John Laing Leal MD

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John Laing Leal (1858-1914) was a physician and water treatment expert who, in 1908, was responsible for conceiving and implementing the first disinfection of a U.S. drinking water supply using chlorine. He was one of the principal expert witnesses at two trials which examined the quality of the water supply in Jersey City, New Jersey, and which evaluated the safety and utility of chlorine for production of “pure and wholesome“ drinking water. The second trial verdict approved the use of chlorine to disinfect drinking water which led to an explosion of its use in water supplies of the U.S. Leal contracted a chronic case of amoebic dysentery (most likely from contaminated drinking water) at Folly Island from which he suffered for the next 17 years before the disease caused his death in 1882.

 

John L. Leal was born in Andes, New York, in 1858. In 1862, his father, John R. Leal who was a physician, joined the 144th New York Volunteer Infantry Regiment. Leal saw service in a number of areas during the Civil War including Folly Island during the Siege of Charleston, South Carolina. In 1867, Dr. John R. Leal moved his family from Andes to the rapidly growing industrial city of Paterson, New Jersey.

 

John L. Leal received his primary education at the Paterson Seminary. He attended Princeton College (now Princeton University) from 1876 to 1880. John L. Leal attended medical school at the Columbia College of Physicians and Surgeons from 1880 to 1884 where he received his medical degree. After obtaining his medical degree, Leal opened a medical practice in Paterson, New Jersey, and was appointed City Physician in 1886. Along with other physicians, he founded the outpatient clinic at Paterson General Hospital in 1887 and worked there until 1892. In 1888, he married Amy Arrowsmith and their only son, Graham, was born within the year. Leal’s career in Paterson city government continued with his appointment as Health Inspector in 1891 and Health Officer in 1892. As Health Officer, Leal was responsible for the identification of epidemics of communicable diseases and for the disinfection of the homes of the afflicted. He also oversaw the public water supply and was responsible for constructing the growing network of sewers to remove domestic and industrial wastes from the City. To prevent the spread of contagious diseases, he was responsible for building an Isolation Hospital in Paterson in 1897, which, at the time, was considered a model facility. He published several papers during his tenure as Health Officer including one that described the cause of a waterborne typhoid fever outbreak in Paterson.

 

In 1899, Leal left the city’s service and became the sanitary adviser to the East Jersey Water Company. His decision to focus on matters of public health and the safety of drinking water was driven in part by his personal experiences and from the influence of Garret Hobart, who became the 24th Vice President of the United States in 1896. Toward the end of his life, Leal was President of the Board of Health for the City of Paterson.

 

Leal belonged to a large number of professional associations. In 1884, he was elected a member of the Medical Society of New Jersey, and he was an active member of the Passaic County Medical Society. In 1900, he was Vice President of that organization. Despite his concentration on water treatment affairs after 1899, he was still involved in the Passaic County Medical Society, serving on the Legislative Committee in 1900 and in 1901 he was President. In 1905, he was active in the State Medical Society and he served as a permanent delegate from Passaic County.

 

In 1903, Leal was president of the New Jersey Sanitary Association. On the program for the Sanitary Association meeting on December 4-5, 1903, Leal was noted for giving the President’s Address on “Present Attitude of Sanitary Science“. Moses N. Baker was chair of the Garbage Disposal committee of the association and at a topic session entitled Sewage Disposal in New Jersey, the speakers included Rudolph Hering, Allen Hazen, George W. Fuller and the New Jersey water supply expert Charles A. Vermeule. These professionals interacted with one another throughout their careers.

 

He was a member of the American Medical Association and the American Public Health Association. At the APHA annual meeting in 1897, Leal read a paper entitled, “House Sanitation with Reference to Drainage, Plumbing, and Ventilation“. At the 1902 annual meeting of the APHA in New Orleans, Leal was elected second vice-president of the organization. In 1899, Jersey City entered into a contract with Patrick H. Flynn to build a water supply to replace the one that was significantly contaminated by sewage. A large dam was built on the Rockaway River which resulted in the formation of Boonton Reservoir that had a capacity of over 7 billion gallons of water. During construction, the project was taken over by the Jersey City Water Supply Company (JCWSC), which was a private water company that employed John L. Leal as its sanitary adviser. Included in Leal’s responsibilities was the removal of illegally constructed privies and other obvious sources of sewage contamination from the watershed above Boonton Reservoir. The dam, reservoir and 23-mile pipeline was completed and on May 4, 1904, water from the project was first delivered to Jersey City. As was common at this time, no treatment of any kind was provided to the water supply. City officials were not pleased with the project as delivered by the JCWSC and filed a lawsuit in the Chancery Court of New Jersey. Among the many complaints by Jersey City officials was the contention that the water served to the city was not “pure and wholesome“ as required by the contract.

