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Biomedical subjects

C Barr

Publications and source records attributed to C Barr.

At least 19 recordsLinked to original sources
PubMed2001

Factors affecting reliability and confidence of DSM-III-R psychosis-related diagnosis.

The relationships between interrater diagnostic reliability, confidence in diagnosis, DSM-III-R criteria ambiguity and case report data quality were examined in 20 case vignettes describing psychosis-related symptomatology. Each of seven diagnosticians made DSM-III-R diagnoses and gave confidence ratings for those diagnoses, as well as ratings on quality of data presented and clarity of diagnostic criteria for each vignette. As hypothesized, confidence ratings significantly predicted interrater diagnostic agreement. Clarity of DSM-III-R criteria positively correlated with both interrater reliability and confidence. Case report data quality correlated with diagnostic confidence but, contrary to the authors' hypothesis, did not correlate with interrater agreement. The authors conclude that confidence ratings may be useful indices of diagnostic reliability among experienced clinicians and suggest that the case report method allows for reliable diagnoses to be made.

Adult↗
PubMed2000

Dopamine genes and ADHD.

Family, twin, and adoption studies have documented a strong genetic basis for ADHD/HKD, but these studies do not identify specific genes linked to the disorder. Molecular genetic studies can identify allelic variations of specific genes that are functionally associated with ADHD/HKD, and dopamine genes have been the initial candidates based on the site of action of the stimulants drugs, which for a half century have provided the primary pharmacological treatment for ADHD/HKD. Two candidate dopamine genes have been investigated and reported to be associated with ADHD/HKD: the dopamine transporter (DAT1) gene [Cook et al., American Journal of Human Genetics 1995;56:993-998, Gill et al., Molecular Psychiatry 1997;2:311-313] and the dopamine receptor D4 (DRD4) gene [LaHoste et al., Molecular Psychiatry 1996;1:121-124: Smalley et al., 1998;3:427-430; Swanson et al., Molecular Psychiatry 1998;3:38-41]. Speculative hypotheses [Swanson and Castellanos, NIH Consensus Development Conference: Diagnosis and Treatment of Attention Deficit Hyperactivity Disorder, November 1998. p. 37-42] have suggested that specific alleles of these dopamine genes may alter dopamine transmission in the neural networks implicated in ADHD/HKD (e.g. that the 10-repeat allele of the DAT1 gene may be associated with hyperactive re-uptake of dopamine or that the 7-repeat allele of the DRD4 gene may be associated with a subsensitive postsynaptic receptor). These and other variants of the dopamine hypothesis of ADHD will be discussed.

Alleles↗
PubMed2000

One-year follow-up of opiate injectors treated with oral methadone in a GP-centred programme.

AIMS: To examine changes in drug-related behaviour in opiate-dependent injectors treated with oral methadone, in a shared care scheme where consumption of the daily dose is usually supervised by a community pharmacist. DESIGN: One-year cohort study. SETTING: Recruitment from the main routes into methadone prescribing in Glasgow during 1996: General Practitioner Drug Misuse Clinic Scheme and the Drug Problem Service. PARTICIPANTS: Current opiate injectors entering methadone treatment. FINDINGS: Among the 204 injectors recruited, 148 (73%) were re-interviewed at 6 months and 118 (58%) at both 6 and 12 months. Twenty-nine per cent of the cohort remained continuously on methadone for 12 months. In that group, over the 12-month period, self-reported daily opiate injecting reduced from 78% to 2%; overdose in the previous 6 months from 24% to 2%; mean daily drug spend from 50 Pounds to 4 Pounds; and mean monthly number of acquisitive crimes reduced from 13 to three. Assuming participants lost to follow-up were unchanged, significant improvements in the total cohort were seen in daily opiate injecting (from 80% at recruitment to 43% at 12 months), overdose (from 27% to 15%), mean daily drug spend (from 63 Pounds to 38 Pounds) and mean monthly number of acquisitive crimes (from 18 to 11). Discontinuation of treatment was mainly due to imprisonment (39%) or sanctions by the prescriber (33%). CONCLUSION: Treatment of opiate-dependent drug injectors with methadone in a community-wide general practitioner-centred scheme, with supervised daily consumption, was associated with major beneficial change for a substantial proportion of patients.

Adult↗
PubMed1999

Genetic locus heterogeneity in Lafora's progressive myoclonus epilepsy.

