Effects of crossover application of sulindac and azelastine on enalapril-induced cough.
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Biomedical subjects
Publications and source records attributed to M Fujishima.
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The role of dopaminergic agents (DA) in the regulation of growth hormone (GH) secretion was investigated in patients with untreated acromegaly. TRH (0.5 mg iv), bromocriptine (Br) (2.5 mg orally) or L-Dopa (500 mg orally) loading tests were performed, and serum levels of TSH, GH and prolactin (PRL) were measured. Patients were defined as responders to TRH when peak TSH level after TRH test was higher than 5 microU/ml. Br or L-Dopa was considered to be effective when serum GH or PRL levels were suppressed more than 50% of the basal value. The patients were classified into large adenoma group with suprasellar extension or cisternal herniation (L group, n = 7) and intrasellar small adenoma group (S group, n = 11) which was further divided into TRH responder (Sr group, n = 4) and TRH non-responder with suppressed TSH (Ss group, n = 7). Br was effective in 7 or 100% of 7 patients in the Ss group but only in one or 25% of 4 patients in the Sr group. Br was also effective in 5 or 71% of 7 patients in the L group, although most of them were responders to TRH. Percent inhibition of serum GH levels by Br was significantly higher in the Ss group (82.3 +/- 12.3%, p less than 0.001) and in the L group (64.7 +/- 20.5%, p less than 0.05) compared with that in the Sr group (29.3 +/- 21.6%). Suppression of serum GH level by L-Dopa was also observed in the Ss group. In contrast to the difference in the response of GH, serum PRL level was equally suppressed by Br or L-Dopa in each group. Suppression of TSH by administration of exogenous T4 had no effect on the GH suppression effect of Br in the Sr group. Considering the dual effects of DA to enhance growth hormone-releasing hormone (GHRH) secretion in the hypothalamus and to suppress GH secretion in the pituitary gland, these findings suggest that the paradoxical effect of DA to suppress serum GH level is observed when the hypothalamo-pituitary axis is disturbed mechanically by large adenoma in the L group or functionally in the Ss group probably due to enhanced secretion of somatostatin which suppresses TSH secretion and impairs the effect of GHRH.
A newly developed calcium antagonist, nilvadipine, was administered to 7 hypertensive patients aged 75.6 y. Nilvadipine 4 mg b.d. decreased the average 24-h blood pressure significantly from 169/89 mmHg to 152/81 mmHg after 7 to 14 days without any change in the pulse rate. The circadian patterns of blood pressure and pulse rate were not affected by nilvadipine. Although the present study was a preliminary one done over a short period in a small number of patients, the results suggest that nilvadipine exerts an antihypertensive effect without altering the circadian pattern or the variability of blood pressure in elderly hypertensive patients.
Excitatory (glutamate, aspartate) or inhibitory amino acids (gamma-aminobutyric acid: GABA, taurine) and glutamine contents were examined in acutely induced cerebral ischemia in spontaneously hypertensive rats. At 20 min ischemia most of these amino acids remained unchanged, but glutamine significantly decreased by 14% in the CA3 hippocampal subfield. At 60 min ischemia glutamate significantly decreased by 14% in the CA3, aspartate by 17-26% in the CA3, cingulate cortex, septum and striatum. In contrast, GABA significantly increased by 48-106% in the cortices (frontal, parietal and cingulate), striatum and nucleus accumbens, but insignificantly in hippocampal subfields. Likewise, taurine increased in the parietal cortex and nucleus accumbens. Glutamine showed heterogeneous changes (increase in the nucleus accumbens and decrease in the CA3). Amino acid levels change during ischemia, but their changes are varied in each area, implying that different reaction of amino acids may explain the selective vulnerability to cerebral ischemia.
To investigate small bowel motility in gastrointestinal amyloidosis, lactulose breath hydrogen tests were performed on 16 patients with histologically proven amyloidosis and 12 age- and sex-matched controls. Fasting breath hydrogen concentration (FBHC) was not significantly different between the two groups, but there was a tendency for FBHC in symptomatic amyloidosis patients (median 31.5, range 3-78 ppm) to be higher than in asymptomatic amyloidosis patients (4, 0-34 ppm, 0.05 less than P less than 0.1) and controls (6, 1-19 ppm, 0.05 less than P less than 0.1). Orocecal transit time (OCTT) was significantly delayed in the amyloidosis group (median 150, range 40-220 min) when compared to the controls (60, 20-110 min, P less than 0.01), but OCTT was not statistically different between symptomatic and asymptomatic amyloidosis patients. These data suggest an impaired motility of the stomach and small intestine in gastrointestinal amyloidosis and the possible role of small intestinal dysfunction such as bacterial overgrowth and malabsorption in the occurrence of symptoms in this disorder.
