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Biomedical subjects

J Bruce

Publications and source records attributed to J Bruce.

At least 55 records · Page 3Linked to original sources
PubMed2000

International adoption of institutionally reared children: research and policy.

This article summarizes the research on the developmental outcomes of postinstitutionalized children and discusses the implications for social policy. Postinstitutionalized children often reach their adoptive families with varying degrees of physical growth retardation, cognitive delays, and socioemotional problems. Many children demonstrate remarkable recovery following adoption. Unfortunately, some of the children continue to display significant problems that require professional intervention. It appears that the children's recovery may be influenced by their early experiences with their birth family and in institutional care, and there is suggestive evidence that postadoption experiences also play a role. These findings indicate that preadoption and postadoption services may support the outcome of postinstitutionalized children.

Adoption↗
PubMed2000

Initial response to portoenterostomy determines long-term outcome in patients with biliary atresia.

PURPOSE: The aim of this study was to assess the efficacy of portoenterostomy in biliary atresia and determine factors that predict outcomes. METHODS: The outcomes after portoenterostomy for biliary atresia from 1976 to 1996 were graded into 3 defined groups: G (good, jaundice free); I (intermediate, progressive liver disease with liver transplant if needed after 3 years of age); P (poor, liver transplant or death at less than 3 years of age). RESULTS: Twenty-seven of 49 children (55%) who underwent portoenterostomy responded. Of these, 13 (26%) were jaundice free (G). Of 14 children (28%) in I, 6 underwent liver transplant after 3 years of age. Of 22 children (44.8%) in P, 14 (28%) died before 3 years and 8 underwent liver transplant before 3 years. Thus, 42% of the children in this series are surviving with native liver. Age at operation in P was significantly different compared with G. Preoperative values of bilirubin and alanine transaminase were comparable in the 3 groups. Postoperative values of bilirubin and alanine transaminase were lower in G and I compared with P Complications were significantly lower in group G. CONCLUSIONS: Portoenterostomy alone in biliary atresia is beneficial in 40% of cases. Factors associated with the outcome include age at operation, postoperative cholangitis, and change in values of bilirubin and alanine transaminase. A classification based on decline of bilirubin and enzyme levels 3 months after portoenterostomy is proposed to predict the long-term outcome of an individual case of biliary atresia. It is particularly relevant in the intermediate group in which timing of referral may preclude or compromise liver transplant.

Alanine Transaminase↗
PubMed2000

The contemporary outcome of gastroschisis.

BACKGROUND: The aim of this study was to evaluate the contemporary outcome in the management of gastroschisis. METHODS: A retrospective analysis was conducted of 91 babies admitted over a 7-year period to a single neonatal surgical unit with a diagnosis of gastroschisis. RESULTS: An antenatal diagnosis was made in 89 (98%) cases. Surgical intervention occurred in 90 babies, at a mean of 5 hours (range, 0.5 to 17) postdelivery. In 72 (80%) cases, primary closure of the abdominal defect was achieved, with a silo fashioned in the remaining 18 (20%). One child died before abdominal closure. The median time to full oral feeding was 30 days (range, 5 to 160 days), and to discharge was 42 days (range, 11 to 183 days). Those children who required a silo, took longer to feed (P =.008) and stayed longer in the hospital (P =.021). The 8 (8.8%) children with an intestinal atresia, required significantly more operative procedures (P =.0001) and took significantly longer to achieve full oral feeding (P =.04), but the presence of an atresia was not an independent risk factor for mortality. There were 7 deaths (7.7%), 3 within the first 7 days. Of the deaths, 5 (71%) were caused by overwhelming sepsis. CONCLUSIONS: The contemporary mortality rate from gastroschisis is less than 8%, and minimizing septic complications would contribute significantly to reducing this. Strategies designed to improve morbidity must focus on optimizing management of those factors associated with a prolonged recovery, namely intestinal atresia, prematurity, and the use of a silo.

