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Biomedical subjects

M Perry

Publications and source records attributed to M Perry.

At least 55 records · Page 3Linked to original sources
PubMed1998

Specificity, isotype, and titer distribution of anticardiolipin antibodies in CNS diseases.

BACKGROUND AND PURPOSE: There is an association between anticardiolipin antibodies (aCL) and ischemic stroke. There are, however, also occasional reports linking aCL with other CNS diseases (OND), particularly with multiple sclerosis (MS). Hence, we studied the specificity of aCL for ischemic stroke. METHODS: Prospective, consecutively identified patients evaluated for aCL (immunoglobulin G [IgG] and immunoglobulin M [IgM] isotypes) were divided into two groups: ischemic stroke (first ever) and OND (stroke-free subjects affected by OND). RESULTS: The ischemic stroke group (n = 300) and the OND (n = 149) differed in the following risk factors: age (64 +/- 14 versus 58 +/- 15 years; p < 0.001) and proportions of African Americans (67% versus 29%; p < 0.001); current cigarette smoker (26% versus 17%; p = 0.028); hypertensive (69% versus 34%; p < 0.001); diabetic (18% versus 7%; p = 0.001); history of angina (16% versus 8%; p = 0.015) or myocardial infarction (15% versus 3%; p < 0.001). There were higher rates of aCL positivity (26% versus 17%; p = 0.050), IgG-aCL > 10 GPL (23% versus 11%; p = 0.003) or IgG aCL > 20 GPL (12% versus 4%; p = 0.012) among the stroke group than among the OND group. No differences in IgG-aCL positivity were found between the MS group and the rest of the OND group but the MS patients had a higher rate of IgM-aCL positivity than the other OND patients. CONCLUSION: IgG-aCL positivity does not appear to be a marker for CNS disease generally but of ischemic stroke.

Antibodies, Anticardiolipin↗
PubMed1997

Effect of antihypertensive drug treatment on cardiovascular outcomes in women and men. A meta-analysis of individual patient data from randomized, controlled trials. The INDANA Investigators.

BACKGROUND: Trials of drug therapy for hypertension have shown that such therapy has a clear overall benefit in preventing cardiovascular disease. Although these trials have included slightly more women than men, it is still not clear whether treatment benefit is similar for both sexes. OBJECTIVE: To quantify the average treatment effect in both sexes and to determine whether available data show significant differences in treatment effect between women and men. DESIGN: Subgroup meta-analysis of individual patient data according to sex. Analysis was based on seven trials from the INDANA (INdividual Data ANalysis of Antihypertensive intervention trials) database and was adjusted for possible confounders. PATIENTS: 20,802 women and 19,975 men recruited between 1972 and 1990. INTERVENTIONS: Primarily beta-blockers and thiazide diuretics. RESULTS: In women, treatment effect was statistically significant for stroke (fatal strokes and all strokes) and for major cardiovascular events. In men, it was statistically significant for all categories of events (total and specific mortality, all coronary events, all strokes, and major cardiovascular events). The odds ratios for any category of event did not differ significantly between men and women. In absolute terms, the benefit in women was seen primarily for strokes; in men, treatment prevented as many coronary events as strokes. Graphical analyses suggest that these results could be completely explained by the difference in untreated risk. CONCLUSIONS: In terms of relative risk, treatment benefit did not differ between women and men. The absolute risk reduction attributable to treatment seemed to depend on untreated risk. These findings underline the need to predict accurately the untreated cardiovascular risk of an individual person in order to rationalize and individualize antihypertensive treatment.

Adrenergic beta-Antagonists↗
PubMed1997

Risk of unanticipated intraoperative events in patients assessed at a preanaesthetic clinic.

