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Biomedical subjects

J Innes

Publications and source records attributed to J Innes.

At least 19 recordsLinked to original sources
PubMed1999

Decreased morbidity and use of hospital services in English HIV-infected individuals with increased uptake of anti-retroviral therapy 1996-1997. National Prospective Monitoring System Steering Group.

OBJECTIVE: To investigate the relationship between changing morbidity patterns, the use of hospital services by HIV-infected patients and the uptake of antiretroviral therapy (ART) in England. DESIGN: Prospective serial cross-sectional analyses based on data collected through the National Prospective Monitoring System (NPMS), a multi-centre prospective monitoring system. SETTING: HIV-infected patients seen in 10 clinics, five London and five non-London, during the three semesters, 1 January 1996 to 30 June 1997. MAIN OUTCOME MEASURES: The mean use of hospital services per patient-year, mean new HIV-related opportunistic illnesses per 1000 patient-years and percentage uptake of ART. RESULTS: The use of inpatient services changed particularly among AIDS patients. The mean number of inpatient days for AIDS patients decreased from 19.7 [95% confidence interval (CI) 13.7-25.7] in 1996 to 11.2 (95% CI 6.1-15.6) per patient-year in 1997. Concurrently the number of new AIDS-defining events decreased significantly from 567 (95% CI 529-607) to 203 (95% CI 183-225) per 1000 patient-years. The overall uptake of ART increased significantly from 33% (95% CI 31-35%) to 50% (95% CI 48-52%), and a switch from mono or dual to triple therapy or quadruple or more therapy was observed. However, by mid-1997 only 29% (95% CI 26-32%) of asymptomatic patients and 51% (95% CI 49-54%) of patients with symptomatic non-AIDS were on ART, compared with 69% (95% CI 66-71%) of AIDS patients. CONCLUSION: The observed reduction in new AIDS-defining events has led to a reduction in the need for inpatient hospital care and has been associated with an increased uptake of ART, including a switch to triple therapy. All of these factors are likely to have contributed to the observed reduction in mortality among English AIDS patients. As the overall uptake of ART remained relatively low in English centres further improvements can be anticipated. However, the medium to long-term effects of these treatment regimens will need to be closely monitored.

Anti-HIV Agents↗
PubMed1998

Variation in IgG1 heavy chain allotype does not contribute to differences in biological activity of two human anti-Rhesus (D) monoclonal antibodies.

BACKGROUND: Pooled human anti-Rhesus D antiserum is currently administered for the prevention of RhD alloimmunization. Increased demand, and decreased supply, of donated pooled antiserum has led to the investigation of the suitability of human monoclonal anti-RhD antibodies for use in its place. However, it is unclear which biological properties of monoclonal antibodies are important for function in RhD-positive foetal red cell clearance and the prevention of alloimmunization. Various antibodies behave differently in a number of in vitro assays of biological function. OBJECTIVES: To compare the function and structure of two human anti-RhD IgG1 monoclonal antibodies which differ in their ability to promote red cell lysis in vitro. In particular to examine whether the functional differences correlate to differences in the IgG1 heavy chain constant region (allotype). STUDY DESIGN: We report here the cloning, characterization and re-expression in stable myeloma cell transformants of cDNAs coding for two such antibodies, secreted by the heterohybridoma cell lines ESD-1 (THERAD 03) and LHM 70/45.3 (THERAD 06). The cDNAs were then recombined to exchange portions of the Fc encoding regions and the recombinant antibodies were assayed in vitro to determine RhD-positive red cell-dependent activity. RESULTS: Recombinant THERAD 03 and 06 antibodies behaved identically to the parent antibodies. The 'inactive' THERAD 06 did not have biological activity reconstituted by exchange with the THERAD 03 Fc regions, nor was THERAD 03 activity abolished by the reciprocal Fc region exchange. CONCLUSIONS: Human monoclonal anti-RhD antibodies can be cloned and re-expressed in stable cell lines, and exhibit identical properties to the parent antibodies. Differences in biological activity cannot be attributed to differences in IgG1 heavy chain allotype.

Antibodies, Monoclonal↗
PubMed1998

The use and cost of HIV service provision in England in 1996. National Prospective Monitoring System (NPMS) Steering Group and NPMS Working Party on Costs.