Birth Weight↗
PubMed2000

Distinct FTDP-17 missense mutations in tau produce tau aggregates and other pathological phenotypes in transfected CHO cells.

Multiple tau gene mutations are pathogenic for hereditary frontotemporal dementia and parkinsonism linked to chromosome 17 (FTDP-17), with filamentous tau aggregates as the major lesions in the CNS of these patients. Recent studies have shown that bacterially expressed recombinant tau proteins with FTDP-17 missense mutations cause functional impairments, i.e., a reduced ability of mutant tau to bind to or promote the assembly of microtubules. To investigate the biological consequences of FTDP-17 tau mutants and assess their ability to form filamentous aggregates, we engineered Chinese hamster ovary cell lines to stably express tau harboring one or several different FTDP-17 mutations and showed that different tau mutants produced distinct pathological phenotypes. For example, delta K, but not several other single tau mutants (e.g., V337 M, P301L, R406W), developed insoluble amorphous and fibrillar aggregates, whereas a triple tau mutant (VPR) containing V337M, P301L, and R406W substitutions also formed similar aggregates. Furthermore, the aggregates increased in size over time in culture. Significantly, the formation of aggregated delta K and VPR tau protein correlated with reduced affinity of these mutants to bind microtubules. Reduced phosphorylation and altered proteolysis was also observed in R406W and delta K tau mutants. Thus, distinct pathological phenotypes, including the formation of insoluble filamentous tau aggregates, result from the expression of different FTDP-17 tau mutants in transfected Chinese hamster ovary cells and implies that these missense mutations cause diverse neurodegenerative FTDP-17 syndromes by multiple mechanisms.

Animals↗
PubMed2000

Regulation of vasoactive intestinal peptide receptor expression in developing nervous systems.

Vasoactive intestinal peptide (VIP) is a 28-amino acid peptide that has several functions, including the regulation of water and electrolyte secretion, hormone and cytokine release, bronchodilitation, and neurogenesis. VIP effects are mediated by specific G-protein coupled receptors. Three distinct receptor subtypes, with differing affinity for VIP, have been cloned and characterized as receptors 1 and 2 (VPAC1 and VPAC2) and pituitary adenylate cyclase activating polypeptide receptor (PAC1). Our laboratory has demonstrated that upregulation of VPAC1 in SK-N-SH neuroblastoma cells results in marked shift in cell type to the glial lineage with a corresponding loss of neuronal lineage and suppression of xenograft tumor growth. To understand the molecular mechanisms responsible for regulation of the VPAC1 gene in neuronal lineage, we have cloned and sequenced 2.6-kb of the 5'-flanking sequences of the human VPAC1 gene. Sequence analysis demonstrated that the human VPAC1 promoter sequence contains putative binding sites for several known transcription factors, including Sp1, NFkB, and cETS-1. To study the temporal and spatial expression pattern of human VPAC1 promoter sequences, we have generated transgenic mice expressing the bacterial beta-galactosidase gene under the control of the 2.6-kb 5'-flanking and promoter sequence of the human VPAC1 gene. Transgene expression was detected in brain, spinal cord, and lung in 14-day-old animals. Taken together, these results demonstrate that VPAC1 may play an important role in the nervous system, and suggest a role for VIP in neuronal differentiation.

Animals↗
PubMed2000

Profile of care given to patients with blunt chest injuries within the first 48 hours.

This study was conducted in the trauma unit of a large academic hospital in Johannesburg, South Africa. The study aimed at describing the nature of care that patients with blunt chest injuries received during the first 48 hours after injury. A descriptive survey was chosen using retrospective and prospective record review to obtain data. The sample comprised 60 records of patients who were admitted to the hospital due to blunt chest injuries between January 1997 and June 1998. Descriptive statistics were used to present and analyse data. The study showed that: (i) Blunt chest trauma victims received a thorough initial assessment and care. No missed injuries were identified on subsequent assessment; (ii) More than half of the patients spent over one hour in the accident/emergency department before admission to the trauma ward or intensive care unit (ICU); (iii) Motor vehicle accidents (MVA) were the commonest cause of injury while pedestrian vehicle accidents (PVA) were often fatal; (iv) Nurses are good providers of care but poor in prescribing and documenting care; (v) Pain assessment and psychosocial care was often neglected; (vi) Less than half the patients developed complications during the first 48 hours; pain and pneumonia being the most common complications encountered.