In 1995, we mapped a gene for Lafora's progressive myoclonus epilepsy in chromosome 6q23-25. In 1997 and 1998, we reduced the size of the locus to 300 kb, and an international collaboration identified mutations in the protein tyrosine phosphatase gene. Here, we examine for heterogeneity through the admixture test in 22 families and estimate the proportion of linked families to be 75 to 85%. Extremely low posterior probabilities of linkage (Wi), exclusionary LOD scores, and haplotypes identify 4 families unlikely to be linked to chromosome 6q24.

Chromosomes, Human, Pair 6↗
PubMed1998

Directions of aetiologic research on attention deficit hyperactivity disorder.

OBJECTIVE: The aim of this paper is to review and integrate recent literature on aetiological factors that have been postulated for attention deficit hyperactivity disorder (ADHD). METHOD: Recent studies relating to perinatal brain damage, intra-uterine toxic effects, neurochemical, brain imaging and genetic studies are reviewed, and those considered most significant are discussed. Where possible, recent findings are integrated and directions of future research are suggested. Clinical implications are briefly discussed. RESULTS: Perinatal studies indicate that children with a birth weight under 750 g may be disadvantaged for attentional skills. Magnetic resonance imaging (MRI) and steady state visually evoked potential studies show differences in prefrontal, caudate and parietal areas in ADHD children, suggesting right hemispheric dysfunction. Functional MRI studies hold promise in further elucidating attentional systems in the central nervous system that are involved in ADHD. Genetic studies suggest genes related to dopaminergic systems may be important. CONCLUSIONS: Recent research on ADHD has made considerable advances, particularly in the areas of brain imaging and genetic studies. Genetic studies should provide further aetiological understandings of ADHD, leading to more targeted treatments.

Attention Deficit Disorder with Hyperactivity↗
PubMed1996

Laparoscopic hernia repair in Leicester General Hospital: a prospective audit of 94 patients.

Conventional hernia repair is effective in terms of cure but is associated with considerable postoperative pain and delay in return to normal activity. Laparoscopic repair has the potential to reduce pain and speed return to normal activity, but there have been few published reports of the outcome of this operation in the UK. We present a prospective audit of 94 patients who underwent laparoscopic repair. Of the 94 patients, 87 (92.6%) were male and 7 (7.4%) were female. Thirteen of the repairs were bilateral and 12 were recurrent. Two had to be converted to open repair. The mean operating time for unilateral repair was 56 min and for bilateral repair 98 min. Sixty-three patients (67%) were discharged within 24 h and 21 (22.4%) were discharged within 48 h. There were minor complications in 20 patients (21%), eight of whom (8.5%) developed a haematoma. The other minor complications included seromas (2), bruising at the site of the entry port (2), hyperaesthesia in the groin (2), port hernia (1), shoulder tip pain after surgery (3) and postoperative urinary retention (2). Nine (9.5%) patients claimed to have had no pain or discomfort at all; 35 (37.2%) were pain and discomfort free in 2 weeks. Thirty-two (34%) patients returned to normal activities in 2 weeks. With a median follow-up of 8 months 3 (3.2%) recurrences were noted. It is emphasised that this series represents a learning curve and that the operation is developmental. We are now restricting laparoscopic repair to recurrent and bilateral hernias where the technique offers particular advantages.

England↗
PubMed1994

The future research agenda. A view from the pharmaceutical industry.

As a responsible partner in healthcare systems, the pharmaceutical industry hopes to see a research agenda on pharmaceutical issues that will provide more information on trends in healthcare reform affecting medicines. Urgent questions include whether some forms of cost containment are harming innovation and the quality of care, and what constructive alternatives to policies such as reference pricing can the industry offer?

Drug Costs↗
PubMed1994

Laparoscopic cholecystectomy in Leicester: an audit of 555 patients.

