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Biomedical subjects

R Mann

Publications and source records attributed to R Mann.

At least 19 recordsLinked to original sources
PubMed1992

Comparison of a second-generation combination chemotherapeutic regimen (m-BACOD) with a standard regimen (CHOP) for advanced diffuse non-Hodgkin's lymphoma.

BACKGROUND: In 1984, the Eastern Cooperative Oncology Group began a randomized controlled clinical trial of patients with advanced (stage III or IV) diffuse mixed or diffuse large-cell lymphoma to determine whether complete-remission rates, survival, and toxicity differed when patients were treated with a chemotherapeutic regimen containing cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP), as compared with a regimen containing bleomycin, doxorubicin, cyclophosphamide, vincristine, dexamethasone, methotrexate, and leucovorin (m-BACOD). METHODS: From July 1984 through January 1988, 392 patients were enrolled, 325 of whom (83 percent) were eligible for the analysis and capable of being evaluated. The extent of disease was defined according to standard staging techniques, including bilateral bone-core biopsies in 88 percent of patients. Randomization was stratified according to age (< 60 or > or = 60 years), performance status (0, 1, or other), stage (III or IV), and histologic presentation (diffuse mixed or diffuse large-cell lymphoma). RESULTS: After a median follow-up of four years, there were no significant differences in rates of complete remission, time to treatment failure, disease-free survival, or overall survival in the patients treated with CHOP as compared with those treated with m-BACOD. However, there was more severe and life-threatening pulmonary, infectious, and hematologic toxicity associated with the m-BACOD regimen. In an attempt to measure the importance of dose intensity in the 325 patients who could be analyzed, we retrospectively calculated dose intensity (measured in milligrams per square meter of body-surface area per week) and normalized dose intensity (defined as a percentage of the prescribed dose) for all drugs. The median normalized dose intensity for both cyclophosphamide and doxorubicin was found to be greater in the patients treated with CHOP than in those treated with m-BACOD. CONCLUSIONS: For patients with stage III or IV diffuse mixed or diffuse large-cell lymphoma, CHOP is superior to m-BACOD, but the role of dose intensity is not yet clear.

Age Factors↗
PubMed1992

t(11;18)(q21;q21) is a recurrent chromosome abnormality in small lymphocytic lymphoma.

We have identified two cases of previously untreated, small lymphocytic lymphoma with extranodal involvement, which had a reciprocal translocation, t(11;18)(q21;q21), as the sole cytogenetic abnormality. These two cases are remarkably similar to two previously reported cases carrying this translocation with regard to clinical features, cytogenetic abnormality, histologic subtype, and immunophenotype. Molecular genetic analysis of these two cases revealed clonal gene rearrangement of the IGH locus but only germline configuration of the BCL2 oncogene at 18q21 when probes and conditions that usually identify BCL2 rearrangement in lymphomas were used. Lymphomas bearing an (11;18) rearrangement appear to make up a phenotypically identifiable subgroup. Identification of the genes at the translocation breakpoints will be important.

Aged↗
PubMed1992

Gastric and colorectal cancer in the rural Indian subcontinent: a survey of patients attending mission hospitals.

37 missionaries working in India, Nepal, Pakistan, Bangladesh and Bhutan completed questionnaires regarding their clinical practice during the year 1980. Information was collected on the frequency of both gastric and colorectal cancers. More than 500,000 out-patients were reviewed and over 100,000 inpatients treated. A total of 291 gastric tumours and 169 colorectal carcinomas were diagnosed. Surgery was performed in 82% of the hospitals but only 36% had a histology service. In India and Pakistan there was no significant difference between the incidence of gastric and colorectal neoplasms. The relative risk of developing gastric rather than colorectal cancer in Bangladesh was 8 (95% confidence limits 4.5-14.2) and in Nepal the relative risk was 4 (95% confidence limits 2.0-7.0). A significant variation in the occurrence of cancer was observed between countries. Nepal had the highest and Pakistan the lowest numbers of both gastric and colorectal tumours. It seems likely that local environmental factors, such as diet, play a significant role in the development of these tumours.