PURPOSE: To determine the risk of unanticipated intraoperative events (UIE) in patients assessed at a preanaesthetic clinic compared with those not assessed at the clinic. METHODS: Preoperative and intraoperative data were collected on 6130 elective surgical patients by procedural anaesthetists over a 12-month-period at an Australian tertiary referral hospital. The procedural anaesthetists rated the level of preparation and identified predefined unanticipated intraoperative events. A logistic regression model was used to identify significant risk factors of UIE and was further validated on another sample of 482 patients (one month) by a goodness-of-fit test. RESULTS: Of the 6130 elective surgical patients, 2000 (33%) had been assessed at the preanaesthetic clinic. There was a greater proportion of ASA II to IV patients seen at the clinic than patients not assessed at the clinic (chi 2(3) = 689.92, P < 0.001). Nonclinic patients were more likely to be inadequately prepared than clinic patients (RRunadjusted = 1.61, 95% CI: 1.25 to 2.04, P < 0.001). The overall incidence of intraoperative events was 4.14% (95% CI: 3.64% to 4.64%). Despite adjusting for the preparation level, type of anaesthesia, admission category, ASA physical status and duration of anaesthesia, clinic patients were 1.94 (95% CI: 1.42 to 2.64) times more likely to experience an UIE than nonclinic patients (P < 0.001). CONCLUSION: Although clinic patients were more often optimally prepared, their adjusted risk of UIE was higher than nonclinic patients. The procedural anaesthetist needs to be vigilant with these high risk patients, even if they have been assessed at a preanaesthetic clinic.

Adult↗
PubMed1997

Hypertension-related morbidity and mortality in the southeastern United States.

Stroke mortality is higher in the Southeast compared with other regions of the United States. The prevalence of hypertension is also higher (black men = 35%, black women = 37.7%, white men = 26.5%, white women = 21.5%), and the proportion of patients whose hypertension is being controlled is poor, especially in white and black men. The prevalence of hypertension-related complications other than stroke is also higher in the Southeast. The five states with the highest death rates for congestive heart failure are all in the southern region. Of the 15 states with the highest rates of end-stage renal disease, 10 are in the Southeast. Obesity is very prevalent (24% to 28%) in the Southeast. Although Michigan tops the ranking for all states, 6 of the top 15 states are in the Southeast, as are 7 of the 10 states with the highest reported prevalence regarding no leisure-time physical activity. Similar to other areas of the United States, dietary sodium and saturated fat intake are high in the Southeast; dietary potassium intake appears to be relatively low. Other factors that may be associated with the high prevalence, poor control, and excess morbidity and mortality of hypertension-related complications in the Southeast include misperceptions of the seriousness of the problem, the severity of the hypertension, lack of adequate follow-up, reduced access to health care, the cost of treatment, and possibly, low birth weights. The Consortium of Southeastern Hypertension Control (COSEHC) is a nonprofit organization created in 1992 in response to a compelling need to improve the disproportionate hypertension-related morbidity and mortality throughout this region. The purpose of this position paper is to summarize the data that document the problem, the consequences, and possible causative factors.

Adult↗
PubMed1997

Effect of antihypertensive treatment in patients having already suffered from stroke. Gathering the evidence. The INDANA (INdividual Data ANalysis of Antihypertensive intervention trials) Project Collaborators.

BACKGROUND AND PURPOSE: Drug treatment of high blood pressure has been shown to reduce the associated cardiovascular risk. Stroke represents the type of event more strongly linked with high blood pressure, responsible for a high rate of death or invalidity, and with the highest proportion of events that can be avoided by treatment. Hypertensive patients with a history of cerebrovascular accident are at particularly high risk of recurrence. Specific trials of blood pressure lowering drugs in stroke survivors showed inconclusive results in the past. METHODS: We performed a meta-analysis using all available randomized controlled clinical trials assessing the effect of blood pressure lowering drugs on clinical outcomes (recurrence of stroke, coronary events, cause-specific, and overall mortality) in patients with prior stroke or transient ischemic attack. RESULTS: We identified 9 trials, including a total of 6752 patients: 2 trials included 551 hypertensive stroke survivors; 6 trials of hypertensive patients included a small proportion of stroke survivors (536 patients); 1 trial included stroke survivors, whether hypertensive or not (5665 patients). The recurrence of stroke, fatal and nonfatal, was significantly reduced in active groups compared with control groups consistently across the different sources of data (relative risk of 0.72, 95% confidence interval: 0.61 to 0.85). There was no evidence that this intervention induced serious adverse effect. CONCLUSIONS: Blood pressure lowering drug interventions reduced the risk of stroke recurrence in stroke survivors. Available data did not allow to verify whether such benefit depends on initial blood pressure level. More data are needed before considering antihypertensive therapy in normotensive patients at high cerebrovascular risk.

