RHEUMATIC FEVER IN COLLEGE STUDENTS

The results of three independent surveys concerned with rheumatic fever and heart disease in students at the University of California were assembled and found to be in close agreement. A full 2 per cent of all students believed they had had rheumatic fever; and several times that proportion gave a history of one of the rheumatic manifestations. Only 0.25 per cent had demonstrable rheumatic heart disease and 0.1 per cent had congenital heart disease.Physiologic murmurs may occur in 3 per cent or more of students entering college.Penicillin prophylaxis is important in persons with rheumatic heart disease, but it is important not to put a label of rheumatic heart disease on persons who think they have had rheumatic fever but who have no demonstrable heart disease. Long term penicillin prophylaxis or other long term prophylactic procedures directed against rheumatic fever are not indicated unless the diagnostic criteria for rheumatic fever are clearly met or unless rheumatic heart involvement is definitely present.     

Diseases of the heart in a working population; a study of morbidity and mortality in relation to cardiac status and nature of job

A sample consisting of 2,252 persons among 20,199 Los Angeles civil service employees was observed for the occurrence of heart disease. The first examination measured the prevalence. Based upon the diagnosis of 165 cases of heart disease, the prevalence was 73 per 1,000 persons examined. Two reexaminations, at intervals of 12 to 18 months, of persons with normal heart on the first examination were carried out and 52 additional cases were diagnosed. There were also 13 deaths of heart disease in persons first diagnosed as having normal heart, making a total of 65 "new" cases (36.6 per 1,000) during the 30-month period of observation. An annual estimated heart disease incidence of 15 per 1,000 appears reasonable. Based on 89 deaths, the cardiovascular disease death rate was 11 per 1,000 among persons entering the study with normal heart, and 133 per 1,000 persons diagnosed as having heart disease at entry. The ratio of newly diagnosed cases to deaths of heart disease was 4 to 1.Among men diagnosed as having normal heart there was little difference in death rates whether their jobs were physically strenuous or sedentary. Among the men with heart disease, however, the highest death rates are observed among those employed at sedentary jobs and at light exertion. This may, of course, be an indication of the employee's selection of the job rather than the effect of inactivity. The relative usefulness of minifilm x-ray, electrocardiograms and questioning as to history were considered.     

DISEASES OF THE HEART IN A WORKING POPULATION—A Study of Morbidity and Mortality in Relation to Cardiac Status and Nature of Job

A sample consisting of 2,252 persons among 20,199 Los Angeles civil service employees was observed for the occurrence of heart disease. The first examination measured the prevalence. Based upon the diagnosis of 165 cases of heart disease, the prevalence was 73 per 1,000 persons examined.Two reexaminations, at intervals of 12 to 18 months, of persons with normal heart on the first examination were carried out and 52 additional cases were diagnosed. There were also 13 deaths of heart disease in persons first diagnosed as having normal heart, making a total of 65 “new” cases (36.6 per 1,000) during the 30-month period of observation. An annual estimated heart disease incidence of 15 per 1,000 appears reasonable.Based on 89 deaths, the cardiovascular disease death rate was 11 per 1,000 among persons entering the study with normal heart, and 133 per 1,000 persons diagnosed as having heart disease at entry. The ratio of newly diagnosed cases to deaths of heart disease was 4 to 1.Among men diagnosed as having normal heart there was little difference in death rates whether their jobs were physically strenuous or sedentary. Among the men with heart disease, however, the highest death rates are observed among those employed at sedentary jobs and at light exertion. This may, of course, be an indication of the employee''s selection of the job rather than the effect of inactivity. The relative usefulness of minifilm x-ray, electrocardiograms and questioning as to history were considered.     

