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Biomedical subjects

A Hill

Publications and source records attributed to A Hill.

At least 127 records · Page 7Linked to original sources
PubMed1997

Tuberculosis in National Health Service hospital staff in the west Midlands region of England, 1992-5.

BACKGROUND: This study was designed to assess the current incidence of tuberculosis (TB) in National Health Service hospital staff in the West Midlands region of England and to evaluate the effectiveness of occupational health screening and surveillance procedures. METHODS: A four year prospective study (1992-5) was carried out with case ascertainment through occupational health departments and the Midlands Thoracic Society registry of rare respiratory diseases. RESULTS: No case was known to an occupational health department that was not notified by the registry and, in addition, the registry yielded a further six cases. There were 26 cases of active TB, of which 24 presented with symptoms and 12 had no pre-employment screening. All except one doctor were foreign born--mainly from the Indian subcontinent (ISC)--and of recent UK entry, whilst all except one nurse were white females. The following are annual TB incidences per 10(4) (95% confidence interval): ISC and non-white doctors 17.0 (7.8 to 26.2), not significantly greater than in the local ISC and non-white social class 1 working age population (11.8 (8.5 to 15.1)); white nurses 0.6 (0.2 to 1.0), significantly greater (p < 0.05) than that of white women in the local social class 2 working age population (0.2 (0.1 to 0.3)); others (mortuary attendant, physiotherapist, radiographer and theatre technician) 1.0 (0.02 to 2.0), not significantly greater than in the local social class 2 working age population (0.6 (0.5 to 0.7)). CONCLUSIONS: Case ascertainment via the registry was complete. Most cases of TB were in nurses and doctors, more commonly in doctors. However, all but one of the doctors were foreign born and probably had reactivation of infection acquired abroad rather than infection occupationally acquired in the UK. All but one of the nurses, however, were UK born and may have had occupationally acquired disease, their incidence being higher than in the community. As most cases present with symptoms, there needs to be continued emphasis on prompt reporting of suspicious symptoms both before and during employment, and pre-employment BCG vaccination where appropriate.

Adult↗
PubMed1997

Randomized trial comparing epirubicin, cisplatin, and fluorouracil versus fluorouracil, doxorubicin, and methotrexate in advanced esophagogastric cancer.

PURPOSE: We report the results of a prospectively randomized study that compared the combination of epirubicin, cisplatin, and protracted venous infusion fluorouracil (5-FU) (ECF regimen) with the standard combination of 5-FU, doxorubicin, and methotrexate (FAMTX) in previously untreated patients with advanced esophagogastric cancer. PATIENTS AND METHODS: Two hundred seventy-four patients with adenocarcinoma or undifferentiated carcinoma were randomized and analyzed for survival, tumor response, toxicity, and quality of life (QL). RESULTS: The overall response rate was 45% (95% confidence interval [CI], 36% to 54%) with ECF and 21% (95% CI, 13% to 29%) with FAMTX (P = .0002). Toxicity was tolerable and there were only three toxic deaths. The FAMTX regimen caused more hematologic toxicity and serious infections, but ECF caused more emesis and alopecia. The median survival duration was 8.9 months with ECF and 5.7 months with FAMTX (P = .0009); at 1 year, 36% (95% CI, 27% to 45%) of ECF and 21% (95% CI, 14% to 29%) of FAMTX patients were alive. The median failure-free survival duration was 7.4 months with ECF and 3.4 months with FAMTX (P = .00006). The global QL scores were better for ECF at 24 weeks, but the remaining QL data showed no differences between either arm of the study. Hospital-based cost analysis on a subset of patients was similar for each arm and translated into an increment cost of $975 per life-year gained. CONCLUSION: The ECF regimen results in a survival and response advantage, tolerable toxicity, better QL and cost-effectiveness compared with FAMTX chemotherapy. This regimen should now be considered the standard treatment for advanced esophagogastric cancer.

Adenocarcinoma↗
PubMed1997

Development of a screening questionnaire for the general hospital and general practices.

