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Biomedical subjects

N Brown

Publications and source records attributed to N Brown.

At least 73 records · Page 4Linked to original sources
PubMed2000

Mortality of patients admitted with a suspected acute myocardial infarction in whom the diagnosis is not confirmed.

AIMS: To examine the survival of patients admitted with a suspected acute myocardial infarction in whom the diagnosis was not confirmed ('possible myocardial infarction'). METHODS AND RESULTS: A cohort study based on the Nottingham Heart Attack Register of 1716 sequential patients discharged alive from two acute teaching hospitals following admission in 1992. The main outcome was mortality following hospital discharge after 5 years of follow-up. Survival of the cohort of patients in whom myocardial infarction was suspected but not confirmed was 58% (95% C.I. 56 to 60%) after 5 years of follow-up, compared with an expected survival of 76% in an age/sex matched general population. Patients with ECG abnormalities that were not diagnostic of myocardial infarction had a 5-year survival of 56%, compared with 77% in those without such changes (P<0.00001). In the 703 patients who died in the first 5 years of follow-up, the cause of death was cardiovascular in at least 53% of cases. Survival following hospital discharge was worse than that in patients discharged alive in the same year following a confirmed myocardial infarction (63% vs 69% after 4 years of follow-up P=0.0016). CONCLUSION: Patients in this study had a substantially increased risk of death in the 5 years after discharge from hospital, compared with an age- and sex-matched population, and worse than patients discharged following a confirmed myocardial infarction. Almost half of those with ECG changes at the time of their admission died over the next 5 years. As over half of all deaths in this cohort were due to cardiovascular causes, further work is needed to identify patients at high and low risk of subsequent mortality who may warrant investigation and treatment following hospital discharge.

Aged↗
PubMed2000

Relationship of vascular maturation in breast cancer blood vessels to vascular density and metastasis, assessed by expression of a novel basement membrane component, LH39.

Angiogenesis, the formation of new vessels, has been demonstrated to be an indicator of prognosis in breast cancer patients. The extent of differentiation of the tumour vessels may affect access of peripheral white cells and egress or invasion of tumour cells. This has not been assessed in relation to tumour microvessel density or other variables and may be a marker of vascular remodelling. LH39 is a monoclonal antibody recognizing an epitope located at the lamina lucida of mature small veins and capillaries but not in newly formed vessels. To study vascular differentiation in breast tumours, we examined the vascular maturation index (VMI) in 12 normal and 50 breast carcinomas and this was correlated with different clinicopathological variables including angiogenesis. Mature vessels were defined by staining with antibodies to both LH39 and to CD31, using double immunohistochemistry, whereas immature vessels stained only for CD31. VMI was defined as the % fraction of mature vessels (LH39-positive) / total number of vessels (CD31-positive). The VMI was significantly higher in normal (54-68.5%; median 66.5%) than in tumours (0-47%; median 8.8%) (P = 0.0005). There was a significant inverse correlation between the tumour VMI and nodal status (Fisher's exact test, P = 0.01) and between high VMI and low thymidine phosphorylase (TP) expression (Mann-Whitney U-test, P= 0.01). No significant association between VMI and tumour size, oestrogen receptor, epidermal growth factor receptor, grade, angiogenesis, patient age, or E-selectin was seen. There was a significant reduction in relapse-free survival (P = 0.01) with high angiogenesis. These findings show that the VMI gives new information on the mechanism of tumour angiogenesis independently from microvessel quantitation, there is a wide variation in the differentiation of tumour vasculature but the degree of capillary differentiation is not associated with quantitative angiogenesis. The VMI identifies a subset of patients who have a high chance of regional node involvement.

Adult↗
PubMed2000

Comparison of the SF-36 health survey questionnaire with the Nottingham Health Profile in long-term survivors of a myocardial infarction.

BACKGROUND: Health-related quality of life, an important outcome measure in health interventions, can readily be assessed by questionnaire. Two widely evaluated examples are the Short Form 36 (SF-36) and Nottingham Health Profile (NHP) questionnaires, but as yet the discriminatory power of these tools has not been compared in a large population of patients with coronary heart disease. METHODS: All 4-year survivors of a myocardial infarction, identified from the Nottingham heart attack register, were sent the SF-36, NHP and additionally the Rose angina and dyspnoea questionnaires. Mean scores on the SF-36 and NHP were compared with age- and sex-adjusted norms in patients under and over 65 years. Sensitivity of the respective tools was assessed in distinguishing patients with differing degrees of cardiovascular symptomatology. RESULTS: In patients under 65 years the SF-36 and NHP differed to the same extent from normative data--scores were lower in the comparable domains physical functioning/mobility, bodily pain/pain and energy/vitality, but not in mental health/emotional reaction scores. In social functioning/social isolation results were disparate--SF-36 scores were lower and the NHP similar to normative data. In patients over 65 years mean scores in all five domains were not significantly different from normative data for either tool. The SF-36 was more sensitive than the NHP at detecting the impact of breathlessness, particularly in patients with mild symptoms. Similarly, the SF-36, but not the NHP, could distinguish the effect of differing degrees of angina severity and frequency on social functioning. CONCLUSION: At least in myocardial infarction survivors, the SF-36 appears a more sensitive tool and may have benefits for assessing health-related quality of life in this patient group.