Bangladesh↗
PubMed1992

Enhancement of incisional wound healing and neovascularization in normal rats by thrombin and synthetic thrombin receptor-activating peptides.

To better define thrombin-receptor interactions, we synthesized human thrombin peptides and identified binding-domain peptides that bind thrombin receptors and activate mitogenic signals (Glenn, K.C., G.H. Frost, J.S. Bergmann, and D.H. Carney. 1988. Pept. Res. 1:65-73). Treatment of full dermal dorsal incisions with a single topical application of thrombin receptor-activating peptide (TRAP-508) or human alpha-thrombin in saline enhances 7-d incisional breaking strength in normal rats up to 82% or 55% over saline-treated controls, respectively. Control wounds require approximately 11.5 d to achieve breaking strength equivalent to TRAP-treated wounds at day 7. Thus, a single application of TRAP accelerates healing, shifting the time course forward by up to 4.5 d. Histological comparisons at day 7 show more type I collagen, less evidence of prolonged inflammation, and an increase in number and maturity of capillaries in TRAP- and thrombin-treated incisions. Angiograms also show 50-65% more functional vascularization going across thrombin- and TRAP-treated surgical incisions. Thus, alpha-thrombin and thrombin peptides, such as those released following injury, appear to initiate or enhance signals required for neovascularization and wound healing. The ability to accelerate normal wound healing events with synthetic peptides representing receptor binding domains of human thrombin may offer new options for management of wound healing in man.

Amino Acid Sequence↗
PubMed1991

Aminergic innervation of the gall bladder in man and dog.

This study has compared the innervations of human and canine gall bladders, using immunohistochemical localization of neuron-specific enolase to visualize all intramural nerves and localization of tyrosine hydroxylase, DOPA decarboxylase and serotonin to visualize different populations of aminergic neurons. The vasculature, the wall smooth musculature and the intramural ganglion cells receive a substantial sympathetic innervation, in both species. By contrast, the mucosa appears to be supplied almost entirely by non-sympathetic fibres. On the basis of DOPA decarboxylase immunoreactivity, a large proportion of the biliary sympathetic nerves in both species may be dopaminergic. Human gall bladder also contains a population of putatively tryptaminergic, intramural neuron-like cells. However, there was no evidence for tryptaminergic innervation of effector structures in the gall bladder wall.

Adult↗
PubMed1991

Sympathetic innervation of the liver in man and dog: an immunohistochemical study.

The sympathetic innervation of human and dog livers was examined by immunohistochemical localization of neuron-specific enolase to visualize the total complement of hepatic nerves and the localization of two enzymes involved in catecholamine synthesis, tyrosine hydroxylase and dihydroxyphenylalanine decarboxylase, to visualize sympathetic nerves. Similar results were obtained for both man and dog. About 60% of the non-myelinated axons supplying the hepatic parenchyma, and virtually all those supplying the vasculature, appeared to be sympathetic. The pattern of dihydroxyphenylalanine decarboxylase immunoreactivity was compatible with innervation of the intrahepatic hepatic arteries and portal veins by dopaminergic as well as by noradrenergic sympathetic nerves. By contrast, there was no evidence for a dopaminergic component in the parenchymal sympathetic innervation.

Animals↗
PubMed1991

Exposure of humans to ambient levels of ozone for 6.6 hours causes cellular and biochemical changes in the lung.

