Microencapsulated sodium butyrate reduces the frequency of abdominal pain in patients with irritable bowel syndrome.

AIM: Abdominal pain, defaecation disorder and change of bowel habit are the commonest symptoms of irritable bowel syndrome (IBS). The effect of microencapsulated sodium butyrate (MSB) was assessed on the severity of symptoms in patients with IBS. METHOD: Sixty-six patients treated with one of the standard pharmacological therapies for at least 3 months were included in the study. They were randomized to receive MSB as a supplemental treatment to standard therapy or to receiving a placebo. Previous pharmacological therapy was continued throughout the study in both arms. Clinical evaluation was performed at baseline, 4 and 12 weeks. Each assessment was documented by a validated visual analogue score questionnaire measuring the severity of selected clinical symptoms, a closed-end questionnaire measuring the frequency of selected clinical symptoms and a single closed-end question measuring the subjective improvement of symptoms. RESULTS: After 4 weeks there was a significant decrease of pain during defaecation in the MSB group which extended to improvement of urgency and bowel habit at 12 weeks. Reduction of abdominal pain, flatulence and disordered defaecation was not statistically significant. CONCLUSIONS: MSB as a supplemental therapy can reduce the frequency of selected clinical symptoms in patients with IBS, without significant influence on reducing symptom severity.

Pouchitis may increase the risk of dysplasia after restorative proctocolectomy in patients with ulcerative colitis.

AIM: Dysplasia of the pouch mucosa after restorative proctocolectomy is rare. The aim of this study was to establish whether there is a correlation between pouchitis and dysplasia. METHOD: A group of 276 patients treated for ulcerative colitis by restorative proctocolectomy between 1984 and 2009 was analysed. The presence or absence of pouchitis and dysplasia within the pouch was evaluated. RESULTS: Inflammation was diagnosed in 66 (23.9%) patients, low-grade dysplasia in five (1.8%), high-grade dysplasia in three (1.1%), and cancer in one patient (0.4%). The prevalence of low-grade dysplasia was significantly higher in patients with inflammation than in those without (P < 0.04). High-grade dysplasia was significantly more frequent in pouchitis than in non-inflamed pouches (P < 0.01). Logistic regression analysis suggested that the occurrence of mucosal inflammation increased the risk of low grade dysplasia. CONCLUSION: Patients with chronic pouchitis are at risk of dysplasia and require surveillance of the pouch.

Telomeres, the nucleolus and aging.

Reactivation of telomerase in cultured human cells extends their replicative life span beyond the Hayflick limit. How telomere shortening triggers cell senescence and whether it contributes to aging in vivo are under investigation. Studies in yeast have revealed another site critical to cellular aging: the nucleolus. The accumulation of ribosomal DNA circles is a cause of aging in this organism. The possible relevance of this mechanism to human aging is also being considered.

Dyskeratosis congenita, telomeres and human ageing.

As normal humans age, telomeres shorten in tissues that contain dividing cells, and this has been proposed both as a cause of ageing and as a tumor-suppressor mechanism. The surprising finding that cells from individuals with the rare inherited disorder dyskeratosis congenita (DKC) have reduced levels of telomerase and shortened telomeres might provide the first direct genetic test of the function of telomeres in intact humans.

Structural analysis of hepatitis B surface antigen by monoclonal antibodies.

A method has been developed for the analysis of hepatitis B surface antigen (HBsAg) antigenic structure at the molecular level that creates "fingerprints" or "signatures" of various hepatitis B viral (HBV) strains. This technique employs high affinity IgM and IgG monoclonal antibodies (anti-HBs) directed against distinct and separate determinants on HBsAg. In performing this antigenic structural analysis, separate binding curves for different monoclonal anti-HBs are generated by measuring immunoreactivity in serial dilutions of HBsAg-positive serum by radioimmunoassay. Since the HBsAg concentration in serum is unknown, the binding profiles of groups of samples are aligned by an iterative least-squares procedure to generate the numerical signature characteristic of the viral strain. The numerical signatures are then displayed on a computer-graphic plot. The signature profiles of HBsAg subtypes are a true reflection of their antigenic structure, and in vertical and horizontal transmission studies the molecular characteristics of the viral epitopes are conserved. By signature analysis we found substantial antigenic heterogeneity among the ayw3 strain both in the U.S. and France, as well as in populations of the Far East and Africa. Populations in Ethiopia, Gambia, and the Philippines were infected with two antigenically distinct HBV strains. In some newly identified HBV strains, it was found that epitopes identified by some monoclonal antibodies were absent or substantially reduced, which suggested that a genetic mutation may have occurred. Thus this study suggests that there is far more antigenic heterogeneity in HBV than previously recognized. These variants are antigenically distinct from each other at the epitope level, and were heretofore unrecognized by polyvalent anti-HBsAg antibodies.

