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Biomedical subjects

R Ebert

Publications and source records attributed to R Ebert.

At least 19 recordsLinked to original sources

[Diagnostic and therapeutic problems in Lamblia infections].

A 28-year-old woman complained of chronic diarrhoea of about one year's duration, made worse by taking food. As a lactose tolerance test showed evidence of severe intolerance she was given a lactose-free diet, but this brought no improvement. Duodenal biopsy showed villous atrophy, and in the duodenal juice there were numerous flagellated lamblia. After a single oral dose of 2 g tinidazole the diarrhoea stopped, the lamblia disappeared, and the lactose intolerance and villous atrophy cleared up. Lamblia were also detected in the duodenal juice of a 50-year-old woman, but her infection was much more difficult to treat. Tinidazole (single dose of 2 g), metronidazole (800 mg twice daily for 6 days), ornidazole orally 500 mg twice daily for 10 days and ornidazole intravenously 500 mg twice daily for four days all proved ineffective. However, after a 5-day course of epsilon-9-aminacridine (100 mg three times daily by mouth) the diarrhoea ceased and both vegetative forms and lamblia cysts disappeared. These cases emphasize that lambliasis should be considered as a possible cause of severe chronic diarrhoea even when there is no history of travel abroad and when the symptoms are atypical. Conventional chemotherapeutic agents may be ineffective.

Adult

Characterization of the Syrian hamster c-Ha-ras gene and intron-D-exon transcript.

The coding sequences as well as 5'- and 3'-flanking sequences of the Syrian hamster c-Ha-ras gene were deduced from cDNA clones derived from embryo fibroblast cell lines. Sequences of introns B, C, and D were obtained from genomic DNA after amplification by the polymerase chain reaction. Sequence comparisons with rat, mouse, and human c-Ha-ras genes revealed a high degree of homology. One of 12 cDNA clones contained intron-D-exon (IDX) sequences due to alternative splicing that would encode a p19 Ha-ras gene product. Conservation between species suggests a functional role for the IDX, possibly as a negative control of p21 Ha-ras expression.

Amino Acid Sequence

Basal and nutrient-stimulated pancreatic and gastrointestinal hormone concentrations in type-1-diabetic patients after successful combined pancreas and kidney transplantation.

The secretion of pancreatic and gastrointestinal hormones in the basal state and after nutrient stimuli (50 g glucose, 50 g protein, or 30 g triglyceride administered on separate occasions) was assessed in ten previously type-1-diabetic patients after successful combined kidney and pancreas transplantation (systemic venous drainage). Fasting values were compared to matched non-diabetic kidney-transplanted patients and related to kidney function (endogenous creatinine clearance) and to the type and dosage of immunosuppressive medication. In the fasting state, only IR insulin concentrations were higher in pancreas-kidney-transplanted patients (by 88%; P = 0.001) than in the kidney graft recipients. There were significant inverse correlations of plasma C-peptide, GIP, and gastrin immunoreactivity to endogenous creatinine clearance (kidney function). In response to nutrients, insulin secretion (IR insulin, C-peptide) was significantly stimulated by glucose, and - to a lesser degree - also by protein. Pancreatic glucagon was suppressed by glucose and stimulated by protein ingestion. GIP was raised after glucose and triglyceride more than after protein (P = 0.0003). GLP-1 immunoreactivity was stimulated by all nutrients, with a tendency towards higher responses to protein and fat (P = 0.06). Gastrin was mainly raised by protein. In conclusion, the overall pattern of pancreatic and gastrointestinal hormone release is normal in patients after combined pancreas-kidney-transplantation, but there are some peculiarities due to (a) systemic venous drainage of the pancreas graft (elevated fasting IR insulin) and (b) impaired kidney function (negative correlation of fasting plasma values to endogenous creatinine clearance for C-peptide, GIP, and gastrin).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult

Endocrine response to intragastric and intravenous glucose challenge in the denervated dog pancreas.

The functional connection between the gut and the islet cells comprises nerves and gastrointestinal hormones. In this study, we quantified the incretin effect and the glucose tolerance (KG value) before and after denervation of the pancreas in dogs in order to find out whether the incretin effect is mediated by nerves. The participation of nerves was estimated by comparing metabolic tests before and after total extrinsic pancreatic denervation in 10 dogs. Fifty-nine percent of the insulin response after intragastric glucose was calculated preoperatively to be the result of incretin factors, a value similar to the 62% found in the postoperative series (with denervated pancreas). The response of GIP to intragastric glucose was not significantly different between pre- and postoperative tests. The KG values pre- and postoperative were in the same range. From our data, we conclude that extrinsic nerves of the pancreas do not seem to play an important role in mediating glucose homeostasis in dogs.

