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Biomedical subjects

N Martin

Publications and source records attributed to N Martin.

At least 109 records · Page 6Linked to original sources
PubMed1999

Perceptual variation in grading hand, hip and knee radiographs: observations based on an Australian twin registry study of osteoarthritis.

OBJECTIVE: The radiographic diagnosis of osteoarthritis (OA) in the peripheral skeleton is dependent on the skilled examination of several morphological characteristics of the condition as visualised on plain radiographs. However, the process is perceptual and generally enhanced by comparison against photographic standards. This study assessed the intra-rater and inter-rater reliability of radiologists experienced in reporting hand, hip and knee films derived from a community-based sample when using the photographic atlas recently developed by Burnett et al. METHODS: This study was part of a multifaceted diagnostics protocol, evaluating methodological issues, in the conduct of genetic research in osteoarthritis. From a cohort of 118 twin pairs, registered with the Australian Twins Registry (ATR), standard clinical examinations were performed on 74 complete and 11 incomplete pairs of twins over age 50 years, followed by standard AP hand, AP pelvis and AP standing radiographs of the knees. The pairs were selected both to represent twin pairs who had previously self reported a diagnosis of OA, as well as those who had not. Radiologists read the films blind to the original self reported diagnosis and without reference to their pairing. The films were read by comparison against photographic standards and were scored according to specific features. All films were read independently by two consultant radiologists blind to one another's assessments, and selected films were thereafter assigned for rereading. Inter-rater and intra-rater agreement were different for different features, different anatomic areas, and, for the former, were different for the two radiologists. RESULTS: Inter-rater agreement was different for different anatomic areas, different radiographic features, and the two radiologists. Intra-rater agreement for the presence or absence of OA was as follows: actual observed agreement = 0.79 to 0.97 and 0.83 to 0.98; adjusted kappa statistic = 0.58 to 0.94 and 0.67 to 0.96; inter-rater agreement was as follows: actual observed agreement = 0. 77 to 0.97; adjusted kappa statistic = 0.54 to 0.94. Agreement was generally high in most of the principal target joints for OA: DIP, PIP, 1st CMC, hip and knee. CONCLUSIONS: Although assessor agreement was not perfect, it is concluded that for genetic epidemiology purposes, while duplicate assessments may be advantageous, it is possible for radiographs to be examined accurately by a single experienced assessor. However, for less experienced assessors independent examinations should be made by at least two assessors and either a consensus reached on disparate examinations or an algorithm developed to adjudicate any discrepancies.

Adult↗
PubMed1999

Heritability of social cognitive skills in children and adolescents.

BACKGROUND: Social cognitive skills are those which enable understanding of social situations; they are relevant to a variety of psychiatric disorders including autism, schizophrenia and externalizing behaviour problems in children. AIMS: To examine the heritability of social cognitive skills. METHOD: Using a population-based sample of twins aged 5-17, the genetic and environmental influences on social cognitive skills were examined. RESULTS: Male scores were higher than female scores (P < 0.001), indicating poorer social cognition among males. A heritability of 0.68 (95% CI 0.43-0.78) was found, with shared environmental influences accounting for only 0.05 of the variance (95% CI 0.00-0.28). This could be removed from the model without worsening the fit. There were no significant differences in genetic effects between the genders, but age-related changes were found, with younger twins showing greater genetic influence on social cognition. CONCLUSIONS: Social cognition appears to be under considerable genetic influence in the population and shows significant male-female differences. No gender differences in genetic influences on the variance of scores were found, but the effects of age were significant.

Adolescent↗
PubMed1999

Short term cardiovascular effects of aldosterone in healthy male volunteers.

