Premature ischaemic heart disease and the gene for coagulation factor V.
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Biomedical subjects
Publications and source records attributed to R R Taylor.
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1. Neutrophil function was studied in 10 males presenting with acute myocardial infarction (MI) within 6 h of onset and in 10 normal males. Neutrophil production of platelet-activating factor (PAF), determined by bioassay, that of leukotriene B4 by HPLC, and the activity of an enzyme involved in the synthesis of PAF, acetyltransferase (AT), were measured before and after stimulation with opsonized zymosan and calcium ionophore, A23187. 2. The neutrophil count was significantly raised at presentation in those with MI (8.2 +/- 0.8 vs 2.8 +/- 0.3 (s.e.m.) x 10(9) cells/L, P < 0.001; t-test, 18 d.f.). Production of PAF per neutrophil in response to both stimulants was greater than normal in those with MI (zymosan: 21 +/- 4 vs 12 +/- 1 ng/10(7) cells, P < 0.05; ionophore: 174 +/- 18 vs 113 +/- 11 ng/10(7) cells, P < 0.02) despite normal leukotriene B4 production and depressed AT activity. By 7 days, the neutrophil count had significantly fallen but it remained greater than normal as did PAF production. 3. Acute MI is associated with increased potential for production of PAF by neutrophils which may be important in the pathogenesis of MI.
MSP2 is a merozoite surface protein of Plasmodium falciparum and, as such, is a potential component of a malaria vaccine. In this study, we have used a panel of recombinant MSP2 antigens in enzyme-linked immunosorbent assays to investigate the recognition of MSP2 by antibodies from malaria-immune human serum. These recombinant antigens include full-length proteins of serogroups A and B and fragments representing the conserved, group-specific, or repeat regions of each serogroup. Ninety-five percent of the serum samples tested contained MSP2-specific antibodies: 81% of serum samples tested responded to serogroup A, and 86% responded to serogroup B. The antibody response is directed almost exclusively towards dimorphic and polymorphic regions of MSP2; the conserved regions are rarely recognized, and antibodies to serogroups A and B do not cross-react. Interestingly, the antibody response is predominately of the cytophilic and complement-fixing subclass immunoglobulin G3.
BACKGROUND: Single-agent causes of pelvic inflammatory disease (PID) are uncommon. Streptococcus pneumoniae, as the suspected sole causative bacterium, has been reported since the 1800s. In the postantibiotic era, 46 cases have been reported, with a high mortality rate. CASE: We report a case of S pneumoniae as a single bacterial etiology of PID. This single bacterial species was documented by separate cervicovaginal, culdocentesis and laparoscopic cultures. CONCLUSION: It is unusual to identify an uncommon, single organism as the causative bacterial species in PID in an immunocompetent patient without evidence of a primary infectious pneumococcal source.
In contrast to previously studied non-fermentative arginine-hydrolysing (F-/A+) Mycoplasma species, M. gallinarum cells suspended in a salts solution oxidised ethanol and L-lactic, pyruvic and 2-oxobutyric acids. The organic acids were additionally shown effectively to replace arginine as energy sources in growth media. However, their presence did not inhibit arginine hydrolysis, nor did arginine inhibit organic acid catabolism. The ability to oxidise organic acids is a potentially useful diagnostic character enabling sub-division of the F-/A+ Mycoplasma species. M. gallinarum also differed from previously studied F-/A+ mycoplasmas in possessing relatively high NADH oxidase activity and producing H2O2 as only a minor product of NADH oxidation.
Epithelial ovarian carcinoma regularly metastasizes to peritoneal surfaces throughout the abdomen and pelvis. Gastrointestinal involvement is usually limited to seromuscular involvement of the small and large bowel and its mesentery. Gastrointestinal invasion is most often superficial, mesentery is shortened, and intestinal lumens are narrowed. Transmural invasion is less common, as is gastrointestinal hemorrhage. We present a case of life-threatening intralumenal gastric hemorrhage from an intramural gastric metastasis of epithelial ovarian carcinoma effectively palliated with a gastric resection. Intralumenal gastric metastasis represents an unusual trophism of recurrent epithelial ovarian carcinoma. Surgical intervention for life-threatening hemorrhage, while not curative, may provide effective palliation in the otherwise fully functional patient and thereby reducing the need for medical attention and the anxiety assigned to recurrent gastrointestinal hemorrhage. Palliative maneuvers for gastric metastasis may require a multidisciplinary approach.
