Biomedical subjects
Publications and source records attributed to R Murray.
The results of 77 caesarean sections in cattle carried out in a seven-person practice over a period of 16 months are described and evaluated. The standardisation of the surgical technique, the speed of decision making in dealing with dystocia, and the education of the farmers contributed to the 84 per cent calf survival rate, and post surgical complications were few. There was only one fatality in a dam.
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In studies of antigenic peptide presentation, we have found a healthy volunteer whose lymphoblastoid cells were unable to present three different virus-derived epitopes to cytotoxic T lymphocytes (CTL) despite expressing the correct restricting HLA-B27 molecules on the cell surface. B cell lines were established from other members of the donor's family, including individuals suffering from ankylosing spondylitis and related diseases, and were tested for their ability to function as target cells in the same assay. None of the eight B cell lines that expressed HLA-B27 presented a known peptide epitope to CTL. However, cells from a family member that expressed HLA-B8 could present an epitope peptide restricted by that molecule. The B27 molecule in this family proved to be the B2702 subtype on isoelectric focusing gels, appearing in exactly the same position as B2702 from other cell lines that did present the peptide. To exclude mutations resulting in noncharged amino acid substitutions, cDNA coding for B2702 was cloned from the proband's cell line and sequenced. No coding changes were found. The cloned cDNA was transfected into HLA-A- and B-negative HMy/C1R cells, and the B2702 molecules generated in this environment rendered these cells, after incubation with peptide, susceptible to lysis by peptide-specific CTL. These data are compatible with the presence of a factor(s), possibly HLA linked, interfering with antigen presentation by otherwise normal B2702 molecules in this family.
Conjugate formation between cytotoxic T lymphocytes (CTL) and target B cells, as observed in vitro, is mediated by interactions between adhesion molecules on the two cell surfaces rather than involving immune recognition through the T cell receptor. It is still not clear to what extent such adhesive contacts facilitate the process of immune recognition and target cell lysis. However, work on the Epstein-Barr virus (EBV)-associated malignancy Burkitt's lymphoma (BL) has suggested that down-regulation of one particular adhesion molecule, the lymphocyte function-associated antigen LFA-3, on the tumor cell surface is a key factor in allowing these target cells to escape EBV-specific T cell surveillance. To examine this directly, we used a cDNA for the full-length transmembrane form of LFA-3 to construct a recombinant vaccinia virus (Vacc-LFA 3), which is capable of restoring surface LFA-3 in adhesion molecule-negative BL cell lines to levels as high as seen in EBV-transformed lymphoblastoid cell lines (LCL); biochemical studies confirmed expression of the authentic N-glycosylated protein. The recombinant vaccinia-encoded LFA-3 was functional as an adhesion molecule since BL cells acutely infected with Vacc-LFA-3 then acquired the ability to form conjugates with activated T cells in vitro. However, there was no clear dependence upon LFA-3 when such BL cell lines were tested as targets for cytotoxic T lymphocytes (CTL). Firstly, LFA-3- BL cells could be killed by allospecific CTL recognizing HLA class I alloantigens, in some cases as efficiently as the corresponding LCL. In other cases where lysis was slightly below that of the LCL, Vacc-LFA-3 infection of the BL cells increased lysis up to, but never beyond, LCL values. Secondly, we studied the sensitivity of BL to EBV-specific HLA class I-restricted CTL using a BL target line which was LFA-3- but which expressed the same spectrum of EBV target proteins as an LCL. This line was not recognized by appropriately HLA-matched effectors, even after restoration of LFA-3 expression. We conclude that the LFA-3 status of BL cells influences their conjugate forming ability in in vitro assays but not necessarily their sensitivity to immune T cell-mediated cytolysis.
Toremifene is an antiestrogen that binds strongly to estrogen receptors (ER). A total of 19 previously treated postmenopausal women with metastatic breast cancer whose performance status was good and whose ER status was positive or unknown were studied to determine the maximum tolerated dose of toremifene. Cohorts of patients received 200, 300, or 400 mg/m2 p.o. daily until relapse or unacceptable toxicity had occurred. Nausea, vomiting, and dizziness were dose-related. Three of five patients receiving 400 mg/m2 experienced moderate or severe vomiting and another developed reversible disorientation and hallucinations. Mild sweating, peripheral edema, vaginal discharge, and hot flushes were encountered at all doses. Reversible corneal pigmentation was identified in seven cases but was not of clinical importance. The pharmacokinetics of toremifene was studied weekly and in detail on day 42 using a high-performance liquid chromatographic (HPLC) assay that identified the parent compound and three active metabolites, N-desmethyltoremifene, (deaminohydroxy)toremifene, and didemethyltoremifene. Steady state was achieved at 1-3 weeks. The toremifene area under the curve and the maximal concentration were dose-dependent at high doses. The recommended phase II dose is 300 mg/m2 p.o. daily.