Activities of Daily Living↗
PubMed2000

Cognitive, mood, and functional evaluations using touchscreen technology.

We describe the design and development of the Cognitive Evaluation Protocol (CEP), a computer software program for evaluating cognitive and functional capacities and mood. The program is self-administered by subjects using touchscreen monitors for input. Stimuli in CEP subtests are randomized to reduce the effects of learning on repeated assessments. Findings demonstrate that a) minimum instruction is required for touchscreen use, even for computer-naive subjects; c) both normative subjects and psychiatric patients respond positively to self-administered evaluations; and c) CEP can be used for within-subject repeated evaluations with minimal distortion of results due to practice effects. The CEP Report Generator provides immediate printed performance results and creates a database for long-term digital storage and information use.

Affect↗
PubMed2000

Memory, attention, function, and mood among patients with chronic posttraumatic stress disorder.

We report a study of memory, attention, function, and mood among 36 male Vietnam War Veterans suffering from chronic posttraumatic stress disorder (PTSD). PTSD subjects (N = 36) were in good physical health, suffering from moderate depression, and not knowingly suffering from other mental disorders. Control subjects (N = 18) were in good physical health, not knowingly suffering from a mental disorder, and matched with PTSD subject for age, sex, and level of education. Assessment instruments for PTSD subjects included the PostTraumatic Stress Diagnostic Scale (clinician administered), the Hamilton Depression Rating Scale (clinician administered), and the Cognitive Evaluation Protocol (CEP), a touchscreen computer assessment instrument that is self-administered by subjects. CEP was administered twice to PTSD subjects 1 month apart; other instruments were administered at the beginning of the study. Control subjects took CEP once and were administered the Hamilton Depression Rating Scale and the PostTraumatic Stress Diagnostic Scale once. Compared with control subjects, PTSD subjects performed significantly less well on CEP for the three cognitive domains of attention, memory, and function and had highly elevated depression scores. An interaction between depression and memory was found but not with depression and attention. There was no evidence of reduced information processing speed among PTSD subjects. Comparisons between the three assessment instruments showed a high degree of cross-assessment agreement. The findings are consistent with reports that chronic PTSD is associated with compromised memory, attention, and function. The study documents the feasibility of using self-administrated touchscreen computer programs to evaluate and track features of mental disorders.

Affect↗
PubMed2000

Chest pain, enzymes and hypothyroidism.

Hypothyroidism is a common disorder and when presenting with classical symptoms and signs is easy to recognise. However, hypothyroidism may present in a manner suggestive of an acute myocardial infarction with an elevated creatine kinase and electrocardiographic abnormalities. We report a case of severe hypothyroidism presenting as a cardiac event whose symptoms and signs dispersed following treatment with thyroxine.

Chest Pain↗
PubMed2000

Using telephone prompts to improve initial attendance at a community mental health center.

Contacting patients by telephone before their appointment has been shown to increase clinic attendance in various settings. However, no such studies have been conducted in New Zealand, which has a unique mix of publicly funded secondary care and largely privately funded primary care. A controlled prospective study of telephone prompting was carried out in a New Zealand publicly funded community mental health center. One group of 190 patients was phoned the day before their initial appointment, and their attendance rate was compared with that of 496 patients not phoned. Ninety-six percent of the patients who were successfully contacted kept their appointment, compared with 76 percent of those not contacted.

Adolescent↗
PubMed2000

Implantation and decidualization defects in prolactin receptor (PRLR)-deficient mice are mediated by ovarian but not uterine PRLR.

