Reduced metabolic efficiency in patients with Crohn's disease.

Malnutrition is frequently seen in patients with inflammatory bowel disease, and parenteral or enteral nutrition is considered essential in this patient group. However, many patients with Crohn's disease have difficulties in gaining weight in response to overfeeding, suggesting reduced energy retention. Substrate utilization and nutrient balances as well as changes in body composition were followed in 10 patients with Crohn's disease immediately in the course of remission on low-dose steroid treatment, during an eight-day period of continuous enteral nutrition at constant (protocol 1:1.5-fold basal energy expenditure) and increasing (protocol 2:0.5- to 2.0-fold basal energy expenditure) nutrient supply. Energy, substrate, and nitrogen balances all became positive in response to overfeeding. However, fat was predominantly oxidized at an infusion rate of 1.2 g/kg body wt/day, whereas carbohydrates and proteins were effectively stored. A positive energy balance was reached at an energy infusion rate exceeding 31 kcal/kg body wt/day and corresponding substrate supplies of 1.6, 1.7, and 1.1 g/kg body wt/day for carbohydrates, fat, and protein, respectively. Nitrogen balance normalized at a supply of 0.14 g/kg body wt/day, which also reduced myofibrillar protein breakdown. Considering the relative contributions made by these nutrients in the diets, an accumulation of carbohydrates and protein but a depletion in fat became evident from nutrient balances. In fact, body weight increased by 0.12 kg/day, which was explained by an increased extracellular (+0.18 kg/day) and body cell mass (+0.04 kg/day) at reduced fat mass (-0.10 kg/day). Concomitantly, plasma T3 and insulin secretion both increased, whereas sympathetic nervous system activity decreased with overfeeding. This is contrary to data observed in healthy subjects.(ABSTRACT TRUNCATED AT 250 WORDS)

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)

Metabolic responses to lipid infusions in patients with liver cirrhosis.

Energy expenditure, whole body substrate oxidation rates and arterial substrate concentrations were measured in 14 patients with liver cirrhosis and 13 control subjects before and during sequential infusions of a long chain (LCT) or a medium chain triglyceride emulsion (MCT) without and with concomitant insulin plus glucose infusions. Resting energy expenditure, basal substrate oxidation rates and the arterial concentrations of glucose, lactate, triglycerides and ketones were normal, whereas plasma free fatty acids and glycerol were both increased in patients with liver cirrhosis. The arterial plasma triglyceride and free fatty acid concentrations as well as whole body lipid oxidation rate rose in response to LCT in both groups and the maximum lipid oxidation rate was 1.1 or 1.3 mg/kg fat free mass x min in controls and in cirrhotics, respectively (n.s.). Concomitantly, glucose oxidation rate fell to 65% of basal values in controls (p < 0.01), but remained nearly unchanged in the cirrhotic group (89% of the basal value; n.s.). The increase in plasma ketones was reduced to 67% of control values in liver cirrhosis (p < 0.01). Only a slight effect on energy expenditure was observed in both groups. When compared to controls, liver cirrhosis impaired insulin-induced increases in glucose disposal (-30%, p < 0.01) and in non oxidative glucose metabolism (-93%, p < 0.01). Concomitantly, normal increases in energy expenditure, glucose oxidation rate and the arterial plasma lactate concentrations and normal decreases in lipolysis, lipid oxidation and ketogenesis were observed in patients with liver cirrhosis. When lipids were given together with glucose, energy expenditure and lipid oxidation increased in controls, but glucose was the preferred fuel oxidised and lipid-induced thermogenesis was reduced in the cirrhotic group. Using a 50% MCT-emulsion, plasma free fatty acid concentrations further increased, but energy expenditure and lipid oxidation remained unchanged in both groups and further increases in plasma ketones were only observed in controls. Infusing glycerol in a subgroup of patients showed no thermogenic effect and a reduced glycerol clearance in liver cirrhosis.

Lipoprotein (a): a risk factor for retinal vascular occlusion.

