Orchid Blossoms on the 24th Floor in February
Every year or so, an orchid blossoms in the corner office of Target Health Inc. on the 24th Floor at 261 Madison. With the temperature in February reaching 60 degrees in NYC, maybe Biology is telling us something.
Orchid Blossoms on 24th Floor ©Target Health Inc.
For more information about Target Health contact Warren Pearlson (212-681-2100 ext. 165). For additional information about software tools for paperless clinical trials, please also feel free to contact Dr. Jules T. Mitchel or Ms. Joyce Hays. The Target Health software tools are designed to partner with both CROs and Sponsors. Please visit the Target Health Website.
Joyce Hays, Founder and Editor in Chief of On Target
Jules Mitchel, Editor
QUIZ – Gall Bladder
Source: From Wikimedia Commons, the free media repository
The gallbladder is a small pouch that sits just under the liver and stores bile produced by the 1) ___. After meals, the gallbladder is empty and flat, like a deflated balloon. Before a meal, the gallbladder may be full of bile and about the size of a small pear. In response to signals, the gallbladder squeezes stored 2) ___ into the small intestine through a series of tubes called ducts. Bile helps digest fats, but the gallbladder itself is not essential. Removing the gallbladder in an otherwise healthy individual typically causes no observable problems with health or digestion yet there may be a small risk of diarrhea and fat malabsorption. For unclear reasons, substances in bile can crystallize in the gallbladder, forming gallstones. Common and usually harmless, 3) ___ can sometimes cause pain, nausea, or inflammation. t’s not clear what causes gallstones to form. Doctors think gallstones may result when your bile contains too much cholesterol. Normally, bile contains enough chemicals to dissolve the cholesterol excreted by the liver. But if the liver excretes more cholesterol than the bile can dissolve, the excess cholesterol may form into crystals and eventually into stones. Too much bilirubin may be another cause of gallstones. Bilirubin is a chemical that’s produced when the body breaks down red blood cells. Certain conditions cause the liver to make too much bilirubin, including liver cirrhosis, biliary tract infections and certain blood disorders. The excess bilirubin contributes to gallstone formation. If the gallbladder doesn’t empty completely or often enough, bile may become very concentrated, contributing to the formation of gallstones.
Inflammation of the gallbladder is called cholecystitis, and is often due to a gallstone in the gallbladder. Cholecystitis causes severe pain and fever, and can require surgery when 4) ___ continues or recurs. Although rare, 5) ___ of the gallbladder can affect the gallbladder. It is difficult to diagnose and usually found at late stages when symptoms appear. Symptoms may resemble those of gallstones. An impacted gallstone can block the ducts that drain the pancreas. Inflammation of the pancreas, or pancreatitis, is the result, a serious condition. Abdominal ultrasound is a noninvasive diagnostic test in which a probe on the skin bounces high-frequency sound waves off structures in the belly. Abdominal 6) ___ is an excellent test for gallstones and to check the gallbladder wall. In a nuclear medicine test, called HIDA scan or cholescintigraphy, radioactive dye is injected 7) ___ intravenously and is secreted into the bile. Cholecystitis is likely if the scan shows bile doesn’t make it from the liver into the gallbladder.
Using a flexible tube inserted through the mouth, through the stomach, and into the small intestine, a doctor can see through the tube and inject dye into the bile system ducts. Tiny surgical tools can be used to treat some gallstone conditions during ERCP. ERCP stands for: Endoscopic Retrograde Cholangiopancreatography. Magnetic resonance cholangiopancreatography (MRCP) is also a good diagnostic tool: An MRI scanner provides high-resolution images of the bile ducts, pancreas, and gallbladder. MRCP images help guide further tests and treatments. Endoscopic ultrasound is another helpful diagnostic, in which a tiny ultrasound 8) ___ probe on the end of a flexible tube is inserted through the mouth to the intestines. Endoscopic ultrasound can help detect choledocholithiasis and gallstone pancreatitis. Although they may be used to look for other problems in the abdomen, X-rays generally cannot diagnose gallbladder disease. However, X-rays may be able to detect gallstones.
During gallbladder surgery (cholecystectomy), a surgeon removes the gallbladder, using either laparoscopy (several small cuts) or laparotomy (traditional “open“ surgery with a larger incision). Infection may be present during cholecystitis. Though antibiotics don’t typically cure cholecystitis, they can prevent an 9) ___infection from spreading. After surgery for gallbladder cancer, chemotherapy and radiation may be used to help prevent cancer from returning. An oral medication, ursodeoxycholic acid is for people with problems from gallstones who are not good candidates for 10) ___surgery, this oral medicine is an option. Ursodeoxycholic acid may help dissolve small cholesterol gallstones and reduce symptoms. Another oral solution is called Chenix.