 

The first trial was held before Frederick W. Stevens, Vice Chancellor of the Chancery Court of New Jersey. The first day of trial was February 20, 1906, and the trial was not completed until dozens of witnesses had been heard over 40 days of trial comprising hundreds of exhibits and thousands of pages of testimony. On May 1, 1908, Vice Chancellor Stevens issued a 100-page opinion that supported many of the contract claims made by the JCWSC but, most importantly, found (for the plaintiffs) that two to three times per year, water that could not be considered “pure and wholesome“ was delivered to Jersey City from the Boonton Reservoir water supply. In his final decree dated June 4, 1908, Stevens ordered the JCWSC to pay for the construction of sewers to remove contaminants from the Rockaway River watershed or create “other plans or devices“ which could be used instead to produce water of the required purity. The JCWSC was given three months to come up with “other plans or devices“ and to present them to a special master, Justice William J. Magie.

 

As a physician who was trained in bacteriology, Leal knew that chlorine killed bacteria. As Health Officer for Paterson, Leal used solutions of chloride of lime (calcium hypochlorite) to “disinfect“ homes where scarlet fever, diphtheria and other communicable diseases were found. He was also aware of previous efforts to use chlorine in drinking water supplies. In 1897, high concentrations of chlorine derived from chloride of lime were used to disinfect the reservoir and pipelines of Maidstone, England, after an outbreak of typhoid fever. In 1905, Dr. Alexander Cruickshank Houston devised a crude sodium hypochlorite feed system to kill typhoid bacteria in the water supply of Lincoln, England, that was being treated with an inadequate filtration system. During Leal’s testimony in the second trial, he made extensive references to the Lincoln example. He also stated in the trial that he had conducted laboratory disinfection experiments using chlorine as early as 1898.

 

On June 19, 1908, Leal hired George W. Fuller to construct a chlorination plant at Boonton Reservoir to disinfect the water for Jersey City as a representation of “other plans or devices“. At the time, Fuller was, perhaps, the most respected sanitary engineer in the U.S. In 99 days, Fuller designed the chlorination plant and supervised its construction. Dilute solutions of chloride of lime were accurately fed by gravity to the water being treated. Fuller based his design on the successful aluminum sulfate feed system that he had built at the Little Falls Water Treatment Plant in 1902. The chlorination plant at Boonton Reservoir treating an average of 40 million gallons per day went on-line on September 26, 1908. Since then, water from this source has been continuously chlorinated, making it the water supply with the longest history of disinfection.

 

The second trial began on September 29, 1908, before Justice Magie. The purpose of this trial was to determine if the chloride of lime system that had been installed by JCWSC was effective in controlling harmful bacterial levels and capable of providing water that was “pure and wholesome“. Over 38 days, dozens of witnesses were heard and hundreds of exhibits were submitted. More than three thousand pages recorded the testimony of expert witnesses for both sides including William T. Sedgwick, George C. Whipple, Earle B. Phelps, Charles-Edward A. Winslow and a number of other experts for the plaintiffs and John L. Leal, George W. Fuller and Rudolph Hering (among others) for the defendants. Justice Magie issued his ruling on May 9, 1910, which was a victory for the defendants. Chlorine was an acceptable treatment for the removal of pathogens from drinking water and for making the water “pure and wholesome“ for human consumption. “I do therefore find and report that this device is capable of rendering the water delivered to Jersey City, pure and wholesome, for the purposes for which it is intended, and is effective in removing from the water those dangerous germs which were deemed by the decree to possibly exist therein at certain times.“ The ruling by Justice Magie was supported on appeal by the New Jersey Court of Errors and Appeals and the New Jersey Supreme Court.

 

 

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Death rates for typhoid fever in the U.S. 1906-1960

 

Leal’s application of chlorine disinfection technology and his defense of the chemical’s use, contributed significantly to the eradication of typhoid fever and other waterborne diseases in the U.S. On September 26, 1908, only the Jersey City water supply was disinfected using chlorine. A survey of water utilities showed that by 1914, over 21 million people were being served chlorinated water in the U.S. By 1918, more than 1,000 North American cities were using chlorine to disinfect their water supplies, which served approximately 33 million people. Statistics on the typhoid fever death rate in the U.S. showed a dramatic decrease in deaths due to this dreaded disease after the wide introduction of chlorine for disinfection. Filtration of water supplies contributed to the decrease in the typhoid fever death rate but chlorination is generally acknowledged as having a major impact on increased life expectancy in the U.S.

 

Unfortunately, Leal is seldom given credit for his pioneering work in the disinfection of drinking water. George A. Johnson was a plant operator and laboratory technician who worked on the chlorination plant at Boonton Reservoir. His later writings gave no credit to Leal and, by inference, Johnson took the credit for the decision to use chlorine on the Jersey City water supply. The record shows that Leal came up with the idea to disinfect the water supply of Jersey City and he should be given the credit for this major advance in public health.