Conventional coronary risk factors have not consistently been found to be related to restenosis after coronary angioplasty. Apolipoprotein E (apo E) gene polymorphism and/or plasma apo(a) levels were determined in 195 subjects undergoing prospective follow up and angiographic study 6 months after elective balloon angioplasty of a previously untreated coronary obstruction. Restenosis (stenosis > or = 50% plus loss of > or = 50% of initial gain) had occurred in 59 of 150 subjects for whom E genotypes were available. The apo epsilon 4 allele frequency in those with restenosis was higher than those without (0.20 vs. 0.10, P < 0.01), attributable to an excess of epsilon 4 homozygotes in the restenosis group (5 of 59 vs. 1 of 91, P < 0.04). Restenosis was not related to plasma apo(a) and the apo epsilon 4 allele was not associated with elevated levels of apo(a) as has been reported elsewhere. No relationship was found between E genotype and serum lipid and lipoprotein levels; paradoxically, LDL cholesterol was significantly lower and HDL cholesterol higher in those with restenosis. In conclusion, homozygosity for apolipoprotein epsilon 4 appears to be an important determinant of restenosis after coronary angioplasty.
OBJECTIVE: To study the plasma degradation of platelet-activating factor in severely ill patients with clinical sepsis. DESIGN: A prospective, nonrandomized control study. SETTING: Intensive care unit in a university hospital. PATIENTS: Thirteen critically ill male patients with clinical sepsis, due to medical or surgical illness, and ten normal male volunteers were studied. Measurements were repeated in seven patients who survived. MEASUREMENTS AND MAIN RESULTS: The plasma activity of acetylhydrolase, the lipoprotein-associated enzyme that hydrolyses platelet-activating factor to its biologically inactive lyso-derivative was determined using an optimized enzyme assay. The plasma half-life of platelet-activating factor was also measured, along with phospholipase A2 activity, lyso-platelet-activating factor, and serum lipid concentrations. Patients results were compared with those results of normal controls and followed once in survivors. Acetylhydrolase activity in the patient group was significantly lower than in normal subjects (median 34, interquartile range 17 to 54 nmol/min/mL vs. median 60, interquartile range 56 to 80 nmol/min/mL; p < .002), while overall, the plasma half-life of platelet-activating factor did not differ significantly between the groups. However, the half-life of platelet-activating factor in six patients who died (median 3.3, range 3.3 to 4.3 mins) was significantly greater than in either survivors (median 2.1, range 1.4 to 2.9 mins; p < .001) or the normal group (median 2.5, range 2.2 to 2.8 mins; p < .001). Consistent with theoretical prediction, a significant linear relationship existed between platelet-activating factor half-life and the reciprocal of acetylhydrolase activity in the patient group (p < .05). Plasma phospholipase A2 activity was markedly increased in the patient group, while plasma lyso-platelet-activating factor and serum lipid concentrations were severely decreased. CONCLUSIONS: Depression of acetylhydrolase activity was consistent with the concentration of lipids with which it is associated. Platelet-activating factor half-life was relatively well preserved because of the nature of its relationship with enzyme activity. The half-life was prolonged in those patients with the worst outcome and the breakdown in plasma degradation of platelet-activating factor could have contributed to pathophysiology in these subjects.
