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Biomedical subjects

S Hall

Publications and source records attributed to S Hall.

At least 91 records · Page 5Linked to original sources

Excitatory action of N-methyl-D-aspartate on the rat locus coeruleus is mediated by nitric oxide: an in vivo voltammetric study.

Biochemical, electrophysiological and behavioural studies have provided evidence that activation of N-methyl-D-aspartate (NMDA) receptors contributes to the hyperactivity of noradrenergic neurons of the locus coeruleus (LC) in precipitated opioid withdrawal. Recently, it was demonstrated that central administration of nitric oxide (NO) synthase inhibitors suppresses this hyperactivity suggesting that NO mediates the NMDA receptor activation of LC in opioid withdrawal. Using a combination of microdialysis and in vivo voltammetry, this study examined whether local application of NMDA to the LC in opioid naive animals mimics the NO-dependent LC response seen in opioid withdrawal. In the urethane anaesthetized rat, perfusion of the LC (2 microliters min-1) with a solution of NMDA (5 mmol) via a microdialysis probe for 9 min resulted in a rapid and robust increase (290.1 +/- 32.2% above baseline) in the catechol oxidation current (CA.OC) recorded from the LC using differential normal pulse voltammetry (DNPV). The NMDA microdialysis also produced a large increase in the blood pressure (150.4 +/- 6.9% above baseline). An injection of the non-competitive NMDA receptor antagonist (+)MK-801 (0.5 mg kg-1 i.v.), given 45 min after the start of NMDA application, rapidly returned both the CA.OC signal and the blood pressure response to baseline levels. Pretreatment of animals with intraventricular nitric oxide synthase (NOS) inhibitor, N omega-nitro-L-arginine methyl ester (L-NAME) (100 micrograms) significantly inhibited NOS activity in the LC, PAG-PVG and cerebellum. This dose of L-NAME, administered prior to application of NMDA by microdialysis abolished the NMDA-induced rise in the CA.OC recorded in the LC and the increase in systolic blood pressure. The results show that in voltammetry experiments, NMDA produces hyperactivity of LC and hypertension, responses that are dependent upon the synthesis of NO. Thus, in opioid naive rats, regional NMDA application via microdialysis mimics characteristics of the LC response that occur during the antagonist-precipitated opioid withdrawal.

Animals↗

An immunohistochemical study of palmar and plantar digital nerves.

We present a qualitative and semi-quantitative description of palmar and plantar digital nerves obtained from cadavers prepared for routine class dissection. The fingertips of the three most functionally important and sensitive digits, namely thumb, index and middle fingers, received more myelinated axons than those of the ring and little fingers. In both palmar and plantar nerves the numbers of myelin basic protein (MBP)-positive myelinated axons decreased proximodistally along each digit and also from thumb to little finger and hallux to little toe respectively. Our results suggest that there are up to ten times more myelinated axons in palmar digital nerves than in plantar nerves.

Aged↗

Is there a doctor in the house? Integrating medical education and home health care.

This article describes how one rural home health agency collaborated with a school of medicine to integrate medical education into the daily operations of the agency. Noteworthy aspects of this project include integration of home care concepts at all levels of the medical school curriculum, use of an advanced practice nurse to coordinate the program, collaboration between the home health agency and the schools of medicine and nursing, and reliance on telecommunication technology to minimize the barriers related to transportation to and scheduling of physician visits.

Clinical Competence↗

A four year prospective study of age-related cognitive change in adults with Down's syndrome.