Laparoscopic techniques have revolutionised the surgical approach to cholecystectomy, even though there have been no published randomised controlled trials to demonstrate the safety of this approach. We present an audit of 555 patients offered laparoscopic cholecystectomy. In all, 54 patients (9.7%) were converted to an open procedure. Peroperative cholangiography (POC) was attempted in 190 cases (34.2%) and achieved in 141 (25.4%). Major complications occurred in 26 cases (4.7%) including 5 (0.9%) deaths, two of whom had major pre-existing morbidity. There was one common bile duct (CBD) injury (0.18%). There were 30 patients (5.4%) found to have CBD stones, 27 of which were cleared at ERCP, and three converted to open exploration. Cholecystectomy by any route is a major operation and we conclude that careful case selection remains imperative. However, morbidity is favourable compared with open cholecystectomy, and comparable with other reports using the laparoscopic technique. Our experience of CBD injury (0.18%) is also acceptable compared with the risk of injury during open cholecystectomy. There were 312 patients (56.2%) who did not undergo perioperative CBD imaging with ERCP or POC and three of these developed early symptomatic retained stones. This group requires further follow-up.

Adolescent↗
PubMed1992

Periodontal changes by HIV serostatus in a cohort of homosexual and bisexual men.

UNLABELLED: These data represent 20 months of follow-up on 114 homo/bisexual men. Periodontal changes were analyzed in relation to HIV-1 serostatus, immune status, age and plaque. Gingival index (GI), plaque index (PI), and relative attachment levels recorded by the computerized Florida disk probe were performed every 4 months. A threshold of > or = 3.0 mm of relative attachment loss (RAL) was selected as a significant longitudinal change. RAL > or = 3 mm occurred 6.16 times (95% CI = 1.95, 19.40) more frequently among subjects with T4 counts < 200 compared to subjects with counts of 200 or more. Among older subjects (age > or = 35 years), the incidence (33%) of RAL > or = 3 mm was significantly higher (p = 0.004) in more immunosuppressed subjects (T4 < 200) compared to the incidence (5%) in less immunosuppressed subjects (T4 > or = 200); this association was not significant in younger subjects less than 35 years old (p = 0.55). In 78 subjects present at all follow-up visits, averaged GI increased and were significantly higher in the seropositive subjects compared to seronegative subjects, but, GI was not related to T4 cell counts within the seropositive group. Separate linear regression of GI by PI by HIV serostatus revealed a significantly higher slope in the seropositive group compared to the seronegative group (p = 0.04), suggesting greater sensitivity to plaque in the seropositive group. CONCLUSION: immunosuppression, especially in combination with older age, may be a risk factor for attachment loss, and HIV seropositivity, independent of T4 cell counts, may be a risk factor for gingival inflammation.

Adult↗
PubMed1991

Empowering middle managers in hospitals with team-based problem solving.

A team-oriented problem-solving procedure using management project teams was developed to improve quality of care and productivity in a private, nonprofit hospital. A focus group of managers developed the procedure, endorsed by top management. The work of four manager teams that followed the procedure saved the hospital more than $500,000.

Decision Making, Organizational↗
PubMed1991

Nondairy-creamer-induced kwashiorkor: 5-year follow-up.

Failure to thrive may not be a result of organ disease, physical abuse, or intentional neglect. We describe an infant who developed kwashiorkor with a high-fat, low-protein, nondairy coffee creamer diet. The elimination diet was administered on the advice of a family friend for a facial rash. The child presented at 10 months of age with decreased weight for height, rash, hepatomegaly, edema, hypoproteinemia, hypoalbuminemia, anemia, hypoglycemia, and evidence of hepatic sequestration of lipids. A rapid recovery of biochemical abnormalities was evident on reinstitution of a full diet. An intellectual assessment at age 5 years showed normal results.

Female↗
PubMed1989

Transforming growth factor alpha and its receptor in neural retina.

Transforming growth factor alpha (TGF-alpha) stimulates mitosis of many ectodermal cells but has not previously been studied for its role in neural tissues such as retina. We examined bovine retina for the presence of TGF-alpha mRNA, TGF-alpha protein and for the presence and location of the TGF-alpha/EGF receptor. Biochemical studies demonstrated a high level (770 fmol/mg protein) of specific, high affinity (Kd = 2 nM) TGF-alpha/EGF receptors in membrane homogenates of neural retina, but undetectable binding to homogenates of retinal pigment epithelium. Light microscopic autoradiograms of sections of neural retinal tissue incubated with 125I-EGF indicated that specific TGF-alpha/EGF receptors were present on one or more cell types of the retina with the exception of the outer segments of the photoreceptor cells. In addition, retinal cells appear to synthesize TGF-alpha since both mRNA for TGF-alpha and TGF-alpha protein (4.2 ng/mg protein) were detected in retinal extracts using cDNA hybridization and TGF-alpha RIA techniques. The role(s) of TGF-alpha and its receptor in retina is unknown, but it is possible that they interact via an autocrine/paracrine mechanism to influence retinal regeneration, proliferative retinopathies or neural transmission.