 

 

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Grave Monument to Dr. John L. Leal

 

On May 5, 2013, a number of people gathered at the gravesite of Leal in Paterson, New Jersey and dedicated a monument to him as a “Hero of Public Health.“ Present at the dedication were members of the New Jersey Section of the American Water Works Association and two great grandsons of Leal. In August 2013, the American Water Works Association established a major annual award in honor of Leal. Entitled the Dr. John L. Leal Award, the purpose of the award is to recognize any individual, group, or organization that has made a notable and outstanding public health contribution to the water profession. The first award will be given at the AWWA annual conference in June 2014.

 

ONCOLOGY

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Dietary Protein Sources in Early Adulthood and Breast Cancer Incidence

 

According to an article published online in the British Medical Journal (10 June 2014), a study was performed to investigate the association between dietary protein sources in early adulthood and risk of breast cancer. The investigation was a prospective cohort study performed in the United States. Study participants included 88,803 premenopausal women from the Nurses’ Health Study II who completed a questionnaire on diet in 1991. The main outcome measure was incident cases of invasive breast carcinoma, identified through a self-report and confirmed by a pathology report.

 

A total of 2,830 cases of breast cancer were documented during the 20 years of follow-up. Results showed that a higher intake of total red meat was associated with an increased risk of breast cancer overall (relative risk 1.22; Ptrend=0.01, for highest fifth vs. lowest fifth of intake). However, overall, higher intakes of poultry, fish, eggs, legumes, and nuts were not related to breast cancer. When the association was evaluated by menopausal status, higher intake of poultry was associated with a lower risk of breast cancer in postmenopausal women (0.73; Ptrend=0.02, for highest fifth vs. lowest fifth of intake) but not in premenopausal women for highest fifth vs. lowest fifth of intake). In estimating the effects of exchanging different protein sources, substituting one serving/day of legumes for one serving/day of red meat was associated with a 15% lower risk of breast cancer among all women and a 19% lower risk among premenopausal women. Also, substituting one serving/day of poultry for one serving/day of red meat was associated with a 17% lower risk of breast cancer overall and a 24% lower risk of postmenopausal breast cancer. Furthermore, substituting one serving/day of combined legumes, nuts, poultry, and fish for one serving/day of red meat was associated with a 14% lower risk of breast cancer overall and premenopausal breast cancer.

 

The authors concluded that higher red meat intake in early adulthood may be a risk factor for breast cancer, and replacing red meat with a combination of legumes, poultry, nuts and fish may reduce the risk of breast cancer.

Loss-of-Function Mutations in APOC3, Triglycerides, and Coronary Disease

 

Plasma triglyceride levels are heritable and are correlated with the risk of coronary heart disease. Sequencing of the protein-coding regions of the human genome (the exome) has the potential to identify rare mutations that have a large effect on phenotype. As a result, a study published online in the New England Journal of Medicine (18 June 2014), sequenced the protein-coding regions of 18,666 genes in each of 3734 participants of European or African ancestry in the Exome Sequencing Project. Tests were conducted to determine whether rare mutations in coding sequence, individually or in aggregate within a gene, were associated with plasma triglyceride levels. For mutations associated with triglyceride levels, the study subsequently evaluated their association with the risk of coronary heart disease in 110,970 persons.

 

Results demonstrated an aggregate of rare mutations in the gene encoding apolipoprotein C3 (APOC3) associated with lower plasma triglyceride levels. Among the four mutations that drove this result, three were loss-of-function mutations: a nonsense mutation (R19X) and two splice-site mutations (IVS2+1G- to-A and IVS3+1G-to-T). The fourth was a missense mutation (A43T). Approximately 1 in 150 persons in the study was a heterozygous carrier of at least one of these four mutations. Triglyceride levels in the carriers were 39% lower than levels in noncarriers (P<1×10-20), and circulating levels of APOC3 in carriers were 46% lower than levels in noncarriers (P=8 x10-10). The risk of coronary heart disease among 498 carriers of any rare APOC3 mutation was 40% lower than the risk among 110,472 noncarriers (odds ratio, 0.60; P=4 x10-6).

 

The authors concluded that rare mutations that disrupt APOC3 function were associated with lower levels of plasma triglycerides and APOC3, and that carriers of these mutations were found to have a reduced risk of coronary heart disease.

 

TARGET HEALTH excels in Regulatory Affairs. Each week we highlight new information in this challenging area.

 

FDA Approves Sivextro to Treat Skin Infections

 

The FDA has approved Sivextro (tedizolid phosphate), a new antibacterial drug, to treat adults with skin infections. Sivextro is approved to treat patients with acute bacterial skin and skin structure infections (ABSSSI) caused by certain susceptible bacteria, including Staphylococcus aureus (including methicillin-resistant strains (MRSA) and methicillin-susceptible strains), various Streptococcus species, and Enterococcus faecalis. Sivextro is available for intravenous and oral use. Sivextro is the second new antibacterial drug approved by the FDA in the past month to treat ABSSSI. On May 23, the agency approved Dalvance (dalbavancin), also to treat patients with ABSSSI caused by Staphylococcus aureus and various Streptococcus species.

