The Butajira rural health project in Ethiopia: epidemiological surveillance for research and intervention in primary health care.

Ten study populations sampled from a total of 86 communities in a rural Ethiopian area, have been registered and followed for a period of four years. A baseline census revealed a median age of 15 years, a literacy rate of 24%, poor housing and environmental conditions, and low utilization of the existing health care facilities. A surveillance system was established which made it possible to estimate the occurrence of vital events. This showed a crude birth rate of 40.3/1000, a crude death rate of 16.4/1000, a life-expectancy at birth of 48 years, an infant mortality rate of 114/1000, a yearly child (1-4 years) mortality rate of 36/1000, and an under-five mortality rate of 210/1000. The implications of these data in terms of the planning and operations of research and health services are discussed, and on-going and projected studies are outlined emphasizing the methodological potentials of this epidemiological study base.


Recruitment and participation of general practitioners in a multipractice study of smoking cessation.

In May 1986, all 398 general practitioners (GPs) in western Norway were invited by letter to take part in a multipractice intervention study of smoking cessation among pregnant women. The aims of the intervention study were: 1) to find out how a smoking cessation model can be implemented in ordinary consultations in general practice, and 2) to compare smoking cessation in pregnant and non-pregnant women. The intervention study lasted for three years. 187 (47%) GPs completed the study. Working in a group practice, working on regular salary, having started specialization in general practice, being less than 40 years of age, and being a non-smoker were significantly more common among the participating GPs. They also had significantly fewer consultations per week than their non-participating colleagues. A stepwise multiple logistic regression analysis revealed that smoking habits predicted participation in the study far more than any other predictor.


Urinary incontinence in women and the effects on their lives.

The aim of this study was to assess and analyse the effects of urinary incontinence in women and to examine the relationship between these effects and the type and severity of incontinence. 110 women aged 20 to 65 who had reported urinary incontinence to their general practitioners underwent a comprehensive history and a complete urodynamic evaluation. The reported consequences of incontinence included low self-esteem, changing life-style in order to avoid potentially embarrassing situations, and all kinds of practical worries. Fear of the odour played the most important part and was mentioned as being the worst effect in 40% of the cases. Most of the women appeared to cope adequately with the unpleasant aspects of this condition. More effects were associated with urge incontinence than with stress incontinence, while there was a significant relationship between the objective severity of the incontinence and its psychosocial impact. The main conclusion is that although urinary incontinence is not a severe physical disability, a spectrum of psychological problems is associated with it. In particular, the fear of being smelt was of the utmost importance.


Intervention in alcohol abuse among macrocytic patients in general practice.

The study examined the effectiveness of routine intervention in alcohol abuse by a general practitioner, with help of a laboratory test. Patients diagnosed as abusers because of high erythrocyte mean cell volume value (MCV) and having no other cause for it were randomly allocated to two groups: 1) an intervention group, comprising 92 patients (69 men and 23 women), who were invited for follow-up at three-monthly intervals for a year; 2) a control (mini-intervention) group, 86 patients (71 men and 15 women), who were followed-up only after 12 months. Follow-up attendance was poor, particularly in the intervention group. In general, MCV-values were unchanged in the groups at the end of the study, though there was a clear trend for the female controls to have lower values (101.9 fl at the start, 98.5 fl at the end, p = 0.06). Altogether 11% (4/38) of the women and 7% (10/140) of the men had clearly reduced their alcohol consumption after one year, and this was also seen in their MCV-values. Mini-intervention, especially in women with an abnormal laboratory value, seems to be, with the help of MCV, at least as effective a way of counselling nonalcoholic abusers as a more systematic intervention.


An evaluation of a commercial co-agglutination test for the diagnosis of group A streptococcal tonsillitis in a family practice.

The result of a rapid co-agglutination test was compared with the clinical diagnosis of group A streptococcal tonsillitis, a laboratory culture from the throat serving as the correct result. The study was carried out in a family practice, with two GPs partaking: it included 105 consecutive patients. The outcome of the rapid test was significantly correlated to the degree of growth determined by throat culture, and it was superior to the clinical judgement. The statistical analysis of the results of the rapid test revealed (95% confidence limits in brackets) a specificity of 97% (91-100), sensitivity of 68% (48-84), a positive predictive value of 90% (70-99), and a negative predictive value of 89% (81-95). Although the co-agglutination test was superior to the clinical diagnosis, the sensitivity of this test is rather low when compared with other recently evaluated rapid tests for use in family practice.


Diagnosis of pneumonia in adults in general practice. Relative importance of typical symptoms and abnormal chest signs evaluated against a radiographic reference standard.

The diagnostic value of typical symptoms and abnormal chest signs for pneumonia have been evaluated against a radiographic reference standard in 402 adult patients with respiratory tract infection in general practice. Pneumonia was diagnosed in 20 patients by a positive chest radiograph. The doctors diagnosed pneumonia in seven of these on the basis of history and physical examination alone, and in addition in 22 patients with normal radiographs. The diagnostic value of the typical symptoms cough, chest pain, and dyspnoea, reported by the patients on a questionnaire, increased with increasing intensity of the symptoms, and both "very annoying lateral chest pain" and "very annoying dyspnoea" had likelihood ratios (LR) between 4 and 5. The LR of crackles was 3.7. When evaluated against the doctor's clinical diagnosis of pneumonia as reference standard, crackles achieved an LR of 14.8, while the typical symptoms achieved lower LRs than when evaluated against the radiographic reference standard. These discrepancies, which were confirmed by logistic regression, indicate that crackles and other abnormal chest findings are interpreted too frequently as features of pneumonia and that the importance of typical symptoms is underestimated in the diagnosis of pneumonia.


Laboratory tests for pneumonia in general practice: the diagnostic values depend on the duration of illness.

The usefulness in the diagnosis of pneumonia of temperature and the laboratory tests: erythrocyte sedimentation rate (ESR), leucocyte count, and C-reactive protein (CRP) was evaluated against a radiographic reference standard in 402 adult patients with respiratory tract infection in general practice. Radiographic pneumonia was diagnosed in 20 patients. CRP and ESR were the most useful tests. CRP greater than 50 mg/l had lower sensitivity and likelihood ratio (LR), 0.50 and 4.8, respectively, compared with previous studies of selected patient populations. Among patients whose duration of illness exceeded six days the corresponding LR was 11.3, due to a higher specificity in this subgroup of patients. ESR and oral temperature were also more useful in this subgroup than in patients with a shorter duration of illness. A highly significant diagnostic contribution of adding ESR and CRP to history and physical examination, particularly when the illness had lasted one week or more, was demonstrated by logistic regression.


The changing geographical coherence of measles morbidity in the United States, 1962-88.

Geographical coherence may be defined as the degree to which the behaviour of a time series in one geographical area corresponds with the time series behaviour in another. This paper illustrates the concept using the epidemiological time series of reported monthly measles morbidity for the states of the United States for the 27 years from January 1962 to December 1988. Over this period, as measles morbidity has declined in response to vaccination campaigns, and as the seasonal peaking of the disease in late spring has become less pronounced, the geographical coherence has altered at the national, divisional, regional and state levels. There was a steady decline in coherence from 1962 to 1980. In 1981, a dramatic reduction occurred, but there has been some recovery since. The implications for spatial forecasting models of these reducing levels of coherence are discussed.


Short and medium term projections of the AIDS/HIV epidemic by a dynamic model with an application to the risk group of homo/bisexual men in Amsterdam.

Several methods exist for short term projection of the numbers of AIDS cases. Some use extrapolation of empirical curves fitted to data up to a given time, whereas others such as the popular method of 'back projection' or actuarial methods also use information about the process. In this paper we describe a dynamic model based on a distributed modelling technique allowing for variability both in infectiousness and in age distribution of the population at risk. Some model parameters are taken from the literature, others are estimated from AIDS incidence data from the homo/bisexual population in Amsterdam. The model described here simulates prevalence and incidence of HIV infection. We present prediction intervals for two years from January 1990 onwards. We discuss three scenarios based on the estimated model, two of which consider early treatment with anti-viral drugs. Given the model and the state of the epidemic in Amsterdam, early treatment intervention must be combined with very drastic measures for reducing infectivity in order to have any serious impact on the course of the epidemic.


Analysis of disease risks using ancillary risk factors, with application to job-exposure matrices.

Epidemiological studies of disease can make use of ancillary risk-factors, acquired from individuals outside the disease study. For example, several disease studies might use the same job-exposure matrix to quantify risks due to occupational exposure to industrial agents. We construct a graphical model to combine a logistic regression disease model with models for the ancillary data and the risk-factor distribution in the population. We estimate the graphical model using Gibbs sampling, and in simulations compare it with methods of direct substitution into logistic regression.


Methods for comparing cumulative hazard functions in a semi-proportional hazard model.

Graphical methods based on the analysis of differences between log cumulative hazard functions are considered for a two-group semi-proportional hazard model which allows for interaction between treatments and covariates. Confidence procedures and test statistics that can be used to test for interaction and for main effects are developed. Their use is illustrated by applying them to the analysis of kidney transplant data from the University of California, San Francisco.


Evaluations of methods for statistical surveillance.

The needs for statistical surveillance in different areas of medicine are described. The predictive value of an alarm and other measures for the evaluation of alarm procedures are suggested. The measures are used to evaluate some common methods of continual surveillance of time series. It is demonstrated that some methods have about the same properties at the start of the surveillance period as later. This is however not the case for all methods. For some methods the consequence of an early alarm should be quite different from that of a late one.


Sensitivity and specificity for correlated observations.

A general estimating equation approach is used to obtain estimates of sensitivity and specificity when the data consist of correlated binary outcomes. First order approximations to the variances of estimated sensitivity and specificity for prospective and retrospective studies are given. Data from a dental study are used to motivate and illustrate the methods.


A goodness-of-fit approach to inference procedures for the kappa statistic: confidence interval construction, significance-testing and sample size estimation.

We propose a new procedure for constructing a confidence interval about the kappa statistic in the case of two raters and a dichotomous outcome. The procedure is based on a chi-square goodness-of-fit test as applied to a model frequently used for clustered binary data. The procedure provides coverage levels that are accurate in samples of smaller size than those required for other procedures. The procedure also has use for significance-testing and the planning of corresponding sample size requirements.


