Preliminary joint neutron time-of-flight and X-ray crystallographic study of human ABO(H) blood group A glycosyltransferase.

The biosyntheses of oligosaccharides and glycoconjugates are conducted by glycosyltransferases. These extraordinarily diverse and widespread enzymes catalyze the formation of glycosidic bonds through the transfer of a monosaccharide from a donor molecule to an acceptor molecule, with the stereochemistry about the anomeric carbon being either inverted or retained. Human ABO(H) blood group A α-1,3-N-acetylgalactosaminyltransferase (GTA) generates the corresponding antigen by the transfer of N-acetylgalactosamine from UDP-GalNAc to the blood group H antigen. To understand better how specific active-site-residue protons and hydrogen-bonding patterns affect substrate recognition and catalysis, neutron diffraction studies were initiated at the Protein Crystallography Station (PCS) at Los Alamos Neutron Science Center (LANSCE). A large single crystal was subjected to H/D exchange prior to data collection and time-of-flight neutron diffraction data were collected to 2.5 Šresolution at the PCS to ∼85% overall completeness, with complementary X-ray diffraction data collected from a crystal from the same drop and extending to 1.85 Šresolution. Here, the first successful neutron data collection from a glycosyltransferase is reported.

Microscopic model of the actin-myosin interaction in muscular contractions.

We define and study a detailed many body model for the muscular contraction taking into account the various myosin heads. The state of the system is defined by the position of the actin and by an internal coordinate of rotation for each myosin head. We write a system of Fokker-Planck equations and calculate the average for the position, the number of attached myosin heads, and the total force exerted on the actin. We also study the correlation between these quantities, in particular between the number of attached myosin heads and the force on the actin.

Effect of dietary flaxseed, flax oil and n-3 fatty acid supplement on hepatic and plasma characteristics relevant to fatty liver haemorrhagic syndrome in laying hens.

1. Two experiments were carried out to investigate the effect of dietary flaxseed, flax oil and n-3 fatty acid supplementation (Dry n-3) on hepatic fat content, plasma triglycerides, hepatic haemorrhage score, egg production, food intake and body weight in an inbred line of Single Comb White Leghorns (UCD-003) predisposed to fatty liver haemorrhagic syndrome (FLHS) and normal SCWL hens. 2. Feeding diets containing 100 g/kg ground flaxseed, 40 g/kg flax oil, or 100 g/kg Dry n-3 reduced body weight and significantly reduced hepatic fat content compared to feeding the control diet with animal and vegetable oil as a fat source. 3. Hepatic malondialdehyde, an indicator of lipid peroxidation within the liver, was not significantly affected by dietary treatment. 4. Normal SCWL hens tended to have higher egg production, greater body weight, greater food intake and higher blood triglyceride concentrations than UCD-003 hens, although the strain effects were not significant. Liver weight as a percent of body weight was significantly lower in normal SCWL hens. Treatments by strain interactions were not found. 5. The result suggested that dietary flaxseed, flax oil and Dry n-3 decrease hepatic fat content and reduce body weight, 2 of the predisposing factors believed to contribute to FLHS onset. However, haemorrhages were still apparent in both strains regardless of treatment, indicating that other unknown underlying mechanisms may also be responsible for FLHS.

Achalasia in patients over 65.

Achalasia is a disease of undertermined etiology characterized by a defect in the innervation of esophageal smooth muscle causing aperistalsis of the esophageal body, increased lower esophageal sphnicter (LES) tone and inappropriate relaxation of the LES during swallowing. Several of the manometric and radiographic features of achalasia are also seen in individuals without the disease but they are reported much more frequently in older populations. We reviewed our cases of new onsst achalasia in patients over age 65 to see if their presentation and response to treatment might differ from that reported in younger patients. We found dysphagia to be the predominant symptom in our elderly patients just as it is in younger patients. Chest pain, on the other hand, was significantly less common. Additionally, our achalasia group had a high response rate to pneumatic dilatation, confirming an earlier study that showed greater efficacy in older patients than in younger patients.

