Congenital infections with reovirus.

Congenital reovirus, type 2 infections were produced after intraperitoneal inoculations of brood mothers on the 1st, 3rd, 6th, 10th, and 15th day of gestation. The offspring presented with a varied syndrome. About a quarter of a total of over 200 mice showed symptoms within the first 14 days of life; namely, lassitude, retarded growth, and roughening of fur. Some died, apparently of respiratory or renal failure. Post mortem examination showed marked interstitial pneumonia and subcortical renal tubular necrosis. Reovirus was isolated in high titer from the kidney and lungs as well as from blood, hearts, hind limbs, and brains in lesser titer. At 3 wk of age over 50 apparently well mice were sacrificed, and virologic, serologic, and pathologic study was done. High titers of virus were again found in the kidney, lung, blood, brain, heart, and skeletal muscle, but all tissues appeared normal histologically. Type-specific serum antibody titers in these mice were approximately those of their mothers. Another half of these mice showed decreased spontaneous activity and growth retardation which appeared between the 15th and 36th days of life. Three of these mice with late illnesses had marked proptosis and conjunctivitis. A subepidermal conjunctival and extraocular muscle lymphocytic infiltrate was observed on section, and reovirus was isolated from these eyes in tissue culture. Again blood, brain, kidney, liver, spleen, myocardium, and skeletal muscle were studied, and were found to be normal histologically and not to contain reovirus. Finally, the rest of the mice remain well to date. At 3 months of age, 10 of them were sacrificed. All had lost their maternal antibody and contained no reovirus, type 2 hemagglutinating inhibiting antibodies. No developmental abnormalities were observed. These data suggest that prolonged reovirus infections may be established by means of congenital inoculation of the developing fetus. Tolerant infection with immune paralysis seems to have been established.

Are the adverse effects of glitazones linked to induced testosterone deficiency?

BACKGROUND: Adverse side-effects of the glitazones have been frequently reported in both clinical and animal studies, especially with rosiglitazone (RGZ) and pioglitazone (PGZ), including congestive heart failure, osteoporosis, weight gain, oedema and anaemia. These led to consideration of an evidence-based hypothesis which would explain these diverse effects, and further suggested novel approaches by which this hypothesis could be tested. PRESENTATION OF HYPOTHESIS: The literature on the clinical, metabolic and endocrine effects of glitazones in relation to the reported actions of testosterone in diabetes, metabolic syndrome, and cardiovascular disease is reviewed, and the following unifying hypothesis advanced: "Glitazones induce androgen deficiency in patients with Type 2 Diabetes Mellitus resulting in pathophysiological changes in multiple tissues and organs which may explain their observed clinical adverse effects." This also provides further evidence for the lipocentric concept of diabetes and its clinical implications. TESTING OF THE HYPOTHESIS: Clinical studies to investigate the endocrine profiles, including measurements of TT, DHT, SHBG, FT and estradiol, together with LH and FSH, in both men and women with T2DM before and after RGZ and PGZ treatment in placebo controlled groups, are necessary to provide data to substantiate this hypothesis. Also, studies on T treatment in diabetic men would further establish if the adverse effects of glitazones could be reversed or ameliorated by androgen therapy. Basic sciences investigations on the inhibition of androgen biosynthesis by glitazones are also warranted. IMPLICATIONS OF THE HYPOTHESIS: Glitazones reduce androgen biosynthesis, increase their binding to SHBG, and attenuate androgen receptor activation, thus reducing the physiological actions of testosterone, causing relative and absolute androgen deficiency. This hypothesis explains the adverse effects of glitazones on the heart and other organs resulting from reversal of the action of androgens in directing the maturation of stem cells towards muscle, vascular endothelium, erythroid stem cells and osteoblasts, and away from adipocyte differentiation. The higher incidence of side-effects with RGZ than PGZ, may be explained by a detailed study of the mechanism by which glitazones down-regulate androgen biosynthesis and action, resulting in a state of androgen deficiency.

Some effects of emotion on the normal and abnormal heart.

Increased heart rate and catecholamine secretion are induced by certain emotions. Automobile driving in busy city traffic, racing driving, speaking before an audience, and parachute jumping are associated with sinus tachycardia 120-180 per minute, and increase in the plasma levels of adrenaline and/or noradrenaline. Electrocardiographic changes, chiefly ST depression, may occur in a small proportion of persons without ischemic symptoms and with normal resting tracings. Patients with clinical coronary disease, angina, and ischemic ST changes and arrhythmias may be induced by the emotional stimuli associated with car driving and public speaking; plasma catecholamine levels are increased in proportion to the intensity of the stimulus. beta-blockade reduces the tachycardia, and prevents in whole or in part the ST changes, arrhythmia and symptoms associated with emotional challenge to the heart. We would like to leave the reader with a final morsel of food for thought. Emotion may parallel exercise in its ability to accelerate the heart rate up to 180 per minute in healthy subjects, comparable to the maximum reached during physical exertion. Thus, there are good grounds to advise persons at risk not only against violent exercise but also against exposing themselves to intense emotion. At the same time, we would not advocate emotional overprotection, and we believe our ideas would be misinterpreted if healthy persons were to be deterred on the grounds of apprehension or nervousness from facing up to reasonable everyday professional or social challenges.