On the sample size for studies based upon McNemar's test.

When computing the sample size for studies using McNemar's test, one needs to know the probability of discordance and the odds ratio to be detected. In many studies, the investigator is unable to specify the probability of discordance, but can state, at least approximately, the marginal probabilities of each variable. This information leads to restrictions on the possible values of the cell probabilities and provides a range of admissible values for the off-diagonal cells. We compute the sample size needed in these circumstances and compare them to the results cited by Schlesselman and Connett et al. These sample sizes for the method are quite close to those found in the Monte Carlo study of Connett et al.


[Multiple neoplasms: etiological problems and possibilities for prevention].

The authors present a review of the literature concerning multiple malignancies in a single patient. They emphasize etiological aspects and possible preventive strategies in a clinical entity which appears to be recognized with an increasing frequency.


[Pelvic venous compression syndrome: description of a case and literature review].

A case of a genuine common iliac vein compression (Cockett's syndrome) is reported. From review of the literature, it appears that the treatment should be essentially medical. Surgery is indicated in case of severe post-thrombotic sequellae.


[Fetal alcohol syndrome].

Ethanol teratogenicity manifests itself in the form of the foetal alcohol syndrome (FAS). This syndrome is characterised by growth delay, impairment of the central nervous system, and various facial dysmorphisms. We report the case of a 19 month-old boy affected by FAS. In addition to the three common features of FAS, this patient disclosed organic (digestive and cardiac) malformations and cellular chemotaxis deficiency. We have reviewed the literature to provide an update on the clinical signs of FAS. The abnormalities provoked by foetal exposure to ethanol can be very varied, none of them being specific.


[Primary hyperoxaluria type 1, peroxisomal disease: therapeutic consequences].

On the occasion of a combined liver-kidney graft doing well after 3 years, the molecular anomalies responsible for primary hyperoxaluria type 1 are discussed. This rare condition may be listed in the expanding group of hereditary diseases involving peroxisomes, cellular organelles with increasingly recognised functions. Recent progress in the molecular biology of this disease have led to the proposal of of new transplant strategies for its cure.


[Subcutaneous apomorphine infusion in the treatment of Parkinson disease].

Apomorphine, a dopamine-agonist was applied as s. c. infusions to 7 patients with idiopathic Parkinson's disease. The indications were longlasting akinetic episodes (4 patients) and therapeutically resistant invalidating motoric fluctuations ("on-off") as well as hyperkinesia (3 patients) on anti-Parkinson medication. The effect of apomorphine as an anti-Parkinson therapeutic was verified using clinical scales and a portable activity-monitoring device. The s. c. infusion therapy (20-90 mg/die, or 0.025-0.01 mg/kg/die respectively) was effective in the akinetic patients interrupting akinesia and the inability to swallow. An improvement was also registered in patients with "on-off" and hyperkinesia using longlasting subcutaneous apomorphine infusions. The therapy was continued over a longer period of time with 2 patients as outpatients. The side-effects were nausea and local subcutaneous indurations at sites of infusions.


[Potential use of the sauna in the long-term treatment of hypertensive cardiovascular circulation disorders--a comparison with kinesiotherapy].

The authors report about the long-term response (one and three years) of blood pressure and heart frequency under rest and load (50 W) in patients with hypertension, coronary heart disease, essential hypertension and after aortocoronary venous-bypass operation (ACVB) (n = 65) under regular visits (twice a week) to the Finnish sauna. In comparison, 68 hypertensive patients who took a regular kinesiotherapy (running and swimming) were studied. Besides the parameters of heart circulation mentioned above, peripheric microcirculation (M. tibialis anterior) by means of xenon-133 muscle clearance and central hemodynamics by means of LVEF (single probe with In 113) were studied in CHD-patients. Cardiac output at rest and under 50 W load was recorded in hypertensive patients. It was shown that regular balneotherapy had a positive effect on regulation of blood pressure and hemodynamics in patients with hypertension or CHD with hypertension, as had kinesiotherapy in hypertensive patients.


[Main involvement of the central nervous system in alcoholism].

The effects of alcohol on the central nervous system can be subdivided into three main categories: the effects of acute intoxication (drunkenness, acute encephalopathy, stroke), the effects of tolerance and ethanol withdrawal (delirium tremens, seizures) and the delayed manifestations of chronic alcohol consumption (cerebellar degeneration, Wernicke's encephalopathy, dementia).


[Livedo racemosa, skin necrosis at the basal toe joint].

An 81 year old male patient treated by sulfonylurea and diet was known to have type II diabetes for three years. Because of pulmonary embolism phenprocoumon had been administered for four months. Painful livedo racemosa developed acutely on both lateral sides of the feet and the left knee. A necrosis of the skin over the base of the left small toe developed within a few days. On the basis of the clinical picture cholesterol-embolism was diagnosed. Since anticoagulation is known to promote cholesterol-embolism it was discontinued. Prostaglandin E1 infusions into both legs were administered. Within 3 months the cutaneous lesions healed completely.


[Interleukins].

Interleukins are polypeptide hormones which are primarily but not exclusively synthesized by cells of the immune system (monocytes/macrophages, T- and B-lymphocytes). Up to now 12 interleukins (IL-1 to IL-12) have been described. The central function of the interleukins is the orchestration of the different cells of the immune system during host defence against pathogens. Besides the regulated stimulation of the immune reaction against foreign antigens, interleukins are involved in the stimulation of unspecific inflammatory reactions and in the induction of the acute phase response.


[Magnetic resonance imaging in spinal cord diseases: 127 cases].

Acute or chronic spinal cord syndromes with or without evidence of cord compression are a common diagnostic problem in neurology. Magnetic resonance imaging (MRI) was performed on 127 patients to assess the sensitivity of this examination in detecting local spinal cord lesions. The most common location noticed in this study were the cervico-thoracic (40.9%) and cervical regions (33.8%). A total spine examination accounted for 14.9% of the examinations performed, and the lumbar spine was evaluated in 10.2%. An increased signal corresponding to plaques of multiple sclerosis was the most frequent diagnosis (25 cases), followed by cervical narrowing of the spinal canal and cervical disk diseases (23 cases), neoplasms (15 cases), spinal cord infarctions (12 cases), spinal infections (6 cases) and spinal cord injuries (3 cases). A myelopathy of undetermined etiology was diagnosed in 19 cases. MRI is very sensitive in multiple sclerosis, but it is not possible to diagnose the disease from abnormal scan only, other supportive laboratory results, such as oligoclonal bands, are necessary. MRI is very useful in evaluating intraspinal cord parenchymal lesions, such as neoplasms or congenital abnormalities.


[Rhabdomyolysis in body building. Report of a case and literature review].

A 24-year-old man was sent to the emergency unit and evaluated with the symptom of acute right-sided chest pain. Myocardial infarction and pulmonary embolism were excluded. A creatine kinase (CK) serum concentration of 17,034 U/l (normally up to 270) was found. The patient gave a history of excessive body-building exercises on the previous day. During the follow-up period symptoms resolved within several days, and CK values gradually diminished. A review of current literature on rhabdomyolysis in patients with body-building is presented.


[Cerebral complications and general anesthesia].

Postoperative cerebral dysfunction is usually assumed to be a consequence of anaesthesia. Temporary postoperative confusion is quite common. This review points out that the anaesthetic technique is clinically relevant for mental dysfunction only in the few hours immediately following operation. Of primary importance are the preoperative state of the patient, the drugs used in the perioperative period, the type and duration of the operation, the technique of postoperative analgesia and sedation and the postoperative clinical course of the patient. Cerebral infarction is a very severe but rather rare complication which occurs mainly after the operation. The incidence of perioperative cerebral infarction is about 1% in 65-year-old patients and increases with higher age. An asymptomatic preoperative carotid bruit is not a risk factor; therefore, invasive investigations are not warranted. The most frequent cause for cerebral insults are emboli. Intraoperative hypotensive periods are very rarely responsible for cerebral insults. Peripheral and central nervous lesions due to positioning of the patient for the operation occur not frequently and are certainly an avoidable neurologic complication. Hypoxic cerebral damages are usually the consequence of anaesthetic mismanagement. Today they are very rare, due to modern monitoring techniques.


[Cerebrovascular accidents and surgery].

There are very few observations on the occurrence of stroke after general surgery; the incidence lies between 0.2 and 0.7%. On the other hand, cerebrovascular accidents are mainly seen after cardiac and carotid surgery, where the incidence is high (5%). Strokes are also an important cause of morbidity and mortality following orthotopic transplantations, particularly heart, heart/lung and liver transplantations.


[Spinal lesions in surgery of the aorta].

Aortic diseases in particular aneurysms may be accompanied by spinal ischemia occurring either spontaneously or as complications of surgical interventions. Surgery of the abdominal or thoraco-abdominal aorta is followed in 5 to 15% by ischemia of the spinal cord, in exclusively abdominal interventions in 1.5%. Clinical manifestation depends largely on anatomy of the spinal vessels. If complete transverse myelopathy does not occur, presentation as anterior or posterior arterial ischemic syndrome is common. Other forms of myelopathy are rare. Perfusion deficits through intercostal and lumbar arteries are important in pathogenesis. The great radicular artery is particularly important. Ischemia occurs after hypotensive episodes (ruptured aneurysm) intraoperative clamping of the suprarenal aorta or by occlusion (thrombotic, arterio-arterial embolism). Careful surgical techniques are important for prevention of these neurologic complications. Possibilities for treatment and chances for spontaneous recovery of established spinal-cord lesions are poor.


[Ilio-inguinal and genito-femoral neuralgia. Causes, clinical aspects, therapy].

Entrapment neuropathy of the ilioinguinal and of the genito-femoral nerves is a rare but sometimes very painful complication of abdominal surgery (herniorrhaphy, appendectomy, nephrectomy, gynecological surgery, removal of bone from the inner table of the iliac crest, etc.). Sometimes symptoms develop during a normal pregnancy or delivery. Spontaneous entrapment of the ilioinguinal nerve as it passes through the Mm. obliquus internus and transversus abdominis has also been observed. We have operated such a case. The causes, features and the associated findings of entrapment neuropathy of the two nerves are pointed out. In the frequent cases attributable to previous surgery the retroperitoneal resection of the nerves is advocated instead of a local revision, which is usually unsuccessful due to the impossibility of finding and restoring the fine nerves in a dense scar.


