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Biomedical subjects

J Holmes

Publications and source records attributed to J Holmes.

At least 37 records · Page 2Linked to original sources

Follicle-stimulating hormone or human menopausal gonadotropin for ovarian stimulation in in vitro fertilization cycles: a meta-analysis.

OBJECTIVE: To reanalyze the results of using FSH alone and hMG during IVF treatment, taking into account the different protocols of administration of superactive GnRH agonist analogs. DESIGN: Meta-analysis. SETTING: The London Women's Clinic. PATIENT(S): Women undergoing IVF treatment. INTERVENTION(S): A meta-analysis of published randomized controlled trials from 1985 to 1999 of the use of FSH versus hMG for ovarian stimulation during IVF treatment. The common Peto odds ratio was calculated with use of a fixed effect model. The overall log odds ratio was estimated after demonstrating the consistency or homogeneity of the study results. MAIN OUTCOME MEASURE(S): Clinical pregnancy rate per cycle of IVF. RESULT(S): The results suggested that in the "long and short GnRH agonists protocol" of IVF, FSH, and hMG were equally effective in achieving ovarian stimulation, and there were no differences in the clinical pregnancy rates per cycle of IVF. However, in protocols where no pituitary desensitization was used, FSH alone was more efficacious. CONCLUSION(S): The optimum choice of gonadotropin preparation for ovarian stimulation during IVF treatment is influenced by the regimen of pituitary desensitization used. The optimum gonadotropin to be used when GnRH antagonists are used has yet to be determined.

Clinical Protocols↗

Psychiatric illness predicts poor outcome after surgery for hip fracture: a prospective cohort study.

BACKGROUND: Hip fracture is common in the elderly. Previous studies suggest that psychiatric illness is common and predicts poor outcome, but have methodological weaknesses. Further studies are required to address this important issue. METHODS: We prospectively recruited 731 elderly participants with hip fracture in two Leeds hospitals. Psychiatric diagnosis was made within 5 days of surgery using the Geriatric Mental State schedule and other standardized instruments, and data on confounding factors was collected. Main study outcomes were length of hospital stay, and mortality over 6 months after fracture. RESULTS: Fifty-five per cent of participants had cognitive impairment (dementia in 40% and delirium in 15%), 13% had a depressive disorder, 2% had alcohol misuse and 2% had other psychiatric diagnoses. Participants were likely to remain in hospital longer if they suffered from dementia, delirium or depression. The relative risks of mortality over 6 months after hip fracture were increased in dementia and delirium, but not in depression. CONCLUSIONS: Psychiatric illness is common after hip fracture, and has significant effects on important outcomes. This suggests a need for randomized, controlled trials of psychiatric interventions in the elderly hip fracture population.

Aged↗

A family-based and case-control association study of the dopamine D4 receptor gene and dopamine transporter gene in attention deficit hyperactivity disorder.

Attention deficit hyperactivity disorder (ADHD) is a highly heritable psychiatric condition of early childhood onset characterised by marked inattention, hyperactivity and impulsiveness. Molecular genetic investigations of ADHD have found positive associations with the 480-bp allele of a VNTR situated in the 3' untranslated region of DAT1 and allele 7 of a VNTR in exon 3 of DRD4. A number of independent studies have attempted to replicate these findings but the results have been inconsistent. We used both family-based and case control approaches to examine these polymorphisms in a sample of 137 children diagnosed with ICD-10, DSM-IV or DSM-III-R ADHD. We found no evidence of association with the DAT1 polymorphism, despite a sample size that has up to 80% power to detect a previously reported effect size. We observed a significant increase in the DRD4 7 repeat allele amongst ADHD probands (21.7%) and their parents (18.9% in mothers, 22.3% in fathers), compared to ethnically matched controls (12.8%). However TDT analysis showed no preferential transmission of allele 7 to ADHD probands.

Adult↗

The links between joint damage and disability in rheumatoid arthritis.