An acute (2 h) exposure of humans to 0.4 ppm ozone initiates biochemical changes in the lung that result in the production of components mediating inflammation and acute lung damage as well as components having the potential to lead to long-term effects such as fibrosis. However, many people are exposed to lower levels of ozone than this, but for periods of several hours. Therefore, it is important to determine if a prolonged exposure to low levels of ozone is also capable of causing cellular and biochemical changes in the lung. Nonsmoking males were randomly exposed to filtered air and either 0.10 ppm ozone or 0.08 ppm ozone for 6.6 h with moderate exercise (40 liters/min). Bronchoalveolar lavage (BAL) was performed 18 h after each exposure, and cells and fluid were analyzed. The BAL fluid of volunteers exposed to 0.10 ppm ozone had significant increases in neutrophils (PMNs), protein, prostaglandin E2 (PGE2), fibronectin, interleukin-6 (IL-6), and lactate dehydrogenase (LDH) compared with BAL fluid from the same volunteers exposed to filtered air. In addition, there was a decrease in the ability of alveolar macrophages to phagocytize yeast via the complement receptor. Exposure to 0.08 ppm ozone resulted in significant increases in PMNs, PGE2, LDH, IL-6, alpha 1-antitrypsin, and decreased phagocytosis via the complement receptor. However, BAL fluid protein and fibronectin were no longer significantly elevated. We conclude that exposure of humans to as low a level as 0.08 ppm for 6.6 h is sufficient to initiate an inflammatory reaction in the lung.

Adolescent↗
PubMed1991

Tuberculosis.

Explore the source record for details and available documents.

Antitubercular Agents↗
PubMed1991

Neuronal metabolism and DOPA decarboxylase immunoreactivity in terminal noradrenergic sympathetic axons of rat.

This study was undertaken to determine whether immuno-histochemical staining for DOPA decarboxylase (DDC) is present in axons of rat noradrenergic sympathetic neurons. A sparse plexus of varicose axons exhibiting DDC-like immunoreactivity (DDC-IR) was associated with blood vessels and acini in the submandibular gland, but this was much less extensive than the population that exhibited tyrosine hydroxylase-like immunoreactivity (TH-IR). The varicose terminal TH-IR axons in atrium, spleen, and vas deferens were devoid of DDC-IR both in grown rats and during the post-natal period of axon growth, although weak DDC-IR was seen in large pre-terminal nerve bundles. Similar patterns of staining were seen with paraffin-embedded and with frozen, formaldehyde-fixed material. No enhancement of DDC-IR was seen in any tissue after chronic alteration of catecholamine turnover with reserpine or alpha-methyl-para-tyrosine, and the numbers of submandibular DDC-IR axons were not increased by disruption of axonal transport with colchicine or by decentralization of the superior cervical ganglion. We conclude that terminal noradrenergic axons contain insufficient DDC-IR for microscopic visualization, regardless of their metabolic state, reinforcing previous evidence that DDC-IR can be used as a histochemical marker for dopaminergic axons. By this criterion, the rat submandibular gland may receive a sparse dopaminergic innervation.

Animals↗
PubMed1991

Role of bradykinin in ovine endotoxemia.

We determined if the cardiopulmonary response to endotoxin (LPS) is mediated by bradykinin (BK). Sheep (n = 30) were prepared for chronic study with cardiopulmonary catheters, and chronic lung lymph fistulae. They were divided into the following study groups: A) BK infusion; B) LPS; C) LPS with angiotensin converting enzyme inhibitor (ACEI); D) ACEI alone; E) LPS with BK antagonist. Cardiac index and mean arterial pressure fell (6.9 +/- 0.4 to 5.3 +/- 0.3 L/min/m2 and 93 +/- 4 to 72 +/- 3 mmHg, respectively), and pulmonary lymph flow increased (10.5 +/- 3.0 to 17.8 +/- 4.3 ml/hr) during BK infusion. Addition of ACEI during BK infusion reduced the amount of BK necessary to induce a comparable response (125 to 2 micrograms/kg/hr). Administration of ACEI to LPS animals did not significantly alter their cardiopulmonary responses. BK antagonist did not change the response to LPS. Although the kallikrein-kinin pathway is believed to be activated during the septic response, our data do not lend support for the hypothesis that bradykinin is an important mediator of the cardiopulmonary changes.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1990

The effect of venous obstruction in infected pedicle flap.

