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Biomedical subjects

S Newman

Publications and source records attributed to S Newman.

At least 91 records · Page 5Linked to original sources

Alzheimer's disease families with amyloid precursor protein mutations.

Early onset Familial Alzheimer's Disease (FAD) is an autosomal dominant disease with apparent complete penetrance. It is genetically heterogeneous with some families carrying mutations in the amyloid precursor protein (APP) gene which segregate with the disease. In addition, there is allelic heterogeneity with four mutations associated with FAD. Three mutations have been reported at APP 717, just distal to the C-terminus of the beta-amyloid domain, APP 717 val-ile, APP 717 val-phe, and APP 717 val-gly, which are associated with autopsy-proven Alzheimer's disease (AD). APP 670/671 lies at the N terminus of the beta-amyloid domain and is associated with clinically diagnosed FAD in two Swedish families. FAD tends to have prominent myoclonus and this is shared by the cases with APP mutations. In two unrelated UK families with APP 717 val-ile mutations there was early prominent memory impairment with dyscalculia proceeding to generalized cognitive impairment with a lack of insight. There was a late development of a gait disturbance with extrapyramidal features in some members. Positron emission tomography (PET) with fluorodeoxyglucose demonstrated posterior bitemporal biparietal hypometabolism in one case. Magnetic resonance imaging (MRI) showed generalized cerebral atrophy particularly affecting the temporal lobes and hippocampus. At autopsy, a single case showed extensive beta-amyloid deposition with congophilic angiopathy and widespread senile plaques and neurofibrillary tangles. The cytoskeletal pathology associated with abnormally phosphorylated tau was similar to cases of sporadic AD. In addition, there were widespread cortical and subcortical Lewy bodies. A single family with the APP 717 val-gly mutation also showed prominent myoclonus, lack of insight, and seizures, PET, in a single case, showed classical biparietal bitemporal hypometabolism. Autopsy, in a single case, showed diffuse deposits of beta-amyloid throughout the cortex with frequent neuritic plaques and neurofibrillary tangles. No other inclusion bodies were seen. There was severe congophilic angiopathy. The age at onset of APP mutations is around 50 years of age by contrast to other early onset FAD pedigrees.

Alzheimer Disease↗

Hyperperfusion and cerebral dysfunction. Effect of differing acid-base management during cardiopulmonary bypass.

Alterations in cerebral blood flow (CBF) occurring during cardiopulmonary bypass (CPB), which are thought to be responsible for increased morbidity, are probably related to changes in arterial carbon dioxide during acid-base management. In this study, 70 patients undergoing elective coronary artery bypass surgery (CABS) were randomised to one of two differing, but widely practised, cardiopulmonary bypass acid-base protocols; pH-stat and alpha-stat. Cerebral blood flow was measured during surgery using the xenon-133 isotope clearance technique. Cerebral oxygen metabolism was measured as the cerebral metabolic rate for oxygen (CMRO2) and matching of the cerebral blood flow to oxygen demand as the cerebral extraction ratio for oxygen (CERO2). Detailed neuropsychological tests were conducted in all patients before surgery and repeated at 6 weeks after surgery for assessment of changes in cognitive function. During hypothermic (28 degrees C) CPB, CBF was significantly greater (P < 0.001) in the pH-stat group (41 ml/100 g per min; 95% confidence intervals (CI), 39-43) than in the alpha-stat group (24 ml/100 g per min; 95% CI, 22-26). The cerebral extraction ratio for oxygen indicated a degree of mismatch of cerebral perfusion and demand during CPB in both pH-stat and alpha-stat groups (0.12; 95% CI, 0.11-0.14 and 0.25; 95% CI, 0.22-0.28, respectively). This mismatch was far more pronounced in the pH-stat group than in the alpha-stat group, indicating greater disruption in cerebral autoregulation in the former group.(ABSTRACT TRUNCATED AT 250 WORDS)

Acid-Base Equilibrium↗

Familial Alzheimer's disease. A pedigree with a mis-sense mutation in the amyloid precursor protein gene (amyloid precursor protein 717 valine-->glycine).

