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Biomedical subjects

D R Morgan

Publications and source records attributed to D R Morgan.

At least 37 records · Page 2Linked to original sources

Ultrasound-guided Tru-cut biopsy of the breast.

Ultrasound-guided automated Tru-cut needle biopsy may be used as an alternative to fine needle aspiration cytology for the assessment of discrete mass lesions of the breast. This is a retrospective study of 187 biopsies, comparing the results with a final diagnosis obtained from subsequent excision or outpatient follow-up. Biopsies were performed using a spring-loaded gun under ultrasound guidance. Invasive malignancy was demonstrated in 114 biopsies, 98 of which were subjected to surgery, with no false-positives. Twelve biopsies contained 'atypical cells', pre-invasive malignancy or risk factors for invasive carcinoma, ten of which proved to be invasive malignancy on excision. Normal or benign tissue was found in 61 biopsies, but of those that proceeded to excision biopsy, 16 were invasive or in situ carcinoma. The sensitivity of the procedure for detecting significant pathology was 88.7%, and the specificity 100%. When used as part of triple assessment, the sensitivity increases to 97.9%. Ultrasound-guided Tru-cut needle biopsy is a well-tolerated and reliable procedure for providing a tissue diagnosis of malignancy before definitive treatment, and obviating the need for formal excision biopsy of lesions for which there is a low index of suspicion.

Adult↗

Endoscopic sclerotherapy compared with percutaneous transjugular intrahepatic portosystemic shunt after initial sclerotherapy in patients with acute variceal hemorrhage. A randomized, controlled trial.

BACKGROUND: Hemorrhage from esophageal varices remains a substantial management problem. Endoscopic sclerotherapy was preferred for more than a decade, but fluoroscopically placed intrahepatic portosystemic stents have recently been used with increasing frequency. OBJECTIVE: To compare sclerotherapy with transjugular intrahepatic portosystemic shunt (TIPS) in patients with bleeding from esophageal varices. DESIGN: Randomized, controlled clinical trial. SETTING: Three teaching hospitals. PATIENTS: 49 adults hospitalized with acute variceal hemorrhage from November 1991 to December 1995: 25 assigned to sclerotherapy and 24 assigned to TIPS. INTERVENTION: Patients assigned to repeated sclerotherapy had the procedure weekly. In those assigned to TIPS, an expandable mesh stent was fluoroscopically placed between an intrahepatic portal vein and an adjacent hepatic vein. MEASUREMENTS: Pretreatment measures included demographic and laboratory data. Postrandomization data included index hospitalization survival, duration of follow-up, successful obliteration of varices, rebleeding from varices, number of variceal rebleeding events, total days of hospitalization for variceal bleeding, blood transfusion requirements after randomization, prevalence of encephalopathy, and total health care costs. RESULTS: Mean follow-up (+/-SE) was 567 +/- 104 days in the sclerotherapy group and 575 +/- 109 days in the TIPS group. Varices were obliterated more reliably by TIPS than by sclerotherapy (P < 0.001). Patients having TIPS were significantly less likely to rebleed from esophageal varices than patients receiving sclerotherapy (3 of 24 compared with 12 of 25; P = 0.012). No other follow-up measures differed significantly between groups. A trend toward improved survival, which was not statistically significant, was noted in the TIPS group (hazard ratio, 0.53 [95% CI, 0.18 to 1.5]). CONCLUSIONS: In obliterating varices and reducing rebleeding events from esophageal varies, TIPS was more effective than sclerotherapy. However, TIPS did not decrease morbidity after randomization or improve health care costs. It seemed to produce better survival, but the increase in survival was not statistically significant.

Adult↗

Chloroplast gene sequence data suggest a single origin of the predisposition for symbiotic nitrogen fixation in angiosperms.

Of the approximately 380 families of angiosperms, representatives of only 10 are known to form symbiotic associations with nitrogen-fixing bacteria in root nodules. The morphologically based classification schemes proposed by taxonomists suggest that many of these 10 families of plants are only distantly related, engendering the hypothesis that the capacity to fix nitrogen evolved independently several, if not many, times. This has in turn influenced attitudes toward the likelihood of transferring genes responsible for symbiotic nitrogen fixation to crop species lacking this ability. Phylogenetic analysis of DNA sequences for the chloroplast gene rbcL indicates, however, that representatives of all 10 families with nitrogen-fixing symbioses occur together, with several families lacking this association, in a single clade. This study therefore indicates that only one lineage of closely related taxa achieved the underlying genetic architecture necessary for symbiotic nitrogen fixation in root nodules.