Academic Medical Centers↗
PubMed1999

Phase I trial of interferon gamma retroviral vector administered intratumorally with multiple courses in patients with metastatic melanoma.

The purpose of this study was to determine the safety and antitumor activity of IFN-gamma retroviral vector in patients with advanced melanoma. Seventeen patients (9 single courses, 8 multiple courses) received a total of 363 intratumor injections of IFN-gamma retroviral vector (1 x 10(7) PFU/ml administered at 0.3, 0.5, and 1.0 ml per cohort). No grade III/IV adverse events were attributed to study medication. Replication-competent retrovirus was not detected in any of the 17 patients by polymerase chain reaction studies. Eight patients showed elevated anti-tumor antibody responses in comparison with baseline by ELISA. One of nine patients treated with a single course had an optimal response of stable disease, compared with eight of eight multiple-injected patients. Median survival of single-injected patients was 150 days, and patients who received multiple injections have still not achieved median survival duration, with four of eight still living (p = 0.0462, Wilcoxon; p = 0.0273, log rank). We conclude that intratumor injection of IFN-gamma is safe and well tolerated. Evidence of antitumor activity is suggested in patients with advanced malignancy that received multiple injections.

Adult↗
PubMed1999

A phase I study of high-dose BCNU, etoposide and escalating-dose thiotepa (BTE) with hematopoietic progenitor cell support in adults with recurrent and high-risk brain tumors.

This phase I dose-escalation study was performed to determine the tolerability of three-drug combination high-dose BCNU (B) (450 mg/m2), escalating-dose thiotepa (500-800 mg/m2) and etoposide (1200 mg/m2) in divided doses over four days in 22 adults with malignant primary brain tumors. Patients received G-CSF and hematopoeitic support with peripheral blood progenitor cells (PBPC) (n = 18) or both PBPC and marrow (n = 4). The maximum tolerated dose of thiotepa with acceptable toxicity was determined as 800 mg/m2. The 100-day mortality rate was 9% (2/22). Grade III/IV toxicities included mucositis (71%), diarrhea (29%), nausea/vomiting (19%), and hepatic toxicity (14%). Neurological toxicities occurred in 24% and included seizures (two patients) and encephalopathy (three patients). Encephalopathy was transient in two patients and progressive in one patient. All patients had neutropenic fever. Median time to engraftment with absolute neutrophil count (ANC) >0.5 x 10(9)/l was 10 days (range 8-30 days). Platelet engraftment >20 x 10(9)/l occurred after 11 days (range 9-65 days). In the eighteen patients supported solely with PBPC, there was a significant inverse correlation between CD34+ dose and days to ANC (rho = -0.78, p = 0.001) and platelet engraftment (rho = -0.76, p = 0.002). Overall, 11% of evaluable patients (2/18) had a complete response to BTE. Median time to tumor progression (TTP) was 9 months, with an overall median survival of 17 months. BCNU (450 mg/m2), thiotepa (800 mg/m2) and etoposide (1200 mg/m2) in divided doses over four days is a tolerable combination HDC regimen, the efficacy of which warrants further investigation in adults with optimally resected chemoresponsive brain tumors.

Adult↗
PubMed1999

Maltreated and nonmaltreated preschoolers' conceptions of hypothetical and actual moral transgressions.

