Biomedical subjects
Publications and source records attributed to S Whitehead.
A 57-year-old man presented on multiple occasions to various hospitals with thrombocytopenia and complaints of easy bleeding. Despite his repeated denials of quinine use, laboratory investigations confirmed a diagnosis of quinine-induced thrombocytopenia. He appeared to have factitious disorder and to have discovered a novel means of precipitating symptoms.
Systematic sequencing of the genome of Saccharomyces cerevisiae has revealed thousands of new predicted genes and allowed analysis of long-range features of chromosomal organization. Generally, genes and predicted genes seem to be distributed evenly throughout the genome, having no overall preference for DNA strand. Apart from the smaller chromosomes, which can have substantially lower gene density in their telomeric regions, there is a consistent average of one open reading frame (ORF) approximately every two kilobases. However, one of the most surprising findings for a eukaryote with approximately 6,000 genes was the amount of apparent redundancy in its genome. This redundancy occurs both between individual ORFs and over more extensive chromosome regions, which have been duplicated preserving gene order and orientation. Here we report the entire nucleotide sequence of chromosome XIII, the sixth-largest S. cerevisiae chromosome, and demonstrate that its features and organization are consistent with those observed for other S. cerevisiae chromosomes. Analysis revealed 459 ORFs, 284 have not been identified previously. Both intra- and interchromosomal duplications of regions of this chromosome have occurred.
We investigated the effects of cocultured macrophages on progesterone release from granulosa cells obtained at different stages of the rat estrous cycle and determined whether the immunosuppressive actions of the synthetic glucocorticoid can modulate the effects of cocultured macrophages. Basal and hCG-stimulated progesterone release from granulosa cell-only cultures varied according to the stage of the estrous cycle at which granulosa cells were obtained, but macrophages exerted profound inhibitory effects on both basal and hCG-stimulated steroidogenesis at all stages. These inhibitory effects were partially reversed by the addition of dexamethasone (5 x 10(-7) to 5 x 10(-5) M) to the culture medium. Measurement of nitrite accumulation in the media, as an index of nitric oxide production, showed that granulosa cells produce very low levels of this metabolite compared with macrophages, although granulosa/luteal cells from freshly ruptured follicles of estrous rats produced significantly higher concentrations of nitrite compared with granulosa cells obtained from diestrous and proestrous rats. Dexamethasone had only limited effects in suppressing the accumulation of nitrite, showing that the macrophages were synthesizing nitric oxide synthase and suggesting that the action of dexamethasone was independent of nitric oxide. Macrophages also inhibited the steroidogenic response of granulosa cells to forskolin (5 x 10(-6) M to 10(-4) M) and dibutyryl cAMP (1mM and 0.5 mM) and the potentiation of the response by the addition of hCG. However, this inhibition was reversed by the presence of 5 x 10(-6) M dexamethasone, and responses were comparable with those measured from granulosa cell-only cultures. Overall, the results suggest that macrophage inhibition of progesterone synthesis acts at a site distal to the generation of cAMP and that dexamethasone reverses this inhibition.
The aim of the study was to assess the completeness and accuracy of cancer registration for cutaneous malignant melanoma. The study was conducted in seven health districts in England and one health board in Scotland from 1987 to 1989 with a total resident population of 3.6 million. Records from pigmented lesion clinics and pathology laboratories collected during the Cancer Research Campaign's health education programme to promote the early detection of melanoma were matched with cancer registrations from a total of five regional cancer registries. In England 74% out of a total of 642 cases of invasive malignant melanomas (ICD 172) and 44% out of a total of 155 in situ melanomas (ICD 232) had been registered compared with 96% and 100% respectively in Scotland. A significantly higher proportion of late-stage cases was found among registered than among non-registered cases in England (P < 0.001). In all registries the majority of superficial spreading in situ melanomas were miscoded as invasive cases. The annual incidence of invasive malignant melanoma in the English study areas was found to be seven per 100,000 in men and 11 per 100,000 in women, similar to that reported in Scotland. The registries are best at recording thick or late-stage melanomas. As the skin cancer target for Health of the Nation depends on monitoring trends in the incidence of malignant melanoma, future improved ascertainment of cases and changes in the type of cases being registered must be taken into account.
From 1987 to 1989 a campaign to promote the early detection of cutaneous malignant melanoma was conducted in the areas of seven health authorities in England and Scotland (total population 3.6 million). Data were collected on 17,155 patients attending pigmented lesion clinics (PLCs) in each study area during the campaign. After a dramatic rise in PLC referral rates in the first month of the campaign the average monthly referral rate among the target population in the study period settled to an average of 13 per 10(5), a twofold increase compared with the pre-campaign period. Over 85% of patients at all PLCs were seen within 4 weeks of referral from their general practitioners. The melanoma to non-melanoma detection ratio was (1:33). The organization of future early detection initiatives needs careful review and planning, in order to improve their effectiveness in all sections of the population, and to enable health services to cope with the increased work-load.
