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Biomedical subjects

J Watt

Publications and source records attributed to J Watt.

At least 37 records · Page 2Linked to original sources

Exogenous sex hormone use, correlates of endogenous hormone levels, and the incidence of histologic types of sarcoma of the uterus.

BACKGROUND: We analyzed data from a population-based, multi-center, case-control study to determine whether the occurrence of histologic types of uterine sarcoma is related to exogenous hormone use and/or to two correlates of endogenous estrogens: excess weight and cigarette smoking. METHODS: One hundred sixty-seven women with newly-diagnosed uterine sarcoma (56 leiomyosarcoma, 85 mixed mullerian tumors, and 26 endometrial stromal sarcomas) were interviewed by telephone regarding possible risk factors for these neoplasms, For comparison, 208 women identified at random from the general population of the study areas were interviewed as controls. RESULTS: Use of oral contraceptives was positively associated with the risk of leiomyosarcoma (odds ratios [OR] = 1.7, 95% confidence interval [CI] = 0.7, 4.1), primarily among women who last used these medications 15 or more years prior to diagnosis. Use of noncontraceptive estrogens was directly associated with the risk of mixed mullerian tumors, but only among recent and long-term users of these medications. Women in the highest quantile of body mass index (> or = 27.5 kg/m2) one year prior to diagnosis were at increased risk of each type of uterine sarcoma (leiomyosarcoma, OR = 2.5, 95% CI = 1.1, 5.7; mixed mullerian tumors, OR = 2.9, 95% CI = 1.3, 6.7; stromal sarcoma, OR = 3.5, 95% CI = 1.1, 10.9). Women who had ever smoked cigarettes were at reduced risk of leiomyosarcoma (OR = 0.6, 95% CI = 0.3, 1.1) and stromal sarcoma (OR = 0.5, 95% CI = 0.2, 1.2), but the relationship was not more pronounced among heavy smokers; no association with smoking was observed with mixed mullerian tumors. CONCLUSIONS: Several of these findings parallel those from studies of endometrial carcinoma and may indicate a role for unopposed estrogen in the etiology of histologic types of uterine sarcoma.

Adolescent↗

Cultured rat microglia express C1q and receptor for C1q: implications for amyloid effects on microglia.

Senile plaques, the pathological hallmark of Alzheimer's disease (AD), are associated with complement components, including C1q. Reactive microglia appear to be involved in the later stages of plaque development. Since tissue macrophages are known to synthesize C1q, cultured rat microglia were examined for C1q immunoreactivity. Anti-C1q staining was detected, particularly in process-bearing microglia, indicating constitutive expression of C1q. Thus, microglia could provide a source of C1q for plaques even before becoming reactive. Since it has been previously shown that C1q binds beta 1-42, the major constituent of senile plaques, and since beta 1-42 is toxic to microglia in vitro, we asked if preincubation of beta 1-42 with C1q alters either metabolic indices of amyloid-induced degeneration in microglial cultures or the formation of amyloid deposits on these cells. While electron microscopic analysis of negatively stained amyloid fibrils confirmed that pre-incubation with C1q induced the association of C1q with the fibrils, no effect of the binding of C1q to beta 1-42 on beta 1-42 toxicity in microglia was observed. Interestingly, immunoreactivity for the C1q receptor that is known to modulate phagocytosis was found and was up-regulated in non-process-bearing microglia by interferon-gamma. While these data exclude a role for the C1q receptor in beta 1-42 toxicity in microglia, the observed expression and up-regulation of C1q receptor on microglia by interferon-gamma would be consistent with a role for C1q in complement-mediated inflammatory responses in AD and as a potential activator of microglial function in plaques.

Alzheimer Disease↗

The effect of epidural anaesthesia on peripheral resistance and graft flow following femorodistal reconstruction.

OBJECTIVE: To determine the extent to which epidural anaesthesia influences peripheral resistance and graft blood flow following femorocrural reconstruction. DESIGN: Prospective, controlled study measuring blood flow, arterial pressure and peripheral resistance in femorocrural bypass grafts for 20 min following onset of epidural anaesthesia with 15ml of 0.25% bupivacaine. PATIENTS: Twenty patients undergoing femorocrural reconstruction for critical lower-limb ischaemia with in situ long saphenous vein, under general anaesthesia. Ten patients had epidural cannulae inserted preoperatively and injected with bupivacaine after completion of the graft. RESULTS: Peripheral resistance fell in all 10 patients receiving epidural anaesthesia from a mean (range) of 1.07 PRU (0.32-2.2) to 0.49 PRU (0.19-0.72), compared to control values of 0.95 PRU (0.39-2.0) to 0.91 PRU (0.41-1.51; P < 0.01, Wilcoxon). There was a tendency for blood pressure to fall in the study patients (not significant) but graft blood flow still increased from 98 ml min-1 (41-221) to 160 ml min-1 (101-250), compared to flow in the control patients of 101 ml min-1 (45-176) at baseline to 104 ml min-1 (56-168; p < 0.01) at 20 min. CONCLUSIONS: Epidural anaesthesia significantly decreases peripheral resistance and increases graft blood flow in femorocrural grafts and would appear, therefore, to be of benefit for patients undergoing femorodistal reconstruction.