 

The application for Sivextro, intended to treat serious or life-threatening infections, was designated as a qualified infectious disease product (QIDP) and received an expedited review. Sivextro’s QIDP designation also qualifies it for an additional five years of marketing exclusivity to be added to certain exclusivity periods already provided by the Food, Drug and Cosmetic Act.

 

Sivextro’s safety and efficacy were evaluated in two clinical trials with 1,315 adults with ABSSSI. Participants were randomly assigned to receive Sivextro or linezolid, another antibacterial drug approved to treat ABSSSI. Results showed Sivextro was as effective as linezolid for the treatment of ABSSSI. The most common side effects identified in the clinical trials were nausea, headache, diarrhea, vomiting and dizziness. The safety and efficacy of Sivextro have not been evaluated in patients with decreased levels of white blood cells (neutropenia), so alternative therapies should be considered.

 

Sivextro is marketed by Cubist Pharmaceuticals, based in Lexington, Massachusetts

 

Open-faced Homage to Burgers

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Veggie Burger with all the toppings  ©Joyce Hays, Target Health Inc.

 

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Veggie Burger with all the toppings except grated soy mozzarella ©Joyce Hays, Target Health Inc.

 

Ingredients

  • 1 cup quinoa
  • 2 cups water
  • 1 zucchini
  • 1/2 cup olive oil, divided
  • 1 large shallot, minced (used to make the burger)
  • 1/2 teaspoon crushed red pepper flakes
  • 4 large Portobello mushrooms caps, used as burger buns
  • 2 large Portobello mushroom caps, (stems removed) finely chopped in a food processor)
  • Kosher salt and freshly ground pepper, to taste
  • 1 1/2 cups Panko
  • 1/2 cup mashed cooked yam, more if needed. Bake 3 yams.
  • Avocado topping
  • 6 Tablespoons tomato, chopped, for garnish
  • Daikon sprouts, for garnish (optional)
  • Thinly sliced fried shallot “sticks,“ for garnish
  • Chunk of soy mozzarella, freshly grated for garnish

 

Directions

1. In a pan, saute the sliced shallot sticks, to be used for garnish, and set aside. Sticks should be the size of a toothpick, cut in half.

 

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Cooking the Portobello caps.  ©Joyce Hays, Target Health Inc.

 

2. In the same pan, add 1 teaspoon olive oil, 1 garlic clove, sliced, a few Tablespoons of chicken stock and cook both sides of the 4 caps of large Portobello mushrooms. Then set aside. These will serve as half a bun for the burgers.

 

3. Cook the quinoa. Rinse the grains well. Bring the water to a boil and add the quinoa, cooking until it is translucent and tender, and the germ has spiraled out from the grain, 12 to 15 minutes, careful not to overcook. Drain, measure 2 cups and set aside. This makes about 2 1/2 cups cooked quinoa, more than is needed for the rest of the recipe; the remainder can be eaten by itself or added to soups or salads.

 

4. While the quinoa is cooking, coarsely grate the zucchini. Spread the grated zucchini out on a kitchen towel, then roll up the towel and wring it to squeeze out as much moisture as possible. Set aside.

 

5. In a large saute pan, heat the olive oil over low heat and add the minced shallot and red pepper flakes. Cook until the shallots are soft, about 3 minutes.

 

6. To the pan, add the mushroom puree and zucchini, and cook for 3 more minutes to soften, stirring often.

 

7. Place the mixture in a large bowl and add the quinoa, then add salt and pepper to taste. Set aside to cool.

 

8. Now, add the Panko and mashed yam to the large bowl.

 

9. With your hands, knead the mixture to fully incorporate and form the burger base. If the burger is too soft to hold together, add more mashed yam to bind. Make 6 patties by pressing the mixture firmly with your hands.

 

10. Heat a thin layer of olive oil in a large skillet or grill pan over medium heat. Cook the patties until golden-brown on both sides, 3 to 4 minutes per side.

 

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Cooked patties on cooked Portobello “bun“ ©Joyce Hays, Target Heath Inc.

 

11. Place a cooked patty on one of the large cooked Portobello caps.

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First spread the avocado topping on the cooked burger; then I added shallots. ©Joyce Hays, Target Health Inc.

 

12. Spread a tablespoon of avocado topping on each burger. Top each with a tablespoon of chopped tomato and small handful of daikon sprouts. Also, sprinkle the fried shallot sticks on top of the burgers.. Serve the burgers open-faced, so to speak.

 

Okay, so it was our anniversary weekend and I wanted to contribute a recipe just for him. This was taking a real gamble, since often he’s on the hunt and comes home a rough and tumble paleo-man. But I wanted to relax with some chilled wine and our 34 years of great memories. I decided to experiment further in order to get a veggie burger to be proud of. You wouldn’t be reading this, if I had failed.

 

He loved it!

 

I think part of the reason, this turned out to be such a good recipe, is that everything about this burger (visually) was based on a hamburger/cheeseburger, that we all have enjoyed. You could call my approach, a pastiche, a homage, to the beef burgers we all grew up with. This recipe is such a delicious alternative, that it holds its own as a succulent veggie burger with fabulous toppings. I urge you to try it.

