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Biomedical subjects

M Adams

Publications and source records attributed to M Adams.

At least 37 records · Page 2Linked to original sources
PubMed1998

Major depression in individuals with a history of childhood physical or sexual abuse: relationship to neurovegetative features, mania, and gender.

OBJECTIVE: Numerous studies have linked childhood trauma with depressive symptoms over the life span. However, it is not known whether particular neurovegetative symptom clusters or affective disorders are more closely linked with early abuse than are others. In a large community sample from Ontario, the authors examined whether a history of physical or sexual abuse in childhood was associated with particular neurovegetative symptom clusters of depression, with mania, or with both. METHOD: The World Health Organization Composite International Diagnostic Interview was used to assess 8,116 individuals aged 15-64 years. Each subject was asked about early physical and sexual abuse experiences on a structured supplement to the interview. Six hundred fifty-three cases of major depression were identified. Rates of physical and sexual abuse in depressive subgroups defined by typical and reversed neurovegetative symptom clusters (i.e., decreased appetite, weight loss, and insomnia versus increased appetite, weight gain, and hypersomnia, respectively) and by the presence or absence of lifetime mania were compared by gender. RESULTS: A history of physical or sexual abuse in childhood was associated with major depression with reversed neurovegetative features, whether or not manic subjects were included in the analysis. A strong relationship between mania and childhood physical abuse was found. Across analyses there was a significant main effect of female gender on risk of early sexual abuse; however, none of the group-by-gender interactions predicted early abuse. CONCLUSIONS: These results suggest an association between early traumatic experiences and particular symptom clusters of depression, mania, or both in adults.

Adult↗
PubMed1998

The relationship of antiphospholipid antibodies to thromboembolic events in pediatric patients with systemic lupus erythematosus: a cross-sectional study.

The purpose of this study was to evaluate pediatric patients with systemic lupus erythematosus (SLE) to determine 1) the incidence of thrombosis, 2) the incidence of antiphospholipid antibodies, and 3) whether there is an association between the presence of antiphospholipid antibodies and thrombosis. We performed a cross-sectional cohort study in 59 consecutive SLE patients who had been managed at rheumatology clinics in two pediatric hospitals. A history, questionnaire, and chart review were completed by the study nurse blinded to laboratory results. Only the thrombotic events that could be substantiated by review of radiographic tests were accepted. The presence of antiphospholipid antibodies was determined by prospective analysis for a lupus anticoagulant and anticardiolipin antibodies on two separate occasions at least 3 mo apart. Patients were considered to be positive if one or more tests were positive on both occasions. Thirteen thrombotic events occurred in 10 of the 59 patients (17%). Fourteen patients (24%) were classified as positive for lupus anticoagulant, and 19 patients (27%) were classified as positive for anticardiolipin antibodies. A significant relationship between the presence of a lupus anticoagulant and a thrombotic event was shown: odds ratio 28.7 (95% confidence interval 4.03-138.2, p < 0.001). A nonsignificant trend was seen for the presence of an anticardiolipin antibody and a thrombotic event: odds ratio 2.12 (95% confidence interval 0.71-22.8, p=0.08). We conclude that in pediatric patients with SLE: 1) a significant proportion of patients have thrombotic events, 2) a significant proportion of patients have antiphospholipid antibodies, and 3) there is a significant relationship between the presence of a lupus anticoagulant and thrombotic events.

Adolescent↗
PubMed1998

Distribution of tissue plasminogen activator insertion/deletion polymorphism in myocardial infarction and control subjects.