PAGET'S DISEASE—Changes Occurring Following Treatment with Newer Hormonal Agents

From experience in six cases the anabolic steroid hormones, especially long-acting testosterone and estrogen preparations, are the treatment of choice in Paget''s disease, as in postmenopausal osteoporosis. Details of the management of three patients over a period of four years are presented.Roughly 4 per cent of the population, mostly persons over 40, show some evidence of Paget''s disease. Only a small number of them, however, have severe manifestations requiring treatment, such as pain, howing or fracture of the bones, pressure on nerves or heart failure. In rare cases malignant changes occur in the involved bone.Since the cause of Paget''s disease is not known, treatment in the past has been largely empirical. Reifenstein and Albright had advocated the therapeutic use of calcium, vitamin D and ascorbic acid, and, in postmenopausal women, administration of estrogens; but with fractures or immobilization, intake of calcium-containing foods, such as milk, must be restricted to avoid dangerous piling up of calcium and kidney stones, and fluids must be forced. In recent years anabolic steroid hormones, principally oral androgens and estrogens, have been employed by Gordan and others to promote bone repair, lessen bone pain and decrease urinary excretion of calcium. While these hormones probably do not arrest the disease, they seem to stabilize it and bring relief of symptoms.More recently, Albright and Henneman demonstrated that very large doses of corticotropin (ACTH) or cortisone resulted in immediate cessation of bone pain, decrease in urinary excretion of calcium and histologic evidence of regression of the disease process. The large doses required, however, also produce dangerous side effects, such as psychosis and osteoporosis, indicating that such treatment probably should not be continued over long periods.     

Illness, suffering and voluntary euthanasia

It is often accepted that we may legitimately speak about voluntary euthanasia only in cases of persons who are suffering because they are incurably injured or have an incurable disease. This article argues that when we consider the moral acceptability of voluntary euthanasia, we have no good reason to concentrate only on persons who are ill or injured and suffering.     

BODY BUILD AND LONGEVITY

The very expression “well built” has become a part of our language. It implies that persons of a particular build or structure are better coordinated or somehow can function better than other people and may, therefore, be expected to have a greater life span. Variations in the structure of individuals are marked and serve to distinguish fairly definite types. Insurance experience has crystallized into a number of fairly definite conclusions with regard to the relative longevity of certain of these types. Extremes of stature, for example, are decided handicaps. Extreme overweight and underweight carry with them increased mortality and correspondingly shorter life. Very heavy people are more likely to succumb prematurely to such conditions as diabetes, organic heart disease, renal impairment, hardening of the arteries, and very light persons, particularly at the younger ages, are more likely to develop tuberculosis. Insurance experience has confirmed the popular judgment that the individuals who approach the mean of these body measures are better able to withstand the hazards of life and to round out a fairly full expectation.     

Environmental Tobacco Smoke Exposure and Heart Disease: A Critique of the Claims of Glantz and Parmley

Background—A review by Glantz and Parmley published in 1995 and subsequently widely cited claims to demonstrate that passive smoke exposure increases the risk of heart disease. We have critically examined this claim in the light of the published evidence which they cite and of more recent publications. Methods and results—An updated review of the epidemiological evidence reveals no association between heart disease and ETS exposure in the workplace. Claims of an association with spousal smoking are weakened by the existence of various forms of bias in the studies. They are also undermined by recent reports from three large studies without evident major weaknesses which find essentially no association with spousal smoking. Interpretation of the experimental clinical studies is problematic because it is not possible to expose humans to ETS without their knowledge. For several reasons, short-term effects of exposure to unrealistically high concentrations of ETS throw no useful light on risk of coronary atherogenesis from long-term realistic exposure. In particular, the fact that humans can adapt to reduced ambient oxygen availability needs to be allowed for. Effects of counts of anuclear endothelial cell carcasses in circulating blood after ETS exposure are uninterpretable without basic information on the significance of this endpoint. The need for a realistic animal model for coronary atherosclerosis is not fulfilled by short-term studies in rats, rabbits, hamsters, birds or dogs in which aortic atheromatous plaque formation is used as a surrogate endpoint. Stress from confinement within cages, from the noise of fans and from irritation from high ETS concentrations needs to be controlled for, particularly in experiments on rabbits and birds. This has not been done and there is generally a serious dearth of information on the non-specific or specific effects of other environmental chemicals on many of the endpoints that have been used. Studies on the possible role of platelets in the aetiology of coronary heart disease are difficult to interpret because of confusion between their possible long-term role in atherogenesis and their putative involvement in thrombus formation which results in myocardial infarction. Evidence from an inadequately designed one-day study involving persons exposed to unmeasured amounts of ETS in a hospital corridor provides no insight into mechanisms involved in coronary atherogenesis. A study of the effect of exposure to ETS on the diameter of the brachial artery diameter is open to criticism because of the way in which subjects were recruited and failure to control for potentially important confounders. Conclusion — The available experimental and epidemiological evidence does not justify a conclusion that ETS exposure increases the risk of heart disease.     

