Chronic hypertension induced by streptozotocin in rats

Summary An intravenous injection of 40 or 65 mg/kg streptozotocin induced not only diabetes but also severe hypertension in rats. Whereas the hyperglycemia developed fully within a few days after the injection of streptozotocin, the hypertension progressively advanced and reached maximum level several weeks after the treatment and lasted more than 20 weeks. Twenty mg/kg streptozotocin did not induce hyperglycemia but significantly increased blood pressure several weeks after the treatment. Arrest of growth, polyuria, glycosuria, hyperlipemia and lenticular cataracts developed in the animals treated with 40 or 65 mg/kg streptozotocin, but in none of the animals treated with 20 mg/kg. In histological examinations in the 24th week after the treatment, degranulation and necrosis in the pancreatic -cells, and vacuolization and deposition of PAS-positive materials in the renal proximal tubules were found in the animals treated with 40 or 65 mg/kg streptozotocin.     

Gender difference of clinical features in Japanese patients with alcoholic liver cirrhosis]

Gender difference of alcohol intake and laboratory data was investigated in 165 Japanese patients with alcoholic liver cirrhosis. Mean age of first drinking and habitual drinking were higher in female. Duration of drinking was shorter in female. Although cumulative alcohol intake was larger in male, mean daily alcohol intake did not differ in both gender. Moreover, daily alcohol intake adjusted to body weight was significantly larger in female. Body mass index, serum levels of total protein, albumin and cholinesterase were significantly decreased in female. Platelet counts on admission did not differ in both gender. However, it was significantly increased in female after one month abstinence. C reactive protein, ammonia and serum levels of total bilirubin were significantly higher in female as compared to male. In conclusion, female alcoholics seems to progress to liver cirrhosis earlier because of high daily alcohol intake adjusted to body weight, poor nutritional condition and inflammation caused by endotoxin.     

Effect of CYP2D6 genotypes on the metabolism of haloperidol in a Japanese psychiatric population.

We investigated the effect of CYP2D6 genotypes on plasma levels of haloperidol (HAL) and reduced haloperidol (RHAL) in 88 Japanese schizophrenic inpatients being treated with HAL. Some subjects carrying CYP2D6*5 allele (CYP2D6*1/CYP2D6*5, CYP2D6*5/CYP2D6*10) showed extremely high concentrations of both HAL and RHAL, and the groups with CYP2D6*5 allele seemed to have higher plasma concentrations of HAL (1.14+/-0.69 ng/ml/mg) and RHAL (1.10+/-1.05 ng/ml/mg) than the other groups. Among those without CYP2D6*5 allele, there were no significant differences in plasma concentrations of HAL and RHAL between those without CYP2D6*10 allele (HAL=0.68+/-0.31 ng/ml/mg, RHAL=0.28+/-0.37 ng/ml/mg), those with one CYP2D6*10 (HAL=0.70+/-0.23 ng/ml/mg, RHAL=0.31+/-0.16 ng/ml/mg) and those with two CYP2D6*10 alleles (HAL=0.69+/-0.14 ng/ml/mg, RHAL=0.40+/-0.09 ng/ml/mg), although there was a tendency of higher plasma concentration of RHAL in those with two CYP2D6*10 alleles. At a lower daily dosage of HAL (<10 mg/day), the subjects with two or one CYP2D6*10 allele(s) showed significantly higher plasma concentrations of RHAL (0.43+/-0.23 ng/ml/mg, 0.34+/-0.16 ng/ml/mg) than those without CYP2D6*10 allele (0.18+/-0.16 ng/ml/mg). The results of this study indicate that CYP2D6*10 allele plays significant but modest role in HAL metabolism in Japanese; nevertheless, we should not lump CYP2D6*10 allele with CYP2D6*5 allele because these two mutated alleles seem to have different impacts in the metabolism of HAL.     

