Jules Mitchel Receives Red Jacket Award and Time For a Vacation

 

To our loyal readers, friends and colleagues: We are taking time off from the last half of August and the first half of September. See you in September. We started ON TARGET in 1994, first sending the newsletter out by fax. Our weekly newsletter is now being shared with over 6,000 readers each week.

 

For more than a dozen years, PharmaVOICE magazine has been recognizing the most inspirational, motivational, and transformative individuals throughout the life-sciences industry in its annual July/August PharmaVOICE 100 issue. These individuals illustrate what it means to think bigger, do more, and lead with passion and integrity. This year’s distinguished honorees were nominated by thousands of PharmaVOICE readers and were selected for inclusion based on substantive accounts describing how they have inspired or motivated their colleagues, peers, and even competitors; their positive impact on patients, their organizations, and the industry at large; their innovative and game-changing strategies and thinking; their mentorship and guidance to the next generation of leaders; as well as their willingness to give their time and resources to their communities and philanthropic causes. The PharmaVOICE 100 is the premier awards program whose honorees represent a broad cross section of the global life-sciences industry, including the pharmaceutical, biopharmaceutical, biotechnology, contract research, clinical trial, research and development, patient education, advertising, digital, marketing, technology, academia, as well as multiple other sectors. This diverse group of individuals is also unique in that they represent a wide variety of functional areas – ranging from the clinic to the C-suite.

 

Please join the Celebration on September 14 in New York City, where PharmaVoice will be recognizing this year’s honorees as well as PharmaVOICE 100 honorees throughout the years. This is the one event designed to encourage collaboration and networking among a diverse and executive leadership audience. For more details about the third annual PharmaVOICE 100 Celebration, please go to: http://www.pharmavoice.com/pv100-celebration.

 

One of the criteria for being named a Red Jacket is having been recognized previously as a PharmaVOICE 100 honoree, but it’s much more than that. These individuals, who cross a multitude of industry sectors, have raised the bar in terms of what it means to be an inspired leader for their teams, their companies, their communities, and for the industry at large.

 

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. 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

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D N A

DNA is a double helix formed by base pairs attached to a sugar-phosphate backbone.

 

People have known for many years that living things inherit traits from their 1) ___. That common-sense observation led to agriculture, centuries ago, the purposeful breeding and cultivation of animals and plants for desirable characteristics. Firming up the details took quite some time, though. Researchers did not understand exactly how traits were passed to the next 2) ___ until the middle of the 20th century. Now it is clear that genes are what carry our traits through generations and that genes are made of deoxyribonucleic acid (DNA). But genes themselves don’t do the actual work. Rather, they serve as instruction books for making functional molecules such as RNA 3) ___ ___ and proteins, which perform the chemical reactions in our bodies. Occasionally, there is a kind of typographical error in a 4) ___ DNA sequence. This mistake – which can be a change, gap or duplication – is called a mutation. A mutation can cause a gene to encode a protein that works incorrectly or that doesn’t work at all. Sometimes, the error means that no protein is made. Not all DNA changes are harmful. Some mutations have no effect, and others produce new versions of proteins that may give a survival advantage to the organisms that have them. Over time, 5) ___ supply the raw material from which new life forms evolve.

 

Our modern understanding of DNA’s role in heredity has led to a variety of practical applications, including forensic analysis, paternity testing, and genetic screening. Thanks to these wide-ranging uses, today many people have at least a basic awareness of DNA. All living things are made of cells. The 6) ___ in the human body have 23 pairs of chromosomes, which are made of DNA, and which reveal a lot about each individual.