Aged↗
PubMed1997

IgG anticardiolipin antibody titer > 40 GPL and the risk of subsequent thrombo-occlusive events and death. A prospective cohort study.

BACKGROUND: Anticardiolipin antibodies (aCL) have been associated with an increased risk of stroke and thrombo-occlusive events. Little is known about the influence of aCL on recurrent thrombo-occlusive events. METHODS: Consecutively identified patients (n = 132) with focal cerebral ischemia [stroke = 112, transient ischemic attack (TIA) = 20] harboring aCL of at least 10 GPL units at the time of their index event were prospectively followed to estimate the effect of aCL titer on time to and risk of subsequent thrombo-occlusive events (stroke, TIA, deep venous thrombosis, pulmonary embolism, myocardial infarction) and death. On the basis of prior literature, we divided patients into those with aCL < or = 40 GPL (n = 111; mean age, 63 +/- 14 years; mean follow-up, 1.95 years) and those with aCL > 40 GPL (n = 21; mean age, 54 +/- 20 years; mean follow-up, 1.50 years). RESULTS: There was no difference between groups for prevalence of hypertension, diabetes mellitus, cigarette smoking, atrial fibrillation, prior TIA, or sex. The GPL > 40 group was younger (54 +/- 20 versus 63 +/- 14 years; P = .055), had more prior strokes [9/21 (48%) versus 27/111 (20%); P = .030], more frequent subsequent thrombo-occlusive events and death [15/21 (71%) versus 51/111 (48%); P = .030], and a shorter median time (years) to event (0.15 versus 0.61, log rank P = .005). The risk ratio for recurrent event and death with GPL > 40 obtained from Cox proportional hazards models, adjusted for prior strokes, prior TIAs, hypertension, diabetes mellitus, atrial fibrillation, and cigarette smoking was 1.9 (95% confidence interval, 1.0 to 3.5; P = .051). CONCLUSIONS: Our data suggest that subsequent thrombo-occlusive events and death after focal cerebral ischemia associated with IgG aCL may occur sooner and more frequently with GPL > 40.

Adult↗
PubMed1997

Autoactivation of Xenopus MyoD transcription and its inhibition by USF.

Members of the MyoD family of muscle-specific transcription factors play central roles in the formation and differentiation of skeletal muscle; however, steps involved in the initiation and subsequent regulation of myogenic factor expression are poorly understood. To investigate mechanisms underlying muscle cell type-specific MyoD gene expression, the functions of regulatory elements that control Xenopus MyoDa gene transcription were analyzed. We show that E boxes in the XMyoDa promoter have dual functions. These sites bind myogenic basic helix-loop-helix proteins and serve as target sites for direct autoactivation. In addition, these regulatory elements bind other, more widely expressed proteins that repress promoter activity. In particular, the binding of the transcriptional regulatory protein USF to a conserved site in the XMyoDa promoter decreased basal activity of the promoter and inhibited MyoD-dependent autoactivation. The results suggest that XMyoD transcription and myogenic factor activity is governed by a competition between muscle-specific, positive-acting factors and widely expressed repressors for binding to common regulatory sites.

Animals↗
PubMed1996

Transglutaminase forms midkine homodimers in cerebellar neurons and modulates the neurite-outgrowth response.

Midkine is a prominent acyl donor substrate for the protein cross-linking enzyme transglutaminase type 2 in rat brain neurons. Transglutaminase type 2 and midkine immunoreactivity are regionally colocalized in developing cerebellar cortex. Monomeric midkine is present in the embryonic dorsal rhombic lip which gives rise to the cerebellar cortex. A high-molecular weight (29-30 kDa) midkine appears during postnatal cerebellar development. The presence of the high-molecular weight midkine in cultured cerebellar cortical interneurons is dependent upon culture conditions. Transglutaminase catalyzes the calcium-dependent cross-linking of midkine predominantly into 29-30 kDa dimers. Dimer-formation of midkine in vitro and in cultured neurons is reduced in the presence of a transglutaminase inactivator. Neurons plated onto previously cross-linked midkine exhibit larger growth cones and enhanced neurite outgrowth compared to those plated onto monomeric midkine alone.

Aging↗
PubMed1996

Preservation of viable biological samples for experiments in space laboratories.

