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Biomedical subjects

S Palmer

Publications and source records attributed to S Palmer.

At least 91 records · Page 5Linked to original sources
PubMed1998

Multiple concurrent reverse transcriptase and protease mutations and multidrug resistance of HIV-1 isolates from heavily treated patients.

BACKGROUND: Drug resistance of HIV-1 is an obstacle to the long-term efficacy of antiretroviral therapy. OBJECTIVE: To characterize reverse transcriptase and protease genes of multidrug-resistant HIV-1 isolates. DESIGN: Descriptive case series. SETTING: Academic medical center. PATIENTS: Four consecutive patients with HIV-1 infection were selected because they had previously received many antiretroviral drugs and had not achieved plasma HIV-1 RNA suppression despite treatment with several three-drug combinations. MEASUREMENTS: Reverse transcriptase sequencing, protease sequencing, and drug susceptibility testing of HIV-1. RESULTS: Isolates of HIV-1 from the four patients shared seven protease mutations and eight reverse transcriptase mutations. These mutations were present in biological clones and at three time points in three of the patients. Susceptibility testing showed high-level resistance (30-fold to >100-fold) to zidovudine, lamivudine, saquinavir, indinavir, and nelfinavir and lower-level resistance (3-fold to 5-fold) to didanosine, zalcitabine, and stavudine. CONCLUSIONS: Simultaneous resistance to almost all available antiretroviral drugs may occur in HIV-1. The concordance and persistence of mutations in drug-resistant HIV-1 isolates suggest that some combinations of reverse transcriptase and protease mutations give the virus a selective advantage in the presence of various drug combinations.

Acquired Immunodeficiency Syndrome↗
PubMed1998

Drug susceptibility of subtypes A,B,C,D, and E human immunodeficiency virus type 1 primary isolates.

We determined the susceptibility to antiviral drugs of clinical isolates of human immunodeficiency virus type 1 (HIV-1) subtypes A, B, C, D, and E. Isolates from treated and untreated patients were tested for sensitivity to zidovudine (ZDV), lamivudine (3TC), didanosine (ddI), nevirapine (NVP), foscarnet (PFA), and ritonavir (RNV). The susceptibility to these different drugs was broadly similar between the different subtypes of HIV-1. Isolates of subtype D showed a tendency toward slightly lower susceptibility to all the antiviral drugs, which could be related to the rapid growth characteristics of these isolates.

Anti-HIV Agents↗
PubMed1998

Successful allogeneic bone marrow transplant for chronic myeloid leukaemia despite previous interferon-induced cardiomyopathy.

We report a patient with CML who developed a reversible dilated cardiomyopathy with cardiac failure following 10 months of IFN therapy. Despite the previous cardiomyopathy, he tolerated subsequent allogeneic BMT without any adverse cardiac events. Reversible IFN-induced cardiomyopathy should not be considered a contraindication to bone marrow transplantation.

Adult↗
PubMed1998

The human FXY gene is located within Xp22.3: implications for evolution of the mammalian X chromosome.

It has been proposed that the pseudoautosomal region of mammals has evolved by sequential addition of autosomal material onto the X and Y chromosomes followed by movement of the pseudoautosomal boundary to create X-unique regions. We have previously described a gene, Fxy , that spans the pseudoautosomal boundary in mice such that the first three exons of the gene are located on the X chromosome, but the remainder of the gene is located on both X and Y chromosomes. Therefore, this gene might be in a state of transition between pseudoautosomal and X-unique locations. In support of this theory we show here that the human FXY gene is located in Xp22.3 in humans, proximal to the pseudoautosomal boundary.

Amino Acid Sequence↗
PubMed1998

Sudden death in psychiatric patients.

BACKGROUND: The present study investigated histories of prior psychiatric treatment in cases of sudden death reported to the coroner. METHODS: A matching survey linked the register of deaths reported to the coroner with a comprehensive statewide psychiatric case register covering both in-patient and community-based services. RESULTS: Sudden death was five times higher in people with histories of psychiatric contact. Suicide accounted for part of this excess mortality but deaths from natural causes and accidents were also elevated. Schizophrenic and affective disorders had similar suicide rates. Comorbid substance misuse doubled the risk of sudden death in affective and schizophrenic disorders. CONCLUSIONS: The rates of sudden death are sufficiently elevated to raise questions about current priorities in mental health care. There is a need both for greater attention to suicide risk, most notably among young people with schizophrenia, to the early detection of cardiovascular disorders and to the vigorous management of comorbid substance misuse.

Accidents↗
PubMed1998

Serious criminal offending and mental disorder. Case linkage study.

BACKGROUND: A relationship exists between mental disorder and offending behaviours but the nature and extent of the association remains in doubt. METHOD: Those convicted in the higher courts of Victoria between 1993 and 1995 had their psychiatric history explored by case linkage to a register listing virtually all contacts with the public psychiatric services. RESULTS: Prior psychiatric contact was found in 25% of offenders, but the personality disorder and substance misuse accounted for much of this relationship. Schizophrenia and affective disorders were also over-represented, particularly those with coexisting substance misuse. CONCLUSIONS: The increased offending in schizophrenia and affective illness is modest and may often be mediated by coexisting substance misuse. The risk of a serious crime being committed by someone with a major mental illness is small and does not justify subjecting them, as a group, to either increased institutional containment or greater coercion.

