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Biomedical subjects

D R Morgan

Publications and source records attributed to D R Morgan.

At least 73 records · Page 4Linked to original sources
PubMed1987

Ploidy, proliferative activity, cluster differentiation antigen expression and clinical remission in high-grade non-Hodgkin's lymphoma.

Using a large range of monoclonal antibodies to specific cluster differentiation antigens the phenotypes of a series of high-grade non-Hodgkin's lymphomas of B- and T-cell type were investigated. Cell ploidy and proliferative fraction were assessed by fluorescent staining of DNA and flow cytometry and data on the incidence of complete clinical remission were obtained. With the exception of some lymphoblastic lymphomas, high-grade B-cell lymphomas normally expressed the pan B-cell antigens CD19 and CD22 but only immunoblastic lymphomas consistently expressed the pan B marker CD20. Variable, generally weak expression of CD21 was observed whilst CD23 expression was most prevalent in rapidly proliferative cases and in Burkitt's and centroblastic lymphomas. A rapidly proliferative, multilobated B-cell lymphoma displayed phenotypic properties intermediate between centroblastic and immunoblastic lymphomas. The T-cell lymphomas generally showed low proliferative activity and expression of CD4 prevailed over CD8. Most cases also showed CD2 and CD5 positivity with some also showing CD3 and CD7 expression. Patients with rapidly proliferative diploid or DNA aneuploid tumours obtained complete remission more readily than patients with lowly proliferative diploid tumours. An excess of early deaths occurred among T-cell cases.

Adolescent↗
PubMed1987

Establishment of gastric Campylobacter pylori infection in the neonatal gnotobiotic piglet.

Campylobacter pylori, a gram-negative microaerophilic bacterium, has been implicated in the genesis of human gastritis, dyspepsia, and gastroduodenal ulceration. Previous attempts to reproduce the diseases in conventional laboratory animal species have been unsuccessful. To determine if neonatal gnotobiotic piglets were susceptible to C. pylori, we orally challenged two litters (n = 17) with 10(9) CFU after pretreating them with cimetidine. Controls housed in separate units received nothing or peptone water alone. Piglets were examined 1, 2, 3, and 4 weeks after challenge. Colonization by the bacterium and inflammation of the gastric mucosa persisted throughout the study period. Organisms were revealed by Warthin-Starry silver stain to reside between the mucus layer and the gastric epithelium. Culturing of samples from sites along the gastrointestinal tract revealed that the bacterium colonized essentially only the gastric and proximal duodenal mucosae. Gross pathological changes were restricted to the stomachs of infected piglets and consisted of submucosal edema, increased gastric mucus production, and progressive development of mucosal lymphoid follicles. Microscopic lesions consisted of transient neutrophilic infiltrates followed by diffuse and follicular infiltrations of mononuclear leukocytes into the mucosa and submucosa. Alcian blue-periodic acid-Schiff stains suggested that the infection resulted in the depletion of mucopolysaccharide production by deep gastric glands. These data indicate that gnotobiotic piglets reproduce many of the features of diseases associated with C. pylori in humans.

Administration, Oral↗
PubMed1987

Growth of Campylobacter pylori in liquid media.

Until recently, broth cultivation techniques for Campylobacter pylori were unavailable. We developed a method to cultivate bacterial cells within 24 h in liquid media. Cultivation in broth depended on the adequate dispersion of appropriate gases. A static broth at 37 degrees C in a GasPak jar (BBL Microbiology Systems, Cockeysville, Md.) with a CampyPak (BBL) envelope did not support growth after 5 days of incubation. A broth placed in a flask on a Gyrotory water bath shaker (150 rpm; New Brunswick Scientific Co., Inc., Edison, N.J.) fitted with a gassing hood connected to a gas mixture of 10% CO2, 5% O2, and 85% N2 supported good growth. An initial inoculum of 10(5), 10(3) to 10(4), or 10(2) CFU/ml resulted in greater than or equal to 10(8) CFU/ml after incubation for 24, 48, or 72 h, respectively. Under these conditions, the bacteria grew as motile, spiral bacilli rather than the oval and coccal bacilli occasionally reported. Several bases supported good growth when supplemented with serum. For the determination of basal growth conditions, brucella broth base was used. Fetal calf serum (1%) provided maximum growth. Vitox was not necessary for growth and did not augment growth. C. pylori grew over a wide optimal pH range of 5.5 to 8.5.

Campylobacter↗
PubMed1987

Ciprofloxacin or trimethoprim-sulfamethoxazole as initial therapy for travelers' diarrhea. A placebo-controlled, randomized trial.

