Lack of effect of the calcium antagonist isradipine on cyclosporine pharmacokinetics in renal transplant patients.

Hypertension has emerged as a frequent side effect in transplant recipients on effective doses of cyclosporine (CsA). To control hypertension in renal transplant patients, calcium channel blockers have been used; some of these, however, have been shown to cause significant increases in CsA levels. These findings point out that possible interactions of each calcium antagonist with CsA deserve investigation. We performed an open, placebo-controlled study in 12 stable renal transplant recipients to determine whether short-term isradipine influences CsA pharmacokinetics. All patients had mild to moderate hypertension and received triple immunosuppressive therapy with CsA, azathioprine, and prednisolone. Throughout a 4-week period of isradipine treatment, blood CsA levels (specific and nonspecific monoclonal antibodies) remained stable. The mean trough specific level was 121 +/- 14 micrograms/L following placebo, compared to 120 +/- 14 micrograms/L during isradipine. Corresponding non-specific values were 465 +/- 68 and 474 +/- 63 micrograms/L. Also, values for Cmax, AUC, and t1/2 were not significantly changed following 4 weeks of isradipine. Mean arterial pressure was significantly reduced at the end of the study. This study implies that isradipine does not influence CsA metabolism. Further studies should be carried out to determine its long-term effects on CsA pharmacokinetics and renal function in transplanted patients.     

IgM antibodies in sera from patients with chronic active hepatitis reacting with the measles virus matrix protein and nucleoprotein

The antigenic specificity of measles virus IgM antibodies in sera from patients with chronic active hepatitis not caused by hepatitis B virus has been examined. An immunosorbent column containing antihuman IgM covalently bound to Sepharose was used to pick up IgM from the sera. Radiolabelled measles virus antigens were then allowed to react with the IgM antibodies. The immune complexes were eluted and analysed by sodium dodecyl sulfate [SDS]-polyacrylamide gel electrophoresis. Four sera from patients with hepatitis B surface antigen [HBsAg]-negative chronic active hepatitis with high measles virus haemagglutination inhibition [HI] and complement fixation [CF] antibody titres and positive enzyme-linked immunosorbent assay [ELISA] for measles-virus-specific IgM were examined. The results were compared with those obtained using sera from patients with an acute measles virus infection and from healthy controls. In both patient groups, IgM antibodies with specificity against the matrix protein represented the major portion of the measles virus IgM. IgM antibodies against the measles virus nucleoprotein and probably against host-cell-derived actin were also present. The patient sera contained only traces of IgM antibodies with specificity against the measles virus haemagglutinin or fusion protein. No specific IgM antibodies were found in sera from healthy controls.     

Identification of a new locus for autosomal dominant non-syndromic hearing impairment (DFNA7) in a large Norwegian family

Hereditary hearing impairment affects about 1 in 1000 newborns. In most cases hearing loss is non-syndromic with no other clinical features, while in other families deafness is associated with specific clinical abnormalities. Analysis of large families with non-syndromic and syndromic deafness have been used to identify genes or gene locations that cause hearing impairment. The present report describes a large Norwegian family with autosomal dominant non-syndromic, progressive high tone hearing loss with linkage to 1q21-q23. A maximum LOD score of 7.65 (theta = 0.00) was obtained with the microsatellite marker D1S196. Analysis of recombinant individuals maps the deafness gene (DFNA7) to a 22 cM region between D1S104 and D1S466. The region contains several attractive candidate genes. This report supports the idea of extensive genetic heterogeneity in hereditary hearing impairment and represents the first localization of a deafness gene in a Norwegian family.      

Multiple cerebral metastases: detectability with Gd-DTPA-enhanced MR imaging

Sixteen patients with suspected cerebral metastases were studied with magnetic resonance (MR) imaging before and after the intravenous administration of 0.1 mmol/kg of gadolinium diethylenetriaminepenta-acetic acid. The images were interpreted blindly by two neuroradiologists; all clinical, radiologic (computed tomographic and MR imaging), and pathologic data were reviewed to arrive at a final "best diagnosis," which was then compared with the prior blinded interpretations. Of seven patients found to have multiple metastases, six (86%) had at least one tumor nodule depicted by postinfusion MR imaging that was missed by one or both observers on review of preinfusion images alone. Lesions missed on preinfusion studies were usually small nodules hidden by or not detected next to regions of high-signal edema thought to be related to the adjacent tumor nodule. The authors believe that contrast enhancement improves detection of metastatic foci with MR imaging and that the findings indicate broader implications for the detection of multiple lesions from other causes.     

CLINICO-EPIDEMIOLOGICAL ALGORITHM FOR PREDICTING SYSTEMIC ARTERIAL HYPERTENSION AT HIGH ALTITUDE THROUGH MATHEMATICAL MODELLING

A population based hybrid design combining element of cohort and cross-sectional approach was used to develop a simple clinical algorithm to predict individual probability of developing hypertension (systolic BP > 140 mm Hg and/or diastolic BP > 90 mmHg). 3615 soldiers initially normotensive at the time of induction into high altitude, were studied by systematic random sampling. Multiple logistic regression analysis showed a high significant association between hypertension and age, body mass index (BMI), tobacco smoking and alcohol consumption. Using the constant/coefficient values obtained from the logistic model and the receiver operating characteristics (ROC) curve analysis, the following predictive rule was developed – To the age in years, add (BMIx 3.86); also add 5.53 if he is a smoker; and add 19.81 if he consumes alcohol. If the total exceeds 142, the individual is at high risk of developing hypertension. This algorithm carries a sensitivity of 68.2% and specificity of 78.5%.KEY WORDS: Hypertension, High altitude     

Sera from preeclamptic women increase the content of triglycerides and reduce the release of prostacyclin in cultured endothelial cells

The causes of the "endothelial dysfunction" accompanying preeclampsia are unknown. Women with preeclampsia have a marked hyperlipidemia which reflects altered lipid metabolism. We asked if the hyperlipidemic sera of preeclamptic women could cause altered endothelial cell properties. Cultured endothelial cells were incubated with sera from women with preeclampsia (PE) or normal pregnancies as controls. Fifty PE-sera were tested and in 45 cases the endothelial cells acquired a large number of sudanophilic granules which by electron microscopy had lipid appearance. In 31 incubations with 31 individual control sera cellular lipid granules were observed in 4 cases. The cellular triglyceride content was increased to 153 +/- 30 compared to 48 +/- 10 micrograms/mg cell protein in the control cells. Furthermore, the endothelial release of prostacyclin, measured as 6-keto PGF1 alpha, was 8.8 +/- 0.6 ng/mg cell protein in cells incubated with PE-sera as compared to 40.3 +/- 6.4 ng/mg in the control cells. Conclusion: The hyperlipidemic sera from preeclamptic women induced triglyceride accumulation in cultured endothelial cells. This was accompanied by altered endothelial function as demonstrated by reduced prostacyclin release.