Aged↗

Significance of anti-LU8 in pregnancy.

Anti-LU8, an antibody defining a high-frequency antigen in the Lutheran system, was identified in the serum of a gravida 4 para 0 pregnant women who had never been transfused. The antibody consisted of both an IgM and an IgG1 component and was nonreactive in the antibody-dependent cell-mediated cytotoxicity (ADCC) assay. The red cells of the mother and 3 siblings of the patient typed as LU:8,14 and were incompatible with the patient's serum. The baby was born at term with a negative direct antiglobulin test and typed as LU:8,14. There was no clinical evidence of haemolytic disease of the newborn.

Adult↗

The influence of increased health care costs on general practitioner consultations and prescription collection.

AIM: Increased health service charges have led to concern that some patients may be unable to meet these costs, which could compromise their care. Increased costs may affect general practitioner attendance, and/or the collection of a prescription. This study examines both of these factors. METHODS: Between 18 August and 14 September 1992, questionnaires were sent to the consenting patients of 19 general practitioners from the Hutt Valley requesting information regarding the general practice (GP) visit and the prescription. The information included the reason for the GP visit, whether there was any delay and its duration, the reason for any delay, the cost of the visit and whether a prescription was received. Data regarding the prescription included the cost and whether all, some, or none of the items were uplifted, and whether the patient had a community service card. RESULTS: 489 (86%) returned completed questionnaires and 426 received a prescription. Of these, 164 were group 1 community service card holders; one was a group 2 community service card holder; 186 were group 3; 59 did not specify their group; 18 had a chronic-user card. Forty percent (194 patients), delayed going to their doctor, 118 by more than 3 days. The most common reasons for delay were hope that their condition may improve spontaneously and the cost of the consultation or prescription. Possession of a community service card was a significant factor in delay with group 3 (high wage earners) more likely to delay than group 1 (p < 0.0005). Only two patients did not present their prescription. Ninety-three percent of those receiving a prescription presented for dispensing within 24 hours. Ninety-two percent of patients paid for all their prescription items. CONCLUSIONS: Delay in obtaining treatment is common and occurs primarily at the general practitioner consultation. It primarily affects those individuals who were classified as group 3, the group that has taken the burden of recent health service charges increases.

Adolescent↗

Molecular basis for Lewis alpha(1,3/1,4)-fucosyltransferase gene deficiency (FUT3) found in Lewis-negative Indonesian pedigrees.

The Le(a) and Le(b) human blood group antigens are synthesized in tissues producing exocrine secretions; they also circulate in plasma, where they are adsorbed by erythrocytes. They are synthesized by two fucosyltransferases, encoded by Lewis (FUT3) and secretor (FUT2) loci. This genetic model has been challenged because some erythrocyte Lewis-negative individuals express Lewis antigens in saliva. To define the molecular basis of this apparent discrepancy, we sequenced FUT3 in Lewis-negative individuals. We identified two single base pair changes. One, termed L1, yields a Leu-20-->Arg substitution in the enzyme's transmembrane domain. When expressed in COS-7 cells, enzyme substrate affinities are essentially identical to those of wild type. However, the mutant enzyme is found at substantially reduced levels in transfected cells. This suggests that the L1 mutation may alter the Golgi membrane anchoring of the enzyme. It was found alone in double dose in 10 of 30 erythrocyte Lewis-negative individuals, nine of whom express Lewis antigens in saliva. Therefore, L1 can account for erythrocyte/saliva-discrepant Lewis typing results. The L2 mutation creates an Ile-356-->Lys change in the enzyme's catalytic domain and inactivates the enzyme. It was found in double dose in 18 of 19 individuals bearing the double erythrocyte and salivary Lewis deficiency and can account for this phenotype.

Alleles↗

FPTT is a low-incidence Rh antigen associated with a "new" partial Rh D phenotype, DFR.

BACKGROUND: Several Rh D phenotypes with partial D antigens are recognized. Some partial D antigens are associated with low-incidence Rh antigens. New partial D antigens are revealed by an atypical pattern of reactions with anti-D. STUDY DESIGN AND METHODS: The reactions of D variant cells with panels of monoclonal anti-D and with antibodies to low-incidence antigens were compared to those of known D categories to identify a new Rh D phenotype. The inheritance of partial D antigens was studied by Rh phenotyping of the families of the probands. Standard serologic methods were used and family data were analyzed. RESULTS: A new Rh D phenotype, to be called DFR, was identified in 17 probands, two of whom had made anti-D. The partial D antigen carries epD3, epD4, and epD9 and lacks epD8. The presence of other D epitopes is ambiguous; different answers were obtained for the same sample with different monoclonal anti-D of the same apparent epitope specificity. The immunoglobulin class of the anti-D was important: IgG were more successful than IgM monoclonal anti-D in detecting the partial D of DFR. Family studies showed that DFR traveled with Ce more frequently than with cE. The low-incidence antigen FPTT (International Society of Blood Transfusion number 700048) was found on all DFR samples. Family studies demonstrated that FPTT is, as suspected, part of the complex Rh system. CONCLUSION: The partial D of the Rh D phenotype, DFR, is recognized by its pattern of reactions with monoclonal anti-D and its association with the low-incidence antigen FPTT, FPTT has now been numbered Rh50.