Ten affected individuals are described from a kindred with autosomal dominant familial Alzheimer's disease in which a mutation in the amyloid precursor protein gene results in a valine to glycine substitution at amyloid precursor protein 717 which co-segregates with the disease. The mean age at onset of symptoms was 52 years with a range from 40 years to 67 years. The median duration of the disease was 11 years, with a range of 7-16 years. All individuals fulfilled the National Institute for Neurological and Communicative Disorders and Stroke criteria for probable Alzheimer's disease. A homogeneous clinical and neuropsychological pattern was evident within the family. Myoclonic jerks, seizures, depression and a lack of insight were common features. Positron emission tomography demonstrated biparietal bitemporal hypometabolism in the one affected individual who was studied. The diagnosis was confirmed histopathologically in one individual.

Adult↗

Outcome assessment after epidural corticosteroid injection for low back pain and sciatica.

Epidural corticosteroid injection is a relatively effective treatment for low back pain and sciatica with a low incidence of side effects, although the patient's perspective in terms of outcome and satisfaction has not been studied well. The assessment of outcome in low back pain patients is complex. Three types of measure were compared: 1) a clinical score, 2) patient ratings of pain and disability, and 3) patient satisfaction ratings. There were significant discrepancies among the results. Consequently, clinical trials using different outcome measures may reach different conclusions. It therefore is vital to have planned the study carefully in advance, considering the questions to be asked, especially in this area, where patient-derived measures (e.g., "patient satisfaction") are so important. This study of 35 patients showed a fall in clinical signs/symptoms, disability, and pain 1 week after the injection, with maintenance of the reduction in disability at 3 months. Eighty-five percent reported at least some improvement at 1 week and 43% had improvement lasting 3 months. Patients with a more depressed mood had higher levels of disability both before and after the procedure. Anxiety before the procedure did not adversely affect outcome, and it was well tolerated by most patients. At 3 months 83% were satisfied with the treatment they had received and a patient satisfaction questionnaire gave similar results. We continue to recommend this treatment as a well-tolerated procedure, with which most patients are satisfied.

Adrenal Cortex Hormones↗

Measuring management training. Two new instruments.

Seeks to enhance the measurement of training; describes the development of psychometrically sound and practical measures to assess outcomes relating to in-service management training within a National Health Service District. Develops legitimate measurement tools and demonstrates the positive effects of two specific programmes in relation to behavioural change and participant satisfaction. Further work is required to establish how to monitor the effects of the action learning process in terms of cognitive development.

Administrative Personnel↗

A developmental study of specific spelling disability.

Previous studies have identified a group of individuals with specific problems in spelling, and compared them to a group with problems in reading and spelling. Those who are poor at reading and spelling are thought to have more severe underlying language problems. This study compared the cognitive abilities of three groups of children: one specifically spelling disabled, one spelling and reading disabled, and one control group without reading or spelling problems. The groups were identified at age 14. A five-year retrospective analysis of their performance revealed that both of the disabled groups had been significantly poorer than the controls, not only in spelling but also in reading. Both the disabled groups showed other signs often associated with dyslexia such as poor WISC-R Coding and Digit Span. Analyses of their spelling errors did not reveal the superior phonetic abilities which some other studies have found to differentiate specifically spelling disabled from reading + spelling disabled groups. The specific spelling disabled group did show some evidence of superiority in Verbal IQ subtests. These results are consistent with the idea that specific spelling disability is a residual problem of individuals who, possibly by means of underlying verbal strengths, have managed to compensate for earlier reading difficulties.

Achievement↗

Truncation of the carboxy-terminal 28 amino acids of glycoprotein B specified by herpes simplex virus type 1 mutant amb1511-7 causes extensive cell fusion.

Three amber mutations were introduced proximal to the syn3 locus of the herpes simplex virus type 1 glycoprotein B (gB) gene specifying gB derivatives lacking the carboxy-terminal 28, 49, or 64 amino acids. A complementation system that utilized gBs expressed in COS cells to complement gB-null virus K delta T was established. The 49- or 64-amino-acid-truncated gBs failed to complement gB-null virus K delta T, while the 28-amino-acid-truncated gB complemented K delta T efficiently. Mutant herpes simplex virus type 1 KOS (amb1511-7) specifying the 28-amino-acid-truncated gB fused Vero cells extensively.