Maltreated and nonmaltreated preschoolers' (mean age = 4 years 6 months) judgments regarding hypothetical and actual moral transgressions were examined. Thirty-six maltreated children (17 physically abused and 19 neglected) and 19 comparison nonmaltreated children judged, justified, and evaluated affective responses to 6 hypothetical moral transgressions. Perpetrators and victims also judged and evaluated affective responses to actual classroom moral transgressions. All children evaluated moral transgressions as very serious, punishable, and wrong in the absence of rules. Moral judgments and justifications differed as a function of context (hypothetical vs. actual) and type of transgression but not maltreatment status. Affective responses differed as a function of maltreatment subtype and gender. Maltreated and nonmaltreated children may differ in the organization of their affective responses rather than in their moral evaluations.

Analysis of Variance↗
PubMed1999

Dedicated psychiatric care within general practice: health outcome and service providers' views.

Health service reforms have led to relocation of care of the chronic mentally ill from institutions to the community, with subsequent demands on the primary health care team. Few studies have attempted to identify satisfactory models of care for this patient group. This study explores the impact of the employment of a community psychiatric nurse (CPN) by a general practice in Aberdeen city to co-ordinate care of discharged long-stay psychiatric patients resettled in hostels. A similar general practice with a comparable group of registered patients was selected as a control group. Patient health outcome was measured using the Health of the Nation Outcome Scales (HoNOS) and service providers' views on dedicated psychiatric care within general practice were explored using qualitative methods. Improvements in communication, liaison and drug management were reported in the intervention practice. A primary care-based CPN service dedicated to the care of the chronic mentally ill promoted a smooth transfer of care from long-term institutionalized care to the community setting.

Adult↗
PubMed1999

Absence of demonstrable immune dysregulation in motor neuron disease.

Patients with motor neuron disease (MND) (n =33) free of infection were assessed for symptoms of autoimmunity and evidence of peripheral immune activation. Clinical features of autoimmune disease and antinuclear antibodies were notably absent in all patients. Compared with healthy controls, patients with MND had no significant difference in lymphocyte subsets (CD4/8 T cells, B and NK cells). Serum and whole blood endotoxin and phytohaemagglutinin stimulated levels of interferon gamma, granulocyte macrophage colony stimulating factor, interleukin (IL) 1beta, IL4, IL10, tumour necrosis factor alpha and soluble CD23 were no different between patients with MND and healthy controls. Our results confirm the absence of significant elevations of immune regulatory proteins in the peripheral circulation of patients with MND. Copyright 1999 Harcourt Publishers Ltd.

Journal Article↗
PubMed1999

A review of the effectiveness of Smokebusters: community-based smoking prevention for young people.

Smokebusters is a community-based smoking prevention initiative for young children which aims to prevent them from starting to smoke. Despite the increase of Smokebusters clubs throughout the UK and Europe there is little published evidence of the effectiveness of this health promotion intervention. The aim of this study was to conduct a literature review of the effectiveness of established UK and Irish Smokebusters clubs. Over 60 clubs and agencies were contacted with a total of 36 reports received. Of those reviewed, most clubs have conducted process and impact evaluation to assess the popularity and quality of the programme. Attempts have been made to measure children's knowledge, attitudes and behaviour in relation to smoking and the Smokebusters intervention. Only three clubs have conducted long-term outcome evaluations which have measured changes in knowledge, attitudes and smoking behaviour. There is some evidence that changes occur in knowledge and attitudes after the establishment of clubs. To date, there are no reports of sustained change in smoking behaviour following the establishment of Smokebusters clubs.

Adolescent↗
PubMed1999

Section 25 aftercare under supervision: the first eighteen months' experience.

Supervised discharge was introduced, against much professional opposition, in the Mental Health (Patients in the Community) Act 1995. All patients subject to supervised discharge (SD) in a large health district were identified by medical records departments, and the outcome of their SD on 1 October 1997, eighteen months after the legislation came into effect, was assessed. In that first eighteen months, half of the general, rehabilitation and forensic psychiatrists in the trust used SD for 22 patients. Of the 12 orders in effect for over six months, six were renewed at six months and three at one year. In spite of professional hostility and scepticism about the clinical practicalities of SD, the use of the new power has gradually increased with experience. Outcomes to date seem generally positive, but further definitive research is needed.