PRL and its homologs accomplish their biological effects through the PRL receptor (PRLR). We evaluated the expression and function of PRLR in the embryo and uterus during the periimplantation period because PRLR deficiency results in implantation failure. In wild-type mice, PRLR expression was localized to undecidualized stromal cells in the antimesometrial border on days 6-8 of pregnancy. A small population of PRLR-expressing cells was observed adjacent to the ectoplacental cone in the mesometrial stroma. Low levels of PRLR expression were also detected in the developing embryo on days 6-8. To determine the significance of PRLR expression in this distribution, we examined implantation and decidualization in PRLR-/- mice. Progesterone (P4) administration rescued infertility in PRLR-/- mice from the periimplantation period to midgestation. Artificially induced decidualization was absent in pseudopregnant PRLR-/- mice but was identical to wild-type in P4-treated PRLR-/- mice. Furthermore, wild-type and P4-treated PRLR-/- mice had similar expression of the implantation-specific genes, LIF, amphiregulin, HB-EGF, COX-1, COX-2, PPARdelta, Hoxa-10, cyclin-D3, VEGF, and its receptors, Flk-1 and neuropilin-1. Together, these results show that luteal P4 production via ovarian PRLR signaling is required for implantation and early pregnancy. The function of uterine PRLR remains unclear. However, the eventual loss of pregnancy in P4-treated PRLR-/- mice suggests that uterine PRLR may be essential for the support of late gestation.

Animals↗
PubMed2000

Baboon cytochrome P450c11 is encoded by more than one gene.

Two P450c11 genes, sharing 99% homology, were cloned from Cape baboon adrenal tissue using RT-PCR. The cDNAs showed 96% and 94.6% sequence identity to human P450c11 and aldosterone synthase, respectively. One of the gene sequences contained a termination codon in exon one. The cloned cDNAs were expressed in COS 1 cells and the metabolism of deoxycorticosterone to corticosterone investigated. The expressed enzyme exhibited 1 beta hydroxylase activity, but no aldosterone synthase activity.

Adrenal Glands↗
PubMed2000

Development of prediction models for three in vitro embryotoxicity tests in an ECVAM validation study.

Since 1997 the National Center for Documentation and Evaluation of Alternative Methods to Animal Experiments, ZEBET, in Berlin, has been coordinating a validation study aimed at prevalidation and validation of three in vitro embryotoxicity tests, funded by the European Center for the Validation of Alternative Methods (ECVAM) at the Joint Research Center (JRC, Ispra, Italy). The tests use the cultivation of postimplantation rat whole embryos (WEC test), cultures of primary limb bud cells of rat embryos (micromass or, MM, test), and cultures of a pluripotent mouse embryonic stem cell line (embryonic stem cell test or EST). Each of the tests was performed in four laboratories under blind conditions. In the preliminary phase of the validation study 6 out of 20 test chemicals comprising different embryotoxic potential (non, weakly, and strongly embryotoxic) were tested. The results were used to define biostatistically based prediction models (PMs) to identify the embryotoxic potential of test chemicals for the WEC test and the MM test. The PMs developed with the results of the preliminary phase of the validation study (training set) will be evaluated with the results of the remaining 14 test chemicals (definitive phase) by the end of the study. In addition, the existing, improved PM (iPM) for the EST, which had been defined previously, was evaluated using the results of the preliminary phase of this study. Applying the iPM of the EST to the results of this study, in 79% of the experiments, chemicals were classified correctly according to the embryotoxic potential defined by in vivo testing. For the MM and the WEC test, the PMs developed during the preliminary phase of this validation study provided 81% (MM test) and 72% (WEC test) correct classifications. Because the PM of the WEC test took into account only parameters of growth and development, but not cytotoxicity data, a second PM (PM2) was developed for the WEC test by incorporating cytotoxicity data of the differentiated mouse fibroblast cell line 3T3, which was derived from the EST. This approach, which has previously never been used, resulted in an increase to 84% correct classifications in the WEC test.

3T3 Cells↗
PubMed2000

Palatogenesis and potential mechanisms for clefting.

This review concentrates on mechanisms of palatogenesis. This includes theories of shelf elevation, the role of matrix and identification of molecules and growth factors, which have key roles. The areas where failure to develop could potentially lead to clefting are highlighted. A key part of shelf fusion is the breakdown of the medial edge epithelium, a process that is probably dependent on enzymes involved in matrix turnover. There is good evidence that the matrix metalloproteinases may provide a common link to the multiple genetic and environmental factors that are known to cause clefting.

Cleft Palate↗
PubMed2000

Exploration of diagnostic techniques for malignant melanoma: an integrative review.

The aim of this study is to explore the various diagnostic techniques for melanoma and assess their usefulness in the clinical practice of nurse practitioners. After a systematic review of the literature, 55 articles were closely reviewed, and from these, 26 studies were selected. These were original studies in English that examined diagnostic techniques that would improve accuracy for melanoma detection with a formal methods and results section. Six general categories dealing with diagnostic techniques for melanoma were found in the literature. These were naked-eye clinical examination alone, clinical examination with the aid of total-body photographs, epiluminescence microscopy (ELM), digital ELM, computer-assisted techniques, and teledermatology. Because of the research citing the poor diagnostic accuracy (DA) of nondermatologists, increased DA with dermatologists experienced in ELM techniques, and the importance of early melanoma diagnosis, the recommendation is to refer patients with suspicious pigmented skin lesions to experienced dermatologists, preferably those who use ELM or digital ELM.