 

We started our meal with an icy Orvieto and an Ugli tomato salad with endive, thinly sliced mini cucumbers, green olives, and avocados in lemon/oil dressing. (Ugli ripe tomato is a real old fashion beefsteak tomato, without a center core) Then, came the Veggie Burgers with all the colorful toppings.

 

His first bite was a “wow“ which went straight to my heart.

 

We both enjoyed adding the various toppings, which adds to the fun. If you decide to try this recipe, make it an adventure. In advance be sure everyone knows not to expect meat and to have a good time with an adventure of new flavors at the dinner table.

 

If there are theater lovers out there, Saturday, we went to a new play at Lincoln Center (Mitzi Newhouse Theater), “The City of Conversation.“ We recommend it highly. Wonderful acting, gorgeous set, and a plot that will stimulate much discussion. Another wonderful experience for us.

 

When we went out for dinner afterwards, there was a huge vase of perfect red roses, on our table, waiting for me. Need I say more?

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A day of wine and roses.  ©Joyce Hays, Target Health Inc.

 

From Our Table to Yours, Bon Appetit !

Can we answer them before it’s too late?

Source: http://www.popsci.com/article/science/great-arctic-melt-opens-lot-questions?dom=PSC&loc=recent&lnk=8&con=the-great-arctic-melt-opens-up-a-lot-of-questions

Target Health at DIA – San Diego

 

Dean Gittleman, Sr. Director of Operations, Warren Pearlson, Director of Business Development and Neil Lassalle, Office Manager, will be attending the annual DIA in San Diego this year (Booth 1935). Please contact Warren atwpearlson@targethealth.com if you will be attending and interested in learning more about us.

 

Target Health Inc. is Setting Up at DIA

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Space Just for Chatting                                                         Space for Demos

Storm Clouds Rush Into NYC –  on Friday the 13th June 2014 (plus the full moon)

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Storm Clouds From the 24th Floor at 261 Madison, Target Health’s Corporate Headquarters – ©Target Health Inc .

 

ON TARGET is the newsletter of Target Health Inc., a NYC-based, full-service, contract research organization (eCRO), providing strategic planning, regulatory affairs, clinical research, data management, biostatistics, medical writing and software services, including the paperless clinical trial, to the pharmaceutical and device industries.

 

For more information about Target Health contact Warren Pearlson (212-681-2100 ext. 104). 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 HealthWebsite, and if you like the weekly newsletter, ON TARGET, you’ll love the Blog.

 

Joyce Hays, Founder and Editor in Chief of On Target
Jules Mitchel, Editor

 

Breast Cancer

 

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Normal breast on left; cancerous breast on right

 

Breast cancer is a type of cancer originating from breast tissue, most commonly from the inner lining of milk ducts or the lobules that supply the ducts with 1) ___. Cancers originating from ducts are known as ductal carcinomas, while those originating from lobules are known as lobular carcinomas. Breast cancer occurs in humans and other mammals. While the overwhelming majority of human cases are in women, breast cancer can also occur in men. The balance of benefits versus harms of breast cancer screening is controversial.

 

The characteristics of the cancer determine the treatment, which may include surgery, medications (hormonal therapy and chemotherapy), radiation and/or immunotherapy. 2) ___ provides the single largest benefit, and to increase the likelihood of remission (no further sign of the cancer), several chemotherapy regimens are commonly given in addition. Radiation is used after breast-conserving surgery and substantially improves local relapse rates and in many circumstances also overall survival.

 

Worldwide, breast cancer accounts for 22.9% of all cancers (excluding non-melanoma skin cancers) in women. In 2008, breast cancer caused 458,503 deaths worldwide (13.7% of cancer deaths in women). Breast cancer is more than 100 times more common in women than in men, although men tend to have poorer outcomes due to delays in 3) ___. Prognosis and survival rates for breast cancer vary greatly depending on the cancer type, stage, treatment, and geographical location of the patient. Survival rates in the 4) ___ world are high; for example, more than 8 out of 10 women (85%) in England diagnosed with breast cancer survive for at least 5 years. In developing countries, however, survival rates are much poorer.

 

The primary risk factors for breast cancer are female gender and older age. Other potential risk factors include: genetics, lack of childbearing or lack of breastfeeding, higher levels of certain hormones, certain dietary patterns, and obesity. Recent studies have indicated that exposure to light pollution is a risk factor for the development of breast cancer. Smoking tobacco appears to increase the risk of breast cancer, with the greater the amount smoked and the earlier in life that smoking began, the higher the 5) ___. In those who are long-term smokers, the risk is increased 35% to 50%. A lack of physical activity has been linked to ~10% of cases. The association between breast feeding and breast cancer has not been clearly determined; some studies have found support for an association while others have not.

