bluuebunny/crossref_metadata_2025 huggingface dataset:
Turner's Syndrome Associated with Growth Hormone Deficiency
Authors: Duke Eileen M. C. , Hussein Dia M. , Hamilton W.
Published: January 2017

11 out of the 13 children with Turner's syndrome currently attending our endocrine clinic were investigated for possible growth hormone deficiency. The parents of two of the 13 children refused permission for these studies. One child had inadequate hypoglycaemia and the test was not repeated. Six of the ten children with adequate hypoglycaemia had an adequate growth hormone response to hypoglycaemia, while 4 children did not. This contradicts several previous studies on children with Turner's syndrome, which have reported normal growth hormone responses to provocative tests. In the normal population approximately one in 15 has an inadequate growth hormone response to hypoglycaemia.
Teratoma of Testis and Hyperthyroidism
Authors: Stromberg P. , Ratcliffe J. G. , Trotter J. , McAllister J.
Published: January 2017

Four cases of hyperthyroidism were observed in a series of 135 males with a past history of malignant teratoma of testis. None of the patients had evidence of tumour recurrence at the time of diagnosis of hyperthyroidism. Possible mechanisms for this association are discussed.
The Bramwells and Neurology in Edinburgh
Authors: Ashworth B.
Published: January 2017

An account is given of the life and work of Sir Byrom Bramwell (1847–1931), and his son Professor Edwin Bramwell (1873–1952). They were outstanding as clinical observers and teachers.

Byrom Bramwell began his professional work in his father's practice in North Shields. After a brief period of hospital work in Newcastle he moved to Edinburgh. His early struggles in consulting practice were combined with prolific writing of papers and books. He became the leading physician in Scotland.

Edwin Bramwell received extensive postgraduate training as a neurologist and returned to practise in Edinburgh. He became Moncrieff-Amott Professor of Medicine, and was widely known as a clinician, lecturer, and writer on medical subjects. He was particularly active in postgraduate teaching.

Both of the Bramwells became, in their turn, President of the Royal College of Physicians of Edinburgh. Edwin Bramwell was also President of the Association of British Neurologists. They shared an interest in angling which was their principal recreation. Their work is reviewed and considered in its historical perspective.
Antagonism between Non-Steroidal Anti-Inflammatory Drugs and Diuretics
Authors: Rawles J. M.
Published: January 2017

Renal osmolal clearance after a standard water load was measured in healthy volunteers. After flurbiprofen, 100 mg by mouth, the osmolal clearance fell by 29 per cent. After frusemide, 40 mg by mouth or 20 mg intravenously, the osmolal clearance increased by 105 per cent and 140 per cent respectively, but following pre-treatment with flurbiprofen, the corresponding increases in osmolal clearance were only 19 per cent and 70 per cent. The antagonism between non-steroidal anti-inflammatory drugs and diuretics, of which this is an example, may be a common and clinically important drug interaction.
The Assessment of Diabetic Control in Insulin-Independent Patients
Authors: Harrower A.D.B. , Gilmour G. A.
Published: January 2017

All diabetics are at risk from the development of the specific and non-specific complications of the disorder. While good control with relative normoglyacemia may be beneficial, most of the emphasis on maintaining stricter blood glucose control has been aimed at the insulin-dependent diabetic.

Seventy-four sylphonylurea-treated diabetics were observed for a year and their degree of control assessed and compared using simple clinical criteria, plasma glucose levels and haemoglobin A1cconcentrations. Control was considered good in 55.4 per cent, 16.2 per cent and 14.9 per cent using each criterion respectively.

Simple clinical assessment of control is therefore unlikely to achieve normoglycaemia in the majority of such patients. A more wide ranging assessment and a more aggressive approach to therapy may be desirable if better blood glucose control can be shown to produce a reduction in the significant morbidity and mortality in these patients.
Excessive Beer Consumption and Beri—Beri
Authors: Whyte K. F. , Dunnigan M. G. , McIntosh W. B.
Published: January 2017

Alcohol-induced ‘wet’ or cardiac beri-beri is reported in two middleaged males who consumed excessive amounts of beer. The high carbohydrate and satiety value of beer together with its low thiamine content places the alcoholic beer drinker at particular risk of thiamine deficiency.
Value of a Single Night-Time Dose of Potassium Clorazepate in Anxiety: A Controlled Trial Comparison with Diazepam
Authors: Henderson J. G.
Published: January 2017

A total of 29 patients with anxiety or anxiety/hysteria, participated in a double-blind, cross-over trial of two benzodiazepine anxiolytics, diazepam and potassium clorazepate. The problems of a ‘carry-over’ effect and a possible order of drug administration effect are discussed in relation to analysis of results. Clorazepate proved the more effective drug, as shown by a reduction in total symptom scale of Kellner Symptom Rating Test and the reduction in sub-scales for anxiety, depression, somatic complaints and general neurotic symptoms with parallel symptom reduction in linear analogue scales. Side effects were infrequent with both drugs and posed no clinical problem. Potasium clorazepate in a single nightly dose of 15 mg proved to be more effective than thrice daily (5mg) diazepam.
Acute Hepatitis a in West Scotland in 1981 a Change in Pattern
Authors: Follett E. A. C. , McMichael S. , Stewart J. , Cromack S.
Published: January 2017

