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Biomedical subjects

R W Morris

Publications and source records attributed to R W Morris.

At least 19 recordsLinked to original sources

Prospective study of serum total homocysteine concentration and risk of stroke in middle-aged British men.

Moderate hyperhomocysteinaemia is common in the general population and has been linked with cardiovascular disease. However, there are no data from prospective, population-based studies. We examined the association between serum total homocysteine (tHcy) concentration and stroke in a nested case-control study within the British Regional Heart Study cohort. Between 1978 and 1980 serum was saved from 5661 men, aged 40-59 years, randomly selected from the population of one general practice in each of 18 towns in the UK. During follow-up to December, 1991, there were 141 incident cases of stroke among men with no history of stroke at screening. Serum tHcy was measured in 107 cases and 118 control men (matched for age-group and town, without a history of stroke at screening, who did not develop a stroke or myocardial infarction during follow-up). tHcy concentrations were significantly higher in cases than controls (geometric mean 13.7 [95% CI 12.7-14.8] vs 11.9 [11.3-12.6] mumol/L; p = 0.004). There was a graded increase in the relative risk of stroke in the second, third, and fourth quarters of the tHcy distribution (odds ratios 1.3, 1.9, 2.8; trend p = 0.005) relative to the first. Adjustment for age-group, town, social class, body-mass index, hypertensive status, cigarette smoking, forced expiratory volume, packed-cell volume, alcohol intake, diabetes, high-density-lipoprotein cholesterol, and serum creatinine did not attenuate the association. These findings suggest that tHcy is a strong and independent risk factor for stroke.

Adult

Development and persistence of placental glutathione-S-transferase-positive foci in livers of male F344 rats exposed to o-nitrotoluene.

In a previous 13-week study of o-nitrotoluene, a chemical-related increase in liver weight, hepatocellular vacuolization, and oval cell hyperplasia in male F344 rats was reported. In this study, the occurrence and change in number and size of hepatic foci in male F344 rats fed a diet containing 5000 ppm o-nitrotoluene or a control diet for 13 weeks, 26 weeks, and 13 weeks followed by a 13-week recovery period (26-week stop-exposure) were evaluated. The livers were stained immunohistochemically for placental glutathione S-transferase (PGST), a marker of hepatic preneoplasia, and quantified stereologically using computer-assisted image analysis. Exposure to o-nitrotoluene induced PGST-positive (PGST-positive (PGST+) liver foci in all treatment groups. The 26-week continuous-exposure group produced more PGST+ liver foci (961.4 foci/cm3 versus 445.4 foci/cm3) and greater mean focus volume (4.34 microns3 versus 1.34 microns3) than the 13-week continuous-exposure group. In the 26-week stop-exposure group, there were fewer PGST+ liver foci (181.4 foci/cm3) than observed with continuous exposure at 13 weeks or 26 weeks; however, the mean focal volume in the stop-exposure group at 26 weeks (5.33 microns3) was greater than that at 13 weeks (1.34 microns3) or 26 weeks of continuous exposure (4.34 microns3). These findings demonstrate that (1) PGST+ foci are observed after only 13 weeks of exposure to o-nitrotoluene; (2) the number and size of foci increase with continued exposure for 26 weeks; and (3) although the number of PGST+ foci decreases with time after chemical exposure is discontinued, many PGST+ foci do not regress but increase in size during the recovery of 13 weeks. The persistence and increase in size of these foci, even in the absence of chemical exposure, suggest the potential for a hepatocarcinogenic effect in long-term studies for o-nitrotoluene.

Animals

Natural killer cell lymphoproliferative disorder of granular lymphocytes presenting as hemolytic anemia: case report and review of the literature.

Lymphoproliferative disorders of granular lymphocytes (LDGLs) have recently been hypothetically defined based on their immunophenotype, function, and clonality. The majority (129/161) of LDGLs are of the T-cell subset, which is typically associated with neutropenia and occasionally with anemia. The remainder (32/161) are of natural killer cell origin. This subset is associated with neutropenia (52% of cases) and anemia (60% of cases). The anemia most often has no immediately apparent cause. The Coombs test was negative in all cases reported. There is only one reported case of an associated Coombs-negative hemolytic anemia. We report an unusual case of natural killer cell LDGL, defined by morphology and immunophenotypic analysis, presenting as a de novo Coombs-negative hemolytic anemia. The anemia was resistant to steroid therapy. Therapeutic splenectomy resulted in a temporary resolution of the hemolytic process. The splenic pathology is also described.

Aged

The usefulness of intensive care treatment: perspectives of medical and nursing staff.

