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Biomedical subjects

J Welch

Publications and source records attributed to J Welch.

At least 55 records · Page 3Linked to original sources
PubMed1998

Specific IgE to isocyanates: a useful diagnostic role in occupational asthma.

BACKGROUND: Isocyanates are the most frequent cause of occupational asthma in industrialized countries. OBJECTIVE: We sought to investigate the utility of specific IgE measurement in the diagnosis of isocyanate-induced asthma. METHODS: Fifty-eight of 101 patients referred for investigation were diagnosed as having isocyanate-induced occupational asthma by means of history, serial peak flow records, and bronchial provocation tests. Specific IgE antibodies to toluene diisocyanate:human serum albumin (HSA), diphenylmethane diisocyanate:HSA, and hexamethylene diisocyanate: HSA were measured in all patients by Phadebas RAST. RESULTS: Twenty patients had a RAST ratio of 2 or greater to at least one isocyanate. Thirteen (28%) of the 46 patients with a positive provocation test response had a RAST ratio of 2 or greater, and nine (20%) had a RAST ratio of 3 or greater. Raising the RAST cut-off from 2 or greater to 3 or greater reduced its sensitivity but increased the specificity of the test to 100%. RAST measurement was most likely to be positive within 30 days of exposure. Serial measurements suggested that the half-life of the IgE antibodies was approximately 6 months. Evidence of cross-reactivity between isocyanate RAST responses was found in eight subjects. CONCLUSION: Specific IgE to isocyanates is a more specific than sensitive index of occupational asthma. With a RAST score of 3 or greater, it is wholly specific and therefore diagnostic of isocyanate-induced asthma. The sensitivity of specific IgE measurement is highest when blood is taken less than 30 days from last exposure, which is consistent with the observed half-life.

Adolescent↗
PubMed1998

Selective hepatic arterial embolization of grade IV and V blunt hepatic injuries: an extension of resuscitation in the nonoperative management of traumatic hepatic injuries.

BACKGROUND: Recognizing the significant mortality and complications inherent in the operative management of blunt hepatic injuries, hepatic arterial embolization was evaluated as a bridge between operative and nonoperative interventions in patients defined as hemodynamically stable only with continuous resuscitation. METHODS: Seven of 11 patients with grade IV or V hepatic injuries identified by computed tomography underwent hepatic arterial embolization. A prospective evaluation of hepatic embolization based on subsequent hemodynamic parameters was assessed by matched-pair analysis. A summary of this study population's demographic data and outcomes is presented, including age, Glasgow Coma Scale score, Injury Severity Score, Revised Trauma Score, computed tomography grade, intensive care unit and hospital length of stay, transfusion requirements, complications, and mortality. RESULTS: No statistical difference was demonstrated between pre-embolization and postembolization hemodynamics and volume requirements. After embolization, however, continuous resuscitation was successfully reduced to maintenance fluids. Hepatic embolization was the definitive therapy for all seven patients who underwent embolization. CONCLUSION: Results of this preliminary investigation suggest that hepatic arterial embolization is a viable alternative bridging the therapeutic options of operative and nonoperative intervention for a subpopulation of patients with hepatic injury.

Adult↗
PubMed1998

Trisomy 21 associated transient neonatal myeloproliferation in the absence of Down's syndrome.

Although usually associated with Down's syndrome, transient neonatal myeloproliferation (TMD) can occur in the absence of a constitutional trisomy 21. This report describes two such cases, both of whom had a trisomy 21 restricted to clonal cells. Unlike in previous such reported cases, spontaneous morphological, cytogenetic, and molecular remission in both cases was followed by re-emergence, in one case, of an evolved clone with a more malignant phenotype which required pharmacological intervention. Awareness that trisomy 21 bearing leukaemia in the neonatal period can be transient even in the absence of Down's syndrome is important to prevent unnecessary treatment. Equally, such cases require indefinite follow up as a proportion may have a recurrence which may require treatment.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1997

Pharmacokinetics of mercaptopurine: plasma drug and red cell metabolite concentrations after an oral dose.