BACKGROUND: While neuropathological studies indicate a high risk for Alzheimer's disease in adults with Down's syndrome, neuropsychological studies suggest a lower prevalence of dementia. In this study, cognitive deterioration in adults with Down's syndrome was examined prospectively over 4 years to establish rates and profiles of cognitive deterioration. METHODS: Fifty-seven people with Down's syndrome aged 30 years or older were assessed using a battery of neuropsychological tests on five occasions across 50 months. Assessments of domains of cognitive function known to change with the onset of Alzheimer related dementia were employed. These included tests of learning, memory, orientation, agnosia, apraxia and aphasia. The individual growth trajectory methodology was used to analyse change over time. RESULTS: Severe cognitive deterioration, such as acquired, apraxia and agnosia, was evident in 28.3% of those aged over 30 and a higher prevalence of these impairments was associated with older age. The rate of cognitive deterioration also increased with age and degree of pre-existing cognitive impairment. Additionally, deterioration in memory, learning and orientation preceded the acquisition of aphasia, agnosia and apraxia. CONCLUSIONS: The prevalence of cognitive impairments consistent with the presence of Alzheimer's disease is lower than that suggested by neuropathological studies. The pattern of the acquisition of cognitive impairments in adults with Down's syndrome is similar to that seen in individuals with Alzheimer's disease who do not have Down's syndrome.

Adult↗

Paediatric cardiac anaesthesia in a developing country. Guatemala Heart Team.

During the week of October 15-24, 1995 a team of 65 medical, anaesthesiology, surgical, nursing and paramedical personnel travelled to Guatemala City, Guatemala to perform cardiac surgery on children with complex congenital and acquired valvular heart disease. During this mission 42 patients had their lesions surgically repaired. Cardiopulmonary bypass was required in 36 cases. There were no anaesthetic or surgical deaths. All six patients who did not require cardiopulmonary bypass were extubated in the operating room. Of the patients who required cardiopulmonary bypass, 23 were extubated in the operating room (64%). There was no intraoperative anaesthetic morbidity nor postoperative respiratory complications. No patients was reintubated after planned extubation. Cardiac surgery in paediatric age patients can safely be performed in developing countries if close attention is paid to proper patient selection and one maintains the standards of care practised in developed countries.

Adolescent↗

Functional recovery and timing of hospital discharge after primary total hip arthroplasty.

BACKGROUND: Early discharge programmes in hospitals are encouraged to increase financial efficiency and bed availability, but standards of clinical care must not be compromised. Criteria for safe hospital discharge must be established and objective data are needed to assess how rapidly patients can achieve these discharge criteria. METHODS: A prospective study was performed on 65 patients (mean age = 71 years) scheduled for primary total hip arthroplasty (THA). The Modified Barthel Index (MBI) was measured pre-operatively and postoperatively at set intervals to asses recovery of function after THA. A score of 90 out of a possible 100 was used as a discharge criterion and indicated that the patient was functionally independent for safe hospital discharge. In addition, a combined score for thigh flexion and extension isokinetic peak strength was recorded for each patient before and after surgery. The number and nature of comorbidities and complications were also recorded. RESULTS: The length of hospital stay in this sample varied from 5 to 39 days. The MBI scores increased rapidly between days 3 and 5, then began to plateau from day 8 onwards. Based on the MBI, 58% of patients were fit for discharge at or before day 8. The remainder were fit for discharge from day 10 onwards (mean = 14.2 days). The latter group who required an extended hospital stay were older (P = 0.003), had more identified comorbidities (P = 0.01) and were weaker in their hip musculature prior to surgery (P = 0.001), compared to those who were discharged by day 8. A logistic regression analysis indicated that the pre-operative MBI score and hip strength score were strong predictors of timing for hospital discharge. CONCLUSIONS: A clinical pathway with functional milestones laid out over 8 days would be an appropriate criterion for the discharge of the majority of patients. However, approximately 40% of the patients presented in this study required a longer hospital stay before the criteria for safe discharge could be achieved. These patients can be identified pre-operatively by screening their MBI and composite hip strength scores.

Aged↗

Intercessory Prayer for ill Health: A Systematic Review.