Animals

Lack of effect of synthetic human gastric inhibitory polypeptide and glucagon-like peptide 1 [7-36 amide] infused at near-physiological concentrations on pentagastrin-stimulated gastric acid secretion in normal human subjects.

Gastric inhibitory polypeptide (GIP) and glucagon-like peptide 1 [7-36 amide] (GLP-1) are glucose-dependent insulinotropic gut hormones. Under experimental conditions, both have been shown to reduce stimulated gastric acid secretion. To study their individual and combined effects on pentagastrin-stimulated (0.1 micrograms/kg/h from -90 to 120 min) gastric volume, acid and chloride output, on separate occasions, synthetic human GIP (1 pmol/kg/min) and/or GLP-1 [7-36 amide] (0.3 pmol/kg/min) or placebo (0.9% NaCl with 1% albumin) were infused intravenously (from -30 to 120 min) in 9 healthy volunteers. At 0 min, a glucose infusion was started that mimicked the glycemic profile after an oral glucose load of 50 g/400 ml and allowed for the glucose-dependent insulinotropic action of GIP and GLP-1 [7-36 amide]. Pentagastrin stimulated acid output significantly, but neither GIP nor GLP-1 [7-36 amide] either alone or in combination, reduced pentagastrin-stimulated gastric acid secretion. The circulating concentrations of GIP and GLP-1 [7-36 amide] obtained at steady state during exogenous administration of synthetic peptides were similar to or higher than those reached after oral glucose (endogenous secretion). In conclusion, (penta)gastrin-stimulated gastric acid secretion is not inhibited by physiological circulating concentrations of GIP or GLP-1 [7-36 amide]. Therefore, the insulinotropic action of these intestinal hormones is physiologically more important than their possible role as enterogastrone.

Adult

Role of endogenously released cholecystokinin in determining postprandial insulin levels in man: effects of loxiglumide, a specific cholecystokinin receptor antagonist.

To estimate the contribution of postprandial cholecystokinin (CCK) responses to circulating insulin concentrations and insulin secretion, a specific CCK receptor antagonist (loxiglumide; 10 mg/kg body weight/h) or saline were infused intravenously in normal volunteers, beginning 90 min before insulin secretion was stimulated on separate occasions by the intraduodenal administrations of glucose, glucose and protein, and glucose plus protein with the admixture of pancreatin. The release of CCK (radioimmunoassay) was stimulated by the protein component of the nutrients from basal 2.4 +/- 0.4 to 8.0 +/- 1.2 pmol/l. CCK plasma levels were significantly higher with loxiglumide (p < 0.05). Glucose-dependent insulinotropic polypeptide (GIP) was also released by all nutrient mixtures. Loxiglumide significantly inhibited the amount of bilirubin and pancreatic enzymes recovered from duodenal aspirates. In contrast, in none of the experiments, C-peptide increments and hence insulin secretion rates were altered by loxiglumide. With glucose and protein as intraduodenal stimulus (no pancreatin added), the plasma amino acids rose significantly less (by approximately 50% of the control experiment) and the increment in insulin (but not C-peptide) concentrations was significantly reduced by loxiglumide. This is most likely explained by a change in insulin metabolic clearance. This effect cannot be a primary action of CCK because there was no similar effect of loxiglumide with the same intraduodenal stimulus plus added pancreatin. Pancreatic enzymes reduced maldigestion secondary to loxiglumide effects on pancreatic exocrine secretion: The increment in circulating amino acid concentrations was similar with and without loxiglumide. In conclusion, CCK does not alter insulin secretion and, therefore, is not an incretin hormone in man. Blocking CCK actions on the exocrine pancreas by loxiglumide, however, can secondarily cause reductions in postprandial insulin profiles by altering insulin clearance. These changes are possibly related to reductions in circulating amino acid concentrations.

Adult

[Omeprazole].

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Esophagitis, Peptic

Inhibition of sucrose- and starch-induced glycaemic and hormonal responses by the alpha-glucosidase inhibitor emiglitate (BAY o 1248) in healthy volunteers.

