Low molecular weight heparin (tinzaparin) vs. placebo in the treatment of mild to moderately active ulcerative colitis.

BACKGROUND: Heparin has anti-inflammatory and immunomodulatory activity which may be of therapeutic benefit in the treatment of ulcerative colitis. AIM: To test whether low molecular weight heparin, given subcutaneously, would provide a significant therapeutic response compared with placebo in the treatment of mild to moderate ulcerative colitis. STUDY DESIGN: A prospective, double-blind, randomized, placebo-controlled, multi-centre trial comparing tinzaparin 175 anti-Xa IU/kg/day (innohep, LEO Pharma) subcutaneously for 14 days followed by tinzaparin 4500 anti-Xa IU/day subcutaneously for 28 days with placebo, administered subcutaneously once daily for up to 42 days. The primary outcome measure was the mean change in colitis activity from baseline to the end of study treatment assessed by the sum of scores of stool frequency, rectal bleeding, sigmoidoscopic appearance and histology. Secondary outcome measures included changes in individual activity indices and laboratory parameters. Patients were assessed at weekly intervals for 6 weeks and within 1 week of completing treatment. RESULTS: One hundred patients with active ulcerative colitis (up to six bloody stools per day, no fever, no tachycardia or systemic disturbances) were randomized. Forty-eight received tinzaparin and 52 received placebo. The difference in the mean percentage change in colitis activity from baseline to end of treatment (tinzaparin-placebo) was not statistically significant (P = 0.84). There was no difference between tinzaparin and placebo in any secondary outcome measure. One major bleed (rectal), occurred in a patient receiving placebo. CONCLUSION: This is the largest trial to date of heparin in ulcerative colitis. The results show no benefit of low molecular weight heparin over placebo in mild to moderately active ulcerative colitis.

Helicobacter pylori detection in human biopsies: a competitive PCR assay with internal control reveals false results.

A polymerase chain reaction assay (PCR) for the diagnosis of Helicobacter pylori in human gastric biopsies was developed. To prevent false-negative results while performing PCR on human tissues, an internal control is necessary. Primer set ACT1-ACT2 which specifically amplifies a 542-bp fragment of the 16S rRNA gene of H. pylori was used. dUTP and hot-start were used to prevent false-positives from carryover of previous products and avoid non-specific extension products. A competitive internal control DNA fragment was constructed to detect the presence of inhibitors. Biopsies from 101 unselected patients with gastric symptoms were tested. PCR results were compared with results from microscopy of histological sections and conventional culturing for H. pylori. Forty-two percent of the biopsies were found to contain compounds inhibiting the PCR. The addition of the internal control assures the performance of the PCR assay and is an important quality control parameter.

Effect of intravenous infusion of omeprazole and ranitidine on twenty-four-hour intragastric pH in patients with a history of duodenal ulcer.

The effect on intragastric pH of two different dose regimens of continuous intravenous infusion of omeprazole (4 or 8 mg/h after a bolus of 80 mg), and ranitidine (0.25 mg/kg/h after a bolus of 50 mg) was studied in 10 patients with duodenal ulcer disease in symptomatic remission. The pH was monitored over 24-hour periods during fasting in a cross-over, randomised design including a baseline period. With the high omeprazole dose it was possible to maintain a pH > or = 4 in all patients but 1 and 6 of the patients also maintained a pH > or = 6. The lower dose of omeprazole seemed to be somewhat less effective. Continuous infusion of ranitidine was as efficient as the higher omeprazole infusion although with a tendency to decreased pH levels towards the end of the 24-hour period. Thus, in order to obtain consistently high pH levels of 4-6 over a prolonged period a continuous infusion of omeprazole, an 80-mg bolus plus a continuous infusion of 8 mg/h seem to be needed.

Prophylactic effects of olsalazine v sulphasalazine during 12 months maintenance treatment of ulcerative colitis. The Danish Olsalazine Study Group.

In a Danish multicentre trial we compared the relapse preventing effects of olsalazine and sulphasalazine in patients with ulcerative colitis over a 12 month treatment period. Two hundred and twenty seven patients (118 men) with at least two previous attacks of ulcerative colitis were randomly allocated according to a prearranged treatment schedule to olsalazine 500 mg bd or sulphasalazine 1 g bd in a double blind, double dummy fashion. One hundred and ninety seven patients completed the trial. The relapse rate after 12 month in the olsalazine group was 46.9% v 42.4% in the sulphasalazine group with a 95% confidence interval for the difference in proportions of -9% to 18%. Seven per cent of the patients were withdrawn from the trial because of adverse drug reactions and these were equally distributed between the two groups.