OBJECTIVES: To review the effectiveness of prayer as an additional intervention for those with health problems already receiving standard medical care. SEARCH STRATEGY: Electronic Searches of Biological Abstracts, CINAHL, The Cochrane Controlled Trials Register, EM-BASE, MEDLINE, PsycLIT, and Sociofile were undertaken. All references of articles selected were searched for further relevant trials. SELECTION CRITERIA: Randomised and quasi-randomised trials of personal, focused, committed and organised intercessory prayer on behalf of anyone with a health problem were considered. Outcomes such as achievement of desired goals, death, illness, quality of life and well-being for the recipients of prayer, those praying and the caregivers were sought. DATA COLLECTION AND ANALYSIS: Studies were reliably selected and assessed for methodological quality. Data were extracted by 4 reviewers working independently. Dichotomous data were analysed on an intention-to-treat basis, and continuous data with over 50% completion rate are presented. MAIN RESULTS: There was no evidence that prayer affected the numbers of people dying from leukaemia or heart disease (OR 0.64, CI 0.32-1.27), or that it decreased coronary care complications (OR 1.05, CI 0.49-2.26) or the time participants stayed in hospital. There were significantly fewer 'intermediat//poor outcomes' for those with heart disease in the prayed-for group (OR 0.49, CI 0.30-0.80), and this finding was robust to some changes in definition. CONCLUSIONS: This review provides no guidance for those wishing to uphold or refute the effect of intercessory prayer on the outcomes studied in the available trials. Therefore, in the light of the best available data, there are no grounds to change current practices. There are very few completed trials of the value of intercessory prayer. The evidence presented so far is interesting enough to justify further study. If prayer is seen as a human endeavour it may or may not be beneficial, and further trials could uncover this. It could be the case that any effects are due to elements beyond present scientific understanding that will, in time, be understood. If any benefit derives from God's response to prayer it may be beyond any such trials to prove or disprove.

Journal Article↗

A comparison of four tests of malingering and the effects of coaching.

This study examined the ability of four measures of suboptimal performance to correctly classify four groups of subjects (normal controls, uncoached malingering, coached malingering, and head injured). Only the Portland Digit Recognition Test-Computerized (PDRT-C) identified simulating malingerers with greater than chance accuracy while minimizing false positives. Coached subjects were better able than their uncoached counterparts to avoid detection on all measures. In an additional analysis, a discriminant function using the response latency and total correct scores from the PDRT-C identified 70% of the coached malingerers on cross validation. The three other tests (Nonverbal Forced Choice Test, 21-Item Test, and Dot Counting Test) failed to obtain a satisfactory classification rate for the malingering groups as a whole and coached malingerers in particular.

Journal Article↗

LPL promoter -93T/G transition influences fasting and postprandial plasma triglycerides response in African-Americans and Hispanics.

The lipoprotein lipase (LPL) promoter -93T/G transition has previously been reported as having a triglyceride (Tg)-lowering effect, whereas the D9N variant has been shown to have a Tg-raising effect. These two variants were studied in 66 healthy subjects of Hispanic and 42 subjects of African-American origin, who had participated in a study of postprandial lipemia. While the allele frequency of the -93G was significantly different in the Hispanics and African Americans (0.09: 95% CI 0.04-0.13 and 0.28: 95% CI 0.19-0.38; P=0.0001, respectively), the N9 allele frequency was not different (0.06: 95% CI 0.02-0.1 and 0.05: 95% CI 0.002-0.093, respectively). Linkage disequilibrium between the -93T/G and D9N was highly significant in Hispanics (delta=0.67. P=0.0001), compared to delta=0.09 (NS) in African-Americans. In the combined group, compared to individuals with the common genotype (TT/DD; n=71) with fasting plasma Tg of 1.34 (+/-4.5% SEM) mmol/l, carriers of the G/D haplotype (TG/DD + GG/DD; n=25) had significantly lower plasma Tg levels of 1.08 (+/-10% SEM) mmol/l (P < 0.02). After the fat meal, compared to individuals with neither mutation, TT/DD, the effect of the G/D haplotype was to reduce significantly postprandial Tg (P < 0.036). Retinyl palmitate concentration at 5 hrs was significantly lower in G/D carriers than TT/DD individuals (P < 0.05). The lipid-raising effect of the N9 allele in carriers of the -93G (TG/DN + GG/DN) and effect on postprandial Tg clearance was not significant in this group. Thus carriers of the G/D haplotype have lower fasting plasma Tg and reduced alimentary lipemia. This allele may be associated with reduced risk of coronary artery disease.