We show here that germinal vesicle breakdown of amphibian Bufo and Xenopus oocytes can be induced if ciliate Tetrahymena extracts are injected into them. The activity of meiosis-reinitiation-inducing factor (MRIF) appeared only a M-phase of a synchronously dividing culture, indicating that this MRIF has an important function for induction of M-phase in the mitotic cell cycle. MRIF of Tetrahymena differed from MPF (M-phase-promoting factor), because its action on the induction of GVBD was inhibited by cycloheximide and it could not induce GVBD in starfish oocytes by microinjection. MPF activity was not detected in extracts of vegetatively growing Tetrahymena. Preliminary experiments showed that MRIF was a heat-labile, Ca2(+)-sensitive, and trypsin-sensitive soluble protein.
To search for a reliable marker of medium-term integrated blood glucose level in diabetics on maintenance hemodialysis (HD), plasma fructosamine and glycosylated hemoglobin (Hb) levels were determined every week and blood glucose levels were determined four times every day over 3 weeks. The mean values of fructosamine (mol/L per 40 g of albumin) and of glycosylated Hb of other the study period correlated (r = .746, P less than .001) for combined materials of diabetic and nondiabetic subjects. However, plasma fructosamine values at the end of the study period did not correlate with the overall mean blood glucose values during the preceding 8 to 21 days (r = .372, NS). In contrast, glycosylated Hb values correlated closely with the same mean blood glucose values (r = .703, P less than .001). Fructosamine values significantly decreased during a HD, irrespective of the increases in albumin and total protein. In conclusion, glycosylated Hb was a reliable marker of long-term integrated blood glucose even in diabetics on HD. However, fructosamine was not a reliable marker of medium-term integrated blood glucose in these patients.
We studied the long-term change in glycemic level in a model of non-insulin-dependent diabetes mellitus (NIDDM) induced by neonatal streptozotocin (STZ) treatment in spontaneously hypertensive rats (SHR). Two-day-old male SHR were intraperitoneally injected with 37.5 to 75.0 mg/kg of STZ or vehicle alone as control. According to nonfasting plasma glucose levels at 12 weeks of age, rats were divided into mild (less than 16.8 mmol/L) and severe (greater than or equal to 16.8 mmol/L) diabetes groups. In the mild diabetes group (n = 5), plasma glucose decreased significantly from 14.2 +/- 1.8 mmol/L (mean +/- SEM) at 20 weeks to 7.3 +/- 0.3 mmol/L at 52 weeks (P less than .05) with progressing age. At 52 weeks, overnight fasting plasma glucose levels were significantly lower and serum immunoreactive insulin (IRI) was higher than in controls, respectively (4.1 +/- 0.3 v 5.7 +/- 0.3 mmol/L, P less than 0.01; 625 +/- 50 v 409 +/- 50 pmol/L, P less than .05), and insulinoma was found in 60% of rats. Therefore, the recovery from hyperglycemia may be attributed to the development of insulinoma. In the severe diabetes group (n = 6), plasma glucose remained high until 28 weeks (27.2 +/- 1.5 mmol/L), but thereafter decreased with age, as it did in the mild diabetes group (13.7 +/- 3.5 mmol/L at 52 weeks, P less than .005). However, no insulinoma was found, and the mechanism for the recovery was unclear. The present study demonstrates that hyperglycemia spontaneously ameliorates in a neonatal STZ diabetes model of SHR, although this phenomenon may be strain-related.
Eighteen patients with 20 primary lesions of small intestinal lymphoma of the 'Western' type were examined to determine the double-contrast radiographic features of the disease with pathological correlation. The radiographic appearances on double-contrast study were divided into five groups: polypoid (3 lesions), stricturing (6), non-stricturing (3), aneurysmal (3), and intussusception (5). In the first four groups, ulceration, signs of submucosal tumour, and displacement of adjacent loops were frequent. Two early lesions confined to the submucosal layer were also seen. There was a close association between the radiographic appearance and macroscopic findings of the resected specimens, including the cross section of the tumour, but no correlation with the cell type. These results indicate that the double-contrast study accurately reflects the morphological changes of primary small intestinal lymphoma.