[A case of adiposis dolorosa--Dercum's disease]. / Et tilfaelde af adiposis dolorosa--morbus Dercum.

Adiposis dolorosa or Dercum's disease consists of a painful progressive localized state of obesity with four cardinal symptoms: a) painful circumscribed or diffuse fatty deposits, b) generalized obesity in women usually of menopausal age, c) asthenia, weakness and frequently tendency to fatigue and d) mental phenomena including emotional instability, depression, epilepsy, mental confusion and true dementia. Only a few cases in men have been described. The pain may be treated with intravenous administration of lignocaine or oral mexitil while no causal treatment is known. An illustrative case is reported.

Effect of intravenous omeprazole on twenty-four-hour intragastric pH in patients with a history of peptic ulcer. Comparison of two four-dosage regimens.

To study the effect of intravenously given omeprazole on the 24-hour gastric secretion, 9 male patients with previously endoscopic proven duodenal ulcer disease were studied. Two four-dose regimens only differing in loading doses were compared. The study showed that 40 mg omeprazole, administered intravenously 4 times a day, is able to keep the gastric pH above 4 in 85% of the 24-hour study period and in 65% of the time pH was above 6. The corresponding values from the baseline period were 10 and 6%. There was no additional effect by a larger loading dose.

65 zinc absorption in patients with insulin-dependent diabetes mellitus assessed by whole-body counting technique.

The gastrointestinal absorption of zinc was measured in patients with insulin-dependent diabetes mellitus. The concentration of zinc in serum was similar to healthy individuals. However the urinary excretion rate of zinc relative to the creatinine excretion, was approximately doubled (p less than 0.001) in the diabetics. The absorption of 65Zn tended to be lower in diabetics, but did not reach the level of statistical significance (retention percent 30.6 versus 42.6 (p greater than 0.10). A hypothesis of intracellular zinc depletion with time in insulin-dependent diabetics is proposed.

Distribution of serum zinc between albumin and alpha 2-macroglobulin in patients with different zinc metabolic disorders.

The distribution of total serum zinc between serum albumin and alpha 2-macroglobulin was evaluated by ultracentrifugation in patients with cirrhosis of the liver, insulin-dependent diabetes mellitus, or chronic renal failure. We found that the alpha 2-macroglobulin bound zinc fraction amounts to approximately 6 and 5% of the total serum zinc in patients with cirrhosis of the liver and diabetes mellitus, which corresponds to the distribution in controls. In patients with chronic renal failure, however, the alpha 2-macroglobulin-bound zinc fraction only constitutes approximately 2%, which is significantly less than in controls. Our findings indicate that most of the total serum zinc is bound to serum albumin.

Relationship between serum CK-MB-estimated acute myocardial infarct size and clinical complications.

The relationship between acute myocardial infarct (AMI) size and morbidity and mortality was estimated in 317 patients followed for one year or until death. Infarct size was estimated from serum creatine kinase (CK)-MB levels measured thrice daily. The incidence of ventricular arrhythmias, congestive heart failure, cardiogenic shock, and the cardiac performance during exercise were studied during hospitalization. Hospital mortality and one-year mortality were registered. A positive correlation was found between serum CK-MB-estimated infarct size and the incidence of ventricular arrhythmias (p less than 0.05). Patients with congestive heart failure and patients with cardiogenic shock had significantly larger infarct size than patients without (p less than 0.05-0.01), although there was a substantial overlap. During exercise test the rise in systolic blood pressure correlated negatively and the rise in heart rate correlated positively to estimated infarct size (p less than 0.01). Both hospital mortality and one-year mortality were significantly related to estimated infarct size (p less than 0.01). Thus the infarct size, as estimated from serum CK-MB, seems to be of importance for development of the most common and serious complications after AMI.

Hyperzincuria in insulin treated diabetes mellitus--its relation to glucose homeostasis and insulin administration.