Measurement of red cell 6-mercaptopurine (MP) derived 6-thioguanine nucleotide (TGN) and methylmercaptopurine metabolites (MeMPs) can be used to monitor therapy in children who are administered MP for childhood lymphoblastic leukemia. Red cell TGNs are not influenced by the time of blood sampling in relation to the last MP dose. The purpose of this study was to find out whether the same is true for the MeMPs. Plasma MP and red cell MP metabolite pharmacokinetics were studied in seven children immediately before and for 4 hours after a protocol standardized dose of MP. Duplicate blood samples were taken, one was processed immediately whereas one was left at an ambient temperature for 24 hours. The variation in TGN and MeMP metabolites over the 0- to 4-hour period (10 time points per child) was within the error of the assays used. The coefficients of variation for the TGNs ranged from 2.7% to 7% and for the MeMPs, 4% to 10.7%. There was no difference in the TGN and MeMP concentrations measured when the blood samples were left for 24 hours. If a child takes a MP tablet immediately before a clinic appointment, it has no major influence on MeMP measurements.

Administration, Oral↗
PubMed1997

Measures and meanings: outcome measures in the management of sexually transmitted infections.

Applicable outcome measures in genitourinary medicine (GUM) include compliance with clinical standards of care, symptom control, cure rates of infections, decreased incidence of infections, lack of complications, increase in patients' knowledge or satisfaction, and number of partners treated. Measuring these may be easy in the short-term but result in information of limited usefulness. Longer-term outcomes may be more meaningful, but harder--or impossible--to obtain. Some outcome measures are affected by case mix, so differences between patients may be as much as or more relevant than the care received. Quantitative and qualitative measurements of patient satisfaction are straightforward to obtain and essential in examining care delivery, but may be unrelated to desired clinical outcomes for individuals or populations. Compliance with clinical standards is easy to measure, relatively independent of case mix, and useful if standards are evidence-based and validated. The role and applicability of outcome measures are discussed.

Humans↗
PubMed1997

Improving marketing strategies for wellness.

The authors address the following questions in a research study and propose six hypotheses: Does the desire for exuberant well-being, perceived threat to health, or a combination of both best explain wellness behavior? Threat is the stronger motivation for wellness behavior, followed closely by the desire for exuberant well-being. The authors present a thorough discussion of the implications of such findings for health care organization managers and marketers.

Attitude to Health↗
PubMed1996

Mercaptopurine in childhood leukaemia: the effects of dose escalation on thioguanine nucleotide metabolites.

The current U.K. trial protocol (UKALL XI) for childhood lymphoblastic leukaemia demands mercaptopurine (MP) dose escalation in children who tolerate daily 75 mg/m2 MP (100% dose) without cytopenias. The previous trial (UKALL X) did not. MP metabolism was studied in a group of UKALL XI children (n = 21) who tolerated 100% dosages and who were matched in this respect with a similar group of UKALL X children. Red blood cell MP derived thioguanine nucleotide (TGN) concentrations were measured in both groups under comparable conditions; at 75 mg/m2 MP there was no significant difference. MP dose escalation in the UKALL XI children produced higher TGN concentrations (TGNs at 100% vs 125% dosages, median difference 90 pmol/8 x 10(8) RBCs, 95% CI 25 to 165 pmol, P < 0.02). Assayed at the time of cytopenia induced dose reduction, the UKALL XI children had accumulated significantly higher TGN concentrations than the UKALL X children (median difference 78 pmol/8 x 10(8) RBCs, 95% CI 20 to 144, P < 0.02). These findings indicate that dose escalation in children tolerant of 100% MP dosages produces higher peak TGN concentrations.

Antimetabolites, Antineoplastic↗
PubMed1996

Ethnic differences in women with HIV infection in Britain and Ireland. The study group for the mrc collaborative study of HIV infection in women.

OBJECTIVE: To examine ethnic differences in the socio-epidemiological and clinical characteristics of a cohort of women with HIV infection in Britain and Ireland. DESIGN AND METHODS: Analysis of baseline data (ethnic group, sexual history, likely route of HIV infection, reasons for HIV testing and first AIDS-defining disease) from 400 women with HIV infection recruited into a cohort study from 15 genitourinary medicine/HIV clinics in Britain and Ireland. RESULTS: Sixty-five per cent of women were white and 29% black African. Their median number of lifetime sexual partners was seven and three, respectively (P < 0.001). Ninety-three per cent of black African and 43% of white women were probably infected through sexual intercourse. Injecting drug use was the most likely route of infection in 55% of white women, but none of the black African women. Perceived risk (33%) or investigation of symptoms (26%) were the most common reasons for HIV testing. Seven per cent of white women and 16% of black African women (P < 0.001) had AIDS when HIV infection was diagnosed. The distribution of first AIDS-defining diagnoses differed (P = 0.001) by ethnic group. For white women, the most common disease was Pneumocystis carinii pneumonia; for black African women it was pulmonary tuberculosis. CONCLUSION: There are important differences between black African and white women in sexual history and route of transmission, disease stage at diagnosis and pattern of AIDS-defining diseases.