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The aim of this study was to determine whether a 4-wk handgrip training program would elicit changes in endothelium-dependent and endothelium-independent vasodilatation in resistance vessels of the human forearm. Minimum vascular resistance after a 10-min ischemic stimulus, an index of peak vasodilator capacity, was also determined. Forearm blood flow response to the endothelium-dependent vasodilator methacholine chloride did not change over the 4-wk-intervention period either in the group undertaking training (n = 11) or in control subjects (n = 6). Similarly, the response to sodium nitroprusside was not influenced by the handgrip training program. Peak vasodilator capacity of the trained forearms significantly increased, whereas no change was evident in the untrained limbs. These results suggest that 4 wk of forearm exercise training enhances peak vasodilator capacity of the vasculature without influencing stimulated activity of the nitric oxide dilator system.
Gynecologic malignancies, representing 13% of all cancers affecting women, have a major impact on women's health. Cervical, endometrial, and ovarian cancers comprise the majority of these tumors and contribute significant morbidity and mortality to the female population. While cervical and endometrial cancers can be detected early in their development, sadly, many patients present with advanced disease, as do the majority of patients with ovarian cancer. Unfortunately, advanced cases of these malignancies are usually lethal despite modern therapeutic modalities. In order to impact upon these grim statistics, gynecologic researchers have turned to molecular biology in an attempt to elucidate the etiology of these cancers. Recent research describing dominant oncogene and tumor suppressor gene mutations common to these malignancies is providing a basis for the molecular genesis of these cancers. This information should offer new avenues for the development of early detection and chemoprevention, as well as novel treatment strategies.
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Platelet-activating factor (PAF) is a potent phospholipid mediator which has been implicated in the pathophysiology and complications of diverse clinical illness such as myocardial infarction and shock. 10 normal males, 13 presenting with acute myocardial infarction and 13 with clinical sepsis were studied. In myocardial infarction, plasma PAF, platelet PAF receptor number and platelet-associated PAF were not significantly different from normal. In clinical sepsis, plasma PAF was not different and platelet-associated PAF was slightly, but not significantly, higher. Similarly, in this group, the production of PAF from resting and stimulated neutrophils was not different from normal. Despite significant experimental evidence from animal studies for the involvement of PAF in cardiovascular disorders, this clinical study provides little direct evidence to support this view. Our results suggest that PAF is maintained at a relatively constant circulating level, a consequence of metabolic regulation and a high avidity for platelets and neutrophils.
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OBJECTIVE: To determine whether slow-release enteric coated aspirin (100 mg daily), commenced before operation, improves the patency of saphenous vein (SV) coronary artery bypass grafts at six months. DESIGN AND SETTING: Double-blind, randomised, placebo-controlled study at a teaching hospital. RESULTS: One hundred and forty patients were randomly allocated to receive enteric coated aspirin or matching placebo. Similar groups of 50 (aspirin) and 52 (placebo) subjects completed the six months follow-up and had an angiogram to assess patency. Five patients treated with aspirin and nine who received placebo had at least one occluded SV graft; the distal ends of 6 of 128 SV grafts in aspirin-treated patients (4.7%) and 13 of 145 SV grafts in patients in the placebo group (9.0%) were occluded--the difference was not significant. An arterial graft was occluded in one other patient in each group (3% of arterial grafts). There was more postoperative blood loss, on average, in patients treated with aspirin, but the difference was not significant. Only one patient was withdrawn from long-term therapy because of possible gastrointestinal symptoms; most withdrawals from the trial were necessitated by commencement of aspirin or non-steroidal anti-inflammatory therapy for musculo-skeletal disorders. CONCLUSIONS: The coronary bypass graft occlusion rate six months after surgery was low, and was lower on average in aspirin treated subjects but not significantly so. Long-term treatment with low-dose aspirin is recommended unless contraindicated.