[Heart sounds--a mathematical transformation of blood pressure? On the origin of heart sounds].

Two main theories exist concerning the origin of the heart sounds. The first proposes that rapid pressure fluctuations cause the cardiac valve leaflets to vibrate and produce the sound. The second theory suggests that sudden pressure perturbations cause the entire cardiohemic mass to vibrate as a whole. In 35 patients (26 men and 9 women, aged 18 to 73) with various heart diseases microtransducer catheters (Millar) were used to simultaneously record aortic pressures and aortic internal phonocardiograms in order to determine if they had a common mode of origin and propagation. The propagation velocities of the first heart sound and the foot of the aortic pressure pulse were found to be similar, 5.24 +/- 0.61 m/s and 5.97 +/- 1.87 m/s respectively (+/- SE). It was possible to derive facsimiles of the aortic internal phonocardiogram by double differentiation of the corresponding aortic pressure pulse and conversely to derive the pressure pulse by double integration of the phonocardiogram. These data support the concept that the low-frequency pressure variations produced by the entire cardiohemic mass, which predominate in the aortic pressure pulse waveforms, are generated and propagated in the same manner as the high-frequency pressure variations, which are the first and second heart sounds.


[Elevation of the ST-segment in the electrocardiogram and ischemic injury current].

The TQ segment depression and the ST segment elevation in the electrocardiogram during acute myocardial ischemia are caused by flow of injury current. This current flows between potential gradients across the ischemic border. The initial change is the TQ segment depression, which is brought about by a positive shift of the resting membrane potential of the ischemic cells. After 1 to 2 minutes ST segment elevation develops as a consequence of the action potential shortening and loss of plateau. The loss of potassium ions and ensuing extracellular K+ accumulation is the major cause of the alterations in action potential. After 15 to 20 minutes of ischemia, electrical cell-to-cell uncoupling occurs and interrupts the flow of injury current (decrease of TQ segment depression and ST segment elevation), producing conduction block.


[Coronary thrombosis--an old concept in a new light].

The morphologic-clinical links in acute myocardial ischemia have been established in the last few years. Angiographic and biochemical investigations have contributed to the understanding of the connection between the acute coronary lesion (fissure or rupture of a plaque, dissection) and the dynamic process of thrombus formation, lysis and coronary spasm that occur during the first minutes and hours of acute myocardial ischemia. Deep arterial lesions with thrombotic tendency also occur after coronary bypass operations, thrombolysis and PTCA. Conventional antithrombotic substances like aspirin and heparin are only partially effective, and new compounds are tested which either inhibit platelet aggregation or thrombin formation more completely. Hopefully, these new drugs will prevent reocclusion after thrombolysis and restenosis after PTCA more effectively.


[Myocardial infarct without classical Q-waves in the ECG].

In this article the ECG pattern of myocardial infarction not associated with the commonly seen pathologic Q waves (greater than 0.03 s) or QS waves is discussed. In a short introduction the differential diagnosis of pathologic Q or QS waves is recalled. Thereafter, the authors insist on their experience, that the diagnosis of infarction should generally be based on the combination of RIsk factors, THOracic pain, a pathologic ECg and elevated cardiac ENzymes. Therefore, the diagnosis of a myocardial infarction should be made only, if it is 'RITHOCGENE' (abbreviation of the above-mentioned combination). The typical or possible 'non-Q-wave infarction' ECG patterns are listed, including a normal ECG.


[Non-invasive assessment of left ventricular diastolic function disorder using Doppler echocardiography].

Symptoms of a variety of cardiac diseases may well be caused predominantly by diastolic dysfunction, which appears to be one of the first detectable cardiac alterations. Diastole represents a complex interplay of multiple factors. Doppler echocardiography offers a noninvasive and relative simple method to assess left ventricular volumetric filling rates. The pulsed-wave Doppler method enables us to measure mitral flow velocities. Two distinct mitral flow velocity patterns have been recognized for situations with diastolic dysfunction. The pattern of delayed relaxation was reported in primary and in secondary left ventricular hypertrophy, myocardial ischemia and infarction and in dilated cardiomyopathy. The pattern of increased stiffness was described in constrictive pericarditis, restrictive processes and in heart transplant rejection. Doppler echocardiography has shown to be a helpful diagnostic tool, but a number of factors influencing mitral flow measurements have to be considered in each case, as there are age, heart rate, loading conditions and mitral regurgitation. Further studies are needed with respect to future control of therapeutic interventions and prognostic statements.


[Complementary information from Doppler echocardiography in the electrocardiogram in the basic assessment of chronic coronary heart disease, especially following a myocardial infarct. Observations from an ambulatory cardiology clinic].

In chronic ischemic heart disease, Doppler echocardiography (DE) at rest permits semiquantitative evaluation of scarring and remodelling processes, global ventricular function and, frequently, regional wall motion state. Late complications are detected, namely infarct expansion, true and false ventricular aneurysm, mitral insufficiency, thrombus formation, and associated valvular and aortic diseases are discovered. We studied 100 patients with known chronic coronary artery disease referred for noninvasive evaluation, including electrocardiogram (ECG) and DE. In all patients, the global left-ventricular function was satisfactorily assessable. In roughly two thirds of the documented infarctions. DE confirmed the ECG diagnosis and permitted a more precise diagnosis in the majority of them in terms of localization and/or dimension of the necrosis. In one third of the patients. DE clarified inconclusive ECG tracings. Thus, the baseline noninvasive investigation with ECG and DE is a potent tool in the management of chronic ischemic heart disease, serving as a guide to further investigation and to treatment adjustments.


[The elderly patient in cardiology].

This paper summarizes the special aspects of cardiovascular disease in the elderly. Arterial hypertension, heart failure and electrical disturbances may often lead to a different therapeutic approach in this clinical setting. Myocardial infarction is often complicated and may lead to considerable disability; therefore, thrombolytic therapy should be considered also in elderly patients. Coronary angioplasty and heart surgery are successfully performed in patients greater than or equal to 80 years of age, but special consideration has to be given to the functional states and the presence of concomitant disease in these patients.


[Urinary tract infection in women in daily clinical practice].

Questions concerning the clinical picture, diagnosis and treatment of uncomplicated urinary tract infections in women related to daily practice are discussed on the basis of personal experience and a review of the literature. Indications and rationale for a single-dose therapy with Cotrimoxazole, Trimethoprim or Fosfomycin are detailed. Special considerations are given to therapeutical approaches to recurrent infection as well as special situations like asymptomatic bacteriuria, acute urethral syndrome, bacteriuria in pregnancy and nosocomial, catheter-associated infections are discussed.


[The value of CT and MRI in the assessment of basal encephaloceles in children].

Basal cephaloceles of the child are rare pathologies which require accurate preoperative imaging work-up. The CT and MR studies of six children with surgically proven basal cephalocele were retrospectively reviewed to evaluate the role of CT and MR in the preoperative work-up of a basal cephalocele of the child. In five patients, MR allowed to define the nature and topography of the cephalocele, and allowed an accurate depiction of the optic tract, ante- and post-hypophysis and associated agenesis of corpus callosum when present. 3-D CT allowed in one case a more precise depiction of the basal bony defect. MRI allows in a non invasive and non ionising way the best depiction of herniating meninges, brain or ventricles as well as associated cerebral anomalies.


[Assessment of blood flow in hart and large vessels using Doppler color flow mapping].

Two-dimensional echocardiography allows the noninvasive assessment of the morphology and the movement of cardiac structures, including valves and ventricular walls. Color Doppler flow imaging presents a spatial visualization of blood flow, superimposed on two-dimensional echocardiographic images. The color indicates the direction of flow. Turbulent flow is readily identified by the 'mosaic pattern' of the color flow signal. The method facilitates the detection and localization of obstruction to flow, valvular regurgitation or a shunt.


[Transesophageal echocardiography: technique, indications and findings].

The introduction of transesophageal echocardiography (TEE) as a 'semi-invasive' technique with few complications in clinical practice represents a major diagnostic advance in the evaluation of cardiac disease. The close anatomic vicinity of the transducer to the heart and thoracic aorta allows the use of high frequency devices with better resolution compared to transthoracic echocardiography. Furthermore, the diagnostic gain when evaluating structures that are poorly visualized by the transthoracic approach such as the left atrial appendage, interatrial septum, prosthetic valves and the thoracic aorta is highly improved by TEE. Major indications for TEE include the search for a cardiac source of embolism and cardiac tumors, the work-up prior to balloon mitral valvuloplasty, the evaluation of prosthetic valves and the search for vegetations and aortic dissection. After a short summary of patient preparation, instrumentation and examination technique, the major indications, contraindications and complications are reviewed on the basis of our own experience and the literature.


[Percutaneous endoscopic gastrostomy (PEG) for long-term nutrition--comparison of 2 different caliber tubes].

Percutaneous endoscopic gastrostomy (PEG) is often used nowadays for long-term enteral nutrition in patients with swallowing disorders and severely altered esophageal-duodenal transit. The most common indications for gastrostomy tubes were neurological disturbances and malignancies of the oropharynx and esophagus. We compared in a prospective sequential trial PEG-tubes of two different sizes (2.9 mm [CH-9] vs. 4.8 mm [CH-15]) with respect to placement, complications, durability and handling. The tube was successfully placed in 51 of 52 patients (98%). In 1 patient placement was impossible due to missing diaphanoscopy. The mean observation period was 22 weeks for the CH-9-tubes (n = 28) and 14 weeks for the CH-15-tubes (n = 23). The only early complication was 1 case with a hemorrhage at the site of implantation (CH-15). In both groups 2 cases of local infection were noted. In the CH-9-group 2 PEG-tubes disappeared into the stomach and in 1 case a cicatricial granuloma developed. In the CH-15-group a leak occurred 10 days after implantation. All complications were treated conservatively. There was no causal relationship between the size of tube and the complications. The period of implantation was mostly limited by the death due to the underlying disease of the patient and was not related to the type of PEG-tube. We conclude the both PEG-tubes were easy to place, safe and effective means of providing enteral nutrition. We would, however, recommend CH-15-tubes for long-term nutrition, since in our experience they were less frequently obstructed and handling for the nurses was easier.