Attentional problems of closed head-injured (CHI) children were examined using an information processing (IP) approach. Based on Sternberg's (1969) additive factor method (AFM), the study examined attentional processes in terms of four stages and their corresponding task variables. A visual-spatial choice reaction-time task was undertaken with two groups of CHI children (severe and mild to moderate) and corresponding matched control groups. Results indicated that for this task both the CHI and the normal children exhibited a similar mode of linear, sequential information processing. It was found that the severe group was impaired not only in terms of slowed motor execution but also in terms of response selection. This group showed no impairment on the feature extraction, stimulus identification, and motor adjustment stages of processing. No evidence of impairment on any of the stages was found for the mild group. The utility of the AFM and implications of these findings are discussed with reference to CHI children and to neuropsychological assessment and rehabilitation.
Medical humanities is an innovative way of learning. Discussing literary texts of nursing practice has been used to help students analyse attitudes, values and ethics; it has also been used to help practitioners review and reflect on their own experience and philosophy of nursing. In nursing education, it has been used to explore difficult issues in a safe environment. The value of this approach in nursing education and practice is that it can encourage reflection, promote self-awareness and stimulate debate on difficult issues: for example, death and dying, power and institutionalization (of patients and staff) and pain. This paper gives a detailed worked example of how a literary text can be used in this way, the aim being to provide a resource which readers can then use with a group of students or colleagues. Finally, the authors explore the question of where medical humanities might have a place in the curriculum: as a lecture/tutorial in a course (e.g. Ethics), as a module in the curriculum, as a method of teaching nursing subjects (e.g. communication skills), as a discussion group (outside the curriculum), as a study guide, using literary texts alongside nursing text books. Any of these strategies can be a powerful vehicle for preserving the 'human factor' in both nursing education and continuing professional development.
The earliest recorded occupational health service in this country was that established in a cotton spinning factory at Quarry Bank Mill in Cheshire. The mill was built in 1784 by Samuel Greg and his partners. They employed local labour and also some parish apprentices. Happily, Samuel Greg was a good christian and, having created a modern factory and a model village with a church and a school, he was equally concerned for the physical welfare of his employees. Accordingly, he appointed a doctor to make pre-employment examinations of the apprentices and to visit regularly to deal with the health problems of a community of some 400 people. The man he chose was Peter Holland of Sandlebridge, who had served his medical apprenticeship under Dr Charles White of Manchester. The first record of the employment of a doctor was in 1796, but from 1804 to 1845 (doubtless in response to the early factory legislation) each visit of the doctor was entered in a day book with either an indication of fitness to work or details of the treatment required. The complete record consists of two hardback foolscap notebooks that provide a fascinating insight into the medical practice of the times when the industrial revolution was just getting under way. One of the more interesting features is the preservation of medical secrecy. Dr Holland made his comments on the case in shorthand and his instructions in longhand. By a fortunate coincidence the key to the shorthand was discovered and this has now been largely transcribed. Although much of the content of the diaries is the day by day practice of medicine at the time, there are many illuminating glimpses of the early practice of occupational medicine.
A summer peak was found in first admissions to hospitals in England and Wales between 1976 and 1986 for both affective psychoses and schizophrenia, but not for neurotic conditions or personality disorders. There was no significant relationship between age at first admission and season of admission. The summer peak was most prominent for mania, where it was present in both sexes; for schizophrenia, it was present only in females. These findings suggest that schizophrenia in females, and mania in both sexes, have some aetiological or precipitating factor in common.
1) During exercise, the body's ability to safely regulate internal temperature is influenced by the environment, exercise intensity, clothing, and the athlete's level of fitness and acclimation. 2) Effective thermoregulation during exercise in the heat requires the evaporation of sweat. The onset of sweating during exercise is triggered by an increase in core body temperature. 3) Dehydration compromises cardiovascular and thermoregulatory function, limits physical work capacity, and increases the risk of heat-related health problems. 4) Physiological and behavioral adaptations help the body cope with the combined demands imposed by exercise and environment. 5) Ad libitum fluid intake is insufficient to protect against dehydration.
Lyme neuroborreliosis is one of the chronic manifestations of Lyme disease and is caused by the neurotropic spirochete, Borrelia burgdorferi. Two of the three stages of Lyme disease potentially involve the central nervous system: a second stage that may manifest as meningitis, cranial neuritis, or radiculoneuritis; and a third stage, or chronic neuroborreliosis, with parenchymal involvement. The tertiary stage may mimic many conditions, including multiple sclerosis, polyneuropathy, viral encephalitis, brain tumor, vasculitis, encephalopathy, psychiatric illness, and myelopathy. We report a 10-year-old child with signs, symptoms, and radiological manifestations of intracranial mass lesions, without previously recognized manifestations of Lyme disease. This proved to be Lyme neuroborreliosis, documented by histological and serological examination, which responded well to antibiotic therapy. The need to establish a tissue diagnosis of intracranial mass lesions is emphasized, and the utility of a computed tomographic-guided stereotactic system for this purpose is discussed.