OBJECTIVE: The characteristic joint damage and disability of rheumatoid arthritis (RA) increase slowly over 10-20 yr. Although it is generally believed that persisting inflammatory synovitis causes joint damage and subsequent disability, the strength of their relationship has not been systematically evaluated. This review describes their progression and interrelationship in treated RA. METHODS: MEDLINE and Current Contents databases were searched for the combined terms of rheumatoid arthritis AND X-rays, Health Assessment Questionnaire, slow-acting anti-rheumatic drugs and all identifiable synonyms. This search identified 1303 articles and from these we evaluated in detail 23 reports on the progression of joint damage, 12 reports on the progression of disability and 25 reports dealing with their interrelationship. Additional information was obtained from four data sets comprising 725 RA patients studied cross-sectionally and 33-126 cases followed prospectively for 1-5 yr. X-ray damage was primarily assessed by Larsen and Sharp indices, and disability by the Health Assessment Questionnaire (HAQ). RESULTS: Joint damage and disability both increase throughout the duration of RA. Although disability (HAQ score) is correlated with disease duration (correlation coefficients between 0.27 and 0.30), the link between X-ray damage and disability is stronger (correlation coefficients between 0.30 and 0.70). In the earliest phases of RA, X-ray damage and HAQ scores are not related. By 5-8 yr, there are significant correlations with correlation coefficients between 0.30 and 0.50. In late RA (>8 yr), most studies show highly significant correlations between 0.30 and 0.70. CONCLUSIONS: Joint damage progresses constantly over the first 20 yr of RA. It accounts for approximately 25% of disability in established RA. The link between damage and disability is strongest in late (>8 yr) RA. However, avoiding or reducing joint damage in both early and established/late RA is likely to maintain function.

Arthritis, Rheumatoid↗

Use of out-of-hospital interventions for the pediatric patient in an urban emergency medical services system.

OBJECTIVE: To determine appropriateness of out-of-hospital interventions by emergency medical services (EMS) personnel on children with respiratory illnesses. METHODS: A retrospective, cross-sectional study was performed on a random sample of 304 children transported by an urban EMS system during 1994. Data were abstracted from EMScan (a computerized database of all EMS dispatches) and the EMS narrative records. Appropriate utilization of interventions was determined by comparison with the standard EMS protocol for respiratory complaints in this system. An assessment of whether interventions were inappropriately underutilized or inappropriately overutilized was made. Effect of severity of illness, patient age, transport times, and use of medical command on the use of interventions was evaluated. RESULTS: Two hundred three patients (67%) were classified as having respiratory distress. Overall, 56% of the patients received appropriate interventions, 39% received one or two inappropriate interventions, and 5% received three or more inappropriate interventions. Rates of inappropriate utilization with 95% CI for each intervention were: oxygen 16% (95% CI = 12 to 20), assisted ventilation 2% (95% CI = 0.5 to 4), medication use 9% (95% CI = 6 to 13), vascular access 11% (95% CI = 7 to 14), phlebotomy 9% (95% CI = 6 to 13), and cardiac monitoring 18% (95% CI = 14 to 22). Oxygen and medications were underutilized (p < 0.005), whereas vascular access, cardiac monitoring, and phlebotomy were overutilized (p < 0.005). Online medical command (used in 9% of transports) improved appropriate use of vascular access [OR 8.3 (95% CI = 3 to 25) (p < 0.001)] and cardiac monitoring [OR = 3 (95% CI = 1 to 8) (p < 0.05)]. CONCLUSIONS: Emergency medical services personnel underutilized oxygen and medications and overutilized vascular access, phlebotomy, and cardiac monitoring in children with respiratory illness in this urban setting. Increasing patient age, transport times, and illness severity tend to increase the use of certain interventions, while contact with online medical direction seems to improve appropriate use of interventions.

Adolescent↗

The burden of personality disorder: a district-based survey.

Patients with a clinical diagnosis of personality disorder (PD) often suffer prolonged distress. They are a considerable burden on psychiatric services and they are experienced as difficult to manage by their keyworkers. This paper describes the creation of a community-based case register of patients suffering from PD. It explores the relationship between psychological distress, personality dysfunction, service utilisation and keyworker stress. Mental Health workers were asked to identify those patients on their caseload whose primary problem was PD. This list provided the basis for the case register. Patients completed the revised Personality Diagnostic Questionnaire IV (PDQ 4); the General Health Questionnaire (GHQ); and the Beck Depression Inventory - 21 item (BDI). A brief, semi-structured interview was conducted by Community Psychiatric Nurses to estimate service utilisation and keyworker stress. The mean GHQ was 14.58; the mean BDI score was 28.22. The mean number of PDs per patient was 4.5. One quarter of patients (21/80) had been admitted at least once to a psychiatric ward in the previous year and 17% (13/80) had presented to casualty at least once in the previous two months. 57% of the patients had weekly or more contacts with a helping agency. The number of PD diagnoses per patient as measured by the PDQ 4 was not found to be predictive of stress experienced by CPNs, whereas high BDI and GHQ scores were strongly correlated. Similarly, the number of admissions to a psychiatric ward was associated with high BDI and GHQ scores but not with number of PDs per patient. It is feasible to establish a case register of all patients in the district with PD. There are high levels of depression and distress amongst patients with PD being treated as outpatients. Service utilisation and keyworker stress are not predicted by number of PDs per patient but are strongly associated with distress as measured by the GHQ and BDI. The implications of these findings are discussed.