Mutations in the WRN gene in mice accelerate mortality in a p53-null background.

Werner's syndrome (WS) is a human disease with manifestations resembling premature aging. The gene defective in WS, WRN, encodes a DNA helicase. Here, we describe the generation of mice bearing a mutation that eliminates expression of the C terminus of the helicase domain of the WRN protein. Mutant mice are born at the expected Mendelian frequency and do not show any overt histological signs of accelerated senescence. These mice are capable of living beyond 2 years of age. Cells from these animals do not show elevated susceptibility to the genotoxins camptothecin or 4-NQO. However, mutant fibroblasts senesce approximately one passage earlier than controls. Importantly, WRN(-/-);p53(-/-) mice show an increased mortality rate relative to WRN(+/-);p53(-/-) animals. We consider possible models for the synergy between p53 and WRN mutations for the determination of life span.

Targeted gene therapy for breast cancer with truncated Bid.

We studied the efficiency of the proapoptotic factor tBid, targeted to tumor cells using the promoters of the hTERT, Survivin and Muc1 genes, in killing breast cancer cells. tBid is the active fragment of the proapoptotic protein Bid and is generated in response to death receptor activation. When placed under control of a strong CMV promoter, tBid was highly efficient in killing breast cancer cells. When expression of tBid was driven by tumor-specific promoters, the magnitude of killing was significant in cell lines with high levels of promoter activity. For successful gene therapy with targeted tBid, it is therefore crucial to be able to predict promoter activity prior to selection of the therapeutic construct. To test whether gene expression could serve as a predictor, we correlated expression of Survivin, hTERT and Muc1 genes with the activity of the corresponding promoters in a panel of breast cancer cell lines. Expression of the Muc1 gene correlated well with the activity of its promoter and the resultant tumor cell killing. For the hTERT and Survivin promoters, however, promoter activity did not correlate well with the expression of the corresponding genes. The implications and possible mechanism of these discrepancies are discussed.

Association of the Bloom syndrome protein with topoisomerase IIIalpha in somatic and meiotic cells.

Bloom syndrome (BS) is characterized by genomic instability and cancer susceptibility caused by defects in BLM, a DNA helicase of the RecQ-family (J. German and N. A. Ellis, The Genetic Basis of Human Cancer, pp. 301-316, 1998). RecQ helicases and topoisomerase III proteins interact physically and functionally in yeast (S. Gangloff et al., Mol. Cell. Biol., 14: 8391-8398, 1994) and in Escherichia coli can function together to enable passage of double-stranded DNA (F. G. Harmon et al., Mol. Cell, 3: 611-620, 1999). We demonstrate in somatic and meiotic human cells an association between BLM and topoisomerase IIIalpha. These proteins colocalize in promyelocytic leukemia protein nuclear bodies, and this localization is disrupted in BS cells. Thus, mechanisms by which RecQ helicases and topoisomerase III proteins cooperate to maintain genomic stability in model organisms likely apply to humans.

Periovulatory endocrine events in the stumptailed monkey (macaca arctoides).

