Improved correlation of sweat chloride quantification by the CF Indicator System and the Gibson-Cooke Sweat Test.
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Biomedical subjects
Publications and source records attributed to I Brown.
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In 1985, residents of a suburban community in South Florida became concerned when several young women were diagnosed with breast cancer. First as individuals, then through a community-based effort, they attempted to gain attention and action on what they believed to be a cluster of breast cancer. Through their efforts to find out whether some agent or toxic exposure existed in the community that might have caused breast cancer, the women formed a community-based organization. This paper describes the activism of the women to resolve the issue through an epidemiologic study of the breast cancer occurrence in their community. Furthermore, it substantiates the need and role of rational community response in resolving community threats and concerns.
Alpha-particle track autoradiography has been used to define the in vivo cellular and intracellular distribution of radioactivity from the potential high linear energy transfer endoradiotherapeutic drug, 6-[211At]-astato-2-methyl-1,4-naphthoquinol bis(diphosphate) in tumor and relevant critical normal tissues of mice bearing a transplanted murine rectal carcinoma. A strikingly selective uptake of this compound into tumor cells, particularly into specific tumor cell nuclei, has been demonstrated. Its localization in certain tumor cells appears to depend on the presence of an onco-product, in this case an alkaline phosphatase isoenzyme, which is synthesized in some tumor cells and to which the compound targets. In curable tumors, it selectively concentrates in cells which may be regarded as tumor stem cells. There is low uptake into normal cells, particularly those in bone marrow, colon, and lung, where its sequestration is mainly extranuclear.
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Non-Hodgkin's lymphoma in association with Crohn's disease is a rare occurrence. A case of high grade B-cell lymphoma arising in an isolated segment of ileal Crohn's disease is described and the mechanisms for its possible causal association are discussed.
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Epidermal growth factor receptor can be used as a biological marker in tumours. We examined 199 samples from 150 patients with ovarian cancer first by using a single point screen, then by full Scatchard analysis, over a concentration range between 0.086-16.6 nM. Taking as positive those samples which showed a 20% difference between total binding and non specific binding, the EGFR was present in 39.7% of samples ranging from 36.4% in those tumours which were classified as being mucinous to 47.7% in the undifferentiated group. Thirty-six samples had a low affinity component (Kd greater than 1 nM), 27 had a high affinity component (Kd less than 1 nM) and 16 had both high and low affinity components to the EGFR. There was no statistical difference between degree of differentiation of the tumour and the presence of the EGFR nor between stage of the disease and EGFR presence.
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Eight female patients who fulfilled DSM-III criteria for posttraumatic stress disorder (PTSD) took part in this study. They were each assessed using the dexamethasone suppression test, the desipramine/growth hormone stimulation test, which examines alpha-2-adrenoceptor functioning, and the buspirone/prolactin test, which is thought to examine 5-HT receptor functioning. A control group consisting of age- and sex-matched healthy subjects was also tested. For each subject the three tests were conducted over 5 days. Hormone assays were carried out blind to diagnosis. Overall no differences on any of the three tests were detected between the patients and controls. The results do not support a link between PTSD and major depression.
A pilot study of holograms as substitutes for study casts during routine clinical treatment was carried out by four clinicians on 56 patients over a 6-month period. Three of the clinicians found holograms to be as informative as study casts and equally or more convenient, but one clinician considered holograms to be inferior to study casts in both these respects. In addition, replicate quantification of malocclusions by means of the Summers index showed very similar rates of random error for holograms and for study casts and no significant systematic error between the scores obtained. Currently available holograms merit further investigation as alternatives to study casts. Refinement to further improve the convenience, informativeness, and economy of the holograms is also being undertaken.
Interviews were conducted with parents of 100 children taken to a 'school attendance committee', because of persistent failure to attend school. Clinical assessment of the attendance problem was carried out so that children were categorized as 'school refusers' (N = 24), 'truants' (N = 53), 'both refusers and truants' (N = 9), or as 'neither' (N = 14). Any ICD-9 psychiatric disorder was separately identified. Cluster analysis of information collected in a standard way indicated that there was a group of children with the features of 'school refusal' who often had generalized neurotic disorders as well and who were mostly girls, another group with the features of 'truancy' all of whom had conduct disorders who were mainly boys, and a third cluster of children who were usually 'truants' but less often psychiatrically disturbed. The study provided evidence for the existence of school refusal with and without generalized neurotic disturbance in a non-clinical population.
Three thousand seven hundred and eighty-three patients with non-malignant hypertension attending the Glasgow Blood Pressure Clinic between 1968 and 1983 were followed prospectively for an average of 6.5 years. Left ventricular hypertrophy (LVH) was present at the outset in 34.5% of the men, and 12.8% had ST-T changes. The corresponding figures for women were 21.5% and 8.8%. The prevalence of LVH increased with the severity of hypertension and was higher for a given blood pressure level in men than in women. All-cause age-adjusted mortality, expressed as deaths per 1000 patient-years, was 27.6 for men with normal electrocardiographs, 43.2 for men with LVH only (P less than 0.001) and 56.9 for men with LVH and ST-T changes (P less than 0.001). Similar trends were seen in women. The excess risk associated with LVH, with or without ST-T changes, could not be explained by age, increased blood pressure at referral to the clinic, or smoking habit, when these factors were considered either separately or in combination (regression analysis). Thus, our study demonstrates that LVH, with or without ST-T changes is an independent risk factor for mortality in hypertensive patients.