Chronic nephrotoxicity was investigated in rats orally administered germanium dioxide (GeO2) and carboxyethylgermanium sesquioxide (Ge-132) for 24 weeks. Increased BUN and serum phosphate as well as decreased creatinine clearance, weight loss, anemia and liver dysfunction were apparent at week 24 only in the GeO2 treated group. Vacuolar degeneration and granular depositions were observed by light microscope in the degenerated renal distal tubules in the rats of this group, with the semiquantitative scores of tubular degeneration being 95 +/- 9% in the GeO2 group, 3 +/- 1% in the Ge-132 group and 1 +/- 1% in the control group, respectively. Electron microscopy revealed electron-dense inclusions in the swollen mitochondrial matrix of the distal tubular epithelium in the GeO2 group. Although systemic toxicities were reduced after GeO2 was discontinued at week 24, renal tubulointerstitial fibrosis became prominent even at week 40 (16 weeks after discontinuation). A Ge.K alpha X-ray spectrum was clearly demonstrated in the mitochondrial matrix of the distal tubular epithelium in the GeO2 group with the help of electron probe X-ray microanalysis. On the other hand, neither toxic effects nor renal histological abnormalities were manifested in either the Ge-132 or the control group. The renal tissue content of germanium was high at weeks 24 and 40 in the GeO2 group. From these results, it is concluded that GeO2 causes characteristic nephropathy while Ge-132 does not. In addition, it appears that residual GeO2 remains for a considerably long time even after the cessation of GeO2 intake.
Aluminium hydroxide, a phosphate binder, is regarded as a strong candidate to halt the progression of chronic renal disease. In order to determine the most effective time to start treatment, aluminium hydroxide was administered either immediately (ADR-0w), or at 8 weeks (ADR-8w) or 16 weeks (ADR-16w) after repeated injection of Adriamycin (ADR) inducing glomerular sclerosis. In the aluminium hydroxide-untreated group the survival rate at the end of the experiment was 50%, while the early initiation of aluminium hydroxide (ADR-0w) resulted in a greater survival rate of 90%. Serum phosphate concentration and serum calcium-phosphate product were significantly less in the aluminium hydroxide groups (ADR-0w, 8w, 16w) than in the untreated group after week 20. Urinary protein excretion was significantly less in the ADR-0w and ADR-8w groups at week 12 or 16 compared to the aluminium hydroxide-untreated group. Blood urea nitrogen in the aluminium hydroxide groups was significantly less than that in the untreated group at week 34. Histological examination revealed that glomerular sclerosis was less severe in the ADR-0w and ADR-8w groups than in the aluminium hydroxide-untreated group, and glomerular hypertrophy was significantly decreased in the ADR-0w group. We conclude that early treatment with aluminium hydroxide was effective in preventing renal deterioration in focal glomerular sclerosis induced by Adriamycin.
The haemodynamic effects of recombinant human erythropoietin (rHuEpo) on anaemic haemodialysis patients suffering from chronic hypotension were examined. rHuEpo increased the haematocrit to around 30% and increased diastolic blood pressure by 12.4%, statistically significant. Correspondingly, the total peripheral resistance index increased 42.3% while the cardiac index decreased 24.4% (P less than 0.05) respectively. Blood volume, plasma renin activity and plasma noradrenaline did not change significantly. The extent of blood pressure elevation and haemodynamic alteration did not differ from our previous report on anaemic haemodialysis patients without hypotension. The incidence of hypotensive episodes and fluid supplementation did not change significantly after rHuEpo treatment. In conclusion, by using rHuEpo, approximately a 10% increase of blood pressure can be expected. However no substantial improvement in hypotensive episodes can be expected in chronic haemodialysis patients suffering from hypotension.
We describe three cases of adult T-cell leukemia/lymphoma (ATL) with malignant cell infiltration into the stomach. Case 1, a 63-year-old man, had a large ulcerative lesion on the lesser curvature of the upper stomach. Case 2, a 44-year-old man, had an irregular depressed lesion simulating a IIc-type early gastric cancer on the posterior wall of the mid portion of the stomach. Case 3, a 58-year-old man, had multiple irregular depressed lesions on the lesser curvature of the lower part of the stomach. In all cases, histologic examinations of the biopsy specimens confirmed ATL-cell infiltration into the stomach. In cases 1 and 2, repeated roentgenographic and endoscopic examinations revealed the characteristic changes of the gastric lesions over the course of time.