Which patients' states or circumstances effect the judgement of Intensive Care specialist (IC) medical and nursing staff as to how useful intensive care treatment is? Do IC medical and nursing staff differ significantly in their attitudes regarding the usefulness of IC treatment? Or do they show similarity in their attitude but differ as a group from broader community views of the usefulness of IC treatment? To gain insight into these questions a group of IC staff (35 medical, 108 nursing) and pre-clinical students (110 medical, 136 nursing) responded to a questionnaire asking them to consider how 12 patient factors including age, functional state, socioeconomic factors, length and cost of the IC stay, culpability, disease state and length of survival after IC unit discharge effected their judgement of the usefulness of IC treatment for an individual patient. Results indicated that: (i) medical and nursing students felt IC treatment more useful than IC staff regardless of the patient characteristic; (ii) IC doctor and nurse responses were very similar; (iii) IC staff considered that IC treatment "tended to be useless" or was "useless" if the patient had required "institutional care", was in a "vegetative" state before or after IC treatment, belonged to the pathology groups of "malignancy" and "diseases of ageing", belonged to the diagnostic groups "AIDS" and "quadriplegia", or where survival post discharge from IC was expected to be "< 3 months"; and (iv) cost and length of stay in IC were not factors that negatively effected any groups perception of the usefulness of IC treatment.

Adult

Alterations in endotracheal tube position during general anaesthesia.

The effect of head and neck movement and Trendelenburg tilt on endotracheal tube position, relative to the carina, was studied in fifty adult patients requiring intubation for elective surgery. On average, inward movement, that is shortening of the distance between the endotracheal tube tip and the carina, resulted from neck flexion (mean = -5.5 mm), whereas outward movement occurred with neck extension (mean = 6.3 mm). Neck rotation, to right and left, and Trendelenburg tilt did not show any trend towards inward nor outward movement (mean = 0.3 mm/1.7 mm/-0.6 mm, respectively). Whilst these mean positional changes for flexion and extension confirm the findings of earlier investigations, our range of maximum inward and outward displacement for flexion (23 mm in/19 mm out), extension (21 mm in/33 mm out), rotation to right (19 mm in/17 mm out), to left (22 mm in/19 mm out) and Trendelenburg tilt (22 mm in/16 mm out) indicate that for any given postural change in any one patient, the direction and magnitude of endotracheal tube displacement is not readily predictable.

Adult

Periodicity of suicide attempts reported to a poison control center.

Suicide attempts make up a significant percentage of intentional overdoses and tend to utilize more poison control center (PCC) resources than any other type of call. In order to determine whether time imparts patterns on these suicide calls, we studied all suicide calls to our PCC over a 2-y period. Particular attention was given to the epidemiology and time of call. Suicide exposures (N = 4031) were extracted from PCC records from January 1988 through December 1989 with particular attention to time of day and age and sex of the patient. Data were computer analyzed using standard ANOVA, cosinor and non-linear regression techniques. Serial frequency and spectral analyses were performed using time series procedures. Significant circadian rhythms were noted for all age ranges with peak time (ie acrophase) for calling the PCC occurring in the early evening. However, individuals over the age of 50 y called earlier than younger aged groups. In addition, the 13 to 19-y age group exhibited a significant annual rhythm by peaking in suicide calls to the PCC on January 28 +/- 12.4 d.

Adolescent

Neuropeptides induce rapid expression of endothelial cell adhesion molecules and elicit granulocytic infiltration in human skin.

Inflammatory cell infiltrates and cell adhesion molecule expression have been examined in normal human skin after intradermal injection of sensory neuropeptides substance P (n = 6), vasoactive intestinal polypeptide (n = 6), and calcitonin gene-related peptide (n = 6) together with PBS as control (n = 4). Each neuropeptide induced rapid, time-dependent neutrophil influx into dermis, which was initially observed at 15 min and persisted for 8 h after injection. Increases in numbers of neutrophils with time after substance P, vasoactive intestinal polypeptide and calcitonin gene-related peptide were highly significant when compared with controls p < 0.005, p < 0.005, p < 0.005, respectively (analysis of variance). Substance P additionally induced marked eosinophilic accumulation at 4 and 8 h in four of six subjects. These changes paralleled rapid translocation of P-selectin from cytoplasmic Weibel-Palade granules to luminal membranes by 15 min, and significant up-regulation of E-selectin expression at 4 and 8 h. Increases in percentage of E-selectin positive vessels with respect to time after each neuropeptide were highly significant when compared with controls, p < 0.005, p < 0.005, p < 0.005 (ANOVA), respectively, and were significantly correlated with neutrophil infiltrates, r = 0.55, p < 0.001. VCAM-1 was not expressed, and constitutive ICAM-1 expression on dermal endothelium was unchanged at all time points examined (0-8 h). Induction of endothelial adhesion molecule expression by neuropeptides provides a mechanism for neutrophil accumulation in neurogenic inflammation. Substance P-induced eosinophil accumulation in the absence of VCAM-1 expression suggests that mechanisms distinct from VCAM-1/very late antigen-4 binding mediate selective tissue eosinophilia.

Adult

Designer hips.

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Humans

Circannual and menstrual rhythm characteristics in manic episodes and body temperature.