Clinical evidence of rapid, nongenomic aldosterone effects in the cardiovascular system has been provided by clinical studies; an increase in systemic vascular resistance (SVR) was shown by invasive techniques within 3 min after injection of aldosterone. Here, we study the dose dependency and the later course of the rapid aldosterone effects by noninvasive techniques. In 12 healthy male volunteers, SVR and heart rate variability were determined by impedance cardiography and digital electrocardiography, respectively, for 8 h after the injection of 0.05 or 0.5 mg aldosterone in a double blind, placebo-controlled, 3-fold cross-over study. No significant differences were observed for baseline values among the three treatments. The area under the curve of SVR during the first 45 min after injection was significantly different between the periods with the highest areas under the curve seen after the injection of 0.5 mg aldosterone (mean +/- SD, 40.4 +/- 12.8 vs. 36.8 +/- 10.3 for 0.05 mg aldosterone and 36.8 +/- 10.4 for placebo; P = 0.05). Individual comparisons showed significant differences at 6 and 30 min between placebo and the 0.5 mg aldosterone period (P < 0.05), with values for the 0.05 mg aldosterone period similar to those for the placebo period. From 330-390 min, opposite changes occurred; SVR was depressed during the 0.05 mg (P < 0.05) and 0.5 mg aldosterone periods compared with that during the placebo period. These delayed effects may reflect an increased vagal tone in the aldosterone groups, as demonstrated by higher values of the time domain parameter of heart rate variability pNN50. This study provides further evidence for clinically detectable rapid cardiovascular aldosterone effects in vivo obtained by noninvasive techniques. The data are consistent with the view of aldosterone as a rapid modulator of cardiovascular responses acting through nongenomic mechanisms.

Adult↗
PubMed1999

Comparing the biological and cultural inheritance of personality and social attitudes in the Virginia 30,000 study of twins and their relatives.

Measures of four dimensions of personality (Psychoticism, Extraversion, Neuroticism, and Lie scores) and six aspects of social attitudes (to sex, taxation, militarism, politics, religion and a general conservatism scale) were obtained by mailed questionnaire from 29,691 US subjects including adult twins (n = 14,761) their parents (n = 2360), their spouses (n = 4391), siblings (n = 3184) and adult children (n = 4800). After correction for the average effects of age, sex and source of sample, familial correlations were computed for 80 distinct biological and social relationships. The data allow for the estimation of the additive and non-additive effects of genes, assortative mating, vertical cultural inheritance and other non-parental effects of the shared environment on differences in personality and social attitudes. The interaction of genetic and environmental effects with sex may also be analyzed. Model-fitting analyses show that personality and social attitude measures differ markedly in major features of family resemblance. Additive and dominant genetic effects contribute to differences in both personality and attitudes, but the effects of the family environment, including vertical cultural transmission from parent to child, are much more marked for social attitudes than for personality. There is substantial assortative mating for social attitudes and almost none for personality. The causes of family resemblance depend significantly on sex for almost every variable studied. These findings clarify and extend the more tentative findings derived from previous twin, family and adoption studies.

Adult↗
PubMed1999

Involvement of desmoplakin phosphorylation in the regulation of desmosomes by protein kinase C, in HeLa cells.

In the present study, we have examined how modulation of protein kinase C (PKC) activity affected desmosome organization in HeLa cells. Immunofluorescence and electron microscopy showed that PKC activation upon short exposure to 12-O-tetradecanoylphorbol 13-acetate (TPA) resulted in a reduction of intercellular contacts, splitting of desmosomes and dislocation of desmosomal components from the cell periphery towards the cytoplasm. As determined by immunoblot analysis of Triton X-100-soluble and -insoluble pools of proteins, these morphological changes were not correlated with modifications in the extractability of both desmoglein and plakoglobin, but involved almost complete solubilization of the desmosomal plaque protein, desmoplakin. Immunoprecipitation experiments and immunoblotting with anti-phosphoserine, antiphosphothreonine and anti-phosphotyrosine antibodies revealed that desmoplakin was mainly phosphorylated on serine and tyrosine residues in both treated and untreated cells. While phosphotyrosine content was not affected by PKC activation, phosphorylation on serine residues was increased by about two-fold. This enhanced serine phosphorylation coincided with the increase in the protein solubility, suggesting that phosphorylation of desmoplakin may be a mechanism by which PKC mediates desmosome disassembly. Consistent with the loss of PKC activity, we also showed that down-modulation of the kinase (in response to prolonged TPA treatment) or its specific inhibition (by GF 109203X) had opposite effects and increased desmosome formation. Taken together, these results clearly demonstrate an important role for PKC in the regulation ofdesmosomal junctions in HeLa cells, and identify serine phosphorylation of desmoplakin as a crucial event in this pathway.