The purpose of this study was to develop a sensitive as well as brief screening questionnaire by combining the well-known instruments CAGE and the Michigan Alcoholism Screening Test (MAST) in detecting patients with alcohol dependence or abuse in general hospitals and general practices. The number of items was reduced by means of logistic regression and item analysis based on data of 1,167 consecutive admissions of a general hospital who completed both questionnaires. Further data were derived from a sample of 774 patients from 10 randomly selected general practices. A solution with nine items was validated in a second sample of 436 hospital inpatients. In all three samples, cases screening positive were interviewed using the Schedules for Clinical Assessment in Neuropsychiatry to provide ICD-10 and DSM-III-R or DSM-IV diagnosis. In addition, 103 subjects with negative screening results were interviewed in the second general hospital sample. On grounds of the data of all three samples, a solution of seven items was chosen. This instrument comprises two CAGE and five MAST questions (Leubeck Alcohol Dependence and Abuse Screening Test; LAST) and was significantly higher in sensitivity than CAGE and SMAST. Data were robust in all three samples. It is concluded that the LAST is an optimized instrument for use in general hospital and general practice.

Adolescent↗
PubMed1997

Intraventricular hemorrhage and posthemorrhagic hydrocephalus. Current and potential future interventions.

Enhanced survival of very premature infants may be regarded as the most striking demonstration of the major improvements in perinatal medicine during the last two decades. This article discusses recent perinatal interventions in the context of the pathogenesis and know risk factors for intraventricular hemorrhage (IVH). In addition, controversies related to the evolution and management of posthemorrhagic hyrdocephalus (PHH) are examined, and current concepts concerning potential brain injury to PHH are reviewed.

Brain Diseases↗
PubMed1996

A conserved domain of the viviparous-1 gene product enhances the DNA binding activity of the bZIP protein EmBP-1 and other transcription factors.

The maize VP1 protein is a seed-specific regulator of gene expression that effects the expression of a subset of abscisic acid (ABA)-regulated genes that are expressed during the maturation program of the seed. In addition, VP1 has pleiotropic effects on seed development that are not related to ABA. In transient expression assays, VP1 has been shown to transactivate gene expression through at least two distinct promoter elements: the G boxes from the ABA-inducible wheat Em gene and the SphI box from the maize C1 gene. We have investigated how VP1 can transactivate gene expression through diverse promoter elements by analyzing its association in vitro with EmBP-1, a factor that binds the Em promoter. We demonstrate that VP1 can greatly enhance the DNA binding activity of EmBP-1 in a gel retardation assay. This enhancing activity has also been observed on transcription factors as diverse as Opaque-2, Max, Sp1, and NF-kappaB. Deletion of a small but highly conserved region (BR2) in VP1 eliminates the enhancement in vitro as well as the ability of VP1 to transactivate Em gene expression in a transient expression assay. A 40-amino acid fragment from VP1 sandwiched between the maltose-binding protein and LacZ can confer the enhancement function to this fusion protein in vitro. A weak and relatively nonspecific interaction between BR2 and DNA is demonstrated by UV cross-linking. The in vitro properties we observe for VP1 might explain the regulatory effects of VP1 on a diverse set of genes and why mutations in the vp1 locus have pleiotropic effects.

Base Sequence↗
PubMed1996

Changes in plasma HIV-1 RNA and CD4+ lymphocyte counts and the risk of progression to AIDS. Veterans Affairs Cooperative Study Group on AIDS.