Most reports in the literature deal with groups when summarizing the timing of affective disorders along the scale of the year and the menstrual cycle. In order to look for any regularity in timing of manic episodes in a single individual along these two time scales, a woman with a history of mania only, caused by schizoaffective disorder and on maintenance therapy with thioridazine hydrochloride self-measured basal body temperature daily and recorded onset and duration of manic episodes for 11 years. Statistically significant rhythms were found in body temperature with periods equal to the menstrual cycle and the year, with acrophase (highest values) during the luteal phase and winter, respectively. The timing of 11 manic episodes was not random but occurred during distinct portions of the menstrual cycle and the year. Most manic days occurred near menstruation or during the follicular phase of the menstrual cycle (up to ovulation) and between December and May (winter-spring). A temporal schedule for psychopharmacological treatment designed from individualized, longitudinal records that adjusts daily dosages according to both time of year and stage of menstrual cycle might alleviate or minimize the occurrence, magnitude and/or duration of mania and possibly other affective disorders that are found to be associated with underlying biological periodicities.

Adult

Laboratory and animal model evaluation of the Cryotech LCS 2000 in hepatic cryotherapy.

Hepatic cryotherapy is increasingly used in the treatment of patients with multiple hepatic metastases, particularly from colorectal cancer. The Cryotech LCS 2000 system, with insulated shaft-circulated liquid nitrogen probes, was designed for this purpose and was evaluated on the bench and in an animal model. The 9-mm probe was considerably more effective than the 5-mm probe when judged on time to create an iceball of a given diameter. The use of thawing gas reduced the time until the probe could be removed from 25 to 5 min but heated gas only produced a further reduction of 2 min. In the animal model, significant reduction in treatment times occurred with vascular inflow occlusion. The zone of necrosis as a percentage of the original iceball diameter was significantly higher following a twin freeze/thaw cycle. The relationship of the edge of the iceball to the eventual zone of hepatic necrosis was studied using different unabsorbable markers. India ink and sutures proved unreliable but a Teflon cannula was more successful and the margin was only of the order of 2 mm. The discrepancy between this observation and the percentage of the original iceball diameter which apparently becomes necrotic (64 and 82%) for single- and double-freeze lesions, respectively, suggests that the cryolesion undergoes shrinkage within 1 month and that the diameter of necrosis underestimates the true zone of destruction.

Animals

Excess melanocytic nevi in children with renal allografts.

BACKGROUND: Renal allograft transplantation is associated with an increased incidence of malignant melanoma. The development of excess melanocytic nevi may be an indicator of this risk. OBJECTIVE: This study determines the prevalence of melanocytic nevi in children who have received renal allografts. METHODS: Total and regional melanocytic nevi counts were made in 38 children (27 boys, 11 girls) with a renal allograft and in 38 individually age- and sex-matched healthy controls; counts were related to age, sex, skin type, and duration of immunosuppression. RESULTS: There was a significant increase in the total number of nevi in the renal transplant group compared with the control group (p < 0.05), with most marked increases occurring on the back and at acral sites. A strong positive correlation between nevi count and duration of immunosuppression independent of age was observed (p < 0.005). CONCLUSION: Excess numbers of melanocytic nevi occur in children with renal allografts. These patients constitute a risk group for malignant melanoma and require continued assessment.

Adolescent

Assessment of proliferating cell nuclear antigen expression in precursor stages of gastric carcinoma using the PC10 antibody to PCNA.

Immunohistochemistry using the PC10 antibody to proliferating cell nuclear antigen (PCNA) was applied to archival material from mucosa adjacent to gastric carcinoma ('normal', hyperplasia, complete and incomplete intestinal metaplasia and dysplasia) and non-cancer controls (normal and complete intestinal metaplasia). Overall, increased PCNA indices, with expansion and altered location of the proliferative zones, were observed in carcinoma fields and compared with controls (P < 0.001). These differences were particularly significant in 'normal' mucosa far from carcinoma as compared with normal in controls (P < 0.001). In carcinoma 'fields' distinct patterns of PCNA expression were noted in complete and incomplete intestinal metaplasia. Similarly, in dysplastic lesions high PCNA indices were present either throughout the gland or found predominantly in the upper compartment. We conclude that these differences in PCNA index and staining patterns might prove useful in monitoring the evolution of the disease in the follow-up of patients at risk of developing gastric cancer.

Antibodies, Monoclonal

Analysis of cell proliferation data.

When estimating the labeling index is of interest, the design of experiments raises a number of methodological questions: How many cells should be scored? How big a difference in labeling index is likely to be detectable? What is the potential effect of low growth fraction on detecting a treatment effect? What are appropriate ways of expressing treatment effects on labeling index? Data from two labeling index experiments are used to shed light on these questions. The answers to all questions depend on the level of labeling index under consideration: a low frequency of labeling makes it important to count more cells, but this should not be done at the expense of using fewer animals. Detecting differences between treated and control groups when labeling index is low or when growth fraction is low is difficult, and caution must be used when expressing treatment effect as fold increase when labeling index is small.

Analysis of Variance