Amino Acid Sequence↗

Mood and psychiatric disturbance in HIV and AIDS: changes over time.

A sample of 26 HIV seronegative, 59 HIV seropositive asymptomatic and 7 HIV seropositive symptomatic homosexual and bisexual men were assessed over two visits, a mean of 11 months apart, using the BDI, STAI, and CIS. Significant differences emerged between the symptomatic group and the other two groups. Past psychiatric history and the somatic items in the assessments accounted for some of these differences. The seropositive asymptomatic and the seronegative groups did not differ on any of the mood or psychiatric assessments, suggesting minimal effect on psychological well-being of seroconversion in the absence of symptoms.

Acquired Immunodeficiency Syndrome↗

Fixed effects in the formation of a composite line of beef cattle: I. Experimental design and reproductive performance.

Red Angus (RA) dams were mated to Charolais (C) or Tarentaise (T) sires to produce crossbred (F1) progeny. Members of the F1 generation, differing in breed direct effects, were mated to produce an F2 generation with an expected breed composition of 1/2 RA, 1/4 C, and 1/4 T. Two breed groups within the F2 generation differing in breed maternal effect ([C x RA] x [T x RA] and [T x RA] x [C x RA]) were identified separately. These breed groups were crossed to produce an F3 generation and, likewise, the two resulting F3 generation breed groups were crossed to produce an F4 generation. No distinction was made among breed groups subsequent to the F3 generation. Pregnancy rates averaged 90.9% over 11 yr, with 82.0% of cows exposed weaning a calf. Among formative generations of this composite population, F2 had greatest pregnancy, calving, and weaning rates. Age of dam significantly affected pregnancy rate, calving difficulty, and gestation length. Older cows tended to express higher pregnancy rates and longer gestation lengths than did younger cows (P < .01). Males calves had a 1.7% greater weaning rate than female calves (P < .05), but matings producing male calves had longer gestation lengths (P < .05) and were 8.5% more likely to experience calving difficulty (P < .01). Individual breed additive effects (calves from C or T sires mated to RA dams) were important for calving difficulty only (P < .05), where C-sired matings experienced greater calving difficulty. Differences between C x RA and T x RA dams, indicative of maternal breed additive effects, were not detected.(ABSTRACT TRUNCATED AT 250 WORDS)

Analysis of Variance↗

Fixed effects in the formation of a composite line of beef cattle: II. Pre- and postweaning growth and carcass composition.

Generation, age of dam, sex of calf, and certain covariates were studied to elucidate their effect on traits related to growth and carcass characters measured on individuals from a stabilized three-breed composite (1/2 Red Angus [RA], 1/4 Charolais [C], 1/4 Tarentaise [T]). There was evidence that sires had been selected for yearling weight. Thus, an animal model was fitted to the data to estimate the effects free of bias due to selection. Differences between generations were not different from zero (P > .05) for birth weight, weaning weight, and preweaning ADG. There were few important differences between generations for carcass traits as well. This may have been caused by confounding of individual and maternal heterotic effects with direct and maternal components of the model, or the partial confounding of years, age of dam, and generation. Birth weight was curvilinear with respect to calving day (P < .01). Age of dam was important for all growth traits except postweaning ADG. In general, growth of calves increased with increasing age of dam, as did carcass weight and predicted retail product. Individual breed additive effects (differences between calves sired by C and T sires mated to RA dams) were positive for birth weight (P < .01), weaning weight (P < .05), carcass weight (P < .05), and predicted retail product (P < .05). Maternal breed additive effects (differences between calves out of C x RA or T x RA dams) were also positive for weaning weight (P < .05), carcass weight (P < .05), and fat depth (P < .05).(ABSTRACT TRUNCATED AT 250 WORDS)

Age Factors↗

Factors influencing surgical wound healing and their anesthetic implications.