DNA, or deoxyribonucleic acid, is the hereditary material in humans and almost all other organisms. Nearly every cell in a person’s body has the same DNA. Most DNA is located in the cell nucleus (where it is called nuclear DNA), but a small amount of DNA can also be found in the mitochondria (where it is called mitochondrial DNA or mtDNA). The information in DNA is stored as a code made up of four chemical bases: adenine (A), guanine (G), cytosine (C), and thymine (T). Human DNA consists of about 3 billion bases, and more than 99 percent of those bases are the same in all people. The order, or 7) ___, of these bases determines the information available for building and maintaining an organism, similar to the way in which letters of the alphabet appear in a certain order to form words and sentences. DNA bases pair up with each other, A with T and C with G, to form units called base pairs. Each base is also attached to a sugar molecule and a phosphate molecule. Together, a base, sugar, and phosphate are called a nucleotide. Nucleotides are arranged in two long strands that form a spiral called a double helix. The structure of the double 8) ___ is somewhat like a ladder, with the base pairs forming the ladder’s rungs and the sugar and phosphate molecules forming the vertical sidepieces of the ladder.

 

An important property of DNA is that it can replicate, or make copies of itself. Each strand of DNA in the double helix can serve as a pattern for duplicating the sequence of bases. This is critical when cells divide because each new cell needs to have an exact copy of the DNA present in the old cell. It may be surprising, then, to realize that less than a century ago, even the best-educated members of the scientific community did not know that DNA was the hereditary material! The work of Gregor Mendel showed that traits (such as flower colors in pea plants) were not inherited directly, but rather, were specified by genes passed on from parents to 9) ___. The work of additional scientists around the turn of the 20th century, including Theodor Boveri, Walter Sutton, and Thomas Hunt Morgan, established that Mendel’s heritable factors were most likely carried on chromosomes. Scientists first thought that proteins, which are found in chromosomes along with DNA, would turn out to be the sought-after genetic material. Proteins were known to have diverse amino acid sequences, while DNA was thought to be simply a repetitive polymer, due in part to an incorrect (but popular) model of its structure and composition. Today, we know that DNA is not actually repetitive and can carry large amounts of information, and that DNA itself is the actual 10) ___ material

 

Punnett Square animation, explaining basic genetic inheritance

 

Test your DNA

 

The 23andMe PGS test uses qualitative genotyping to detect clinically relevant variants in the genomic DNA of adults from saliva collected using an FDA-cleared collection device

Sources: https://ghr.nlm.nih.gov/primer/basics/dna; KhanAcademy.com; Wikipedia

 

ANSWERS: 1) parents; 2) generation; 3) ribonucleic acid; 4) gene’s; 5) mutations; 6) cells; 7) sequence; 8) helix; 9) offspring; 10) genetic

Gregor Mendel (1822-1884)

This photo is from a book published in 1913 by R.C. Punnett, of Punnett Square fame, on Mendelism. Private Collection, Jules T. Mitchel. ©Target Health Inc.

 

 

Gregor Johann Mendel was a scientist, Augustinian friar and abbot of St. Thomas’ Abbey in Brno, Margraviate of Moravia. He was born in a German-speaking family in the Silesian part of the Austrian Empire (today’s Czech Republic) and gained posthumous recognition as the founder of the modern science of genetics. Though farmers had known for millennia that crossbreeding of animals and plants could favor certain desirable traits, Mendel’s pea plant experiments conducted between 1856 and 1863 established many of the rules of heredity, now referred to as the laws of Mendelian inheritance.

 

Mendel worked with seven characteristics of pea plants: plant height, pod shape and color, seed shape and color, and flower position and color. Taking seed color as an example, Mendel showed that when a true-breeding yellow pea and a true-breeding green pea were cross-bred their offspring always produced yellow seeds. However, in the next generation, the green peas reappeared at a ratio of 1 green to 3 yellow. To explain this phenomenon, Mendel coined the terms “recessive“ and “dominant“ in reference to certain traits. (In the preceding example, the green trait, which seems to have vanished in the first filial generation, is recessive and the yellow is dominant.) He published his work in 1866, demonstrating the actions of invisible “factors“ – now called genes – in predictably determining the traits of an organism. The profound significance of Mendel’s work was not recognized until the turn of the 20th century (more than three decades later) with the rediscovery of his laws. Erich von Tschermak, Hugo de Vries, Carl Correns, and William Jasper Spillman independently verified several of Mendel’s experimental findings, ushering in the modern age of genetics.