[How reliable is oscillometric blood pressure determination at the finger using the Omron device?].

The precision of oscillometric blood-pressure measurements on the finger with the model HEM-812F, manufactured by Omron, was compared to the standard method. The digital measurements from 180 inpatients (115.0 +/- 1.2 mmHg systolic, 68.8 +/- 0.8 mmHg diastolic) were significantly lower than oscillometric measurements from the upper arm using a Bosomat (121.3 +/- 1.4 mmHg systolic, 74.2 +/- 0.9 mmHg diastolic). Correlation coefficients were r = 0.713 for systolic and r = 0.683 for diastolic values, with significant variance of individual values. In direct comparison of the two methods immediately after ergometry the differences were even greater (57 mmHg systolic, 32 mmHg diastolic). Significantly lower digital pressures at the finger were noted in comparison with direct blood-pressure measurements after punction of the femoral artery. Because of significant differences of blood-pressure measurements compared to the Riva-Rocci method, the digital measurement with the HEM-812F device (Omron) can not be generally recommended.


[Intestinal leiomyoma. Case report and discussion of the difficult assessment of grade].

The case of a male patient operated for a leiomyoma of the jejunum is presented. The clinical symptoms, the morphological differential diagnosis and the problems evaluating aggressiveness of this tumour are discussed. We intend to demonstrate that histopathological diagnostic implicate a certain grade of uncertainty too. With the example of leiomyoma we like to show that diagnosis means a tight cooperation of the clinician and his pathologist by collecting clinical and histomorphological data.


[Magnetic resonance imaging: cardiological diagnosis].

Cardiovascular magnetic resonance imaging (MRI) has been in clinical use for barely a decade. During this relatively short period MRI has established itself as an important diagnostic instrument. MRI is an intrinsically three-dimensional, completely noninvasive technique. Its inherent high contrast between the flowing blood on the surrounding tissue make MRI an ideal diagnostic method for cardiovascular diseases, since it does not expose patients and staff to ionizing radiation and there is no need for the application of contrast media. The high spatial and excellent contrast resolution are the basis for the distinct delineation of the cardiovascular pathoanatomy. Infarcted and non-infarcted myocardium may be differentiated by the assessment of tissue relaxation times. With the use of Cine MRI, global and regional ventricular function may be quantified and bloodflow within cardiac chambers may be analyzed. Today's indications for cardiovascular MRI based on personal experience and the literature are presented.


[Digital subtraction angiography for the assessment of myocardial perfusion].

Coronary angiography does not only permit to evaluate the severity of coronary disease but also to assess coronary flow reserve in various myocardial perfusion areas by digital processing. Use of colour flow mapping allows the assessment of both, density as well as distribution velocity of contrast-medium (= parametric imaging). The advantage of this technique is given by the possibility to assess coronary flow reserve not only at rest but also under physiologic situations such as bicycle ergometry. Clinical investigations have shown that coronary flow reserve determined after papaverine administration does not correlate with physiologic conditions such as physical exercise.


[Positron emission tomography in cardiological diagnosis: principles and clinical application].

Positron emission tomography (PET) is an emerging new cardiac imaging modality which allows sophisticated tissue characterization using radiopharmaceuticals. This technique provides absolute quantification of regional tracer concentration using short-lived isotopes such as carbon-11, oxygen-15 and nitrogen-13, which can be easily incorporated in many compounds without changing their biological behaviour. These technical advantages are somewhat offset by the high cost of this technology which includes camera as well as on site cyclotron required for the preparation of radiopharmaceuticals. Recent clinical dates suggest that unique information can be obtained with PET. Using blood flow tracers in combination with PET, coronary artery disease can be detected and localized with high diagnostic accuracy. First studies comparing Tl-201 SPECT and PET in the same patient population indicate diagnostic superiority of PET. In combination with tracer kinetic models, regional myocardial blood flow can be quantitated and the functional significance of coronary artery stenosis defined by regional coronary reserve measurements. The assessment of regional glucose metabolism by PET with the tracer F-18 deoxyglucose has received wide clinical acceptance. Metabolic imaging in patients with advanced coronary artery disease allows the delineation of ischemically compromised but viable myocardium. Selection of patients for revascularization based on this scintigraphy tissue characterization has been shown to have a high predictive value for subsequent tissue recovery. Comparison of PET/FDG imaging with thallium-201 scintigraphy for assessment of tissue viability indicate that, in patients with fixed thallium-201 defects, additional diagnostic information can be obtained by this more expensive technology.(ABSTRACT TRUNCATED AT 250 WORDS)


Management of ureteric calculi (minimally invasive therapy of ureteric stones).

As documented with results obtained in 1685 patients the treatment of ureteric stones is today based on ESWL in situ and ureteroscopy with semirigid, ultrathin ureteroscopes and laser lithotripsy. All stones in the upper third of the ureter and larger stones in the distal third of the ureter are preferably treated with ESWL in situ whereas smaller stones in the distal ureter are better treated endoscopically. Midureteric stones remain the domain of primary ureteroscopy; with moderate obstruction in the asymptomatic patient it may also be acceptable to wait for the stone to pass into the distal ureter spontaneously to be treated by ESWL in situ there. Manipulating stones back into the kidney and treating them by ESWL there (pushback/ESWL) offers no advantage over ESWL in situ, as the results are similar, yet morbidity is higher. Blind instrumentation and open surgery have lost all justification.


Long term follow-up after ESWL of large kidney stones.

In 76 patients (53 women and 23 men) aged 24-92 years, extracorporeal shock wave lithotripsy (ESWL) was performed between June 1986 and December 1988 as monotherapy for large kidney stones (diameter > 2.5 cm). There were 41 complete and 24 partial staghorn calculi. The patients were treated with the Dornier HM3 lithotripter under sedoanalgesia. Of the 60 patients with large stones whose last ESWL treatment was at least 24 months earlier, only 15 ultimately came for this long-term control check-up. Reports on 15 other patients were received from their doctors stating that the patients were doing well, not having new stone episodes. These subjects had to be excluded from final evaluation since they did not fulfill all requirements. Thirty patients had either moved out of the area or were from distant locations and therefore unable to appear. Creatinine was normal and urinalyses negative in these 15 patients; 12/15 were stone-free. The ones who were not had small remnants in the lower pole calices which did no harm at all. One patient already had elevated pretreatment blood pressure; 6/14 with normal blood pressure before ESWL showed elevated values 30 or more months after hte last ESWL. Radio-isotope examinations with separate clearance tests demonstrated no real evidence of loss of kidney function on the treated in comparison with the untreated side. Sonographic findings on the longitudinal and transverse diameter of the treated and untreated kidneys with regard to total number of shock waves did not show marked differences as they all remained below the 9% limit.


The "TUR-Catheter", a new catheter for postoperative drainage of the bladder.

A new catheter for postoperative irrigation of the bladder after operation of the prostate or bladder is introduced. Instead of 1 to 3 large holes measuring 5.5-6.5 mm by 2.5-3 mm at its tip, as in common catheters, it has 32 drainage holes, each of them measuring 1.5 mm in diameter. This type of construction still secures sufficient unhindered drainage of the bladder, even if the majority of holes is obstructed. Thus, postoperative tamponade is prevented.


[Single lung transplantation].

Thirteen single lung transplantations have been performed in our department for non-infected end-stage lung diseases. Two patients died after surgery; a female patient died of uterine carcinoma one year and six months after the operation. The remaining ten patients are alive; they have resumed an active life and often working. The number of single lung transplantation is rapidly growing in the world, whereas heart-lung transplantation is regressing considerably.


[Cytokines-endothelium interaction: its role in the thrombotic process].

The in vivo relationship between the immune and the coagulation systems is a well documented fact. In a number of pathological conditions, thrombosis is not understood isolately, but in the context of inflammation and immunity. The mediators in these complex multidirectional interactions are the cytokines, a group of soluble peptides which act on surface cellular receptors, with immunoregulatory properties. These molecules influence negatively the physiological antithrombogenic situation by two different mechanisms. They are involved in processes which disrupt the endothelial integrity, and at the same time, they are capable of activating the endothelium in a prothrombotic manner, by stimulating procoagulant activities and by inhibiting different anticoagulants.


[Health effects of chronic exposure to tobacco smoke on a non-smoker population].

A study devised to evaluate the effects of chronic exposure to tobacco smoke on the health of a population of non-smokers was conducted in a prison. Fourteen volunteers among male, non-smoking prisoners in good health and without history of lung disease were put for thirty days in a cell that was already occupied by three smokers. These subjects were examined on arrival and on the 30th day of their imprisonment. The examination included filling a questionnaire concerning daily habits and food, respiratory function tests, measurement of CO in the expired air, measurement of nicotine, cotinine, thiocyanates and cadmium concentrations in blood and in urine, and measurement of mutagenic substances excreted. The purpose of the study was to detect possible changes in the variables tested between the first and last days of confinement. No significant difference could be demonstrated within this lapse of time. These results are in agreement with the data available in the literature. In the present state of our knowledge, it is difficult to find evidence of a biological impact, notably on the concentrations of the specific indicators nicotine and cotinine, in subjects passively exposed to tobacco smoke.


[Nutrition of the terminally ill patient: dietetic guidelines].

Food is a factor of great importance in personal relationship during the terminal phase. There are numerous causes of appetite and taste disturbances that must be known by the family and physician. Some ideas are provided about the different ways to improve nutrition and appetite as a part of a plurisymptomatic management to maintain the patient's comfort until his last days of life.


[Bilateral chylothorax after mild trauma: apropos of a case].

The authors report a new case of bilateral chylothorax predominant on the left side, which occurred after movements of body trunk hyperextension in a 52-year old woman without any notable history. The clinical signs revealing the lesion were left thoracic pain and dyspnoea. The effusion had been preceded by a painless and transient left cervical tumefaction. The outcome was favourable after two left pleural draining punctures and rest.


[Giant cell tumors of the ribs. Apropos of a case].

The authors report a case of grade I-II giant-cell tumour of the ribs extending to the thorax and the vertebral column. The tumour was treated by surgical resection followed by vertebral curettage in two stages and adjuvant regional radiotherapy. Giant-cell tumours of the ribs are exceptional and rarely found in the literature. They raise a therapeutic problem (surgery is essential, but radiotherapy is controverted), and a prognostic problem (there is always a potential risk of recurrent malignancy).