Wound healing, a complex physiological process, begins within seconds of assault. Wounds, whether traumatic or surgically produced, demand optimal performance from all body systems for proper healing. Healing is delayed or impossible when the body cannot respond adequately due to disease, infection, or altered metabolic response. The anesthesia team plays an integral part in establishing successful wound healing.

Anesthesia↗

Work-related back pain.

Sylvia Newman and Cathy Callaghan suggest that much can be done to reduce the incidence of musculoskeletal pain among nursing and midwifery staff following their survey of Brighton Health Care employees.

Absenteeism↗

Pulmonary deposition of inhaled terbutaline: comparison of scanning gamma camera and urinary excretion methods.

Deposition from a multidose powder inhaler (Turbuhaler, Astra) delivering 500 micrograms of terbutaline sulfate per metered dose was compared by two techniques in a group of six healthy volunteers. The deposition of the radionuclide 99mTc, which was used to label terbutaline sulfate powder, was quantified by gamma camera (G-method). Simultaneously, the gastrointestinal absorption of swallowed drug was blocked with activated charcoal, and the amount of terbutaline in a urine sample, collected over a period of 48 h and corrected by a pharmacokinetic internal standard of intravenous deuterated terbutaline, was used as a measure of lung deposition (U-method). The mean (standard deviation) depositions in lung were 26.9 (3.8%) of the dose for the G-method and 21.1 (3.2)% of the dose for the U-method. Possible reasons for the differences between the two means are discussed. Both methods are suitable for assessing deposition from medical aerosol inhalers; the U-method requires access to gas chromatography-mass spectrometric equipment, and the G-method requires access to gamma camera facilities.

Administration, Inhalation↗

Developmental expression of G protein alpha subunits in mouse spermatogenic cells: evidence that G alpha i is associated with the developing acrosome.

Guanine nucleotide-binding proteins (G proteins) are important signal transducing molecules found in all cells. G proteins are associated with the plasma membrane/outer acrosomal membrane region of acrosome-intact sperm and at least one G protein is involved in the zona pellucida-induced acrosome reaction. With the goal of elucidating the functions of these proteins during spermatogenesis, we investigated the types of G proteins present in spermatogenic cells and when they first become associated with the developing acrosome. Using bacterial toxin-catalyzed [32P]ADP-ribosylation in conjunction with immunoprecipitation and immunofluorescence utilizing antibodies directed against specific regions of various G protein isotypes, the alpha subunits of Gi1, Gi2, Gi3, and G(o) were detected in mouse spermatocytes and spermatids. An antiserum recognizing a conserved sequence of G alpha i subtypes localized to the proacrosomal granules of spermatocytes and the developing acrosome of spermatids. Levels of G alpha o diminished as spermatocytes developed into spermatids such that G alpha o was not detected in cauda epididymal sperm. Immunoreactivity using G alpha o-specific antisera did not display a distinct regionalization within any of the spermatogenic cell types. G alpha s was not detected in the developing spermatogenic cells or sperm. The association of G alpha i with the developing acrosome suggests a role for G proteins may have a role in acrosome biogenesis as well as being part of a complex required later for signal transduction leading to acrosomal exocytosis.

Acrosome↗

Interactions among emergent relations during equivalence class formation.

The interactions among symmetry, transitivity, and equivalence tests during the formation of 3-member equivalence classes were studied with 14 college students. After training AB and BC, a test with BA, CB, AC, and CA was conducted concurrently. Failure led to serial testing with probes for CA equivalence, BA symmetry, CA equivalence, CB symmetry, CA equivalence, AC transitivity, and CA equivalence. For five subjects, equivalence tests were passed immediately once BA and CB symmetry as well as AC transitivity had been induced. Thus, symmetry and transitivity were precursors for successful performance on equivalence tests. The conjoint function of symmetry and transitivity was assessed with the equivalence probes. As the equivalence probes were passed immediately, the presence of symmetry alone and transitivity alone were sufficient for their conjoint function without additional intervention. For different subjects, transitivity alone and symmetry were induced either directly with BA, CB, or AC probes or indirectly with equivalence probes. Equivalence probes can also induce various combinations of symmetry and transitivity. Thus, different subjects formed classes in various patterns at different rates.

Adolescent↗