 

Mendel was the son of Anton and Rosine (Schwirtlich) Mendel, and had one older sister, Veronika, and one younger, Theresia. They lived and worked on a farm which had been owned by the Mendel family for at least 130 years. During his childhood, Mendel worked as a gardener and studied beekeeping. Later, as a young man, he attended gymnasium in Opava (called Troppau in German). He had to take four months off during his gymnasium studies due to illness. From 1840 to 1843, he studied practical and theoretical philosophy and physics at the Philosophical Institute of the University of Olomouc, taking another year off because of illness. He also struggled financially to pay for his studies, and Theresia gave him her dowry. Later he helped support her three sons, two of whom became doctors. He became a friar in part because it enabled him to obtain an education without having to pay for it himself. As the son of a struggling farmer, the monastic life, in his words, spared him the “perpetual anxiety about a means of livelihood.“

 

When Mendel entered the Faculty of Philosophy, the Department of Natural History and Agriculture was headed by Johann Karl Nestler who conducted extensive research of hereditary traits of plants and animals, especially sheep. Upon recommendation of his physics teacher Friedrich Franz, Mendel entered the Augustinian St Thomas’s Abbey in Brno (called Brunn in German) and began his training as a priest. Born Johann Mendel, he took the name Gregor upon entering religious life. Mendel worked as a substitute high school teacher. In 1850, he failed the oral part, the last of three parts, of his exams to become a certified high school teacher. In 1851, he was sent to the University of Vienna to study under the sponsorship of Abbot C. F. Napp so that he could get more formal education. At Vienna, his professor of physics was Christian Doppler. Mendel returned to his abbey in 1853 as a teacher, principally of physics. In 1856, he took the exam to become a certified teacher and again failed the oral part. In 1867, he replaced Napp as abbot of the monastery. After he was elevated as abbot in 1868, his scientific work largely ended, as Mendel became overburdened with administrative responsibilities, especially a dispute with the civil government over its attempt to impose special taxes on religious institutions. Mendel died on 6 January 1884, at the age of 61, in Brno, Moravia, Austria-Hungary (now Czech Republic), from chronic nephritis. Czech composer Leo? Jan?cek played the organ at his funeral. After his death, the succeeding abbot burned all papers in Mendel’s collection, to mark an end to the disputes over taxation.

 

Gregor Mendel, who is known as the “father of modern genetics“, was inspired by both his professors at the Palacky University, Olomouc (Friedrich Franz and Johann Karl Nestler), and his colleagues at the monastery (such as Franz Diebl) to study variation in plants. In 1854, Napp authorized Mendel to carry out a study in the monastery’s 2 hectares (4.9 acres) experimental garden, which was originally planted by Napp in 1830. Unlike Nestler, who studied hereditary traits in sheep, Mendel focused on plants. Mendel carried out his experiments with the common edible pea in his small garden plot in the monastery. These experiments were begun in 1856 and completed some eight years later. In 1865, he described his experiments in two lectures at a regional scientific conference. In the first lecture he described his observations and experimental results. In the second, which was given one month later, he explained them. After initial experiments with pea plants, Mendel settled on studying seven traits that seemed to be inherited independent of other traits: seed shape, flower color, seed coat tint, pod shape, unripe pod color, flower location, and plant height. He first focused on seed shape, which was either angular or round. Between 1856 and 1863 Mendel cultivated and tested some 28,000 plants, the majority of which were pea plants (Pisum sativum). This study showed that, when true-breeding different varieties were crossed to each other (e.g., tall plants fertilized by short plants), one in four pea plants had purebred recessive traits, two out of four were hybrids, and one out of four were purebred dominant. His experiments led him to make two generalizations, the Law of Segregation and the Law of Independent Assortment, which later came to be known as Mendel’s Laws of Inheritance.

