[A case of liver cirrhosis and diabetes mellitus with prolonged hepatic encephalopathy and uncontrollable hyperglycemia].
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Biomedical subjects
Publications and source records attributed to M Fujishima.
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We herein report a case of a 46-yr-old female with Ménétrièr's disease associated with Helicobacter pylori (H. pylori) infection, in whom the appearance of enlarged gastric folds and hypoproteinemia were both successfully treated by antibacterial treatment. The patient had been treated with famotidine for 3 yr under a diagnosis of Ménétrièr's disease, which caused an increase in her serum protein concentration to a level at which she suffered no clinical problems; however, the concentration never reached a normal range, and the presence of enlarged gastric folds also remained unchanged. Because H. pylori colonization was detected in the stomach and was also retrospectively recognized in the initial histologic specimens, antibacterial treatment with omeprazole, clarithromycin, and metronidazole was thus attempted. As a result of the successful eradication of H. pylori, the enlarged gastric folds returned to normal and the serum protein concentration thus increased to a normal level after the treatment. The etiology of Ménétrièr's disease remains unknown; however, the above findings suggest that H. pylori infection may in some cases cause Ménétrièr's disease and should therefore be carefully treated in any patient with this condition.
BACKGROUND: Oral sulindac is known to reduce polyps in patients with familial adenomatous polyposis (FAP). The authors speculated that rectal administration of indomethacin would be effective therapy for adenomas in the rectal remnant of FAP. METHODS: Eight patients with FAP who had been treated by total colectomy with ileorectal anastomosis were administered an indomethacin suppository (50 mg) once or twice daily during a period of 4 or 8 weeks. The number of polyps at the same site within the rectum was counted under proctoscopy prior to, at the end of, and after the treatment. In four patients, proliferative activity of the rectal mucosa was assessed by immunohistochemical staining for MIB-1. RESULTS: In six of the eight patients who initially had ten or more polyps, the number of polyps decreased to fewer than five, whereas such a decrease could not be observed in the remaining two patients. In the six patients, the number of polyps increased after indomethacin was discontinued. The proliferative activity of the rectal mucosa was higher at the end of treatment than it was prior to indomethacin administration. CONCLUSIONS: Indomethacin suppositories may be effective in the management of rectal adenomatosis in patients with FAP.
We measured the cerebral blood flow at rest and during hemorrhagic hypotension in 7 rats of each group using laser-Doppler flowmetry. Simultaneously, the absolute baseline cerebral blood flow values in the parietal cortex were quantified with the hydrogen clearance method. Baseline mean arterial pressure was significantly lowered, by 29 mm Hg, in the amlodipine-treated group, while the baseline cerebral blood flow was 36 +/- 4 ml/100 g/min (mean +/- S.D.) which was almost the same as the 40 +/- 5 in the control group. The lower limits of the cerebral blood flow autoregulation, defined as the mean arterial pressure at which the cerebral blood flow decreased by 10% of the baseline value, were shifted to a lower level of 107 +/- 9 mm Hg in the treated group compared with 133 +/- 5 mm Hg in the control (P < 0.001). The results demonstrated that, in hypertensive rats with amlodipine treatment, cerebral perfusion was preserved at a lower blood pressure level, which is advantageous under hypotensive conditions.
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The relationship between diabetic nephropathy and an insertion (I)/deletion (D) polymorphism in intron 16 of the angiotensin-converting enzyme (ACE) gene is still under debate. The association of ACE gene polymorphism with nephropathy and retinopathy was therefore examined in 362 Japanese patients with non-insulin-dependent diabetes mellitus (NIDDM) and 105 healthy control subjects. Distribution of the ACE genotype did not differ between healthy control subjects and diabetic patients without complications. However, the frequency of the D allele was significantly higher in the diabetic subjects with nephropathy than in those without (0.32 in normoalbuminuric patients vs 0.44 in albuminuria patients with albuminuria) (chi 2 = 7.7; p = 0.006). There was no significant association between ACE genotype and retinopathy. These observations thus demonstrate a significant association of the ACE gene polymorphism with nephropathy, but not with retinopathy, in Japanese patients with NIDDM.
Brain ischemia is often accompanied by acute gastric lesions. To clarify the underlying mechanism, the influence of acute ischemic insult to the brain on gastric hemodynamics and mucosal integrity was examined in spontaneously hypertensive rats. One hour after brain ischemia, gastric mucosal blood flow decreased to 71% of the preischemic levels in the control rats but was preserved significantly better, at 94 and 108%, in the prazosin-treated and guanethidine-treated rats, respectively. Vagotomy almost abolished the decrease in gastric mucosal blood flow during cerebral ischemia. Intragastric 0.6 N hydrochloric acid administered just after reperfusion induced more severe hemorrhagic ulcers in the control than in the prazosin-treated and vagotomized groups. These results suggest that noradrenergic neurons acting through alpha1-adrenoceptors contributes to the decrease in gastric mucosal blood flow, and the subsequent disturbed integrity of the gastric mucosa, through the vagal adrenergic pathway during brain ischemia in spontaneously hypertensive rats.
