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Biomedical subjects

J Hill

Publications and source records attributed to J Hill.

At least 199 records · Page 11Linked to original sources

The Adult Personality Functioning Assessment (APFA): factors influencing agreement between subject and informant.

The Adult Personality Functioning Assessment (APFA) provides ratings of interpersonal and social role performance in six domains over substantial periods of time. Ratings based on subject and informant accounts using the APFA were compared. There was good agreement for estimates of levels of dysfunction, and moderate agreement for type of dysfunction. An anticipated under-reporting of difficulties by subjects was not found. The extent of personality dysfunction was predictive of whether a close informant was available; however, closeness of informant was not consistently associated with subject-informant agreement.

Adaptation, Psychological↗

Administration of hepatitis A vaccine to a military population by needle and jet injector and with hepatitis B vaccine.

Military personnel are an important target population for hepatitis A immunization. Soldiers are often given vaccines by jet injector and may be required to receive multiple vaccines at one time. Formalin-inactivated hepatitis A vaccine containing 360 ELISA units of antigen was evaluated at Fort Campbell. Volunteers received vaccine at 0, 1, and 6 months as follows: group 1, hepatitis A vaccine by needle; group 2, hepatitis A vaccine by jet injector; group 3, hepatitis B vaccine by needle; and group 4, both hepatitis vaccines by needle in separate arms. Immune response and reactogenicity were evaluated. After two doses, recipients of vaccine administered by jet injector had a higher prevalence of antibody than those who received vaccine by needle (93% vs. 79%). By the 8th month, the vaccine was 100% immunogenic by either route or with hepatitis B vaccine. No interaction between hepatitis A and B vaccines was detected.

Adult↗

Dose-response relationship and time-course of the effect of inhaled magnesium sulphate on airflow in normal and asthmatic subjects.

1. Magnesium is a dietary cation with a wide range of actions of potential relevance to asthma. 2. To determine the dose-response relationship and time-course of the effect of inhaled magnesium sulphate on the airway, we have studied the effect of 0, 90, 135, 180 and 360 mg of magnesium sulphate given by nebulizer on specific airways conductance (sGaw) in 20 normal subjects, and forced expiratory volume in one second (FEV1), forced vital capacity (FVC), flow at 25% forced vital capacity (Vmax25) and peak expiratory flow (PEF) in 19 asthmatic subjects. 3. On five occasions after baseline measurements of airway calibre, one of the five doses of magnesium sulphate in 3 ml normal saline was administered by nebulizer in a randomized, double-blind design. Measurements of sGaw or FEV1, FVC, Vmax25 and PEF were made at 5 and 10 min after nebulization and at 10 min intervals thereafter up to 90 min. 4. There was no significant difference in the mean area under the curve (AUC) for change from baseline in sGaw or maximum increase from baseline between doses in normal subjects. 5. In asthmatic subjects there was no significant difference in the mean AUC for change from baseline in FEV1, FVC or Vmax25 when compared between doses by analysis of variance. There was a difference in the mean AUC for change from baseline in PEF between doses (ANOVA P for all groups 0.052) but this can be explained by a detrimental effect of the maximum dose of magnesium sulphate. 6. It would appear that inhaled magnesium does not act as a bronchodilator in normal or asthmatic subjects.

Administration, Inhalation↗

The C-terminal zinc finger of GATA-1 or GATA-2 is sufficient to induce megakaryocytic differentiation of an early myeloid cell line.

The GATA-1 and GATA-2 transcription factors, which each contain two homologous zinc fingers, are important hematopoietic regulators expressed within the erythroid, mast cell, and megakaryocytic lineages. Enforced expression of either factor in the primitive myeloid line 416B induces megakaryocytic differentiation. The features of their structure required for this activity have been explored. The ability of 12 GATA-1 mutants to promote 416B maturation was compared with their DNA-binding activity and transactivation potential. Differentiation did not require any of the seven serine residues that are phosphorylated in vivo, an N-terminal region bearing the major transactivation domain, or a C-terminal segment beyond the fingers. Removal of a consensus nuclear localization signal following the second finger did not block differentiation or nuclear translocation. The N-terminal finger was also dispensable, although its removal attenuated differentiation. In contrast, the C-terminal finger was essential, underscoring its distinct function. Remarkably, only 69 residues spanning the C-terminal finger were required to induce limited megakaryocytic differentiation. Analysis of three GATA-2 mutants led to the same conclusion. Endogenous GATA-1 mRNA was induced by most mutants and may contribute to differentiation. Because the GATA-1 C-terminal finger could bind its target site but not transactivate a minimal reporter, it may direct megakaryocytic maturation by derepressing specific genes and/or by interacting with another protein which provides the transactivation function.