 

A specific illustration: Crossing tall and short plants clarifies some of Mendel’s key observations and deductions.

 

At the time, gardeners could obtain true-breeding pea varieties from commercial seed houses. For example, one variety was guaranteed to give only tall pea plants (2 meters or so); another, only short plants (about 1/3 of a meter in height). If a gardener crossed one tall plant to itself or to another tall plant, collected the resultant seeds some three months later, planted them, and observed the height of the progeny, he would observe that all would be tall. Likewise, only short plants would result from a cross between true-breeding short peas. However, when Mendel crossed tall plants to short plants, collected the seeds, and planted them, all the offspring were just as tall, on average, as their tall parents. This led Mendel to the conclusion that the tall characteristic was dominant, and the short recessive. Mendel then crossed these second-generation tall plants to each other. The actual results from this cross were: 787 plants among the next generation (“grandchildren“ of the original cross of true-breeding cross of tall and short plants) were tall, and 277 were short. Thus, the short characteristic – which disappeared from sight in the first filial generation – resurfaced in the second, suggesting that two factors (now known as genes) determined plant height. In other words, although the factor which caused short stature ceased to exert its influence in the first filial generation, it was still present. Note also that the ratio between tall and short plants was 787/277, or 2.84 to 1 (approximately 3 to 1), again suggesting that plant height is determined by two factors. Mendel obtained similar results for six other pea traits, suggesting that a general rule is at work here: That most given characteristics of pea plants are determined by a pair of factors (genes in contemporary biology) of which one is dominant and the other is recessive.

 

Mendel presented his paper, “Versuche uber Pflanzenhybriden“ (“Experiments on Plant Hybridization“), at two meetings of the Natural History Society of Brno in Moravia on 8 February and 8 March 1865. It generated a few favorable reports in local newspapers, but was ignored by the scientific community. When Mendel’s paper was published in 1866 in Verhandlungen des naturforschenden Vereins Brunn, it was seen as essentially about hybridization rather than inheritance, had little impact, and was only cited about three times over the next thirty-five years. His paper was criticized at the time, but is now considered a seminal work. Notably, Charles Darwin was unaware of Mendel’s paper, and it is envisaged that if he had, genetics as we know it now might have taken hold much earlier. Mendel’s scientific biography thus provides one more example of the failure of obscure, highly-original, innovators to receive the attention they deserve.

 

Mendel began his studies on heredity using mice. He was at St. Thomas’s Abbey but his bishop did not like one of his friars studying animals, so Mendel switched to plants. Mendel also bred bees in a bee house that was built for him, using bee hives that he designed. He also studied astronomy and meteorology, founding the ‘Austrian Meteorological Society’ in 1865. The majority of his published works were related to meteorology. Mendel also experimented with hawkweed (Hieracium) and honeybees. He published a report on his work with hawkweed, a group of plants of great interest to scientists at the time because of their diversity. However, the results of Mendel’s inheritance study in hawkweeds was unlike his results for peas; the first generation was very variable and many of their offspring were identical to the maternal parent. In his correspondence with Carl Nageli, he discussed his results but was unable to explain them. It was not appreciated until the end of the nineteen century that many hawkweed species were apomictic, producing most of their seeds through an asexual process. None of his results on bees survived, except for a passing mention in the reports of Moravian Apiculture Society. All that is known definitely is that he used Cyprian and Carniolan bees, which were particularly aggressive to the annoyance of other monks and visitors of the monastery, such that he was asked to get rid of them. Mendel, on the other hand, was fond of his bees, and referred to them as “my dearest little animals“.