Blood samples were obtained frequently from stumptailed monkeys (Macaca arctoides) at midcycle and assayed for FSH, LH, 17 beta-estradiol, and progesterone. Periovulatory endocrine events were generally similar to those which have been described in rhesus monkeys and women. Although the midcycle patterns of estradiol in individual monkeys appeared quite varied, careful evaluation indicated the following general characteristics: 1) a plateau or transient decline in estradiol 30-44 h before the LH peak, 2) a sharp rise in serum estradiol before the initiation of the LH rise, 3) a diminution in serum concentrations or a decline in the rate of estradiol increase at the initiation of the LH rise, and 4) an elevation in estradiol at the time of the highest serum LH value. The first elevation in serum progesterone occurred 0-12 h before the LH peak and after the initiation of the LH surge. An unusual finding was a second midcycle rise in serum FSH, which occurred 2-3 days after the LH peak in 10 of 13 menstrual cycles. The biological significance of this second FSH rise in stumptailed monkeys is not known with certainty, but available evidence suggests that it enhances postovulatory progesterone and estrogen syntheses. Two methods are presented for the RIA of serum FSH in the stumptailed macaque.

TRH-induced TSH response in healthy volunteers: relationship to psychiatric history.

The authors measured thyroid-stimulating hormone (TSH) response to thyrotropin-releasing hormone in 32 healthy volunteers who had never sought or received psychiatric treatment. Nine (28%) had a family or personal history of depression or alcoholism. Five of these nine subjects and one of 22 subjects without such a history showed TSH blunting (TSH data were not available for one subject). This difference was statistically highly significant. Although there were sex differences in TSH response, TSH blunting occurred most frequently in men with a family or personal history of depression or alcoholism. The fault may have utility as a marker of past episodes or as a true marker of trait.

Ethanol consumption and susceptibility of the pancreas to cerulein-induced pancreatitis.

Despite the fact that alcoholism is one of the major causes of pancreatitis, the pathogenesis of this disorder remains obscure. Factors such as the pattern of ethanol consumption, diet, and genetic predisposition may be contributing factors. The failure to produce alcoholic pancreatitis in experimental animals suggests that experimental provision of ethanol may only increase the predisposition to pancreatitis. To test this possibility, we developed an assay system using the in vitro model of cerulein-induced pancreatitis. In this system, pancreatic lobules were first exposed to a supraphysiologic concentration (10(-6) M) of the cholecystokinin analogue, cerulein, after which homogenates were incubated for up to 6 h. Activation of trypsinogen and chymotrypsinogen was observed only in cerulein-treated preparations. We then investigated the effects of the duration of ethanol feeding on cerulein-induced changes in rat pancreas. The pancreata from rats fed ethanol for 9-12 months were more susceptible to cerulein-induced activation of chymotrypsinogen compared to the pancreata from pair-fed control animals. This susceptibility also paralleled morphologic changes, such as dilatation of endoplasmic reticulum, only in the ethanol-fed group. In contrast, during the early stages (up to 3 months) of ethanol consumption, there was resistance (p < 0.01) to cerulein-induced changes. These results suggest that long-term ethanol consumption increases susceptibility to pancreatitis and raises the possibility that a similar mechanism may operate in human alcoholics.

Axial bone mineral density in patients with acromegaly.

RATIONALE AND OBJECTIVES: The purpose of this study was to assess the influence of long-term elevated levels of growth hormone and insulin-like growth factor I on bone mineral density (BMD) of the spine in patients with acromegaly. MATERIALS AND METHODS: The spinal BMD in 40 patients with acromegaly was measured with quantitative computed tomography. The result was expressed as the mean of six measurements of consecutive vertebral bodies and as a z score. Twenty age- and sex-matched healthy persons also underwent spinal BMD measurement and served as controls. RESULTS: In 36 of the 40 patients, the BMD z score ranged within 2 standard deviations (SDs) above or below the mean. Only two patients (one man and one woman) had enhanced BMD loss (below 2 SD). Two other female patients had BMD values of more than 2 SD above the mean. Differences between patient subgroups were not statistically significant, but a statistically significant (P < .05) positive correlation was found between basal serum concentration of growth hormone and spinal BMD for the entire patient group. No correlation between BMD and basal serum concentration of insulin-like growth factor I was found. CONCLUSION: Hypersecretion of growth hormone in patients with acromegaly, regardless of other factors, has no evident effect on BMD of the lumbar spine.