Platelet-activating factor (PAF) contributes to a range of pathophysiological responses in severe illness. To examine PAF metabolism in acute malaria, venous blood was drawn from 10 untreated adults with falciparum malaria, from 8 with untreated vivax malaria, and from 10 controls. Plasma lyso-PAF, produced from PAF through the enzyme acetylhydrolase (AH), was bioassayed, after acetylation to PAF, by platelet [14C]-serotonin release. AH activity was measured by hydrolysis of [3H]-acetyl-PAF. Amounts of plasma lyso-PAF were lower in falciparum (median [range] 24 [9-221] ng/ml) and vivax (35 [7-236] ng/ml) infected patients than in controls (399 [212-504] ng/ml; P < 0.01), and correlated significantly with serum total and HDL-cholesterol (P < 0.001). Plasma AH activities were similar in the control, falciparum and vivax malaria groups. These data suggest that in malaria plasma lyso-PAF values fall together with other blood lipids, but independently of changes in AH activity. This may reflect a generalised decrease in lipid and phospholipid synthesis. However, the reduction of plasma lyso-PAF concentrations in our patients was much greater than that of serum lipoproteins. This is consistent with conversion of lyso-PAF to PAF or with increased PAF-receptor interactions. These two possibilities would have pathophysiological implications.
BACKGROUND: Platelet-activating factor is a biologically potent phospholipid that may mediate cell damage in patients with myocardial ischemia. In plasma, its inactivation to lyso-platelet-activating factor is catalyzed by a specific, lipoprotein-associated acetylhydrolase. Because lipoprotein levels decrease after myocardial infarction, a possible reduction was suspected to occur in plasma degradation of platelet-activating factor. METHODS: Degradation of platelet-activating factor was examined in an optimized assay of acetylhydrolase activity and in relation to the in vitro plasma half-life of platelet-activating factor. These, plasma lyso-platelet-activating factor and serum lipids, were measured in 12 men with acute myocardial infarction at presentation and at 2 and 7 days later. RESULTS: Acetylhydrolase activity was depressed at day 2 and at day 7. The corresponding increase in plasma half-life of platelet-activating factor was minimal and insignificant. A significant linear relation existed between the half-life of platelet-activating factor and the reciprocal of acetylhydrolase activity at each time of study, indicating a hyperbolic relation between the two. By day 2, total and low-density lipoprotein cholesterol had decreased but showed no further change by day 7; high-density lipoprotein cholesterol had not decreased at day 2 but was depressed by day 7. Plasma lyso-platelet-activating factor had decreased by day 2 and had returned to its initial level by day 7. CONCLUSIONS: Acute myocardial infarction is associated with depression of plasma acetylhydrolase activity, and because of the hyperbolic relation between the plasma enzyme activity and the half-life of platelet-activating factor, the latter shows negligible change. Hence, the mechanism for the inactivation of any platelet-activating factor that might be released as a consequence of tissue damage is preserved.
Patients with a cytologic diagnosis of either atypical squamous cells of undetermined significance (squamous ACUS) (191), atypical squamous cells suggestive of papillomavirus (ACPV) (79), low grade squamous intraepithelial lesion (LSIL) (184) or atypical glandular cells of undetermined significance (glandular ACUS) (30) obtained over an 18-month period were evaluated colposcopically at the National Naval Medical Center. The diagnosis of squamous atypia rendered using the Bethesda System was reduced when compared to the diagnosis of atypia rendered using traditional cytologic terms (1.9% versus 7.2%). Results from colposcopic evaluations of patients with squamous ACUS demonstrated similar rates of underlying dysplasia as in studies using older terminology (low grade dysplasia in 14% and high grade in 6% of the referrals). Colposcopic evaluation of patients with a referral diagnosis of squamous ACPV demonstrated rates of underlying low grade dysplasia double that of the diagnosis of squamous ACUS but half that of a diagnosis of LSIL (25% versus 14%, and 48%, respectively). Colposcopic evaluation of glandular ACUS rendered a diagnosis of high grade dysplasia more than three times (20%) as often as of squamous ACUS (6%). While the Bethesda System reduces inconsistencies in the diagnosis of atypical cytologic changes, a separate category (ACUS) appears to be useful in identifying underlying, unsuspected low grade dysplasias in our laboratory. In addition, glandular atypias herald a significant rate of underlying high grade dysplasias and warrant immediate colposcopic investigation.