Cyclosporine therapy affects aminotransferase activity but not hepatitis C virus RNA levels in chronic hepatitis C

Interferon (IFN) therapy is of proven efficacy in chronic hepatitis C, but it is not universally effective and is often limited by side effects. Cyclosporine A (CsA) is a potent immunosuppressant widely used in organ transplantation. We conducted a pilot study to determine whether CsA therapy could affect aminotransferase activity and hepatitis C virus RNA levels in patients with chronic hepatitis C. Cyclosporine A was administered to 10 patients (mean age of 59 years; male: female = 9:1) who did not respond to IFN therapy previously and who had elevated serum alanine aminotransferase (ALT) values for at least 6 months. All patients were positive for HCV-RNA by RT-PCR with genotype 1b. Their mean duration of hepatitis was 15 years. Oral CsA was given for 3 months in a dose that was increased at 1 month intervals from 1.5–2.0 to 2.0–3.0 and 3.0–4.0 mg/kg per day. All patients completed the treatment schedule, although two patients developed mild non-symptomatic hypertension. Serum ALT levels gradually decreased in all but one patient. The mean percentage decrease was 59.5% at the end of therapy (from 153 ± 82 to 62 ± 48 IU/L; P < 0.02). The ALT levels fell to the normal range in five patients, although once therapy was discontinued the enzyme levels tended to return to pretreatment levels. Serum aspartate aminotransferase and g-glutamyl transpeptidase levels similarly decreased. The serum HCV-RNA titre, determined by competitive RT-PCR, did not change in any patient throughout the study period. There were no appreciable alterations in other laboratory tests, such as serum creatinine levels and lymphocyte subsets, except for an increase in serum alkaline phosphatase levels. These findings suggest that CsA, even in a relatively low dose, reduces serum aminotransferase levels without serious side effects in patients with chronic-hepatitis C, although an antiviral effect was not noted.     

Acute disseminated encephalomyelitis associated with Mycoplasma pneumoniae infection

An 8 year old girl with acute disseminated encephalomyelitis (ADEM) is described. Elevated serum antibody titers suggested recent Mycoplasma pneumoniae infection. T2-weighted image of magnetic resonance imaging (MRI) disclosed multiple lesions of high signal intensity in bilateral basal ganglia and thalami as well as in the white matter. Postcontrast T1-weighted image revealed an enhanced lesion in the deep white matter. She showed rapid clinical improvement in response to corticosteroid therapy. The lesions had disappeared completely on MRI performed 10 weeks after the onset. ADEM is believed to be a demyelinating disorder of probable autoimmune etiology. MRI findings in this case may support the hypothesis that the primary pathological event is vascular injury and demyelination occurs only as a secondary phenomenon.     

The effect of emphysema on lung function and survival in patients with idiopathic pulmonary fibrosis

Background and objective: In this study the prevalence, lung function and prognosis of IPF combined with emphysema were evaluated. Methods: Consecutive patients with usual interstitial pneumonia (UIP) on high‐resolution computed tomography (HRCT), with or without emphysema, were assessed retrospectively. The area of fibrosis in the base of the lungs was assessed by HRCT as minimal (<2 cm from the subpleura), moderate (≥2 cm from the subpleura, <1/3 of the area of the base of the lungs) or severe (≥1/3 of the area of the base of the lungs). Results: Among 660 patients with UIP on HRCT, 221 showed upper‐lobe emphysema. Pulmonary function results for patients with UIP and UIP/emphysema, respectively, were: FVC, 71.8% and 87.1%; FEV1%, 86.7% and 87.9%; and DL_CO, 74.3% and 65.2% of predicted. The relationship between FVC, the extent of fibrosis and survival was investigated in 362 patients with records of pulmonary function tests and no lung cancer at the time of entry into the study. Although the extent of fibrosis was similar between the groups, 71.3% of UIP patients met the lung volume criteria for IPF (FVC <80% of predicted), whereas only 26.5% of UIP/emphysema patients met the lung volume criteria for IPF. Median survival was 7.5 years in the UIP group and 8.5 years in the UIP/emphysema group. Conclusions: Emphysema was a common finding in patients with UIP. Patients with UIP and emphysema had greater lung volumes and better survival compared with those with UIP alone.     