 

A new pathway that can stop breast cancer cells from spreading has been discovered. Working with human breast cancer cells and a mouse model of breast cancer, scientists identified a new protein that plays a key role in reprogramming cancer cells to migrate and invade other organs. When that protein is removed from cancer cells in mice, the ability of the cells to metastasize to the lung is dramatically 6) ___. The primary cause of death from breast cancer is the spread of tumor cells from the breast to other organs in the body. Northwestern Medicine scientists have discovered a new pathway that can stop breast cancer cells from spreading. The protein, hnRNPM, helps launch a cascade of events that enables breast cancer cells to break away from the original tumor, penetrate the blood stream, invade another part of the body and form a new nodule of that tumor.

 

“Our research suggests that hnRNPM could be an effective target to stop cancer cells from spreading,“ said Northwestern Medicine scientist Chonghui Cheng, M.D. “So far there isn’t a really good target that can cure breast cancer. The more we understand of cancer metastasis and the pathways that control it, the better we will be able to stop breast cancer from 7) ___.“ Cheng is an assistant professor of medicine in hematology/oncology at Northwestern University Feinberg School of Medicine. She also is a member of the Robert H. Lurie Comprehensive Cancer Center of Northwestern University. The study was published June 1 in the journal Genes & Development.

 

Cheng and colleagues did experiments using human cells and identified hnRNPM’s role in controlling the processes linked to tumor metastasis. Then they removed the protein in a mouse model of breast cancer and discovered the cancer’s ability to spread was significantly reduced. Collaborating with Kalliopi Siziopikou, M.D., a professor in pathology and director of the breast pathology program at Feinberg, the scientists looked at breast cancer tumor specimens from patients and levels of hnRNPM in those samples. They found aggressive breast tumors, including those that show metastatic traits, expressed higher levels of hnRNPM. “This confirmed hnRNPM’s role in the metastasis of human breast cancer,“ Cheng said. “Now we’re investigating how the protein works in order to be able to develop a drug that could prevent tumor metastasis.

 

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The pink ribbon is a symbol to show support for breast cancer awareness

 

Double mastectomy halves death risk for women with BRCA-related breast cancer. Women with BRCA-related breast cancer who have a double mastectomy are nearly 50% less likely to die of breast cancer within 20 years of diagnosis compared to women who have a single 8) ___, according to a new study led by Toronto, Women’s College Hospital’s Kelly Metcalfe. The findings, published in the British Medical Journal, suggest a double mastectomy may be an effective first-line treatment for women with early-stage breast cancer who carry a BRCA1 or BRCA2 genetic mutation. The BRCA1/2 genes belong to a class of genes that typically act to protect individuals from acquiring cancer, yet women who inherit a mutated form of the genes have a high risk of developing breast and ovarian 9) ___.

 

“Women with a BRCA mutation have a 60-70% chance of developing breast cancer in their lifetime, and once diagnosed, a further 34% chance of developing breast cancer in the opposite breast within 15 years,“ said Kelly Metcalfe, an adjunct scientist at Women’s College Research Institute and professor at the University of Toronto. “For these women, we need to think about treating the first breast cancer, but also about preventing a second breast cancer.“ To compare the survival rates of women with BRCA-related breast cancers, researchers assessed the medical records of 390 women with stage one or two breast cancer and a BRCA1 or BRCA2 mutation. The women were required to have been initially treated with a single or double mastectomy. The researchers found:

 

  • Women who had a double mastectomy had a 48% greater likelihood of surviving compared to women with a single mastectomy
  • For women who developed a new breast cancer in the opposite breast, the risk of dying of breast cancer was doubled
  • At twenty years, the survival rate was 88% for women with a double mastectomy and 66% for women with a single mastectomy

 

“Our study’s results provide evidence that in order to improve survival in women with BRCA-associated breast cancer, we need to prevent new breast cancers from developing after an initial diagnosis,“ said Dr. Steven Narod, a co-author of the study and a senior scientist at Women’s College Research Institute. “This study highlights the importance of providing genetic testing for BRCA1 and BRCA2 at the time of breast cancer diagnosis if appropriate. This genetic information could help women make decisions that ultimately may increase their chance of surviving breast cancer.“

 

Last year, Hollywood actress Angelina Jolie, publicly announced her decision to opt for a double mastectomy and breast reconstruction surgery after discovering she had the BRCA1 gene. The then 37 year-old actress said doctors estimated she had a 50% risk of developing ovarian cancer and an 87% risk of breast cancer. While existing research widely supports the benefit of a double mastectomy in preventing breast cancer in women with the gene mutation, the study’s researchers caution more research is necessary to confirm the benefit of a double mastectomy in reducing the risk of death in women diagnosed with BRCA-related 10) ___ cancer.

 

Women’s College Hospital is a teaching hospital in downtown Toronto, Ontario, Canada. It is located at the north end of Hospital Row, a section of University Avenue where several major hospitals are located. Women’s College Hospital began as Woman’s Medical College in 1883. On June 13, 1883, Dr. Emily Stowe (1831-1903) the first Canadian woman licensed to practice medicine in Canada – led a group of her supporters to a meeting at the Toronto Women’s Suffrage Club, stating “that medical education for women is a recognized necessity, and consequently facilities for such instruction should be provided.“ The motion was seconded adding “that the establishment of such a school was a public necessity and in the interests of the community.“ Less than six months after this meeting, on October 1, 1883, Toronto Mayor A.R. Boswell formally opened Woman’s Medical College.