Animals↗
PubMed1999

Telemetry monitoring in acute and critical care.

With the expansion of higher acuity patients in noncritical care areas, the perceived need for arrhythmia monitoring has also escalated. For institutions pursuing this expansion, many factors must be kept in mind, including patient criteria for telemetry initiation and discontinuation, staff competency of ECG interpretation, safety, technology required, usability, and cost effectiveness. All of these issues must be addressed according to the individual institution's needs and the needs of the patient populations they serve.

Acute Disease↗
PubMed1999

Intraarterial thrombolysis for treatment of acute stroke: experience in 26 patients with long-term follow-up.

BACKGROUND AND PURPOSE: Since the approval of intravenous tissue plasminogen activator for acute ischemic stroke, great interest has been generated in cerebral fibrinolysis. Our purpose was to assess long-term outcome and hemorrhagic risk in patients with anterior circulation ischemic stroke treated with intraarterial urokinase. METHODS: Twenty-six patients were treated within 6 hours of ictus; of these, 21 were followed up for an average of 23 months. Angiographic reperfusion was classified according to thrombolysis in myocardial infarction (TIMI) grades. The Rankin Scale (RS) and the modified Barthel Index (mod BI) were used as outcome measures (good outcome: RS = 0-2, mod BI = 16-20; poor outcome: RS = 3-5, mod BI < or = 15). RESULTS: Ten of the 21 patients (average age, 48 years) had a good outcome; three (average age, 71 years) had a poor outcome; eight patients (average age, 78 years) died. Partial/complete (successful) recanalization was observed in 11 of 26 patients and minimal or no (unsuccessful) recanalization in 15. Recanalization favored a better outcome: nine of 21 had successful recanalization, with a good outcome in seven; 12 of 21 had unsuccessful reperfusion, with poor outcome/death in nine. Poor outcome was noted in five patients with internal carotid artery (ICA) bifurcation occlusions, four of whom had unsuccessful recanalization and poor outcome or death. Hemorrhage occurred in 10 of the 26 patients, with clinical deterioration in three. The average dose of urokinase was higher in the hemorrhage group, and mortality was higher in patients who hemorrhaged. CONCLUSION: Intraarterial thrombolysis is feasible in the setting of acute stroke. Successful reperfusion is associated with a better outcome, and the prevalence of hemorrhage does not exceed that which occurs in the natural history of embolic stroke. Poor outcome or death is associated with nonrecanalization, older age, hemorrhage, and ICA bifurcation occlusions.

Acute Disease↗
PubMed1999

Perceptual variation in categorizing individuals according to American College of Rheumatology classification criteria for hand, knee, and hip osteoarthritis (OA): observations based on an Australian Twin Registry study of OA.