Of 207 homosexual or bisexual patients with the acquired immune deficiency syndrome (AIDS), 24 with the AIDS related complex, and 39 with asymptomatic HIV infection, 32 patients were found to have mycobacterial infection. Mycobacterium tuberculosis was found in 13 patients with AIDS and in two with the AIDS related complex. M avium-intracellulare was found in 15 patients with AIDS and was disseminated in 12. One patient was infected with M kansasii and one with M ulcerans. Invasive procedures were frequently required to obtain positive bacteriological results. Subclinical carriage of M avium-intracellulare and other mycobacteria thought to be nonpathogenic was common in patients seronegative for the human immunodeficiency virus and at all stages of human immunodeficiency virus infection. All but one isolate of M tuberculosis were fully sensitive to standard antimycobacterial antibiotics. Response to treatment was usually rapid. M avium-intracellulare isolates were all resistant to first line agents in vitro, and antibiotics such as ansamycin and amikacin were required to obtain a clinical response.
Data from 121 consecutive patients with hypertension and renovascular disease, first diagnosed between 1975 and 1982 in Glasgow and Newcastle, were analysed retrospectively to determine the factors which influenced their outcome. Thirty-six patients died between the data of arteriography and 1st January 1987, giving five and ten year survival rates of 83% and 67%. Survival was greatly reduced in comparison with that of age-sex-matched controls in the general population of the West of Scotland, and was also less than that of essential hypertensives matched for age, sex, initial diastolic blood pressure and smoking habit who had attended the Glasgow Blood Pressure Clinic during the same period. Multivariate analysis showed that age, cigarette smoking and presence of atheromatous disease were significantly and independently related to outcome among the patients with renovascular disease, whereas male sex, centre of origin, severity of hypertension when first seen, initial renal function and presence of bilateral disease were not. Despite a trend towards benefit from surgical intervention (ten year survival in medical group 62%, in surgical group 71%; p = 0.19) our data do not prove that intervention is better than medical treatment, largely because the decision on intervention was not randomised. A prospective trial would be required to answer this important question.
The investigations concerning a targeted radiotherapy for pigmented melanoma with a radiolabeled phenothiazine derivative, 3,7-(dimethylamino)phenazathionium chloride [methylene blue (MTB)], were continued using melanotic and amelanotic sublines of B16 melanoma. Two radionuclides, 125I and 211At, emitting Auger electrons and alpha particles, respectively, replaced 35S previously studied since their biological effectiveness is significantly higher. In vitro autoradiography revealed a selective accumulation of methylene blue labeled with either of the radioisotopes in pigmented melanoma cells but its absence in nonpigmented cells. Treatments with [125I]MTB and [211At]MTB were performed both in vitro and in vivo, with their effectiveness determined by lung clonogenic assay. [125I]MTB proved to be relatively ineffective when incorporated into melanosomes distributed in the cytoplasm, i.e., too far away from the genome. Conspicuous therapeutic effects were achieved with [211At]MTB for pigmented melanoma only. 211At itself did not affect either of the investigated sublines of B16 melanoma confirming once again the high affinity of methylene blue to melanin. Calculations of cumulative radiation doses from [211At]MTB deposited in melanotic melanoma tumors and pigmented normal organs which would be at a particular risk led to the conclusion that [211At]MTB could be used for a highly selective and very efficient targeted radiotherapy of pigmented melanomas without damaging normal tissues.
In order to study the mechanisms of synaptogenesis in the rat cerebellar cortex, a library of monoclonal antibodies has been generated against proteins of the isolated synapse. One recognizes a glycosylated 38 kDa protein that is concentrated in the synaptic vesicle fraction and resembles synaptophysin biochemically in its molecular weight, charge, and pattern of glycosylation. In the adult cerebellar cortex, the antisynaptophysin(mabQ155) immunoreactivity is codistributed with synapses. Immunoreactivity is strongest in the molecular layer where punctate deposits of reaction product outline the Purkinje cell dendrites. Discrete small profiles, consistent with the distribution of basket cell axon terminals, surround the Purkinje cells, and in the granular layer the synaptic glomeruli are intensely stained. There is no immunoreactivity in the white matter axon tracts. Electron microscope immunocytochemistry confirms the synaptic location of the antigen and suggests that the reaction product is associated with synaptic vesicles. Both round and flat vesicle populations are immunoreactive. Antisynaptophysin(mabQ155) has been used to follow synaptogenesis in the developing rat cerebellum. In the newborn rat (P0), despite the paucity of synapses, there is some specific immunoreactivity, especially in the subcortical white matter. Electron microscopy shows that the antigenicity is associated with vesicles within growth cones, filopodia, and immature axon profiles. During development, antisynaptophysin immunoreactivity increases progressively, along with the maturing cell populations, for both the granule cell-Purkinje cell and the mossy fiber-granule cell synapses. Quantitative biochemical analysis confirms the cytochemical results. These data suggest that neuronal growth cones express a synapse-specific antigen before complete morphological synapses are present.