Adolescent↗

Determination of platinum in rat dorsal root ganglion using ICP-MS.

This study evaluated the performance of inductively coupled plasma mass spectrometry for the determination of platinum (Pt) in rat dorsal root ganglion. The method detection limit was found to be 0.008 ng/mL of Pt, which corresponds to 4 pg of Pt per milligram of ganglia. The standard deviations in the tissue matrix were 5.7% or better and minimum matrix effect was observed. Compared to indium, the use of iridium or a combination of iridium and bismuth as internal standard(s) provided more accurate measurement. The Pt in the tissue digestate was stable for a minimum of 46 d at levels above 0.05 ng/mL. Flow injection analysis using undiluted digestates resulted in approximately 20% signal enhancement. Internal standard correction was necessary to obtain accurate results. The method was used in initial studies in which rats were dosed with cisplatin and has shown that Pt accumulates and persists in dorsal rat ganglion following treatment.

Animals↗

Autologous haematopoietic stem cell transplants for autoimmune disease--feasibility and transplant-related mortality. Autoimmune Disease and Lymphoma Working Parties of the European Group for Blood and Marrow Transplantation, the European League Against Rheumatism and the International Stem Cell Project for Autoimmune Disease.

This ongoing multicentre prospective phase I/II trial enrolled 74 consecutive patients from 22 centres worldwide with severe autoimmune disease, 35 with rheumatological disorders, 31 with neurological, five with haematological and three with vasculitides. They were treated with autologous peripheral blood or bone marrow transplants according to predetermined criteria. Two patients died after mobilisation before transplant. Seventy-two patients were given 73 transplants, seven bone marrow, and 66 mobilised peripheral blood stem cell transplants. The graft was manipulated to remove T and/or B cells in 43 cases. All 73 transplants engrafted. Five patients died of transplant-related complications: two from bleeding, three from infections. Two patients died of progressive disease. The transplant-related mortality at 1 year of 9% (1-17%; 95% CI) is comparable to the transplant-related mortality of 6% (3-9%; 95% CI) in patients transplanted during the same period in Europe for non-Hodgkin's lymphoma in sensitive relapse (P = 0.39). Sixty patients are evaluable for response, 40 patients (65%) showed some improvement in their disease. Haematopoietic stem cell transplants are feasible for patients with severe refractory autoimmune disease. Transplant-related mortality is comparable to results in patients with non-Hodgkin's lymphoma in responsive relapse. Two-thirds of the patients show at least some response. These preliminary data are promising. Although associated with considerable risk, randomised trials comparing autologous stem cell transplants to conventional therapy are warranted.

Adolescent↗

Ghosts in the consulting room. An attachment perspective on intergenerational transmission.

Intergenerational transmission of attachment patterns--Selma Fraiberg's classic account of 'ghosts in the nursery'--is one of the basic assumptions of attachment theory, amply confirmed by empirical studies which link narrative style in parents (as measured by the Adult Attachment Interview) with security or insecurity of attachment in infants, as measured by the Strange Situation test. This paper argues that a 'sense of self' and Fonagy's 'reflective function', vital to healthy psychic functioning, arise out of early parental handling, and particularly out of the kind of mirroring experiences hypothesized by Winnicott and elaborated by Gergely and Watson, in which the parent defines her or himself as a 'mirror', by 'marking' (exaggeration of response) and 'contingency' (scrupulously following the child's lead in interactive play). The paper argues that in psychotherapy a similar responsiveness on the part of the therapist is called for. Dealing with 'ghosts in the consulting room' (i.e. transference) is a three phase project comprising (a) calling up the ghosts, through the development of narrative function (b) attempts to expel the ghosts through anger at environmental failure and differentiation of the self from its past (c) coming to terms with ghosts, thus seeing that one's parents were themselves products of intergenerational transmission. An illustrative case is presented.