An insertion (I)/deletion (D) polymorphism in the tissue plasminogen activator (TPA) gene locus has recently been reported to be associated with the risk of myocardial infarction (MI) with increased risk in II/ID subjects compared with DD subjects. To investigate this further, we analysed 529 acute MI cases and 525 population-based control subjects recruited in two centers (Leicester and Sheffield, UK). We found no difference between cases and controls in TPA I/D allele frequencies (cases I = 0.574, controls I = 0.582, p = 0.74) or genotype distribution (cases II 33%, ID 48%, DD 19%; controls II 34%, ID 49%, DD 17%, p = 0.88). Compared with the DD genotype, the age, sex and centre adjusted odds ratios for MI for II genotype was 0.95 (95% confidence interval, 0.64-1.40, p = 0.85) and that for ID genotype was 0.89 (0.62-1.27, p = 0.56). There was no significant effect modification by smoking status, body mass index or cholesterol level. There was no difference in the reported frequency of positive family history of coronary heart disease or mean age at MI in the different genotype groups. We conclude that in our populations the TPA I/D polymorphism is not a major independent risk factor for myocardial infarction.

Aged↗
PubMed1998

Enhanced thrombin regulation during warfarin therapy in children compared to adults.

The intensity of warfarin therapy for prevention of primary and secondary thromboembolic complications in paediatric patients, is extrapolated from guidelines for adults, which may not be optimal. Therefore, we assessed thrombin regulation ex vivo and in vitro in plasmas from 40 children (1 to 18 years old with a median age of 13 years) and 27 adults receiving warfarin with an international normalized ratio of 2 to 3 (child: 2.5 +/- 0.15; adult: 2.4 +/- 0.14). Ex vivo concentrations of prothrombin fragment 1.2 were significantly lower in children (0.30 +/- 0.03 nM) compared to adults (0.45 +/- 0.04 nM; p <0.01). Thrombin generation in defibrinated plasmas (Arvin) was decreased and delayed for children compared to adults when activated by either activated partial thromboplastin time (child = 32 +/- 1.7, adult = 45 +/- 1.9 microM x s) or prothrombin time (child = 35 +/- 0.7, adult = 46 +/- 1.0 microM x s) reagents (p <0.01 for both). Although plasma concentrations of factors (F) II, FVII, FIX, F X, protein C and protein S were similar, more of the thrombin generated was complexed to alpha2 macroglobulin (alpha2M) at times close to peak thrombin activity (60 s) in plasma from children (general linear analysis of variance; p <0.03). Thus, increased alpha2M levels may enhance thrombin regulation in paediatric compared to adult patients receiving warfarin, suggesting that clinical trials in children, using less intense warfarin treatment, may be required to determine optimum therapy.

Adolescent↗
PubMed1998

The development and reliability of the Royal College of General Practitioners' questionnaire for measuring senior house officers' satisfaction with their hospital training.

BACKGROUND: The training provided for senior house officers (SHOs) has been the subject of debate, and variable satisfaction with training has been reported. The reliability of the instruments used for measuring satisfaction has not been adequately addressed. AIM: To develop a reliable questionnaire to measure SHO satisfaction with hospital training. METHOD: A 42-item questionnaire with eight scales was developed using criteria from the joint hospital visiting guidelines of the Royal College of General Practitioners. The questionnaire was sent to SHOs in Anglia before monitoring visits from the royal colleges, the postgraduate dean and the Joint Committee on Postgraduate Training for General Practice. RESULTS: Response rates varied from 37.0% to 100%, with an overall response rate of 58.8%. The internal reliability of the whole questionnaire was 0.82. Levels of internal reliability for the individual scales were satisfactory, Cronbach's alpha coefficient being 0.75 or more in all but two of the scales. Test-retest reliability using Pearson's product moment correlation coefficient was greater than 0.82 for six of the scales. There were significant differences in total satisfaction between SHOs reporting on posts accredited by the different royal colleges and also between SHOs training for general practice and those training to be specialists. CONCLUSION: A reliable questionnaire has been developed to measure SHO satisfaction with hospital training that is acceptable to doctors and feasible to administer. National acceptance of a single questionnaire for monitoring SHO posts would enable standards to be monitored regularly at a time of considerable change in hospital training.

Consumer Behavior↗
PubMed1997

Activators of peroxisome proliferator-activated receptor gamma have depot-specific effects on human preadipocyte differentiation.