The efficacy of ciprofloxacin was compared with that of trimethoprim-sulfamethoxazole in a placebo-controlled trial of the 5-day treatment of acute diarrhea among 181 adults recently arrived in Guadalajara, Mexico. Both antimicrobial agents were significantly (p less than 0.0001) more efficacious than placebo in the treatment of diarrhea, with the average duration of diarrhea being 29, 20, and 81 hours, respectively, in the ciprofloxacin, trimethoprim-sulfamethoxazole, and placebo treatment groups. The antimicrobial agents were also more efficacious than placebo in treating diarrhea caused by enterotoxigenic Escherichia coli, invasive enteropathogens, and unknown pathogens. Both antimicrobials were effective in treating mild-to-moderate and moderate-to-severe disease, and both were well tolerated. Ciprofloxacin appears to be a logical alternative to trimethoprim-sulfamethoxazole in the initial treatment of acute travelers' diarrhea.

Adult↗
PubMed1986

Comparison of loperamide with bismuth subsalicylate for the treatment of acute travelers' diarrhea.

Loperamide hydrochloride was compared with bismuth subsalicylate for the treatment of acute nondysenteric travelers' diarrhea in 219 students visiting seven countries in Latin America. Subjects whose condition was not improved with therapy could elect to take trimethoprim-sulfamethoxazole. Persons receiving loperamide passed fewer unformed stools when compared with the bismuth subsalicylate group during the first four hours of therapy, from four to 24 hours, and from 24 to 48 hours after therapy was initiated. Among subjects with disease due to enterotoxigenic Escherichia coli, Shigella sp, other pathogens, and unknown agents, fewer unformed stools were passed by the loperamide-treated subjects than the bismuth subsalicylate-treated subjects for all time periods studied. No significant prolongation of disease was seen in subjects with shigellosis treated with loperamide. Eight of the loperamide-treated subjects experienced constipation compared with one in the bismuth subsalicylate-treated group; otherwise, there was no difference in minor side effects experienced between both treatment groups. We conclude that loperamide is a safe and effective alternative to bismuth subsalicylate for the treatment of nondysenteric travelers' diarrhea.

Acute Disease↗
PubMed1986

DNA content and prognosis of non-Hodgkin's lymphoma.

Ninety cases of non-Hodgkin's lymphoma diagnosed prior to the use of modern therapeutic regimens (1963-67) and 88 cases treated with such chemotherapy (1980-85) were studied using conventional morphology and flow cytometry. DNA aneuploidy as determined by flow cytometry was more common among high grade (38%) than low grade (19%) tumours (P less than 0.01). Measurements of proliferative index (S + G2 phase cells) revealed significantly increased values for high grade as compared with low grade lymphomas (P less than 0.001). In the first group of cases (1963-67) the relationship between histological grade and survival just failed to reach statistical significance over the long term (20 yr) (P = 0.1) but proved significant over 3 yr (P = 0.012). Differences in ploidy and proliferative index status were not associated with survival. In the second patient group (1980-85) attainment of complete remission following chemotherapy was associated with the presence of DNA aneuploidy in high grade tumours (P less than 0.05). The limited follow up of this group precluded assessment of survival in relation to ploidy.

Adolescent↗
PubMed1986

Role of a novel antidiarrheal agent, BW942C, alone or in combination with trimethoprim-sulfamethoxazole in the treatment of traveler's diarrhea.

The efficacy of BW942C, a novel enkephalinlike pentapeptide antidiarrheal agent, was compared with the efficacy of trimethoprim-sulfamethoxazole (TMP-SMX) and the combination of the two agents in a placebo-controlled trial of the 72-h treatment of acute diarrhea. Subjects with diarrhea but without bloody stools or fever greater than 102 degrees F (38.9 degrees C) were enrolled. Administered to 134 U.S. adults with diarrhea that developed shortly after their arrival in Guadalajara, Mexico, BW942C was more efficacious than TMP-SMX in relieving diarrhea and cramps in the first 12 h of therapy, especially among subjects with diarrhea caused by enterotoxigenic E. coli. In the BW942C treatment group, 25% of subjects eventually took additional therapy because their diarrhea did not respond to BW942C alone. Neurological side effects such as dizziness and light-headedness occurred more frequently among BW942C-treated subjects. Therapy for 3 days with TMP-SMX provided lasting relief comparable with previously reported 5-day therapy. Use of the combination of both agents provided the benefits of prompt relief afforded by BW942C and lasting relief afforded by TMP-SMX. BW942C might prove to be an agent suitable for the treatment of acute diarrhea, with TMP-SMX reserved for treatment of those who do not respond adequately. The empiric use of the combination of BW942C and TMP-SMX appears appropriate for the treatment of severe nondysenteric disease.

Antidiarrheals↗
PubMed1986

Lack of emergence of resistant fecal flora during successful prophylaxis of traveler's diarrhea with norfloxacin.