Computer analysis of routine pathology work schedules using a simulation programme.

A simulation programme is described which compares the efficiency of laboratory work schedules. The number of days' delay on a sample of request forms submitted to a routine biochemistry laboratory has been calculated for each of three schedules. Analysis of the results indicated that this method of comparing existing and potential work routines is likely to lead to a significant acceleration in the return of pathology results to the clinician.

Raised serum copper and caeruloplasmin levels in subjects taking oral contraceptives.

A marked increase in the serum copper and caeruloplasmin levels in 25 female subjects taking oral contraceptives is noted. The correlation between the copper and caeruloplasmin concentrations, together with the finding of normal urine copper levels in 10 of the subjects, suggests that the increased serum copper is due to increased caeruloplasmin synthesis.

Lipids and lipoprotein fractions after cyclopenthiazide and oxprenolol: a double-blind crossover study.

A double-blind crossover study was carried out to investigate the effects of cyclopenthiazide and oxprenolol on blood lipids in 20 previously untreated patients with mild to moderate hypertension. After a 4-week placebo period, patients received at random either 8-weeks' treatment with the two drugs followed by 8 weeks on cyclopenthiazide alone, or the reversed sequence. Daily doses were 160 mg slow-release oxprenolol and/or 0.25 mg cyclopenthiazide during the first 4 weeks of each treatment period, after which the dosage was doubled. Data from 13 patients who completed the trial showed no significant changes in the blood levels of triglycerides, total cholesterol or LDL and HDL cholesterol fractions. These findings are discussed in relation to published studies on the effects of other beta-blockers on blood lipids.

Psychosomatic aspects in idiopathic infertility: effects of treatment with autogenic training.

It has long been recognised that there is a relationship between emotional stress and some forms of infertility. We have endeavoured to estimate "stress' levels before and after Autogenic Training in 15 couples with infertility of at least two years' duration. Potential stress markers were: plasma prolactin, total urinary free cortisol and catecholamines, and four psychological tests: Spielberger State-Trait anxiety scale, Taylor Manifest Anxiety Scale, the Cattell 16 personality factor questionnaire, and the Eysenck Personality Questionnaire. A control group of ten normal couples was included for comparison. The biochemical finding of higher mean prolactin levels in the female patients vs their controls was of particular interest. The significant reduction of the prolactin level, in parallel with decreased anxiety scores following treatment, supports the hypothesis that the elevated prolactin levels in these patients are indeed linked with emotional stress.

Endocarditis due to enteric bacilli other than Salmonellae: case reports and literature review.

The clinical and pathological findings in two recent patients with non-salmonella enterobacterial endocarditis are described, and those of 42 patients in the literature are summarized. Most of the patients acquired their endocarditis secondary to urinary tract infection and had an acute clinical course characterized by high fever and chills. Thirty-two of these patients died, and all except one had a postmortem examination. The most frequent pathological finding was the occurrence of very large vegetations which caused relatively little destruction of the underlying valve. Prompt diagnosis and antibiotic therapy chosen on the basis of bactericidal as well as bacteriostatic activity against the individual bacterium may improve the prognosis in this disease. Results of tricuspid and pulmonic valvulectomies for bacteriologic failure in pseudomonas and in a few cases of enterobacterial endocarditis appear to warrant a surgical approach in patients with right-sided enterobacterial endocarditis who fail to respond to vigorous medical therapy.

Stress/catecholamine-induced cardiac necrosis. Reduction by beta 1-selective blockade.

Catecholamine-induced cardiac necrosis is a well-described phenomenon. Patients with severe head injury are known to be in a marked hyperadrenergic state and can experience cardiac morbidity; this was confirmed in a pilot study. A further study was then undertaken to examine a possible relationship between plasma catecholamine concentration and cardiac morbidity in patients with severe head injury and to assess the effect of intervention with the beta 1-selective agent atenolol. The study involved 114 hemodynamically stable patients with acute head injury who were randomized, double blind, to either placebo or atenolol given intravenously (10 mg every six hours) for three days and then orally (100 mg once a day) for four days. Both groups were equally stressed in terms of raised arterial norepinephrine levels. In patients receiving placebo, but not in those given atenolol, there was a significant (P less than 0.01) positive correlation between arterial level of norepinephrine and plasma level of cardiac-specific isoenzyme CK-MB. Thirty percent of the placebo group, in contrast to 7.4% of the atenolol group (P less than 0.05), had pathologically elevated CK-MB levels (ie, greater than 3% of total CK, a value compatible with acute myocardial infarction). Atenolol appeared to significantly reduce the likelihood of supraventricular tachycardia and ST-segment and T-wave changes and prevented cardiac necrosis (as determined post mortem). The finding that beta 1-selective blockade significantly inhibits catecholamine-induced necrosis has possible broad clinical implications.