Activation of peroxisome proliferator-activated receptor (PPAR) gamma, a nuclear receptor highly expressed in adipocytes, induces the differentiation of murine preadipocyte cell lines. Recently, thiazolidinediones (TZDs), a novel class of insulin-sensitizing compounds effective in the treatment of non-insulin-dependent diabetes mellitus (NIDDM) have been shown to bind to PPARgamma with high affinity. We have examined the effects of these compounds on the differentiation of human preadipocytes derived from subcutaneous (SC) and omental (Om) fat. Assessed by lipid accumulation, glycerol 3-phosphate dehydrogenase activity, and mRNA levels, subcultured preadipocytes isolated from either SC or Om depots did not differentiate in defined serum-free medium. Addition of TZDs (BRL49653 or troglitazone) or 15-deoxyDelta12,14prostaglandin J2 (a natural PPARgamma ligand) enhanced markedly the differentiation of preadipocytes from SC sites, assessed by all three criteria. The rank order of potency of these agents in inducing differentiation matched their ability to activate transcription via human PPARgamma. In contrast, preadipocytes from Om sites in the same individuals were refractory to TZDs, although PPARgamma was expressed at similar levels in both depots. The mechanism of this depot-specific TZD response is unknown. However, given the association between Om adiposity and NIDDM, the site-specific responsiveness of human preadipocytes to TZDs may be involved in the beneficial effects of these compounds on in vivo insulin sensitivity.

Adipocytes↗
PubMed1997

Three genes encoding zinc finger proteins on human chromosome 6p21.3: members of a new subclass of the Kruppel gene family containing the conserved SCAN box domain.

Five genes encoding zinc finger proteins of the Cys2His2 (or Krüppel) family were identified by direct cDNA hybridization to YACs 753H12 and 638D7, which encompass a region of human chromosome 6p21.3 extending from just centromeric of the microsatellite marker D6S306 to telomeric of D6S1260. The genes span a distance of approximately 1750 kb. The complete cDNA sequence, genomic structure, and tissue distribution of three of the zinc finger proteins, LD65/ZNF165, ZNF192 (previously called LD5-1), and ZNF193, are described. The three zinc finger proteins do not contain either Krüppel-associated box (KRAB) A or KRAB B domain, present in about one-third of all Krüppel-type zinc finger proteins (E. J. Bellefroid et al., 1991, Proc. Natl. Acad. Sci. USA 88: 3608-3612). The three zinc finger proteins do contain the conserved SCAN box domain (A. J. Williams et al., 1995, J. Biol. Chem. 270: 22143-22152). SCAN boxes are found in eight other genes in the GenBank database, five of which are also in the Kruppel family of zinc finger proteins lacking KRAB A and B domains and thereby define a new subclass of zinc finger proteins. In addition, three polymorphisms were identified in ZNF192, one of the zinc finger proteins. One of the three polymorphisms, Pro163Leu, is the second proline in a proline cluster (PEPP) in a region separating the SCAN box from the zinc finger motifs.

Amino Acid Sequence↗
PubMed1997

[Clinical value of somatostatin receptor scintigraphy. Studies of pre- and intraoperative localization of gastrointestinal and pancreatic tumors].

BACKGROUND: [111In-DTPA-D-Phe1]-pentetreotide scintigraphy is able to detect neuroendocrine tumors not shown by radiological methods. PATIENTS AND METHODS: In 270 patients with neuroendocrine gastroenteropancreatic tumors (GEP tumors) 400 somatostatin receptor scintigraphies were performed. 70 patients (38 female, 32 male, aged 28 to 74 [56 +/- 12.6] years) underwent surgery and follow-up over 2 years. The aim of the present study was the comparison of preoperative somatostatin receptor scintigraphy with radiological methods (sonography, CT) and intraoperative localization of GEP tumors with a hand-held gamma-probe. RESULTS: Somatostatin receptor scintigraphy was successful in localizing primary tumors in all patients. Liver- and lymph node metastases could be visualized with a sensitivity of 94 and 95 percent. In 7 patients 35 lesions could be identified by intraoperative tumor localization using a hand held gamma probe. Radiological methods identified only 11, surgical palpation 15 and preoperative somatostatin receptor scintigraphy 27 lesions. CONCLUSION: Somatostatin receptor scintigraphy improves detection of small and occult GEP tumors. Intraoperative probe counting with a hand-held gamma probe can identify tumors even when they are small and impalpable, but receptor positive.

