Claes-Henrik Florén

Magnesium Deficiency in IDDM Related to Level of Glycosylated Hemoglobin

Magnesium and potassium were analyzed in plasma, erythrocytes, and urine collected during 24 h and in muscle biopsies from 25 subjects with insulin-dependent, type I diabetes mellitus (IDDM). Magnesium was also measured in mononuclear cells. The results were compared with those of 28 healthy controls, and were also correlated with the degree of diabetic control as estimated by analysis of the level of glycosylated hemoglobin (HbA1c). Subjects with IDDM had significantly lower muscle (P < 0.01) and plasma (P < 0.001) concentrations of magnesium compared with those of healthy controls. The HbA1c levels correlated significantly with the concentrations of magnesium in muscle (r = −0.62, P < 0.001), plasma (r = −0.62, P < 0.001), and mononuclear cells (r = −0.47, P < 0.05). The results indicate that some patients with IDDM have lowered contents of magnesium in striated muscular and/ or plasma, and that those parameters are dependent on the degree of diabetic control.

Ultrasound examination of the small bowel: comparison with enteroclysis in patients with Crohn disease

BackgroundScreening for inflammatory small bowel disease has hereto relied on barium examination, usually performed after duodenal intubation. A noninvasive technique for imaging of the small bowel in such patients would be preferable.MethodsA total of 59 patients were included in the study. A small bowel barium examination (SBE) was performed after duodenal intubation using a barium and air double-contrast technique. Ultrasound (US) of the right lower quadrant was performed with a 3.5- or 5-MHz transducer. The patients fasted overnight.ResultsIn 37 of 39 patients with a normal SBE, US was also normal. In 20 patients, SBE showed lesions compatible with Crohn disease and in 18 of these the US study showed thickening of the bowel wall. One of these patients later tested positive for Yersinia enterocolitica. There were two false-positive and two false-negative US examinations.For detection of inflammatory disease of the small bowel, US was calculated to have a sensitivity of 0.95, specificity of 0.93, accuracy of 0.93, predictive value of a positive test was 0.90, and a predictive value of a negative test was 0.95.ConclusionsUS, therefore, seems to be a reliable method in the workup of patients suspected of having inflammatory small bowel disease. Thereby, US probably can select patients for SBE.

ColoPlus, a new product based on bovine colostrum, alleviates HIV-associated diarrhoea

Objective. HIV-associated diarrhoea occurs in nearly all patients with acquired immunodeficiency syndrome (AIDS) in the developing countries. Diarrhoea is caused by the HIV-related immune dysfunction and is pivotal in the decrease of the helper T-cell (CD4 + ) population. Enteric pathogens in HIV-associated diarrhoea are, for example, Cryptosporidium, Amoeba and Campylobacter species. Bovine colostrum is the first milk the suckling calf receives from the cow. It is rich in immunoglobulins, growth factors, antibacterial peptides and nutrients. It supplies the calf with a passive immunity before its own active immunity is established. ColoPlus is a product based on bovine colostrum and is designed for slow passage through the gastrointestinal tract, as well as having a high nutritional value. The aim of the study was to investigate whether ColoPlus given orally can influence the severe diarrhoea associated with HIV infection. Material and methods. The study was carried out at Braithwaite Memorial Specialist Hospital, Port Harcourt, Nigeria. Thirty patients with HIV-associated diarrhoea were included in the study. The patients were treated with ColoPlus for 4 weeks in an open-labelled non-randomized study, after an observational period of one week. After a post-treatment period of another two weeks, treatment with anti-HIV drugs was started, if deemed appropriate. The effects on the frequency of stool evacuations per day, on body-weight, fatigue, haemoglobin levels and CD4+ counts before (week 1) and after treatment with ColoPlus (week 7) were measured. Results. There was a dramatic decrease in stool evacuations per day from 7.0±2.7 to 1.3±0.5 (±SD), a substantial decrease in self-estimated fatigue of 81%, an increase in body-weight of 7.3 kg per patient and an increase in CD4+ count by 125%. Conclusion. ColoPlus may be an important alternative or additional treatment in HIV-associated diarrhoea.

Lecithin: Cholesterol acyltransferase in liver disease

Lecithin: cholesterol acyltransferase (LCAT) activity in patients with liver disease has been found to be either normal or lower than normal, but no information on LCAT mass in these patients is available. In this study, LCAT mass concentration together with LCAT activity and cholesterol esterification rate were measured in the plasma of 19 patients with cholestatic liver disease and 21 patients with non-cholestatic liver disease. The LCAT mass in plasma correlated positively with serum albumin (r = 0.69, p less than 0.001) and pre-albumin (r = 0.77, p less than 0.001) and negatively with serum bilirubin (r = -0.42, p less than 0.01) and bile salts (r = -0.43, p less than 0.01), thus reflecting the severity of liver disease and liver protein synthesizing capacity. In plasma, LCAT mass concentration also correlated well with LCAT activity (r = 0.88, p less than 0.001) and cholesterol esterification rate (r = 0.73, p less than 0.001), thereby indicating that the decrease of LCAT activity and cholesterol esterification rate in liver disease is primarily a function of decreased LCAT mass.