The protein moiety of lipoprotein (a) consists of apoB-100 and apolipoprotein (a). Lipoprotein (a) is an independent risk factor for premature atherosclerosis. Apolipoprotein (a) and plasminogen are structurally homologous. Through interference with the fibrinolytic system, lipoprotein (a) may act as a thrombogenic factor. In the present study, we determined lipoprotein (a) concentrations in 84 patients (60 men and 24 women) with retinal vascular occlusion (RVO) and in 2 groups of healthy volunteers (n = 40 and 46). In all, 29% of the patients had Lp (a) levels of above 300 mg/l. In the two reference groups, only 10% and 9% of the subjects exceeded this level. According to the chi-square test, the association between Lp (a) levels and RVO was significant. Lp (a) concentrations did not differ between patients with arterial occlusion and those with venous occlusion. No difference in the total cholesterol, triglyceride, or LDL-cholesterol values was observed between patients and controls. We therefore conclude that Lp (a) represents an independent risk factor for RVO.

[Lipolysis and lipid oxidation of weight stable patients with malignant tumors of the digestive system]. / Lipolyse und Lipidoxidation bei gewichtsstabilen Patienten mit malignen Tumoren des Verdauungstraktes.

Tumor-caused weight loss is frequently associated with a high rate of lipolysis and fat oxidation. In order to differentiate the effect of weight-loss from the tumour-dependent regulation of fat metabolism, we studied weight-stable and well nourished patients (ideal body weight 109 +/- 4% (+/- SEM), body mass index 25.1 +/- 0.9 kg/m2). Parameters of lipolysis (glycerol-, fatty acid concentrations) and the calorimetric determined fat oxidation rate of five male tumor patients were examined before and during an euglycaemic insulinclamp (0.2 mU insulin/kg/min). Concomitant with a high rate of lipolysis (glycerol concentration 112 +/- 20 mumol/l, free fatty acid concentration 0.72 +/- 0.13 mmol/l) and fat oxidation (60% of energy expenditure) there was a low normal insulin level (5.9 +/- 0.5 mU/l). Insulin reduced lipolysis and fat oxidation and stimulated glucose oxidation. Weight-stable tumor patients have a high basal rate of lipolysis and fat oxidation; yet the insulin dependent regulation of the fat metabolism is intact, as we have already shown for weight-losing cancer patients.

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.

[What is the role of nutrition in Crohn disease? A contribution to the importance of dietary therapy in regional enteritis]. / Welche Rolle spielt die Ernährung beim Morbus Crohn? Ein Beitrag zur Bedeutung der diätetischen Therapie der Enteritis regionalis.

The clinical appearance of Crohn's disease (CD) is especially marked by nutritional deficits and insufficiencies. For a long time the goal of nutritional care was reduced to the readjustment of the nutritional status. The development and clinical use of controlled parenteral nutrition (TPN) and enteral nutritive solutions (EN) did not only emphasize this therapeutical issue, but furthermore showed positive effects on the conservative as well as on the surgical treatment concepts. Therefore today artificial nutritional support is a firm part of therapy in acute, active phases or in the contact of surgical management of CD. This is especially valid in children, where complications in general and growth failure in particular can be reduced. EN is the preferred feeding method in most of the cases, due to a lower complication rate and reduced cost when compared to TPN. The question regarding the importance of nutritional support as primary therapy has also been investigated. The results differ extensively, but point towards the conclusion that patients with solitary small bowel disease do profit from this therapeutical concept. Nevertheless it is unclear, how TPN or EN interfere in the pathophysiology or -biochemistry in this process. A question about reduction e.g. of allergic components of daily diet did stimulate new theories regarding the hypothesis of a possible causal relationship between diet and the pathogenesis of CD. Investigations on dietary habits and daily dietary therapy did not reveal an overall accepted dietary guideline. Nevertheless it seems obvious that dietary counselling has a positive effect on the disease process. It does appear, that today in the acute, active phase as well as in the long term management of Crohn's disease nutritional-care is an important therapeutical method.

[Pathogenesis of alcohol-induced hyperlipidemia: case report of hypertriglyceridemia over 10,000 mg%]. / Pathogenese der alkoholinduzierten Hpyerlipidämie: Fallstudie einer Hypertriglyceridämie über 10,000 mg%.

