Early intervention in schizophrenia.
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Biomedical subjects
Publications and source records attributed to H Jackson.
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A hospital-based study in the northwest of Cambodia identified 453 blind adults and 30 blind children seen consecutively at the provincial ophthalmic department between January and September 1994. Blindness was defined as a visual acuity of less than 3/60 in the better eye. Cataract was the cause of blindness in 266 (59%) adults, of which 15 cases (3.3%) were surgical complications. Sixty-three cases (14%) were due to glaucoma and 53 (11.5%) patients had corneal scars, of which 12 (2.5%) were due to trachoma. Bilateral trauma, usually due to landmine injuries, accounted for 17 patients (4%). Of the 30 blind children, corneal scarring accounted for 12 cases (40%), congenital causes for 14 (47%) and optic atrophy secondary to meningitis for 4 (13%). There is at present an inadequate ophthalmological service for the vast majority of people living outside the capital Phnom Penh. These hospital-based data suggest that there is a need to train general doctors to surgically manage patients with visual loss from cataract and glaucoma, which together account for 70% of all cases of blindness, and highlight the need for a large population-based survey.
The relative population sizes of mpl ligand-responsive megakaryocytic cells were investigated, and all megakaryocytes grown in culture were assessed. Three groups were analyzed: 1) immature cells with the ability to form single mature megakaryocytes; 2) cells with the ability to divide once before forming megakaryocytes (doublets); and 3) progenitor cells with the ability to form colonies, i.e., to undergo both cytokinesis and maturation. Immature cells forming single megakaryocytes proved most sensitive to the mpl ligand. Committed megakaryocyte progenitors required approximately 30 times more mpl ligand to achieve maximum growth than did the immature megakaryocyte population. Similar numbers of committed megakaryocyte progenitors responded to interleukin (IL)-3 and to mpl ligand. The amplification potential of these progenitor cells responding to each growth factor was assessed by measuring the number of megakaryocytes per colony. In response to mpl ligand progenitor, cells generated smaller colonies, with most cell divisions completed at a signifcantly earlier time point compared with progenitor cells responding to IL-3. The growth of more primitive megakaryocyte progenitors was best achieved in combination with other growth factors, notably IL-3; mpl ligand alone was ineffective in this regard. A novel finding was the significant number of megakaryocytes that grew in culture as closely coupled pairs (doublets). Data reported indicate that doublet formation may be a result of detection and stimulation of immature megakaryocytes rather than the diminished mpl ligand responsiveness of a proportion of megakaryocyte progenitors. By combining the number of mpl ligand-responsive cells forming single megakaryocytes with those forming megakaryocyte doublets, it is estimated that the size of the immature megakaryocyte pool greatly exceeds previous calculations. Thus we conclude that the immature megakaryocyte population is significantly larger than previously estimated and that these cells are the most sensitive to mpl ligand. Accordingly, these cells are potentially crucial in bone marrow responsiveness to mpl ligand that results from acute thrombocytopenia, being capable not only of endomitosis and maturation but perhaps of cell division as well.
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Ocular trauma is a major cause of monocular blindness in both the developed and developing world, but is not seen as a significant cause of bilateral blindness. Trauma is therefore generally thought of as a major cause of blind eyes without being a major cause of blind people. Because of the difficulties of surgical treatment of ocular trauma in many developing countries, long-term management is usually aimed at prevention, e.g. by improving safety standards in the workplace. The situation in countries such as Cambodia, which have high landmine densities, is different. Cambodia has an estimated 4-10 million landmines which cause significant morbidity and mortality. This hospital-based study of blindness in the north-west of Cambodia found that of 453 bilaterally blind individuals, 17 (4%) were blind as a result of trauma, and 14 of these were males 15-35 years old. Fourteen cases were due to bilateral penetrating injuries caused by landmine explosions, and usually occurred in association with other severe injury. The other main causes of blindness were cataract (59%), glaucoma (14%) and corneal scarring (12%). Penetrating ocular trauma is a significant cause of bilateral blindness in Cambodia, and predominantly affects young men. It is estimated that it would take 250 years to clear Cambodia of landmines at current activity levels.
