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Biomedical subjects

T White

Publications and source records attributed to T White.

At least 91 records · Page 5Linked to original sources

A randomised controlled study of close monitoring of vulnerable psychiatric patients.

The care programme approach was introduced in mental health services in the UK in 1991. It was intended to improve the quality of care and prevent patients losing contact with care services and, by implication, to reduce psychiatric admissions. We did a study to find out if the approach worked. 400 patients from a London inner-city area who had been identified as psychiatrically vulnerable and included on a case register of patients with special needs were randomised into two groups of 200 each. One group received close supervision by nominated key-workers (as recommended in the care programme approach of the UK Department of Health), and the other received standard follow-up from psychiatric and social services. Outcome was recorded after eighteen months. Data on 393 patients was available for analysis. Of 197 patients allocated to standard care, 64 (32.5%) were lost to follow-up compared with 40 (20.4%) of 196 patients receiving close supervision (p = < 0.005). However, patients under close supervision had significantly more admissions (30% vs 18%, chi 2 = 7.61, p < 0.01) and spent 68% more days in hospital than the standard group. The findings of greater hospital-bed use, which differ from those of studies with community-based psychiatric teams, suggest that close supervision by a single key worker, as recommended in the care programme approach, will lead to greater success in maintaining contact with vulnerable patients, but is likely to lead to more psychiatric admissions.

Adult↗

Serum cystatin C measured by automated immunoassay: a more sensitive marker of changes in GFR than serum creatinine.

Serum cystatin C has been suggested as a new marker of GFR. For the introduction of this marker into clinical use a rapid and automated method is required. We have developed and validated an assay for serum cystatin C using latex particle-enhanced immunoturbidimetry. Intra- and inter-assay precision were < 3% and < 5% across the assay range. Analytical recovery was 93 +/- 3.8% and no lack of parallelism was demonstrated. Regression analysis of a method comparison with an enzyme-enhanced radial-immunodiffusion method, gave PETIA = 0.074 + 0.93 x SRID, r = 0.98, N = 100. Inter-assay precision profiles showed cystatin C was measured with two-fold better precision than creatinine on the same analyzer. Cystatin C measurement was neither interfered with by icterus nor by hemolysis. 1/cystatin C versus 1/creatinine concentrations gave r = 0.67, N = 469. Comparison of Cr EDTA GFR with 1/cystatin C and 1/creatinine gave r = 0.81 and 0.50, respectively, N = 206. Calculating diagnostic sensitivity for abnormal GFR showed cystatin C to be significantly (P < 0.05) more sensitive than creatinine (71.4 vs. 52.4%). Cystatin C measurement using PETIA technology can be automated on the same instruments used routinely for the measurement of creatinine and offers better analytical performance and probably improved clinical sensitivity as a screening test for early renal damage.

Biomarkers↗

Perioperative myocardial ischaemia in patients undergoing transurethral surgery: a pilot study comparing general with spinal anaesthesia.

We have studied the incidence and duration of perioperative myocardial ischaemia using ambulatory ECG monitoring in 100 patients undergoing transurethral surgery, who were allocated randomly to receive either general or spinal anaesthesia. The overall incidence of myocardial ischaemia increased from 18% to 26% between the preoperative and postoperative periods. Patients with ischaemic heart disease had a significantly greater incidence of myocardial ischaemia after operation than patients without known ischaemic heart disease (P < 0.05). There was an increase in both the incidence and duration of myocardial ischaemia after operation with both anaesthetic techniques, but no significant difference between the two.

Aged↗

Familial aggregation of adolescent personality disorders.

OBJECTIVE: A family study of DSM-III-R personality disorders was conducted in the families of 66 clinically referred adolescents to examine the validity of personality disorder diagnoses in adolescents. METHOD: Semistructured interviews of Axis I and II disorders, including the Structured Clinical Interview for DSM-III-R Personality Disorders, were used to directly interview 66 clinically referred adolescents and their adult first-degree family members, combining family study and family history data. RESULTS: The relatives of adolescents with avoidant personality disorder had an increased prevalence of avoidant and cluster A (schizoid, schizotypal, and paranoid) personality disorders. The relatives of adolescents with borderline personality disorder demonstrated increased rates of borderline and avoidant personality disorders, even after adjusting for comorbidity. CONCLUSIONS: The results of this study support the validity of Axis II diagnoses, particularly avoidant and borderline disorders, in adolescents.

