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Biomedical subjects

F W Schmidt

Publications and source records attributed to F W Schmidt.

At least 19 recordsLinked to original sources

Energy expenditure and substrate oxidation in patients with cirrhosis: the impact of cause, clinical staging and nutritional state.

Many clinicians subjectively feel that cirrhotic patients frequently have clinical signs of hypermetabolism. However, it is unknown whether hypermetabolism is a constant feature of chronic liver disease, corresponds to liver destruction and repair or is of prognostic value. This article is about resting energy expenditure and substrate oxidation rates in 123 patients with biopsy-proven cirrhosis differing with respect to cause, duration of the disease, biochemical parameters of parenchymal cell damage, cholestasis, liver function, number of complications, clinical staging and nutritional state. Resting energy expenditure varied between 1,090 and 2,300 kcal/day and differed from the predicted values in 70% of the patients. Resting energy expenditure was closely related to fat-free mass, and 52% of the variability could be explained by fat-free mass, age and sex. Of all the patients, 18% were hypermetabolic and 31% were hypometabolic. Hypermetabolism showed no strict association with the cause of cirrhosis, the duration of the disease, liver function, cholestasis, cell damage, clinical staging, blood hemoglobin, plasma thyroid hormone levels or human leukocyte antigens. An increased resting energy expenditure was associated with significant losses of muscle, body cell mass and extracellular mass at unchanged body fat, whereas fat and fat-free mass were increased in hypometabolic patients when compared with normometabolic patients. Lipid oxidation was increased, but glucose oxidation was reduced in nearly all patients with cirrhosis. This was most pronounced at advanced stages of liver disease. Although similar with respect to liver function and clinical staging, 76.2% of hypermetabolic patients had transplants within the observation period, compared with only 16.7% and 8.1% in the normometabolic group and hypometabolic group, respectively. Posttransplantation mortality was independent of pretransplantation resting energy expenditure, but it increased significantly in patients with losses in body cell mass. In conclusion, hypermetabolism is not a constant feature of cirrhosis and results more from extrahepatic than from hepatic factors. It may cause malnutrition and contributes to the clinical outcome of patients with chronic liver disease.

Adult

Mechanism of insulin resistance associated with liver cirrhosis.

Insulin-induced glucose metabolism was investigated in 26 patients with biopsy-proven liver cirrhosis and 10 control subjects. Two glucose clamp protocols together with continuous indirect calorimetry were performed to examine whether reduced rates of glucose oxidation and/or nonoxidative glucose metabolism explain insulin resistance in liver cirrhosis. Using a 4-hour, two-step protocol (0-2 hours, plasma glucose 5.2 mmol/L, plasma insulin 92 mU/L to test the half-maximum response; 2-4 hours, hyperglycemia 10.0 mmol/L, plasma insulin 442 mU/L to test the maximum cellular glucose disposal) liver cirrhosis reduced glucose disposal to 45% and 60% of control values, respectively. Simultaneously, insulin-induced increases in glucose oxidation, plasma lactate levels, and lipogenesis were normal, whereas nonoxidative glucose metabolism was reduced (-82% and -47% of controls, respectively). To determine whether reduced nonoxidative glucose metabolism was caused by reduced glucose disposal, glucose disposal was "matched" to normal values in a subgroup of cirrhotic patients. Nonoxidative glucose metabolism values were normal, but plasma lactate concentrations disproportionally increased (+96%) after "matching" glucose disposal. Insulin resistance was independent of the etiology of the cirrhosis, the biochemical parameters of parenchymal cell damage and liver function, and the clinical and nutritional state of the patients. It is concluded that liver cirrhosis impairs insulin sensitivity and maximum cellular glucose disposal. Reduced glucose disposal is caused by defective glucose storage. Insulin resistance is independent of the etiology of liver cirrhosis and of the clinical and nutritional state of the patient.

Adult

Resting energy expenditure and the thermic effect of adrenaline in patients with liver cirrhosis.

