Moment analysis of drug disposition in kidney. II: Urine pH-dependent tubular secretion of tetraethylammonium in the isolated perfused rat kidney

Effects of urine pH on the renal tubular secretion of an organic cation (tetraethylammonium, TEA) and an organic anion (p-aminohippurate, PAH) were investigated using the isolated erythrocyte-perfused rat kidney. The method was based on a multiple indicator dilution experiment and noncompartmental moment analysis. Treatment with sodium bicarbonate and sodium dihydrogen phosphate increased and decreased urine pH, respectively, but affected neither the condition of the perfused kidney nor the renal handling of albumin and inulin. In TEA studies, the increase of urine pH prolonged the mean residence time in renal epithelial cells (T cell) and reduced the apparent secretion intrinsic clearance, but did not influence the volume of distribution in the kidney (Vd drug). The decrease of urine pH did not affect these kinetic parameters. By contrast, PAH secretion was constant against the change of urine pH. Since any change in the basolateral membrane transport is reflected in Vd drug, the net transport from blood to cells can be regarded as similar under these treatments. On the other hand, the prolonged T cell of TEA with the increased urine pH suggested a slow transport from cells to lumen across the brush-border membranes. The present results coincide with the hypothetical mechanism that organic cations are secreted via an active transport system, coupled to the countertransport of H+ into cells. In conclusion, the present method is useful to separately evaluate the transmembrane transport across both sides of the renal epithelial cells in a morphologically intact kidney.     

Enhanced clearance of lactic dehydrogenase-5 in severe combined immunodeficiency (SCID) mice: effect of lactic dehydrogenase virus on enzyme clearance.

The lactic dehydrogenase (LDH) level in plasma and the clearance of LDH in C.B-17 scid (severe combined immunodeficiency; SCID) mice were compared with those in C.B-17 or BALB/cCrSlc mice with or without lactic dehydrogenase virus (LDV) infection. The resting enzyme level in SCID mice showed little difference from that in C.B-17 or BALB/cCrSlc mice. The degree of increased plasma LDH level in SCID mice was lower than that in C.B-17 and BALB/cCrSlc mice after LDV infection. To assess the mechanisms of decrease in LDH elevation in SCID mice infected with LDV, virus replication was compared in SCID and BALB/cCrSlc mice. The infectivity titre of plasma in SCID mice was higher (more than 10 times) than that in BALB/cCrSlc mice. Moreover, the percentage of virus antigen positive Kupffer cells was higher in SCID mice than that in BALB/cCrSlc mice. The level of endogenous LDH release as a result of carbon tetrachloride treatment was similar in the SCID and BALB/cCrSlc mice. The clearance rate of endogenous LDH was greater in SCID mice than in BALB/cCrSlc mice with or without LDV infection. The rate of clearance of intravenously injected porcine LDH-5, but not porcine LDH-1, was enhanced in SCID mice as compared with that in BALB/cCrSlc mice. Furthermore, carbon clearance was higher in SCID mice than that in BALB/cCrSlc mice. These results suggest that the smaller increase of plasma LDH after infection might be due, at least in part, to the enhanced LDH-5 clearance function by macrophages in SCID mice.     

Postoperative infection with methicillin-resistant Staphylococcus aureus and its control measures in patients with esophageal cancer--prediction of high risk patients]

Whether or not compromised host defense prior to surgical treatment is related to development of infection with methicillin-resistant staphylococcus aureus (MRSA) following major surgery was examined. Of 22 patients undergoing esophagectomy for cancer between 1989 and 1990, 5 were free from MRSA colonization and infection (group I) while 8 had MRSA colonization without infection (group II) and 9 had MRSA infection (group III). Levels of neutrophil cytocidal functions, complements, immunoglobulins and cell-mediated immunity were not significantly different among these three groups. The mean of anti pneumococcal polysaccharide (PPS)-IgG was significantly lower in group III than in group I (p < 0.05) and tended to be lower than in group II (P = 0.08). All infected patients showed a titer < 600 EU while all but one non-infected patient did so > 600 EU. Serum IgG2 levels positively correlated with anti-PSS IgG levels. Thus, we concluded that a preoperative evaluation of antibody response against polysaccharides and serum IgG2 levels can serve to predict development of MRSA-related infection following esophageal surgery.     

A case of subacute idiopathic pure pan-dysautonomia--recovery with prednisolone therapy

A 52-year-old man had, after an episode of fever in June 1989, developed orthostatic dizziness followed by sexual impotence, dysuria, decreased sweating and weight-loss, which progressed gradually and reached their maximum seven months after the onset. He was given 400 mg of droxydopa and 8 mg of midodrine HCL per day without apparent benefits, and was admitted to our hospital. His blood pressure (mmHg) and heart rate were 167/102 and 68 in supine position, and 74/41 and 62 in sitting position. Skin was dry. Pupillary reactions were sluggish. Left pupil was slightly irregular. Other cranial nerves, sensory and somatic motor functions were normal. Laboratory tests revealed as follows: slight anemia, ESR 42 mm/hour, serum IgG 2236 mg/dl, CSF protein 64 mg/dl and positive tests for non-specific autoantibodies. Nerve conduction studies and electromyogram were normal. Autonomic function tests showed postganglionic impairments of sympathetic and parasympathetic systems. The sural nerve biopsy disclosed normal myelinated fibers, but decreased unmyelinated fiber density to 60% of the control value. No demyelinating lesions, cell infiltration or amyloid deposits were seen. Under the diagnosis of idiopathic pure pan-dysautonomia, prednisolone, initially 60 mg daily, was added. Within 10 days, he showed marked improvement of general conditions. No exacerbation was seen during reduction or after withdrawal of prednisolone. Repeated tests showed normalizing laboratory data and regression of autonomic deficits. A year after onset he regained normal social life.(ABSTRACT TRUNCATED AT 250 WORDS)     