Antibodies, Monoclonal↗

Successful transfusion in the presence of anti-K4 (anti-Kpb).

A 71-year-old group A, DC female, with anti-K4(-Kpb), -E, and -S was admitted for her second coronary artery surgery. Four units of autologous red blood cells (1BCs) were transfused perioperatively, and four units of homologous K:-4, E-, S- RBCs were transfused over the next 24 hours. Ten units of fresh frozen plasma and 28 units of platelets were also transfused. Continued bleeding necessitated calling donors from other states in AUStralia and from the International Panel of Donors of Rare Type, Bristol, UK, maintained by the World Health Organization. Four units of group 0, K:4, E-, S- KHCs were transfused in the next 24 hours while the K:-4 blood was in transit. No immediate signs of a transfusion reaction were noted. Blood pressure, temperature, bilirubin, and urinary output were normal, and an increase in hemoglobin was observed. A positive direct antiglobulin test was evident 3 days posttransfusion of the incompatible units and was still present 8 days later. Anti-A and anti-K4 were eluted from the patient's RBCs. The titer of anti-K4 increased from 8 preoperatively to 2,048 19 days posttransfusion of K:4 RBCs. Subsequent transfusions were not required, and the patient was discharged 3 weeks after the operation without further incident.

Journal Article↗

Surgeon James Ramsay, 1733-1789: the Navy and the slave trade.

The end of the American War of Independence in 1783 coincided with two very different, but closely related initiatives: the settlement of New South Wales and the fight against the slave trade. In both, James Ramsay, a naval surgeon, played a decisive role. James Ramsay was born on 25 July 1733 at Fraserburgh on the Aberdeenshire coast. After a grammar school education, he was apprenticed to a Dr Findlay, surgeon and physician in Fraserburgh. Through his proficiency in Latin, he obtained a small bursary which enabled him to enter King's College in the University of Aberdeen and brought Ramsay under the influence of Dr Thomas Reid, the professor of moral philosophy, who exercised a profound influence on Ramsay's thinking (Vol 17, pp 632-3).

History, 18th Century↗

Prescribing for childhood asthma in the Wellington area: comparison with international guidelines.

AIMS: An international paediatric asthma consensus group has outlined the rational approach to the treatment of childhood asthma. We have examined the prescription of asthma treatment to children in Wellington to assess to what extent these guidelines have been adopted by general practitioners. METHODS: During the period 1 May-11 June 1991, the prescriptions for 228 asthmatic children, dispensed at 30 randomly selected pharmacies in the greater Wellington area, were reviewed. RESULTS: Eighty-four per cent of the children were prescribed beta 2 adrenoceptor agonists. Of these, 80% of those under five years, and 27% over five years of age, received these agents by the oral route. In almost half, these drugs were prescribed on a regular basis. Fifty-two per cent of patients were prescribed some form of antiinflammatory therapy (inhaled or oral steroids, ketotifen or sodium cromoglycate). Only 2% received sodium cromoglycate. CONCLUSION: Although approximately half of these children received some form of antiinflammatory therapy, the minimal use of sodium cromoglycate, and high frequency of regular scheduled beta 2 adrenoceptor agonist use, suggests that the guidelines for asthma management in children may not have been widely adopted by primary care physicians in Wellington.

Adolescent↗

The pre-ulcerative phase of carrageenan-induced colonic ulceration in the guinea-pig.

The pre-ulcerative phase of carrageenan-induced colonic ulceration was investigated in guinea-pigs supplied 3% degraded carrageenan as an aqueous solution as drinking fluid for 2 or 3 days during which no ulceration of the bowel was observed with the naked eye or dissecting microscope. Mucosal microscopic changes, from caecum to rectum, were multifocal and included cellular infiltrates, dilatation of glands, crypt abscesses, micro-ulcers and sulphated polysaccharide in the lamina propria. Sulphated polysaccharide was also demonstrated histologically for the first time within the surface epithelium and showed ultrastructural features similar to carrageenan. The results indicate that colonic epithelium in the guinea-pig is capable of macromolecular absorption. Carrageenan, a highly active polyanionic electrolyte, within the surface epithelial cells is most likely a primary factor in the breakdown of mucosal integrity. Macromolecular absorption causing enteropathy of the large bowel is a new pathophysiological concept which may have implications in man, particularly in the pathology of large bowel disease.

Animals↗