In 1981, 151 cases of laboratory confirmed Hepatitis A infection were diagnosed in West Scotland, an increase of more than three-fold over both 1979 and 1980. The majority (54%) were in children under 15 years of age, case numbers then declining with age, apart from a rise in numbers in the 21–30 age group. Almost all children infected were Scottish children. Significant numbers were associated with contact with a known case (25%) or travel abroad (16%). Few cases were diagnosed in the first five months of the year. This upsurge in laboratory-diagnosed cases was associated with an increase in notifications of viral hepatitis to the Registrar General for Scotland for the first time in 10 years.
Reactive Arthritis—Infectious Agents and Genetic Susceptibility in the Pathogenesis of Sero-Negative Arthritis
Authors: Ford M. J. , Hurst N. P. , Nuki G.
Published: January 2017

In this review we discuss the role of genetic and infectious factors in the aetiology of ‘reactive’ arthritis. Two broad categories of reactive arthritis are considered—the sero-negative HLA B27 related spondarthritides, and a miscellaneous group of reactive arthritides occuring after bacterial infection but which are not HLA B27 related.
Successful Treatment of Multiresistant Pseudomonas Peritonitis with Combination of Azlocillin and Amikacin
Authors: Leung A. C. T. , Gribben J. , Sleigh J. D. , Jones J. M. Boulton
Published: January 2017

Multiresistant Pseudomonas infection remains a problem in hospital practice. We report a case of pseudomonas peritonitis successfully treated by a combination of azlocillin and amikacin. This is the first case report of the intraperitoneal use of azlocillin.
Beta-Adrenoceptor Blockade and Intrinsic Sympathomimetic Activity — Relevance in the Treatment of Ischaemic Heart Disease
Authors: Northcote R.J. , Ballantyne D.
Published: January 2017

Beta adrenoceptor blockade has become one of the major therapeutic interventions in the medical management of ischaemic heart disease over the last 15 years. A number of beta adrenóceptor blockers have been developed with differing pharmacological properties including cardioselectivity and intrinsic sympathomimetic activity (ISA). The relevance of this latter property has been in some doubt. A number of reports suggest that ISA confers haemodynamic benefits although there does not appear to be any clear therapeutic advantage. In addition it would appear that patients with severe or rest angina might benefit more from a pure beta antagonist rather than one with ISA when the beta blocker is used as monotherapy, but this situation rarely arises.

This paper reviews and assesses the value of treatment of ischaemic heart disease with beta blockers possessing intrinsic sympathomimetic activity.
Self Poisoning. A Review of Patients Seen in the Victoria Infirmary, Glasgow
Authors: Willox D.G.A.
Published: January 2017

Seventy-three patients who had taken a deliberate overdose were seen over a six-week period. Self poisoning was found to be most common in females aged 20 to 29 years and in the unemployed (60%). Most patients had also taken alcohol (63%). The benzodiazepines were the most common drug taken (56%) and most drugs taken were prescribed by the patient's General Practitioner (G.P.) (81%). One-third of those involved had consulted their G. P. within one week of taking the overdose and 40 per cent had a history of previous self poisoning. Eighty-six per cent were admitted to the wards directly from the casualty department and of these, three-quarters were referred for a psychiatric opinion. Fourteen per cent of all patients seen were admitted for further treatment to a psychiatric hospital.
Drug Abuse in Body Builders in the West of Scotland
Authors: McKillop G.
Published: January 2017

Forty one amateur body builders in a West of Scotland gymnasium were questioned about body building drug usage during the period January 1984 to January 1985.

Eight out of 41 (19.5%) had used drugs to enhance their physique and performance. Anabolic and androgenic agents were mainly used but diuretics, thyroxine and human chorionic gonadotrophin were also used. Those who took drugs, in all cases, took combinations of drugs.

Drug dosage was generally much in excess of that normally recommended, though there were no serious side effects at the time of the study.

If this experience was typical nationwide it would represent a significant number of body builders abusing drugs. In no case was there any medical supervision.
Carcinoid Tumour Presenting as Recurrent Gastric Outlet Obstruction: A Case of Long-Term Survival
Authors: Green S.T. , Drury J.K. , McCallion J. , Erwin L.
Published: January 2017

A rare gastric tumour which presented on two occasions with gastric outlet obstruction is described. The important feature is that a gastric tumour presenting in this manner is not necessarily carcinoma.
Failure to Diagnose the Milk-Alkali Syndrome
Authors: Canning G. , Slater S. D.
Published: January 2017

A case of recurrent hypercalcaemia due to chronic continuous ingestion of a calcium-containing antacid is described in whom the diagnosis was delayed because of an insufficiently detailed drug history. Specific named enquiry must be made of all the various calcium-containing drugs when seeking a history of excessive calcium intake if the diagnosis of the milk-alkali syndrome is not to be missed.
Seasonal and Climatic Variation in Cholesterol and Vitamin C: Effect of Vitamin C Supplementation
Authors: MacRury S.M. , Muir M. , Hume R.
Published: January 2017