OBJECTIVE: The American College of Rheumatology (ACR) classification criteria for osteoarthritis (OA) permit the categorization of individuals for hand, knee, and hip OA and are of defined sensitivity and specificity. They depend on both clinical and radiographic aspects of OA. The clinical diagnosis of OA in the peripheral skeleton is dependent on the skilled examination of several clinical features characteristic of the condition, while the interpretation of radiographs is a perceptual skill based on appreciating specific structural features on plain radiographs. We investigated the interrater reliability of the ACR classification criteria for OA when applied in a community based sample. METHODS: The study was part of a multifaceted diagnostics protocol, evaluating methodologic issues, in the conduct of genetic research in OA. From a cohort of 118 pairs of twins registered with the Australian Twins Registry (ATR), standard clinical examinations of hands, knees, and hips were performed on 74 complete and 11 incomplete pairs of twins over age 50 years. The pairs were selected to represent both twin pairs who had previously self-reported a diagnosis of OA, as well as those who had not. Rheumatologists who performed the assessments were blind to the original self-report. All subjects were examined independently by one of 2 pairs (NB/AK or NB/KM) of consultant rheumatologists, blind to one another's assessments. Each rheumatologist separately assessed the hands, knees, and hips, rating them clinically by ACR criteria for OA. The observations were made without reference to any radiographic or serologic information. RESULTS: Interrater agreement was different for the 3 different anatomic areas and was different for the 2 pairs of rheumatologists. The actual (observed) interrater agreements based on ACR clinical criteria were as follows: hand OA NB/AK = 0.92, NB/KM = 1.00; knee OA NB/AK = 0.94, NB/KM = 0.92; hip OA NB/AK = 0.98, NB/KM = 0.97. Interrater agreement based on ACR clinical criteria, as assessed by the adjusted kappa statistic, was as follows: hand OA NB/AK = 0.84, NB/KM = 1.00; knee OA NB/AK = 0.87, NB/KM = 0.84; hip OA NB/AK = 0.95, NB/KM = 0.93. CONCLUSION: Since clinical agreement was extremely high in all 3 anatomic sites, and for both pairs of assessors, we conclude that for genetic epidemiology purposes, subjects can be examined by a single experienced rheumatologist using the ACR classification criteria.

Australia↗
PubMed1998

Safety and immunogenicity of HIV recombinant envelope vaccines in HIV-infected infants and children. National Institutes of Health-sponsored Pediatric AIDS Clinical Trials Group (ACTG-218).

Study objectives were to evaluate the safety and immunogenicity of three HIV recombinant glycoproteins in HIV-infected infants and children between 1 month and 18 years of age with asymptomatic (P-1) infection. Using Chiron rgp 120 (SF-2) 15 or 50 microg; MicroGeneSys rgp 160 (IIIB) 40 or 320 microg; Genentech rgp120 (MN) 75 or 300 microg; or adjuvant control (Alum or MF-59), children were randomized to a double-blind, placebo-controlled, dose-escalating study of vaccine administered intramuscularly at entry and 1, 2, 3, 4, and 6 months later. No adverse events were attributed to study vaccines. Between 30% and 56% of volunteers exhibited a lymphoproliferative response as defined in terms of stimulation index (SI) to vaccine antigens; 65% of vaccinees but none of placebo recipients exhibited moderate or strong responses after enzyme immunoassay to HIV specific antigens. CD4 cell counts and quantitative HIV culture did not differ significantly among vaccine and control groups, nor were differences found among groups in HIV disease progression. The rgp160 and gp120 subunit vaccines were safe and immunogenic in this population.

AIDS Vaccines↗
PubMed1998

Assay of paclitaxel (Taxol) in plasma and urine by high-performance liquid chromatography.

A new, rapid and sensitive high-performance liquid chromatographic method for the analysis of paclitaxel (Taxol) in human plasma and urine was developed and validated. After addition of an internal standard, paclitaxel was extracted from plasma or urine by a liquid-liquid extraction using diethyl ether. Extraction efficiency averaged 90%. Chromatography was performed isocratically on a reversed-phase column monitored at 227 nm. Retention times were 7.7 and 6.7 min for paclitaxel and docetaxel, respectively, and the assay was linear in the range 25-1000 ng/ml. The limits of quantification for paclitaxel were 25 and 40 ng/ml in plasma and urine, respectively. The assay was shown to be suitable for pharmacokinetic studies of children involved in a phase I clinical trial.