1. Resting energy expenditure and the metabolic responses to adrenaline (infusion rate: 0.03 micrograms min-1 kg-1 fat-free mass for 1 h) were investigated in 25 patients with liver cirrhosis. The patient group was heterogeneous and varied with respect to the aetiology of cirrhosis, the clinical condition (i.e. Child A or B), the nutritional status and the degree of hyperinsulinaemia. 2. When compared with 10 healthy control subjects the basal plasma adrenaline and noradrenaline concentrations were both increased in cirrhosis and remained elevated during adrenaline infusion (+39% and +31%, respectively; P < 0.05). Concomitantly, the peripheral plasma insulin concentration and the molar C-peptide/insulin ratio were increased in liver cirrhosis (+96% and +30%, respectively; P < 0.05). Hyperinsulinaemia was more pronounced in patients with ethanol-induced liver cirrhosis. 3. When expressed per kg fat-free mass, resting energy expenditure was enhanced in liver cirrhosis (+21%; P < 0.05) and was more pronounced (i.e. resting energy expenditures of +35% to +49% above estimated values) in patients with ethanol-induced cirrhosis, at advanced stages of the disease and in association with decreased body cell mass. 4. Infusion of adrenaline increased heart rate, O2 consumption and the plasma concentrations of glucose, lactate, free fatty acids, glycerol and 3-hydroxybutyrate, and similar transient increases and subsequent decreases in the respiratory quotient were observed in both groups. However, the lipolytic, ketogenic and thermic responses were reduced in cirrhotic patients. Reduced metabolic responses were more pronounced in hyperinsulinaemic patients.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult

Bismuth subsalicylate in the treatment of H2 blocker resistant duodenal ulcers: role of Helicobacter pylori.

Fifty nine patients with Helicobacter pylori positive duodenal ulcers that failed to heal after a six week course of treatment with H2 blockers were randomly assigned to one of the following three regimens: (i) bismuth subsalicylate, 600 mg three times daily (n = 19), (ii) ranitidine, 300 mg at night (n = 20), (iii) bismuth subsalicylate plus ranitidine (n = 20). Cumulative ulcer healing rates after four and eight weeks respectively were as follows: bismuth subsalicylate 74% (14/19) and 95% (18/19), ranitidine 40% (8/20) and 65% (13/20), bismuth subsalicylate plus ranitidine 80% (16/20) and 95% (19/20). Bismuth subsalicylate treatment was better than ranitidine at both four and at eight weeks (p less than 0.05). The clearance rates for H pylori after four weeks were: bismuth subsubsalicylate 58%, ranitidine 0%, bismuth subsalicylate plus ranitidine 55%. After stopping bismuth therapy bacterial recrudescence frequently occurred. After bismuth treatment 86% (19/22) of ulcers had healed if H pylori had been cleared, whereas only 65% (11/17) had healed if H pylori persisted (NS). This study shows that bismuth subsalicylate is more effective in the treatment of resistant duodenal ulcers than standard dose ranitidine. It may be that suppression of H pylori by bismuth subsalicylate promotes ulcer healing.

Bismuth

[Chemoembolization of hepatocellular carcinoma in cases of isolated liver involvement].

Chemoembolization is an effective treatment for hepatocellular carcinoma, giving results equally as good as surgical therapy for T2 tumours. Survival can be prolonged and side-effects can be reduced by combining Lipiodol and Gelfoam for chemoembolization, employing a modified technique, with repeated procedures, and using appropriate follow-up treatment. The toxicity of the procedure is acceptable, but it requires supportive therapy necessitating an intense interdisciplinary co-operation.

Aged

[Malignant peritoneal mesothelioma with unusual and extensive metastasis].