Vitamin C (ascorbic acid) is an important anti-oxidant which may help to reduce free radical damage and atheroma formation in blood vessels. In a study in which a group of healthy volunteer subjects were followed up for 12 months and a group of patients with vascular disease taking Vitamin C supplements were followed for 23 months, we confirmed previous findings of seasonal variations in ascorbic acid and cholesterol and have shown an inverse relationship between leucocyte ascorbic acid and serum cholesterol levels. In healthy control subjects the increase in ascorbate and fall in cholesterol during the summer months was reversed when the weather changed to a more winter pattern, presumably due to dietary alterations. We found that ascorbic acid levels were lower in patients with peripheral vascular disease and that although normal ascorbic acid levels were achieved with Vitamin C supplementation, when supplements were stopped at the height of a normal summer, there was a fall in ascorbic acid and a rise in serum cholesterol to winter levels. Given these findings we suggest that patients with vascular disease should have Vitamin C supplements throughout the year.
Medical Clinic Referral Letters Do They Say What They Mean? Do They Mean What They Say?
Authors: Hodge J.A.H. , Jacob A. , Ford M.J. , Munro J.F.
Published: January 2017

Consecutive general practitioner referrals to three general medical clinics were examined prospectively to assess whether the reason for referral was being correctly interpreted by consultants. The resultant data revealed that although this was not always the case, such misunderstandings did not appear to affect subsequent management. Explicit reasons for referral in the referral letter however could improve both the quality and value of out-patient consultations.
Creutzfeldt-Jakob Disease in Scotland and Northern Ireland 1980–1989
Authors: Esmonde T.G. , Will R.G.
Published: January 2017

The epidemiological and clinical features of Creutzfeldt-Jakob disease have never before been studied in Scotland and Northern Ireland. Case records for those dying with this diagnosis were obtained for the period 1980–89. Over the ten year period, 25 definite or probable cases were identified, giving an annual incidence of 0.37 cases/million. There were more cases in the second half of the decade, and this was most likely due to increased ascertainment. One pair of cases occurred in close proximity to each other. Sex distribution showed an excess of males (male female ratio = 1.8: 1). Mean age at onset was 65.2 years, and mean duration of disease was 5.3 months. The presenting symptoms and clinical features were similar to those noted in previous studies of other populations. There was no excess of cases in occupations linked to food, farming, or medical/paramedical work.
Outcome of Treating Thyrotoxic Patients with a Standard Dose of Radioactive Iodine
Authors: Johnson J.K.
Published: January 2017

This is a report of an audit exercise that was designed to study the effectiveness of treating thyrotoxic patiients with a standard dose — 370 MBq — of radioactive iodine (131l). This treatment was received by 183 patients in one centre between 1977 and 1989. The results were assessed from the answers to 114 questionnaires that had been completed by the patients' general practitioners. The patients were aged between 28 and 85 years; 86% were female; 42% had been treated previously with anti-thyroid drugs. Ninety-five of the patients (83%) became euthyroid after a single dose of 131l; 18 required one further dose; and one required two further doses. At the time of the survey, 32 (28%) were euthyroid, while 82 patients (72%) had become hypothyroid and required treatment with thyroxine. Within five years of treatment, 85% of the patients had become hypothyroid. These results are compared with those from two other centres.
A Local Review of Domiciliary Consultations
Authors: Mackay K.
Published: January 2017

This report examines the trends and patterns of domiciliary consultations within Lothian Health Board area. Lothian Health Board is the second largest health board in Scotland. It is a teaching board with a mixed urban and rural population of 750,000. This is a retrospective study of data on domiciliary consultations from the Information and Statistic Division of the Common Services agency for the years 1986 to 1991. Comparison of total figures nationally and locally and an examination of numbers of visits among specialties within the health board area.

Between 1986 and 1991 the total number of domiciliary consultations in Scotland dropped by 27%. During the same period the average rate for three of the four Scottish teaching boards fell by 32% while for Lothian it fell by 20%. Average teaching board figures dropped consistently each year but Lothian figures showed more fluctuation, in particular, a drop of 20% between 1990 and 1991. The large drop in domiciliary visits was reflected in two of the three main specialties for the same period.
Recreational Overdosage of Carbamazepine in Paisley Drug Abusers
Authors: Crawford P.J. , Fisher B.M.
Published: January 2017

Oral drug abuse is a major social and medical issue. Paisley, in the West of Scotland, has become infamous for its problem with oral temazepam abuse. With the crack down on the prescription of temazepam in our area and the resultant lack of its supply on the streets, drug abusers appear to be experimenting with new drugs for their psychotropic effects. We report five cases of recreational carbamazepine overdosage in young temazepam abusers.
Reaudit of Acute Asthma Admissions Using a Severity Marker Stamp and Determinants of an Outcome Measure
Authors: Mathur R. , Clark R.A. , Dhillon D.P. , Winter J.H. , Lipworth B.J.
Published: January 2017

Subsequent to the implementation of a severity marker stamp in case notes, an audit was performed in 86 admissions with acute asthma to a specialist centre over a 12 month period. Compared to previous audit the documentation of severity markers was significantly better (PEFR: 52% vs 83%p=0.001, Respiratory rate: 44% vs 81%p=0.001, ABG: 72% vs 80%p=0.04, air entry: 58% vs 86%p=0.001, speech: 27% vs 86%p=0.001, exhaustion: 4% vs 86%p=0.001). In contrast to the previous audit where no patient received Fi02 >0.35, 66% of the cases in the repeat audit received Fi02 0.60 (p=0.001).