Antineoplastic Agents, Phytogenic↗
PubMed1998

DNA binding by cut homeodomain proteins is down-modulated by casein kinase II.

The Drosophila and mammalian Cut homeodomain proteins contain, in addition to the homeodomain, three other DNA binding regions called Cut repeats. Cut-related proteins thus belong to a distinct class of homeodomain proteins with multiple DNA binding domains. Using nuclear extracts from mammalian cells, Cut-specific DNA binding was increased following phosphatase treatment, suggesting that endogenous Cut proteins are phosphorylated in vivo. Sequence analysis of Cut repeats revealed the presence of sequences that match the consensus phosphorylation site for casein kinase II (CKII). Therefore, we investigated whether CKII can modulate the activity of mammalian Cut proteins. In vitro, a purified preparation of CKII efficiently phosphorylated Cut repeats causing an inhibition of DNA binding. In vivo, overexpression of the CKII alpha and beta caused a decrease in DNA binding by Cut. The CKII phosphorylation sites within the murine Cut (mCut) protein were identified by in vitro mutagenesis as residues Ser400, Ser789, and Ser972 within Cut repeat 1, 2, and 3, respectively. Cut homeodomain proteins were previously shown to function as transcriptional repressors. Overexpression of CKII reduced transcriptional repression by mCut, whereas a mutant mCut protein containing alanine substitutions at these sites was not affected. Altogether our results indicate that the transcriptional activity of Cut proteins is modulated by CKII.

Amino Acid Sequence↗
PubMed1998

Structure and expression of Wnt13, a novel mouse Wnt2 related gene.

We have identified a novel mouse member of the Wnt family, Wnt13. Among mouse Wnt genes, Wnt13 is most closely related to Wnt2. Sequence comparisons and chromosomal localization strongly suggest that Wnt13, rather than Wnt2, is the mouse orthologue of both the human WNT13 and Xenopus XWnt2 genes. Wnt13 is expressed in the embryonic mesoderm during gastrulation. At later stages, transcripts are detected in the dorsal midline of the diencephalon and mesencephalon, the heart primordia, the periphery of the lung bud and the otic and optic vesicles. These data suggest that Wnt13 function might partially overlap with those of other Wnt genes in the cell signaling mechanisms controlling mesoderm specification during gastrulation and some aspects of brain, heart and lung formation.

Amino Acid Sequence↗
PubMed1998

Donor-derived Plasmodium vivax infection following volunteer unrelated bone marrow transplantation.

A 14-year-old girl from the UK underwent volunteer unrelated donor bone marrow transplant (VUD BMT) for accelerated phase chronic myeloid leukaemia. On day +40 she became febrile, and peripheral blood smears demonstrated a 1% Plasmodium vivax parasitaemia. Although she had never been outside the UK, her male donor had documented Plasmodium vivax infection during a vacation in Papua New Guinea. Following appropriate treatment, he had been asymptomatic for 11 months before marrow harvesting. This is the first case report of malarial transmission by VUD BMT, and illustrates the potential problem of recrudescence of latent, dormant forms of Plasmodium vivax infection following transplantation into an immuno-compromised recipient. Even after appropriate therapy, malarial infection should be included in the differential diagnosis for all post-transplant febrile episodes.

Adolescent↗
PubMed1998

Depression, cognition, and functional correlates of recovery outcome after traumatic brain injury.

The present study investigated the prevalence and magnitude of depressive symptomatology in a sample of patients who had sustained traumatic brain injury (TBI) six months earlier. Depression was examined as a function of recovery outcome status, and its association with neuropsychological functioning, personal competency, and employability was also explored. Subjects were 100 patients who had previously sustained moderate-to-severe TBI who were enrolled as research subjects in the UCLA Brain Injury Research Center, and 30 matched control subjects who had sustained traumatic injuries other than to the head six months prior to evaluation. The results showed a significant association between depression and recovery status as measured by the Glasgow Outcome Scale (GOS). A significant majority of depressed subjects were found in the poorer GOS outcome groups (severe and moderate disability), compared to TBI subjects who had good GOS outcomes, and control subjects. This association was also reflected in the magnitude of the mean depression scores on two self-report measures of depression. However, no association was found between depression status and performance on the neuropsychological measures. Effects of depression were found only on an examiner-rated Patient Competency scale, and a metacognition measure based on self-report. These results are discussed in terms of brain injury severity, recovery status, and metacognition issues in TBI and other disorders.