Tumor vascularity under angiotensin II-induced hypertension--angiographic observations

The selective increase in tumor blood flow under angiotensin II-induced hypertension was observed to be the result of passive vascular beds irresponsive to angiotensin II. We investigated whether or not increased tumor blood flow resulting from angiotensin II-induced hypertension could be recognized on angiographic findings. Angiography under angiotensin II-induced hypertension was performed in 51 patients with various cancers, and angiographic findings indicating increased tumor vascularity were recognized in 40 (78.4%) of them. Based on the assumption that the increase in tumor oxygen tension was brought about by increased tumor blood flow, the possibility of utilizing this phenomenon in hyperbaric oxygenation radiotherapy was suggested.     

Statistical analysis of the prostatic cancer patients detected from 1985 to 1989 in and around Gunma prefecture]

Prostatic cancer is one of the most common malignant tumors in the field of urology. The number of patients is increasing rapidly and its importance as a mortal disease is gathering attention. In 1985, we organized a registration system for prostatic cancer patients found in and around Gunma prefecture. In this study, we analyzed the clinical characteristics of the 730 patients registered from 1985 to 1989. The results were as follows. Mean age was 74.0 years old and the number of the patients was the greatest in the eighth decade. Voiding disturbance was the most common chief complaint, followed by pollakisuria, gross hematuria and miction pain. Stage and grade distribution were as follows. Stage A 16.2%, B 21.1%, C 17.0%, D 45.7%, well differentiated 27.4%, moderately differentiated 48.2% and poorly differentiated 24.5%, respectively. A statistically significant relationship between stage and grade was observed. Bone was the most common metastatic site. The highest incidence of bone metastasis was in lumbar vertebra, followed by ribs, ilium, thoracic vertebra and ischium. The value of PAP, ALP and ESR tended to be higher in high stage patients, and that of Hb was lower. Fifty two patients were detected by mass screening. Most of these patients were in an early stage. Most of the patients were treated by hormonal therapy. LH-RH agonists constituted 39.2% of the cases given hormonal therapy.     

Correlations between bone mineral density and demographic, lifestyle, and biochemical variables in community-dwelling Japanese women 69 years of age and over

Introduction A few epidemiologic studies have comprehensively attempted to identify risk factors for low bone mineral density (BMD) in elderly Asian women. The purpose of this study was to identify demographic, lifestyle, and biochemical factors correlated with BMD in elderly Japanese women 69 years of age and over.Methods The study design was cross-sectional. The subjects were 583 ambulatory women aged 69 years and over, and their average age was 74.3 (SD 4.4) years. Predictor variables were age, reproductive history, anthropometric indices, grip strength, calcium intake, lifestyle information, and serum 25-hydroxyvitamin D, 1,25-dihydroxyvitamin D (1,25(OH)₂D), osteocalcin (OC), and undercarboxylated osteocalcin (ucOC) values. The outcome variable was forearm BMD measured with a DTX-200 osteometer.Results Simple linear regression analyses showed that BMD was significantly positively associated with body height, weight, body mass index, grip strength, serum albumin concentration, and “housework,” and negatively associated with age, years since menopause, age at menarche, number of children, serum 1,25(OH)₂D concentration, serum OC concentration, and ucOC concentration. The stepwise multiple regression analysis showed that weight (β=0.00316, SE=0.00028, R²=0.180), age (β=−0.00321, SE=0.00050, R²=0.108), log-transformed serum OC (β=−0.0445, SE=0.0064, R²=0.053), log-transformed serum 1,25(OH)₂D (β=−0.0401, SE=0.0074, R²=0.050), “farmwork” (β=0.00904, SE=0.00426, R²=0.005), and serum 25(OH)D concentration (β=0.000281, SE=0.000120, R²=0.003) were significantly associated with BMD.Conclusion It was concluded that body weight is a major predictor of forearm BMD among the factors measured in this study in independent Japanese women 69 years of age and over and that serum 1,25(OH)₂D concentration may be associated with cortical BMD. Maintenance of body weight is very important for maintaining BMD in this population, unless a large weight aggravates obesity-related diseases. A follow-up study is needed to confirm these findings.     

Impact of lymph node metastasis on survival in patients with pathological T1 carcinoma of the ampulla of vater

To determine the prognostic factors for patients with pathological T1 (pT1) carcinoma of the ampulla of Vater, 36 consecutive patients with carcinoma of the ampulla of Vater who underwent surgery were retrospectively analyzed in terms of clinicopathological features. The overall 5-year Kaplan-Meier survival in all patients was 50.2%, and the median survival of all patients was 64.0 months. Factors favorably influencing a long-term outcome were the absence of lymph node metastasis (P<0.0001), the absence of ulcer formation of the tumor (P=0.0062), and the absence of tumor invasion into the duodenum (P = 0.0025) and the pancreas (P=0.0098). In a multivariate analysis, lymph node metastasis was the only predictor of survival (P=0.0023). In the pT1 stage patients, 20% of the patients had lymph node metastasis, and their survival was statistically poor compared to the pT1 patients without lymph node metastasis (P=0.017). As for survival after the operation, there was no significant difference between pancreatoduodenectomy and pylorus-preserving pancreatoduodenectomy.