The absorbable deoxynojirimycin derivative emiglitate (BAY o 1248) is a potent competitive inhibitor of small intestinal alpha-glucosidases in man. In two similar randomized, placebo-controlled, double blind investigations, the efficacy, duration of action and tolerability of single doses of 10, 20 and 40 mg emiglitate have been assessed in healthy male volunteers after repeated sucrose or maize-starch loads at 08.00, 12.00 and 17.00 h. Even at the lowest dose used, emiglitate almost abolished the glycaemic (-88%) and hormonal responses after the first sucrose meal, simultaneously evoking significant hydrogen evolution (mean peak H2-concentration greater than 100 ppm), which was not related to the dose, and which induced unacceptable symptoms of carbohydrate malabsorption, i.e. at the dosages tested, the inhibition of glycaemic and hormonal responses was at the expense of intolerable gastrointestinal adverse effects. Flattening of postprandial responses of blood glucose, serum insulin and gastric inhibitory polypeptide was still apparent after a second sucrose load 4 h later, demonstrating long-lasting inhibition of alpha-glucosidase activity. After starch, the dose dependency of inhibition emerged more clearly than after sucrose, i.e. the reduction was less pronounced. However, emiglitate led to significant reduction of the glycaemic and hormonal rises after both the first and second starch meals. Symptoms of carbohydrate malabsorption were absent after 10 mg and were negligible with 20 mg or 40 mg emiglitate. Breath hydrogen concentration increased gradually, indicating slight but significant carbohydrate malabsorption after the highest dose of the alpha-glucosidase inhibitor. The results show that a single morning dose of 20-40 mg emiglitate might be useful in the control of postprandial hyperglycaemia after breakfast and lunch.(ABSTRACT TRUNCATED AT 250 WORDS)

1-Deoxynojirimycin

Reduced secretion of gastric inhibitory polypeptide in Turner patients with impaired glucose tolerance.

There is a well documented increase in the incidence of abnormal glucose tolerance in patients with Turner syndrome. To elucidate the pathophysiology of this phenomenon, we studied the serum concentrations of gastric inhibitory polypeptide (GIP)--as probably the most important hormonal factor of the entero-insular axis--in relation to impaired glucose tolerance in this syndrome. Oral glucose tolerance tests were performed in 12 Turner patients with simultaneous determination of plasma glucose, insulin and GIP. An impaired glucose tolerance (iGT) was found in four patients with a chronological age between 12.3 and 14.9 years. These patients were compared with four Turner patients of similar age and weight and a normal glucose tolerance (nGT). The highest insulin level occurred 90 min after stimulation in the patients with iGT compared to 30 min in the nGT group. Interestingly, the total areas under the insulin curves were not different. Stimulated plasma GIP concentrations and the areas under the GIP curves were significantly lower in iGT compared to nGT patients. A disturbed entero-insular axis might contribute to the delayed--rather than diminished--release of insulin in patients with Turner syndrome and impaired glucose tolerance.

Adolescent

Effect of exogenous or endogenous gastric inhibitory polypeptide (GIP) on plasma triglyceride responses in rats.

We examined the effects of exogenous and endogenous GIP on plasma triglyceride levels in rats, pretreated with a fat-enriched diet, during intraduodenal infusion of a lipid test meal (Lipomul, 8 ml/h). Following the fat load the plasma triglyceride levels increased nearly linearly from a fasting value of 0.621 +/- 0.031 mmol/l to 3.32 +/- 0.403 mmol/l at 150 min. Simultaneously, the plasma GIP levels rose from 47.1 +/- 5.1 at fasting to a peak value of 268.4 +/- 32.2 pmol/l at 120 min. When porcine GIP was infused intravenously during the fat load, the plasma triglyceride increments were significantly smaller (control 1.64 +/- 0.264 mmol/l versus 0.949 +/- 0.114 mmol/l during GIP infusion at 60 min; p less than 0.002). GIP infusion in the absence of the fat load did not change fasting triglyceride levels. The effect of endogenous GIP was investigated by neutralization of GIP by injection of GIP antiserum (0.3 ml). Rats pretreated with the antiserum exhibited a significantly greater triglyceride increment late in the time course of the fat load. These data demonstrate that exogenous and endogenous GIP are able to lower the plasma triglyceride response to a fat load. Both, inhibition of fat absorption or stimulation of triglyceride uptake by peripheral tissues may be responsible for the GIP effects. The gut peptide GIP seems to represent an important hormonal regulator of postprandial triglyceride response.

Animals

Inhibition of glycemic and hormonal responses after repetitive sucrose and starch loads by different doses of the alpha-glucosidase inhibitor miglitol (BAY m 1099) in man.

