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Biomedical subjects

A Davis

Publications and source records attributed to A Davis.

At least 145 records · Page 8Linked to original sources
PubMed1997

Linkage of a neurophysiological deficit in schizophrenia to a chromosome 15 locus.

Inheritance of a defect in a neuronal mechanism that regulates response to auditory stimuli was studied in nine families with multiple cases of schizophrenia. The defect, a decrease in the normal inhibition of the P50 auditory-evoked response to the second of paired stimuli, is associated with attentional disturbances in schizophrenia. Decreased P50 inhibition occurs not only in most schizophrenics, but also in many of their nonschizophrenic relatives, in a distribution consistent with inherited vulnerability for the illness. Neurobiological investigations in both humans and animal models indicated that decreased function of the alpha 7-nicotinic cholinergic receptor could underlie the physiological defect. In the present study, a genome-wide linkage analysis, assuming autosomal dominant transmission, showed that the defect is linked [maximum logarithm of the odds (lod) score = 5.3 with zero recombination] to a dinucleotide polymorphism at chromosome 15q13-14, the site of the alpha 7-nicotinic receptor. Despite many schizophrenics' extremely heavy nicotine use, nicotinic receptors were not previously thought to be involved in schizophrenia. The linkage data thus provide unique new evidence that the alpha 7-nicotinic receptor gene may be responsible for the inheritance of a pathophysiological aspect of the illness.

Auditory Perception↗
PubMed1997

Von Willebrand factor and soluble E-selectin in hyperlipidaemia: relationship to lipids and vascular disease.

Our objective was to determine whether endothelial cell products von Willebrand factor and soluble E-selectin are related to serum lipids, lipoprotein (a), and vascular disease in patients with hyperlipidaemia. In order to achieve our aim, blood samples were obtained for four experiments from 1) 160 patients (49 with symptomatic vascular disease) with hypercholesterolaemia and an equal number of age and sex matched controls; 2) 31 patients who were studied serially before and after successful resolution of their hypercholesterolaemia; 3) 15 patients with hypertriglyceridaemia; and 4) 20 controls, half of whom consumed a lipid-rich breakfast. von Willebrand factor and soluble E-selectin were measured by enzyme linked immunosorbent assay (ELISA) using commercial reagents. In experiment (1) von Willebrand factor was increased in the patients with hypercholesterolaemia (P=0.0077) and was higher still in patients with vascular disease (P<0.0001). Soluble E-selectin was not influenced by hypercholesterolaemia or vascular disease. The correlation of von Willebrand factor with total and LDL cholesterol (both P<0.001) remained after both age and blood pressure were controlled. Experiment (2) showed that serial studies in patients over an average of 7 months a reduction in total cholesterol was associated with a reduction in von Willebrand factor (r=0.51, P=0.002). Experiment (3) demonstrated that von Willebrand factor was not increased in patients with hypertriglyceridaemia (median 8.9 mmol/L), and in experiment (4) a lipid-rich breakfast taken by fasted, healthy controls produced an increase in serum triglycerides (P<0.01) but did not influence von Willebrand factor over an 8 hour period. We conclude that von Willebrand factor, but not soluble E-selectin, is raised in hypercholesterolaemia and therefore may be a potential indicator of endothelial cell physiology in subjects with, or at risk of, atherosclerotic vascular disease.

Adult↗
PubMed1997

Solvation effects are responsible for the reduced inhibitor affinity of some HIV-1 PR mutants.

The formulation of HIV-1 PR inhibitors as anti-viral drugs has been hindered by the appearance of protease strains that present drug resistance to these compounds. The mechanism by which the HIV-1 PR mutants lower their affinity for the inhibitor is not yet fully understood. We have applied a modified Poisson-Boltzmann method to the evaluation of the molecular interactions that contribute to the lowering of the inhibitor affinity to some polar mutants at position 82. These strains present drug resistance behavior and hence are ideally suited for these studies. Our results indicate that the reduction in binding affinity is due to the solvation effects that penalize the binding to the more polar mutants. The inhibitor binding ranking of the different mutants can be explained from the analysis of the different components of our free energy scoring function.

Arginine↗
PubMed1997

Residual stresses in oscillating thoracic arteries reduce circumferential stresses and stress gradients.