The mean duration of admission was five days and showed highest partial correlation (r=0.6) to the time in hours for the pulse to fall to 80/min. Multiple linear regression showed that this was the only variable best predicting the duration of admission (R2=0.3). Admission pulse rate (p=0.04) andserum K+(p=0.04) best discriminated between patients admitted for over and under five days. Logistic regression identified only the admission pulse as significant in calculating the odds of the patient staying in the hospital for >5 days.
Scotland's First Iron Lung
Authors: Porter I.A. , Williams M.J.
Published: January 2017

The history of artificial ventilation and the development of the iron lung in the USA by Drinker and his colleagues is discussed. The building and use of an iron lung by Dr R G Henderson in Aberdeen in 1933 is described. The development of other types of ventilator in the UK is recorded and the circumstances whereby positive pressure ventilation was introduced in Denmark in 1952 is outlined.
Heart and Arterial Disease Risk Factors Measured in an Office Workforce: Changes from 1993 to 1996
Authors: McEwan S.R. , Hau C. , Daly F. , Forbes CD
Published: January 2017

Screening for cardiovascular risk factor prevalence was arranged in an office workforce in Scotland with two screenings taking place three years apart, in order to measure and attempt to modify individual risk factor profiles, and in order to explore the nature and extent of any changes. There were some increases over time for both sexes, with increased tobacco usage for men, significant increases in diastolic blood pressure for both sexes and a significant increase in mean cholesterol levels for women. A separate analysis was restricted to those individuals screened on both occasions and sought to explore the effect of personal counselling and advice: in fact there were significant increases in tobacco usage for women, with more starting smoking than stopping, and for both sexes there were significant rises in cholesterol levels and increases in body mass index for many individuals. There was significantly increased use of wine and spirits by both sexes.
The Outcome of the First 165 Orthotopic Liver Transplants in Scotland
Authors: Bathgate A.J. , Garden O.J. , Forsythe J.R.L. , Madhaven K.K. , Finlayson N.D.C. , Simpson K.J. , Hayes P.C. , MacGilchrist A.J.
Published: January 2017

The Scottish Liver Transplant Unit is now in its sixth year of existence. We present the outcome of the first 165 transplants which have at least 12 months follow up. The overall patient (n=143) survival rates at 1, 3 and 5 years were 86.6%, 79.3% and 74.7% and the graft survival rates were 76.9%, 69.1 % and 64.8%. The one year survival rate for patients with chronic liver disease (n=113) was 89.2% compared with 76.6% for acute liver failure (Breslow= 0.05). The one year survival rate for the first 71 patients receiving their primary graft was 81.7% compared with 91.5% for the subsequent 71 patients (Breslow = 0.09). The majority of deaths (n=29) were due to sepsis (n=7), at operation (n=6) or due to graft vascular insufficiency (n=4). There were two cases ofde novo haematological malignancy. The outcome of the first 165 transplants in Scotland compares very well with other countries throughout the world.
Polaroid Photographic Referral for Skin Cancer — A Potentially Useful Method of Reducing Time to Surgery
Authors: Khan F. , McGregor J. C.
Published: January 2017

A prospective trial was conducted on twenty-five patients referred by dermatologists during 1998 using a referral letter and an accompanying polaroid photograph for prospective plastic surgical management of skin cancers. Using the description and the photograph, suitable patients were given dates for operation without requiring a plastic surgery out-patient clinic appointment. This enabled, not only a saving in the cost of an out-patient appointment, but a significant reduction in waiting time to surgery.
Primary Ciliary Dyskinesia Syndrome and Primary Generalised Epilepsy
Authors: Shepherd R.C.
Published: January 2017

A child with primary ciliary dyskinesia syndrome (PCDS) developed primary generalised epilepsy (PGE). The PGE had characteristics of both childhood absence epilepsy (CAE) and juvenile myoclonic epilepsy (JME). The association of PCDS and PGE has not previously been recorded.
Transatlantic city, part 2: Late entrepreneurialism
Authors: Peck Jamie
Published: January 2017

The first installment of this two-part paper made a case for a conjunctural approach to urban studies, reserving a special place for the provisional formulation and ongoing revision of midlevel theories – from the entrepreneurial city to austerity urbanism and financialised urban governance – while positioning abstraction and contextualisation as simultaneous, dialogic practices. It follows that such arguments can be developed only so far in the absence of concrete cases, where conjunctural accounts actually gain traction, direction and purpose. Seeking to operationalise some of these methodological principles by way of a situated, single-city case study, this part of the paper returns to the financially challenged casino capital of Atlantic City, tracing its long (and notorious) history of entrepreneurial dealings, from Republican machine control to the ‘experiment’ with legalised gambling that was launched in the mid-1970s, and positioning the structural crisis that preceded the casino pact with the existential crisis that has been generated in the wake of the failure of this distinctive local growth machine. Atlantic City made a very large wager that did not pay off, the unravelling of its much-emulated model of entrepreneurial urbanism dramatising a distinctly ‘late-entrepreneurial’ moment of fiscally mandated governance and political crisis.
Who Will Make Room for the Intersexed?
Authors: Haas Kate
Published: January 2017

Between 1.7 and 4% of the world population is born with intersex conditions, having primary and secondary sexual characteristics that are neither clearly male nor female. The current recommended treatment for an infant born with an intersex condition is genital reconstruction surgery to render the child as clearly sexed either male or female. Every day in the United States, five children are subjected to genital reconstruction surgery that may leave them with permanent physical and emotional scars. Despite efforts by intersexed people to educate the medical community about their rejection of infant genital reconstruction surgery, the American medical community has not yet accepted the fact that differences in genital size and shape do not necessarily require surgical correction.