A 53-year old woman developed excessive hypertriglyceridemia (greater than 10,000 mg/dl) with features of toxic liver damage after prolonged ethanol ingestion. Lipoprotein-lipase-activity was not decreased, apolipoprotein-C-II analysis, as shown by gel-electrophoresis, revealed a regular pattern. Treatment with parenteral nutrition and abstinence of ethanol resulted in a complete normalization of plasma triglycerides after transient remnant-hyperlipidemia. Decrease of triglycerides was accompanied by declining liver enzyme activities. As suggested by unimpaired activity of lipolysis, the extent of hypertriglyceridemia may be explained by a reversible receptor mediated defect of hepatic catabolism, aggravated by hepatic overproduction of triglyceride-rich-particles. Although receptor dysfunction is not yet understood, the transient appearance of remnant particles may be a helpful criteria in diagnosis of ethanol induced hypertriglyceridemia.

Results of a stimulatory therapy of low bone metabolism in osteoporosis with (1-38)hPTH and diphosphonate EHDP. Protocol of study I, osteoporosis trial Hannover.

In contrast to prevention, the therapy of manifest osteoporosis remains a clinically significant problem. So far all therapeutic attempts have yielded unsatisfying results. For this reason we have tried to achieve a positive bone balance by sequential stimulation and inhibition of the osseous metabolism. The therapy consisted of six 14-day courses with 400 units (1-38)hPTH per day and, in addition, starting with the 2nd week of PTH therapy, EHDP 5 mg per kg body weight per day for a total of 2 weeks. Already the initial therapeutic course resulted in a stimulation of decreased bone metabolism which could be documented by an increase in the calcium-47 accretion rate (six patients). An increase of the alkaline phosphatase could be noted (four patients); this, however, did not correlate with the calcium accretion. A positive calcium balance could, nonetheless, only be attained in four of eight patients within this period, while neither the alkaline phosphatase nor the kinetics would allow a prediction of this effect. Changes of the balance coincided with equal changes in the net calcium absorption. The urinary calcium excretion increased temporarily during the therapeutic phase. We were not able to detect an influence on the vitamin D metabolites. Histomorphometric studies did not demonstrate an increase in bone mass in the iliac creast after six therapeutic courses. Nevertheless, progressive deformations of vertebral bodies did not occur. We conclude that already after 2 weeks this therapeutic concept can lead to a stimulation of bone metabolism.

Comparison between simvastatin and bezafibrate in effect on plasma lipoproteins and apolipoproteins in primary hypercholesterolaemia.

The ability of simvastatin, a competitive inhibitor of 3-hydroxy-3-methylglutaryl coenzyme A reductase, to lower lipid levels in 16 patients with primary hypercholesterolaemia was compared with that of bezafibrate in a 16-week, double-blind, parallel, placebo-controlled trial that was continued in an open crossover fashion. Simvastatin was better than bezafibrate at lowering total and low-density lipoprotein (LDL)-cholesterol and apolipoprotein B concentrations (30.4% [p less than 0.001], 37.3% [p less than 0.001], and 37.8% [p less than 0.001] vs 17.0%, 19.6%, and 24.0%, respectively). Both drugs increased the high-density lipoprotein (HDL)-cholesterol and apolipoprotein A-I, but this change was significant only with bezafibrate (p less than 0.05). Bezafibrate and simvastatin reduced triglycerides by 25.6% (p less than 0.001) and 13.7% (p less than 0.05), respectively. Very low-density lipoprotein (VLDL)-cholesterol was significantly reduced only by bezafibrate (44.3%, p less than 0.001). Both drugs were tolerated well and no serious side-effects were noted. The results show that simvastatin was more effective than bezafibrate in lowering total-cholesterol, LDL-cholesterol, and apolipoprotein B, while bezafibrate was better at lowering triglycerides and VLDL-cholesterol and at raising HDL-cholesterol and apolipoprotein A-I.

Accuracy and reproducibility of a quantitative electrophoresis of plasma lipoproteins: interlaboratory comparison and verification by ultracentrifugation.

Fifty-three samples of sera from normal subjects and from patients with type IIa, IIb and IV hyperlipoproteinemia were shipped from Hannover to the collaborative laboratories in Vienna and Mannheim, which participated in the quantification of their lipoprotein fractions based on polyanion precipitation of electrophoretically separated lipoproteins followed by densitometric measurement of alpha-, prebeta- and beta-lipoproteins. Total serum cholesterol and cholesterol calculated from quantified lipoprotein fractions were highly correlated, the correlation coefficients ranged between r = 0.93-0.98. Furthermore, we found a high concordance comparing the beta-, and prebeta- and alpha-cholesterol with data obtained from lipoprotein fractionation and subsequent cholesterol measurement by ultracentrifugation. The obtained correlation coefficients were always higher than r = 0.91. High accuracy and reproducibility of the quantitative lipoprotein electrophoresis justify its recommendation for wide use in the field of clinical chemistry.