The purpose of this paper is to examine the effects of residual stresses and strains in the oscillating arteries on the stress distribution in the vascular wall. We employ a static theory of large elastic deformations for orthotropic material (Chuong and Fung, 1986, J. biomech. Engng 108, 189-192) with the acceleration term added to make the theory dynamic. We use the static elastic parameters of residual stresses in our analysis because the dynamic parameters are not available in the literature. Our analysis reveals that the effect of considering the residual stresses is to decrease the very large circumferential stresses at the inner wall by 62% and reduces the stress gradient through the arterial wall by 94% compared to the case when residual stresses are ignored. Thus, because the arteries do contain residual stresses, the consequent lower stresses at the inner wall and the reduced stress gradient may reduce the progression of atheroma. Our computations show that the stress gradients do not depend on the heart rate.

Animals↗
PubMed1997

Control of schistosomiasis--a global picture.

The control of schistosomiasis has been a challenging task for most endemic countries. Thus, despite the concerted efforts to date, schistosomiasis remains a major public health concern, second only to malaria in the tropics and subtropics. In this review, Lorenzo Savioli and colleagues highlight changes in schistosomiasis prevalence and distribution over the past decades, discuss the success and limitations of the various control strategies, and present possible control initiatives for the future.

Journal Article↗
PubMed1997

Limb salvage surgery and adjuvant radiotherapy for soft tissue sarcomas of the forearm and hand.

Twenty-five consecutive patients with soft tissue sarcoma of the forearm and hand were assessed for limb-salvage surgery and were entered into a prospective study evaluating oncologic details and functional outcome. Seventeen patients had received incomplete primary excision elsewhere and presented with local recurrence or residual disease. Three had pulmonary metastases at the time of presentation. Twenty-three patients were candidates for limb-salvage surgery and 20 received adjuvant radiotherapy. The mean follow-up period was 37 months. There was local recurrence in three patients who had initially received marginal excision of the primary sarcoma, and three patients died of systemic disease. Limb function was assessed prospectively using both patient-based and clinician-based functional scoring systems and revealed good to excellent results in all but three patients. Eighty-eight percent of those who survived and did not require amputation were able to return to occupational and activities of daily living with no or minimal functional limitation. This study demonstrates that limb-salvage surgery, with adjuvant radiotherapy when necessary, is an effective alternative to amputation in the majority of patients with sarcoma of the forearm and hand. Radiation toxicity is rarely a problem.

Activities of Daily Living↗
PubMed1997

Arrhythmia and mortality after the Mustard procedure: a 30-year single-center experience.

OBJECTIVES: Our purpose was to assess the risk factors for late mortality, loss of sinus rhythm and atrial flutter after the Mustard operation. BACKGROUND: The Mustard operation provides correction of cyanosis with low surgical risk in transposition of the great vessels. However, right ventricular failure, loss of sinus rhythm, atrial flutter and death are frequent long-term complications. METHODS: Records of 534 children who underwent the Mustard operation at a single center since 1962 were reviewed for demographic, anatomic, electrocardiographic and physiologic predictors and outcomes. RESULTS: There were 52 early deaths (9.7%). Survival analysis was undertaken for 478 early survivors with a mean follow-up interval of 11.6 +/- 7.2 years. There were 77 late deaths (16.1%), with sudden death (n = 31) the most frequent cause. Survival estimates were 89% at 5 years and 76% at 20 years of age. Risk factors were an earlier date of operation, operative period arrhythmia and an associated ventricular septal defect. Risk (hazard) of late death declined in the first decade, with further peaks in the second decade. Sinus rhythm was present in 77% at 5 years and 40% at 20 years. Loss of sinus rhythm was associated with previous septectomy, postoperative bradycardia and late atrial flutter. Freedom from atrial flutter was 92% at 5 years and 73% at 20 years of age. Risk factors for atrial flutter were the occurrence of perioperative bradyarrhythmia, reoperation and loss of sinus rhythm during follow-up. Risk of atrial flutter demonstrates a late increase. CONCLUSIONS: Ongoing loss of sinus rhythm and late peaks in the risk of atrial flutter and death necessitate continued follow-up.