Breath test diagnosis of Helicobacter pylori in peptic ulcer disease: a noninvasive primary care option.

BACKGROUND: Helicobacter pylori is implicated as the causative agent for most duodenal and gastric ulcers. Invasive (endoscopy and biopsy) and noninvasive (serology, breath test) methods are currently available for definitive diagnosis of infectious peptic ulcer disease. METHODS: Twenty-six patients with chronic gastritis symptoms underwent upper endoscopy, biopsy, rapid urease test, and [14C]urea breath test for the detection of H pylori. RESULTS: Twenty of 26 patients (77 percent) had biopsy-proved H pylori infection. All 20 (100 percent) with definite H pylori proved by invasive diagnosis had strongly positive results on urea breath test. Six patients with absence of H pylori on biopsy had negative urea breath test results. The urea breath test displayed 100 percent sensitivity, specificity, and predictive value compared with endoscopy and biopsy. CONCLUSIONS: [14C]Urea breath testing is comparable to endoscopy and biopsy in the diagnosis of H pylori infection and could become useful in primary care settings for noninvasive evaluation of peptic ulcer disease.

Long-term prognosis of well-differentiated adenocarcinoma in endoscopically removed colorectal adenomas.

Thirty-six malignant polyps were identified that met the following criteria: well-differentiated adenocarcinoma and complete excision endoscopically. Location, type, size, distance of the cancer to the cautery mark, and lymphovascular involvement were analyzed to determine if they affected findings at surgery or risk of recurrent cancer. There were 20 patients and 21 polyps in the nonsurgical group, and 15 patients and polyps in the surgical group. One patient from each group had residual cancer after endoscopic removal of the polyp. The only factor that had an adverse effect on outcome was the distance of the cancer to the cautery mark (< 1 mm). Although rectal location was associated with the residual cancer, poor prognosis could have been predicted by the inadequate margins. This long-term follow-up (65 months average) study supports previous observations that an adequate margin is the most important factor in predicting the prognosis of endoscopically resected colorectal adenomas containing well-differentiated adenocarcinomas.

The influence of liver disease and portal hypertension on bleeding in Mallory-Weiss syndrome.

The records of 79 patients admitted to the hospital from January 1985 through December 1990 for acute esophageal hemorrhage were analyzed to determine the influence of liver disease and/or portal hypertension on the severity of bleeding from Mallory-Weiss syndrome. Forty-two patients had bled from Mallory-Weiss syndrome; 8 had liver disease and nonbleeding esophageal varices, 6 had liver disease without varices, and 28 had no evidence of liver disease. The severity of bleeding was determined by the transfusion requirement for each group. The number of units of blood needed for patients with liver disease was significantly increased (p < 0.005) over the number of units necessary for patients without liver disease. There was no statistically significant difference in the transfusion requirement between liver disease patients with and without varices (i.e., portal hypertension). The transfusion requirement was also unrelated to the Child classification of hepatic functional reserve. We conclude that the severity of bleeding from Mallory-Weiss syndrome is primarily related to the status of liver function and that portal hypertension does not make an additive contribution.

The limited role of total parenteral nutrition in the management of pancreatic pseudocyst.

Total parenteral nutrition (TPN) for the nonoperative treatment of acute pancreatic pseudocyst has been of hypothetical benefit. We reviewed pseudocyst hospital admissions in 40 patients treated with TPN who had serial imaging studies. The mean cyst size was 7.4 cm on presentation, decreasing to 5.6 cm after nonoperative treatment with TPN (mean 32.5 days). After a nonoperative period, 68 per cent of cysts regressed, completely in 14 per cent, partially in 54 per cent. Except for a patient with cyst-related obstructive jaundice, there were no complicated pseudocysts. Only 12 (28%) patients underwent cyst drainage. Fifteen patients (35%) sustained catheter-related complication, which included sepsis (26%), pneumothorax (9%), hydropneumothorax (2%), and septic right atrial thrombosis (2%), in the course of hospitalization. The majority of TPN-treated patients had a clinical and radiographic regression of their pseudocyst. However, the increased risk of catheter-related complications in this group suggests that this therapy should be limited to patients who are unable to sustain enteral nutrition.