In two randomized, placebo-controlled, double-blind studies, the efficacy, duration of action and tolerability of a single morning dose of 25, 50, and 100 mg miglitol (BAY m 1099), an absorbable inhibitor of intestinal alpha-glucosidases, were assessed after repetitive sucrose or maize-starch loads (50 g of carbohydrates in 400 ml of water each at 08.00, 12.00, and 17.00 h). With sucrose, miglitol reduced the postprandial rise in blood glucose, serum insulin and serum gastric inhibitory polypeptide concentrations at any dosage. This effect was dose-dependent and confined to the first carbohydrate load in the morning, thus indicating the duration of alpha-glucosidase inhibition of less than 4 h. Sucrose malabsorption, indicated by breath hydrogen responses, occurred dose-dependently with 50 and 100 mg, but not with 25 mg of miglitol. Similarly, symptoms of carbohydrate malabsorption were absent with 25 mg of the inhibitor and mild to moderate after 50 and 100 mg of miglitol. With starch as the substrate, BAY m 1099 led to a significant amelioration of glycemic and hormonal rises after the first meal, but not thereafter. A numerical dose dependency was recognized, but this was not significant at the 5% level. Symptoms of carbohydrate malabsorption were absent with 25 mg and negligible with 50 mg BAY m 1099, but occurred almost regularly with the 100-mg dose. Breath hydrogen concentrations increased gradually with the dose of miglitol administered. A single morning dose of 25-100 mg of miglitol thus may be useful for the control of postprandial hyperglycemia after breakfast. Due to the duration of action of less than 4 h, this substance should be given with the three main meals.

1-Deoxynojirimycin

Future preparation of occupational health nurse managers.

This article presents the results of a national survey of job activities of corporate level occupational health nurse managers. The survey was designed to identify the relative amount of time spent and importance attributed to specific areas of their current job. In general this sample tended to have more management experience and educational preparation than previously cited studies: over 50% had completed a graduate degree. The scores for importance and time spent were highly correlated. That is, occupational health corporate nurse managers seemed to allocate their time to job responsibilities they considered most important. Management activities related to policy, practice standards, quality assurance, staff development, and systems for client care delivery appear to represent the core responsibilities of occupational health nursing management. Curriculum recommendations for management positions in occupational health include: health policy, program planning, and evaluation; business strategy; applications of management information systems; quality assurance; and marketing.

Curriculum

[Ultrasonically guided fine-needle puncture. The limits of the method in the abdomen and retroperitoneal space].

The sensitivity and specificity of ultrasound-directed fine-needle biopsy in the differentiation of malignancy or otherwise of structures in the abdomen or retroperitoneal space which look suspicious on ultrasound was evaluated from results in 558 patients (306 men, 252 women). Data from two different centres were used to characterize further the influence of different techniques of puncture, cytopathologists and groups of patients on the validity of the examination. Sensitivity (in the two centres) was 88 and 80%, respectively, specificity 100 and 99%. The validity of the examination was the same at both centres. In both centres the sensitivity was worst for pancreatic tissue, at only 72 and 61% respectively, compared with other organs (e.g. liver, lymph nodes, kidney) (P less than 0.05). Fine-needle biopsy of abdominal and retroperitoneal organs will thus be subject to a not insignificant number of false-negative results of cytological examination.

Abdomen

Activation of cellular oncogenes by chemical carcinogens in Syrian hamster embryo fibroblasts.

Carcinogen-induced point mutations resulting in activation of ras oncogenes have been demonstrated in various experimental systems such as skin carcinogenesis, mammary, and liver carcinogenesis. In many cases, the data support the conclusion that these point mutations are critical changes in the initiation of these tumors. The Syrian hamster embryo (SHE) cell transformation model system has been widely used to study the multistep process of chemically induced neoplastic transformation. Recent data suggest that activation of the Ha-ras gene via point mutation is one of the crucial events in the transformation of these cells. We have now cloned the c-Ha-ras proto-oncogene from SHE cDNA-libraries, and we have performed polymerase chain reaction and direct sequencing to analyze tumor cell lines induced by different chemical carcinogens for the presence of point mutations. No changes were detectable at codons 12, 13, 59, 61, and 117 or adjacent regions in tumor cell lines induced by diethylstilbestrol, asbestos, benzo(a)pyrene, trenbolone, or aflatoxin B1. Thus, it is not known whether point mutations in the Ha-ras proto-oncogene are essential for the acquisition of the neoplastic phenotype of SHE cells. Activation of other oncogenes or inactivation of tumor suppressor genes may be responsible for the neoplastic progression of these cells. However, in SHE cells neoplastically transformed by diethylstilbestrol or trenbolone, a significant elevation of the c-Ha-ras expression was observed. Enhanced expression of c-myc was detected in SHE cells transformed by benzo(a)pyrene or trenbolone.

Animals