Adolescent↗

Improving the interpretation of electrocardiographs in an accident and emergency department.

In this study we have examined the ability of senior house officers in the Accident and Emergency (A&E) Department to interpret electrocardiographs (ECGs) and tested the value of a single seminar and guidelines on interpretation. We prospectively audited ECG interpretation taken from notes over a two-month period and repeated this audit following a single seminar by a consultant cardiologist and after the issue of guidelines. A formal test of interpretation of a set of 20 ECGs by senior house officers in A&E was also carried out. 245 case notes were reviewed and in one third the ECG was interpreted incorrectly by senior house officers in A&E but incorrect clinical management followed in only 3.2% of cases. Following the intervention, 242 case notes were reviewed and serious misinterpretations were halved as was the number of patients mismanaged as a result (1.7%). In conclusion, formal training in ECG interpretation can reduce serious errors.

Clinical Competence↗

Biosynthetic basis of incompatible histo-blood group A antigen expression: anti-A transferase antibodies reactive with gastric cancer tissue of type O individuals.

The expression of incompatible A carbohydrate antigens in some adenocarcinomas may provide an explanation for the generally observed lower incidence of adenocarcinoma among types O and B versus type A individuals. The chemistry and genetic basis of incompatible A expression is largely unknown. Here, we have screened 31 cases of gastric tumors of phenotype O for the expression of blood group A gene-defined glycosyltransferase by immunohistology on frozen sections using newly developed monoclonal antibodies to the transferases. Three cases were positive, and transferase expression was confirmed by enzyme analysis of extracts from the specimens. Blood group A carbohydrate antigens were also identified immunohistologically in these three cases as well as in five other cases. Thin-layer chromatography immunostaining analysis of glycolipid extracts from the three cases did not confirm the chemical presence of A antigen. The ABO genotype of all patients was found to be OO, showing that all carried O alleles with a structural defect at nucleotide position 261 leading to a shift in the reading frame. The data suggest that incompatible A antigen expression is a result of transferase expression derived from the ABO genes.

ABO Blood-Group System↗

Bacteriophage T4 Alc protein: a transcription termination factor sensing local modification of DNA.

Bacteriophage T4 Alc protein participates in shutting off host transcription after infection of E. coli. It is demonstrated that Alc acts as a site-specific termination factor. The Alc sites occur frequently in E. coli DNA, resulting in early cessation of elongation in several tested transcription units. Alc-dependent termination requires unimpeded propagation of the elongating complex as it approaches the Alc site. Temporary halting of RNA polymerase within 10-15 bp before the Alc site prevents termination. Bacteriophage T4 transcription is protected from the action of Alc by overall substitution of cytosine with 5-hydroxymethyl cytosine in T4 DNA. In vitro methylation of CpG sequences in the vicinity of an Alc site abolishes the effect of Alc. Thus, Alc-dependent termination involves local sensing of the state of cytosine modification and a short-term "memory" of recent pausing.

Bacteriophage T4↗

Inhibition of complement alternative pathway in mice with Fab antibody to recombinant adipsin/factor D.

Mouse adipsin is a serine protease secreted mainly by adipocytes. Similarly to factor D of human complement, it cleaves factor B. That adipsin is the equivalent of human factor D in the mouse is further suggested by their structural homology. Specific antisera against recombinant mouse adipsin (r-adipsin) were produced in rabbits. Anti-r-adipsin IgG was shown to bind to radiolabeled r-adipsin and to inhibit its hemolytic activity. In vitro, these antibodies Ab and Fab fragments thereof inhibited the adipsin/factor D hemolytic activity of mouse serum. They also blocked C3 activation induced by cobra venom factor (CVF), but did not interfere with classical pathway function. After intravenous injection of anti-r-adipsin Fab into BALB/c mice, the adipsin/factor D hemolytic activity of serum was abolished during a 4-h period. The C3 depleting effect of CVF injected intravenously was significantly delayed in BALB/c mice which had been pretreated with anti-r-adipsin Fab. These experiments demonstrate that mouse adipsin is the only form of mouse factor D and that anti-r-adipsin antibody can be used to produce a specific inhibition of the alternative pathway in vivo.