The effect on the detection and characteristics of melanoma, resulting from the Cancer Research Campaign's health education programme to promote the early detection of melanoma in the general population, was studied from 1987 to 1989. The seven study areas in England and Scotland yield a target population of 3.6 million. Data were collected from local clinic-based registers, pathology laboratories, and the cancer registries. The average annual incidence rates of melanoma were seven and 12 per 10(5) in males and females, respectively, age-standardized to England and Wales, 1988. These rates are similar to the national figures for Scotland, where there is a national melanoma register, but higher than those reported by the English and Welsh cancer registries. The incidence was significantly higher in females than males (P < 0.001), and increased with age. Fifty-three per cent and 65% of cases in males and females, respectively, were thin (Breslow thickness < or = 1.5 mm), similar to the national figures from Scotland. No significant decrease in the incidence of late-stage tumours was found in either sex as a result of the campaign. Because of difficulties with ascertainment of cases in England, the main evaluation will focus on future trends in mortality rates for melanoma.
The clinical and haematological features of 77 patients of Bini and 107 patients of Yoruba origin with homozygous sickle cell (SS) disease have been compared. The Bini population were generally younger and had a slightly lower incidence of alpha thalassaemia but even after correction for age and alpha thalassaemia status, this group had significantly lower HbA2 and higher HbF and MCV values. Clinically the Bini group had significantly less dactylitis and more acute chest syndrome. The decreased frequency of dactylitis is consistent with the higher HbF level in the Bini population and the mechanism of the other effects are discussed.
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Deferoxamine (DF) has antimalarial activity that can be demonstrated in vitro and in vivo. This study is designed to examine the speed of onset and stage dependency of growth inhibition by DF and to determine whether its antimalarial activity is cytostatic or cytocidal. Growth inhibition was assessed by suppression of hypoxanthine incorporation and differences in morphologic appearance between treated and control parasites. Using synchronized in vitro cultures of Plasmodium falciparum, growth inhibition by DF was detected within a single parasite cycle. Ring and nonpigmented trophozoite stages were sensitive to the inhibitory effect of DF but cytostatic antimalarial activity was suggested by evidence of parasite recovery in later cycles. However, profound growth inhibition, with no evidence of subsequent recovery, occurred when pigmented trophozoites and early schizonts were exposed to DF. At this stage in parasite development, the activity of DF was cytocidal and furthermore, the critical period of exposure may be as short as 6 hours. These observations suggest that iron chelators may have a role in the treatment of clinical malaria.
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A 23 year old male patient presented with a venous thrombosis in the right calf. This was followed by symptoms, signs and electromyographic findings suggestive of a tarsal tunnel syndrome. Symptoms were briefly relieved by surgical division of the flexor retinaculum. Subsequently, patient developed swelling in the calf and was found to have a malignant ("Triton") tumour of the tibial nerve and required above knee amputation. In the absence of obvious foot or ankle deformity, caution should be exercised in making the diagnosis of tarsal tunnel syndrome.
Patients are rarely consulted about the major planning decisions which affect them more than anyone else. The present study, completed in 1984, sought the views of patients in the Industrial Therapy Department of a large psychiatric hospital due for closure in the next decade. Areas covered included what patients felt about the department, attitudes to staff, pay rates and working conditions, and preferences in future care. Results showed a positive attitude to Industrial Therapy tempered by some suggestions for improvement. A preference by a majority of patients for living in the community was backed by a realistic interpretation of the problems involved.
A 61 year-old woman presented with general malaise, hair loss, pure red cell aplasia (PRCA) and thymoma: no growth of erythropoietic colonies in vitro (BFU-E) was observed in the presence of her own serum. The thymoma was removed: after the operation no improvement of her anaemic condition was observed and colony growth was very poor, although T-depleted narrow preparations showed a modest BFU-E formation in autologous serum. Following treatment with azathioprine, a complete recovery was seen, associated with normal BFU-E formation in vitro. This observation suggests that a complex inhibition of erythropoiesis may operate in PRCA involving both humoral and cellular factors; thymectomy alone may not be sufficient to restore haemopoiesis, but has to be followed by immune suppressive treatment.
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A method of measuring the function of the calf muscle pump using in vivo 99Tcm-labelled red cells is described. This new, non-invasive method can provide detailed information about the emptying and refilling of the deep and superficial veins of the calf which may prove to be superior to those methods of assessment currently used in the selection and follow-up of patients for venous surgery.
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