 

During Mendel’s own lifetime, most biologists held the idea that all characteristics were passed to the next generation through blending inheritance, in which the traits from each parent are averaged. Instances of this phenomenon are now explained by the action of multiple genes with quantitative effects. Charles Darwin tried unsuccessfully to explain inheritance through a theory of pangenesis. It was not until the early twentieth century that the importance of Mendel’s ideas was realized. By 1900, research aimed at finding a successful theory of discontinuous inheritance rather than blending inheritance, led to independent duplication of his work by Hugo de Vries and Carl Correns, and the rediscovery of Mendel’s writings and laws. Both acknowledged Mendel’s priority, and it is thought probable that de Vries did not understand the results he had found until after reading Mendel. Though Erich von Tschermak was originally also credited with rediscovery, this is no longer accepted because he did not understand Mendel’s laws. Though de Vries later lost interest in Mendelism, other biologists started to establish modern genetics as a science. All three of these researchers, each from a different country, published their rediscovery of Mendel’s work within a two-month span in the Spring of 1900. Mendel’s results were quickly replicated, and genetic linkage quickly worked out. Biologists flocked to the theory; even though it was not yet applicable to many phenomena, it sought to give a genotypic understanding of heredity which they felt was lacking in previous studies of heredity which focused on phenotypic approaches. Most prominent of these previous approaches was the biometric school of Karl Pearson and W. F. R. Weldon, which was based heavily on statistical studies of phenotype variation. The strongest opposition to this school came from William Bateson, who perhaps did the most in the early days of publicizing the benefits of Mendel’s theory (the word “genetics“, and much of the discipline’s other terminology, originated with Bateson). This debate between the biometricians and the Mendelians was extremely vigorous in the first two decades of the twentieth century, with the biometricians claiming statistical and mathematical rigor, whereas the Mendelians claimed a better understanding of biology. (Modern genetics shows that Mendelian heredity is in fact an inherently biological process, though not all genes of Mendel’s experiments are yet understood.) In the end, the two approaches were combined, especially by work conducted by R. A. Fisher as early as 1918. The combination, in the 1930s and 1940s, of Mendelian genetics with Darwin’s theory of natural selection resulted in the modern synthesis of evolutionary biology.

 

In 1936, R.A. Fisher, a prominent statistician and population geneticist, reconstructed Mendel’s experiments, analyzed results from the F2 (second filial) generation and found the ratio of dominant to recessive phenotypes (e.g. green versus yellow peas; round versus wrinkled peas) to be implausibly and consistently too close to the expected ratio of 3 to 1. Fisher asserted that “the data of most, if not all, of the experiments have been falsified so as to agree closely with Mendel’s expectations,“ Mendel’s alleged observations, according to Fisher, were “abominable“, “shocking“, and “cooked“. Other scholars agree with Fisher that Mendel’s various observations come uncomfortably close to Mendel’s expectations. Dr. Edwards, for instance, remarks: “One can applaud the lucky gambler; but when he is lucky again tomorrow, and the next day, and the following day, one is entitled to become a little suspicious“. Three other lines of evidence likewise lend support to the assertion that Mendel’s results are indeed too good to be true. Fisher’s analysis gave rise to the Mendelian Paradox, a paradox that remains unsolved to this very day. Thus, on the one hand, Mendel’s reported data are, statistically speaking, too good to be true; on the other, “everything we know about Mendel suggests that he was unlikely to engage in either deliberate fraud or in unconscious adjustment of his observations.“ A number of writers have attempted to resolve this paradox. One attempted explanation invokes confirmation bias. Fisher accused Mendel’s experiments as “biased strongly in the direction of agreement with expectation to give the theory the benefit of doubt“. This might arise if he detected an approximate 3 to 1 ratio early in his experiments with a small sample size, and, in cases where the ratio appeared to deviate slightly from this, continued collecting more data until the results conformed more nearly to an exact ratio.