Arrhythmias, Cardiac↗
PubMed1997

Mutant presenilins of Alzheimer's disease increase production of 42-residue amyloid beta-protein in both transfected cells and transgenic mice.

The mechanism by which mutations in the presenilin (PS) genes cause the most aggressive form of early-onset Alzheimer's disease (AD) is unknown, but fibroblasts from mutation carriers secrete increased levels of the amyloidogenic A beta 42 peptide, the main component of AD plaques. We established transfected cell and transgenic mouse models that coexpress human PS and amyloid beta-protein precursor (APP) genes and analyzed quantitatively the effects of PS expression on APP processing. In both models, expression of wild-type PS genes did not alter APP levels, alpha- and beta-secretase activity and A beta production. In the transfected cells, PS1 and PS2 mutations caused a highly significant increase in A beta 42 secretion in all mutant clones. Likewise, mutant but not wildtype PS1 transgenic mice showed significant overproduction of A beta 42 in the brain, and this effect was detectable as early as 2-4 months of age. Different PS mutations had differential effects on A beta generation. The extent of A beta 42 increase did not correlate with presenilin expression levels. Our data demonstrate that the presenilin mutations cause a dominant gain of function and may induce AD by enhancing A beta 42 production, thus promoting cerebral beta-amyloidosis.

Alzheimer Disease↗
PubMed1997

Long-term protection of chimpanzees against high-dose HIV-1 challenge induced by immunization.

A combination AIDS vaccine approach consisting of priming with adenovirus-HIV-1MN gp160 recombinants followed by boosting with HIV-1SF2 gp120 was evaluated in chimpanzees. Long-lasting protection, requiring only three immunizations, was achieved against a low-dose challenge with the SF2 strain of HIV-1 and a subsequent high-dose SF2 challenge administered 1 year later without an intervening boost. Notably, neutralizing antibody responses against both clinical and laboratory isolates developed in three chimpanzees and persisted until the time of high-dose challenge. The possibility that cytotoxic T-lymphocytes contribute to low-dose protection of a chimpanzee lacking neutralizing antibodies is suggested. Our results validate the live vector priming/subunit booster approach and should stimulate interest in assessing this combination vaccine approach in humans.

Adenoviridae↗
PubMed1997

Caudal tramadol for postoperative analgesia in pediatric hypospadias surgery.

Ninety boys, aged 13-53 months, undergoing repair of hypospadias, were allocated randomly to receive 0.8 ml kg-1 of one of three solutions into the caudal extradural space: group B received bupivacaine 2 mg kg-1, group T received tramadol 2 mg kg-1 in 0.9% saline and group BT a mixture of both. Postoperative pain was assessed hourly for 12 h after injection using a modified TPPPS pain score and additional analgesia was administered to those children whose pain scores were > 3/10. Nine patients (30%) in group T required additional analgesia within 1 h of surgery compared with only two (6.7%) and three (10%) patients in groups B and BT, respectively (P = 0.04). Mean duration before additional analgesia was required in the remaining patients was 9.3 (SD 3.0) h in group B, 10.7 (2.2) h in group T and 10.5 (2.0) h in group BT (P > 0.20). There were no significant differences between the groups in mean ventilatory frequency, sedation scores, incidence of emesis, facial flushing or pruritus. We conclude that caudal tramadol had a slow onset of action and that the addition of tramadol to bupivacaine, when both drugs were administered caudally, did not significantly prolong the duration of action of bupivacaine.

Analgesia, Epidural↗
PubMed1997

The environmental geochemistry and bioaccessibility of mercury in soils and sediments: a review.

There have been many studies of mercury geochemistry in the environment and its bioconcentration/bioaccumulation through the aquatic food chain. However, there is a dearth of information regarding the bioaccessibility of mercury in human receptors exposed primarily by soil ingestion. This paper reviews the current state of knowledge of mercury bioaccessibility and speciation in soils, and the utility of speciation methods to estimate mercury bioaccessibility. We conclude that additional research is necessary to determine: (1) whether analytical measurements can adequately determine the bioaccessibility of mercury in sediments and soils; (2) the accuracy of in vitro analyses in assessing mercury bioaccessibility; (3) the ability of mercury to cross tissue membranes of the mouth, esophagus, stomach, and the small and large intestines; (4) the speciation and distribution of mercury in biological fluids; and (5) mercury bioavailability using an in vivo animal model relevant to human gastrointestinal tract conditions.