The level of MAP kinase activity in the stomach stump in rats after subtotal gastrectomy.

MAPK (Mitogen-Activated Protein Kinase) is one of the elements of kinase cascades (MAPK, MEK-MAP kinase, kinase, Raf-1, Ras) regulating cellular proliferation and differentiation processes. It seems that the changes in its number and activity may be the factor having influence on carcinogenesis. In some human carcinomas a significant increase of its activity is observed, in others a decrease of its activity is described. Our research aimed at the evaluation of the dynamics of precancerous and cancerous changes in the stomach stump in rats after the experimental, partial stomach resection. Apart from histological and ultrastructural examination we also determined the activity of the sub-unit p42 MAP kinase. The material comprised segments of gastric mucosa of the stomach stump of 15 rats after subtotal gastrectomy. Part of the rats after the procedure were administered carcinogen orally (MNNG). On the histological and ultrastructural examination we used routine methods, the activity of MAP kinase was determined by western-blotting method with the use of IgG against MAPK p42, Santa Cruz #154). In 8 examined rats we observed the increase of MAP kinase activity. We established probable correlation (without statistical analysis, regarding miserly material) between the increase of MAPK activity and histological and ultrastructural changes. Among three cases diagnosed as adenoma tubulare in two we observed the increase of MAPK activity. A clear increase of this kinase was also present in the stomach stump of a rat, which was diagnosed as adenocarcinoma. On the basis of our research carried so far we think that the increase of the MAPK activity may be one of the causes of the neoplasm development. It seems important to obtain the confirmation of our results and to establish a possible usefulness of MAPK activity determination as a prognostic indicator in case of the neoplasm of stomach stump.

CT appearance of bilateral, acute thrombosis of the main cerebral arteries.

Acute thrombosis within the lumen of the intracranial artery may occasionally be demonstrated on precontrast CT. The hyperdensity follows the course of the occluded segment of the vessel and an area of low attenuation in the territory of the involved artery is usually present, consistent with infarction. Usually, a single vessel is involved; occlusion of multiple branches occurs less commonly. This report demonstrates a case of diffuse bilateral thrombosis of the main arteries of the anterior circle of Willis.

Ultrastructural changes in the small bowel epithelium after total gastrectomy.

The purpose of the study was to analyze ultrastructural changes in the small bowel mucosa in patients after total gastrectomy. We studied mucosal specimens obtained from 25 patients during control gastroscopy. The specimens were routinely processed for examination in transmission electron microscopy. Early after the operation (up to 6 months) we observed marked inflammatory reaction, disordered architecture of the small bowel mucosa epithelium, the presence of dysplasia-like changes and foci of dysplasia. Later on the structure of the mucosa returned to normality. Only a few dysplastic changes were seen. No relationship was found between altered epithelial structure and type of operation. In conclusion, the epithelium of the small bowel does not transform to a gastric type epithelium.

Ultrastructural changes in the small intestinal epithelium after total resection of the colon.

UNLABELLED: The aim of the study was to analyze ultrastructural changes in the mucosa of the small intestine after total resection of the colon in 29 patients (familial polyposis in 21, ulcerative colitis in 8). We studied specimens of the small intestinal mucosa obtained from ano- and rectoscopy. The specimens were routinely processed for transmission electron microscopy. Early after the operation (up to 4-5 months) we observed marked structural disorders of the mucosal epithelium and regenerative cell atypia (dysplasia-like changes). At 6 months after the operation we found rapidly progressing normalization of the epithelial mucosa and its mimicking the epithelium of the colon: increased amount of mucous cells, formation of vacuolized cells, almost complete atrophy of microvilli on the surface of enterocytes, increase of the intercellular space (retention space). Foci with dysplasia features were quite numerous in group I, in contrast to group II where they were sporadic. CONCLUSION: the epithelium of small intestinal mucosa has the ability of convergence towards the epithelium of colon.

Endoscopical and histological aspects of inflammatory changes in J-pouch mucosa.