Animals↗
PubMed1987

Differential expression of the human thymosin-beta 4 gene in lymphocytes, macrophages, and granulocytes.

A cDNA clone encoding human thymosin-beta 4 was isolated from a cDNA library prepared from peripheral blood leukocytes of a patient with acute lymphocytic leukemia. This clone contained the entire coding sequence of 43 amino acid residues of thymosin-beta 4 and had an initiation codon and two termination codons. The amino acid and nucleotide sequences in the coding region were well conserved between rat and human. Nine of 132 nucleotides were different in the coding sequences (93% homology), but the deduced amino acid sequences were identical. No signal peptide was found in the deduced protein sequence. Human thymosin-beta 4 mRNA, approximately 830 nucleotides in length, was about 30 nucleotides larger than rat thymosin-beta 4 mRNA. Expression of the human thymosin-beta 4 gene in various primary myeloid and lymphoid malignant cells and in a few human hemopoietic cell lines was studied. Northern blot analyses of different neoplastic B lymphocytes revealed that steady state levels of thymosin-beta 4 mRNA varied as a function of differentiation stage. Thymosin-beta 4 mRNA levels were decreased in myeloma cells as are class II human leukocyte antigen, Fc receptor, and complement receptor, suggesting a relationship between thymosin-beta 4 and the immune response. Thymosin-beta 4 mRNA was more highly expressed in mature granulocytes than in immature blastic cells. Treatment of THP-1 cells, a human monocytic cell line, with recombinant human interferon-lambda reduced the levels of thymosin-beta 4 mRNA. Its level decreased after differentiation of THP-1 cells into Ia+ macrophages, but increased after differentiation of HL-60 cells into Ia- macrophages. The pattern of thymosin-beta 4 gene expression suggests that it may play a fundamental role in the host defense mechanism.

Amino Acid Sequence↗
PubMed1985

Oral manifestation of disseminated Mycobacterium avium intracellulare in a patient with AIDS.

The acquired immune deficiency syndrome (AIDS) is characterized by a selective suppression of the immune system that renders patients susceptible to infection by a variety of opportunistic organisms. Among these is Mycobacterium avium intracellulare. AIDS victims often have oral manifestations of Kaposi's sarcoma and candidiasis. This article reports an unusual oral presentation of disseminated infection with Mycobacterium avium intracellulare in a patient with AIDS.

Acquired Immunodeficiency Syndrome↗
PubMed1984

Phase-I study of intravenous modified lipid A.

Endotoxin and the lipid-A portion of the molecule have a variety of biological effects, including the induction of necrosis and regression of malignancy. To date extensive clinical trials of endotoxin as a potential therapeutic agent have been shunned due to the toxicity of the material. Several lipid-A analogues have been described which have reduced toxicity and retain antitumor activity. We have investigated in a phase-I trial the clinical toxicity and immunological effects of monophosphoryl lipid A prepared from Salmonella typhimurium and Salmonella minnesota. Patients entered on the study received IV monophosphoryl lipid A twice weekly for a total of 4 weeks. At least three patients were entered sequentially at each of the dose levels of 10, 25, 50, 100, and 250 micrograms/m2 body surface area. One patient was treated at the dose level of 500 micrograms/m2. The major clinical toxicity was fever, chills, and rigor, which occurred in over 50% of the treatments at doses of 250 micrograms/m2. Two instances of bronchospasm occurred in one patient who received 250 micrograms/m2. One patient received 500 micrograms/m2 and became hypotensive. Sequential clinical data showed no evidence of renal or hepatic toxicity. A transient decrease in the WBC and platelets occurred during the first 24 h after therapy. Immune function testing measured T cells, monocyte cytostasis, monocyte suppressor cell activity, and NK activity. These data suggested a shift in monocyte populations with activated cells moving into the tissue. Direct objective antitumor activity or necrosis was not observed in this group of patients. We conclude that monophosphoryl lipid A can be given to patients in a dose of up to 100 micrograms/m2 with acceptable toxicity. Its clinical activity as a single agent in combination with other immunomodulators remains to be demonstrated.

Animals↗