Treatment by corticosteroid and plasma exchange in 5 cases of renal cholesterol embolic disease

Cholesterol arterial embolization is a systemic disease resulting from cholesterol crystal embolization to multiple organs, including the kidney, skin, brain, eye, gastrointestinal tract and extremities. In general, it is associated with high morbidity and mortality, but no optimal treatment has yet been developed. In this paper, we report five patients with cholesterol atheroembolic renal failure. In three of the five patients, combined therapy with corticosteroids and plasma exchange was performed. The three patients survived. On the other hand, the two remaining patients died of multifactorial causes. In this report, the literature on steroid therapy for cholesterol atheroembolic renal disease is reviewed and the efficacy of combined therapy by use of corticosteroids and plasma exchange is evaluated.     

Two cases of methicillin-resistant Staphylococcus aureus (MRSA) sepsis following craniotomy

We report here two cases of MRSA sepsis following craniotomy. In case 1, a petroclival meningioma was subtotally removed and lumbar drainage was inserted postoperatively to prevent cerebrospinal fluid leakage. Ventriculo-peritoneal shunt was performed after meningitis was treated with vancomycin and panipenem/betamipron. Two weeks after the procedure, the patient revealed continuous spiking fevers related to MRSA sepsis, which did not improve with vancomycin and arbekacin administration. The focus of infection was found by scintigraphy and CT by 67Ga to be spondylo-diskitis at the level of L2-L3. The lesion was removed and bone from the iliac crest grafted. In case 2, seven days after surgery for multiple meningioma, the patient exhibited spiking fevers and swelling in the left leg. The central venous catheter was removed from the left femoral vein and MRSA was found from blood culture. The patient was treated with arbekacin (200 mg/day). Venous thrombosis diagnosed by CT was treated with heparin. Symptoms related to the infection and laboratory data did not improve because the concentration of arbekacin in the blood did not reach an effective level. The symptoms markedly improved when the dose of arbekacin was doubled (400 mg/day).     

PSA doubling time in prostate cancer relapsed after endocrine therapy

PURPOSE: The PSA level of prostate cancer patients generally declines after endocrine therapy, but elevates when the cancer relapses in most cases. However, the rate of elevation differs with the case. We investigated the PSA doubling time (PSA-DT) of the prostate cancer patients whose PSA declined after endocrine therapy and later re-elevated, and investigated the relationship with other parameters. PATIENTS AND METHODS: We investigated 55 prostate cancer patients who underwent endocrine therapy between 1991 and 1998. Their PSA re-elevated continuously after their PSA fell below 10 ng/ml after the endocrine therapy as the first line treatment. First, the correlation coefficients with time and PSA were calculated in order to decide whether their PSA elevation was exponential or linear. PSA-DT was calculated thereafter, and compared with the clinical stage, pathological differentiation, clinical relapse style, time from the beginning of the therapy to PSA relapse, pre-treatment PSA value, and prognosis. The relationship between PSA-DT and each clinical parameter was tested using the Kruskal-Wallis test. Differences in survival rates and PSA-DT were calculated using the log-rank test. RESULTS: PSA elevated exponentially after cancer relapsed. PSA-DT in all cases ranged from 0.5 to 26.3 months, with an average of 4.4 +/- 4.8 (S.D.) months and the median was 2.5 months. PSA-DT was significantly (p < 0.01) short when the pre-treatment clinical stage was high, the time from the beginning of the therapy to PSA relapse was short, or the pre-treatment PSA value was high. PSA-DT tended to be short when the pre-treatment pathological differentiation was low, but not significantly. PSA-DT tended to be short when the cancer relapsed as distant metastasis rather than regional relapse, but not significantly. Prognosis from the initial treatment and PSA relapse was significantly poor when the PSA-DT was short. CONCLUSIONS: PSA elevated exponentially in the relapsed prostate cancer patients after the endocrine therapy. PSA-DT was distributed in a very wide range, and this value was considered to reflect the malignant potential and prognosis of the cancer. PSA-DT may be useful for determining the strategy after relapse.