Lymphocytic colitis. A definable clinical and histological diagnosis.

We reviewed colorectal biopsies and clinical records from 36 patients with chronic watery diarrhea who had been diagnosed as having microscopic colitis and compared their histologic features with the more detailed and precise criteria for lymphocytic colitis. Published pathologic criteria for lymphocytic colitis were applied to the biopsies and compared. Focal or diffuse nature of the lymphoid infiltrate were noted separately. The focal lymphoid infiltrate was related to lymphoid aggregates in the lamina propria of the mucosa. Eighteen cases had focal lymphoid cell infiltration, and 16 of them had associated diverticula, polyps, or both. Eighteen cases had diffuse lymphoid cell infiltration, and six of them had diverticula or polyps. Results indicate that focal cellular infiltration strongly predicts associated diverticula or polyps. The group with no diverticula or polyps most closely conformed to histologic criteria for lymphocytic colitis (Kruskal-Wallis P < 0.02). We conclude that lymphocytic colitis comprises a well-defined group of cases within the large and less-defined group of microscopic colitis.

Premalignant lesions of the gastrointestinal tract. Surveillance regimens for three treatable disorders.

Barrett's esophagus, ulcerative colitis, and adenomatous colorectal polyps have been proven to be precursors of cancer. Early treatment and appropriate esophagoscopic or colonoscopic surveillance for recurrence or disease progression in these patients can save lives. Dr Schuman discusses typical regimens and special considerations in follow-up of these disorders.

The practice outcomes of a course in flexible sigmoidoscopy for primary care physicians.

A mail survey of 430 participants in a 2-day course on flexible sigmoidoscopy presented over the past 6 years was conducted to determine the extent to which flexible sigmoidoscopy was subsequently utilized in physician practice. Eighty percent of respondents performed the procedure in their practices on a regular basis. Two-thirds of the patients underwent sigmoidoscopy for screening. The course in flexible sigmoidoscopy appears to potentiate the motivation of primary care physicians to incorporate complete colorectal cancer screening in their practice.

The association of multiple colonic adenomatous polyps with cancer of the colon.

We reviewed our colonoscopy data for the past 10 yr for patients with five or more polyps to determine the association of multiple adenomatous polyps and colon cancer. During that period, 3,834 patients underwent colonoscopy. Fifty-two patients with five or more polyps at the initial colonoscopy were found. In 25 patients (group I) there were at least five synchronous adenomas, and in 27 patients (group II) a combination of adenomas and hyperplastic polyps totaling five or more. The number of polyps ranged from five to 30 (median, six). There was no significant difference in the location of polyps between groups I and II. Eight of 52 patients (15%) were found to have colon cancer at the initial colonoscopy. In group I, there were six cancers (24%), five of which were in the cecum. Two of 27 patients (7%) in group II had cancer, one of which was located in the cecum. Patients with five or more adenomas at the index colonoscopy are at high risk of having colon cancer that is particularly prone to arise from the right side of the colon.

The Bouveret syndrome: an unusual cause of hematemesis.

Gallstones are usually silent. Less commonly, patients with cholelithiasis develop symptoms and/or complications; biliary fistula occurs in 3% to 5% of the cases. When a large stone is passed and occludes the duodenum, gastric outlet obstruction (the Bouveret syndrome) may result. In reported cases, the stones are usually larger than 2.5 cm. The usual presenting symptoms are those of bowel obstruction: abdominal pain, nausea, and vomiting. Less commonly, the patients experience melena and, rarely, hematemesis. We describe a patient who had the largest stone reported to cause hematemesis rather than bowel obstruction and to be diagnosed endoscopically. The 5 X 4 X 3 cm stone was extracted surgically. Endoscopic diagnosis and extraction of stones up to 3 cm in size has been reported, avoiding the need for surgery.