Early detection of cutaneous microcirculatory change during hemorrhage using a laser Doppler flowmetry

The purpose of the present study was to evaluate the usefulness of cutaneous microcirculatory monitoring during hemorrhage. We observed changes in cutaneous blood volume, velocity and flow of five adult rabbits during hemorrhage by using a laser Doppler flowmetry. Mean arterial blood pressure, heart rate and blood gas values were measured. Cutaneous blood volume, velocity and flow decreased significantly after drawing 10 mL/kg of blood, while heart rate, mean arterial blood pressure and blood gas did not change. The decrease of cutaneous blood velocity preceded that of blood volume and was associated more deeply with the reduction of blood flow. In conclusion, cutaneous microcirculatory monitoring using laser Doppler flowmetry is a sensitive technique for detecting early changes of circulatory failure caused by hemorrhage.     

Sex-related Differences in Rat Liver Microsomal Enzymes and Their Induction by Doxapram

Abstract— The effects of doxapram on the hepatic microsomal mono-oxygenase system of male and female rats were investigated. Male and female rats were administered doxapram (10–120 mg kg^?1 day^?1, i.p.) for 4 days. In female rats, administration of doxapram (20, 40, 60, 80, 100 and 120 mg kg^?1) elevated the parameters in a dose-dependent manner while doxapram (100 and 120 mg kg^?1) elevated the levels of cytochrome P450 and hexobarbitone hydroxylase in male rats. Doxapram (40 mg kg^?1) caused induction of hepatic drug metabolism typified by an increase of hepatic microsomal cytochrome P450 content and activities of hexobarbitone hydroxylase, benzphetamine N-demethylase and ethylmorphine N-demethylase in female rats, but no change in male rats. These findings were supported by the results of SDS/polyacrylamide-gel electrophoresis. However, 7-ethoxycoumarin O-de-ethylase and arylhydrocarbon hydroxylase activities were significantly increased in male rats. NADPH-cytochrome c reductase and NADH-cytochrome c reductase activities, and cytochrome b₅ content were unaffected in rats of both sexes. The sex-dependent cytochrome P450 species may be selectively sensitive to the action of doxapram.     

Neurological Manifestations Associated with Cold Hemagglutinin Syndrome Report of Two Cases

Two cases of cold hemagglutinin syndrome associated with neurological manifestations were reported. One was a 52-year-old woman with acute hemolytic anemia which developed following grippe. Cold hemagglutinin titer was elevated to 1:1,024. Neurological manifestations were apathy, confusion, auditory hallucination and EEG abnormality. Steroid administration cleared these neurological abnormalities and EEG was reverted to normal. The other was a 77-year-old man with chronic hemolytic anemia. Cold hemagglutinin titer was extraordinarily elevated (1:32,768, 1:524,-288). Neurological abnormalities were almost confined to the cerebellar system. Hormonal therapy was completely unrewarding and the patient was incapacitated from his daily activity. From the literature some of the reported cases of hemolytic anemia associated with neurological abnormalities, particularly in reference to cold hemagglutinin syndrome, were briefly described. The present authors consider 2 reported cases fall in the category of “Syndromes neuro-hémolytiques” by French school.     

Lower Pacemaker in High Degree Atrioventricular Block is Modulated Electrotonically by Atrial Excitations

To see if the lower pacemaker in patients with atrioventricular (AV) block was modulated electrofonically by atrial excitation, we studied R-R intervals in two groups of AV block patients using a phase response curve (PRC). Group f consisted of 20 patients with high degree AV block, including seven patients in whom complete AV block was transiently observed in the course of acute inferior myocardial infarction. Group II consisted of 19 parents with complete AV block. In every patient, PRC was obtained from the continuous electrocardiogram by plotting each R₁-R₂ interval (response) on the ordinate as a function of the R₁-P_x interval (phase, x = 1, 2 …) on the abscissa, In Group I, the R-R interval was prolonged when the P wave fell in (he initial half of (he R-R interval, and was abbreviated when the P wave fell in the later half of the cycle. In Group II, the fluctuation of the R-R interval was minimum. In ten group I patients, with the improvement of the AV block, PRC became sharper and transition from prolongation to shortening occurred at shorter R-P intervals. We conclude that, in Group I, lower pacemaker was modulated electrotonicalIy by atrial excitations through decreased electrical coupling along the AV node.