Base Sequence↗

Intake of carbohydrate and its components--international comparisons, trends over time, and effects of changing to low-fat diets.

Carbohydrate constitutes the major source of dietary energy for all peoples of the world. However, it has been difficult to make accurate determinations of intakes of carbohydrate and its constituents because of lack of individual assessments in which carbohydrate components are included. For many countries, only food balance information is available and values for total carbohydrate are often derived by difference. Available information indicates that carbohydrate consumption decreased in many industrialized nations as prosperity led to an increased consumption of fat. Fat intakes have fallen over the past two decades and carbohydrate intakes have increased, but still do not approach the 60-70%contribution of carbohydrate to total energy in developing countries. A negative image for carbohydrate has led to a reluctance to accept it as a legitimate dietary component, particularly in North America. New evidence of the beneficial effects of starch in the diet indicates that increased consumption of carbohydrate, especially in the form of starch, should be promoted in Western countries.

Adult↗

Effect of green lentils on colonic function, nitrogen balance, and serum lipids in healthy human subjects.

Green lentils are an increasingly popular food, but their effects on human colonic function and serum lipids have been studied little. Nine healthy males aged 19-38 y consumed for 3-wk periods a controlled Western diet and the same diet supplemented with 130 g dry lentils/d [which contained 11.8 g non-starch polysaccharide (NSP)] incorporated into loaves, cakes, and soups. Protein was equilibrated with soy protein isolate and carbohydrate with soft drinks. Radioopaque markers were used to calculate mean transit time (MTT) and to correct fecal weight for infrequency of bowel movements. Feces were collected throughout the study and blood was taken on 2 d at the end of each period. Lentils increased fecal weight from 131 +/- 12 g/d (means +/- SEM) to 189 +/- 17.4 g/d (44.9%) (P < 0.005). MTT was unchanged: 46 +/- 6 h for the control diet and 43 +/- 4 h for the lentils (NS). Fecal nitrogen was increased to 2.49 +/- 0.08 g/d for lentils compared with 1.74 +/- 0.09 g/d for the control diet (P < 0.001) and urine nitrogen decreased to 15.31 +/- 0.52 g/d with the lentils compared with 15.90 +/- 0.51 g/d for the control diet (P < 0.05); nitrogen balance was unaffected. Serum lipids were unchanged by addition of lentils to the diet. Green lentils were effective in increasing fecal weight and can therefore make a valuable contribution to a healthy diet.

Adult↗

A high-throughput assay for cyclic nucleotide phosphodiesterases.

The search for cyclic nucleotide phosphodiesterase inhibitors in large chemical and natural product libraries is limited by assay throughput. A high-throughput assay that can monitor different phosphodiesterase activities would be useful for these inhibitor searches. We have developed a sensitive phosphodiesterase assay which is based on the selective precipitation of the radiolabeled 5'-nucleotide product by zinc and barium. This assay is unique to previous precipitation methods in that it measures product formed, either GMP or AMP. The procedure was adapted to a microtiter plate format for high-throughput, making it possible to perform in excess of 960 assays per day. This method was used to determine accurate enzyme kinetic constants for three different phosphodiesterases. The results agree favorably with literature values. Using the cyclic guanosine 3',5'-monophosphate-specific phosphodiesterase, IC50 values for the inhibitors M&B 22,948 and 3-isobutyl-1-methylxanthine were also determined. Demonstration of appropriate Km and inhibitor IC50 values verifies the ability of this new assay to identify selective cyclic nucleotide phosphodiesterase inhibitors.

3',5'-Cyclic-GMP Phosphodiesterases↗

Helicobacter acinonyx sp. nov., isolated from cheetahs with gastritis.