Both arteriosclerosis and leukoaraiosis have a close relationship with hypertension, but the relationship between cerebral hemodynamics and leukoaraiosis in hypertensive patients has not been fully examined. To clarify this issue, we measured the regional cerebral blood flow (rCBF) and cerebrovascular response to hypercapnia in hypertensive patients with various degrees of leukoaraiosis. The subjects consisted of 7 normotensive normal controls and 17 hypertensive patients. The hypertensive patients were divided into three groups according to the severity of white matter lesions (leukoaraiosis) on MRI and the presence of dementia, namely, (1) negative or mild leukoaraiosis without dementia, (2) moderate to severe leukoaraiosis without dementia and (3) severe leukoaraiosis with dementia. Both the rCBF and the cerebrovascular response to hypercapnia were measured by the O-15 H2O bolus-injection method and positron emission tomography. The rCBF in hypertensive patients without dementia did not decrease when compared with the normotensive controls, but the rCBF in hypertensive patients with dementia markedly decreased in the cerebral cortices and white matter. On the other hand, the cerebrovascular response to hypercapnia declined with the severity of leukoaraiosis, and it decreased most severely in patients with severe leukoaraiosis and dementia. Our results indicate that the reduction in the cerebral hemodynamic reserve capacity has a close relationship with the severity of leukoaraiosis in hypertensive patients, although the rCBF is maintained in hypertensive patients without dementia, and suggest that arteriosclerotic change reduces cerebrovascular CO2 response and causes a leukoaraiosis in hypertensive patients.
This is the first multi-hospital epidemiological study to elucidate the prevalence and characteristics of urinary incontinence in elderly inpatients throughout Japan. Of the 2586 subjects to whom questionnaires were issued, 1563 (60.4%) (65 to 102 years old, 598 men, 965 women) were suitable for the study. A total of 817 patients were hospitalized in geriatric hospitals; that is, geriatric facilities under the regulation of the Department of Health and Welfare. All patients were evaluated by medical doctors for the following items: age, sex, duration of hospitalization, activities of daily living, medical diagnosis, presence or absence of urinary incontinence, type of urinary incontinence, and therapy for urinary incontinence. The prevalence of urinary incontinence in patients under 70, 70-79, 80-89, and over 90 years old was 59.3%, 67.7%, 79.8%, and 82.2%, respectively. Overall, 1142 patients (72.0%) suffered from urinary incontinence. Cerebrovascular disease was the major cause of admission to hospital in patients with urinary incontinence (37.0%). The most frequent type of urinary incontinence was functional urinary incontinence in patients who were mentally and/or physically unable to go to the bathroom without aid (21.5%). Specifically, 38.1% of patients in geriatric hospitals were diagnosed as having functional urinary incontinence, in contrast to only 3.9% of patients in non-geriatric units. In patients with dementia, 88.7% were incontinent, whereas in patients without dementia, the prevalence of urinary incontinence was much lower (51.5%, p < 0.001). Another predisposing factor for urinary incontinence was urinary tract infection. The prevalence of urinary incontinence in patients with and without urinary tract infection was 87.8% and 59.5%, respectively (p < 0.001). Almost all patients with poor activities of daily living (who were bedridden) suffered from urinary incontinence (98.5%). On the other hand, urinary incontinence was not so frequent in patients who could walk (26.9%). Pad (42.8%) and indwelling bladder catheter (18.3%) were the major means of management of incontinence, whereas behavioral therapy (4.9%) and surgery (0.5%) were not common. These results suggest that elderly patients with treatable urinary incontinence do not receive adequate therapy in Japan.