 

Sources: Northwestern University: Y. Xu, X. D. Gao, J.-H. Lee, H. Huang, H. Tan, J. Ahn, L. M. Reinke, M. E. Peter, Y. Feng, D. Gius, K. P. Siziopikou, J. Peng, X. Xiao, C. Cheng. Cell type-restricted activity of hnRNPM promotes breast cancer metastasis via regulating alternative splicing. Genes & Development, 2014; 28 (11): 1191 DOI: Women’s College Hospital: K. Metcalfe, S. Gershman, P. Ghadirian, H. T. Lynch, C. Snyder, N. Tung, C. Kim-Sing, A. Eisen, W. D. Foulkes, B. Rosen, P. Sun, S. A. Narod. Contralateral mastectomy and survival after breast cancer in carriers of BRCA1 and BRCA2 mutations: retrospective analysis. BMJ, 2014; 348 (feb11 9): g226 DOI; Wikipedia, ScienceDaily.com; WebMD.com, MedicineNet.com

 

ANSWERS: 1) milk; 2) Surgery; 3) diagnosis; 4) Western; 5) risk; 6) decreased; 7) spreading; 8) mastectomy; 9) cancers; 10) breast

Frances Burney, Early Mastectomy Patient

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Writer, Frances Burney (1752 – 1840)

 

Because of its visibility, breast cancer was the form of cancer most often described in ancient documents. Because autopsies were rare, cancers of the internal organs were essentially invisible to ancient medicine. Breast cancer, however, could be felt through the skin, and in its advanced state often developed into fungating lesions: the tumor would become necrotic (die from the inside, causing the tumor to appear to break up) and ulcerate through the skin, leaking fetid, dark fluid.

 

The oldest description of cancer was discovered in Egypt and dates back to approximately 1600 BCE. The Edwin Smith Papyrus describes 8 cases of tumors or ulcers of the breast that were treated by cauterization. The writing says about the disease, “There is no treatment.“ For centuries, physicians described similar cases in their practices, with the same conclusion. Ancient medicine, from the time of the Greeks through the 17th century, was based on humoralism, and thus believed that breast cancer was generally caused by imbalances in the fundamental fluids that controlled the body, especially an excess of black bile. Alternatively, patients often saw it as divine punishment. In the 18th century, a wide variety of medical explanations were proposed, including a lack of sexual activity, too much sexual activity, physical injuries to the breast, curdled breast milk, and various forms of lymphatic blockages, either internal or due to restrictive clothing. In the 19th century, the Scottish surgeon John Rodman said that fear of cancer caused cancer, and that this anxiety, learned by example from the mother, accounted for breast cancer’s tendency to run in families.

 

Although breast cancer was known in ancient times, it was uncommon until the 19th century, when improvements in sanitation and control of deadly infectious diseases resulted in dramatic increases in lifespan. Previously, most women had died too young to have developed breast cancer. Additionally, early and frequent childbearing and breastfeeding probably reduced the rate of breast cancer development in those women who did survive to middle age. Because ancient medicine believed that the cause was systemic, rather than local, and because surgery carried a high mortality rate, the preferred treatments tended to be pharmacological rather than surgical. Herbal and mineral preparations, especially involving the poison arsenic, were relatively common. Before the 20th century, breast cancer was feared and discussed in hushed tones, as if it were shameful. As little could be safely done with primitive surgical techniques, women tended to suffer silently rather than seeking care.

 

In 1811, Physician/Surgeon Baron Larrey co-led the surgical team that performed a pre-anesthetic mastectomy on Frances Burney in Paris. Her detailed account of this operation gives insight into early 19th century doctor-patient relationships, and early surgical methods in the home of the patient. Larrey directed the Grande Armee of Napoleon to develop mobile field hospitals, or “ambulances volantes“ (flying ambulances), in addition to a corps of trained and equipped soldiers to aid those on the battlefield. Before Larrey’s initiative in the 1790s, wounded soldiers were either left amid the fighting until the combat ended or their comrades would carry them to the rear line. The practice of triage pioneered by Dominique Jean Larrey during the Napoleonic Wars (1803-1815).

 

In August 1810, novelist, Frances Burney developed pains in her breast, which her husband suspected could be due to breast cancer. Through her royal network of acquaintances she was eventually treated by several leading physicians and finally, a year later, on 30 September 1811, she underwent a mastectomy performed by “7 men in black, Dr. Larrey, M. Dubois, Dr. Moreau, Dr. Aumont, Dr. Ribe, & a pupil of Dr. Larrey, & another of M. Dubois“. The operation was performed in the manner of a battlefield operation under the command of M. Dubois, then accoucheur (midwife or obstetrician) to the Empress Marie Louise, Duchess of Parma, and considered to be the best doctor in France. Burney was later able to describe the operation in detail, since she was conscious through most of it, as it took place before the development of anesthetics.