In a procedure called, extracorporeal shock-wave lithotripsy: High-energy shockwaves are projected from a machine through the abdominal wall, breaking up gallstones. Lithotripsy works best if only a few small gallstones are present. In a procedure called, contact solvent dissolution: a needle is inserted through the skin into the gallbladder, and chemicals are injected that dissolve gallstones. This technique is rarely used.
Sources: WebMD.com; MayoClinic.org; Wikipedia
ANSWERS: 1) liver; 2) bile; 3) gallstones; 4) inflammation; 5) cancer; 6) ultrasound; 7) intravenously; 8) probe; 9) infection; 10) surgery
A Glimpse into the Disease and Trauma of Andy Warhol’s Life
Andy Warhol (1928-1987) in 1975. Source: Mondadori Publishers, gettyimages.co.uk, Public Domain, Wikimedia Commons
Retired Seattle surgeon and medical historian, John A. Ryan Jr. with his wife, Jody
Though Andy Warhol’s death has been associated with routine gallbladder surgery over the past three decades, one medical expert is saying that the legendary pop artist’s death shouldn’t be considered such a shock. “This was major, major surgery – not routine – in a very sick person,“ medical historian and retired surgeon Dr. John Ryan told The New York Times in a recent phone interview. Ryan, is the meritus chief of surgery at Virginia Mason Hospital in Seattle, Washington, and has been spending the past four years since his retirement studying Warhol’s medical history. Warhol’s family had a history of gallbladder issues, and Warhol himself had been very ill for at least a month before his death. However, his fear of hospitals combined with his hefty workload made him put his health on the back-burner.
In terms of Warhol’s early health: in third grade, he had Sydenham’s chorea (also known as St. Vitus’ Dance), the nervous system disease that causes involuntary movements of the extremities, which is believed to be a complication of scarlet fever which causes skin pigmentation blotchiness. Often bedridden as a child, he became an outcast at school and bonded with his mother. At times when he was confined to bed, he drew, listened to the radio and collected pictures of movie stars around his bed. Warhol later described this period as very important in the development of his personality, skill-set and preferences. After graduating from high school, his intentions were to study art education at the University of Pittsburgh in the hope of becoming an art teacher, but his plans changed and he enrolled in the Carnegie Institute of Technology in Pittsburgh, where he studied commercial art.
Warhol went in for a seemingly simple gallbladder operation in 1987 but ended up dying just 12 hours later – shocking the nation. But now, Dr. Ryan says we should have seen the icon’s death coming. According to Dr. Ryan, who presented his findings, last week at the annual meeting of the Pacific Coast Surgical Association, Warhol’s death should not have come as such a surprise. Looking at the pop artist’s medical history, Dr Ryan discovered that Warhol had almost 15 years of gallbladder trouble and a family history of it as well. Warhol’s father had his gallbladder removed in 1928, the same year his son was born. Warhol had been sick for at least a month before his death, although he had attempted to hide it. His fear of hospitals was another factor in his lack of receiving any serious treatment. The revered artist had a fear of hospitals which had delayed his ability to receive serious treatment. Further medical records research showed Dr Ryan that Warhol was dehydrated and gaunt from having barely eaten in the previous month. Additionally, Warhol had been taking speed daily for years. And he was still feeling the effects of a brush with death in 1968 after he was shot by Valerie Solanas, a radical feminist writer. At that time, he had been declared dead in the emergency room and had nine damaged organs – Warhol’s surgeon gave even odds on the artist lasting the night. His recovery left him with a lifetime of trouble with eating and swallowing, as well as a split in his abdominal muscles that gave him a large hernia. After he survived the gunshot wounds, for the rest of his life, Warhol had to wear a special truss or corset to hold his innards together.
So in 1987, on top of the gallbladder removal, and repair to his stomach wall, according to reports, the operation seemed to go well, and Warhol was in his room making calls that evening. A private nurse who went to check on him at 4am said he still seemed fine. But about two hours later, Warhol was found blue and unresponsive, and resuscitation efforts failed. An autopsy concluded that �ventricular fibrillation’ was the cause of death, meaning that Warhol’s heart had quivered and stopped. Stewart Redmond Walsh, a professor of vascular surgery at the National University of Ireland, Galway, has researched sudden death after surgery, and says it’s more common than we think. He explained that when a sick body goes through the trauma of a major surgery, the entire body feels the stress, not just the organ being operated on, which can be fatal. When Dr Ryan entered the data from Warhol’s case into the new Surgical Risk Calculator of the American College of Surgeons, it put such a patient’s chance of dying at 4.2 percent.