In order to elucidate some pathogenic factors of diabetic hyperzincuria we studied 60 adult insulin treated diabetic out-patients (40 males and 20 females), all with normal serum creatinine concentrations and absence of proteinuria during a 24-h period. Diabetic males and females both had significantly (p less than 0.01) increased zinc excretion rates (1.14 +/- 0.06 (S.E.M.) mumol/mmol creatinine and 1.37 +/- 0.10 mumol/mmol creatinine) compared with normal males and females (0.55 +/- 0.06 and 0.48 +/- 0.08, respectively). The urinary zinc excretion rate correlated positively with the degree of glycosuria (r = 0.36, p less than 0.01), but was not associated with the duration of the disease. However, serum zinc levels gave no evidence of a state of zinc depletion in these patients. It was calculated that zinc originating from a diabetic bone loss and the exogenous insulin administration accounted for only a small part of the hyperzincuria. Compensatory hyperabsorption and/or increased zinc content in the diabetic diet may therefore serve to explain the lack of zinc depletion in the presence of hyperzincuria.

Zinc metabolism in patients with chronic renal failure during treatment with 1.25-dihydroxycholecalciferol: a controlled therapeutic trial.

Serum concentrations and urinary excretion rates of zinc, calcium and magnesium were measured in 17 patients with chronic renal failure before and after treatment with 1.25(OH)2D3 or vitamin D3. Initially the patients showed hypozincemia (P less than 0.001), hypocalcemia (P less than 0.01) and hypermagnesemia (P less than 0.01). The distribution of zinc between albumin and alpha 2-macroglobulin was calculated. The reduction in serum zinc was due to a fall in the albumin bound fraction, which could not be explained by a reduction in the serum albumin concentration. During treatment with 1.25(OH)2D3 no significant changes in serum and urinary levels of zinc and magnesium were observed, while the serum concentrations and urinary excretion rates of calcium increased. It is concluded that 1.25(OH)2D3 and vitamin D3 are of minor importance in the intestinal absorption of zinc and magnesium.

Zinc depletion in alcoholic liver diseases.

Liver and serum zinc concentrations were investigated in 24 patients with alcoholic liver diseases, 22 patients with non-alcoholic liver diseases, and in 36 control subjects. The liver samples were obtained by percutaneous liver biopsies, and the ratio of hepatocytes to fibrous connective tissue was estimated. The liver zinc concentration was expressed in relation to the amount of hepatocytes, and the serum zinc concentration was calculated in relation to total, albumin-, and alpha 2-macroglobulin-bound serum zinc. The results show that the liver zinc concentration was decreased in patients with alcoholic liver diseases (P < 0.01), in contrast to in patients with non-alcoholic liver diseases. Albumin-bound serum zinc was decreased in both groups (P < 0.001). The results indicate that alcoholic liver damage is associated with zinc deficiency.

Influence of a non-steroid antirheumatic drug on serum and urinary zinc in healthy volunteers.

The effects of a commonly used non-steroid anti-inflammatory drug (naproxen) on zinc metabolism was studied in healthy volunteers. A significant increase in the urinary zinc excretion rate was found during treatment with naproxen, with a mean increase in the order of 35%. At the end of the treatment period the urinary zinc excretion fell towards normal, and after withdrawal of naproxen the urinary excretion rate became normal. During the treatment period the serum zinc concentration was virtually unchanged, being comparable to the initial and post-treatment values. The mechanism by which naproxen induces hyperzincuria is not known. Protein binding interaction or a direct renal action of naproxen implying a decrease in the maximum tubular reabsorption capacity (Tmax) would lead to an increase in zinc excretion. Prolonged studies in patients with rheumatoid arthritis, both untreated and treated with prostaglandin inhibitors, are needed however in order to evaluate the possibility of a zinc depletion.

Hypozincaemia after jejuno-ileal bypass.

Serum zinc, albumin, alpha 2-macroglobulin, calcium, and magnesium were measured in 39 jejuno-ileal shunt-operated patients. The binding of serum zinc to albumin and alpha 2-macroglobulin were calculated. The results demonstrate that the patients as a group had a highly significant hypozincaemia (P less than 0.001), caused by a reduction of the albumin-bound serum zinc (P less than 0.001). Furthermore, the patients showed hypocalcaemia (P less than 0.001) and hypomagnesaemia (P less than 0.001). The findings indicate that patients with jejuno-ileal bypass for gross obesity develop deficiency of the divalent cations.