Administration, Oral↗
PubMed1997

PTFE-encapsulated endovascular stent-graft for transjugular intrahepatic portosystemic shunts: experimental evaluation.

PURPOSE: To evaluate the safety and efficacy of a stent-graft designed for a transjugular intrahepatic portosystemic shunt (TIPS), assess angiographic and hepatic biologic responses to polytetrafluoroethylene (PTFE)-encapsulated stents, and compare with a bare stent. MATERIALS AND METHODS: Twelve TIPS (eight with flexible PTFE-encapsulated balloon-expandable stent-grafts and four control TIPS with bare Wallstents) were created in 12 pigs. Shunt venography was performed at 1-month intervals and necropsy of graft-containing animals at 1, 2, 3, 4, and 5 months. Control animals were sacrificed at 6 weeks. Detailed histopathologic analyses were performed. RESULTS: The stent-grafts were readily deployed in all cases. Seven of eight graft TIPS remained fully patent during the follow-up period without luminal encroachment. Typical myofibrolasts proliferated on the abluminal surface of the graft, without extension into the lumen. No inflammatory reaction was present. Cellular overgrowth from the hepatic vein occluded the end of one graft at 3 months, partly related to rapid axial growth of that animal. The endoluminal surface of this shunt was otherwise patent. At 4-6 weeks, one control TIPS was occluded and the other three showed 45%-85% stenoses. No bile staining was seen in any case. CONCLUSION: This PTFE-encapsulated stent-graft is biocompatible and safe to place. It markedly improves TIPS patency, providing almost uninterrupted, unimpeded patency in this model.

Animals↗
PubMed1997

Epidemiology of permanent childhood hearing impairment in Trent Region, 1985-1993.

This retrospective study of permanent childhood hearing impairment (PCHI) > or = 40 dB HL in children born between 1985 and 1993 and resident in Trent Health Region, achieved an ascertainment of 92.9% of that expected from previous studies and 100% for the subset of children born between 1985 and 1990. The prevalence rate of all permanent hearing impairment > or = 40 dB HL for the birth cohort 1985-90 is 133 (95% confidence interval, (ci) 122-145) per 100,000 live births (1 in 750). Sixteen per cent of PCHI were postnatally acquired, late-onset or progressive impairments. Excluding these, the prevalence rate for congenital impairments is 112 (ci 101-123) per 100,000 (1 in 900). The rate for profound impairments > or = 95 dB HL is 24 (ci 20-30) per 100,000 live births (1 in 4150). Prevalence was increased sixfold for children with a history of neonatal intensive care and 14-fold for children with a family history, compared with children with no risk factors. A more than two-fold increase in prevalence was seen in Asian children. For the congenitally-impaired children born between 1985 and 1990, 29% had a stay in neonatal intensive care > or = 48 hours, 30% had a family history of permanent childhood hearing impairment, and 12% had a cranio-facial abnormality (CFA). Over 59% were potentially detectable by a targeted neonatal screening programme using these three high-risk factors. For 1985-1993, the overall yield of the targeted neonatal screening programmes available in three of the 11 health districts was 15% but increased over time. The overall yield from the Health Visitor distraction test was 30% but lower in districts with neonatal screening programmes. Only 59% of children had a stated aetiology, classified by time of onset into genetic, including syndromes and CFA (41%), pre- or peri-natal (10%), post-natally acquired (6%), and uncertain onset (2%). Just under 40% of the children were said to have another clinical or developmental problem, about half of whom had at least two additional problems. The median age at referral, confirmation of the impairment, prescription of the hearing aid and fitting of the hearing aid were, respectively, 10.4 months, 18.1 months, 24.4 months and 26.3 months. A more severe impairment was associated with earlier age. Small improvements in the median age of hearing aid prescription and fitting were seen over time. Twenty-five per cent of children were referred for genetic counselling, the proportion increasing systematically with the severity of the impairment. Based on evidence of the yield from hearing screens we suggest a wider implementation of neonatal screening and further consideration of the role of the health visitor distraction test in the identification of children with PCHI. To facilitate further assessment of services for hearing-impaired children we suggest implementation of a co-ordinated shared list of children with permanent hearing impairment on a region-wide basis to provide adequate numbers for comparison over time, and the routine collection of a minimum set of data for each child.