Andy Warhol suffered from many health problems throughout his life
Andy Warhol’s family suffered from a history of gallbladder illness. In 1928, his father Orenja, had his gallbladder removed. And less than 12 hours after a routine gallbladder removal, Warhol passed away from complications.
At the age of eight, Warhol came down with a rare disease known as chorea, or St. Vitus’ dance, characterized by involuntary movement, disturbed gait, grimacing, and hypotonia, or abnormally low muscle tone. Originally, Warhol was diagnosed with rheumatic fever. At the time, before antibiotics, approximately 10 percent of cases of rheumatic fever worsened and became chorea. Warhol stayed in bed for about ten weeks. When he finally returned to school, he had a relapse of the illness on the first day and returned to bed.
Blotchy skin is a common symptom of chorea. By the time Warhol became famous, in the early 1960s, the blotches had gone away, but they marked his face in adolescence and early adulthood, and he had bad skin his entire life. He wrote: �I had another skin problem, too – I lost all my pigment when I was eight years old. Another name people used to call me was “Spot“.
Warhol also had a huge drug problem. His New York City studio, the Factory was the hip hangout for amphetamine (speed) users. In particular, Warhol was addicted to Obetrol, marketed today as Adderall, a fairly common drug used to treat ADHD. He took a daily dose throughout his life.
In June 1968, he was shot at close range by Valerie Solanas, a radical feminist writer. For the rest of his life he wore a corset that held his bowels together where his ruined abdominal muscles could no longer.
He also worried about �catching’ cancer, his fluctuating weight, colds that he was convinced presaged pneumonia, about brain tumors and strokes, blood pressure and blackouts. In the last years of his life, Warhol worried most about AIDS, and carefully avoided those (even close friends or ex-lovers) whom he knew to be suffering from the �magic disease’.
Sources: NY Times, Wikipedia, DailyMail.uk.com;
Experimental PFSPZ Malaria Vaccine Provides Durable Protection Against Multiple Strains
Malaria is transmitted to humans through the bite of infected mosquitoes, which inject immature malaria parasites called sporozoites into a person’s bloodstream. The parasites travel to the liver, where they mature, multiply and spread via the bloodstream throughout the body causing malaria symptoms including chills, fever, headache, nausea, sweating and fatigue. According to the World Health Organization, 214 million people were infected with malaria globally in 2015 and 438,000 people died, mostly young African children. The species Plasmodium falciparum is the most common cause of malaria morbidity and mortality in Africa. In the United States, travel-related malaria is a concern for international tourists, aid workers and military personnel worldwide.
According to an article published in the Proceedings of the National Academy of Sciences (PNAS; 21 Feb 2017), an investigational malaria vaccine has protected a small number of healthy U.S. adults from infection with a malaria strain different from that contained in the vaccine. The National Institute of Allergy and Infectious Diseases (NIAID), part of the National Institutes of Health, sponsored and co-conducted the Phase 1 clinical trial.
The PfSPZ Vaccine used in this study was developed by Sanaria Inc., of Rockville, Maryland. The vaccine contains weakened P. falciparum sporozoites that do not cause infection but are able to generate a protective immune response against live malaria infection. Earlier research at the NIH Clinical Center with the PfSPZ Vaccine found it to be safe, well-tolerated and protective for more than a year when tested in healthy U.S. adults against a single Africa-derived malaria strain matched to the PfSPZ Vaccine. The study enrolled 31 healthy adults ages 18 to 45 years and each study subject was assigned to receive three doses of the PfSPZ Vaccine at eight-week intervals by rapid intravenous injection. Nineteen weeks after receiving the final dose of the test vaccine, participants who received the vaccine and a group of non-vaccinated volunteers were exposed in a controlled setting to bites from mosquitoes infected with the same strain of P. falciparum parasites (NF54, from Africa) that were used to manufacture PfSPZ Vaccine. Results showed that 9 of the 14 participants (64%) who received PfSPZ Vaccine demonstrated no evidence of malaria parasites, while all 6 of the non-vaccinated participants who were challenged at the same time had malaria parasites in their blood. Of the 9 participants who showed no evidence of malaria, six participants were again exposed in a controlled setting to mosquito bites, this time from mosquitoes infected with a different strain of P. falciparum parasite, 33 weeks after the final immunization. In this group, 5 of the 6 participants (83%) were protected against malaria infection, while again, none of the 6 participants who did not receive the vaccine and were challenged were protected. All participants who became infected with malaria immediately received medical treatment.