A 43-year-old alcohol-dependent man had sustained three acute episodes of chronic pancreatitis. At the third hospital admission enlarged axillary and supraclavicular lymph nodes, widening of the mediastinum and bone metastases were noted. Cytological examination of a needle biopsy of the supraclavicular lymph node revealed a poorly differentiated adenocarcinoma. Because of the marked enlargement of the pancreas and the history, a rapidly and unusually metastasizing carcinoma of the pancreas was diagnosed. In view of the rapid deterioration of the patient no chemotherapy was begun and he died 4 weeks after admission. Autopsy confirmed the chronic pancreatitis but no carcinoma of the pancreas. Instead there was a peritoneal mesothelioma with extensive lymphogenous and haematogenous metastases. The incidence of this tumour is ever increasing. It should be included in the differential diagnosis, because survival time can be increased if the correct diagnosis is made very early.

Adult

Pathophysiology and clinical basis of prevention and treatment of complications of chronic liver disease.

Chronic liver failure is characterized by the appearance of jaundice, ascites, encephalopathy and/or gastrointestinal bleeding. Acute episodes of hepatic decompensation are frequently precipitated by additional events, e.g. septicaemia, diuretic therapy or excessive protein intake. Identification, correction and treatment of these precipitating factors are first steps in the management of chronic liver failure. Nutritional support is important in the treatment of cirrhotic patients, because malnutrition is one of the major determinants of patient outcome. Management of encephalopathy reduces the appearance of gut-derived nitrogenous toxins and corrects imbalances in amino acid metabolism. Treatment of ascites is salt restriction supported by gentle and incremental administration of diuretics. Ursodesoxycholic acid has become a new and promising modality in the management of cholestatic liver diseases. If conservative therapy fails to recompensate liver function, liver transplantation may be indicated.

Ascites

Assessment of pretransplant prognosis in patients with cirrhosis.

The objective of this prospective study was to assess the prognostic value of dynamic liver function tests and traditional methods of evaluating liver function in potential candidates for hepatic transplantation. Patients who underwent orthotopic liver transplantation within the follow-up period of 120 days were excluded. The study included 107 adult and 57 pediatric patients with cirrhosis. Postnecrotic cirrhosis was present in 107 and biliary cirrhosis in 57 of 164 patients. During the follow-up period, 26 of 164 patients died of their liver disease. At the time of inclusion, we recorded monoethylglycinexylidide (MEGX) formation from lidocaine, indocyanine green (ICG) half-life, bilirubin and albumin serum concentration, activity of cholinesterase and alkaline phosphatase, prothrombin time, the clinical complication of ascites, and--in adults--the Pugh score also. These variables were subjected as covariates to a survival analysis (Cox proportional hazards regression model) using separately the data from adults, pediatric patients, all patients with postnecrotic cirrhosis, and all patients with biliary cirrhosis. In all of these four subgroups there was a significant relationship between MEGX and ICG test results and the 120-day survival. In the stepwise analysis, none of the remaining parameters contributed to a further relevant improvement of our predictive ability when added to the values of ICG and MEGX. Our results suggest that the ICG and the MEGX test are superior to conventional liver function tests and the Pugh score in assessing short-term prognosis in cirrhotics independently from the etiology of the underlying liver disease. These findings may have important implications for determining the optimum timing of transplantation.

Adolescent

Circadian pattern of intragastric acidity in duodenal ulcer patients: a study of variations in relation to ulcer activity.

The relation between intragastric acidity and duodenal ulcer activity was studied prospectively in 21 patients with endoscopically proved duodenal ulcers. The 24 hour intragastric acidity was measured on four separate occasions by continuous recording using combined glass electrodes: (a) in the presence of an ulcer crater without treatment; (b) during active ulceration being treated with ranitidine; (c) during early healing after a six week course of ranitidine; (d) during late healing six months after acute ulceration. Intragastric acidity was also monitored in 20 healthy subjects. At all stages of ulcer activity and during all predefined time periods, duodenal ulcer patients had significantly higher gastric acidity than healthy control subjects. Duodenal ulcer patients showed a similar circadian pattern of intragastric acidity during exacerbation of ulcer disease and in remission during the early and late ulcer healing periods. These results argue against a direct relation between the activity of duodenal ulcer disease and gastric acidity. It is concluded that the chronic recurrent course of duodenal ulcer disease does not result from a fluctuation in intragastric acidity.