Sudden death due to physical exercise in the elderly

Physical exercise has a beneficial effect to the humans. Sudden death in healthy persons engaged in physical exercise is extremely rare since healthy heart is protected from complications. The records of five elderly men who died during or immediately after exercise in the period between 1988-2001 in our region have been given, out of 23 men (and no one woman) aged 14-68 who died due to physical exercise in that time. They have been engaged in tennis, jogging and swimming recreatively. In all of them coronary heart disease has been found by the forensic autopsy. Only one has had arterial hypertension, symptoms of chest pain few years before accident and acute myocardial infarction has been found. The other four have been without symptoms. In three of them myocardial scars have been found of past myocardial infarctions. In all of them the thickness of the left ventricle wall was 15 mm or more (from 15 to 25 mm). It seems that the thickness of the wall of the left ventricle increases cardiovascular risk in persons without symptoms. In Croatia about 7% of the whole population are engaged in recreation. In this population 13% are elderly: 40,950. The reported five deaths due to recreational physical exercise in the elderly reached 1/114,660 persons every three years, or 1/573,300 persons during fourteen years.     

Properties of plasma low density lipoproteins in patients with hypertriglyceridemia and ischemic heart disease

It has been shown that low-density plasma lipoproteins in patients with ischemic heart disease and hypertriglyceridemia are heavier in density, smaller in size, more negatively charged and more inclined to peroxide modification and aggregation than in healthy persons. The protein in the composition of such lipoproteins deviates towards the water phase, which may result in the masking of the domen, recognized by the BE-receptor and may lead to hyperlipidemia of a retaining character.     

Dairy products and cardiovascular disease

PURPOSE OF REVIEW: Although it has often been postulated that the consumption of dairy products is associated with a high risk of coronary heart disease, study results have been conflicting. This review summarizes recent observational and human intervention trial findings on dairy products and cardiovascular disease. RECENT FINDINGS: Results from more recent observational studies on dairy products and milk disagree. This may be because of the very different methods used combined with several methodological problems. A somewhat surprising beneficial association between the intake of dairy products and the metabolic syndrome was observed in some studies, although not in a single study of elderly women. Milk may have the same cholesterol-raising properties as butter, whereas cheese does not seem to increase plasma cholesterol. Some milk products fermented by specific bacterial strains have been shown to have rather moderate cholesterol-reducing properties. There is also good evidence that certain fermented products (especially by Lactobacillus helveticus) have a mildly decreasing effect on hypertension, probably because of bioactive peptides. SUMMARY: When guiding principles such as balance, variety and moderation are stressed, there is no strong evidence that dairy products increase the risk of coronary heart disease in healthy men of all ages or young and middle-aged healthy women. Human studies should investigate the role of dairy products with respect to sex and age by including classic and novel risk markers of coronary heart disease. Specific fermented milks may be beneficial in the future prevention of hypertension. The beneficially neutral effect of cheese on coronary heart disease risk factors should be elucidated further.     

Does type 2 diabetes predispose to osteoporotic bone fractures?

Chronic complications of diabetes are associated mainly with changes in major and small arterial vessels as well as in peripheral and autonomic fibers of the nervous system. For years it has been suggested that DM2 does not predispose to osteoporosis because bone mineral density (BMD) in DM2 patients is commonly normal or even increased. However, results of recent large cross-sectional studies have indicated that patients with DM2 have significantly increased risk of bone fractures, predominantly hip fractures (by 70%). Results of these studies suggest that the increased risk of fractures in DM2 is independent of BMD. In this group of patients is frequently associated the loss of vision caused by diabetic eye disease, peripheral neuropathy, arterial hypertension, orthostatic hypotonia (caused by autonomic neuropathy or/and by concomitant antihypertensive treatment), and ischemic disease of the brain, heart and lower extremities--conditions that predispose to falls. There are no specific methods of prophylaxis and treatment of osteoporosis associated with diabetes; therefore they should be based on widely accepted principles as in non-diabetic populations. It seems that in DM2 patients the most purposeful strategy could be the popularization of healthy attitudes aiming the elimination of unfavorable dietetic and environmental factors, such as low physical activity, smoking, and low vitamin D intake, as well as education against falls.     