The authors also found that the PfSPZ Vaccine activated T cells, a key component of the body’s defenses against malaria, and induced antibody responses in all vaccine recipients. Vaccine-specific T-cell responses were comparable when measured against both of the malaria challenge strains, providing some insights into how the vaccine was mediating protection.
Ongoing research will determine whether protective efficacy can be improved by changes to the PfSPZ Vaccine dose and number of immunizations. Accordingly, a Phase 2 efficacy trial testing three different dosages in a three-dose vaccine regimen is now underway in 5-to 12-month-old infants in Western Kenya to assess safety and efficacy against natural infection.
Sanaria Inc., designed, manufactured, and provided PfSPZ Vaccine and the heterologous challenge mosquitoes. NIAID supported the development of the experimental vaccine through several Small Business Innovation Research grants.
Survival Rate May Be Improving for Extremely Preterm Infants
Data reported during the past 5 years indicate that rates of survival have increased among infants born at the borderline of viability, but less is known about how increased rates of survival among these infants relate to early childhood neurodevelopmental outcomes. A study appearing in the New England Journal of Medicine (2017; 376:617-628) has shown that very early preterm infants are more likely to survive than in previous years, and the survivors are less likely to have neurological problems. The study found that of the more than 4,000 infants born at 11 sites within the network from 2000 to 2011, survival rates increased from 30% to 36%, and the proportion of survivors who did not have a neurological or developmental impairment increased from 16% to 20%. The authors theorize that these improvements are a result of advances in the care provided to expectant mothers and their newborns.
Infants in the study were born between the 22nd and 24th week of pregnancy, far earlier than the 40 weeks generally expected for a pregnancy to reach term. Those born from 2008 to 2011 had the lowest death rate (64%). From 2004 to 2007, the death rate was 70%, unchanged from 2000 to 2003.
According to the authors, the results encompass trends for a large number of infants at multiple research sites, but they should not be used to predict the outcome for an individual child. In addition, providing care to infants born so early is often challenging. Physicians and family members can be reluctant to expose an infant to sometimes painful life-support procedures. Those offered active treatment may survive, but may have hearing loss, blindness, cerebral palsy, and severe intellectual disability. The authors added that in the past, many experts had feared that advances leading to improvements in survival among extremely preterm infants might also result in a higher proportion of infants with disabilities. However, in the current study, it was found that across all three time intervals, the percentage of infants who survived with a disability did not change significantly. Finally, the authors wrote that the increases in overall survival and survival without neurological harm likely result from improvements in the care given to mothers and newborns. One potential contributing factor is the wider use of antenatal steroids. These drugs, which are given to women at risk for preterm birth, help the infant’s lungs mature, leaving the infant less reliant on ventilation therapy, which can sometimes damage the lungs and lead to infections.
FDA Clears Test To Identify Organisms that Cause Bloodstream Infections and Provide Antibiotic Sensitivity Results
Bacterial or yeast blood infections can occur in patients of all ages, but are particularly severe in infants, the elderly and those with weakened immune systems. If not treated rapidly, such bloodstream infections can lead to severe complications, such as septic shock and death.
The FDA has marketing clearance of the PhenoTest BC Kit, performed on the Pheno System. This is the first test to identify organisms that cause bloodstream infections and provide information about which antibiotics the organism is likely to respond to (antibiotic sensitivity). The test also reduces the amount of time it takes to provide this important information, which can guide antibiotic treatment recommendations more quickly. Unlike traditional identification and antibiotic susceptibility tests that may take 24 to 48 hours after detection in a positive blood culture to provide test results, the PhenoTest BC Kit can identify bacteria or yeast from a positive blood culture in approximately 1.5 hours. For certain organisms, the test also provides important information to guide treatment recommendations in approximately 6.5 hours after the organisms are detected from blood cultures.
The test can identify 14 different species of bacteria and two species of yeast that cause bloodstream infections, while also providing antibiotic sensitivity information on 18 selected antibiotics for a subset of the identified organisms as appropriate. The test can also identify the presence of two indicators of antibiotic resistance, which can occur when potentially harmful bacteria change in a way that reduces or eliminates the effectiveness of antibiotics.