Genital reconstruction surgery may involve removing part or all of the penis and scrotum or clitoris and labia of a child, remodeling a penis or creating a vaginal opening. While the initial surgery is typically performed in the first month of a child's life, genital reconstruction surgery is not only performed on infants.
Ethos and Economics: Examining the Rationale Underlying Stem Cell and Cloning Research Policies in the United States, Germany, and Japan
Authors: Campbell Angela
Published: January 2017

The governance of reproductive science is fraught with controversy in nearly every jurisdiction across the globe. Worldwide, legislators and policy makers have struggled to craft meaningful and ethical parameters for the regulation of this new and evolving area of biotechnology. In most countries, it is agreed that some form of regulatory oversight over reproductive technologies is necessary. There is far less consensus, however, as to the type of regulatory structure that should be established. Recent debates over reproductive science have focused on two of the most controversial practices in this area: embryonic stem cell research and cloning technology. Specifically, interested parties have struggled over whether these practices are so egregious that they should be altogether prohibited, or whether they ought to be permitted, but subject to particular legislative limits and regulatory oversight.

The difficulties that most countries have experienced in devising legislation pertaining to embryonic stem cell and cloning research emanate from the moral ambiguity that characterizes this area of science.
Ethical and Legal Aspects of Using an Identical Twin as a Skin Transplant Donor for a Severely Burned Minor
Authors: Tilden Samuel J.
Published: January 2017

On January 7, 2003, Sydney Cowan, a healthy six-year-old girl, underwent skin harvesting, specifically to be used for her badly burned identical twin sister, Jennifer. A day earlier, the Probate Court of Jefferson County, Alabama, after considering whether a healthy minor twin sibling could serve as a skin donor for her severely burned sister, authorized parental consent to the surgery. More accurately, the court addressed whether Sydney could undergo surgical procedures that provided her with no physical benefit, but, rather, resulted in harmful effects, such as acute postoperative pain, permanent residua, and potential long-term emotional and psychological dysfunction.

Although the transplants were extraordinarily successful, and the newspaper article depicted Sydney's participation in heroic terms, the harvesting of Sydney's skin was ethically problematic. Specifically, I assert that the use of an incompetent minor as a skin transplant donor, even if an identical twin, is not justified unless the transplant will save the recipient's life.
Defining a Standard of Care in the Practice of Acupuncture
Authors: Kung Christine C.
Published: January 2017

In 1971, New York Times journalist James Reston watched as brain surgery was preformed in the former Red Cross Hospital in Shanghai with acupuncture as the only anesthesia. “[Patients] were anesthetized merely by the insertion of very thin three-inch stainless steel needles into the body … and they were not only perfectly conscious while their skulls were laid open before us but remarkably alert within half an hour after the operation.” One patient, a fifty-four-year-old man named Chuan Leao, had been suffering from epilepsy as a result of a large tumor in the frontal lobe of his brain. “He seemed sensibly puzzled by being introduced to a couple of American strangers during his ordeal but was courteous and patient, and we listened to his comments while the tumor was removed and even watched him eat oranges slices and ask for more while the operation was going on.”
The Vioxx Story: Would it Have Ended Differently in the European Union?
Authors: Thomas W. John
Published: January 2017

The rise and fall of the pain-killer Vioxx is one of the most remarkable marketing stories in pharmaceutical history. A true riches to rags tale, its events unfolded with lightning speed in an industry defined by lethargy.

On May 20, 1999, the Merck Company secured FDA approval of Vioxx for the management of acute pain in adults and for relief of the signs and symptoms of osteoarthritis. From that date through August 2004, 105 million Vioxx prescriptions were filled in the US and an undetermined number were filled outside the US. In 2003 alone, Merck's worldwide Vioxx sales totaled $2.5 billion.

