to determine whether infectious trachoma can be completely eliminated from severely affected villages by treatment with azithromycin. The study was a cross-sectional survey of 2 villages in Ethiopia previously enrolled and monitored over 42 months as part of a larger, group-randomized clinical trial. A total of 758 individuals were evaluated who resided in 2 villages with high baseline trachoma prevalence, of a total population of 768 (98.7%). For the study, all members of the 2 villages were offered 6 biannual mass treatments with oral azithromycin. At 42 months, each current village member was examined. The right upper tarsal conjunctiva was everted and swabbed. Samples were processed for evidence of Chlamydia trachomatis RNA. The main outcome measure was clinical activity by World Health Organization simplified grading scale for trachoma and laboratory evidence of chlamydial RNA. Results showed that average antibiotic coverage over the study period was 90% and 94% in the 2 villages. Clinical trachoma activity in children aged 1 to 5 years decreased from 78% and 83% in the 2 villages before treatment to 17% and 24% at 42 months. Polymerase chain reaction (PCR) evidence of infection in the same age group decreased from 48% to 0% in both villages at 42 months. When all age groups were examined, there were zero cases with evidence of chlamydial RNA among 758 total villagers tested. According to the authors, biannual mass distribution of azithromycin can locally eliminate ocular chlamydial infection from severely affected communities.

TARGET HEALTH excels in Regulatory Affairs and works closely with many of its clients performing all FDA submissions. TARGET HEALTH receives daily updates of new developments at FDA. Each week, highlights of what is going on at FDA are shared to assure that new information is expeditiously made available.

Medical Food

The term medical food, as defined in section 5(b) of the Orphan Drug Act (21 U.S.C. 360ee (b) (3)) is “a food which is formulated to be consumed or administered enterally under the supervision of a physician and which is intended for the specific dietary management of a disease or condition for which distinctive nutritional requirements, based on recognized scientific principles, are established by medical evaluation.” The FDA advises that it considers the statutory definition of medical foods to narrowly constrain the types of products that fit within this category of food (see Food Labeling; Reference Daily Intakes and Daily Reference Values; Mandatory Status of Nutrition Labeling and Nutrition Content Revision proposed rule (56 FR 60366 at 60377, November 27, 1991)).

Medical foods are distinguished from the broader category of foods for special dietary use and from foods that make health claims by the requirement that medical foods be intended to meet distinctive nutritional requirements of a disease or condition, used under medical supervision and intended for the specific dietary management of a disease or condition. The term “medical foods” does not pertain to all foods fed to sick patients. Medical foods are foods that are specially formulated and processed (as opposed to a naturally occurring foodstuff used in a natural state) for the patient who is seriously ill or who requires the product as a major treatment modality. In general, to be considered a medical food, a product must, at a minimum, meet the following criteria:

  1. the product must be a food for oral or tube feeding;
  2. the product must be labeled for the dietary management of a specific medical disorder, disease, or condition for which there are distinctive nutritional requirements;
  3. the product must be intended to be used under medical supervision 

The following criteria that clarify the statutory definition of a medical food can be found in the agency’s regulations at 21 CFR 101.9(j) (8). A food is a medical food exempt from nutrition labeling only if:

  1. It is a specially formulated and processed product (as opposed to a naturally occurring foodstuff used in its natural state) for the partial or exclusive feeding of a patient by means of oral intake or enteral feeding by tube;
  2. It is intended for the dietary management of a patient who, because of therapeutic or chronic medical needs, has limited or impaired capacity to ingest, digest, absorb, or metabolize ordinary foodstuffs or certain nutrients, or who has other special medically determined nutrient requirements, the dietary management of which cannot be achieved by the modification of the normal diet alone;
  3. It provides nutritional support specifically modified for the management of the unique nutrient needs that result from the specific disease or condition, as determined by medical evaluation;
  4. It is intended to be used under medical supervision; and
  5. It is intended only for a patient receiving active and ongoing medical supervision wherein the patient requires medical care on a recurring basis for, among other things, instructions on the use of the medical food.

 

Examples of Medical Foods include:

Folgard RX 2.2®: This medical food is indicated for the management of elevated homocysteine, or hyperhomocysteinemia, associated with cardiovascular disease, stroke, and other diseases. Folgard is a formula containing folic acid, vitamin B6 and vitamin B12, designed to lower plasma homocysteine levels.

LimbrelTM: This medical food is used in the nutritional management of metabolic processes associated with osteoarthritis. Damaged joints release excess phospholipids, which increase the production of prostaglandins and leukotrienes, leading to an inflammatory response. Limbrel is formulated with naturally occurring ingredients that inhibit the two enzymes lipoxygenase and cycloxygenase responsible for the production of inflammatory irritants.

 

For more information about our expertise in Regulatory Affairs, please contact Dr. Jules T. Mitchel or Dr. Glen Park.