BACKGROUND: Clinical trials of antiretroviral drugs can take years to complete because the outcomes measured are progression to the acquired immunodeficiency syndrome (AIDS) or death. Trials could be accelerated by the use of end points such as changes in CD4+ lymphocyte counts and plasma levels of human immunodeficiency virus type 1 (HIV-1) RNA and beta 2-microglobulin, but there is uncertainty about whether these surrogate measures are valid predictors of disease progression. METHODS: We analyzed data from the Veterans Affairs Cooperative Study on AIDS, which compared immediate with deferred zidovudine therapy. Patients' plasma levels of HIV-1 RNA and beta 2-microglobulin were measured in stored plasma. RESULTS: Among the 129 patients in the immediate-treatment group, 34 had disease that progressed to AIDS, as compared with 57 of the 141 patients in the deferred-treatment group (P = 0.03). Progression to AIDS correlated strongly with base-line CD4+ lymphocyte counts (P = 0.001) and plasma levels of HIV-1 RNA (P < 0.001), but not with base-line levels of beta 2-microglobulin (P = 0.14). A decrease of at least 75 percent in the plasma level of HIV-1 RNA over the first six months of zidovudine therapy accounted for 59 percent of the benefit of treatment, defined as the absence of progression to AIDS (95 percent confidence interval, 13 to 112 percent). Plasma beta 2-microglobulin levels and CD4+ lymphocyte counts explained less of the effect of treatment. A 75 percent decrease in the plasma HIV-1 RNA level plus a 10 percent increase in the CD4+ lymphocyte count could explain 79 percent of the treatment effect (95 percent confidence interval, 27 to 145 percent). CONCLUSIONS: Treatment-induced changes in the plasma HIV-1 RNA level and the CD4+ lymphocyte count, taken together, are valid predictors of the clinical progression of HIV-related disease and can be used to assess the efficacy of zidovudine and possibly other antiretroviral drugs as well.

Acquired Immunodeficiency Syndrome↗
PubMed1996

Sonohysterographic imaging of the endometrial cavity.

Vaginal ultrasound is the most effective method of imaging the contents of the true pelvis in the female. Saline influsion sonohysterography (SIS) is a simple refinement of the standard vaginal sonographic exam. Here, we briefly describe and demonstrate our use of this latter technique.

Endometrial Neoplasms↗
PubMed1996

Fluorescent multiplex microsatellites used to define haplotypes associated with 75 CFTR mutations from the UK on 437 CF chromosomes.

The cystic fibrosis (CF) transmembrane conductance regulator (CFTR) gene contains three highly informative microsatellites: IVS8CA, IVS17bTA, and IVS17bCA. Their analysis improves prenatal/ carrier diagnosis and generates haplotypes from CF chromosomes that are strongly associated with specific mutations. Microsatellite haplotypes were defined for 75 CFTR mutations carried on 437 CF chromosomes (220 for delta F508, 217 for other mutations) from Northern Ireland and three English regions: the North-West, East Anglia, and the South. Fluorescently labelled microsatellites were amplified in a triplex PCR reaction and typed using an ABI 373A fluorescent fragment analyser. These mutations cover all the common and most of the rare CF defects found in the UK, and their corresponding haplotypes and geographic region are tabulated here. Ancient mutations, delta F508, G542X, N1303K, were associated with several related haplotypes due to slippage during replication, whereas other common mutations were associated with the one respective haplotype (e.g., G551D and R560T with 16-7-17, R117H with 16-30-13, 621 + 1G > T with 21-31-13, 3659delC with 16-35-13). This simple, fast, and automated method for fluorescent typing of these haplotypes will help to direct mutation screening for uncharacterised CF chromosomes.

Chromosomes, Human↗
PubMed1996

Pain memories in phantom limbs: a case study.

Pain experienced in a limb prior to amputation may influence the course of phantom limb pain many months later. Katz and Melzack (1990) found that 42% of their sample reported a 'somatosensory pain memory' which resembled the quality and location of a painful, or non-painful pre-amputation sensation. For many amputees, pain memories are vivid experiences which incorporate both emotional and sensory aspects of the pre-amputation pain (Katz 1992). Katz and Melzack (1990) suggest that sensory input will 'trigger' somatosensory pain memories while the affective component of a pain memory is generated by the intensity, quality and location of the current experience of phantom limb pain. The present case study used a diary design to examine whether 'triggers' could be identified for somatosensory pain memories. Over a 9-month period, the patient reported daily experience of ongoing phantom limb pain, generally confined to the distal part of the limb, and 5 episodes of injury-related phantom limb pain, primarily experienced in the calf of the missing limb. A 'trigger' was identified for each of the episodes of injury-related phantom limb pain, and a significant finding in this study was that two episodes of injury-related phantom limb pain were associated with cognitive and/or emotional, rather than sensory 'triggers'.