The fall happened even more quickly than the rise. In March 2000, Merck published a study raising the specter of cardiovascular problems associated with taking Vioxx. In November 2000, The New England Journal of Medicine published a study raising similar concerns. In February 2001, an FDA advisory panel became sufficiently concerned about the association of Vioxx and cardiovascular events that it advised the FDA to require a label warning about the possible link.
Cheaper Clinical Trials: The Real Solution to the Biologic Industry's Gordian Knot
Authors: Montas Alana
Published: January 2017

Biologics include a wide range of products, such as vaccines, allergenics, gene therapies, and tissues, among others. Biologics are complex combinations of sugars, proteins, or nucleic acids that are produced by biotechnology methods or other advanced technology. Biologics often represent the only medical treatment for complex medical conditions such as: Hepatitis B; Measles, Mumps, Rubella and Varicella; and Tetravalent meningococcal conjugate among others. As a result, biologic sales are growing at twice the rate of chemical pharmaceuticals and are expected to exceed $158 billion by 2015. Various interest groups, including patients, insurers, and regulatory agencies, raised concerns about the financial impact that biologics may have on health care costs. Congress and the Food and Drug Administration (FDA) faced pressure to provide a solution to the soaring biologic costs, namely through a regulatory pathway for generic biologics (“follow-on biologics”) to manufacture cheaper products. Although a regulatory pathway for generic chemical pharmaceuticals (“generic”) exists under the Hatch-Waxman Act, a similar regulatory pathway for follow-on biologics did not exist prior to 2010.
Deficiencies of the FDA in Evaluating Generic Formulations: Addressing Narrow Therapeutic Index Drugs
Authors: Hottinger Michelle , Liang Bryan A.
Published: January 2017

Generic drugs represent a significant portion of the medical arsenal in treating disease. As copies of originator drugs, these drugs have been permitted abbreviated approval under the Hatch-Waxman Act. Yet with the current cost focus upon generic formulations, potential safety issues with generics have arisen. Although there is an established criterion of “bioequivalence” that generic formulations must demonstrate, narrow-therapeutic index drugs for sensitive clinical circumstances such as epilepsy, antiplatelet therapies, and mental health treatments may require different regulatory treatment than other generic drugs. Further, in these circumstances, differences in generic formulations may lead to adverse clinical outcomes due to less stringent bioequivalence tolerances. Yet there is no mandate for comparison between different generic formulations. Countries outside the United States advocate for narrowing tolerance ranges for these high risk health situations and the drugs for their treatment. We argue in this paper that additional patient safety matters must be taken into account for narrow therapeutic disease drugs, and regulatory bodies should emphasize greater tightness in bioequivalence before these narrow-therapeutic drug generic formulations are approved.
When the First Amendment and Public Health Collide: The Court's Increasingly Strict Constitutional Scrutiny of Health Regulations That Restrict Commercial Speech
Authors: Rauer Samantha
Published: January 2017

In Sorrell v. IMS Health Inc., the Supreme Court departed from traditional commercial speech doctrine in striking down Vermont's Prescription Confidentiality Law under a heightened level of scrutiny. The Prescription Confidentiality Law was Vermont's attempt to prevent pharmacies from sharing information about doctors’ prescribing habits with drug manufacturers without the consent of the doctor. The law aimed to protect doctors, as well as to promote public health, by regulating speech and conduct that is arguably commercial in nature. The Court has purported to subject regulation of commercial speech to only an intermediate level of scrutiny since Virginia State Board of Pharmacy v. Virginia Citizen's Consumer Council, Inc. established that as the proper standard. Thus, it was inconsistent for the Court to categorize the commercial speech regulation in Sorrell as “content-based” and thus subject to a stricter level of review. The invalidation of the Prescription Confidentiality Law, however, is only the most recent development in the Court's strict treatment of health-related regulations infringing on commercial speech. The Court has been moving toward a more stringent level of scrutiny since first applying the commercial speech doctrine in a public health context in Rubin v. Coors.
A Comprehensive Strategy to Overhaul FDA Authority for Misleading Food Labels
Authors: Pomeranz Jennifer L.
Published: January 2017

The modern food environment is considered a primary driver of obesity and other nutrition-related chronic diseases. A significant contribution to this environment is the proliferation of claims on food packaging that provides a misleading picture of a product's healthfulness. The Food and Drug Administration (FDA) is the agency responsible for food labels but it lacks the regulatory authority and adequate resources to address the majority of questionable labeling practices. The FDA's current system of enforcement is thus essentially based on voluntary compliance and consumer- and manufacturer-initiated litigation has not successfully filled the regulatory gap. This manuscript reviews the current state of food labeling claims and the FDA's inadequate authority over misbranded food products. It analyzes competing views on regulatory compliance strategies and argues that a regulatory overhaul consistent with the best science and the First Amendment is necessary. With increased resources and authority, the FDA can meet current public health challenges and adequately ensure that labels are clear and consumers are properly informed and protected.
Use of Beta-Blocking Agents with Group Therapy in a Smoking Withdrawal Clinic
Authors: Dow Robert J , Fee Walter M
Published: January 2017

A controlled trial was carried out into the relative efficacy of two beta-blocking agents (oxprenolol and metoprolol) as adjuncts to group therapy in a smoking withdrawal clinic. There was no evidence to indicate that these were of specific value in assisting smoking withdrawal.
Low-Dose 131I in Treatment of Graves' Disease
Authors: Lowdell C P , Spathis G S , Cosgrove D O , Dobbs H J , McCready V R , Harmer C L
Published: January 2017

One hundred and sixty-four patients with Graves' disease were treated with low-dose radioiodine (2 mCi), with a mean follow up of 4 1/2 years. At this time 74 (45%) were euthyroid having had a single dose, with a total of 131 (80%) being controlled with one or more doses. Three (2%) were still toxic but their mean follow up was only 3 years. Thirty (18%) were rendered hypothyroid, two-thirds of these after a single dose of 2 mCi 131I. The one-year incidence of hypothyroidism was 6%, with an incidence at 6 years of 20%. Previous surgery, medical treatment and thyroid antibody status appeared to have no influence on the outcome.
Prognostic Value of Tissue Polypeptide Antigen in Urological Neoplasia
Authors: Costello C B , Kumar S
Published: January 2017