Animals↗

Cell-specific posttranslational processing of the surfactant-associated protein SP-B.

Pulmonary surfactant-associated protein B (SP-B) is a 9-kDa lung-specific protein expressed in alveolar epithelial type II cells and Clara cells. The protein markedly increases the surface activity of phospholipids and is an active component in some surfactants in clinical use. SP-B is produced from a 43-kDa precursor protein by proteolytic cleavage of flanking regions from both the NH2- and COOH-terminal ends of the active protein. In this study we have compared the nature of the posttranslational processing of the SP-B precursor in type II cells and in a heterologous cell line transfected with the SP-B precursor. We found that isolated type II cells produce the 9-kDa form of SP-B from the precursor through a series of intermediates detectable in the cell lysates. In contrast Chinese hamster ovary cells stably transfected with the full-length human SP-B precursor produce the precursor and a 26-kDa intermediate but not the 9-kDa protein. The precursor protein in both cell types is glycosylated with NH2-linked sugars. Our results suggest there is cell specificity in the posttranslational processing of the SP-B precursor.

Animals↗

Expression of histo-blood-group-A/B-gene-defined glycosyltransferases in normal and malignant epithelia: correlation with A/B-carbohydrate expression.

Malignant transformation of oral and bladder epithelia is often associated with loss of histo-blood-group-A- and -B-carbohydrate antigens, whereas these antigens, which are absent in normal adult distal colon (but present in fetal colon) reappear in malignant distal colon. In order to gain insight into the genetic basis of the biosynthetic regulation for these changes, we have correlated the expression of the A- and B-carbohydrate antigens with that of the A/B-gene-defined glycosyltransferases in colon, bladder and oral carcinomas by immunohistology. A newly developed anti-A/B-transferase monoclonal antibody (MAb) was used to demonstrate the in situ localization of transferase expression at the individual cell level with correlation to carbohydrate antigen expression, and gave the essential information that the transferase is derived from the ABO gene complex. The reappearance of A- and B-carbohydrate antigens in carcinomas of the distal colon was found to be unrelated to the expression of the A/B-transferase proteins, which were expressed throughout normal adult colon in accordance with previous enzymatic studies. In contrast, the loss of A- and B-carbohydrate antigens in malignant bladder and oral epithelia was accompanied by concordant loss of enzymes.

ABO Blood-Group System↗

Purification of PKC-I, an endogenous protein kinase C inhibitor, and types II and III protein kinase C isoenzymes from human neutrophils.

Human neutrophil protein kinase C (PKC) activity is inhibited by an endogenous protein found primarily in the pellet fraction from homogenized specific granules, which was both heat- and proteinase-sensitive [Balazovich, Smolen & Boxer (1986) J. Immunol. 137, 1665-1673]. We now report that two PKC isoenzymes and the endogenous PKC inhibitor, which we named PKC-I, were purified from human neutrophils. A neutrophil soluble fraction that was subjected to DEAE-Sephacel chromatography yielded highly enriched PKC because, by definition, enzymic activity was strictly dependent on Ca2+ and phosphatidylserine. Hydroxyapatite chromatography resolved two peaks of PKC activity. Type II and Type III PKC isoenzymes were each identified on Western blots by using isoenzyme-specific monoclonal antibodies. Unlike rat brain, from which PKC isoenzymes were also purified, Type I PKC was not detected in human neutrophils. Western blots indicated that both Type II and Type III PKC isoenzymes had molecular masses near 80 kDa. In agreement with other reports, PKC was autophosphorylated in vitro. PKC-I, an endogenous neutrophil inhibitor of PKC, was purified to apparent homogeneity by DEAE-Sephacel and S-400 Sephacel chromatography. PKC-I had a molecular mass of 41 kDa. PKC-I inhibited purified PKC activity stimulated by 1,2-diacylglycerols in a concentration-dependent manner, and inhibited PKC-dependent phosphorylation of proteins present in neutrophil cytosol.

Animals↗