The aim of the study was endoscopic and histological evaluation of mucosal inflammatory changes in the ileal reservoir after restorative proctocolectomy with ileoanal anastomosis (IPAA) because of FAP (27 patients) and ulcerative colitis (34 patients). Endoscopic symptoms of pouchitis (edema, granularity, contact bleeding, loss of vascular pattern, mucus, erosions) were found in 13 patients (4 were operated on because of FAP, 9 because of UC). A statistically significant difference (p < 0.0001) was found between endoscopic inflammatory index in UC (4.0 +/- 0.5) and in FAP (1.00 +/- 0.00). The endoscopic changes were correlated with the Moskowitz histological classification, in 12 acute score and in 6 chronic score were above 4 points. In 18 patients histological diagnosis of pouchitis was made (5 in FAP, 13 in UC). Acute pouchitis occurred in 12 patients and chronic in 6. In one patient histological changes resembled Crohn's disease. Regular endoscopic control with histological examination and verification of inflammatory lesions in the ileal reservoir is necessary.

Telemedicine in rural areas. Experience with medical desktop-conferencing via satellite.

Cooperation between physicians in hospitals in rural areas can be assisted by desktop-conferencing using a satellite link. For six weeks, medical desktop-conferencing was tested during daily clinical conferences between the Virchow-Klinikum, Berlin, and the Medical Academy, Wroclaw. The communications link was provided by the German Telekom satellite system MCS, which allowed temporary connections to be established on demand by manual dialling. Standard hardware and software were used for videoconferencing, as well as software for medical communication developed in the BERMED project. Digital data, such as computed tomography or magnetic resonance images, were transmitted by a digital data channel in parallel to the transmission of analogue video and audio signals. For conferences involving large groups of people, hardware modifications were required. These included the installation of a video projector, adaptation of the audio system with improved echo cancellation, and installation of extra microphones. Learning to use an unfamiliar communication medium proved to be uncomplicated for the participating physicians.

[Typing of methicillin resistant strains of S. haemolyticus isolated from patients and from the hospital ward environment]. / Typowanie metycylinoopornych szczepów S. haemolyticus izolowanych od chorych oraz ze srodowiska oddzialu.

Biotyping, antibiograms and fingerprinting were used to determine the relation of 16 methicillin-resistant S. haemolyticus isolated from drains in patients who underwent intraabdominal surgery to 9 methicillin-resistant strains of S. haemolyticus isolated at the same time from hospital environment. The comparison of biochemical properties of the examined strains showed a large variety of biochemical profiles as well as antibiotic patterns of susceptibility. The differences in sensitivity to the antibiotics used were not distinct. Biotyping and antibiograms did not permit determination of the relation of the investigated strains. Only the results of fingerprinting allowed for the division of the 25 examined strains into three genotypes demonstrating three main patterns of PCR products. 16 strains of 25 showed the same pattern of PCR products. This results suggests the presence of a source of infection on the clinical ward. A nurse may have been the source of infection because the same genotype of S. haemolyticus was isolated from her nasal anterior as from the majority of patients.

[Peritonitis determined by the site of intra-abdominal surgery]. / Zakazenie jamy otrzewnowej zaleznie od miejsca operacji brzusznej.

The aim of this study was to determine bacterial flora infecting the peritoneal cavity during intraabdominal surgery by site of operation. Three groups of patients were examined. 29 patients who underwent surgery on the stomach, duodenum, biliary tract or pancreas, 15 patients operated on because of acute appendicitis and 63 patients operated on because of colon or rectum tumours. At the end of the operation but before closure cultures were obtained by swab from the completed anastomosis site. Samples were placed into transport medium and transported promptly to the laboratory. The results of the bacteriological examinations showed that the peritoneal cavity of all patients operated on were infected with bacteria characteristic for the digestive tract, especially by Enterobacteriaceae spp., Enterococcus spp. and Bacteroides spp. From patients operated on because of rectum or colon tumours 3 or 4 bacterial species were isolated most often and they were often infected with P. aeruginosa and C. albicans. This was in contrast to patients from the other groups. In patients infected with polymicrobial flora, B. fragilis and E. coli or enterococci and E. coli and enterococci were most often seen.