 

In his 2004, J.W. Porteous concluded that Mendel’s observations were indeed implausible. However, reproduction of the experiments has demonstrated that there is no real bias towards Mendel’s data. Another attempt to resolve the Mendelian Paradox notes that a conflict may sometimes arise between the moral imperative of a bias-free recounting of one’s factual observations and the even more important imperative of advancing scientific knowledge. Mendel might have felt compelled “to simplify his data in order to meet real, or feared, editorial objections.“ Such an action could be justified on moral grounds (and hence provide a resolution to the Mendelian Paradox), since the alternative – refusing to comply – might have retarded the growth of scientific knowledge. Similarly, like so many other obscure innovators of science, Mendel, a little known innovator of working class background, had to “break through the cognitive paradigms and social prejudices of his audience. If such a breakthrough “could be best achieved by deliberately omitting some observations from his report and adjusting others to make them more palatable to his audience, such actions could be justified on moral grounds.“

 

Daniel L. Hartl and Daniel J. Fairbanks reject outright Fisher’s statistical argument, suggesting that Fisher incorrectly interpreted Mendel’s experiments. They find it likely that Mendel scored more than 10 progeny, and that the results matched the expectation. They conclude: “Fisher’s allegation of deliberate falsification can finally be put to rest, because on closer analysis it has proved to be unsupported by convincing evidence.“ In 2008 Hartl and Fairbanks (with Allan Franklin and AWF Edwards) wrote a comprehensive book in which they concluded that there were no reasons to assert Mendel fabricated his results, nor that Fisher deliberately tried to diminish Mendel’s legacy. Reassessment of Fisher’s statistical analysis, according to these authors, also disprove the notion of confirmation bias in Mendel’s results.

 

Rare Genetic Susceptibility to the Common Cold

 

Colds contribute to more than 18 billion upper respiratory infections worldwide each year, according to the Global Burden of Disease Study. According to an article published online in the Journal of Experimental Medicine (12 June 2017), a rare genetic mutation has been identified that results in a markedly increased susceptibility to infection by human rhinoviruses (HRVs) — the main causes of the common cold. The rare mutation was identified in a young child with a history of severe HRV infections. Several weeks after birth, the child began experiencing life-threatening respiratory infections, including colds, influenza and bacterial pneumonia. Because her physicians suspected she might have a primary immune deficiency – a genetic abnormality affecting her immune system – they performed a genetic analysis. The analysis revealed that she had a mutation in the IFIH1 gene that caused her body to make dysfunctional MDA5 proteins in cells in her respiratory tract. Previously, it was found that laboratory mice lacking functional MDA5 could not detect genetic material from several viruses, making them unable to launch appropriate immune responses against them. Similarly, the authors found that mutant MDA5 in the girl’s respiratory tissues could not recognize HRVs, preventing her immune system from producing protective signaling proteins called interferons. HRV thus replicated unchecked in the girl’s respiratory tract, causing severe illness. These observations led the authors to conclude that functional MDA5 is critical to protecting people against HRV. Fortunately, with intensive care, the child survived numerous bouts of severe illness, and her health has improved as her immune system matured and formed protective antibodies against various infectious agents.

 

To explore whether other people experience poor health related to the IFIH1 gene, the authors analyzed a database of over 60,000 volunteers’ genomes. While rare, the team found multiple variations in IFIH1 that could lead to less effective MDA5. Interestingly, most people with these variations lived normal lifespans and had healthy children, leading the authors to suspect that other genetic factors may have compensated for the abnormality, or that people experienced frequent HRV infections but did not report them. The Centers for Disease Control and Prevention estimates the average healthy adult has about 2 to 3 colds per year, but the range varies widely based on lifestyle and environment. For most people, infection with HRVs leads to minor illness that does not require medical attention, but the viruses can cause serious complications in people with severe asthma, chronic obstructive pulmonary disease, and other health problems. However, no antiviral therapies exist for HRVs, so these patients — like the child in the study — receive supportive care and are advised to take steps to avoid exposure. Insights from this study may lead to new strategies for treating patients with severe HRV complications and inadequate MDA5 responses.

 

New Treatment for CHAPLE Disease, a Rare Immune Disorder

 

CHAPLE disease is a form of primary intestinal lymphangiectasia (PIL), or Waldmann’s disease, first described in 1961 by Thomas A. Waldmann, M.D., an NIH Distinguished Investigator at the National Cancer Institute, at NIH.