Adult↗

Convergence of Schiff base costimulatory signaling and TCR signaling at the level of mitogen-activated protein kinase ERK2.

Schiff base formation on specialized T cell surface amines provides a costimulatory signal to T cells through a mechanism that activates Na+ and K+ transport, substantially enhancing TCR-dependent IL-2 production. Schiff base-forming molecules that mimic the natural carbonyl donor potently enhance immune responses and provide the first mechanism-based, orally active immunopotentiatory agents. In the present study, costimulation by the Schiff base-forming molecule tucaresol was investigated at the level of mitogen-activated protein kinase (MAPK) in T cell lines. Both TCR-directed stimulation by anti-CD3 and Schiff base stimulation by tucaresol produced a distinct mobility shift in MAPK, characterized by direct immunoblotting of cell lysate proteins subjected to SDS-PAGE, that corresponded with increased phosphorylation. Combined TCR-CD3 and tucaresol stimulation substantially enhanced and prolonged the MAPK response, providing a biochemical basis for the costimulatory nature of the pathway utilized by Schiff base signaling. The MAPK affected was identified by immunoprecipitation as ERK2. Both the direct effects and the TCR signal-enhancing effects of tucaresol on MAPK activation were also demonstrated in a functional MAPK assay measuring substrate phosphorylation. Borohydride reduction of tucaresol's Schiff base-forming carbonyl group abolished both enhancement of MAPK phosphorylation and IL-2 production, as did a selective inhibitor of the MAPKK, MEK1. Tucaresol had no effect on TCR-mediated rises in intracellular free Ca2+ or inositol 1,4,5-triphosphate generation, while tucaresol signaling occurred normally in the lck-deficient J.CaM1.6 T cell line, consistent with convergence of tucaresol- and TCR-induced signals downstream of early TCR-mediated events.

Benzaldehydes↗

Epidemic of asthma in a wood products plant using methylene diphenyl diisocyanate.

Eighteen employees with lower respiratory symptoms later confirmed to be occupational asthma were referred for evaluation. All were employees of a single wood products plant using heated methylene diphenyl diisocyanate (MDI) in the manufacture of a synthetic wood product. Of the 18, 15 had no prior airway symptoms or other known bronchial injury, and 16 had positive methacholine bronchial provocation tests. All cases occurred during a 2.5-year period after exposure to a new manufacturing process using steam-heated MDI resin in a new manufacturing facility. Initially, employees developed symptoms related to the start-up process in the plant, with possible higher MDI exposures and probable higher resin temperatures. Later, most employees who developed new symptoms worked in areas of the plant where they were exposed mostly to heated boards. This suggests MDI sensitization arising at lower temperatures than previously considered likely for this substance.

Adult↗

Hypertension and identification of toxin in human urine and serum following a cluster of mussel-associated paralytic shellfish poisoning outbreaks.

Following four outbreaks of paralytic shellfish poisoning on Kodiak Island, Alaska, during 1994, medical records of ill persons were reviewed and interviews were conducted. Urine and serum specimens were analyzed at three independent laboratories using four different saxitoxin binding assays. High-performance liquid chromatography was used to determine the presence of specific toxin congeners. Among 11 ill persons, three required mechanical ventilation and one died. Mean peak systolic and diastolic blood pressure measurements were 172 (range 128-247) and 102 (range 78-165) mmHg, respectively, and blood pressure measurements corresponded with ingested toxin dose. All four different laboratory methodologies detected toxin in serum at 2.8-47 nM during acute illness and toxin in urine at 65-372 nM after acute symptom resolution. The composition of specific paralytic shellfish poisons differed between mussels and human biological specimens, suggesting that human metabolism of toxins had occurred. The results of this study indicate that saxitoxin analogues may cause severe hypertension. In addition, we demonstrate that saxitoxins can be detected in human biological specimens, that nanomolar serum toxin levels may cause serious illness and that human metabolism of toxin may occur. Clearance of paralytic shellfish poisons from serum was evident within 24 hr and urine was identified as a major route of toxin excretion in humans.