3T3 Cells↗

In vitro formation, disposition and toxicity of N-acetoxy-sulfamethoxazole, a potential mediator of sulfamethoxazole toxicity.

Variation in the formation and disposition of the hydroxylamine of (SMX-HA) is thought to play an important role in the pathogenesis of sulfamethoxazole (SMX)-induced idiosyncratic adverse drug reactions. We hypothesized that, in analogy to carcinogenic arylamines, SMX-HA might be further converted to an electrophilic N-acetoxy metabolite which could play a role in mediating SMX toxicity. Accordingly, we chemically synthesized N-acetoxy-SMX, and examined the characteristics of its formation, metabolism, cytotoxicity and mutagenicity in human and bacterial test systems. The human arylamine N-acetyl-transferases, (NAT)1 and NAT2, were capable of converting SMX-HA to N-acetoxy-SMX. NAT1 and NAT2 possessed similar affinities for SMX-HA (apparent Km values of 650 and 520 microM, respectively), but the apparent maximal velocity of the NAT1-mediated acetylation was higher than that of NAT2. (1332 vs. 37 nmol/min/U of immunoreactive NAT protein). Human peripheral blood mononuclear cells 12,000 x g supernatant fractions converted N-acetoxy-SMX mainly back to SMX-HA, and also to a lesser extent to SMX, at clinically relevant concentrations. Similar pathways were observed in human hepatic cytosolic fractions. In a cytotoxicity assay, N-acetoxy-SMX was significantly more toxic to human peripheral blood mononuclear cells than SMX-HA (16.6 vs. 11.5% dead cells at a concentration of 300 microM). N-acetoxy-SMX was weakly mutagenic to the Salmonella typhimurium TA100 strain in the Ames test. These data suggest that the N-acetoxy metabolites of sulfonamides could potentially play a role in mediating sulfonamide idiosyncratic adverse drug reactions.

Acetyltransferases↗

The Bateman bipolar prosthesis: a prospective study in primary osteoarthritis.

We present a prospective study of Bateman bipolar prosthesis performed over 5 years in Perth. All patients were treated for primary osteoarthritis using a cementless straight Moore stem and the bipolar acetabular component. Assessment was made at 6-monthly intervals. Harris hip scores were calculated and radiological parameters of inner bearing movement, component migration and proximal osteoporosis were assessed. The group comprised 76 prostheses in 72 patients. The mean Harris hip score at 3 years follow-up was 85, however with a wide range between 55 and 99. A total of 30% of patients at 3 years follow-up had a Harris hip score at less than 70. Twenty-seven per cent of the prostheses at 3 years had restriction of movement at the inner bearing and 43% were judged to have moderate or severe stress shielding around the proximal femur. The clinical results were unpredictable with thigh pain being a significant problem. Because of the unpredictable results we would not advocate the use of the Bateman prosthesis in primary osteoarthritis.

Adult↗

High level expression and characterisation of Plasmepsin II, an aspartic proteinase from Plasmodium falciparum.

DNA encoding the last 48 residues of the propart and the whole mature sequence of Plasmepsin II was inserted into the T7 dependent vector pET 3a for expression in E. coli. The resultant product was insoluble but accumulated at approximately 20 mg/l of cell culture. Following solubilisation with urea, the zymogen was refolded and, after purification by ion-exchange chromatography, was autoactivated to generate mature Plasmepsin II. The ability of this enzyme to hydrolyse several chromogenic peptide substrates was examined; despite an overall identity of approximately 35% to human renin, Plasmepsin II was not inhibited significantly by renin inhibitors.

Amino Acid Sequence↗

Antegrade enemas for the treatment of severe idiopathic constipation.