Age Distribution↗
PubMed1997

Reconstruction of massive bone defects with allograft in revision total knee arthroplasty.

Allograft bone was used to reconstruct a defect in the proximal aspect of the tibia or the distal aspect of the femur, or both, in thirty knees of twenty-eight patients who had a revision total knee arthroplasty. The average age of the patients at the time of the index procedure was 65.8 years (range, twenty-four to eighty-nine years). At an average of fifty months (range, twenty-four to 132 months; median, thirty-six months) postoperatively, the score for twenty-three knees (twenty-one patients) had increased by at least 20 points, and these knees did not need additional operative treatment. Thus, the rate of success was 77 per cent. The procedure was considered a failure for the remaining seven knees because of infection (three), loosening of the tibial component (two), fracture of the graft (one), and non-union at the allograft-host junction (one). Properly applied allograft can be used to reconstruct massive bone defects, provide stability and support for implants, and restore bone stock in the event that additional operative treatment is necessary.

Adult↗
PubMed1997

Work redesign in the intensive care unit setting.

One of the most challenging things that health care providers can be asked to do is change the way that they practice. This article describes such a scenario. The staff of one particular surgical intensive care unit, caring primarily for open-heart surgery patients, has been challenged to increase its nurse:patient ratio without compromising the quality care that staff has been accustomed to providing. This article reviews the process of data gathering, the evaluation of data, and the implementation of the nurse:patient ratio changes. It also describes the outcome criteria used to evaluate the practice changes.

Cardiac Surgical Procedures↗
PubMed1997

A critical review of the role of neonatal hearing screening in the detection of congenital hearing impairment.

BACKGROUND: This review was commissioned because of the increasing doubt about the ability of existing screening programmes (mainly the health visitor distraction test (HVDT) at 7-8 months) to identify children with congenital hearing impairment, and technological advances which have made neonatal hearing screening an alternative option. OBJECTIVES: To review the available literature on the screening of permanent childhood hearing impairment. To provide commissioners and providers of health care with information about how to deliver a more uniform service, better outcomes, and more cost-effective screening. To identify areas for further research and service development. HOW THE RESEARCH WAS CONDUCTED: The research involved a review of the available published and unpublished literature, and a comprehensive survey of current pre-school hearing screening provision in the UK coupled with a health economics study of hearing screening costs. The research also included a number of focus groups and visits to key centres in the UK and North America. RESEARCH FINDINGS: EPIDEMIOLOGY OF PERMANENT CHILDHOOD HEARING IMPAIRMENT: There are approximately 840 children a year born in the UK with significant permanent hearing impairment likely to affect their own and their family's quality of life. Present services will miss about 400 of these children by 1 1/2 years of age, and about 200 of these children by 3 1/2 years of age. Such late identification of hearing impairment greatly reduces the responsiveness of the services for individual children. EVIDENCE FOR IMPROVED OUTCOMES WITH EARLIER IDENTIFICATION: Hearing-impaired children identified late are at risk of substantial delay in their acquisition of language and communication skills, with consequent longer-term risk to education achievement, mental health and quality of life. Theoretical arguments on neural development support the limited evidence here for the increased benefit for child and family associated with very early identification. In general, parents and professionals want very early identification, which, if implemented properly, does not cause undue anxiety. CURRENT UK PRACTICE: The survey of current practice indicated a major problem with poor information systems. This problem was further highlighted as a major concern by the multi-disciplinary focus groups. Practice varies. There are two District-wide programmes in which all newborn babies are neonatally screened, a large number of ad hoc programmes for neonatal screening of 'at-risk' babies, a variety of early surveillance programmes, and widespread use of the HVDT. Intervention and habilitation for the majority of those screened neonatally is routinely undertaken within 6 months of birth. For those screened only by the health visitor, identification was on average at about 26 months of age with intervention at about 32 months on average. (ABSTRACT TRUNCATED)

Child, Preschool↗