Compatibility in porcelain to metal systems: Part 3.

As described in parts one and two of this article, all the steps leading to the finished casting can influence the compatibility between porcelain and alloy. This final part of the article will examine the influences of metal conditioning and thermal handling on the completed restoration.


Management and leadership--is your laboratory on automatic pilot?

Many management professionals have attempted to define the relationship between leadership and management. Some believe that leadership and management are interrelated characteristics, with one perhaps an extension of the other; others maintain that they are different qualities altogether. Few would argue with the notion, though, that leadership is a great quality for managers to have. This article explores management and leadership, and looks at some ways to enhance and encourage leadership in your laboratory.


Controlling porosity in microwave processed acrylic.

The purpose of this study is to investigate the relationship of bench curing techniques, processing time and microwave wattage to porosity in the processed acrylic resin.


Engineering and physics in dental technology. 1.

This work is a compilation of the principles of engineering and physics that are involved in the design and construction of various types of prostheses in the dental laboratory. It is intended as a reference of scientific doctrines for dental technicians who wish to advance their knowledge and skills. This article is the first of several that will be published in Trends & Techniques during the next several issues. The article in its entirety is by no means complete--the field is too enormous to identify all the tenets that apply, and future scientific advancement will certainly add others. Some elements of biomechanics are included in this work because of the interrelationship of biomechanics to engineering.


The clinical effects of electrostimulation on salivary function of Sjögren's syndrome patients. A placebo controlled study.

A multi-center double-blind study of an electro-stimulator device was conducted to evaluate its ability to increase the production of saliva and reduce clinical symptomatology. A total of 77 Sjögren's syndrome patients at three centers were assigned to active devices (n = 40) or to placebo devices (n = 37). There were 2 male and 32 female patients assigned to active devices, and 1 male and 36 female patients assigned to placebo devices. The age range with the greatest number of patients was 60-69 years making up more than 31% of the study population. The selection criteria required the patients to have no greater than 0.2 g/min of whole salivary production (approximately 19% of normal salivary production). At the start of the study, the patients assigned the active device had a mean salivary production of 0.06 ml per min (6% of normal) and patients assigned placebo devices had a mean salivary production of 0.07 ml per min (7% of normal). There were three scheduled visits, 2 weeks apart, over a treatment period of 4 weeks. At all visits, the patients using active devices showed a statistically greater (P = 0.005 to 0.02) increase in the production of saliva than placebo patients. The study also evaluated the reduction of patients symptoms associated with xerostomia. Patients showed significant improvement in (1) difficulty in swallowing and (2) burning tongue (P = 0.008). Some patients on their initial visit had no response to the active device and did not show a significant response at subsequent visits.(ABSTRACT TRUNCATED AT 250 WORDS)


Influence of prolonged neuropsychological testing on immunoregulatory cells and hormonal parameters in patients with systemic lupus erythematosus.

The influence of a 2-h neuropsychological stress test on plasma catecholamines, cortisol, and on the distribution of lymphocyte subpopulations was studied in 14 patients with systemic lupus erythematosus (SLE), 10 patients on prednisone treatment (without collagenosis), and 14 sex-and-age-matched healthy controls. Psychological stress induced comparably significant increases in plasma adrenaline and noradrenaline levels as compared with baseline values (P less than 0.05) in all three groups, whereas plasma cortisol remained unchanged. The rise in plasma catecholamines was accompanied by a significant cell mobilization in healthy subjects and prednisone-treated patients, but not in patients with SLE. CD19+ cells increased significantly in number from baseline in healthy subjects and prednisone-treated controls (P less than 0.05), while remaining unchanged in SLE patients. In conclusion, SLE patients showed a reduced cell mobilization due to psychological stress despite hormonal alterations paralleling those of healthy subjects or prednisone-treated patients without collagenosis.


Engineering and physics in dental technology. Part 2.

Part 2 covers the areas of friction and lubricants, cross sections, parallelism, passivity and equilibration, levers, reducing the radius, immobilization, and transmitral of forces. Some elements of biomechanics are included in the article because of the interrelationship of biomechanics to engineering.


Spontaneous expression of immediately-early response genes c-fos and egr-1 in collagenase-producing rheumatoid synovial fibroblasts.

In view of the important role of interstitial collagenase in the pathogenesis of rheumatoid arthritis (RA), we studied the expression of fibroblast-type collagenase in rheumatoid synovium and searched for its potential transcription factors, namely the oncoprotein c-fos and the early-growth-response gene-1 (egr-1), an inducible zinc-finger encoding gene. Elevated levels of RNA sequences complimentary to c-fos and egr-1 cDNA probes could be detected in cytoplasmic extracts of collagenase-expressing synovial fibroblast-like cells when compared to equivalent RNA amounts isolated from control fibroblasts. Utilizing immunocytochemistry, immunoreactivity for c-fos oncoprotein was found in 13 of 19 joint specimens obtained from patients with active RA. These oncoprotein data were positively correlated to the collagenase expression in the same specimens. Moreover, immunohistochemical analysis confirmed the localization of both oncoprotein c-fos and fibroblast-type collagenase within synovial fibroblast-like cells attached to bone erosions.


Rheumatic manifestations of infective endocarditis.

Rheumatic manifestations are common and varied in infective endocarditis. We performed a retrospective case analysis on 87 patients with 93 episodes of infective endocarditis admitted to Flinders Medical Centre over an 11 year period (1980-1990). Disabling musculoskeletal symptoms and signs were documented in 22 (25%) of the patients. Thirteen patients developed severe or moderately severe low back pain during their illness, two with radiological evidence of a septic discitis or vertebral osteomyelitis. Two patients developed polyarthralgia/arthritis, four had septic arthritis (all with acute Staphylococcus aureus endocarditis), three developed severe loin pain, two acute gout, two had severe buttock pain and sacroiliac joint tenderness and two each developed disabling jaw/facial pain, neck/scapular pain and flank pain respectively. Five patients presented initially to the orthopaedic or rheumatological unit for management of their musculoskeletal symptoms. Four of seven patients with Streptococcus bovis endocarditis demonstrated prominent low back pain supporting a previously noted association between this organism and back symptoms. Furthermore, in one patient who had three separate episodes of endocarditis involving three different organisms, florid back symptoms were only seen in the infective episode involving Streptococcus bovis.


Changes in clinical features of patients with systemic lupus erythematosus followed prospectively over 2 decades.

In the past decades the general concept of the disease course and the prognosis of systemic lupus erythematosus (SLE) has changed dramatically. The improvement in prognosis of our SLE patients is often said to be related to the growing awareness of the disease. This study focussed on whether or not the clinical features at the onset of the disease, and at diagnosis, and the clinical course as well as the age at the onset of the disease had changed during the past decades. No obvious differences were observed in the age at the onset of the disease or in the age at diagnosis. Of the 22 clinical signs studied, only the prevalence of Raynaud's phenomenon at the onset of the disease had increased during the past 20 years. At diagnosis, the prevalence of oral ulcers and false positive syphilis test had decreased. Only small differences in the type but not in the number of exacerbations were observed; in the past 20 years, the prevalence of renal involvement increased from 20% to 43%. However, this was not significant. Our results did not support the theory that during the past 2 decades the disease had changed in its expression, neither did we find that the disease is presently diagnosed at an earlier age, as would be expected from the increased awareness of the disease.


Cyclosporin A in a pregnant patient affected with systemic lupus erythematosus.

Few data regarding the use of cyclosporin A (CyA) in pregnancy are available and those available refer mainly to transplant recipients and not to patients with connective tissue diseases. We report the case of a patient with systemic lupus erythematosus (SLE), taking CyA before, during and after her pregnancy at a dose of 4 mg/kg per day. CyA was effective in controlling SLE activity and no side effects were observed in mother or baby. The lack of teratogenicity in this case was in keeping with previous reports in experimental systems, animals and human transplant recipients. If our observation is confirmed by further studies, CyA might become useful in the treatment of pregnant patients with SLE.


Palmar fascial thickening and contractures of fingers resembling arthritis--a paraneoplastic symptom?

A 59-year-old women presented with contractures of the fingers of both hands 11 months before a diagnosis of an ovarian carcinoma with paraaortic lymph node metastases was made. We suggest that the contractures, which were associated with palmar fascial thickening and which clinically resembled arthritis, might have been a paraneoplastic sign.


AB0 and Lewis blood groups in reactive arthritis.

In this study we evaluated secretor status in patients with reactive arthritis. Previous evidence indicates that non-secretion of AB0 and Lewis blood group antigens to saliva and other secretions is associated with susceptibility to certain bacterial infections and certain diseases with suspected autoimmune etiology. Secretor status can be determined based on the Lewis phenotype. We studied AB0, Lewis and Rhesus blood groups of 54 patients with previous reactive arthritis, 26 of whom had uroarthritis and 28 of whom had arthritis after enteric infection. Furthermore, 25 patients with uncomplicated yersiniosis and 57 healthy controls were studied. We did not find any correlation between secretor status and reactive arthritis or gastroenteritis due to Yersinia. AB0 blood group antigen B appeared to be protective against uroarthritis.


Survival in patients with systemic lupus erythematosus in India.

Survival in patients with systemic lupus erythematosus (SLE) in developed countries has improved considerably over the last 2 decades. In India, however, survival in patients with SLE reported 5 years ago from this tertiary referral centre was very poor. The present study was conducted to examine trends, if any, towards improvement in the survival of patients with SLE attending the same centre during the period 1981-1990. No statistically significant change in survival was noted. It appears that improvement in the survival of SLE patients would require an overall improvement in the standard of medical care in India.


Clinical significance of rheumatoid factor isotypes in seropositive arthritis.