Norfloxacin, a new quinolone carboxylic acid derivative, was compared with an identical-appearing placebo preparation in a prospective, randomized, double-blind trial for prevention of traveler's diarrhea among 120 U.S. students arriving in Mexico. Prophylaxis was continued for 2 weeks. Diarrhea was defined as four unformed stools in 24 h plus an additional symptom of enteric disease. In the norfloxacin prophylaxis group, 4 of 56 subjects (7%) experienced diarrhea, compared with 36 of 59 subjects (61%) in the placebo group. The difference was significant (P less than 0.0001). In contrast to our previous experience with use of trimethoprim-sulfamethoxazole to prevent traveler's diarrhea, quantitative stool cultures in the norfloxacin-treated group revealed a significant decline of normal aerobic fecal flora during prophylaxis (P less than 0.0005). Among stool samples from norfloxacin-treated subjects, 32 of 38 (84%) cultured on day 7 and 34 of 37 (92%) cultured on day 14 had no gram-negative bacilli. After norfloxacin was discontinued, fecal flora returned to pretreatment levels. No gram-negative aerobic flora resistant to norfloxacin were found during weekly quantitative cultures before, during, or after therapy.

Bacteria↗
PubMed1986

Cutaneous infection in normal and immunocompromised mice.

Since a model of staphylococcal skin infection adequately reflecting human disease was unavailable, a self-limiting animal infection model specific for virulent Staphylococcus species was developed. A virulent strain of S. aureus, NCTC 9789 (ATCC 27700), was used to develop an infection model in adult, male CF-1 mice treated with 0 to 150 mg of cyclophosphamide (CY) per kg 4 days before challenge. Bacteria were inoculated onto the dorsal side of shaved mice at 0 to 10(6) CFU per mouse. Simultaneously, the skin was gently scraped to remove the superficial layers without drawing blood. The wound was occluded with impermeable film secured with surgical tape. At a CY dose of 50 mg/kg and an inoculum of 10(5) CFU, 89% of the mice (96 of 108) developed large abscesses (approximately 15-mm diameter). Mice which were not immunocompromised developed fewer abscesses (20 of 68). Generally, no abscesses formed when the mice were not wounded (1 of 62), occluded (0 of 89), or inoculated (11 of 50). The abscesses developed 24 to 48 h after challenge and persisted for 2 to 3 weeks. The challenge organism was isolated from the abscesses. The rates of abscess formation of three additional S. aureus strains varied widely in normal and CY-treated mice. Three strains of S. epidermidis, one of Micrococcus varians, and one of S. saprophyticus failed to cause abscesses. Bacterial proliferation studies demonstrated that a strain of S. aureus and a strain of S. epidermidis proliferated to the same levels 48 h after challenge. Immunosuppression and wounding had little effect on the levels of proliferation of S. aureus (P greater than 0.2). Without occlusion, however, S. aureus proliferated to significantly lower levels (P less than 0.005). This model may be be useful for screening topical anti-infective agents or studying the mechanisms of bacterial pathogenesis and host response.

Abscess↗
PubMed1985

Primary small intestinal lymphoma: a study of 39 cases.

Thirty-nine cases of primary small intestinal lymphoma were studied by morphological and immunohistochemical methods. The adjacent uninvolved mucosa was also examined for features suggestive of coeliac disease. Employing the immunogold silver staining (IGSS) technique and polyclonal primary antisera against alpha-l-antitrypsin, lysozyme and kappa and lambda light chains, 29 cases (74.5 per cent) were found to be B-cell lymphomas, seven (18 per cent) histiocytic tumours, one (2.5 per cent) Hodgkin's disease and two (5 per cent) remained unclassified. No specific lymphoma subtype was found to be associated with cases having the histological features of coeliac disease in the uninvolved adjacent mucosa. In 35 cases sufficient clinical information was available to assess the significance of histological type and stage in relation to survival. Although the histological type did not correlate with survival, stage did and tumours extending beyond the local lymph nodes were associated with a significantly worse prognosis.

Adolescent↗
PubMed1985

Efficacy of bicozamycin in preventing traveler's diarrhea.

Bicozamycin was compared with a placebo in a prospective, randomized, double-blind study of the prevention of acute diarrhea among 30 American travelers newly arrived in Guadalajara, Mexico. None of the 11 subjects given bicozamycin orally for 3 wk at a dosage of 500 mg four times a day developed diarrhea as compared with an incidence of 53% diarrhea (10 of 19 subjects) in the placebo group (p = 0.003). Bicozamycin was well tolerated. Studies of changes in predominant aerobic fecal flora among the 11 subjects treated with bicozamycin showed the appearance of only one highly resistant Citrobacter freundii at the end of 1 wk of therapy and only a total of six resistant isolates at the end of 3 wk. All resistant isolates failed to transfer this resistance to a recipient Escherichia coli. Bicozamycin seems to be well suited and safe as a prophylactic agent against traveler's diarrhea.