Adult↗
PubMed1999

Phase I evaluation of ISIS 3521, an antisense oligodeoxynucleotide to protein kinase C-alpha, in patients with advanced cancer.

PURPOSE: To determine the maximum-tolerated dose (MTD) and pharmacologic behavior of ISIS 3521 (ISI 641A), an antisense phosphorothioate oligonucleotide to protein kinase C-alpha. PATIENTS AND METHODS: Thirty-six patients with advanced cancer received 99 cycles of ISIS 3521 (0.15 to 6.0 mg/kg/d) as a 2-hour intravenous infusion administered three times per week for 3 consecutive weeks and repeated every 4 weeks. Plasma and urine sampling was performed during the first week of treatment and subjected to capillary gel electrophoresis to determine full-length antisense oligonucleotide in addition to chain-shortened metabolites. RESULTS: Drug-related toxicities included mild to moderate nausea, vomiting, fever, chills, and fatigue. Hematologic toxicity was limited to thrombocytopenia (grade 1, four patients; grade 2, one patient; grade 3, one patient). There was no relationship between dose, maximum concentration of the drug (C(max)), or area under the plasma concentration versus time curve (AUC) and coagulation times or complement levels. Dose escalation was discontinued because of the attainment of peak plasma concentrations, which approached that associated with complement activation in primates. Two patients with non-Hodgkin's lymphoma who completed 17 and nine cycles of therapy achieved complete responses. The pharmacokinetic profile of ISIS 3521 revealed a short elimination half-life (18 to 92 minutes), as well as a dose-dependent decrease in clearance and dose-dependent increases in C(max), AUC, and elimination half-life. CONCLUSION: No dose-limiting toxicity of ISIS 3521 was identified, and clinical activity was observed. A short elimination half-life was identified, which suggests that alternate schedules with prolonged administration may be necessary for further clinical development.

Adult↗
PubMed1999

Taking back young lives: policy issues for adolescent girls in the developing world.

This commentary explores the current boundaries of policy thinking about adolescence. It suggests that policy--even that designed to address adolescent sexuality and reproductive health--move substantially beyond the confines of the health sector in looking for solutions. The great diversity of adolescent needs--by age, gender, schooling, and marital status--are highlighted in making the case for a multisectoral adolescent policy.

Adolescent↗
PubMed1999

Tuberculin sensitivity: conversions and reversions in a rural African population.

SETTING: Karonga District, northern Malawi, 1980-1989. OBJECTIVE: To measure and interpret incidence and prevalence of tuberculin sensitivity. DESIGN: Tuberculin testing carried out within two total population surveys. Tuberculin 'positivity' and 'conversion' were defined using criteria recommended by the Tuberculosis Surveillance Research Unit and the American Thoracic Society, respectively. RESULTS: Data on 64,225 tests were available for analysis, including paired results on 6991 individuals tested in both surveys. Frequency distributions of induration varied by age, sex, BCG scar status and zone within the district. The prevalence of 'positivity' was similar in males and females until age 15, then higher among males, and was consistently higher among individuals with than among those without a BCG scar. Tuberculin 'conversion' rates estimated from cross-sectional data ranged from 0.34 to 1.15 per cent per annum. Conversion rates derived from longitudinal data were found to increase linearly with age, and the reversion rates declined rapidly with age among younger individuals. Such trends, which have been reported in other populations, are shown here to arise as an artefact of test instability. Prospective follow-up of observed converters showed greatly increased risks of tuberculosis, in particular during the two years following the second ('converted') test (relative risk > 10). CONCLUSION: Estimation of a convincing 'true' annual risk of infection from tuberculin survey data is not possible from either cross-sectional or longitudinal data, due to misclassifications and the instability of delayed type hypersensitivity over time. An apparent increase in infection risk with age can arise as an artefact of test instability. BCG-induced tuberculin sensitivity declines rapidly in this population in most individuals. It is necessary to consider tuberculin reversions, whether real or apparent, when interpreting tuberculin data on individuals or populations.

Adolescent↗