Age Distribution↗
PubMed1998

Testing the influence of the health belief model and a television program on nutrition behavior.

This study proposed to identify relevant factors of the health belief model (HBM) that provide motivation for people to engage in healthy dietary behavior. The impact of a TV program was also assessed using a longitudinal study with 300 participants and measuring the influence of path coefficients in the HBM that predicted salience, motivation, and healthy eating practices. Findings suggested that nutrition behavior was influenced by susceptibility and efficacy mediated through health motivation and salience. Program viewing boosted salience regardless of age, education, or household size by significantly increasing viewers' confidence in their nutrition knowledge base.

Journal Article↗
PubMed1998

Common errors and controversies in pharmacoeconomic analyses.

The need to demonstrate the cost effectiveness of healthcare interventions has led to a rapid increase in the use of economic tools within pharmaceutical evaluations. Pharmacoeconomics is employed at many stages of the evaluation process, helping to predict which products are likely to be economically viable at an early stage, and providing information to aid price and reimbursement negotiations as well as formulary and purchasing decisions in conjunction with phase III and IV clinical trials. The ability of economic evaluations to accurately determine the best use of society's scarce resources, however, is strongly influenced by the existence of areas of confusion, controversy and dispute which hinder the researcher at every step. A good economic evaluation requires a number of ingredients including: (i) relevant, good quality clinical data, raising issues of trial design, sample size and perspective; (ii) relevant costs and outcomes, measured, valued and discounted credibly and accurately; (iii) appropriate methods of data analysis (statistical, incremental and sensitivity); and, once the trial is over, (iv) presentation of the results in a way which maximises the generalisability of the results and, hence, the usefulness of the research. None of these areas are trouble-free but with understanding and openness, mistakes can be minimised.

Drug Costs↗
PubMed1997

A gene spans the pseudoautosomal boundary in mice.

The X and Y chromosomes of the mouse, like those of other mammals, are heteromorphic over most of their length, but at the distal ends of the chromosomes is a region of sequence identity, the pseudoautosomal region (PAR), where the chromosomes pair and recombine during male meiosis. The point at which the PAR diverges into X- and Y-specific sequences is called the pseudoautosomal boundary. We have completed a genomic walk from the X-specific Amelogenin gene to the PAR. Analysis of this region revealed that the pseudoautosomal boundary of mice is located within an intron of a transcribed gene that encodes a novel RING finger protein. The first three of the exons of the gene are located on the X chromosome whereas the 3' exons of the gene are located on both X and Y chromosomes. This unusual arrangement may indicate that the gene is in a state of transition from pseudoautosomal to X-unique and provides evidence for a process of attrition of the pseudoautosomal region on the Y chromosome.

Amelogenin↗
PubMed1997

Minnesota Multiphasic Personality Inventory profiles of Vietnam combat veterans with posttraumatic stress disorder and their children.

Forty children of 28 fathers who are Vietnam veterans with posttraumatic stress disorder (PTSD) completed the Minnesota Multiphasic Personality Inventory. Each of the fathers had at least one elevated clinical scale. Fathers averaged eight elevated clinical scales, and compared to more recent norms, fathers averaged seven elevated clinical scales. Seventy-eight percent of the children had at least one clinically elevated scale (averaging three elevated clinical scales). Compared to contemporary normal adolescents and adults, 65% of children had at least one clinically elevated scale (still averaging three elevated clinical scales). No consistent MMPI profile patterns emerged within or across the two groups. No gender differences were detected among child MMPI profiles. Forty percent of the children reported illegal drug use, and 35% reported behavior problems. Fifteen percent of children reported previous violent behavior. Eighty-three percent of the children reported elevated Cook-Medley hostility scores as compared to an age-matched national normative sample. Children with higher PK scores were also significantly more likely to report higher Cook-Medley hostility scores. Forty-five percent of children reported significant elevations on the PTSD/PK subscales.

Adolescent↗
PubMed1997

Aggressive surgical management of fibrolamellar hepatocellular carcinoma in puberty.

Extensive right hepatectomy and replacement of the invaded inferior vena cava were performed in a 14-year-old girl with fibrolamellar liver carcinoma. Despite the graft thrombosis the patient was discharged on the 50th post-operative day. After 3 years a solitary lung metastasis was resected and the patient remains with no sign of intra-abdominal or intrathoracic recurrence.

Adolescent↗
PubMed1997

The neuronal nitric oxide synthase inhibitor 7-nitroindazole also inhibits the monoamine oxidase-B-catalyzed oxidation of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine.