The prognostic importance of tissue polypeptide antigen (TPA) in urine samples of patients with urological cancers has been evaluated. TPA concentration correlated well both with the stage of the disease and survival. A simple score system was devised. There was very significant worsening of the prognosis with increasing score.
Campylobacter Colitis: Differentiation from Acute Inflammatory Bowel Disease
Authors: Mee A S , Shield M , Burke Margaret
Published: January 2017

We describe 10 patients with campylobacter colitis who gave a characteristic his tory of an acute diarrhoeal illness, rectal bleeding and colicky abdominal pain. For the majority of patients the clinical and sigmoidoscopic features differentiated campylobacter colitis from acute inflammatory bowel disease. Where doubt remained, evidence of a specific antibody response to campylobacter enabled a presumptive clinical diagnosis to be confirmed.
Isotope Phallogram: Preliminary Communication
Authors: Townell N H , Hilson A J W , Morgan R J , Siraj Q H , Dick R
Published: January 2017

The isotope phallogram is an investigation which uses radioisotope-labelled red cells in the imaging of penile arterial blood flow. In a preliminary series of 12 impotent patients undergoing both internal iliac arteriography and isotope phallography, the penogram index described by Fannous et al. (1982) has been modified to derive an accurate indicator of vascular disease.
More Than Just Sex
Authors: Debrot Anik , Meuwly Nathalie , Muise Amy , Impett Emily A. , Schoebi Dominik
Published: January 2017

Positive interpersonal interactions such as affection are central to well-being. Sex is associated with greater individual well-being, but little is known about why this occurs. We predicted that experienced affection would account for the association between sex and well-being. Cross-sectional results indicated that affection mediated the association between sex and both life satisfaction (Study 1) and positive emotions (however, among men only in Study 2). In Study 3, an experience sampling study with 106 dual-earner couples with children, affection mediated the association between sex and increased positive affect in daily life. Cross-lagged analyses in Study 3 to 4 supported the predicted direction of the associations. Moreover, the strength of the daily association between sex and positive affect predicted both partners’ relationship satisfaction 6 months later. Our findings underscore the importance of affection and positive affect for understanding how sex promotes well-being and has long-term relational benefits.
Differences in Types and Incidence of Neoplasms in Wistar Han and Sprague-Dawley Rats
Authors: Weber Klaus
Published: January 2017

A substantial quantity of data on Sprague-Dawley (SD) and Hannover Wistar rats strains have been published concerning their source, diet, and housing conditions, as well as the incidences of nonneoplastic lesions and neoplasms observed in different laboratories. Differences between the commonly used rat strains provided by different breeders (i.e., CD (SD) vs. Harlan Sprague-Dawley strain or Crl: WI(Han) vs. Wistar Hannover (Han)–derived strain, continued breeding by RCC Ltd., Switzerland, thereafter continued breeding by Harlan) may include, but are not limited to, body weight, incidence, and onset of major nonneoplastic lesions and neoplasms, and these can impact the development of a nonclinical safety program. Fisher 344 (F344) and SD rat strains generally have the highest tumor incidences, exceeding that in Wistar rats. Certain tumors are more commonly observed in one strain, and for some, the difference in incidence may be so significant that the tumor may even be considered characteristic for a specific strain (e.g., thymoma in Wistar and amphophilic renal adenoma in SD).
Ventricular endomyocardial fibrosis in a pregnant female with Behçet’s disease
Authors: Mirfeizi Zahra , Memar Bahram , PourZand Hoorak , Molseghi Mohammad Hadi , Rezaei Shahmirzadi Arash , Abdolahi Nafiseh
Published: January 2017

A 32-year-old pregnant woman, diagnosed with Behçet’s disease 6 months earlier, presented with recent mild hemoptysis and exertional dyspnea. Transthoracic echocardiography showed an enlarged dysfunctional right ventricle. A large hypoechoic triangular-shaped mass was seen attached to the inner right ventricular wall, filling the cavity. No change in the size of the mass was noted after anticoagulant administration, and right heart failure progressed. Surgery was performed to remove the mass and repair the tricuspid valve. This was a very rare presentation of Behçet’s disease in pregnancy, which resulted in delivery of a completely healthy baby despite corticosteroid pulse therapy and cyclophosphamide.
Thymoma-associated immunodeficiency: a diagnostic challenge for the clinician
Authors: Narahari Narendra Kumar , Gongati Paramjyothi Kruparao , Kakarla Bhaskar , Nizami Mohammed Ismail , Boddula Rajendra Prasad , Sattavarapu Laxma Reddy
Published: January 2017