Standard viable preservation methods for biological samples using low temperatures have been investigated concerning their storage capabilities under higher temperature levels than usual. For a representative set of organism classes (plants, mammalian cells, arthropods and aquatic invertebrates), the minimum appropriate storage conditions have been identified by screening storage temperatures at -196 degrees, -80 degrees, -20 degrees, +4 degrees, +20 degrees/25 degrees C for periods from 2 days to 4 weeks. For storage below 0 degree C, as a typical cryopreservative, dimethylsulfoxide (DMSO) was used. For some samples, the addition of trehalose (as cryopreservative) and the use of a nitrogen atmosphere were investigated. After storage, the material was tested for vitality. The findings demonstrated that acceptable preservation can be achieved under higher storage temperatures than are typically applied. Small, dense cultured plant cells survive for 21 d when moderately cooled (+4 degrees to -20 degrees C); addition of trehalose enhances viability at -20 degrees C. For mammalian cells, the results show that human lymphocytes can be preserved for 3 d at 25 degrees C, 7 d at 4 degrees C and 28 d at -80 degrees C. Friend leukaemia virus transformed cells can be stored for 3 d at 25 degrees C, 14 d at 4 degrees C and 28 d at -80 degrees C. Hybridoma cells can be kept 7 d at 4 degrees C and 28 d at -20 degrees C or -80 degrees C. Model arthropod systems are well preserved for 2 weeks if maintained at lower temperatures that vary depending on the species and/or stage of development; e.g., 12 degrees C for Drosophila imagoes and 4-6 degrees C for Artemia nauplii. For aquatic invertebrates such as sea urchins, embryonic and larval stages can be preserved for several weeks at +6 degrees C, whereas sperm and eggs can best be stored at + 4 degrees C for up to 5 d at maximum. These results enhance the range of feasible space experiments with biological systems. Moreover, for typical terrestrial preservation methods, considerable modification potential is identified.

Animals↗
PubMed1996

Immunodetection of squamous cell carcinoma-associated variant of nuclear protein.

A new monoclonal antibody, MAb C63.3, was developed by immunizing mice with the high molecular weight fraction of the cytoplasmic proteins from the cervical squamous cell carcinoma. In Western blotting, MAb C63.3 reacted with cytoplasmic and chromatin antigens expressed by cervical and vulvar squamous cell carcinomas and much weaker with normal cervical tissue and skin cells. Different molecular variants of C63.3 chromatin antigens were found in normal tissues (heavy variants, M(r) 65,000 and 59,000) compared to squamous cell carcinomas (light variant, M(r) 48,000). Diagnostic value of the cancer-associated M(r) 48,000 antigen is discussed. MAb C63.3 was internalized by cells and bound to the chromatin which suggests that antigen(s) C63.3 might represent a receptor for a yet unknown ligand (growth factor). It is suggested that the high molecular weight C63.3 antigens play a role in maintaining the nonmalignant phenotype.

Animals↗
PubMed1996

Intraoperative heparinisation, blood loss and myocardial infarction during aortic aneurysm surgery: a Joint Vascular Research Group study.

OBJECTIVES: The primary aim of this prospective multi-centre study involving patients undergoing elective abdominal aortic aneurysm (AAA) surgery was to investigate the relationship between intraoperative intravenous heparinisation, blood loss during surgery and thrombotic complications. METHODS: Two hundred and eighty-four patients were randomised to receive intravenous heparin (n = 145) or no heparin (n = 139). Groups were evenly matched for age, sex, weight, aneurysm size, haemoglobin concentration, platelet counts and distal occlusive disease measured by ankle/brachial systolic pressure. RESULTS: There were no statistically significant differences in blood loss (median 1400 ml vs. 1500 ml; z = 0.02, p = 0.98, 95% C.I. = -200 to 200), blood transfused (4.0 units vs. 4.0 units; z = 1.09, p = 0.28, 95% C.I. = -1 to 0) or distal thrombosis between the two groups. However, analysis of the clinical outcome revealed that 5.7% of the non-heparin group but only 1.4% of the heparinised patients suffered a fatal perioperative myocardial infarction (MI); p < 0.05. All MI, including non fatal events, affected 8.5% and 2% respectively (p = 0.02). CONCLUSIONS: Heparin does not increase blood loss or the need for blood transfusion during surgery. Heparin is not necessary to prevent distal thrombosis when the aorta is cross clamped. The results of the study are consistent with the known mechanisms leading to intraoperative MI and strategies for its prevention. Intravenous heparin, given before aortic cross clamping, is an important prophylaxic against perioperative MI in relation to AAA surgery.