Adolescent↗

A novel high-dose chemotherapy protocol with autologous hematopoietic rescue in patients with metastatic breast cancer or recurrent non-Hodgkin's lymphoma.

In this phase II trial, we used a double dose-intensive chemotherapy and stem cell rescue protocol to treat breast cancer (BCA) patients or non-Hodgkin's lymphoma patients (NHL). The first cycle consisted of high-dose melphalan followed by ABMT. The second cycle used a novel chemotherapy combination; thiotepa, etoposide, carboplatin and cyclophosphamide (TECC) followed by ABMT. We treated 12 patients in total, nine with BCA, three with NHL. All nine BCA patients were treated with the two cycle protocol. The three NHL patients were treated with the second cycle only. Bone marrow (BM, 1 patient), peripheral blood stem cells (PBSC, 10 patients) or both (1 patient) were reinfused 60-72 h after completion of each cycle of chemotherapy. Recovery was rapid; the ANC rose to greater than 500/microl on day +11 (+8 to + 20) and the platelet count to greater than 20000/microl on day +12 (+6 to +20). The toxicities included the expected neutropenic fevers, severe mucositis, diarrhea, and a low incidence of mild renal insufficiency. No patients developed veno-occlusive disease, hemorrhagic cystitis or overt bleeding. With a mean follow-up of 37 months, 83.3% of the patients are alive. Six patients are in complete remission; one patient with BCA relapsed and expired; one patient with NHL is in CR now over 18 months after relapse and subsequent treatment with interferon; one patient is too early to evaluate. Progression-free survival overall is 75%, which is at least equivalent to many other recent studies using similar regimens. In addition, we have also found that delayed addition of G-CSF during the mobilization of PBSC was feasible and resulted in excellent CD34+ cell counts and engraftments, and reduced treatment costs. These results indicate that this chemotherapy is effective with good remission rates and high progression-free survival rates. It is also well tolerated with acceptable toxicities that are manageable. Long-term follow-up of a larger cohort of patients will be needed to ascertain the overall efficacy of this type of therapy.

Adult↗

Unscheduled apoptosis during acute inflammatory lung injury.

Apoptosis is a mode of cell death currently thought to occur in the absence of inflammation. In contrast, inflammation follows unscheduled events such as acute tissue injury which results in necrosis, not apoptosis. We examined the relevance of this paradigm in three distinct models of acute lung injury; hyperoxia, oleic acid, and bacterial pneumonia. In every case, it was found that apoptosis is actually a prominent component of the acute and inflammatory phase of injury. Moreover, using strains of mice that are differentially sensitive to hyperoxic lung injury we observed that the percent of apoptotic cells was well correlated with the severity of lung injury. These observations suggest that apoptosis may be one of the biological consequences during acute injury and the failure to remove these apoptotic cells may also contribute to the inflammatory response.

Journal Article↗

Axonal regeneration through acellular muscle grafts.

The management of peripheral nerve injury remains a major clinical problem. Progress in this field will almost certainly depend upon manipulating the pathophysiological processes which are triggered by traumatic injuries. One of the most important determinants of functional outcome after the reconstruction of a transected peripheral nerve is the length of the gap between proximal and distal nerve stumps. Long defects (> 2 cm) must be bridged by a suitable conduit in order to support axonal regrowth. This review examines the cellular and acellular elements which facilitate axonal regrowth and the use of acellular muscle grafts in the repair of injuries in the peripheral nervous system.

Animals↗