 

According to an article published online in the New England Journal of Medicine (29 June 2017), a genetic cause and potential treatment strategy has been identified for a rare immune disorder called CHAPLE disease. Children with the condition can experience severe gastrointestinal distress and deep vein blood clots. No effective treatments are available to ameliorate or prevent these life-threatening symptoms. The study describes a newly understood mechanism for CHAPLE disease, also known as CD55 deficiency with hyperactivation of complement, angiopathic thrombosis, and protein-losing enteropathy.

 

For the study, genes from 11 children with CHAPLE disease and their families were analyzed. Results showed that each child had two copies of a defective CD55 gene that prevented them from producing a cell surface protein of the same name. The CD55 protein helps regulate the immune system by blocking the activity of complement, a group of immune system proteins that can fight infections by punching holes in the cell membranes of bacteria and other infectious agents. However, complement also can damage the body’s tissues. The study authors found that in CHAPLE disease, uninhibited complement resulting from a lack of CD55 protein damaged blood and lymph vessels along the lower digestive tract, leading to the loss of protective immune proteins and blood cells. In many patients, this process caused a range of symptoms, such as abdominal pain, bloody diarrhea, vomiting, problems absorbing nutrients, slow growth, swelling in the legs, recurrent lung infections, and blood clots.

 

After discovering that complement hyperactivity was driving these severe symptoms, the authors tested drugs already approved by the U.S. FDA for the treatment of other diseases to see if they block this process in samples of patient immune cells. The authors found that complement production decreased when cells were exposed to eculizumab, a therapeutic antibody approved to treat another rare condition called paroxysmal nocturnal hemoglobinuria. The authors plan to study eculizumab in people with CHAPLE disease with the hope that the therapeutic could become the first effective treatment for the disorder.

 

FDA Approves Treatment for Chronic Graft Versus Host Disease

 

Chronic graft versus host disease (cGVHD) is a life-threatening condition that can occur in patients after they receive a stem cell transplant from blood or bone marrow, called hematopoietic stem cell transplantation (HSCT). HSCT is used to treat certain blood or bone marrow cancers. cGVHD occurs when cells from the stem cell transplant attack healthy cells in a patient’s tissues. Symptoms of cGVHD can occur in the skin, eyes, mouth, gut, liver and lungs. The condition is estimated to occur in 30-70% of all patients who receive HSCT.

 

The FDA has expanded the approval of Imbruvica (ibrutinib) for the treatment of adult patients with chronic graft versus host disease (cGVHD) after failure of one or more treatments. This is the first FDA-approved therapy for the treatment of cGVHD. The efficacy and safety of Imbruvica for the treatment of cGVHD were studied in a single-arm trial of 42 patients with cGVHD whose symptoms persisted despite standard treatment with corticosteroids. Most patients’ symptoms included mouth ulcers and skin rashes, and more than 50% of patients had two or more organs affected by cGVHD. In the trial, 67% of patients experienced improvements in their cGVHD symptoms. In 48% of patients in the trial, the improvement of symptoms lasted for up to five months or longer.

 

Common side effects of Imbruvica in patients with cGVHD include fatigue, bruising, diarrhea, low levels of blood platelets (thrombocytopenia), muscle spasms, swelling and sores in the mouth (stomatitis), nausea, severe bleeding (hemorrhage), low levels of red blood cells (anemia) and lung infection (pneumonia). Serious side effects of Imbruvica include severe bleeding (hemorrhage), infections, low levels of blood cells (cytopenias), irregular heartbeat (atrial fibrillation), high blood pressure (hypertension), new cancers (second primary malignancies) and metabolic abnormalities (tumor lysis syndrome). Women who are pregnant or breastfeeding should not take Imbruvica because it may cause harm to a developing fetus or a newborn baby.