Helicobacter pylori and CagA seropositivity and its association with gastric and oesophageal carcinoma

Objective. Helicobacter pylori infection is an established risk factor for non-cardia gastric adenocarcinoma. Infection with H. pylori strains harbouring the cagA pathology island may augment this association. H. pylori infection may at the same time reduce the risk for oesophageal carcinoma. However, prospective data on the association between CagA seropositivity and gastric or oesophageal carcinomas are limited. The purpose of this study was to investigate whether CagA seropositivity among H. pylori seropositive subjects is associated with gastric or oesophageal carcinomas. Material and methods. A nested case-control study was performed in the Malmö Preventive Medicine cohort consisting of 32,906 middle-aged subjects. Tumour cases were identified by the Swedish National Cancer Registry. The Western blot method Helicoblot 2.1 was used to detect H. pylori and CagA seropositivity. Results. Non-cardia gastric adenocarcinoma was associated with H. pylori seropositivity, odds ratio 17.8 (95% CI: 4.2–74.8; 67 cases). The odds ratio for CagA seropositivity among H. pylori seropositive subjects was 9.7 (95% CI: 1.5–∞). No significant associations were found between cardia gastric adenocarcinoma and H. pylori or CagA seropositivity among H. pylori seropositive subjects; odds ratios were 1.5 (95% CI: 0.51–4.8) and 2.7 (95% CI: 0.38–∞), respectively (24 cases). Oesophageal adenocarcinoma and oesophageal squamous cell carcinoma were not significantly associated with H. pylori seropositivity or with CagA seropositivity among H. pylori seropositive subjects; the odds ratios associated with oesophageal adenocarcinoma were 0.46 (95% CI: 0.07–2.6) and 0.38 (95% CI: 0.02–24), respectively. Corresponding odds ratios for oesophageal squamous cell carcinoma were 0.44 (95% CI: 0.15–1.2; 37 cases) and 2.0 (95% CI: 0.24–∞), respectively. Conclusions. CagA seropositivity among H. pylori seropositive subjects is a risk factor for non-cardia gastric adenocarcinoma.

Endotoxin, cytokines, and hyperlipidemia

Endotoxin, a class of lipopolysaccharide molecules derived from the gram-negative bacterial cell wall, consists of three regions: the O-specific polysaccharide, the core polysaccharide, and the lipid A (1). The O-specific polysaccharide, which carries the primary antigenicity of the bacteria, is linked to the core polysaccharide that is common to varieties of bacteria. The latter is bound to lipid A, which possesses most of the biologic activities of endotoxin. Endotoxin stimulates many pathophysiologic responses, including fever, activation of the immune system and the complement cascade, disseminated intravascular coagulation, and disturbances in glucose and lipid metabolism.

Flucloxacillin-induced Cholestatic Liver Damage

Two female patients (75 and 68 yr old) developed jaundice 4 and 7 weeks respectively after treatment with flucloxacillin. Liver biopsies showed intrahepatic cholestasis. After cessation of the drug, the liver tests became normal.

Microcalorimetric investigation of metabolism in rat hepatocytes cultured on microplates and in cell suspensions

In the present work, heat production rate in rat hepatocytes has been measured by use of thermopile heat conduction calorimeters. Both hepatocytes cultured in monolayers on microplates and hepatocytes in suspensions were used for microcalorimetric measurements. The highest heat production rate was found in newly cultured cells; thereafter, a gradual decrease was noted. After 1 day of culture, metabolic activity had reached a steady state that lasted about 4 days. A cell-density dependence of heat production was found, both in cell suspensions and in cultured hepatocytes on microplates. Higher cell concentration in the calorimeter ampoule was accompanied by decreasing heat production per cell. The heat output recorded for hepatocytes cultured on microplates (25 X 10(3) cells) was found to be 0.327 +/- 0.13 nW per cell after 24-48 h. Addition of sodium azide and sodium fluoride to tissue culture medium reduced heat production rate in cultured hepatocytes by 60 and 20%, respectively. Recording of heat production with the present calorimetric technique is relatively simple and fast, and offers the possibility to perform measurements in small samples of cultured hepatocytes on microplates, thus allowing long-term as well as repeated measurements on the same cell population.

Bone mineral density in patients with Crohn's disease during long-term treatment with azathioprine

Florén C‐H, Ahrén B, Bengtsson M, Bartosik J, Obrant K (Lund University, Malmö, Sweden). Bone mineral density in patients with Crohns disease during long‐term treatment with azathioprine. J Intern Med 1998; 243: 123–26.

Low density lipoprotein catabolism is enhanced by the cleaved form of alpha-1-antitrypsin

The frequent occurrence of hypocholesterolaemia following inflammatory processes is well known but unexplained. Elevated plasma levels of serine proteinase inhibitors (serpins) and their complexes with target enzymes have been demonstrated in inflammatory, malignant and infectious diseases which are also often accompanied by low plasma cholesterol levels. Under inflammatory conditions, uncomplexed, but cleaved inactive serpins arising from slow deacylation of the serpin-proteinase complex may be present in the circulation. To determine the influence of native and cleaved forms of serpins, such as alpha-1-antitrypsin (AAT), on lipoprotein metabolism, we investigated the effect of these forms on low density lipoprotein (LDL) catabolism in human HepG2 cell line. We have found that the cleaved form of AAT in concentrations from 125 to 2000 nmol l-1 stimulates LDL binding to the HepG2 cells, by up to 49% with a subsequent increase in LDL uptake and degradation of up to 79 and 65% respectively. Native AAT was also found to increase LDL binding and internalization by 20-25%, independently of the amount of AAT added, an effect most probably due to the cleaved form of AAT produced by local proteolysis of native AAT incubated in the cell culture. Moreover we have shown that the cleaved form of AAT interacts with LDL in vitro, and that such an interaction abolishes AAT ability to stimulate LDL binding and internalization. This study for the first time describes the ability of the cleaved form of AAT to stimulate LDL binding and internalization in HepG2 cell culture, and provides evidence that hypocholesterolaemia occurring during inflammatory processes may be mediated by cleaved forms of serpins.