A new model of soft-tissue infection is used to investigate the effect of the local wound environment on the septic focus. Island pedicle flaps were raised on the buttock of 24 adult ewes and multiply inoculated with Staphylococcus aureus. Flaps with bacterial inoculation, without compromise of venous outflow, showed distal necrosis (mean +/- SEM percent of surface area, 25.8% +/- 8.6%) and developed septic foci with bacterial counts one log less than the amount injected. Flaps with inoculation and venous outflow obstruction underwent subtotal necrosis (mean percent of surface area, 73.3% +/- 11.2%) and had counts two logs higher than the nonobstructed flaps but without discrete septic foci. Flaps without inoculation, with or without venous obstruction, survived completely. Venous outflow obstruction is shown herein to potentiate tissue necrosis by raising bacterial counts in a septic focus and preventing defensive abscess formation by the host.

Animals↗
PubMed1990

Identification of dopaminergic nerves in humans.

It has been well-documented in animal studies that axons of dopaminergic neurons can be distinguished from those of noradrenergic neurons by their content of DOPA decarboxylase (DDC). We now have evidence that DDC immunoreactivity is also specific for dopaminergic axons in the sympathetic nervous system of man. Thus, light microscope immunocytochemistry can be used to screen human tissues for potential dopaminergic inputs, preparatory to functional analysis. Application of this technique has so confirmed the innervation by dopaminergic neurons of human kidney and hepatic vasculature. Although similar nerves are found in kidney and liver of dog, the specific target structures supplied, and therefore the specific functional effects of nerve activation, are different.

Dopamine↗
PubMed1990

Inflammatory bowel disease in the rural Indian subcontinent: a survey of patients attending mission hospitals.

39 missionaries working at 38 separate mission hospitals or clinics in Bangladesh. India, Nepal and Pakistan completed questionnaires about their clinical practice during the previous year, 1980. Data were collected about gastrointestinal disorders, including coeliac disease, tropical sprue, bloody diarrhoea, amoebiasis, typhoid, cholera, inflammatory bowel disease and diverticular disease. More than 386,000 out-patients and over 56,000 in-patients were treated with an estimated 12,272 cases of bloody diarrhoea, 7,310 of amoebiasis, 2,113 of typhoid and 872 cases of intestinal tuberculosis, 74 cases of inflammatory bowel disease were diagnosed, of which 56 were ulcerative colitis and the remainder were said to have Crohn's disease. Surgery was performed in 28 hospitals, but only 10 (26%) had a histology service. Inflammatory bowel disease appears to be a relatively more common cause of diarrhoea in the Indian subcontinent than in sub-Saharan Africa (z = 5.47, p less than 0.001). The proportion of patients with bloody diarrhoea who have ulcerative colitis Crohn's disease was similar throughout the region. The rate of cases having ulcerative colitis rather than Crohn's disease was greater in India (z = 3.1, p less than 0.005), and in Bangladesh (z = 3.2, p less than 0.005), than in Pakistan (z = 1.28, NS) or Nepal and Bhutan (z = 0, NS). The relative risk of Indians developing ulcerative colitis rather than Crohn's disease is 2.6 (95% confidence limits 1.4-4.8, NS). This may reflect diagnostic difficulties in distinguishing Crohn's disease from intestinal tuberculosis, but it may also shed light on similar differences now being reported in migrant groups in Western Europe.

Bangladesh↗
PubMed1989

Consultations in general practice: a comparison of patients' and doctors' satisfaction.

OBJECTIVE: To provide an objective means of assessing patients' and doctors' satisfaction with a consultation. DESIGN: Questionnaire study of patients and general practitioners after consultations. SETTING: Urban general practice. SUBJECTS: 250 Patients attending consecutive consultations conducted by five general practitioners. MAIN OUTCOME MEASURE: Identification of deficiencies within a consultation as perceived by both doctors and patients. RESULTS: The doctor's and patient's questionnaires for each consultation were matched and the results analysed on a group basis. The response rate for individual questions was high (81-89%). The doctors and patients significantly disagreed about the doctors' ability to assess and put patients at ease, to offer explanations and advice on treatment, and to allow expression of emotional feelings and about the overall benefit that the patients gained from the consultation. In all cases of disagreement the doctor had a more negative view of the consultation than the patient. CONCLUSIONS: The results of giving structured questionnaires on consultations to both patients and doctors could be a useful teaching tool for established doctors or those in training to improve the quality and sensitivity of care they provide.

Attitude of Health Personnel↗