Adult↗
PubMed1997

Infectious human herpesvirus 8 in a healthy North American blood donor.

BACKGROUND: Molecular studies have provided strong evidence for the association of human herpesvirus 8 (HHV-8) with Kaposi's sarcoma. These data have been supported by serological studies, which have also suggested that HHV-8 can be found in the healthy population. We report the presence of infectious HHV-8 in a healthy donor to a North American blood bank. METHODS: We examined the peripheral blood mononuclear cells or CD19 cells of blood donors by PCR for evidence of HHV-8 infection. The CD19 cells were separated from peripheral blood mononuclear cells by immunomagnetic-bead selection. To enhance detection of HHV-8, the CD19 cells from eleven unsystematically selected blood donors were activated with phorbol ester and recombinant interleukin-6; the culture fluid was filtered and inoculated onto HHV-8-negative target CD19 cells that had been prepared from phytohaemagglutinin-stimulated peripheral blood mononuclear cells. These inoculated target cells were cultured for 3 days and then analysed for HHV-8 sequences by PCR. Serum samples were tested for antibodies to HHV-8 by an indirect immunofluorescence assay. FINDINGS: One blood donor was consistently found to be infected with HHV-8 by PCR after the cell-culture activation procedure. He was seropositive for the virus. The HHV-8 recovered was infectious, as shown by a reverse-transcription-PCR technique that detected HHV-8 RNA in the inoculated target cells. INTERPRETATION: These data provide the first indication that HHV-8 can be recovered from the blood of a healthy individual, a blood donor, and that the virus is infectious. This observation suggests that HHV-8 could be transmitted by blood transfusion, a possibility that merits further study.

Adult↗
PubMed1997

Transcriptional activation by peroxisome proliferator-activated receptor gamma is inhibited by phosphorylation at a consensus mitogen-activated protein kinase site.

The nuclear receptor peroxisome proliferator-activated receptor gamma (PPARgamma) regulates transcription in response to prostanoid and thiazolidinedione ligands and promotes adipocyte differentiation. The amino-terminal A/B domain of this receptor contains a consensus mitogen-activated protein kinase site in a region common to PPARgamma1 and -gamma2 isoforms. The A/B domain of human PPARgamma1 was phosphorylated in vivo, and this was abolished either by mutation of serine 84 to alanine (S84A) or coexpression of a phosphoprotein phosphatase. In vitro, this domain was phosphorylated by ERK2 and JNK, and this was markedly reduced in the S84A mutant. A wild type Gal4-PPARgamma(A/B) chimera exhibited weak constitutive transcriptional activity. Remarkably, this was significantly enhanced in the S84A mutant fusion. Ligand-dependent activation by full-length mouse PPARgamma2 was also augmented by mutation of the homologous serine in the A/B domain to alanine. The nonphosphorylatable form of PPARgamma was also more adipogenic. Thus, phosphorylation of a mitogen-activated protein kinase site in the A/B region of PPARgamma inhibits both ligand-independent and ligand-dependent transactivation functions. This observation provides a potential mechanism whereby transcriptional activation by PPARgamma may be modulated by growth factor or cytokine-stimulated signal transduction pathways involved in adipogenesis.

Animals↗
PubMed1997

A natural transactivation mutation in the thyroid hormone beta receptor: impaired interaction with putative transcriptional mediators.