Acute Disease↗
PubMed1985

A newly recognized cause of travelers' diarrhea: enteroadherent Escherichia coli.

Adherence to HEp-2 tissue culture cells has been proposed as a virulence characteristic of enteropathogenic Escherichia coli (EPEC). A preliminary study revealed that E. coli that adhered to HEp-2 cells, but did not produce conventional enterotoxins and did not belong to recognized EPEC serogroups, could be isolated from adults from the United States who acquired diarrhea in Mexico. The purpose of this study was to determine the prevalence of these enteroadherent E. coli (EAEC) in 188 travelers with diarrhea and in 92 well travelers. EAEC were found in 14.9% of patients with diarrhea and in 7.6% of well individuals. Compared with well travelers, patients with diarrhea in whom no recognized enteropathogen could be identified had a 30.4% prevalence of EAEC (P less than .0003). These results further support our finding that EAEC are associated with diarrhea in travelers to Mexico and may help to explain the effect of antibiotics in the prevention and therapy for travelers' diarrhea in patients with no recognized bacterial enteropathogens.

Adhesiveness↗
PubMed1985

Evaluation of BW942C, a novel antidiarrheal agent, against enterotoxins of Escherichia coli and Vibrio cholerae.

BW942C, an enkephalin-like pentapeptide with anti-diarrheal activity, was tested against crude toxins of Escherichia coli and Vibrio cholerae in the Y-1 adrenal cell assay, rabbit ileal loop assay, and suckling mouse assay. The effects of BW942C on in vitro ion transport were measured in rabbit ileum mounted in Ussing chambers. In vitro, BW942C decreased basal short-circuit current (2.26 and 3.15 mueq cm-2 h-1 in experimental samples and controls, respectively; n = 7, P less than 0.05) and increased basal net Cl absorption (1.59 and 0.50 mueq cm-2 h-1 in experimental samples and controls, respectively; P less than 0.025). Net Na absorption was also increased, but not significantly. BW942C did not block the secretory response to a maximal dose of purified heat-stable toxin. BW942C directly enhanced intestinal fluid absorption. In the Y-1 adrenal cell assay, 5 mg of BW942C per ml inhibited the cytopathic effect caused by cholera toxin or heat-labile enterotoxin of E. coli. In the rabbit ileal loop assay, E. coli heat-stable toxin, E. coli heat-labile enterotoxin, and cholera toxin were inhibited 35 to 70% by administration of BW942C. With the suckling mouse model, the fluid accumulation caused by E. coli heat-stable toxin was ablated by prior treatment with BW942C. The drug is currently being evaluated in patients with acute secretory diarrhea to determine its effect on clinical symptoms.

Animals↗
PubMed1985

Lack of correlation between known virulence properties of Aeromonas hydrophila and enteropathogenicity for humans.

Five strains of Aeromonas hydrophila were selected for use in volunteer challenge trials. All five strains produced cytotoxin, hemolysin enterotoxin, lysine decarboxylase, acetylmethylcarbinol, and DNase. Two strains hydrolyzed esculin. All strains produced purulent hemorrhagic fluid accumulation in rabbit ileal loops, but failed to induce keratoconjunctivitis in guinea pigs. None of the strains produced mannose-resistant hemagglutinins. In challenge studies, diarrhea was demonstrated in only 2 of 57 human volunteers with doses ranging from 10(4) to 10(10) CFU. One person experienced mild diarrhea with 10(9) CFU of strain 6Y. A second person developed moderate diarrhea with 10(7) CFU of strain 3647. At higher doses, no diarrhea was seen in any of the volunteers. The other three strains (B158, SSU, 3284) failed to cause diarrhea and were not recovered from stools of volunteers. Additional virulence properties of A. hydrophila need to be sought before enteropathogenicity for humans can be established.

Aeromonas↗
PubMed1985

Detector for dual-energy digital radiography.

A detection scheme is described that allows one to accomplish dual-energy scanned projection digital radiography without switching the x-ray tube voltage. The method employs a high/low atomic number detector sandwich that simultaneously separates the x-ray beam transmitted by the patient into low and high energy components. To test the method, the response of a scanning linear array of energy-sensitive detectors was simulated, and bone and soft tissue images of an anthropomorphic chest phantom were obtained at 140 kVp. These were compared with similar images obtained by switching the x-ray tube voltage from 80 kVp to a heavily filtered 140 kVp. For comparable entrance skin exposures, the dual-energy detector images required a lower tube load and resulted in higher noise levels. The latter is attributable to the fact that the separation in energy between the high and low energy components is smaller with the dual-energy detector than with the voltage switching technique, and to misregistration problems associated with the simulation methodology. A detector design is also discussed that would result in improved energy separation and lower noise levels. In view of this possibility and the tube loading advantage, the method looks promising for digital scanned projection radiography.

Humans↗