The neurodegenerative properties of the parkinsonian inducing agent 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) are thought to result from inhibition of complex I of the mitochondrial respiratory chain by the monoamine oxidase-B (MAO-B) generated 1-methyl-4-phenylpyridinium metabolite MPP+. Treatment with 7-nitroindazole (7-NI) protects rodents and baboons against MPTP's neurotoxicity, presumably as a consequence of its inhibition of neuronal nitric oxide synthase (nNOS). The results reported in the present communication, while not in conflict with the proposed role of nNOS, raise the possibility that the inhibition of MAO-B by 7-NI also may contribute to the observed neuroprotection.

Animals↗
PubMed1997

Increased activation of the combination of 3'-azido-3'-deoxythymidine and 2'-deoxy-3'-thiacytidine in the presence of hydroxyurea.

The intracellular phosphorylation of 3'-azido-3'-deoxythymidine and 2'-deoxy-3'-thiacytidine was increased two- to threefold by the addition of hydroxyurea (HU) to the single drugs or to the two drugs in combination. The ratios of drug triphosphate to competing cellular deoxynucleoside triphosphate were increased two- to threefold for both 3'-azido-3'-deoxythymidine and 2'-deoxy-3'-thiacytidine in the presence of HU. These HU-induced increases in 3'-azido-3'-deoxythymidine and 2'-deoxy-3'-thiacytidine metabolism may further enhance the anti-human immunodeficiency virus activity of these two drugs.

Anti-HIV Agents↗
PubMed1997

No evidence for uniparental disomy as a common cause of Sotos syndrome.

A number of rare diseases (including Sotos syndrome) of unknown aetiology, which occur mainly sporadically and with features of growth disorder and developmental delay, may be caused by imprinted genes and therefore be associated with UPD. Using 112 dinucleotide repeat DNA polymorphisms, we have examined parental inheritance of all autosome pairs, except chromosome 15, in 29 patients with Sotos syndrome. All informative cases showed biparental inheritance and no cases of UPD were found. We conclude that Sotos syndrome is either not caused by an imprinted gene or that UPD is rare or of a segmental form in its aetiology.

Chromosome Aberrations↗
PubMed1997

Differential effects of the Ca2+ sensitizers caffeine and CGP 48506 on the relaxation rate of rat skinned cardiac trabeculae.

During heart failure, force production by the heart decreases. This may be overcome by Ca2+-sensitizing drugs, which increase myofibril Ca2+ sensitivity without necessarily altering intracellular Ca2+ concentration. However, Ca2+ sensitizers slow the relaxation of intact cardiac muscle. We used diazo-2, a caged chelator of Ca2+, to study the effects of the Ca2+ sensitizers caffeine and CGP 48506 on the intrinsic relaxation rate of cardiac myofibrils. Trabeculae from rat right ventricles were skinned by 1% Triton X-100 and were activated in a 10-microL bath. In steady state experiments, CGP 48506 (10 micromol/L) shifted the force-pCa curve leftward by 0.41+/-0.03 pCa units (mean+/-SEM, n=6). An identical shift was induced by caffeine (20 mmol/L). Photolysis of diazo-2 by a flash of light (160 mJ, 310 to 400 nm) caused an immediate decrease in Ca2+-activated force produced by the trabeculae. Relaxation was fitted by a double-exponential decay, and the rate constants were found to be independent of force and preflash Ca2+ concentration. The initial fast rate, corresponding to myofibrillar relaxation, was increased from 17.3+/-2.0 to 30.9+/-3.7 s(-1) (n=4) by caffeine but was unaffected by CGP 48506 (16.6+/-1.7 and 14.4+/-2.3 s(-1) in the absence and presence of drug, respectively; n=5). Thus, myofibril relaxation need not be slowed by Ca2+-sensitizing agents but can even be accelerated. Despite similarities in their effects on myofibril Ca2+ sensitivity, caffeine and CGP 48506 affect the myofibrils at least partly via different mechanisms.

Animals↗
PubMed1997

The chromosome 6 sequencing project at the Sanger Centre.

Chromosome 6 is probably best known for encoding the major histocompatibility complex (MHC) which is essential to the human immune response. In addition, it has been shown to be associated with many diseases such Schizophrenia, Diabetes, Arthritis, Haemochromatosis, Narcolepsy, Epilepsy, Retinitis Pigmentosa, Deafness, Ovarian Cancer, and many more. Chromosome 6 is about 180 Mb in size and is estimated to encode around 3500 genes of which only about 10% are currently known. It is our aim to map, sequence and annotate the entire chromosome in close collaboration with the chromosome 6 community.

Chromosomes, Human, Pair 6↗
PubMed1997

"Community health care: serving Colorado's uninsured"--a health policy legislative proposal.

The article presents a hypothetical legislative proposal titled "Community Health Care: Serving the Uninsured." Briefly stated, the purpose of this legislation is to encourage public and private initiatives to provide health care for the uninsured, the indigent, and the underinsured citizens of Colorado. Lessons learned from this project can facilitate APNs' understanding of the issues surrounding the development of health policy.

Colorado↗