In this cross-sectional study a comparison was made of rheumatoid factor (RF) isotypes in 203 RF positive patients with arthritis. Of these, 129 had rheumatoid arthritis (RA) and 74 a milder disease that would formerly have been classified as probable RA. The majority (74%) of the RA patients had elevations of two or three RF isotypes compared with only 34% of the patients with the milder form of arthritis. A striking feature was that combined elevation of IgM RF and IgA RF was found in 67% of the RA patients compared to only 20% of the patients with milder arthritis who most frequently had an isolated elevation of IgM RF (41%). RA patients with an isolated elevation of IgA RF were younger and had a shorter disease history than RA patients with an isolated elevation in IgM RF or a combined elevation of IgA RF and IgM RF. The prevalence of raised IgM RF was, furthermore, found to increase with age and disease duration. We conclude that a raised level of IgA RF is an adverse phenomenon in patients with seropositive arthritis while patients with an isolated increase in IgM RF may be expected to experience a relatively mild disease course.


Scanning electron microscopic evaluation of the arthritis in MRL/lpr mice.

The articular surfaces of disarticulated knee joints from MRL/lpr and MRL/n mice, aged 4-33 weeks were examined by light microscopy (LM) and scanning electron microscopy (SEM). Light microscopy did not reliably predict SEM findings. Most of the abnormalities detected by SEM were related to surface disruption of articular cartilage. However, areas of articular cartilage covered by tightly adherent non-confluent monolayers of stellate-shaped cells with intertwining cytoplasmic processes were observed. In these areas the integrity of the underlying cartilage matrix was disrupted, with exposure of collagen fibers. These findings suggested that outgrowth of proliferating synovial cells in the joints of arthritic MRL/lpr mice may lead to cartilage destruction.


Analysis of glycosaminoglycans in human serum after oral administration of chondroitin sulfate.

Chondroitin sulfate was administered orally to six healthy volunteers, six patients with rheumatoid arthritis and six patients with osteoarthritis. Blood was collected at intervals before and after treatment and the glycosaminoglycan concentration was analyzed in serum using a sensitive assay based on the metachromatic reaction with 1,9-dimethylmethylene blue. The glycosaminoglycan concentration in serum before and after ingestion of chondroitin sulfate was statistically unchanged in all of the subjects studied. We suggest that chondroprotection by orally administered chondroitin sulfate is a biologically and pharmacologically unfounded theory. Any possible benefit to osteoarthritic patients after ingestion of chondroitin sulfate should be sought at the gastrointestinal rather than at the plasmatic or articular cartilage level.


Lymphokines and soluble interleukin-2 receptors in juvenile chronic arthritis. Clinical and laboratory correlations.

Serum levels of interleukin (IL)-2, interferon gamma (IFNg) and soluble IL-2 receptors (sIL-2R) were determined in sera from 34 patients with poly- or pauciarticular juvenile chronic arthritis (JCA) by use of enzyme-linked immunosorbent assays (ELISAs). Levels of sIL-2R were elevated in the group of patients compared with those of healthy children and correlated significantly with several parameters of clinical activity, including the functional capacity, joint score, visual-analogue score and erythrocyte sedimentation rate (ESR). Serum IL-2 levels were also elevated in the JCA patients, correlating with the patients functional capacity. Serum levels of IFNg were below the detection limit of the assay. Our data supported the notion that T-cell activation plays a role in the immunopathologic processes leading to clinical JCA.


Arthritis community education by leather puppet (wayang kulit) shadow play in rural Indonesia (Java).

As part of the WHO/International League Against Rheumatism (ILAR) sponsored community organized programme for the control of rheumatic disease (COPCORD), an arthritis community education programme (ACE) was undertaken utilizing the traditional form of entertainment in a rural area in Central Java-the wayang. The point prevalence rate of musculoskeletal complaints was estimated in 4683 men & women aged 15 years and over by house-to-house interviews. From 1105 respondents recording recent musculoskeletal pain, 844 were randomly selected and half the latter attended a puppet shadow play (wayang) incorporating the ACE. The other half, matched for age, sex and educational level who did not see the play, served as controls. A questionnaire containing biphasic choices of correct or incorrect ways of performing activities of daily living (ADL) to minimize musculoskeletal problems was administered to the whole group before, 1 month and 6 months after the wayang. Increased knowledge of correct ways of performing ADL (correct ADL) in the intervention group compared with the control group at 1 and 6 months after wayang was significant (P less than 0.05). Comprehension of correct ADL following the wayang could be demonstrated even in subjects who were illiterate and those who had attended primary school only. Retention of knowledge at the 6 month assessment declined more markedly in the illiterate group. ACE by wayang was shown to be feasible and effective in transferring knowledge on ADL to people with musculoskeletal problems in the sample population in Java. This effect could be shown even in the poorly educated section of the community.(ABSTRACT TRUNCATED AT 250 WORDS)


Influence of topical steroid treatment on maxillary sinusitis.

The clinical efficacy and adverse effects of budesonide administered as a nasal aerosol in addition to sinus washings and erythromycin therapy was assessed by comparison with placebo in a randomized, double-blind study of 40 patients with chronic or recurrent maxillary sinusitis. Most of the patients had been referred for operative treatment. Corticosteroid therapy, 400 micrograms daily, or placebo was continued for 3 months. Budesonide and antral irrigations reduced nasal symptoms more effectively than placebo, and there was a significantly greater reduction in facial pain and sensitivity in the budesonide group than in the placebo group. During the treatment period, mucosal thickening as evaluated by radiology decreased more clearly in the budesonide group than in the placebo group, but the difference did not reach statistical significance. The most frequently isolated bacteria were Staphylococcus aureus, Staphylococcus epidermidis and Haemophilus influenzae. Only 2 of 20 Haemophilus strains were beta-lactamase producers. The cellular picture was dominated by neutrophils in all secretions. There was no significant difference in clinical outcome between the two groups. Topical steroid therapy did not cause any adverse effects.


The value of high-resolution CT-scan for diagnosis of infectious paranasal sinuses disease and endonasal surgery.

Since 1986 the high resolution CT in two planes is part of our preoperative diagnostic program for patients with chronic rhinosinusitis, acute, complicated rhinosinusitis and polyposis nasi. The importance of the CT for diagnosis, localization, and planning the operation shall be demonstrated.


Nasal sensitization of dairy farmers to bovine epithelial and urinary antigens.

Nineteen dairy farmers with nasal symptoms associated with working in cowhouses participated in the study. Nasal challenge with bovine epithelial antigen (BEA) and bovine urinary antigen (BUA) was made before and after the indoor feeding season. Nasal challenge made before the indoor feeding season with BEA was positive in five patients and three of them showed positive reaction in nasal challenge also with BUA. After the indoor feeding season the results in nasal challenge with BEA were approximately equal to BEA and four of them showed positive response in nasal challenge to BUA. However, we did not find any significant increase in sensitivity in nasal challenge to BEA or BUA after the indoor feeding season. In addition to these patients, two patients who were excluded from nasal challenge before the indoor feeding season showed positive results in nasal challenge after the indoor feeding season with both BEA and BUA. Our results suggest that BUA in addition to BEA may have significance to nasal symptoms.


Nasal mucosa reaction. A model for mucosal reaction during challenge.

Rhinological symptoms in aspects of hyperreactivity and allergy are increasing problems. Previous reports on this subject are based on studies of airway obstruction (rhinomanometry), secreted substances during challenge, and symptom scores. To be able to define and evaluate the pathological reactions in nasal hyperreactivity and allergy, it is necessary to find principles to describe and standardize the reactions of the healthy nasal mucosa. The aim of this study was to examine congestion of the nasal mucosa in healthy volunteers. Existing measuring methods, in this aspect, are either indirect or not accurate enough for this purpose. With the development of rhinostereometry, an optical measuring method, it is possible to record nasal mucosa congestion with high accuracy. A nasal challenge test was made in healthy volunteers with gradually raised concentrations of a histamine solution, which was applied to the inferior concha on the right side. Recordings of the mucosal congestion were made with rhinostereometry. We found that it is possible, with statistical significance, to standardize the reactions of the healthy nasal mucosa: There is no congestion more than 0.4 mm with a histamine concentration of less than 4 mg/ml (p less than 0.05); congestion of more than 0.4 mm is present at histamine concentrations of 16 mg/ml (p less than 0.05).


Hereditary haemorrhagic teleangiectasia: unsuccessful treatment with the flashlamp-pulsed dye laser.

In seven patients with hereditary haemorrhagic teleangiectasia (HHT) only one patient had lasting benefit from treatment with the flashlamp-pulsed dye laser. In seven other patients who had received other treatment before, none had any observable effect of this laser. The flashlamp-pulsed dye laser therefore does not seem to be effective in the treatment of nasal teleangiectasias.


Nasal vascularization: experiences using the microcorrosion technique in human foetuses.

The authors have studied the three-dimensional aspect of the vascular architecture of the nasal mucosa, using the microcorrosion method followed by scanning electron microscopical observation of casts of the vascular networks in both the septum and the lateral part of the nose. Batson's compound was introduced into the vascular system through the ascending aorta, in order to obtain a replica of the nasal mucosa vessels. Twelve- to 24-week-old foetuses obtained from spontaneous abortions were used for this purpose.


Fractured-nose reduction under local anaesthesia. Is it acceptable to the patient?

This article examines patients' acceptance of fractured-nose reduction under local anaesthesia, both objectively and subjectively. At each stage of the reduction the level of the discomfort, the patients' experiences were recorded. The success rate of complete reduction of the nasal fracture was found to be 71% and this was similar to that obtained in other studies that have used general anaesthesia. An overall level of discomfort for the procedure in terms a layman can understand was obtained by comparing the manipulation with that of having a tooth filled at the dentist. Sixty-three percent of the patients said that the nasal fracture reduction was no worse or the same as a dental filling. Our study showed that 96% of patients would be willing to undergo the same local anaesthetic procedure if they fractured their nose a second time. We conclude that it is possible to reduce the majority of fractured noses adequately with little inconvenience to the patient under local anaesthesia, and so we recommend that this procedure should be considered in the first-line treatment of the displaced fractured nose.


Nasal mucociliary clearance and resolution of otitis media with effusion in children following adenoidectomy.

Numerous workers have studied the relationship between nasal mucociliary clearance and adenoid removal in terms of nasal function. This study was performed to investigate the role of preoperative saccharin clearance time and velocity determination in selecting children with established otitis media with effusion (OME) for adenoidectomy. Testing was not found to be particularly reproducible and there was no statistically significant relationship between mucociliary parameters and the otoscopic resolution of effusion.