Retinopathy associated with sickle-C and sickle cell disease is well described. Sickle trait and haemoglobin C trait are generally considered benign conditions, with infrequent systemic manifestations. Rare cases of retinopathy in sickle trait, in the presence of contributory factors, exist and we recently reported three such patients. The occurrence of retinopathy in haemoglobin C trait is even less well documented. Haemoglobin C does not cause red blood cell sickling but is known to decrease erythrocyte plasticity and increase blood viscosity. We report three cases in which haemoglobin C trait was associated with significant peripheral vascular occlusion and seafan formation (confirmed by fluorescein angiography) similar to that seen in sickle retinopathy. Two patients had coexistent systemic disease (hypertension and diabetes mellitus). Vitreous haemorrhage was the presenting feature in two patients. It is evident that haemoglobin C trait may be associated with sight-threatening complications.
We have expressed the human thiopurine methyltransferase cDNA in a baculovirus vector in Sf21 (Spodoptera frugiperda) cells. This system expresses the enzyme at levels such that the thiopurine methyltransferase enzyme may be readily visualised by Coomassie blue stained sodium dodecyl sulphate-polyacrylamide gel electrophoresis. The expressed enzyme catalysed the methylation of 6-mercaptopurine with an apparent Km of 892 microM, similar to that observed in human liver cytosol ie. 657 microM however, the Vmax was 13,500 pmole/mg/min, which is approximately 400 times higher than the Vmax observed in human liver cytosol ie. 33 pmole/mg/min. The thiopurine methyltransferase inhibitors 6-thioxanthine, p-methoxybenzoic acid and 3,5-dimethoxy benzoic acid were found to be potent inhibitors of the expressed enzyme.
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OBJECTIVE: To determine the incidence of acute symptomatic toxoplasma retinochoroiditis presenting to ophthalmologists for patients born in Britain and elsewhere. DESIGN: Population based, cross sectional study. SETTING: 11 districts in south Greater London. SUBJECTS: All patients presenting to NHS ophthalmologists with symptoms due to acute toxoplasma retinochoroiditis in 1992-3. MAIN OUTCOME MEASURE: Intraocular inflammation in association with a retinochoroidal scar, active adjoining retinitis, and IgG serum antibodies to toxoplasma. RESULTS: The estimated incidence of acute symptomatic retinochoroiditis for all people born in Britain was 0.4/100,000/year. If a mean of two symptomatic episodes per lifetime is assumed, 100 people born in Britain may be affected each year, about a fifth of the estimated 500-600 congenitally infected people born each year. CONCLUSIONS: A substantial proportion of people with acute symptomatic toxoplasma retinochoroiditis were born outside the country, and the number born in Britain was smaller than the number previously estimated to develop retinochoroidal lesions due to congenital toxoplasmosis. These findings suggest that prenatal screening for toxoplasmosis in Britain may be of limited benefit.
Sickle trait is traditionally considered a benign condition by ophthalmologists. Three cases of sickle retinopathy in subjects with sickle trait are reported. In all cases the onset of retinopathy was related to other contributing factors: in one case a traumatic hyphaema and raised intraocular pressure, in two others diabetes mellitus. Patients with sickle trait are at risk of retinopathy if coincident ocular or systemic disease is present.
New support services are needed as the AIDS epidemic escalates. Home care has been the cornerstone of new developments in Zimbabwe and the southern African region, essentially resource-strapped countries. However, while home care has many benefits, levels of coverage are often low and many patients at some phase of their disease need more than their home can provide, even with access to support services. Hospital admission is often not a viable option and the need may arise for some form of respite or hospice community centre to provide residential care. This option is debated and potential benefits and pitfalls are explored.
An orphan enumeration survey was conducted in 570 households in and around Mutare, Zimbabwe in 1992; 18.3% (95% CI 15.1-21.5%) of households included orphans. 12.8% (95% CI 11.2-14.3%) of children under 15 years old had a father or mother who had died; 5% of orphans had lost both parents. Orphan prevalence was highest in a peri-urban rural area (17.2%) and lowest in a middle income medium density urban suburb (4.3%). Recent increases in parental deaths were noted; 50% of parental deaths since 1987 could be ascribed to AIDS. Orphan household heads were likely to be older and less well-educated than non-orphan household heads. The majority of orphaned children were being cared for satisfactorily within extended families, often under difficult circumstances. Caregiving by maternal relatives represents a departure from the traditional practice of caring for orphans within the paternal extended family and an adaptation of community-coping mechanisms. There was little evidence of discrimination or exploitation of orphaned children by extended family caregivers. The fact that community coping mechanisms are changing does not imply that extended family methods of caring are about to break down. However, the emergence of orphan households headed by siblings is an indication that the extended family is under stress. Emphasis needs to be placed upon supporting extended families by utilizing existing community-based organizations. Orphan support programmes may need to be established initially in high risk communities such as low-income urban areas and peri-urban rural areas.