Acute Disease

Energy expenditure and substrate metabolism in ethanol-induced liver cirrhosis.

Energy expenditure and substrate metabolism were investigated in 10 patients with alcoholic liver cirrhosis (EtOH-Ci) and 10 healthy controls (C). Resting metabolic rate (RMR) varied from 1,269 to 2,467 kcal/day in C and from 1,228 to 2,098 kcal/day in EtOH-Ci. RMR was significantly related to fat-free mass (FFM) in both groups, but EtOH-Ci decreased FFM and increased RMR when expressed per kilogram FFM (+33%). Glucose intolerance, hyperinsulinemia, and a decreased C-peptide-to-insulin ratio were observed in EtOH-Ci after a test meal. Concomitantly, nonoxidative glucose metabolism was reduced in association with normal increases in glucose oxidation. EtOH-Ci reduced insulin sensitivity (-59%) and maximal insulin-dependent glucose disposal (-40%) during a sequential two-step glucose clamp protocol (phase 1: 1 mU.kg body wt-1.min-1 insulin infusion rate + euglycemia; phase 2: 4 mU.kg body wt-1.min-1 insulin infusion rate + 165 mg/dl plasma glucose concentration). This was explained by reduced glucose storage (-99%, -51%) in association with normal responses in glucose oxidation rate, plasma lactate concentration, lipid oxidation rate, and rate of lipogenesis. Defective glucose storage was independent of reduced FFM. EtOH-Ci increased glucose-induced thermogenesis by 57%. We conclude that increased resting metabolic rate, enhanced thermogenesis, defective glucose storage, and normal glucose oxidation together result in increased energy needs and favor negative energy balance in patients with alcoholic cirrhosis.

Adult

The influence of colostral leukocytes on the immune system of the neonatal calf. IV. Effects on bactericidity, complement and interferon; synopsis.

The influence of colostral leukocytes on the bactericidity of whole blood of calves against a strain of E. coli and on the activities of haemolytic complement and interferon-alpha (the antiviral activity of sera resisting an acidic treatment at pH 2 for 6 h) in the serum was investigated during a period of 4 weeks using 4 experimental groups. The calves received either complete colostrum (COL+, n = 16), cell-depleted colostrum (COL-, n = 16), cell-supplemented milk substitute (MS+, n = 7) or pure milk substitute (MS-, n = 6) during their first three days of life. The bactericidity of whole blood of the COL+ group was significantly higher on the second and third days of life while the activity of haemolytic complement was lower after the first week as compared to the COL- group. No interferon-alpha was detectable in the sera of both COL groups. The bactericidity of the MS groups was significantly lower than that of the COL groups after the first day of life. It was significantly lower in the MS+ group after one week of life while the activity of haemolytic complement was higher than that of the MS- group. Three out of 5 MS- and only one out of 7 MS+ calves had low titres of interferon-alpha in their sera on the third day. Three out of 6 MS- calves died and 5 out of 7 MS+ animals. The mean day of death was 4.0 in the MS- and 8.4 in the MS+ group. Based on the in vitro results of this and the previous three communications it can be concluded that leukocytes which are an integral part of normal bovine colostrum, influence immunological reactions of the calf and that they may enhance its defence against infection. Colostral leukocytes in the absence of humoral components of the colostrum are not able to prevent fatal losses in the calves due to natural infection, although their influence on immune responses of the calves was detectable in vitro.

Animals

The influence of colostral leukocytes on the immune system of the neonatal calf. II. Effects on passive and active immunization.

The influence of colostral leukocytes on the concentration of immunoglobulins and antibodies against an enterotoxigenic strain of E. coli in the sera of newborn calves was investigated for four weeks using four experimental groups. The calves received either complete colostrum (COL-, n = 16), cell-supplemented milk substitute (MS+, n = 7) or pure milk substitute (MS-, n = 6) during the first three days of life. The cows were not specifically immunized. The sera of the COL+ calves had significantly higher concentrations of antibodies against E. coli mainly of IgG1 specificity on the second day of life as compared to those of the COL-. The sera of the COL+ calves contained significantly more IgM on days 2 and 5 and slightly more IgA during the first week. Both COL groups had equal concentrations of serum IgG. It appears that colostral leukocytes which are an integral part of the colostrum enhance the passive immunity of the neonatal calf, especially in regard of antibodies and immunoglobulin classes which are essential for intestinal immunity. The concentration of IgM in the sera of the MS+ calves was reduced, that of IgG did not rise to appreciable amounts; the IgA synthesis started one week later as compared to the MS- group. The administration of isolated colostral cells led to an impairment of the natural active immunization.

