Biomedical subjects
Publications and source records attributed to D Morgan.
We describe a case of non-pyothorax-associated primary pleural lymphoma with bone marrow and central nervous system involvement, and complex karyotypic abnormalities involving nullisomy chromosome 17 and multiple breakpoints that are commonly associated with acute leukemia and myeloproliferative diseases.
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PURPOSE: The dose of radiation that locally controls human tumors treated electively or for gross disease is rarely well defined. These doses can be useful in understanding the dose requirements of novel therapies featuring inhomogeneous dosimetry and in an adjuvant setting. The goal of this study was to compute the dose of radiation that locally controls 50% (TCD50) of tumors in human subjects. METHODS AND MATERIALS: Logit regression was used with data collected from single institutions or from combinations of local control data accumulated from several institutions treating the same disease. RESULTS: 90 dose response curves were calculated; 62 of macroscopic tumor therapy, 28 of elective therapy with surgery for primary control. The mean and median TCD50 for gross disease were 50.0 and 51.9 Gy, respectively. The mean and median TCD50 for microscopic disease control were 39.3 and 37.9 Gy, respectively. At the TCD50, an additional dose of 1 Gy controlled an additional 2.5% (median) additional patients with macroscopic disease and 4.2% (median) additional patients with microscopic disease. For both macro- and microscopic disease, an increase of 1% of dose at the TCD50 increased control rates approximately 1% (median) or 2-3% (mean). A predominance of dose response curves had shallow slopes accounting for the discrepancy between mean and median values. CONCLUSION: Doses to control microscopic disease are approximately 12 Gy less than that required to control macroscopic disease, and are about 79% of the dose required to control macroscopic disease. The percentage increase in cures expected for a 1% increase in dose is similar for macroscopic microscopic disease, with a median value of approximately 1%/% and a mean of approximately 2.7%/%.
From 1 April to 31 May 1993, 64 cases of cryptosporidiosis were diagnosed within one district health authority. Forty were classified as primary cases, 35 of whom were clustered in an area supplied by a discrete public water supply that supplied the majority of homes in a large town. Most of the water in this supply is abstracted from boreholes and some is filtered before distribution. Households that received mains water from this supply were 15 times more likely to be affected than households nearby that received water from other sources. A case control study demonstrated a dose response relationship between consumption of water obtained from the town supply and risk of illness. Very low concentrations of cryptosporidial oocysts were detected in the water supply on four occasions several weeks after the outbreak. Environmental investigation failed to reveal a likely mechanism for contamination of the water supply.
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Ornithine decarboxylase (ODC) plays a key role in the biosynthesis of polyamines, which are necessary for cell growth and differentiation. ODC expression is very tightly controlled in all normal cells; however, regulation of its expression is altered in many tumor cells resulting in much higher basal levels of ODC in tumors. To investigate the potential role of ODC overexpression in epidermal tumorigenesis, we constructed a replication-defective retroviral vector to overexpress a truncated ODC protein in epidermal cells. Stable viral infection of mouse epidermal cells dramatically increases not only the basal ODC activity but also the basal putrescine and spermidine levels. In all infected epidermal cells with high polyamine levels, DNA synthesis is increased as measured by [3H]thymidine incorporation into DNA as well as increased bromodeoxyuridine staining in the nuclei of ODC-infected epidermal cells. ODC viral infection of nontumorigenic BK-1 epidermal cells and primary cultures of mouse keratinocytes and fibroblasts from newborn mouse skin yields no tumors when injected s.c. into athymic nude mice or when transplanted as skin grafts onto nude mice. Epidermal cell lines SP-1 and 308 (which possess an activated rasHa gene) are not tumorigenic when injected s.c. into nude mice. However, following infection with the ODC virus, they form tumors filled with keratin and papilloma-like projections of hyperplastic epidermal cells displaying dysplasia and many mitotic figures. These data indicate that ODC overexpression by itself is not sufficient to induce tumors in normal cells but that increased expression of ODC enhances tumor development in initiated premalignant epidermal cells.