Four strains of a novel Helicobacter species were isolated from the stomachs of cheetahs (Acinonyx jubilatus) with gastritis. These isolates were phenotypically similar to Helicobacter pylori. The isolates were gram-negative, spiral bacteria which grew under microaerophilic conditions at 37 degrees C, but not at 25 or 42 degrees C, and produced urease, catalase, oxidase, alkaline phosphatase, and gamma-glutamyl transpeptidase. The isolates did not ferment glucose, mannitol, inositol, sorbitol, rhamnose, sucrose, melibiose, amygdalin, or arabinose; hydrolyze hippurate or indoxyl acetate; or reduce nitrate. They did not produce H2S from triple sugar iron agar, and they did not grow in the presence of 1.0% glycine or 1.5% NaCl. They were resistant to nalidixic acid and sensitive to cephalothin and metronidazole. Cells were typically 0.3 by 2.0 microns and possessed tufts of two to five sheathed, monopolar flagella. The G+C content of strain 90-119 was 30 mol%. Cluster analysis of densitometry scans of polyacrylamide protein gels revealed more than 70% similarity of the cheetah isolates to H. pylori, less than 60% similarity to Helicobacter felis, and less than 50% similarity to Helicobacter mustelae. Complete 16S rRNA sequences were determined for two of the cheetah isolates. Phylogenetic analysis was performed by comparing the cheetah sequences to those of 19 reference strains, including H. pylori, H. felis (two strains), H. mustelae, Helicobacter muridarum, "Flexispira rappini," Wolinella succinogenes, Campylobacter coli, Campylobacter concisus, Campylobacter curvus, Campylobacter fetus, Campylobacter hyointestinalis, Campylobacter jejuni, Campylobacter lari, Campylobacter rectus, Campylobacter sputorum subsp. bubulus, a Campylobacter sp. (pig isolate), [Bacteroides] gracilis, and [Bacteroides] ureolyticus.(ABSTRACT TRUNCATED AT 250 WORDS)

Acinonyx↗

Epizootic gastritis associated with gastric spiral bacilli in cheetahs (Acinonyx jubatus).

An outbreak of vomiting in a group of captive cheetahs (Acinonyx jubatus) was investigated, and histologic examination revealed chronic gastritis characterized by infiltration of lymphocytes and numerous plasma cells and epithelial erosions. Lymphoid follicles, globule leukocytes, scattered neutrophils, and (in one animal) abscessed gastric glands were inconsistent findings. In addition, necropsy of three cheetahs revealed gastric mucosal hyperplasia. Two kinds of bacteria were identified in the stomachs of infected cheetahs. Numerous long, tightly coiled motile Gastrospirillum-like organisms were seen in gastric mucus and in Warthin-Starry-stained sections of mucosa. These bacteria could not be cultured but were transmitted to conventional mice in homogenates of gastric mucosa from infected cheetahs. Ultrastructural examination revealed helical filaments on some of these bacteria. In addition, a smaller Helicobacter sp. was isolated. This organism could be cultured in vitro under microaerophilic conditions. One or both of these bacterial species was probably responsible for the gastritis in these cheetahs.

Acinonyx↗

Motility as a factor in the colonisation of gnotobiotic piglets by Helicobacter pylori.

Non-motile variants of Helicobacter pylori (strain 26695) occurred with a frequency of 1.6 (SD 0.4) x 10(-4) variants/cell/division cycle, and reversion to the motile form occurred with a frequency of less than 10(-7) variants/cell/division cycle. The two forms remained greater than 90% pure for up to 50 cell divisions and differed only in the presence or absence of motility and flagella. Bacteria were recovered from nine of 10 gnotobiotic piglets inoculated orally with motile H. pylori, but from only two of eight inoculated with the non-motile variant. The motile form survived for 21 days in infected piglets, but the non-motile variant survived for only 6 days. Bacteria recovered from piglets inoculated with the non-motile variant were non-motile. These data support the hypothesis that motility is a colonisation factor for H. pylori.

Animals↗

Biotype and macromolecular profiles of cytotoxin-producing strains of Helicobacter pylori from antral gastric mucosa.

Biotype, genome, protein and plasmid profile diversity amongst 40 epidemiologically unrelated strains of Helicobacter pylori was studied. Strains were API Zym biotypes II, III and IV but most (87%) were biotype II. Four subsets of strains were defined on a combination of motility (56% positive) and cytotoxin production (44% positive). A close association (P = 0.45) between these two features was observed for 69% of strains. Each strain of H. pylori had a unique DNA type defined by either HaeIII or HindIII total digest patterns and by ribopatterns, except for DNA of the rare strains not cut by these endonucleases. Strain diversity was confirmed by one-dimensional SDS-PAGE electrophoretic protein patterns. No consistent associations between cytotoxin activity and overall ribopattern or band subsets within a ribopattern were detected. Some strains (39%) contained a plasmid but the presence of plasmids was not consistently associated with either cytotoxin activity, biotype, motility or ribopattern. We conclude that the cytotoxin-producing strains of H. pylori were genomically as diverse as the non-cytotoxin producing strains.