While non-enzymatic glycation of long-lived tissue proteins such as collagen has been implicated in chronic complications of diabetes mellitus, its role in the aetiology of diabetic macroangiopathy has not been elucidated. To test the hypothesis that glycation of collagen abolishes the inhibitory effect of native collagen on the proliferation of human smooth muscle cells, we obtained smooth muscle cells from human gastric arteries and cultured them on dishes coated with glycated or non-glycated collagen. The proliferation of human smooth muscle cells in the presence of 10% fetal calf serum or platelet derived growth factor-BB (10 ng/ml) was inhibited by type 1 collagen coated on the dishes. Glycation of collagen with glucose 6-phosphate for 7 days abolished the growth-inhibitory effect of native collagen. Succinylation of collagen, which like glycation blocked the lysyl residues in collagen, also abolished the growth-inhibitory effect. Adhesion of human smooth muscle cells to collagen-coated dishes was not affected by glycation of collagen. Addition of glycated albumin to the medium did not affect the growth of human smooth muscle cells on plastic dishes. The inhibition of human smooth muscle cell proliferation by collagen was not reversed by the glycation of collagen in the presence of aminoguanidine. Results suggest that early glycation abolishes the inhibitory effect of collagen on human smooth muscle cell proliferation and may thus participate in the progression of macro-angiopathy in diabetes.
We investigated the effects of mild hyperglycemia and insulin treatment on the metabolism of the ischemic brain in spontaneously hypertensive rats with acute hyperglycemia (n = 9), acute hyperglycemia treated with insulin during ischemia (n = 10), and normoglycemia (n = 10). Cerebral blood flow was measured by the H2 clearance method. Cerebral ischemia induced by occlusion of the bilateral carotid arteries. Cerebral glycolytic metabolites were measured enzymatically. Blood glucose levels were significantly higher in hyperglycemic animals (11.8 to 13.7 mM/l) than in normoglycemic animals (6.0 mM/l). At 60 min of ischemia, the blood flow to the parietal cortex was decreased to 3% of the resting value in all groups. Blood glucose levels at 60 min of ischemia in the hyperglycemic rats were 1.9--3 times higher than the treated hyperglycemic rats and normo-glycemic rats. Glucose concentrations were significantly and positively correlated with the ATP level (p < .0001) but not with the lactate levels in the ischemic brain. Our results suggest that mild hyperglycemia may preserve glucose metabolism in the presence of ischemic insult.
To obtain a relatively true mortality from malignant neoplasms, we studied the frequency of cancers in the different sites and the changing patterns of the frequency and sites over time among residents of the community of Hisayama, where an autopsy-based population survey (autopsy rate, 80%) has been conducted since 191. During the 30-year period from 1962 to 1991, we found 438 malignant neoplasms in 407 cases among 1,250 consecutive autopsies. Stomach cancer was not frequent in type of cancer, with 123 cases (9.8%), followed by lung cancer in 62 (5.0%), colorectal cancer in 42 (3.4%), liver cancer in 37 (3.0%), and pancreatic cancer in 30 (2.4%). We compared the mortality from cancers for both autopsy and nonautopsy cases (the proportional mortality) among three 10-year periods. The proportional mortality from all cancers, as well as for lung, colorectal, and liver cancers, showed an increase in recent years, while stomach and pancreatic cancer showed a decrease. These figures were nearly similar to the mortality statistics for the Japanese population as a whole except for the observed decreasing trend in mortality from pancreatic cancer.
It has been shown that carbon monoxide poisoning causes necrosis of the globus pallidum and the cerebral cortex, and a diffuse demyelination of the cerebral subcortical white matter, resulting in the impairment of the higher brain functions manifested as memory disturbances, apraxia, and agnosia. The purpose of the present study was to determine the effects of the lesions in the brain caused by carbon monoxide poisoning on the circadian changes in blood pressure and pulse rate. We measured the ambulatory blood pressure in 15 male patients with the sequelae of acute carbon monoxide poisoning and 16 age- and sex-matched controls. Using either brain computed tomography or brain magnetic resonance imaging, we determined that seven patients had lesions in the globus pallidum bilaterally, four had lesions in the parietotemporooccipital lobe bilaterally, and five had multiple deep white matter lesions. Circadian variations of blood pressure and pulse rate did not show any significant differences in either group. The average 24-h blood pressures were 120.8 +/- 2.2 (systolic)/74.1 +/- 1.5 mm Hg (diastolic) in the patients and 117.4 +/- 2.7/74.5 +/- 2.1 mm Hg in the controls. The daytime (6:00 to 21:00) and nighttime (21:00 to 6:00) blood pressures were 127.3 +/- 2.3/78.0 +/- 1.5 mm Hg and 109.7 +/- 2.4/67.4 +/- 1.7 mm Hg in the patients, and 121.6 +/- 2.9/77.5 +/- 2.2 mm Hg and 110.0 +/- 2.7/69.3 +/- 1.8 mm Hg in the controls, respectively. Furthermore, there were no differences in cardiovascular and plasma catecholamine responses induced by either a head-up tilt or a cold pressor test between the two groups. It is concluded that diffuse or multiple lesions in bilateral cerebral hemispheres caused by carbon monoxide poisoning per se do not affect the circadian changes in blood pressure and pulse rate observed in normotensive subjects.
