Increasing fecal butyrate in ulcerative colitis patients by diet: controlled pilot study

Topical butyrate has been shown to be effective in the treatment of ulcerative colitis (UC). Butyrate is derived from colonic fermentation of dietary fiber, and our aim was to study whether UC patients could safely increase the fecal butyrate level by dietary means. We enrolled 22 patients with quiescent UC (mean age, 44 years; 45% women; median time from last relapse, 1 year) in a controlled pilot trial lasting 3 months. The patients were instructed to add 60 g oat bran (corresponding to 20 g dietary fiber) to the daily diet, mainly as bread slices. Fecal short-chain fatty acids (SCFAs) including butyrate, disease activity, and gastrointestinal symptoms were recorded every 4 weeks. During the oat bran intervention the fecal butyrate concentration increased by 36% at 4 weeks (from 11 +/- 2 (mean +/- SEM) to 15 +/- 2 micromol/g feces) (p < 0.01). The mean butyrate concentration over the entire test period was 14 +/- 1 micromol/g feces (p < 0.05). Remaining fecal SCFA levels were unchanged. No patient showed signs of colitis relapse. Unlike controls, the patients showed no increase in gastrointestinal complaints during the trial. Yet patients reporting abdominal pain and reflux complaints at entry showed significant improvement at 12 weeks that returned to baseline 3 months later. This pilot study shows that patients with quiescent UC can safely take a diet rich in oat bran specifically to increase the fecal butyrate level. This may have clinical implications and warrants studies of the long-term benefits of using oat bran in the maintenance therapy in UC.     

Progression of cardiomyopathy after liver transplantation in patients with familial amyloidotic polyneuropathy, Portuguese type

BACKGROUND: Transthyretin amyloidosis is today an accepted indication for orthotopic liver transplantation (OLT). For several mutations progression of the cardiomyopathy has been observed after OLT. The aim of this study was to assess the course of cardiac involvement in Swedish familial amyloidotic polyneuropathy (FAP), Portuguese type, after OLT. By comparison of the echocardiographic findings before OLT with those obtained after, the course of the heart involvement was followed. METHODS: Twenty-three patients, who had undergone OLT and were examined with echocardiography 1-12 months before OLT, were available for the study. Twenty-one patients were examined 12-27 months after OLT, and 12 were re-examined 52-71 months after OLT. Two-dimensional and M-mode echocardiography were performed in accordance with the standards of the American Society of Echocardiography. RESULTS: A significantly increased septal and left ventricular posterior wall thickness and a significantly increased left atrial dimension was observed at the post-OLT examinations, indicating a progression of the amyloid heart disease. This increase of the cardiac involvement was neither correlated to waiting time for OLT or to pre-operative signs of cardiomyopathy. CONCLUSIONS: Even though the production of the amyloidogenic-mutated transthyretin is stopped by OLT, the cardiomyopathy may progress after the operation even for the Portuguese type of FAP. The increase of the septal and left ventricular posterior wall thickness after OLT is not restricted to patients with signs of left ventricular hypertrophy before the transplantation. The findings have important implications for the follow-up of FAP patients after OLT.     

Inhibition of thrombin generation by the oral direct thrombin inhibitor ximelagatran in shed blood from healthy male subjects

Ximelagatran, an oral direct thrombin inhibitor, whose active form is melagatran, was studied using a model of thrombin generation in humans. Healthy male volunteers (18 per group) received ximelagatran (60 mg p.o.), dalteparin (120 IU/kg s.c.) or a control (water p.o.). Shed blood, collected after incision of the forearm with standardised bleeding time devices at pre-dose, and at 2, 4 and 10 h post-dosing, was analysed for markers of thrombin generation. Statistically significant reductions (p < 0.05) in levels of prothrombin fragment 1+2 (F1+2) and thrombin-antithrombin complex (TAT) in shed blood were detected at 2 and 4 h post-dosing in both the ximelagatran and dalteparin groups. Shed blood F1+2 and TAT levels had returned to pre-dose levels at 10 h post-dosing. Using a shed blood model, we demonstrate that the reversible thrombin inhibitor melagatran and, therefore, oral administration of ximelagatran, inhibits thrombin generation in humans after acute activation of coagulation.     

Limited value of routine microbiological diagnostics in patients hospitalized for community-acquired pneumonia