[Anemophilous fungi: viability and allergenicity].

Three strains of anemophilous fungi (Alternaria, Rhizopus and Monilia) from different genera were studied. We found that the liquid Sabouraud and culture media used in this study lost nutrients after seven days of strain growth, without affecting their viability. This was proven when the fungi were reseeded at 15 and 60 days. Extracts from supposedly sensible patients were developed using intradermoreaction skin tests, finding no significant differences among the results obtained from these tests. We recommended further studies with more prolonged growth periods (90, 120, 180 or more days) to see whether this incides on the viability and allergenicity of the anemophilous fungi.


[Effectiveness of sodium cromoglycate in the reduction of bronchodilator doses in asthmatic patients].

Thirty asthmatic patients, ages ranging from 6 to 72 years, who were submitted to a 14 weeks clinical evaluation, were studied measuring the severity of dysnea, coughing, expectoration and wheezing. Sodium chromoglycate (SCG) was administered in aerosol starting the second week of the study and the doses of bronchial dilators was reduced starting the fourth week, with a 25% decrease in the total established initial dosage, every two weeks. In this study, SCG showed to be useful in decreasing symptoms caused by bronchial hyperreactivity and the use of bronchial dilators in 70% of asthmatics who react with the presence of just one risk factor (cold, the most frequent).


[In vitro and in vivo acari tests].

We studied 40 children with one o more perennial allergic diseases (bronchial asthma, allergic rhinitis, and/or atopic dermatitis) to assess the value in our country of in vivo and in vitro tests more frequently used in the diagnosis of allergy, such as total serum IgE, specific allergen IgE (RAST) and prick skin test in patients sensitives to D. pteronissinus, D. farinae or both. All patients had positive prick skin tests. Total serous IgE was elevated in 95% of cases with poor correlation coefficient (r) between prick skin test reactivity and total serous IgE concentration with no statistical significance. On the other hand, 95% of patients showed a positive RAST with a correlation coefficient of 0.31 (p less than 0.05). We concluded that in our country clinical history and prick skin tests are sufficiently accurate in a reasonable way to make a diagnosis of allergic etiology in patients sensitives to mites of the house dust.


Abnormal auditory brainstem responses and cochlear pathology in rats induced by an exaggerated styrene exposure regimen.

Groups of 12 male 42-day-old rats were exposed to 0 or 800 ppm styrene vapors for 14 hr/day, 5 days/week for 3 weeks. Tone-pip auditory brainstem responses (ABRs) at 4, 8, 16, and 30 kHz were obtained after the last exposure. ABRs were minimally affected at 4 kHz and moderately to severely affected at 8, 16, and 30 kHz as indicated by waveforms which had a decreased amplitude and increased latency as compared to the controls. Missing outer hair cell(s) were evident in the basal and lower middle turns of the organ of Corti. Outer hair cell loss was least in the first row and greatest in the second and third rows. Occasional inner hair cells were also missing in regions of severe outer hair cell loss. The distribution of hair cell loss within the cochlea was consistent with the pattern of ABR alterations. These data document mid-frequency auditory dysfunction in styrene-exposed young adult rats with significant damage to the organ of Corti following an exaggerated styrene exposure regimen.


Light microscopic and ultrastructural pathology of seminiferous tubules of rats given multiple doses of Pasteurella multocida group D protein toxin.

Male Holtzman rats were given subcutaneous doses of a purified Pasteurella multocida group D heat-labile toxin on alternate days for up to 22 days. Rats were necropsied at 18 days or 36 days (14 days after last dose of toxin) or when moribund, and testicles were taken for histologic and ultrastructural examination. Other selected tissues, including liver and spleen, were taken for histologic examination. Histologically, testicular and splenic lesions occurred more consistently and at much smaller doses when compared with lesions in other target organs such as liver. Testicular and splenic lesions were present in all rats (6/6) given 0.8 micrograms/kg toxin and were seen in some rats (1/6) given as little as 0.2 micrograms/kg toxin. Only 3/6 rats given 0.8 micrograms/kg toxin had hepatic lesions; no hepatic lesions were seen at doses of 0.2 micrograms/kg. Testicles from toxin-treated rats were smaller and weighed less than controls. Seminiferous tubules were moderately dilated and lined by polygonal sertoli cells. The normal spermatogenic maturation sequence and mature spermatids were absent, and many tubules contained multinucleate spermatocytes. Severely affected tubules were necrotic and mineralized. Ultrastructurally, there was necrosis of adluminal spermatocytes, multinucleate cell formation, and spaces between Sertoli cell plasma membranes. Testicular lesions were similar to those described for vitamin D-deficient rats, vitamin A-deficient rats, vasectomized rats, and rats given intravenous tumor necrosis factor; however, rats given lethal doses of toxin did not have elevated levels of TNF alpha activity.


Liver tumors in male rats following treatment with glucocorticosteroids.

Male rats treated with either budesonide, prednisolone, or triamcinolone acetonide in drinking water for up to 104 weeks developed slightly increased incidences of basophilic foci, and significantly increased incidences of combined hepatocellular adenomas/carcinomas as compared to controls. Based upon reduced body weight gains and survivals, the doses administered were considered to be toxic. It was concluded that the positive findings represented a class effect, and probably involved glucocorticoid receptors.


Histological sectioning of the rodent larynx for inhalation toxicity testing.

In rodents, the larynx is a major site of histopathologic alteration following inhalation exposure to particulates, vapors, and aerosols. Specifically, the epithelial lining of a narrowly delineated region on the ventral floor of the larynges of rats and mice appears to be especially vulnerable to inhaled materials, and is recognized as a preferred site for histopathological evaluation in inhalation studies. This site is located at the base of the epiglottis, cranial to the ventral laryngeal diverticulum (ventral pouch). The presence of underlying seromucinous glands is critical for histologic identification of this site. We report a histologic sectioning technique, using the ventral laryngeal diverticulum as the anatomical landmark, to obtain tissue sections from this area of predilection in rats and in mice.


Spontaneous renal neoplasms in aged Crl:CDBR rats.

Primary neoplasms of the kidneys occurred in 11/682 male (1.6%) and 2/694 female (0.3%) Crl:CDBr strain Sprague-Dawley rats. Eight of 13 neoplasms were of mesenchymal origin and 5 of 13 were epithelial. Five neoplasms were lipoma (3) or liposarcoma (2). Three of 13 were either hemangioma (1) or mesenchymal tumors (2). The epithelial neoplasms were carcinomas. There was no microscopic evidence of metastasis among those neoplasms judged malignant on morphologic criteria. The overall natural incidence in males was nearly double that compiled for this strain while in females the incidence was similar to that reported for other females.


Prednisone is not a mouse carcinogen.

The carcinogenic potential of prednisone, a synthetic corticosteroid used as an anti-inflammatory and immunosuppressive agent, was investigated by feeding it to Crl:CD-1(ICR) mice (50/sex/dose) at doses of 0.25, 0.50, 1.0, and 5.0 mg/kg/day for 18 months. Prednisone did not significantly increase the incidence of neoplasms (p less than or equal to 0.05); on the contrary, it significantly decreased the incidence of hepatocellular tumors (p = 0.002 in males, p = 0.027 in females), male lacrimal/Harderian gland tumors (p = 0.05), female pulmonary adenomas (p = 0.047), female endothelial cell tumors (p = 0.035), and female lymphosarcomas (p = 0.02). This study suggests that long-term (lifetime) prednisone use does not increase cancer risk and may actually reduce it.


Stereological evaluation of altered hepatocellular foci in control Wistar rats.

Quantitative evaluation and stereological analysis of altered hepatocellular foci (AHF) were performed on hematoxylin and eosin-stained (H&E) liver sections from control Wistar rats from 9 2-yr carcinogenicity studies conducted between 1981 and 1991. Morphologic criteria previously described were used to classify AHF in H&E stained livers into basophilic, eosinophilic, clear, mixed, or vacuolated cell foci. Hepatocellular adenomas were seen in 1.6% of control rats and carcinomas were seen in 0.2%. AHF were diagnosed in 20% of control Wistar rats and were seen only in rats dying after 47 weeks. Basophilic foci were the most common AHF seen; incidences of tigroid and diffuse basophilic AHF were similar. Vacuolated foci were not identified in any rat. The mean number of AHF per cubic centimeter of liver was 101. The mean AHF volume varied from 0.002-0.048 mm3 and the mean volume fraction ranged from 0.005-0.026%. Compared to AHF in aged control Fischer 344 rats, AHF in control Wistar rats were fewer and smaller.


Testicular damage caused by inhalation of ethylene oxide in rats: light and electron microscopic studies.

Although testicular damage caused by ethylene oxide vapor (EtO) has been previously reported, the morphological changes occurring in seminiferous tubules remain unclear. We examined the time course of the testicular lesion induced by EtO in order to clarify its morphogenesis. Wistar rats were exposed to 500 ppm EtO for 6 hr per day, 3 times per week for 2, 4, 6, or 13 weeks through inhalation. In the 2-week exposure group, Sertoli cells often showed condensation and retraction of the cytoplasm, and dilatation of the endoplasmic reticulum (ER). In apical Sertoli cells, processes which encapsulated the heads of elongate spermatids, ectoplasmic specializations, and tubulobulbar complexes were often deformed and many elongate spermatids were degenerated. In the 4- and 6-week exposure groups, many degenerated Sertoli cells were present, and deformed germ cells, sometimes with multinucleation, appeared to make direct contact with each other without interlocation of Sertoli cell lateral processes. A few scattered immature Sertoli cells were evident in the 6-week exposure group. In the 13-week exposure group, seminiferous tubules containing almost all types of germ cells reappeared, mixed with atrophic tubules containing Sertoli cells only. In the former tubules, Sertoli cells often possessed regularly regenerated lateral processes, which were interposed between germ cells. These results indicate that the germ cell damage may be associated with damage to Sertoli cells. In spite of the intermittent exposure, focal regeneration of Sertoli cells appeared after 6 weeks of exposure to EtO and preceded patchy recovery of germ cells. Therefore, the data suggest that Sertoli cell regeneration may permit regeneration of germ cells.


Histologic methods and interspecies variations in the laryngeal histology of F344/N rats and B6C3F1 mice.