Adult↗

Genetic basis of attention deficit and hyperactivity.

BACKGROUND: Hyperkinetic disorder or attention-deficit hyperactivity disorder (ADHD) is an important clinical condition. AIMS: The research evidence for a genetic contribution to ADHD is reviewed. METHOD: Measurement of the phenotype, the extent to which attention deficit and hyperactivity are heritable and molecular genetic findings are discussed. Future research directions are also considered. RESULTS: ADHD is a familial disorder. Available adoption evidence suggests genetic influences are important. Twin studies have primarily focused on trait measures which have consistently been found to be highly heritable Molecular genetic studies of clinical disorder so far have suggested the involvement of the dopamine DRD-4 receptor gene and dopamine transporter gene (DAT1). However, these findings await further replication. CONCLUSIONS: Advances in psychiatric genetics and current research interest in the genetics of ADHD should improve our understanding of aetiological factors and have an impact on treatment.

Attention Deficit Disorder with Hyperactivity↗

Comparative neurotoxicity of oxaliplatin, cisplatin, and ormaplatin in a Wistar rat model.

Oxaliplatin (4 mg/kg), cisplatin (2 mg/kg with 20 mg/kg mannitol) and ormaplatin (2 mg/kg) were administered i.p. twice weekly for 4.5 weeks. Lactose injections (0.9%) were used as a control for oxaliplatin and 0.9% saline injections were used as a control for cisplatin and ormaplatin. Morphometric changes to dorsal root ganglia L4-L6 were quantitated as a measure of neurotoxicity. Drug treatment resulted in a decrease in cell and nuclear area and an increase in the percentage of cells with eccentric nucleoli for neuronal cell bodies in the DRG. Immediately following treatment the order of morphometric changes was ormaplatin > cisplatin > or = oxaliplatin. The accumulation of platinum in the DRG was measured by inductively coupled plasma mass spectrometry. The order of accumulation was cisplatin > oxaliplatin > ormaplatin. Following an 8-week recovery period the order of morphometric changes to the DRG was ormaplatin approximately equal to oxaliplatin > cisplatin. This correlated with a greater retention of platinum by the DRG for ormaplatin and oxaliplatin than for cisplatin. The results suggest that ormaplatin is uniquely neurotoxic immediately following treatment in the Wistar rat model. However, following an 8-week recovery period both ormaplatin and oxaliplatin are more neurotoxic than cisplatin and this neurotoxicity correlates with a greater retention of platinum by the DRG.

Animals↗

Recovery of spermatogenesis following bone marrow transplantation.

Preparative regimens used in bone marrow transplantation usually result in impairment of male fertility. Although recovery of fertility is more likely after chemotherapy-based regimens, this is a rare occurrence after TBI containing regimens. We undertook a cross-sectional study of recovery of spermatogenesis in men who had undergone allogeneic and autologous marrow or peripheral stem cell transplant between 1984 and 1995. We identified six out of 42 patients eligible for analysis to have either recovered fertility or spermatogenesis. Seminal fluid analysis showed that four out of 25 patients recovered sperm counts. This has important implications for patient counselling, post-transplant follow-up and contraceptive advice.

Adult↗

The role of disclosure in coping with HIV infection.

A qualitative investigation was conducted to explore the role of disclosure in HIV infection. Forty homosexual and bisexual men completed a short demographic questionnaire and participated in a one-to-one, semi-structured interview. The interview was designed to address a variety of personal, interpersonal and organizational issues related to their HIV status and participants were invited to talk about their personal experiences from immediately prior to their diagnosis to the time of the interview. The results from the interviews are presented in three sections: immediately post-diagnosis, asymptomatic phase and symptomatic/AIDS phases. The data revealed that disclosing one's HIV status was an acute and recurrent stressor. Immediately post-diagnosis, individuals were more likely to adopt a policy of non-disclosure and this provided them with an opportunity to come to terms with their diagnosis before having to contend with the reactions of others. After this phase, there was evidence that individuals increasingly used disclosure as a mechanism for coping with the disease. Disclosure of one's status was used to increase both practical and emotional support, share responsibility for sex and to facilitate self-acceptance of one's condition. The results from this investigation revealed that disclosure has a dual role in HIV infection acting as both a stressor and a mechanism by which individuals contend with their infection.

Acquired Immunodeficiency Syndrome↗