Diagnosis, Computer-Assisted↗
PubMed1999

Growth and survivorship of dipterocarp seedlings: differences in shade persistence create a special case of dispersal limitation.

A series of growth experiments and observations on natural populations have been carried out on dipterocarp species of contrasting ecology growing in artificial gaps and the forest understorey. These studies have demonstrated that although differences exist between species in photosynthetic and growth responses to the high-light environment, competition for light in canopy gaps is highly asymmetrical and tends to reinforce any pre-existing dominance hierarchy. We propose that differences in seedling persistence in forest canopy shade are highly influenced by species-specific biotic and abiotic interactions. Our experiments suggest that as seedlings, dipterocarp species trade off traits which enhance persistence and growth in shade against those that enhance their ability to exploit gaps. Less competitive species survive for progressively longer periods of time after a gregarious fruiting event. This leads to significant shifts with time in the number of species present in the seedling bank and hence in the importance of interspecific competition in determining which species dominates regrowth in gaps. We propose that this special case of dispersal limitation is more likely to account for coexistence of dipterocarp species than differences in growth responses to gaps of different size, with stochastic and environmental variables interacting to determine species distribution and abundance.

Ecosystem↗
PubMed1999

Age-related changes in the cerebellum: parallel fibers.

Between the ages of 3 and 23 months, the cerebella of NIH Fischer 344 rats lose 30% of the thickness of the molecular layer, 60% of the length of parallel fibers, and 80% of the synaptic varicosities along parallel fibers. Nearly 60% of these synaptic varicosities disappear between 3 and 9 months. Thus, the loss of cerebellar synapses is unusual, may have begun early in life, and continue into old age, causing profound synaptic losses in older rats. In addition to serious implications to functional losses, we speculate that these synaptic losses may trigger other age-related cellular losses in the cerebellum.

Aging↗
PubMed1999

theta, a novel gamma-aminobutyric acid type A receptor subunit.

gamma-Aminobutyric acid type A (GABA-A) receptors are a major mediator of inhibitory neurotransmission in the mammalian central nervous system, and the site of action of a number of clinically important drugs. These receptors exist as a family of subtypes with distinct temporal and spatial patterns of expression and distinct properties that presumably underlie a precise role for each subtype. The newest member of this gene family is the theta subunit. The deduced polypeptide sequence is 627 amino acids long and has highest sequence identity (50.5%) with the beta1 subunit. Within the rat striatum, this subunit coassembles with alpha2, beta1, and gamma1, suggesting that gamma-aminobutyric acid type A receptors consisting of arrangements other than alpha beta + gamma, delta, or epsilon do exist. Expression of alpha2beta1gamma1theta in transfected mammalian cells leads to the formation of receptors with a 4-fold decrease in the affinity for gamma-aminobutyric acid compared with alpha2beta1gamma1. This subunit has a unique distribution, with studies so far suggesting significant expression within monoaminergic neurons of both human and monkey brain.

Amino Acid Sequence↗
PubMed1999

COX-2 compensation in the uterus of COX-1 deficient mice during the pre-implantation period.

Prostaglandins (PGs) produced by cyclooxygenase (COX) participate in many aspects of female reproduction. The two isoforms of cyclooxygenase, COX-1 and COX-2, have distinct expression patterns in the mouse uterus during the peri-implantation period and suggest their independent contribution to uterine PGs. Using wild type and COX-1(-/-) mice, we examined the role of COX-1-derived PGs on day 4 of pregnancy, when its expression is maximal. Uterine vascular permeability was measured by 125I-labeled bovine serum albumin (BSA) uptake, and PG content was measured by gas chromatography-mass spectrometry. Vascular permeability and PG concentrations were reduced in COX-1(-/-) mice, but by less than the expected amount. After ovariectomy, uterine vascular permeability declined in both groups, but returned to baseline in wild type and was exaggerated in COX-1(-/-) females after treatment with ovarian steroids. Most importantly, COX-1(-/-) uteri displayed COX-2 expression on the morning of day 4, when COX-2 is normally absent. This hybridization pattern resembles the native expression of COX-1, and may partially offset the loss of COX-1-derived PGs. These data indicate that COX-1-derived PGs are important during uterine preparation for implantation, and that COX-2 compensation occurs in the absence of COX-1.

Animals↗