Bacterial Proteins↗

Differentiation of strains of Helicobacter pylori by numerical analysis of 1-D SDS-PAGE protein patterns: evidence for post-treatment recrudescence.

Twenty-three pre- and post-treatment isolates of Helicobacter pylori from the antral mucosa of eight patients with dyspepsia and gastritis were compared using 1-D SDS PAGE of proteins. The protein patterns were highly reproducible and were used as the basis for two numerical analyses. The first, based on the total protein patterns, showed that a number of the strains did not cluster with their respective patient set. This was thought to be due to differences in both mobility and intensity of proteins in the major band region. The second analysis, based on partial patterns, excluding the major band region (51-68 kDa), divided the clinical isolates into clearly defined groups corresponding to the patient sets. Although there was a degree of heterogeneity with respect to protein pattern between the pre- and post-treatment isolates of some patients, there was nonetheless clear evidence that each patient was harbouring strains of only a single type. These results suggested that patients were not being reinfected with a different strain but that there was recrudescence of the pre-treatment strain. Protein 'fingerprints' provided a precise and reproducible means of strain differentiation, and revealed that in each patient the same strain persisted after drug therapy even though there was marked patient-to-patient strain variation.

Bacterial Proteins↗

Essential role of urease in pathogenesis of gastritis induced by Helicobacter pylori in gnotobiotic piglets.

A mutant strain of Helicobacter pylori with weak urease activity was created by using N-methyl-N'-nitro-N-nitrosoguanidine. The urease activity of the mutant (0.036 +/- 0.009 nmol of urea per micrograms of bacterial protein per min) was 0.4% of that of the parental strain (8.20 +/- 2.30 nmol of urea per micrograms of bacterial protein per min). The mutant was otherwise indistinguishable from the parental strain. Both demonstrated prominent catalase and oxidase activities, and both produced vacuolating cytotoxin. Restriction endonuclease and sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) patterns and ultrastructure were identical for the two strains. The mutant was fully motile, as evaluated by spreading in soft agar and by direct microscopic examination. Growth rate and colony size and morphology were identical for the mutant and parental strains. Seventeen gnotobiotic piglets were challenged with either the mutant or the parental strain and sacrificed 3 or 21 days after challenge. Gastric tissue was examined histologically and cultured for H. pylori. Of seven piglets challenged with the parental strain, all became infected. H. pylori was not recovered from any of 10 piglets challenged with the urease-negative strain. Lymphofollicular gastritis was present in all seven piglets challenged with the parental strain but in none of the piglets challenged with the urease-negative strain. These results suggest that prominent urease activity is essential for colonization by H. pylori.

Animals↗

Comparison of isolates of Helicobacter pylori and Helicobacter mustelae.

On the basis of analysis of protein profiles, isolates of Helicobacter pylori and Helicobacter mustelae were less than 40% similar. Cytotoxin produced by H. pylori was not detected in isolates of H. mustelae. Both bacterial species agglutinated human erythrocytes. These results substantiate a taxonomic difference between H. pylori and H. mustelae.

Bacterial Proteins↗

Gastritis associated with infection by Helicobacter pylori in humans: geographical differences.

Previous studies have indicated that infection rates of Helicobacter pylori are influenced by geographical factors. The present studies evaluate the characteristics of gastritis, associated with infection by H. pyrlori, and demonstrate relationships between different geographical locations and the extent of inflammatory cell accumulation in the gastric mucosa. Gastric biopsy specimens were obtained from patients infected with H. pylori at three clinical sites (two from North America and one from South America). Gastric inflammation was evaluated by quantitative histomorphometric techniques. Patients from South America had a more severe gastritis than did those from North America. Additionally, in South American patients the neutrophil was the predominant inflammatory cell type in the gastric mucosa. In contrast, the lymphocyte was the primary cell composing the mucosal infiltrate of infected North American subjects. Eosinophil infiltration into the mucosa correlated with the extent of mucosal atrophy; however, there were no differences between the North and South American patient populations in the extent of mucosal atrophy present in the specimens. We conclude that the characteristics (severity and cell type) of gastritis associated with infection by H. pylori are influenced by geographical factors that may be similar to those that modify infection rates for different geographical locations.

Adult↗