 

I mounted, therefore, unbidden, the Bed stead – & M. Dubois placed me upon the Mattress, & spread a cambric handkerchief upon my face. It was transparent, however, & I saw, through it, that the Bed stead was instantly surrounded by the 7 men & my nurse. I refused to be held; but when, Bright through the cambric, I saw the glitter of polished Steel – I closed my Eyes. I would not trust to convulsive fear the sight of the terrible incision. Yet — when the dreadful steel was plunged into the breast – cutting through veins – arteries – flesh – nerves – I needed no injunctions not to restrain my cries. I began a scream that lasted unintermittingly during the whole time of the incision – & I almost marvel that it rings not in my Ears still? so excruciating was the agony. When the wound was made, & the instrument was withdrawn, the pain seemed undiminished, for the air that suddenly rushed into those delicate parts felt like a mass of minute but sharp & forked poniards, that were tearing the edges of the wound. I concluded the operation was over – Oh no! presently the terrible cutting was renewed – & worse than ever, to separate the bottom, the foundation of this dreadful gland from the parts to which it adhered – Again all description would be baffled – yet again all was not over, – Dr. Larrey rested but his own hand, & — Oh heaven! – I then felt the knife (rack)ling against the breast bone – scraping it!

 

She sent her first-person account of this experience months later to her sister Esther without rereading it, and it remains one of the most compelling early accounts of a mastectomy. It is impossible to know today whether the breast removed was indeed cancerous or whether she suffered from mastopathy. She survived and returned to England in 1812 to visit her ailing father and to avoid her young son, Alexander’s conscription into the French army, while still in recovery from her own illness. She lived to be 88 years old, a long life in the 1800s.

 

When surgery advanced, and long-term survival rates improved, women began raising awareness of the disease and the possibility of successful treatment. The “Women’s Field Army“, run by the American Society for the Control of Cancer (later the American Cancer Society) during the 1930s and 1940s was one of the first organized campaigns. In 1952, the first peer-to-peer support group, called “Reach to Recovery“, began providing post-mastectomy, in-hospital visits from women who had survived breast cancer. The breast cancer movement of the 1980s and 1990s developed out of the larger feminist movements and women’s health movement of the 20th century. This series of political and educational campaigns, partly inspired by the politically and socially effective AIDS awareness campaigns, resulted in the widespread acceptance of second opinions before surgery, less invasive surgical procedures, support groups, and other advances in patient care.

 

 

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Breast cancer surgical tools in the 18th century

Hormone Treatment Restores Bone Density in Young Women with Spontaneous Primary Ovarian Insufficiency (POI)

 

Spontaneous primary ovarian insufficiency (POI), which affects 1 in 100 women by age 40, occurs when the ovaries stop producing sufficient estrogen in the absence of a known cause, such as anorexia, chromosome abnormality, or chemotherapy. It is typically characterized by irregular or absent menstrual cycles, hot flashes, and fertility problems. Women with POI have abnormally low levels of reproductive hormones, including estradiol, a type of estrogen produced by the ovary, as well as testosterone, a predominantly male hormone, but also produced by women in smaller amounts. They also have reduced bone mineral density, which can lead to osteoporosis and bone fractures.

 

According to an article published online in the Journal of Clinical Endocrinology & Metabolism (9 June 2014), it has been observed that hormone replacement therapy in young women with primary ovarian insufficiency (POI) led to increases in their bone mineral density, restoring levels to normal.

 

Using bone density scans of the hip and lower spine, the authors measured the effects of two hormone replacement regimens on the bone mineral density of women with POI who were between the ages of 18 and 42. For the study, 145 women with POI were randomly assigned to one of two groups: one group received a 100 mcg estradiol patch, progestin pills, and a 150 mcg testosterone patch, and the other group received a 100 mcg estradiol patch, progestin pills, and a placebo patch. For comparison, the scientists also measured bone mineral density in an untreated group of 70 women with normal ovarian function.

 

Results showed that both hormone treatment regimens led to significant increases in the bone mineral density in the treatment groups. When the study began, women with POI had significantly lower hip and spine bone mineral density levels compared to the control group. By the study’s end, both bone density measures had increased to the same levels as the women without POI. However, the addition of testosterone in the treatment regimen did not prove to be statistically significant in helping increase bone mineral density.

 

According to the authors, further studies with a greater number of women would be needed to produce statistically valid results as to whether testosterone replacement could benefit women with POI. The authors added that while hormone replacement therapy’s effect on bone mineral density has been studied in postmenopausal women, there is limited research on the effects of this therapy in younger women. What the study did demonstrate is that hormone replacement therapy with an appropriate dose of estradiol delivered via a skin patch combined with oral progestin can improve bone density to normal in women with primary ovarian insufficiency.

 

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