The syndrome of resistance to thyroid hormone is characterized by elevated serum free thyroid hormones, failure to suppress pituitary thyrotropin secretion, and variable peripheral refractoriness to hormone action. Here we describe a novel leucine to valine mutation in codon 454 (L454V) of the thyroid hormone beta receptor (TR beta) in this disorder, resulting in a mutant receptor with unusual functional properties. Although the mutant protein binds ligand comparably to wild-type receptor and forms homo- and heterodimers on direct repeat, everted repeat, or palindromic thyroid response elements, its ability to activate transcription via these elements is markedly impaired. The hydrophobic leucine residue lies within an amphipathic alpha-helix at the carboxyl terminus of TR beta and the position of the homologous residue in the crystal structure of TR alpha indicates that its side chain is solvent-exposed and might interact with other proteins. We find that two putative transcriptional mediators (RIP140 and SRC-1) exhibit hormone-dependent association with wild-type TR. In comparison, the interaction of this natural mutant (L454V) and artificial mutants (L454A, E457A) with RIP140 and SRC-1 is markedly reduced. Furthermore, coexpression of SRC-1 is able to restore the transcriptional activity of the L454V mutant receptor, indicating that the interaction of this residue with accessory proteins is critical for transcriptional activation. Finally, the occurrence of the L454V mutation in resistance to thyroid hormone, together with impaired negative regulation of the thyroid-stimulating hormone alpha promoter by this mutant, suggests that the amphipathic alpha-helix also mediates hormone-dependent transcriptional inhibition, perhaps via interaction with these or other accessory factors.

Adaptor Proteins, Signal Transducing↗
PubMed1997

Magnetic source imaging evidence of sex differences in cerebral lateralization in schizophrenia.

BACKGROUND: It has been postulated that schizophrenia represents a disorder of anomalous cerebral lateralization. This study is a replication of earlier preliminary findings using a multichannel neuromagnetometer, suggesting altered lateralization in schizophrenia in male subjects, with an extension of the findings to female subjects. METHODS: We used magnetoencephalography-based magnetic source imaging to estimate the intracranial location of the 100-millisecond latency auditory-evoked field component (M100) in both left and right hemispheres of 20 patients with paranoid schizophrenia and 20 controls without schizophrenia. Neuroanatomical data were obtained by means of magnetic resonance imaging, from which we segmented and computed volumes of both total brain and left and right superior temporal gyri. RESULTS: Locations of M100 source were compatible with neuronal generators located in the transverse gyri of Heschl on the superior temporal gyri in both study groups; M100 sources were asymmetric in all the control subjects. The male patient subgroup exhibited significantly less asymmetry than the control group, while the female patient subgroup actually showed significantly more asymmetry. The male patient subgroup generally had smaller superior temporal gyri than the control group. No evidence of total brain volume differences was observed. CONCLUSIONS: Our findings support previous magnetoencephalography-based studies suggesting anomalous cerebral lateralization in schizophrenia. Further, in extending our studies to female patients, our data suggest that the nature of this anomaly is sex specific, a finding that, to our knowledge, has not previously been reported.

Adult↗
PubMed1997

Oxaprozin and piroxicam, nonsteroidal antiinflammatory drugs with long half-lives: effect of protein-binding differences on steady-state pharmacokinetics.