Anticoagulants↗
PubMed1996

PDGF AA as mediator in nicotine-dependent carcinogenesis.

Effect of nicotine on PDGF AA and PDGF BB interaction with cervical cancer SiHa cells was tested. [125I]PDGF AA was internalized by cells and accumulated in the cytoplasm and nucleus (chromatin). In the absence of nicotine, maximal accumulation of [125I]PDGF AA inside the cells occurred after 1 day of incubation, which was followed by a progressive degradation of the growth factor during the next 2, 3 and 5 days of cell exposure. In the presence or 0.001 or 0.01% nicotine, accumulation of [125I]PDGF AA was slightly higher than in the absence of nicotine, and maximal accumulation occurred after 2 days or incubation. In the presence of 0.1 % nicotine, maximal accumulation occurred after 5 days of incubation and was 20 and 14 times higher in the cytoplasm and chromatin, respectively. Nicotine-postponed degradation and increased nuclear accumulation of PDGF AA resulted in activation of RNA synthesis and cell proliferation. PDGF BB, which was not internalized by cells did not respond to nicotine treatment. The proposed mechanism of nicotine-PDGF AA co-carcinogenesis may involve inhibition of growth factor degradation at the lysosomal level and an increased chromatin accumulation of the non-degraded PDGF.

Becaplermin↗
PubMed1996

The inhibition of antigen-induced eosinophilia and bronchoconstriction by CDP840, a novel stereo-selective inhibitor of phosphodiesterase type 4.

1. The novel tri-aryl ethane CDP840, is a potent and selective inhibitor of cyclic AMP phosphodiesterase type 4 (PDE 4) extracted from tissues or recombinant PDE 4 isoforms expressed in yeast (IC50S: 4-45 nM). CDP840 is stereo-selective since its S enantiomer (CT 1731) is 10-50 times less active against all forms of PDE 4 tested while both enantiomers are inactive (IC50S: > 100 microM) against PDE types 1, 2, 3 and 5. 2. Oral administration of CDP840 caused a dose-dependent reduction of interleukin-5 (IL-5)-induced pleural eosinophilia in rats (ED50 = 0.03 mg kg-1). The eosinophils in pleural exudates from CDP840-treated animals contained higher levels of eosinophil peroxidase (EPO) than cells from control animals, suggesting a stabilizing effect on eosinophil degranulation. CDP840 was approximately equi-active with the steroid dexamethasone in this model and was 10-100 times more potent than the known PDE 4-selective inhibitors rolipram and RP73401. The activity of CDP840 was not influenced by adrenalectomy, beta-sympathomimetics or beta-sympatholytics. 3. Antigen-induced pulmonary eosinophilia in sensitized guinea-pigs was reduced dose-dependently by CDP840 (0.01-1 mg kg-1, i.p.) and intracellular EPO levels were significantly higher. CDP840 was more potent in these activities than CT1731 or rolipram and comparable in potency to RP73401. 4. Rolipram or CDP840 were less active than dexamethasone in preventing neutrophil accumulation, or exudate formation in carrageenan-induced pleurisy in rats and thus do not exhibit general anti-inflammatory activity. 5. In sensitized guinea-pigs, aerosols of the antigen ovalbumin caused a dose-dependent bronchoconstriction demonstrated by an increase in pulmonary inflation pressure. Administration of CDP840 (0.001-1.0 mg kg-1, i.p.), 1 h before antigen challenge, resulted in dose-dependent reduction in response to antigen. This activity was not due to bronchodilatation since higher doses of CDP840 (3 mg kg-1) did not significantly change the bronchoconstrictor response to histamine. Rolipram was approximately 10 times less active than CDP840 in preventing antigen-induced bronchoconstriction. 6. These results confirm the observations that selective PDE 4 inhibitors reduce antigen-induced bronchoconstriction and pulmonary eosinophilic inflammation. CDP840 is more potent than rolipram in inhibiting native or recombinant PDE 4. Unlike the recently described potent PDE 4 inhibitor RP73401, CDP840 is more active than rolipram in the rat IL-5 model following oral administration. The novel series of tri-aryl ethanes, of which CDP840 is the lead compound, could be the basis of an orally active prophylactic treatment for human asthma.