Good’s syndrome or thymoma-associated immunodeficiency is a rare clinical entity that is often presumed to be common variable immunodeficiency, due to lack of awareness and recognition of this syndrome. This syndrome more often goes unrecognized if a thymoma is not detected. An appropriate immunological work-up that aids timely diagnosis and adequate therapy with antimicrobials and intravenous immunoglobulins are mandatory to prevent the long-term complications and mortality associated with this syndrome. We present the clinical and immunological profile of a young man with Good’s syndrome that was initially presumed to be common variable immunodeficiency.
American Business Information in the UK
Authors: Sangster Patricia , Bawden David
Published: January 2017

This paper addresses the question of the need for American business information in the UK in the light of the development of the European Single Market. In order to establish what needs exist and what sources are used, a questionnaire was sent to 80 business libraries throughout the UK, and in-depth interviews were carried out. The surveys show that, although the need for US data is small in some areas, it is still an important part of business information provision and is likely to remain so.
Objective Assessment of Skin Changes in Lower Limb Venous Disease Using a Tissue Tonometer
Authors: Farrah J. , Saharay M. , Smith P. D. Coleridge
Published: January 2017

Background:

Chronic venous disease (CVD) of the lower limbs is a major problem in the western world with 1% of the adult population estimated to be affected at any one time. No objective method is currently available to assess the skin changes of chronic venous disease. We have devised a tissue tonometer to compare skin compliance in patients with venous disease with that in control subjects.

Method:

Eighty-six limbs of 69 patients (34 men, 35 women; mean age 62 years, range 28-90 years) with venous disease confirmed by duplex ultrasonography and 42 limbs of 37 normal controls (23 men, 14 women; mean age 42 years, range 20-90 years) were studied. Patients were assigned to one of three clinical groups based on the Clinical, (a) Etiological, Anatomical and Pathophysiological (CEAP) method of classification and grading of chronic venous disease in the lower limbs: C3, oedema; C4a, pigmentation alone; C4b, lipodermato-sclerosis (LDS). Normal controls were assigned C0. A 4 mm diameter plunger loaded with a 30 g weight was applied to the skin 5 cm proximal to the medial malleolus or over the most severe region of skin change. The movement of the plunger was measured for 5 min using a linear variable differential transformer position detector. The initial displacement of the plunger (within 1 s) reflects the compliance of the skin.

Results:

In C4b patients with LDS, skin compliance is substantially reduced (median plunger displacement in 1 s = 0.81 mm, interquartile range (IQR) 0.67–1.18) compared with C0 control subjects (2.85 mm, IQR 2.39–3.22) (p<0.0005, Mann-Whitney), C4a patients with pigmentation alone without LDS (2.35 mm, IQR 2.04–2.91) (p<0.0005, Mann-Whitney) or C3 patients with venous disease (2.49 mm, IQR 1.58–3.13) (p<0.0005, Mann-Whitney). There were no statistically significant differences between the C0, C3 and C4a groups.

Conclusion:

Tissue tonometry provides an objective means of assessing skin changes in patients with lower limb chronic venous disease. This may be a useful method of measuring skin compliance as a research tool but will have limited clinical application.
Patient Profile of the French Active Population Treated by Phlebotropic Drugs Dispensed on Prescription
Authors: Levy E. , Levy P. , Los F. , Chevalier H.
Published: January 2017

Objective:

To determine the socioeconomic profile of French active purchasers versus active non-purchasers of prescription phlebotropics.

Methods:

A survey of the French adult population from December 1998 to February 1999 profiled active purchasers versus active non-purchasers of prescription phlebotropics in the previous 12 months.

Results:

The overall prevalence of symptomatic lower limb venous disease was 47.4%. Of the general population 26.8% took treatment, including 21.5% with prescription phlebotropics (‘purchasers’). In the active population, purchasers (17.5%) were aged 41.3 years on average and were mostly female (73% vs 44% non-purchasers; p < 0.01), lower paid and less skilled than non-purchasers (office workers: 44% vs 30%; manage-rial/professional: 10% vs 17%), worked in poorer conditions (standing for 4.2 vs 3.1 hours/day) (all p < 0.01), but had better health insurance cover (91% including complementary insurance vs 83% in the overall population). Health status and medical history were worse in purchasers than in non-purchasers.

Conclusions:

Prescription phlebotropic purchasers - a substantial, underprivileged and largely female fraction of the working population - have access to treatment in correlation with an adequate health insurance cover.
A Study of Venous Return from the Leg during Exercise
Authors: Dickey James W.
Published: January 2017

Bi-directional ultrasound velocity detector tracings were made of venous blood flow through the popliteal vein in the following situations: (1) walking normally; (2) walking in place; (3) sitting, foot on floor, with rhythmic plantar and dorsi-flexion; (4) sitting, foot on a treadle device requiring 20 degrees of plantar-flexion and 20 degrees of dorsi-flexion to complete a cycle; (5) using the treadle device while in recumbent position, and (6) pushing the foot in plantar flexion against a pedal equipped with a spring resistance.

These studies show that active walking, which consists of both plantar flexion and dorsi-flexion, produces cephalad return of venous blood from the foot and leg. When the walking cycle is accompanied by weight bearing, plantar flexion produces a greater blood velocity. However, when there is no weight bearing, dorsi-flexion produces a greater blood velocity than plantar flexion.

Therefore, when not bearing weight on the foot, a full range of dorsi-flexion as well as a full range of plantar flexion is essential to utilizing maximum efficiency of the lower extremity muscle pump.