[Digestive function of the residual pancreas after partial duodenopancreatectomy for chronic pancreatitis (author's transl)]. / Verdauungsleistung des Restpankreas nach partieller Duodenopankreatektomie wegen chronischer Pankreatitis.

Forty-eight patients with chronic recurrent pancreatitis treated by resection of the head of the pancreas were restudied more than a year post-operatively. In addition to general features such as symptoms, alcohol consumption and work ability, faecal weight, its fat content, fat and fatty acid balance and faecal chymotrypsin were measured. According to the patients' own estimate, late results were good or very good in 70-90%. Faecal fat content and balance indicated high-grade exocrine pancreatic insufficiency in 80 and 90%, respectively. But it was easily controlled by drugs. In a third of the cases there was the need to supplement the diet with medium-chain triglycerides. Its components are satisfactorily absorbed even when the fat utilisation is severely abnormal.

[Drug therapy of hypercholesterinemias (author's transl)]. / Medikamentöse Therapie der Hypercholesterinmien.

Every permanent substantiated primary hypercholesterolemia which does not respond adequately to diet must be treated with drugs. For monotherapy first of all fenofibrate, bezafibrate and nicotinic acid derivatives are suitable for the treatment of adult patients. For supportive therapy colestyramine and colestipol come into consideration as well as beta-sitosterol. D-thyroxine and etiroxate should be reserved for refractory cases. Drug therapy is only given for secondary hypercholesterolemias in justifiable exceptions.

Lowering effect of fenofibrate (procetofene) on lipoproteins in different types of hyperlipoproteinemias.

The effect of 300 mg Fenofibrate daily on serum lipoprotein concentrations was studied for 6 month in 32 subjects with primary familial hyperlipoproteinemias. In summary Fenofibrate lowered already after one month of therapy the mean cholesterol serum concentrations by 20-25% and serum triglyceride concentrations by 40-45%, when compared with placebo therapy. The greatest effectiveness in the lowering of atherogenic lipoproteins was recorded in type IIa and type III, while good effectiveness was experienced in type IV, though with a limitation of an increase of LDL2 at the upper limit of the normal range. In the case of type II b the effectiveness was limited only to VLDL. Moreover Fenofibrate treatment leads to normalization of lipid composition of the lipoproteins. The HDL showed besides an increase of HDL-phospholipids in type II a no further significant changes. That leads to a more favourable antiatherogenic index, i.e. the relation of HDL-chol. : (LDL-chol. + VLDL-chol.), in all types. The results of this study confirmed that Fenofibrate is a well tolerated drug, which efficiently lowers elevated lipoprotein concentrations.

Polymorphism of apolipoprotein E. II. Genetics of hyperlipoproteinemia type III.

Apolipoprotein E from human serum shows a genetic polymorphism determined by two autosomal codominant alleles, Apo En and Apo Ed. Homozygosity for the gene Apo Ed (phenotype Apo E-D) results in primary dysbetalipoproteinemia, but only some individuals with this phenotype develop gross hyperlipidemia (hyperlipoproteinemia type III). Vertical transmission of dysbetalipoproteinemia represents pseudodominance due to the high frequency of the gene Apo Ed. Dysbetalipoproteinemia is already expressed in childhood. To assess the influence of other genes on the expression of hyperlipidemia in phenotype Apo E-D, comparative studies were carried out in kindreds of hypercholesterolemic (group A) and normo- or hypocholesterolemic probands with dysbetalipoproteinemia (group B). This demonstrated the occurrence of familial (non-type III) forms of hyperlipidemia in group A but not in group B kindreds. Distribution of lipoprotein phenotypes in five of the group A kindreds was consistent with the occurrence of familial combined hyperlipidemia. Apo E phenotypes and hyperlipidemia segregated independently. It is concluded that primary dysbetalipoproteinemia is a frequent monogenic variant of lipoprotein metabolism, but not a disease. Coincidence in one individual of genes for this specific dyslipoproteinemia with any of the genes for monogenic or polygenic forms of familial hyperlipidemia results in hyperlipoproteinemia type III. Hence hyperlipoproteinemia type III is caused by at least two non-allelic genes and is a polygenic disorder.