Cytomegalovirus infection in heart transplant recipients: Preliminary results of a controlled trial of intravenous gamma globulin

Cytomegalovirus (CMV) infection is a major problem during the first twelve weeks after cardiac transplantation. Reactivation of endogenous virus, blood transfusion, and the transplanted heart are sources for CMV infection. Not only can disseminated CMV infection contribute directly to mortality, but CMV infection predisposes to superinfection with bacterial and fungal pathogens. Studies in mice, the premature neonate, and bone marrow transplant recipients suggest that passive immunization with CMV antibody has a modifying effect on CMV infection. By prophylactic administration of intravenous immune globulin in a controlled randomized fashion to cardiac transplant recipients we will address the question of whether passively acquired antibody prevents or modifies infection with CMV or other viral, bacterial, and fungal infections. Thirteen patients undergoing cardiac transplantation at Stanford University were randomized to receive or not receive intravenous immune globulin (IGIV) at a dose of 20 ml/kg twenty-four hours post transplantation and then weekly thereafter for a period of 10 weeks. Six patients seronegative for CMV antibody were randomized separately from seven who were seropositive for CMV antibody. Seven patients randomly selected from these two groups received IGIV. In patients seronegative for CMV, administration of IGIV resulted in serum titers of 1:10,000–1:30,000 measured by radioimmunoassay. Antibody titers were maintained at levels of 1:10,000 to 1:30,000 throughout the 10 week period post transplantation. Antibody remained detectable up to 8 weeks after the last infusion. No significant increases in CMV antibody levels were detectable after IGIV administration in patients seropositive for CMV antibody prior to transplantation. The administration of IGIV in thirty-two large and repeated doses was safe and well tolerated in cardiac transplant recipients. Serum levels of CMV antibody comparable to those observed in normal CMV seropositive individuals were achieved in CMV seronegative transplant recipients and were maintained throughout the period of greatest risk for CMV infection.     

The sensitivity and specificity of the Major Depression Inventory, using the Present State Examination as the index of diagnostic validity

BACKGROUND: A self-rating inventory has been developed to measure DSM-IV and ICD-10 diagnoses of major (moderate to severe) depression by the patients' self-reported symptoms. This Major Depression Inventory (MDI) can be scored both according to the DSM-IV and the ICD-10 algorithms for depressive symptomatology and according to severity scales by the simple total sum of the items. METHODS: The Schedule for Clinical Assessment in Neuropsychiatry (SCAN) was used as index of validity for the clinician's DSM-IV and ICD-10 diagnosis of major (moderate to severe) depression. The sensitivity and specificity of MDI was assessed in a sample of 43 subjects covering a spectrum of depressive symptoms. RESULTS: The sensitivity of the MDI algorithms for major depression varied between 0.86 and 0.92. The specificity varied between 0.82 and 0.86. When using the total score of MDI the optimal cut-off score was estimated 26 and the total score was shown to be a sufficient statistic. LIMITATIONS: The sample of subjects was limited. Patients with psychotic depression were not included. CONCLUSION: The MDI was found to have a sensitivity and specificity which is acceptable. The questionnaire is brief and can be scored diagnostically by the DSM-IV and ICD-10 algorithms as well as by its simple total score.     

Assessment of bioequivalence after subcutaneous and intramuscular administration of urinary gonadotrophins

The objective was to demonstrate bioequivalence between s.c. and i.m. administration of Humegon (FSH/LH ratio 1:1) and Normegon (FSH/LH ratio 3:1). In two randomized, single-centre, cross-over studies, 18 healthy volunteers on each formulation were assigned to one of the two administration sequences. Subjects were given single doses of one of the above gonadotrophins after endogenous gonadotrophin production had first been suppressed using high-dose oral contraceptive. Subsequently, rate (Cmax, tmax) and extent (AUC) of absorption of follicle stimulating hormone (FSH) and luteinizing hormone (LH) were determined for 14 days. For Cmax and AUC, analysis of variance (ANOVA) was performed on log-transformed data and for tmax ANOVA was performed on ranks. Intramuscular and s.c. injections of Humegon were bioequivalent with respect to the main pharmacokinetic parameters, being AUC and Cmax of FSH absorption. Intramuscular and s.c. injections of Normegon were bioequivalent with respect to the AUC of FSH and not bioequivalent with respect to the Cmax of FSH. For tmax of FSH as well as for most LH variables of both preparations, bioequivalence could not be proven due to the high intra- and interindividual variability and/or concentrations being close to the detection limit. Thus, the main pharmacokinetic FSH variables after i.m. and s.c. administration of Humegon and Normegon were bioequivalent.      

Effects of oxytocin in normal man during low and high sodium diets

AIM: We tested the hypothesis that oxytocin in normal man causes natriuresis by means of nitric oxide and/or atrial natriuretic peptide. METHODS: Normal male subjects were investigated after 4 days of sodium controlled diets (30 mmol sodium chloride day(-1), n = 8 or 230 mmol sodium chloride day(-1), n = 6). Oxytocin was infused intravenously (1 pmol kg(-1) min(-1) for 240 min). RESULTS: Mean arterial blood pressure, heart rate and glomerular filtration rate by clearance of chromium-labelled ethylenediaminetetraacetate remained stable. Plasma oxytocin increased from 2 to 3 pg mL(-1) to around 50 pg mL(-1). Oxytocin decreased urine flow (4.2 +/- 0.2--0.75 +/- 0.11 and 4.6 +/- 1.3-1.4 +/- 0.6 mL min(-1), low- and high-salt diet, respectively). During low-salt conditions, oxytocin reduced sodium and potassium excretion (11 +/- 2--4 +/- 2 and 93 +/- 19--42 +/- 3 micromol min(-1), respectively). Plasma renin, angiotensin II, aldosterone and renal excretion of metabolites of nitric oxide (nitrate and nitrite) all decreased. Plasma atrial natriuretic peptide and cyclic guanosine monophosphate were unchanged. A similar pattern was obtained during high-salt conditions but in this case the antinatriuresis was not different from that occurring during the corresponding time control series. CONCLUSIONS: The data reject the hypothesis. In contrast, we found significant antinatriuretic, antikaliuretic and antidiuretic effects, which were not mediated by the renin-angiotensin-aldosterone system, atrial natriuretic peptide, systemic haemodynamics, or processes increasing urinary excretion of metabolites of nitric oxide. The natriuretic effect of oxytocin found in laboratory animals is species-specific.     

Bladder tumour control by abdominal ultrasound and urine cytology

A blind study comparing abdominal ultrasound and cystoscopy was carried out in 186 patients. 20 bladder tumours sized from 2 to 5 mm were overlooked. Combination with urine cytology increased the diagnostic sensitivity. In order to reduce costs and patient inconvenience in the bladder tumour control population abdominal ultrasound and urine cytology is advocated as an alternative to cystoscopy. This control modality seems safe in patients with "low-risk" bladder tumour disease.