The nonsteroidal antiinflammatory drugs (NSAIDs) oxaprozin and piroxicam have long elimination half-lives (t 1/2 approximately 55 hours), permitting once-daily dose regimens. The protein-binding characteristics of these drugs, however, vary widely. This study examines the effect of these binding differences on the drugs' disposition kinetics at steady state. A total of 52 participants (26 young healthy volunteers, and 26 elderly osteoarthritic patients, 15 men and 37 women (2 of them poor metabolizers of debrisoquine [CYP2D6]) completed the two-period, two-treatment, randomized, single-dose and 21-day, once-daily multiple-dose, cross-over study. Doses of oxaprozin and piroxicam were 1,200 mg once daily and 20 mg once daily, respectively. Mean single-dose kinetic parameters of oxaprozin versus piroxicam did not differ more than +/-14% (t1/2, 53.0 versus 57.4 hours; apparent oral clearance adjusted for 70-kg body weight [Clpo], 0.139 versus 0.121 L/hr; apparent volume of distribution adjusted for 70-kg body weight [Vd/F]; 10.2 L versus 9.13 L). Protein binding was plasma-concentration dependent with oxaprozin (range, 10-400 mg/L) but not with piroxicam (range, 1-30 mg/ L). Steady-state conditions were established within 3 days with oxaprozin but took almost 12 days with piroxicam. Compared with the single-dose values, steady-state Clpo (Clpo,ss) and Vd/F of total drug increased with oxaprozin by almost 127% but remained within +/-10% with piroxicam. Post-steady-state apparent t 1/2 of the total and unbound drugs of approximately 62 hours were similarly prolonged with piroxicam but differed substantially with oxaprozin (50.6 hours [total drug] versus 23.8 hours [unbound drug]). Single dose Clpo (Clpo,sd) values of both NSAIDs were significantly correlated in the study populations. With both NSAIDs, Clpo in the two poor metabolizers of debrisoquine was within +/-20% of mean values for the population. Clinically important age- and gender-dependent decreases were not observed in the weight-adjusted, Clpo,sd or Vd/F values of the total drug for either NSAID. Clearances of the two NSAIDs were significantly correlated, suggesting that a common P450 isozyme (most likely CYP2C9, in that piroxicam is a known substrate of this isozyme) may be at least partly involved in the oxidative metabolism of these NSAIDs.

Adult↗
PubMed1997

Collaborative use of informatics among hospitals to benchmark medication use processes.

BACKGROUND: In spring 1995 pharmacists representing each of the 23 member hospitals in Synernet, a hospital cooperative in Maine, decided to collaborate in developing a multihospital medication use evaluation (MUE) program. The committee set up task forces for adverse drug reaction reporting and prevention, MUE plans, and medication error reporting and prevention, for exploration of opportunities to eliminate duplication of efforts, compare performance, and share best practices. PLANNING THE PROGRAM: The members retained a consulting firm to manage the SynRx medication use program from conceptualization through implementation. Modules--on individual drug dosing, switching from intravenous to oral administration, pharmacists' clinical recommendations, and surgical antibiotic prophylaxis--were designed so that participants could adopt the entire plan as a turnkey procedure by inserting their hospital name in the appropriate blanks, modify it to more closely fit their own organizations, use portions of it for inclusion in their current plans, or not use it at all. The goal was to build in maximum flexibility to accommodate the variations in the participating hospital pharmacies and their respective hospitals. RESULTS: Early program benefits include improvements in medication event reporting, documentation of the measured aspects of medication use, delivery of care processes, and administrative efficiency. LESSONS LEARNED AND CONCLUSIONS: The participants, consultants, and programmers involved in the SynRx program learned firsthand the complexity and magnitude of hospital medication use processes. Yet it is possible to overcome the wide variability in systems among hospitals to create standards that allow for more meaningful comparisons of medication use.

Adverse Drug Reaction Reporting Systems↗
PubMed1997

Alcohol-history taking by nurses and doctors--how accurate are they really?

The aim of this study was to look at how nurses and doctors record alcohol histories on the patients under their care and the frequency and appropriateness of the way they use an alcohol withdrawal scale in the acute hospital setting. To achieve these aims patient records were audited and compared at two points in time, in 1992 and 1994. Results of the study showed that nurses and doctors took alcohol histories from patients on approximately three-quarters of occasions and that this level of recording has not changed over time. The adequacy of alcohol-history taking has, however, increased for both nurses and doctors since 1992. At that time, 71% of the alcohol histories taken by nurses and 74% of alcohol histories taken by doctors were judged to be adequate. By 1994, however, 79% of alcohol histories taken by nurses and 77% of histories by doctors were rated as adequate. The increase in the adequacy of history taking by nurses was significant (chi 2 = 5.05; d.f. = 1; P < 0.05) and the increase by doctors was not significant (chi 2 = 1.03; d.f. = 1; P > 0.05). These results are seen as being positively associated with the major governmental nursing initiative in New South Wales, Australia, the New South Wales Strategic Plan for the Nursing Management of Alcohol and Other Drugs.

Aged↗