Class I molecules of the MHC bind foreign and endogenous peptides allowing recognition by the TCR on CTL. The recognition and killing of cells infected with lymphocytic choriomeningitis virus (LCMV) depends on the recognition of LCMV peptides bound to class I MHC. Mutations in class I MHC molecules have enabled the delineation of regions in the class I molecule important for binding peptides and for interaction with the TCR. We have constructed a library of class I mutants using saturation mutagenesis and report a phenotypic change resulting from a single amino acid substitution that results in the heteroclitic (increased) killing of LCMV-infected cells. This amino acid change, asparagine to serine at position 30, is in a conserved region of the class I molecule contacting the alpha 3 domain. This mutation does not result in increased expression of the class I molecule on the cell surface, does not affect the binding of CD8, and does not affect allogeneic recognition. Cold target experiments show that this heteroclitic killing is due to increased recognition by CTL. These data point toward a critical function for this region of the class I molecule in the binding of peptides or their presentation to CTL.
The T1 relaxation time of the basal ganglia (putamen, globus pallidus and head of caudate) and of the frontoparietal centrum semiovale was compared between 49 schizophrenic patients and 36 healthy controls. Previous reports of increased T1 time in the basal ganglia were not confirmed, and group differences were not detected within the white matter. Within patients T1 values could not be related to tardive dyskinesia or other clinical features. Normal variation seen in basal ganglia T1 times is described for the first time: lowest values occur in the globus pallidus and highest in the caudate, and values within the putamen increase rostrally.
In the past 20 years, there have been numerous reports of skin and mucous membrane disorders allegedly caused by the use of carbonless copy paper, to such an extent that some people in Europe were refusing to work with it and concern was expressed in the European Parliament. In view of its undoubted convenience and superiority over carbon paper, the author was asked by the Commission of the European Communities for a report. Based on visits to manufacturers and users and the investigation of complaints, the conclusion is that, as exposure to the constituents of the paper during its manufacture is considerably greater than in its use and no cases have arisen in his experience in the industry, the complaints are more likely to be attributable to "sick building syndrome" than to the specific effect of any component of the paper.
To study selected cardiovascular, thermoregulatory, and hormonal responses to the consumption of glycerol solutions during exercise, nine subjects cycled for 90 min at 50% peak O2 uptake in a 30 degree C, 45% relative humidity environment. Beverages tested included a 10% glycerol solution (G), a 6% carbohydrate-electrolyte beverage (CE), the 6% carbohydrate-electrolyte beverage plus 4% glycerol (CEG), and a water placebo (WP) ingested at regular intervals during the first 60 min of exercise. The beverages were administered in counterbalanced order with subjects serving as their own controls. Ingestion of the glycerol solutions resulted in an increase in plasma osmolality and attenuation of the decrease in plasma volume associated with the WP treatment (P less than 0.05). Plasma renin activity was highest with WP (P less than 0.05), and G was associated with increased antidiuretic hormone levels (P less than 0.05). Ratings of perceived thirst were lowest for CEG and G, and the frequency of gastrointestinal distress was greatest for G (P less than 0.05). However, no differences among beverage treatments were observed for heart rate, esophageal temperature, sweat rate, ratings of perceived exertion, or changes in cortisol and aldosterone levels. These data indicate that there are no substantial metabolic, hormonal, cardiovascular, or thermoregulatory advantages to the consumption of solutions containing 4 or 10% glycerol during exercise.
Pre-morbid schizoid and schizotypal traits and social adjustment were assessed blind to diagnosis by interviewing the mothers of 73 consecutively admitted patients with DSM-III schizophrenia or affective psychosis. Analysis of factors associated with pre-morbid deficits showed a highly significant interaction of diagnosis with sex, such that schizophrenic men showed much greater pre-morbid impairment than either schizophrenic women or men with affective disorder. Poor pre-morbid adjustment predicted an early age at first admission. The results can be explained by a neurodevelopmental disorder in some schizophrenic males.
A case-control study was performed using 90% of all first-contact patients with a clinical diagnosis of schizophrenia residing in the London borough of Camberwell between 1965 and 1984. Cases and controls were obtained from the Camberwell psychiatric case register. Controls were those presenting with first episodes of non-psychotic disorders, matched for age, sex and period. The risk of schizophrenia was greater in those of Afro-Caribbean ethnicity, irrespective of age, gender or place of birth. This risk increased over the study period. The results cannot be explained by changes in the age, gender or ethnic structure of the local population. Effects of misdiagnosis or change in diagnostic practice were reduced by using uniform operational criteria. Possible explanations include maternal exposure to unfamiliar infective agents, a differential fall in the age at onset of illness, or worsening social adversity.
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