The relatively high incidence and variety of lesions induced in the upper respiratory tract of rodents by inhalation of xenobiotics has resulted in considerable attention given to the microscopic anatomy of this area. Specific areas of the rodent laryngeal mucosa appear to be more sensitive to inhaled materials and more likely to contain cellular changes in response to injury. These include the epithelium covering the base of the epiglottis, ventral pouch, and the medial surfaces of the vocal processes of the arytenoid cartilages. There are few good landmarks for trimming rodent larynges to get consistent and accurate sections through these target areas. We have obtained consistently reproducible results by cutting transversely through the easily palpable cricothyroid notch and embedding the entire larynx anterior to this in paraffin with the cut surface against the face of the block. Multiple sections are cut from the caudal larynx toward the epiglottis, unstained sections examined microscopically for orientation, and sections from target areas selected for staining and histopathologic examination. Routine use of these methods for preparation and microscopic examination of sections of the larynx has revealed some variations in normal laryngeal anatomy between Fischer 344 (F344/N) rats and B6C3F1 mice.


Effects of corn oil, time-related changes, and inter-laboratory variability on tumor occurrence in control Fischer 344 (F344/N) rats.

Survival, body weight, and site-specific tumor rates in untreated, corn oil gavage, and water gavage control Fischer 344 (F344/N) rats from 88 National Toxicology Program (NTP) long term carcinogenicity studies were evaluated to determine which factors were primarily responsible for inter-study variability. For male rats, previously-reported decreases in leukemia and increases in body weight, survival, and pancreatic acinar cell tumors attributable to corn oil gavage were confirmed. Corn oil did not appear to affect tumor rates in female rats. The gavage technique per se did not appear to influence tumor rates in rats of either sex. Previously reported time-related increases in certain site-specific neoplasia in control rats appeared to have stabilized in recent years, but control tumor rates are still much greater than those seen a decade ago. More recent studies continue to show increasing rates of leukemia and mammary gland tumors and decreasing survival. Female rats also continue to show time-related increases in maximum mean body weight. Inter-laboratory variability in body weight and in the rates of a number of site-specific neoplasms were also significant. High mean body weights in control groups were found to be associated with increased rates of mammary and pituitary tumors. Our evaluation supports the view that if historical control data are to be utilized in the interpretation of experimental results, primary emphasis should be given to lab and route of administration-specific tumor rates for studies that are contemporary to the study under evaluation. It also suggests that certain experimental design changes (e.g., dietary modifications) may be needed to reduce tumor rates and to increase survival.


Hepatic morphologic and biochemical changes induced by subacute cocaine administration in mice.

The initial event and site of cocaine-induced hepatic injury have not been elucidated. In an attempt to identify the minimal effective dose and the site of injury, we have examined the livers of mice exposed to small daily doses of cocaine, using morphological and biochemical methods. All doses of cocaine greater than 5 mg/kg were able to cause significant elevation of serum glutamic pyruvic transaminase. Light microscopy revealed a progression of centrilobular necrosis as the dose increased from 10-30 mg/kg. The initial morphologic changes observed prior to necrosis included aggregation of intermediate filaments and dilation of rough endoplasmic reticulum with loss of ribosomes. Immunohistochemistry, using antibodies to cytokeratins, showed staining of individual hepatocytes in livers from cocaine-treated animals but not in controls. In contrast to earlier reports, we found little, if any, disruption of mitochondria. In vitro, the direct application of cocaine, norcocaine, and N-hydroxynorcocaine on isolated mitochondria had no effect on the ADP:O or respiratory control ratios, at concentrations up to 2.0 mM. Our studies demonstrate that any early cellular alterations in cocaine-induced hepatic injury are manifested in intermediate filaments and endoplasmic reticulum with no evidence of mitochondrial involvement.


Drug-induced hepatic microgranulomatosis in cynomolgus monkeys.

This report discusses a unique drug-induced hepatotoxicity in cynomolgus monkeys treated orally with a novel potassium sparing experimental diuretic, [2,6-bis(4-chlorophenyl)-4-pyridinecarboxylic acid]. Groups of 6 adult male and female monkeys were treated orally with vehicle diluent, modified vehicle #122 or a suspension of the drug at 5.0, 12.5, or 32.0 mg/kg/day for 2 weeks. Another group of 5 monkeys were treated orally with 25.0 mg/kg/day of the drug for 2 weeks. Disposition of the drugs was evaluated in 2 monkeys in the later group that received 27.4 mg/kg of radiolabelled drug on the 1st and last day of dosing. Hepatic toxicity was characterized biochemically, light and electron microscopically, histochemically, immunocytochemically, and toxico-kinetically. Conjugated serum bilirubin, alanine transaminase, and aspartate transaminase levels were increased in monkeys treated with over 12.5 mg/kg/day of the diuretic. The periacinar hepatic plates of monkeys treated with 25.0 or 32.0 mg/kg/day were distorted by accumulation of PAS and oil red-O positive multinucleated Kupffer cells. The cytosol of these cells was expanded by phagolysosomes containing granular materials of varying electron densities. Granular electron dense materials were also in endothelial cells and bile canaliculi. Fatty change, cholestasis, and rare piecemeal hepatic necrosis were minimal. The drug was primarily excreted through urine. Plasma concentration and half life of the drug were increased with multiple dosing. The highest concentration of unexcreted parent drug was in the liver. Drug-induced noninflammatory hepatic microgranulomatosis, apparently caused by sequestered drug-lipid/mucopolysaccharide complex in the phagocytic cells of the liver, can occur in any species, including humans, if orally administered xenobiotics are presented to the liver in particulate form.


Pathogenesis of blood-filled cavities in estrogen-induced anterior pituitary tumors in male Sprague-Dawley rats.

The formation of blood-filled cavities in developing tumors of the anterior pituitary of estrogen-treated male Sprague-Dawley rats was studied in a serial sacrifice experiment. Two treated and 2 control rats were killed at each of 15 time points ranging from 7-272 days after sc implantation of an estradiol-17 beta pellet. The pituitaries were examined using light and electron microscopy. Changes at 7-9 days after implantation included epithelial cell swelling and trabecular arrangement. At 11-13 days, epithelial cells were further enlarged. Arrangement of epithelial cells in islands and endothelial degeneration were first seen at this interval. Also, any sinusoids were distended, whereas some were compressed by swollen epithelial cells. At 16-81 days, scattered necrotic and immature epithelial cells were present, and cell size decreased. Endothelial degeneration and both distended as well as compressed sinusoids were more prominent at this time. Loss of basement membrane was first seen during this interval. At 114-133 days, small hemorrhagic areas partially lined by epithelium were first seen; sinusoidal compression, endothelial necrosis, and loss of basement membrane were more frequent, but there was less sinusoidal distention. Between 150 and 272 days, epithelial cells were increasingly pleomorphic and arranged in nodules, and there was an increase in number and size of the hemorrhagic areas. Sinusoidal compression, endothelial necrosis, and loss of basement membrane were abundant, whereas sinusoidal distention had almost disappeared at this interval. Local compression of sinusoids and perhaps compression of pituitary surface veins due to epithelial cell swelling, were thought to play a primary role in the development of ischemic endothelial damage leading to loss of endothelial lining and basement membrane, and eventually to the formation of blood-filled spaces partially lined by epithelial cells.


Histopathological effects in Poecilia reticulata (guppy) exposed to methyl mercury chloride.

To evaluate the usefulness of histopathology in aquatic toxicity testing, studies were carried out on the small freshwater fish Poecilia reticulata (guppy) following aqueous methyl mercury chloride exposure. Fish were exposed to concentrations of 0, 1.0, 1.8, 3.2, 5.6, or 10 micrograms/L for 1 and 3 months. Histopathological changes included the occurrence of multiple granulomas in various tissues, in particular, the integument and orbit. These changes were accompanied by hyperplasia of monocytopoietic interrenal tissue, and hepatocellular change which was confirmed by morphometry. The latter findings were probably a result of monocyte "consumption" by granulomas, and hepatic synthesis of ("stress") proteins, respectively. The bile duct and, focally, the proximal intestine, showed hyperplasia of the epithelium. In the testis of sexually mature fish (3-month study), degeneration and necrosis of sperm occurred, with severe cases exhibiting Sertoli cell hypertrophy, interstitial inflammation, and absence of mature sperm. Epidermal mucous cells disappeared in the highest concentration used, and, after 3 months, clusters of undifferentiated basophilic cells were seen in the gas gland, which occasionally were suggestive of malignant growth. The changes in the kidney tubules were characterized by degeneration and necrosis of single cells which also showed mitotic figures. This is considered a result of the mitosis-disturbing activity of methyl mercury (MeHg). It is concluded that MeHg has effects on various target organs in guppies with the occurrence of granulomas as the most sensitive indicator, yielding a no-observed-effect concentration (NOEC) of 1.0 micrograms/L. In contrast to mammalian species, no morphologic evidence for neurotoxicity was found.


Rat urinary bladder hyperplasia induced by oral administration of carbonic anhydrase inhibitors.

The carbonic anhydrase inhibitors, acetazolamide and MK-0927, were given by oral route to male Sprague-Dawley rats at 200 mg/kg/day and 25 mg/kg/day, respectively, for up to 4 weeks. Sequential necropsies were performed and urinary bladders were examined by light microscopy (LM), scanning electron microscopy (SEM), and transmission electron microscopy (TEM). Similar urinary bladder changes were seen with both compounds. SEM evidenced slight multifocal urothelial changes consisting of cell swelling, dissociation, degeneration, and exfoliation after 3 and 5 days of treatment. After 2 and 4 weeks of treatment, elevated or leafy microridges on the luminal cell surfaces were seen together with foci of swollen cells. After a 2-month-recovery-period, the urothelial surfaces were normal. LM and TEM showed multifocal vacuolation of the urothelium associated with inflammation of the underlying lamina propria after 3 and 5 days of treatment. Cellular hypertrophy and hyperplasia of the transitional epithelium was seen after a 5-day treatment, persisted without increasing severity after 2 and 4 weeks of treatment, and totally regressed after the recovery period. It was concluded that, in the rat urinary bladder, oral administration of acetazolamide and MK-0927 induced early degeneration and inflammation followed by epithelial regeneration, resulting in a reversible hyperplasia of the transitional epithelium.