OBJECTIVE: To access concordance between radiological severity of aphthae and the more advanced features of Crohn's disease. PATIENTS AND METHODS: In 75 patients with an established diagnosis of Crohn's disease, we evaluated the radiological severity of colonic aphthae by meticulous double-contrast radiography. The degree of aphthae was defined as follows: AE0 = no lesions; AE1 = small nodules without barium flecks (lymphoid hyperplasia); AE2 = minute barium flecks < or = 1 mm in size with a translucent halo (umbilical or eroded lymphoid hyperplasia); AE3 = barium flecks varying from 2 mm to 5 mm in size (typical aphthoid ulcerations). We compared the degree of the lesions to the disease activity, and reviewed these sequential changes during a mean interval of 10 months. RESULTS: AE3 lesions were more prevalent than AE1 or AE2 lesions in patients with active colitis. AE1 or AE2 lesions were found regardless of the involved bowel sites or the disease activity. Of 44 patients receiving a nutritional diet, 26 patients showed regression of the lesions although most of the patients still exhibited AE1 or AE2 lesions. In two of eight patients without the treatment, the lesions progressed. CONCLUSION: In Crohn's disease, development of aphthoid ulcers is associated with disease activity; lymphoid hyperplasia may exist independently of disease activity.
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Increased synthesis and gene expression of fibronectin or transforming growth factor-beta (TGF-beta) have been reported to be involved in the progressive process of doxorubicin hydrochloride (Adriamycin)-induced nephropathy. In the present study, the effects of dietary protein restriction on the synthesis and gene expression of fibronectin or TGF-beta were investigated by immunoprecipitation, Northern blotting, and TGF-beta bioassay in this model after subjects were given either short- or long-term low-protein diets. In the long-term diet experiment, either a normal protein diet (NPD, 20%) or low-protein diet (LPD, 5%) was fed to the Adriamycin rats for 8 weeks after the injection of Adriamycin. An 8-week LPD significantly ameliorated kidney destruction and remarkably reduced the fibronectin synthesis. Furthermore, the significant decreases of the latent TGF-beta secretion and the expression of TGF-beta 1 mRNA were observed in the Adriamycin rats fed an 8-week LPD. In the short-term diet experiment, an NPD or LPD was fed to the Adriamycin rats for 2 weeks at weeks 4, 8, or 16 after the injection of Adriamycin. A 2-week LPD did not ameliorate kidney damage. Although fibronectin synthesis by the renal cortex in the Adriamycin rats was remarkably reduced by a 2-week LPD, there was no significant decrease in the latent TGF-beta secretion in the Adriamycin rats. The mRNA expressions of fibronectin or TGF-beta 1 were not affected by a 2-week LPD in the Adriamycin rats at any stage. In conclusion, decreased fibronectin and TGF-beta synthesis may be one of the mechanisms by which the long-term dietary protein restriction ameliorates kidney damage. On the other hand, a 2-week LPD affected the only fibronectin synthesis, which thus suggested that an LPD might exert a quicker influence on the protein synthesis of fibronectin than on the transcriptional events of fibronectin.
Spontaneously hypertensive rats (SHR) given streptozotocin (STZ) neonatally developed genetic hypertension and overt hyperglycemia after the onset of puberty. In the present study, gonadectomy was performed before puberty in both males and females of this animal model. Orchidectomy suppressed the development of hypertension in vehicle-treated and STZ-treated SHR (systolic blood pressure at 11 weeks of age: 209 +/- 5 mm Hg in the intact vehicle group v 187 +/- 6 mm Hg in the orchidectomized vehicle group, P < .01; 211 +/- 14 mm Hg in the intact STZ group v 182 +/- 4 mm Hg in the orchidectomized STZ group, P < .001). Furthermore, orchidectomy ameliorated the development of overt hyperglycemia in STZ-treated SHR (nonfasting plasma glucose at 12 weeks of age: 22.1 +/- 0.7 mmol/L in the intact group v 16.1 +/- 2.4 mmol/L in the orchidectomized group, P < .05). On the other hand, orchidectomy did not affect glucose tolerance in vehicle-treated SHR, but attenuated the insulin response to an oral glucose load (P < .05). Orchidectomy significantly decreased urinary albumin excretion and kidney weight in both the vehicle and the STZ groups. Ovariectomy significantly increased body weight gain irrespective of STZ treatment. However, ovariectomy had no effect on hypertension, hyperglycemia, albuminuria, or kidney weight in either vehicle or STZ groups. This study demonstrated that gonadectomy had protective effects against development of hypertension, hyperglycemia, and albuminuria in males but not in females. This suggests that sex hormones may be important as a link between diabetes mellitus and hypertension in males.