The technique of appendicocaecostomy produces a continent catheterizable channel through which colonic washouts are given. This procedure was performed on six women of mean age 33.5 years with severe idiopathic constipation (mean stool frequency less than 1 per week) resistant to medical therapy. All patients had prolonged colonic transit times, three had evidence of obstructed defaecation and all had reduced or absent voluntary anal squeeze pressure. Patients found the appendicocaecostomy and catheterization acceptable, and symptoms of abdominal distension and pain resolved. All patients were able to initiate defaecation and evacuate the colon within 1 h of irrigation, and no patient had appreciable incontinence. Irrigation was necessary every 48-72 h. Adults with intractable constipation and pelvic floor weakness would be at risk of faecal incontinence after ileorectal anastomosis; it is in these patients that appendicocaecostomy has potential for the greatest benefit.

Adult↗

History and examination in the assessment of patients with idiopathic fecal incontinence.

PURPOSE: This study was undertaken to identify those factors from the history and examination which might predict the pathophysiologic basis of idiopathic fecal incontinence. METHODS: In a prospective study of 237 patients with idiopathic fecal incontinence (female to male, 7:1.7; mean age, 54.8 years; median history, 3 years), history, examination, and anorectal physiology studies findings have been analyzed using contingency table analysis. RESULTS: In patients with idiopathic fecal incontinence, anorectal physiology studies have shown that a low maximum basal pressure (< 45 cm H2O) is predominantly attributable to internal and sphincter weakness, and low maximum squeezing pressure (< 76 cm H2O) is indicative of voluntary sphincter deficiency. In this study, a low maximum basal pressure is correlated with leakage, gaping of the anus on traction of the anal verge, and decreased resting tone on digital examination (all P < 0.05). A low maximum squeezing pressure is correlated with incontinence en route to the lavatory, urgency, both stress and urge incontinence of urine, reduced voluntary contraction in the external anal sphincter and puborectalis on digital examination, and a reduced or absent anorectal angle (all P < 0.05). CONCLUSION: This study has shown that an informed history and digital examination can predict the manometric findings of specialist anorectal physiology studies.

Adult↗

Bernard Shaw and the doctors: the art and science of medicine in The Doctor's dilemma.

What did Bernard Shaw really think about doctors? Although any reader with a sketchy understanding of Shaw's work is inclined to think that he condemned the entire profession, a careful reading of his most well-known play featuring medical practitioners reveals a mixed attitude. In The Doctor's Dilemma, one finds a position that may be representative of Shaw's attitude. In this play, he places the entire Edwardian medical establishment--consultants and general practitioners--on stage, and he focuses the attention of this diverse group on the problem of a patient. In doing so, Shaw is able to separate the play's characters into representatives of (l) the new scientific medicine and (2) the venerable art of medicine. He satirizes the arrogance of the former, and he presents the humane attitude of the latter in a favorable light.

History, 20th Century↗

An evaluation of the effectiveness, safety and acceptability of a nurse practitioner in a rheumatology outpatient clinic.

Seventy patients with RA were randomly allocated to either a Rheumatology Nurse Practitioner (RNP) or Consultant Rheumatologist (CR) clinic. They were seen on six occasions in 1 year. Effectiveness and safety were assessed by biochemical, clinical, psychological and functional variables; patient knowledge and satisfaction were measured by questionnaire. At week 0 the groups were well matched clinically and demographically. By week 48 significant improvements had occurred in plasma viscosity and articular index within both groups. In patients managed by the RNP, pain, morning stiffness, psychological status, patient knowledge and satisfaction had all improved significantly (P = 0.001; P = 0.028; P = 0.0005; P < 0.0001; P < 0.0001 respectively), improvements not mirrored by the CR cohort. Between group comparisons also showed significant differences by the end of the study. Compared to the CR patients, the RNP suffered from lower levels of pain (P < 0.05), had acquired greater levels of knowledge (P < 0.0001) and were significantly more satisfied with their care (P < 0.0001).

Adult↗

Amino acids in pneumolysin important for hemolytic activity identified by random mutagenesis.

The structural gene of pneumolysin was randomly mutagenized. A screen, developed to identify mutants with reduced hemolytic activity, identified substitutions within the cysteine-containing region and also at residues toward the N terminus of the toxin. These are the first reported changes within the N-terminal region of the toxin that affect cytolytic activity.

Amino Acid Sequence↗