3',5'-Cyclic-AMP Phosphodiesterases↗
PubMed1996

Clinical safety and efficacy of calf tourniquets.

A clinical study was undertaken to ascertain the utility and complication rate of proximal calf tourniquet use for foot and ankle surgery. The surgical and clinical records of 446 patients undergoing foot and ankle surgery between March 1992 and December 1994 were examined for details pertaining to intraoperative tourniquet use and postoperative evidence of neurologic or vascular complications. All patients who had surgery performed under tourniquet control were included in the study. A total of 454 limbs were operated on: 8 patients underwent bilateral surgical procedures. The patients comprised 172 men and 274 women. The average age was 48.9 (+/-16.0 SD) years. Surgery was completed in one tourniquet period in 435 cases (95.8%) and in two periods of tourniquet inflation in 19 cases (4.2%). The average duration of tourniquet ischemia was 49.2 minutes (+/-30.7 SD) for one tourniquet period and 131.1 minutes (+/-46.0 SD) for two tourniquet periods. No postoperative compromise to either neurologic or vascular function was detected. Specifically, no alteration in peroneal nerve function was seen. We conclude that a calf tourniquet placed proximally with adequate cast padding is a safe and effective method to achieve a bloodless surgical field for foot and ankle surgery.

Adult↗
PubMed1996

Erythrocyte sedimentation rate and C reactive protein in the assessment of suspected bone infection--are they reliable indices?

The child who presents limping or with pain in a limb in the absence of a clear cause is a common problem, yet one which must be taken seriously. In the absence of trauma, infection involving the bone or joint must be carefully excluded clinically and often with the aid of further investigations. Preliminary investigations usually involve measurement of the while cell count (WCC), Erythrocyte Sedimentation Rate (ESR), and C Reactive Protein (CRP) as these are regarded as sensitive indicators for the presence of infection. Radiographs of the appropriate areas may be taken to assess for soft tissue swelling, chronic bone changes or evidence of trauma. The following case report demonstrates that normality of these parameters cannot be used to confidently exclude suppurative osteomyelitis and highlights the value of follow-up in apparently self-limiting conditions.

Blood Sedimentation↗
PubMed1996

Audit of 149 consecutive carotid endarterectomies performed by a single surgeon in a district general hospital over a 12-year period.

Carotid endarterectomy has been established by two large randomised controlled trials (European Carotid Surgery Trial (ECST) and North American Symptomatic Carotid Endarterectomy Trial (NASCET)) as an important surgical procedure for the prevention of ischaemic strokes in patients presenting with transient cerebral ischaemia or non-disabling strokes attributable to severe ipsilateral carotid artery stenosis. The operation carries significant risk of death and stroke and it has been advocated by some that carotid endarterectomy should only be performed in a small number of designated regional centres in order to achieve good surgical results. It is doubtful that the regional centres alone can cope with the increasing numbers of patients requiring carotid endarterectomy and there is therefore a requirement for the procedure to be carried out by vascular surgeons in district general hospitals. It is important that surgical results are audited to ensure that comparable outcomes are achieved. We present an audit of our experience of carotid endarterectomy since 1981. A total of 149 consecutive carotid endarterectomies were performed by a single surgeon with a special interest in carotid surgery. The results are comparable to ECST with a 30-day mortality of 0% and an overall 30-day stroke rate of 5.7% (major strokes) for patients with severe, ie 70-99%, ipsilateral carotid artery stenoses. We have shown that carotid endarterectomy is an operation that can be performed safely and with good results by suitably trained surgeons in district general hospitals.

Adult↗
PubMed1996

Promotion of health information access via Grateful Med and Loansome Doc: why isn't it working?

Information gathered from Grateful Med and Loansome Doc outreach projects, including one involving seven health centers in rural southwest Alabama, raises questions about the effectiveness of such programs. This paper presents a review of the literature on Grateful Med as well as of information access and usage behaviors of physicians, an overview of the Alabama project, and data from other projects. Analysis of the responses and observations of the researchers reveal some strategies for enhancing the outcomes of such projects and improving access to medical care literature by health care professionals at rural sites.

Alabama↗