Animals

The influence of colostral leukocytes on the immune system of the neonatal calf. III. Effects on phagocytosis.

The influence of colostral leukocytes on the activity of phagocytic cells from the blood of calves, in particular the concentration of neutrophils (PMN) in blood, ingestion of Streptococcus agalactiae, reduction of NBT-dye and activity of lysozyme, was investigated for four weeks using four groups. The calves received either complete colostrum (COL+, n = 16), cell depleted colostrum (COL-, n = 16), cell-supplemented milk-substitute (MS+, n = 7) or pure milk-substitute (MS-, n = 6). Calves of the COL+ group had a significantly lower PMN concentration in their blood on day 2 and a significantly higher activity of lysozyme during their first three weeks of life as compared to the COL- animals. A postnatal increase in number of ingested Streptococcus agalactiae test bacteria per 100 phagocytic cells occurred later in the COL+ calves than in the COL-. No difference between both COL groups in NBT-reduction was observed. The calves of the MS+ group showed higher lysozyme activity and a retarded increase in the ingestion of test bacteria during the first week of life as compared to the MS-. The MS+ group had a transient neutrophilia on the second day of life while the concentration of PMN was not altered in the MS- from the first to the second day.

Animals

The influence of colostral leukocytes on the immune system of the neonatal calf. I. Effects on lymphocyte responses.

The influence of colostral leukocytes on lymphocyte counts in the blood of calves and on lymphocyte responses, in particular the Concanavalin A-induced blastogenic response in vitro and the formation of antibodies against sheep erythrocytes, was investigated for four weeks postnatum using four experimental groups. The calves received either complete colostrum (COL+, n = 16), cell-depleted colostrum (COL-, n = 16), colostral cell-supplemented milk substitute (MS+, n = 7) or pure milk substitute (MS-, n = 6) during their first three days of life. In contrast to the calves fed with cell-depleted colostrum (COL-) the calves fed with complete colostrum (COL+) showed no decrease of lymphocyte numbers in the blood on the second day of life, uniform blastogenic responses to two different Concanavalin A concentrations, slightly enhanced antibody formation against sheep erythrocytes and a high spontaneous proliferation of mononuclear cells during the first week of life. In the calves fed with milk-substitute supplemented with colostral cells (MS+) a higher blastogenic response to Concanavalin A and an intensified formation of antibodies against sheep erythrocytes was observed as compared to the MS- calves. A passage of vital colostral lymphocytes through the intestinal wall is postulated. They seem to stimulate and regulate the blastogenic response and enhance the T-helper cell-dependent formation of antibodies against sheep erythrocytes in calves.

Animals

[The Alagille syndrome in an adult].

Severe bleeding from gastric varices occurred in an 18-year-old male known, since he was three years old, to have liver cirrhosis with beginning protal hypertension. The cause of the portal hypertension was chronic cholestasis due to hypoplasia of the interlobular bile ducts. There was also peripheral pulmonary stenosis with pulmonary hypertension (106 mmHg systolic), and a posterior embryotoxon (arcus juvenilis). Skeletal anomalies, particularly of the vertebrae, and a striking facial dysmorphism provided the features of arteriohepatic dysplasia, Alagille's syndrome, an autosomal dominant disease generally becoming manifest during childhood. As the patient's liver functions were only slightly abnormal, liver transplantation was not indicated and a shunt operation performed. A septicaemia developed on the third postoperative day after an at first complication free course, and he died from right-heart failure.

Abnormalities, Multiple