Activities of Daily Living↗
PubMed1998

Neuropsychological, psychosocial and vocational correlates of the Glasgow Outcome Scale at 6 months post-injury: a study of moderate to severe traumatic brain injury patients.

Traumatic brain injury (TBI) subjects at Glasgow Outcome Scale levels 3 (severe disability), 4 (moderate disability), 5 (good recovery), and an other-injury control group (OIC) were compared in terms of neuropsychological, psychosocial, and vocational functioning 6 months after injury. Subjects were a sample of 100 patients with a moderate to severe traumatic brain injury (TBI) and a matched sample of 30 other-injury control subjects (OIC) enrolled in the UCLA Brain Injury Research Center study of TBI outcome. Overall, the results showed a systematic decrease in mean neuropsychological test performance as a function of increasing GOS severity, as well as an increased prevalence of symptoms of depression and lower ratings on measures assessing employability and capacity for self care. TBI patients in the 'severe' and 'moderate disability' groups were distinctly inferior to the 'good recovery' and 'OIC' groups, who were quite similar to each other in terms of cognitive, psychosocial, and vocational outcomes. The results demonstrate overall support for the predictive and concurrent validity of the GOS 6 months post injury. Despite these results, which strengthen the utility and appeal of the GOS for multicentre studies, concerns still remain regarding GOS category 4 (moderate disability), which was shown to lack sufficient discriminability in this study.

Activities of Daily Living↗
PubMed1998

Dating the origin of the CCR5-Delta32 AIDS-resistance allele by the coalescence of haplotypes.

The CCR5-Delta32 deletion obliterates the CCR5 chemokine and the human immunodeficiency virus (HIV)-1 coreceptor on lymphoid cells, leading to strong resistance against HIV-1 infection and AIDS. A genotype survey of 4,166 individuals revealed a cline of CCR5-Delta32 allele frequencies of 0%-14% across Eurasia, whereas the variant is absent among native African, American Indian, and East Asian ethnic groups. Haplotype analysis of 192 Caucasian chromosomes revealed strong linkage disequilibrium between CCR5 and two microsatellite loci. By use of coalescence theory to interpret modern haplotype genealogy, we estimate the origin of the CCR5-Delta32-containing ancestral haplotype to be approximately 700 years ago, with an estimated range of 275-1,875 years. The geographic cline of CCR5-Delta32 frequencies and its recent emergence are consistent with a historic strong selective event (e.g. , an epidemic of a pathogen that, like HIV-1, utilizes CCR5), driving its frequency upward in ancestral Caucasian populations.

Acquired Immunodeficiency Syndrome↗
PubMed1998

Multiple cerebral pseudoaneurysms and hemorrhages: the expanding spectrum of metastatic cerebral choriocarcinoma.

Cerebral metastases occur in 10-20% of patients with choriocarcinoma. Although single oncotic and pseudoaneurysms have been reported, multiple pseudoaneurysms and hemorrhages are rare. A 33-year-old woman developed 10 intracerebral hemorrhages over a 30-day period. Angiogram showed multiple focal areas of delayed contrast washout in distal vessels. Autopsy revealed intravascular choriocarcinoma without true aneurysm formation. A diagnosis of choriocarcinoma should be considered for women of childbearing age presenting with cerebrovascular syndromes, especially those found to have cerebral aneurysm pseudoaneurysm and/or hemorrhage.

Adult↗