AIDS Serodiagnosis↗
PubMed1995

Monoclonal antibodies raised against covalently crosslinked complexes of human immunodeficiency virus type 1 gp120 and CD4 receptor identify a novel complex-dependent epitope on gp 120.

The binding of the human immunodeficiency virus type 1 (HIV-1) envelope glycoprotein, gp120, to its cell surface receptor, CD4, represents a molecular interaction involving distinct alterations in protein structure. Consequently, the pattern of epitopes presented on the gp120-CD4 complex should differ from those on free gp120. To investigate this concept, mice were immunized with covalently crosslinked complexes of viral HIV-1IIIBgp120 and soluble CD4. Two monoclonal antibodies (MoAbs) obtained from the immunized mice exhibited a novel epitope specificity. The MoAbs were marginally reactive with HIV-1IIIBgp120, highly reactive with gp120-CD4 complexes, and unreactive with soluble CD4. The same pattern of reactivity was seen in solid-phase assays using HIV-1(451)gp120. A similar specificity for complexes was evident in flow cytometry experiments, in which MoAb reactivity was dependent upon the attachment of gp120 to CD4-positive cells. In addition, MoAb reactivity was detected upon the interaction of CD4 receptors with purified HIV-1IIIB virions. Notably, seroantibodies from HIV-positive individuals competed for MoAb binding, indicating that the epitope is immunogenic in humans. The results demonstrated that crosslinked gp120-CD4 complexes elicit antibodies to cryptic gp120 epitopes that are exposed during infection in response to receptor binding. These findings may have important implications for the consideration of HIV envelope-receptor complexes as targets for virus neutralization.

Animals↗
PubMed1995

Intracellular metabolites of mercaptopurine in children with lymphoblastic leukaemia: a possible indicator of non-compliance?

As part of a programme assessing the pharmacokinetics of oral thiopurines given for lymphoblastic leukaemia, we assayed intracellular metabolites of mercaptopurine in children from all over the United Kingdom who were given a standard dose of the drug. The metabolites we measured, thioguanine nucleotides and methylmercaptopurines, are products of two competing metabolic pathways and would be expected to show an inverse correlation. A total of 327 children from 17 centres in the UK were studied. All were on the same therapeutic schedule of mercaptopurine. All had been on an unattenuated full protocol-directed dose (at least 75 mg m-2) for a minimum of 7 days before assay. There was a very wide variation in the concentration of the two metabolites measured; the thioguanine nucleotides ranged from 0 to 1255 pmol per 8 x 10(8) red cells (median 289, lower quartile 210, upper quartile 377) and the methylmercaptopurine metabolites ranged from 0 to 46.3 nmol per 8 x 10(8) red cells (median 5.18, lower quartile 2.31, upper quartile 11.59). The anticipated negative correlation was not apparent, but the ratio between the two was not randomly distributed. No child had both metabolite concentrations in the upper quartiles, but in 32 (10%) children the concentration of both metabolites was in the lower quartile. Of the 32, only one metabolite was detected in four and none at all in six. The most likely explanation for these findings is that a minority of children with lymphoblastic leukaemia fail to take oral mercaptopurine either totally or intermittently. The extent of the problem is unknown, but we suspect it may be clinically important in at least 10% of patients.

Adolescent↗
PubMed1995

Family planning in genitourinary medicine: an opportunistic service?

OBJECTIVE: To evaluate and serve the need for contraception in those not using conventional sources of family planning services. SETTING: South London outpatient genitourinary medicine department at King's College Hospital. DESIGN AND SUBJECTS: Prospective study of 200 women seen consecutively in the clinic by the same doctor (LM) during 1993. Women at risk of unwanted pregnancy were identified, and offered immediate contraceptive provision or referral. RESULTS: 15 women (7.5%) were using no contraception, despite being sexually active and not wishing to conceive; of these two presented with an unwanted pregnancy. A further 23 women (11.5%) were not using their chosen contraception effectively, and another 20 women were unclear about contraceptive methods and wanted advice. Young women were most at risk; 14% of those aged 25 years and under were using no contraception. Eight women wished to defer contraceptive advice; of these four defaulted from follow up. Eighteen women (9%) wanted immediate contraceptive supplies. Ten of 18 returned a follow up questionnaire; all these women were satisfied with the contraceptive advice service received. CONCLUSIONS: Absent or ineffective contraception is common in women attending an inner city genitourinary medicine clinic. Immediate provision of contraceptive education, advice and supplies is welcomed by patients.

Adolescent↗