Abscess↗
PubMed1995

A 4-megabase YAC contig that spans the Langer-Giedion syndrome region on human chromosome 8q24.1: use in refining the location of the trichorhinophalangeal syndrome and multiple exostoses genes (TRPS1 and EXT1).

We have constructed a physical map covering over 4 Mb of human chromosome 8q24.1 and used this map to refine the locations of the genes responsible for Langer-Giedion syndrome. The map is composed of overlapping YAC clones that were identified and ordered in relation to sequence tagged sites mapped to the Langer-Giedion chromosomal region on somatic cell hybrids. The minimal region of overlap of Langer-Giedion syndrome deletions, previously identified by analysis of 15 patients, was placed on the map by analysis of 2 patients whose deletions define the endpoints. The chromosome 8 breakpoint of a balanced t(8;9)(q24.11;q33.3) translocation from a patient with trichorhinophalangeal syndrome (TRPS I) was found to be located just within the proximal end of the minimal deletion region. A deletion of 8q24.11-q24.3 in a patient with multiple exostoses was found to overlap the distal end of the LGS deletion region, indicating that the EXT1 gene is distal to the TRPS1 gene and supporting the hypothesis that Langer-Giedion syndrome is due to loss of functional copies of both the TRPS1 and the EXT1 genes.

Animals↗
PubMed1995

HIV positive patients first presenting with an AIDS defining illness: characteristics and survival.

OBJECTIVES: To study the presentation and survival of patients who present with their first diagnosis of being HIV positive at the same time as their AIDS defining illness. DESIGN: Retrospective study of patients presenting with AIDS between 1991 and 1993. SETTING: Department of genitourinary medicine, St Mary's Hospital, London. MAIN OUTCOME MEASURES: AIDS defining illness at presentation and survival after diagnosis of AIDS. RESULTS: Between January 1991 and December 1993, 97 out of 436 patients (22%) presented with their first AIDS defining illness coincident with their first positive result of an HIV test (group B). The remaining 339 patients (78%) had tested positive for HIV-1 infection within the previous eight years and had consequently been followed up in clinics before developing their first AIDS defining illness (group A). The two groups of patients did not differ in age and sex distribution, risk factors for HIV-1 infection, nationality, country of origin, or haematological variables determined at the time of the AIDS defining illness. However, the defining illnesses differed between the two groups. Illnesses associated with severe immunodeficiency (the wasting syndrome, cryptosporidiosis, and cytomegalovirus infection) were seen almost exclusively in group A whereas extrapulmonary tuberculosis and Pneumocystis carinii pneumonia were more common in group B. The survival of patients in group B after the onset of AIDS was significantly longer than that of patients in group A as determined by Kaplan-Meier log rank analysis (P = 0.0026). CONCLUSIONS: Subjects who are HIV positive and present late are a challenge to the control of the spread of HIV infection because they progress from asymptomatic HIV infection to AIDS without receiving health care. The finding that presentation with an AIDS defining illness coincident with a positive result in an HIV test did not have a detrimental effect on survival gives insights into the effects of medical intervention on disease progression after a diagnosis of AIDS.

AIDS Serodiagnosis↗
PubMed1995

Herpes simplex virus turns off the TAP to evade host immunity.

Many viruses have evolved mechanisms to avoid detection by the host immune system. Herpes simplex virus (HSV) expresses an immediate early protein, ICP47, which blocks presentation of viral peptides to MHC class I-restricted cells. The properties of the newly synthesized class I molecules in HSV-infected cells resemble those of cell lines deficient in the transporter associated with antigen processing (TAP) in that class I molecules are retained in the endoplasmic reticulum, and the heavy chain and beta 2-microglobulin subunits dissociate in detergent extracts but the complex can be stabilized by peptides. We show here that ICP47 binds to TAP and prevents peptide translocation into the endoplasmic reticulum.

ATP Binding Cassette Transporter, Subfamily B, Mem↗