After intravenous doses of the plasma-bound radionuclides 59Fe, 114Inm and 109Cd, only a minute percentage localizes in the rat testis and remains largely unchanged with time. Intratesticular injection of appropriately reduced volumes led to much higher proportionate percentage retention of 14, 65 and 11 for 59Fe, 114Inm and 109Cd, respectively. By this route, significant feedback of the elements escaping initial binding was prevented. Distinct but different testicular turnovers were now discernible. As a receptor of fluid and spermatozoa from the testicular tubules, the epididymis provides an indication of entry into and interaction of the metals with spermatogenic cells. For 59Fe no measurable changes were detected, whereas a progressive increase in epididymal 114Inm occurred, which had not reached a plateau by 70 days. 109Cd, now demonstrated within the testicular tubules by autoradiography, remained at constant organ level for upwards of 16 days but had declined by 25% by 57 days. At this point, the epididymis showed a five-fold increase in the radionuclide, declining to one-half this value by 126 days. Since 109Cd is carrier free, the data reflect a body turnover of dietary cadmium. These results, overall, are compatible with the entry of a proportion of each radionuclide into the seminiferous tubules and reaction with spermatogenic cells. Possible interpretations of the observed differences are presented.
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The effect of transforming growth factor-beta 1 (TGF beta 1) on three developmental stages of megakaryocytopoiesis was investigated. Using a murine bone marrow agar culture system, titrated doses of TGF beta 1 were added to cultures assaying primitive high proliferative megakaryocyte progenitors, committed megakaryocyte precursors, and nondividing, endoreduplicating megakaryocytes. The growth of high proliferative megakaryocyte colony-forming cells (HPP-CFU-Mk) that require the growth factors interleukins-1, 3 and 6 (IL-1 + IL-3 + IL-6) for colony detection was abrogated by the addition of 1 ng TGF beta 1/ml. The sensitivity of committed megakaryocyte progenitors (colony-forming unit-megakaryocyte, CFU-Mk) to TGF beta 1 depended on the growth factor combination. TGF beta 1 (1 ng/ml) completely inhibited megakaryocyte colony formation from CFU-Mk only in cultures stimulated by low doses of IL-3. TGF beta 1 (> 10 ng/ml) could only marginally inhibit megakaryocyte colony formation generated in the presence of either high doses of IL-3 or the combination of low dose IL-3 + IL-6. TGF beta 1 inhibited both IL-3-dependent and IL-6-dependent megakaryocyte growth but tenfold higher doses of TGF beta 1 were required to inhibit growth generated by the combination of IL-3 + IL-6. The data showed that the capacity of TGF beta 1 to inhibit distinct differentiation stages of the megakaryocytopoietic lineage depended on the concentration and combination of growth factors involved.
We conducted a survey to determine the prevalence, characteristics, and effects of a history of childhood sexual and physical abuse among professionals responsible for evaluating child sexual abuse allegations. A gender-stratified random sample of 1,635 United States clinicians was drawn from the most current national directories of clinical social work, pediatrics, psychiatry, and psychology. We received 656 completed questionnaires, yielding a 42% response rate. Thirteen percent of the men and 20% of the women reported a personal history of childhood sexual abuse; 7.3% of the men and 6.9% of the women reported a history of physical abuse as children. The modal age at which both genders were sexually abused was 8 years. The modal age at the time of physical abuse was 10 years for both sexes. Of those sexually abused, 50% of both genders were sexually abused for only 1 year. Of those physically abused, more than 50% of both genders were physically abused for 3 or more years. Older females were more likely to report a history of sexual abuse than were their younger cohorts. In this population, physical abuse was overwhelmingly perpetrated by parents. However, the modal perpetrators of sexual abuse (for both females and males) were male acquaintances or male strangers. Fathers and stepfathers were unlikely to be perpetrators of sexual abuse (3% for males and 12% for females) in this sample. For both genders, particularly males, sexually abused respondents were less likely to be married than their nonabused cohorts. Both men and women who had been sexually abused were more likely to be in nonmarital relationships than were those who had not been sexually abused. Women who had been sexually abused were less likely to have raised children than were women who had not been sexually abused. Respondents who had been sexually abused and/or physically abused were more likely to believe allegations of sexual abuse contained in 16 vignettes alleging sexual abuse.
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