Inflammatory bowel disease in 64 black patients: analysis of course, complications, and surgery.

Sixty-four black patients with inflammatory bowel disease (IBD) were seen from 1960 to 1987 at the Medical College of Georgia, representing 22% of all patients with IBD: 38 of them had Crohn's disease (CD) and 26 had ulcerative colitis (UC). In those with CD, the small intestine alone was involved in 16% and ileocolitis was found in 58%; joint disease affected 11 patients (29%) and perianal disease 13 patients (34%). Twenty black patients (53%) underwent one disease-related surgical procedure, and 10 (50%) of those required two or more reoperations. Nine UC patients (35%) underwent surgery, and, except for three cases of sclerosing cholangitis (12%), black patients with UC showed no clinical findings different from white UC patients. In our American black patients, the course of IBD was similar to that of white patients, although in Crohn's disease the reoperation rate and the rate of joint involvement were higher in our black IBD patients; primary sclerosing cholangitis was also found in a larger percentage of black patients with UC than in our white patient population.

Scanning electron microscopy of dysplastic Barrett's epithelium.

Twenty-six patients with Barrett's esophagus (BE) were followed prospectively by endoscopic examination and biopsy. Two biopsies were taken from each of 4 areas of BE. One was processed for light microscopy (LM) and one for scanning electron microscopy (SEM). Those in whom dysplastic BE was demonstrated by LM were reexamined at 6-mo intervals, and the others at yearly intervals. One patient had low grade dysplasia (LGD) by LM on entry, and in 2 others, LGD was recognized on the second examination. These changes have persisted in semiannual examinations over 3, 2, and 2 yr, respectively. SEM prints were examined without knowledge of LM findings, and features that might correlate with LGD by LM were sought. SEM findings were similar to those of Zwas et al. (Gastroenterology 90:1932, 1986) in that most glandular cells had surface features unlike either gastric or intestinal cells but unique to BE. In the patient with LGD on entry, there was an aggregate of very large cells covered by short microvilli with bald patches. In the other patients with LGD, there was more variation in size and shape of cells than in nondysplastic cases.

Recovery from hepatic vein thrombosis (Budd-Chiari syndrome) complicating ulcerative colitis.

A 22-year-old female with active ulcerative colitis developed massive ascites, hypoalbuminemia, and hepatomegaly compatible with thrombosis of the hepatic veins. The diagnosis of Budd-Chiari syndrome was confirmed by ultrasonography, computed tomography, and by liver biopsy. A search of the literature disclosed only three previous reports of Budd-Chiari syndrome occurring in patients with ulcerative colitis. All patients have been young females with active colitis and no other known risk factor for the development of hepatic vein thrombosis. Our patient, unlike the previously reported patients who died, recovered sufficiently to be discharged from the hospital.

The use of the 130-cm colonoscope for screening flexible sigmoidoscopy.

The 130-cm colonoscope was utilized to determine whether a deeper insertion could be accomplished after the usual enema preparation for routine flexible sigmoidoscopy and, if so, to what extent that would enhance the yield of neoplastic findings. Sixty-four patients were examined, and intubation was accomplished to the level of 69 cm compared with 48.1 cm for a matched control group that had flexible sigmoidoscopy with the 60-cm endoscope. Another 24 patients who had a barium enema prep had a significantly greater depth of insertion (81.4 cm). Only two polyps were found proximal to 60 cm. The 130-cm colonoscope does not offer any substantial advantage over the standard 60-cm sigmoidoscope unless a bowel preparation more thorough than enemas is given and then it would probably only be worthwhile using the colonoscope in patients who are above average risk for colorectal neoplasia.