 

Imbruvica, a kinase inhibitor, was previously approved for certain indications in treating chronic lymphocytic leukemia, Waldenstrom’s macroglobulinemia and marginal zone lymphoma, as well as under accelerated approval status for mantle cell lymphoma.

 

The FDA granted this application Priority Review and Breakthrough Therapydesignations. Imbruvica also received Orphan Drug designation for this indication, which provides incentives to assist and encourage the development of drugs for rare diseases. The FDA granted the approval of Imbruvica to Pharmacyclics LLC.

 

Summer Solstice

This delicious (our original recipe) martini took many weeks, before we got exactly the taste we were looking for. That’s why you will see a variety of photographs. Our aim was for a refreshing, immediately delicious flavor with a slight layer of spice; also a light red or dark pink, color. We started with a plethora of ingredients just before dinner. The constant star of them all, is Zubrowka special vodka, delivered directly from Poland, the flavor of which adds a certain punch. It took about eight dinners, before we hit our goal. Now we can share our laborious research, with you. Need I say, we had so much fun, experimenting, on your behalf, of course. :) ©Joyce Hays, Target Health Inc.

 

Here is Dodi, our adorable cat, supervising the project. ©Joyce Hays, Target Health Inc.

 

Ingredients For Two 

Martini shaker, strainer, jigger, towel to catch liquid, while shaking

2.5 teaspoons strawberry puree in bottom of each glass (before pouring)

Vodka, 2 jiggers vodka, plus a splash, into shaker

Strawberry liqueur, 3 jiggers, plus a splash, into shaker

Sparkling rose wine, 6 jiggers, plus a splash, into shaker

Container with ice cubes, drain just before adding to shaker

2 Martini picks

Garnish: 1/2 lime, 6 raspberries

 

Except for this particular, Polish vodka, all of the ingredients are easy to find. For over 30 years, we’ve been ordering from Sherry-Lehmann, a well-known wine and spirits source in Manhattan. If for some reasons, they don’t have what we need, our backup is always Astor Wine & Spirits down on Lafayette Street in the Village. ©Joyce Hays, Target Health Inc.

 

Directions

1. Put the martini glasses in the fridge for 30 minutes of more.

2. Bring all of your ingredients to the same place

3. In a food processor, puree a few fresh strawberries so that you have 1.5 teaspoons of puree for each martini glass.

4. With a small spoon add the puree to the bottom of each glass, before you pour anything.

5. Put three raspberries on each martini pick, then add a pick to each glass.

6. Slice the lime; cut the slice in half, put each half on the edge of glass

7. Measure the vodka, strawberry liqueur and rose wine, and add to the martini shaker.

8. Last, before shaking, add ice cubes bringing the mixture up to the top.

9. Close the shaker tightly, cover shaker with a towel, and shake as vigorously as you can.

10. Pour contents of shaker into glasses. Not necessary to fill up to the very top, since there will be enough in the shaker for round two.

11. Make a toast and enjoy!

 

This was an experiment, using a strawberry as garnish. They’re too big for the garnish on side of a martini glass. Tried it once, didn’t work well. Decided to use the much smaller red raspberries. ©Joyce Hays, Target Health Inc.

 

You’re getting a glimpse of our plant wall, a work in progress. ©Joyce Hays, Target Health Inc.

 

This is a gorgeous martini that will not disappoint. ©Joyce Hays, Target Health Inc.

 

We have been enjoying the Mostly Mozart Festival at Lincoln Center this summer. We recently heard award winning pianist from Iceland, Vikingur Olafsson play Beethoven’s Pathetique, and violinist Thomas Zehetmair in Beethoven’s violin concerto, both brought the house down! No one could stop clapping and cheering! The audience went wild! ©Joyce Hays, Target Health Inc.

 

Beethoven Sonata No. 8 in C minor, Op 13 (Pathetique), 1797

Beethoven Violin Concerto in D Major, 1806

 

From Our Table to Yours

Bon Appetit!