Strengthening the Case for Epilepsy Drug Development: Bridging Experiences from the Alzheimer’s Disease Field—An Opinion

Given the sheer number of drugs (over 20!) available for treatment of seizures, epilepsy can be considered one of the most successful areas in pharmaceutical development and especially for neuroscience. However, despite the large number of drug treatment options available for managing patients with epilepsy, there remains considerable unmet need. For example, the overall impact on seizure control has not been substantial with approximately 30% of patients remaining refractory or their seizures not adequately controlled. Also there is need for epilepsy prevention and for certain sub-populations with severe intractable epilepsy. High unmet need often drives new industry investment into therapeutic market opportunities, however the profound success of antiepileptic drugs has contributed to the hurdles for industry investment in new therapies for epilepsy. Furthermore, the payor environment has also changed with new challenges for evidence generation and demonstration of additive value above existing standard of care treatments. Challenges in translational science, in the clinical trial environment including cost and operational technical difficulty, and in the commercial environment have resulted in the pharmaceutical industry directing investments away from epilepsy into other therapeutic areas such as oncology and immunology as opportunities for higher probabilities of success and returns of investment. The neuroscience area in general is perceived a high risk area and a notable exception has been the active industry involvement in Alzheimer’s disease (AD), especially for therapeutics that could modify the course or prevent AD. AD is a very high risk area with no successful efficacious treatments found to date despite recent failures, there remains promise that therapies are forthcoming. The promise is fueled by a number of innovative factors that reduced R&D challenges in the AD field and contributed to a high level of drug development activity and investment. This paper addresses hurdles facing epilepsy drug discovery and development and focuses on some key solutions that could be eased to facilitate industry interest. Similarities in drug development challenges provide opportunities that bridge experiences and learnings from AD to epilepsy. Overall, the epilepsy field is probably in a good position for advancing into the next generation therapeutics of antiepileptic drugs targeted for increased efficacy in refractory epilepsy and for antiepileptogenesis.

     

Microsporidiosis: human diseases and diagnosis

Microsporidia are considered opportunistic pathogens in humans because they are most likely to cause diseases if the immune status of a host is such that the infection cannot be controlled. A wide spectrum of diseases has been reported among persons infected with microsporidia and different diagnostic techniques have been developed during the last decade.     

Glutamatergic mechanisms in different disease states: overview and therapeutical implications -- an introduction

Summary.  Glutamate is the most widely distributed excitatory transmitter in the central nervous system (CNS). It is acting via large – and still growing – families of receptors: NMDA-, AMPA-, kainate-, and metabotropic receptors. Glutamate has been implicated in a large number of CNS disorders, and it is hoped that novel glutamate receptor ligands offer new therapeutic possibilites in disease states such as chronic pain, stroke, epilepsy, depression, drug addiction and dependence or Parkinson's disease. While an extensive preclinical literature exists showing potential beneficial effects of NMDA-, AMPA-, kainate- and metabotropic receptor ligands, only NMDA receptor antagonists have been characterized clinically to any appreciable degree. In these trials it has been shown that while several compounds are therapeutically active, they also produce serious side effects at therapeutic doses. Current interest largely centers on the development of receptor subtype-selective compounds, namely compounds selective for receptors containing the NR2B subunit. Preclinical findings and the first clinical results are encouraging, and it may be that such subunit-selective compounds may have a sufficiently wide therapeutic window to be safe for human use. Received July 6, 2001 Accepted August 6, 2001 Published online August 9, 2002     

The Heart in Diabetes

Since the introduction of insulin, heart disease has become a major impediment to survival in persons with diabetes mellitus. Coronary disease has increased severity and accelerated development in diabetic persons compared with an age- and sex-matched nondiabetic population. A peculiar vulnerability of women to the influence of diabetes with loss of premenopausal coronary disease protection has been found. The symptomatology of coronary events may differ and coronary care data show a higher incidence of sudden death in diabetic patients who have a myocardial infarction than in their non-diabetic counterparts. Insulin may play a role in the myocardial adjustment to an ischemic insult by enhancing glucose intake and suppressing lipolysis and ketogenesis. Carbohydrate intolerance in dogs, rhesus monkeys and humans appears associated with similar histologic and compositional changes in the myocardium. Abnormalities in diastolic ventricular function not attributable to large- or small-vessel coronary disease have been found in the diabetic subjects of each species. Studies in humans who have diabetes have assessed single pressure-volume relationships and more exacting measures of ventricular compliance are needed. Abnormalities of myocardial function in patients with diabetes have been found using echo and radionuclide techniques. Many of these findings need to be correlated with invasive data or confirmed in larger populations. Autonomic dysfunction is common in diabetic persons and may imply an associated poor prognosis. Reflex abnormalities in parasympathetic function are most prevalent and occur before sympathetic dysfunction.     