The PhenoTest BC Kit works by measuring the similarity of the infection-causing organism’s genetic material to DNA known to be unique to specific bacteria or yeast. Once the organism is identified, it is mixed with antibiotics and the growth of the bacteria is measured by time-lapse images. If the organism does not grow when the antibiotic is present, this means that an antibiotic can possibly be used for treatment. The FDA reviewed the data for the PhenoTest BC Kit through the de novo premarket review pathway, a regulatory pathway for devices of a new type with low-to-moderate-risk that are not substantially equivalent to an already legally marketed device and for which special controls can be developed, in addition to general controls, to provide a reasonable assurance of safety and effectiveness of the devices. The FDA’s decision to allow marketing was based largely on its review of the sponsor’s primary clinical study of 1,850 positive blood cultures. In this study, the PhenoTest BC Kit provided correct identification of the bacteria or yeast in the positive blood culture more than 95% of the time. Results for testing whether the bacteria were sensitive to antibiotics were also accurate when compared to traditional tests.
Risks associated with use of the PhenoTest BC Kit include false positive findings, which can occur when an individual not infected with organisms that cause bloodstream infections receives a test result that incorrectly indicates that he or she is infected. Results obtained from the test should always be interpreted alongside additional laboratory test results. The PhenoTest BC Kit and the Pheno System are manufactured by Accelerate Diagnostics Inc. in Tucson, Arizona.
Kale and Pecorino Salad with Walnuts & Sherry-Soaked Raisins
I am always thinking about kale because our family is focused on health, although we sometimes break away for something sweet. Kale is one of those super healthy foods so I have experimented with many combos of ingredients with kale. © Joyce Hays, Target Health Inc.
1 cup walnut halves and/or pieces, toasted
1/2 cup golden raisins
2 Tablespoons white wine vinegar or champagne vinegar
1 Tablespoon creme sherry
1 Tablespoon water
1/2 cup Panko crumbs
2 or more (optional) cloves garlic, pressed
Pinch kosher salt (optional)
Pinch black pepper
Pinch chili flakes
1 teaspoon curry powder
4 Tablespoons olive oil
1 bunch Tuscan kale washed and patted dry
2 oz. or 1/2 cup pecorino cheese, grated or ground in a food processor
Zest of 1/2 lemon
Juice of 1/2 lemon
Prepare the walnuts:
Heat oven to 350 degrees. Toast walnuts on a baking sheet for 10 minutes, tossing once. Let cool and coarsely chop.
Prepare the raisins:
In a small saucepan over low heat, simmer champagne vinegar, water, creme sherry and raisins for 5 minutes, until plump and soft. Set aside in liquid, for as long as you can. (Keep in the liquid)
Prepare the crumbs:
Toast panko, garlic, curry powder, pinches, pepper, chili flakes and 2 teaspoons of the olive oil in a skillet together with a pinch of salt until golden. Set aside.
Prepare the kale:
1. Trim heavy stems off kale and remove ribs. Stack sections of leaves and roll them into a tube, then cut them into very thin ribbons crosswise.
2. Put kale in a large salad bowl. Add the pecorino, walnuts and raisins (leaving any leftover vinegar mixture in dish), remaining 2 Tablespoons olive oil and lemon juice and toss until all the kale ribbons are coated. Taste and adjust seasonings with salt, pepper and some of the reserved vinegar mixture from the raisins, if needed. Let sit for 10 minutes before serving, if you can. This enables all of the lovely flavors to merge.
3. Add the Panko crumbs, just before you serve the salad, and toss it one more time.
We started with chilled Orvieto, warm Italian bread, olive oil & butter and an antipasto.
Next the kale salad with fresh halibut dipped in egg then panko (mixed with curry and parmesan), and quickly cooked in a small amount of olive oil. For dessert we had spears of fresh mango which we have been eating all week.
This weekend we went to MetOpera and saw, Rusalka an opera by Antonin Dvorak. We love Dvorak, so were looking forward to this. The role of Rusalka was sung by the Latvian soprano, Kristine Opolais; the role of the Prince was sung by (beautiful) tenor, Brandon Jovanovich from Montana.
Below are my two favorite Dvorak compositions; the first is the hauntingly gorgeous First Act aria, Song to the Moon from Rusalka; the second is his magnificent, String Quartet #12 (American). I’m including one other video, which is a cello rendition of Song to the Moon The cellist is the young, Stjepan Hauser, from Croatia.
A glass of icy Proseco. Joyce Hays, Target Health Inc.