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The ability of mu and kappa opioids to alter the discriminative-stimulus and rate-decreasing effects of the 5-HT1A receptor agonist 8-OH-DPAT was examined in rats trained to discriminate either a low (0.1 mg/kg) or a high (0.3 mg/kg) dose of 8-OH-DPAT from water using a two-lever food-reinforced drug discrimination procedure. The mu opioids, morphine and fentanyl, and the kappa opioids, U50,488 and bremazocine, failed to substitute for the 8-OH-DPAT stimulus, even when tested up to doses that substantially reduced rates of responding. During antagonism tests, selected doses of the mu opioids, morphine and fentanyl, administered at various pretreatment times, attenuated the stimulus effects of both training doses of 8-OH-DPAT. Moreover, morphine (135-min pretreat) and fentanyl (15-min pretreat) produced rightward shifts in the 8-OH-DPAT dose-effect curve that were partially surmountable and naltrexone-reversible. In contrast to the effects of the mu opioids, the kappa opioids, U50,488 and bremazocine, failed to alter the stimulus effects of the training dose of 8-OH-DPAT, regardless of dose or pretreatment time. The rate-decreasing effects of 8-OH-DPAT were not altered substantially by either the mu or kappa opioids examined. The present study demonstrates that the stimulus effects, but not the rate-decreasing effects, of 5-HT1A receptor agonists can be modulated by mu opioids, whereas neither of these effects are changed by kappa opioids.
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This paper describes an outbreak of gastrointestinal illness affecting at least 110 people, of whom 41 had microbiological confirmation of Campylobacter jejuni infection. The outbreak of infection was found to have been associated with consumption of inadequately pasteurised milk from a local dairy. The problem of enforcement of food and safety regulations when milk from dairies fails the phosphatase test is discussed. The prevalence of seroconversion to campylobacter in the community is estimated from a sample of cases and controls involved in this outbreak.
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G-CSF-mobilized peripheral blood progenitor cells (PBPC) were utilized in a patient who failed to engraft after an unmanipulated HLA-matched allogeneic bone marrow transplant. Marrow engraftment occurred after repeated conditioning with high-dose cyclophosphamide and PBPC infusion. Severe graft-versus-host disease (GVHD) developed shortly after marrow engraftment. The role of PBPC in allogeneic transplant, the associated potential risk of GVHD, and the necessity of reconditioning before stem cell reinfusion are discussed.
To determine the source and extent of an outbreak of Vibrio cholerae O139 Bengal infections among 630 cruise ship passengers to Southeast Asia, a retrospective cohort study was done. Questionnaires were sent to all passengers from the United States, Canada, and the United Kingdom, and serum samples were requested from all passengers reporting diarrhea. A case was defined as diarrheal illness with onset between 8 and 28 February 1994 and a cholera antitoxic antibody titer > or = 800. Six passengers, including 1 with bacteremia, met the case definition. Illness was associated with eating yellow rice at a buffet restaurant in Bangkok on 10 February (relative risk undefined, P = .005). This international outbreak demonstrates foodborne transmission of Vibrio cholerae O139 Bengal, an emerging cause of epidemic cholera in Asia, to tourists from Western countries. Physicians should suspect infection with either V. cholerae O1 or O139 in any patient with severe watery diarrhea after travel to the developing world.
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A noninvasive technique has been developed and validated for calculating capacitive and oscillatory systemic arterial compliance with the use of pulse wave analysis and a modified Windkessel model. Application of the technique to subjects with hypertension, postmenopausal women with symptomatic coronary artery disease, and appropriate control subjects has confirmed a reduction of oscillatory compliance in the disease states and an increase in capacitive and oscillatory compliances in response to vasodilator drugs. This method should be useful in screening subjects for early evidence of vascular disease and in monitoring the response to therapy.
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The doctor/patient relationship is unique. The doctor's surgery/clinic can be likened to the confessional and the duty of confidence to a patient does not end with the patient's death. It is ongoing. It is accepted that in the Armed Forces, a Commanding Officer can request disclosure of all relevant medical information by his medical officer. The medical officer in this case would need to be guided not only by military law but also by guidelines laid down by the General Medical Council (the GMC 'blue book'). Each case needs to be considered on its own merit. The Medical Defence Union is available to discuss individual cases with its members. (An MDU booklet 'Confidentiality' is available free to members. Application may be made to the Medical Defence Union, 3 Devonshire Place, London W1N 2EA.)
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