Melatonin and the cardiovascular system

Melatonin concentrations in serum, as well as urinary levels of its main metabolite, 6-sulphatoxymelatonin, decrease with age. In the course of aging, the frequency of heart diseases, both acute and chronic, systematically increases. The evidence from the last 10 years suggests that melatonin influences the cardiovascular system. The presence of vascular melatoninergic receptors/binding sites has been demonstrated; these receptors are functionally linked with vasoconstrictor or vasodilatory effects of melatonin. Melatonin can contribute in cardioprotection of the rat heart, following myocardial ischemia. It has been shown that patients with coronary heart disease have a low melatonin production rate, especially those with higher risk of cardiac infarction and/or sudden death. There are clinical data reporting some alterations of melatonin in human stroke and coronary heart disease. The suprachiasmatic nucleus and, possibly, the melatoninergic system may also modulate cardiovascular rhythmicity. Hypercholesterolemia and hypertension are the other age-related symptoms. People with high levels of LDL-cholesterol have low levels of melatonin. It has been shown that melatonin suppresses the formation of cholesterol by 38% and reduces LDL accumulation by 42%. A 10-20% reduction of cholesterol concentration in women using the B-oval pill has been observed. It is a very important because, even a 10-15% reduction in blood cholesterol concentration has bee shown to result in a 20 to 30% decrease in the risk of coronary heart disease. People with hypertension have lower melatonin levels than those with normal blood pressure. The administration of the hormone in question declines blood pressure to normal range. It has been observed that melatonin, even in a dose 1 mg, reduced blood pressure and decreased catecholamine level after 90 min in human subjects. Melatonin may reduce blood pressure via the following mechanisms: 1) by a direct effect on the hypothalamus; 2) as an antioxidant which lowers blood pressure; 3) by decreasing the level of catecholamines, or 4) by relaxing the smooth muscle in the aorta wall.     

Mortality from ischaemic heart disease among patients using anticonvulsive drugs: a case-control study.

Patients who use phenytoin and some other anticonvulsive drugs have been shown to have raised concentrations of plasma high density lipoprotein. As this lipoprotein is known to be inversely associated with the incidence of ischaemic heart disease the causes of death of all patients with epilepsy known to be taking anticonvulsive drugs who died during 1978-80 were studied. Of 1399 deaths of anticonvulsant users, 258 (18.4%) were caused by ischaemic heart disease. This was significantly less (p less than 0.001) than the 382 deaths from ischaemic heart disease (27.3%) observed among paired controls matched for sex, age, and date of death. The total cardiovascular mortality was also lower among patients with epilepsy than among controls (p less than 0.02) despite there being more deaths due to cerebrovascular disease among patients. The difference in mortality from ischaemic heart disease was significant for both sexes and was not accounted for by excess deaths due to any other single cause. Users of phenytoin, carbamazepine, and barbiturates (alone or in combination) showed 29% less mortality due to ischaemic heart disease than respective controls (p less than 0.001).     

Demonstrating Weakly Acid-Fast Tubercle Bacteria in Sputum

Acid-fastness of the tubercle bacteria has long been used as the common method of diagnosis in sputum. It has been suggested sometimes that tuberculosis could occur without demonstrable bacteria, as well as with acid-fast bacteria, non-acid-fast bacteria or granules. It is shown in this paper that some of the sputa which are negative to the standard staining technic will show rods, rods with round polar bodies, or similar bodies without the rod portion. It is also pointed out that the decolorization of the smears by acid alcohol be shortened to approximately 3 to 5 seconds and picric acid be used as a counterstain. These forms are apparently the varying stages of the loss of acid-fastness. It is essential that a counterstain be used which will not interfere, and yellow is indicated because it does not absorb the red rays. Sputa which are negative to the standard acid-fast staining technic but which come from persons with a variable intermittent fever should be stained by this modified technic before they are pronounced germ-free.     

PERIODIC MEDICAL EXAMINATIONS—Disease Detection and Health Promotion

The medical examination of persons who have no medical complaints is a procedure that has different purposes than the traditional diagnostic examination. These include not only the detection of incipient disease but the evaluation of the adjustment of the individual to his environment and an assessment of his personal hygiene. It should be concluded by a discussion of what has been found, and by positive, persuasive advice and education which will lead to better health.Interest in such work and competence for it are not found in every physician. Physicians who do not want to acquire such competences should recognize the fact and refer such work to others who are prepared to cope with it. Inept, incomplete health examinations disappoint the patient and make the physician uncomfortable; thorough, constructive examination and counseling is satisfying and profitable to both.