Current guidelines recommend microbiological diagnostic procedures as a part of the management of patients hospitalized for community-acquired pneumonia (CAP), but the value of such efforts has been questioned. Patients hospitalized for CAP were studied retrospectively, focusing on the use of aetiological diagnostic methods and their clinical impact. Adult patients, without known human immunodeficiency virus infection, admitted to hospital for CAP during 12 months, were evaluated with regard to the importance of aetiological diagnosis for tailoring antibiotic therapy, antibiotic-associated diarrhoea, Clostridium difficile disease, length of hospital stay and mortality. Of the 605 studied patients, 482 (80%) were subjected to Mycoplasma pneumoniae and/or respiratory virus serology and/or cultures of blood and/or sputum. They had a better prognosis than patients not subjected to microbiological diagnostics (mortality within 3 months was 9% vs 24%, p = 0.001), apparently reflecting differences in general health (e.g. less dementia diagnosis) but not the outcome of diagnostics. A presumptive aetiology was obtained only in 132 of the 482 patients, Streptococcus pneumoniae and M. pneumoniae being the most common agents (in 49 and 36 patients, respectively). Establishing an aetiological diagnosis had no impact on the number of in-hospital changes of therapy, on the proportion of new regimens having a narrower antimicrobial spectrum than the initial one or on the outcome. Therapy was changed to a drug directed specifically against the identified pathogen in only 16 out of these 132 patients and again without any overall improvement in the outcome variables. In a setting with a low frequency of antibiotic-resistant respiratory tract pathogens current routine microbiological diagnostics were found to be of limited value for the clinical management of patients hospitalized for CAP. Improved diagnostics in CAP are urgently needed, as establishing an aetiological diagnosis carries a potential for optimizing the antibiotic therapy.     

Carotid artery endarterectomy solely based on duplex scan findings

The purpose of this study was to review experience with carotid artery surgery based on findings obtained solely from duplex scanning with special regard to unexpected findings during surgery and the early outcome. From January 1993 through December 1999, 271 consecutive patients underwent 287 carotid endarterectomies (CEAs), 229 (80%) of which were performed solely based on duplex scan findings. During the study period 5,932 carotid artery duplex scans were performed in 4,466 patients. Of 589 patients with internal carotid artery (ICA) stenosis 70%, 246 underwent CEA compared to 25 of 156 with 50-69% ICA stenosis. The indications for CEA were transient ischemic attack (TIA) in 88 (30.7%), amaurosis fugax in 60 (20.9%), previous stroke in 91 (31.7%) and asymptomatic disease in 48 (16.7%) cases. There were no statistically significant differences between the groups operated on with and without preoperative angiography with respect to the indications for surgery, associated risk factors, or the degree of stenosis on the contralateral side. In patients undergoing surgery without angiography, there were no unexpected findings that influenced the performance of surgery, in all except 1. There were no significant differences in perioperative morbidity and mortality in patients undergoing surgery with and without conventional angiography. The combined mortality and major stroke rates were 3.4% and 2.2%, respectively. It is concluded that CEA can safely be performed without preoperative angiography in cases with conclusive duplex scan findings.     

Postradiation volume changes in gamma unit-treated cerebral arteriovenous malformations

Postradiation changes in angiographically determined nidus volume were quantitatively studied in 22 arteriovenous malformation (AVM) cases treated by gamma unit radiosurgery. The postradiosurgical decrease was statistically significant by post-treatment year 2 (p < .05). In children, AVMs tended to be obliterated more quickly than in adults. Volume reduction was more rapid in nidi receiving 25 Gy or more than in those receiving less than 25 Gy (p < .01). However, there were no significant differences in nidus volume decrease between these two dose groups at the second or third postradiosurgical year. Dose response curves were obtained 1, 2, and 3 years following treatment.     

SIN-1 partially and RGDS totally counteracts platelet aggregation as assessed in vitro by two independent whole blood methods

The cyclic GMP stimulant SIN-1 and the GP IIB/IIIA receptor antagonist RGDS were compared with regard to platelet antiaggregatory effects as measured in vitro by filtragometry and by whole blood aggregometry. In filtragometry platelet aggregation is measured as the time to partial occlusion of a filter in the test unit. β-thromboglobulin concentrations increased over the filter (p<0.002) indicating that in filtragometry part of the mechanism of aggregation could be platelet activation across the filter. In whole blood aggregometry platelet aggregation is induced by a chemical stimulant. As tested in blood from healthy volunteers, linear dose-effect relations were found with both methods, for SIN-1 in the 10⁻⁷–10⁻⁶ M range (p<0.02, filtragometry and p<0.05, whole blood aggregometry) and for RGDS in the 10⁻⁵–10⁻⁴ M range (p<0.0001, filtragometry and p<0.02, whole blood aggregometry). At the highest dose RGDS totally counteracted platelet aggregation in both test systems. Maximal SIN-1 platelet antiaggregatory effects were less (p<0.04, filtragometry and p<0.01, whole blood aggregometry) than for RGDS. SIN-1 concentrations in the 10⁻⁴ M range had no further antiaggregatory effects.

In conclusion, with two principally different methods for the assessment of whole blood platelet aggregation, SIN-1 was found to be a partial antagonist while RGDS a total antagonist.     

Monosodium glutamate: increased neurotoxicity after removal of neuronal re-uptake sites

Microinjections of monosodium glutamate (MSG; 300 μg/0.5 μl) into the hippocampus of the adult rat result in only marginal damage to local neurons. Perforant path transections, removing glutamatergic afferents to hippocampal granule cells, make the latter markedly more vulnerable to a subsequent MSG injection. The principle of modulating toxic effects of MSG by interfering with its neurotransmitter role may have significant impact on our understanding of human neurodegenerative disorders.