OBJECTIVE: The aim of the study was to measure the use and estimate the cost of HIV service provision in England. DESIGN AND SETTING: Standardised activity and case-severity data were collected prospectively in 10 English HIV clinics (5 London and 5 non-London sites) for the periods 1 January 1996 to 30 June 1996 and 1 July 1996 to 31 December 1996 and linked to unit cost data. In total, 5440 patients with HIV infection attended during the first 6 months and 5708 during the second 6 months in 1996. MAIN OUTCOME MEASURES AND RESULTS: The mean number of inpatient days per patient-year for patients with AIDS was 19.7 [95% confidence interval (CI): 13.7 to 25.7] for January to June and 20.8 (95% CI: 15.3 to 26.4) for July to December 1996. The mean number of outpatient visits for asymptomatic patients with HIV infection was 14.8 (95% CI: 11.9 to 17.6) and 13.3 (95% CI: 10.8 to 15.7) for the respective periods and 16.1 (95% CI: 13.21 to 18.97) and 15.7 (95% CI: 11.2 to 20.2), respectively, for patients with symptomatic non-AIDS (i.e. symptomatic patients with HIV infection but without AIDS-defining conditions). Substantial centre-to-centre variation was observed, suggesting that many clinics can continue the shift from an inpatient- to an outpatient-based service. Cost estimates per patient-year for HIV service provision for 1996 varied from 4695 Pounds (95% CI: 3769 Pounds to 5648 Pounds) for asymptomatic patients, to 7605 Pounds (95% CI: 6273 Pounds to 8909 Pounds) for symptomatic non-AIDS patients to 20,358 Pounds (95% CI: 17,681 Pounds to 23,206 Pounds) for patients with AIDS. CONCLUSIONS: Different combinations of antiretroviral therapy affect the cost estimates of HIV service provision differently. Anticipated reduction in inpatient-related activity through the increased use of combination antiretroviral therapy will further shift service provision from an inpatient- to outpatient-based service and reduce costs per patient-year. The extent and duration of such effects are currently unknown. The long term effects of combination treatment on the morbidity and mortality patterns of individuals infected with HIV are also currently unknown, as are their implications on the use and cost of HIV service provision. Multicentre databases like the National Prospective Monitoring System (NPMS) will provide healthcare professionals with information to improve existing services and anticipate the impact of new developments.

Acquired Immunodeficiency Syndrome↗
PubMed1997

The Diabetes Care Support Service for general practitioners in Auckland.

AIMS: Diabetic complications can often be prevented by timely detection and intervention. Optimising diabetes care requires effective monitoring of risk factors at both practice and district level. We describe a novel method which combines district monitoring of diabetes with enhanced diabetes care by individual general practitioners. METHODS: All general practitioners in south and west Auckland (n = 291) were invited to join the Diabetes Care Support Service (DCSS). This involved the identification of all diabetic patients within the practice and the completion of an audit from with key measures of diabetes and its care. RESULTS: Audit was completed for 217 (75%) of general practitioners and 4611 diabetic patients: 39% of general practitioners completed their own audit. The proportion of completed patient assessments ranged between 35% (foot pulses) and 89% (blood pressure). The process was found to be helpful by 88% of general practitioners (who commented). CONCLUSION: The DCSS is a seamless, service-orientated approach to the delivery of diabetes care by primary and secondary services and is likely to improve care district-wide and identify the need for further interventions. Subsequent audit passes will allow the demonstration and monitoring of any changes that occur, as well as the demonstration of its feasibility and acceptability on an ongoing basis.

Blood Pressure↗
PubMed1997

Ultrasound evaluation of blunt abdominal trauma: program implementation, initial experience, and learning curve.

OBJECTIVE: Although sonographic screening for blunt abdominal trauma is gaining acceptance, standards for implementation, training, credentialing, and quality control remain to be established. DESIGN: This prospective study examines a Level I trauma service experience with the de novo establishment of a trauma ultrasound (US) program credentialed through the Department of Surgery under the auspices of Continuous Quality Improvement. MATERIALS AND METHODS: All trauma surgeons attended a combined didactic and "hands on" 8-hour trauma US course. Abdominal sonography was subsequently performed on patients with potential blunt abdominal trauma followed by a standard diagnostic evaluation, which included computed tomographic scan, diagnostic peritoneal lavage, or observation. MEASUREMENTS AND MAIN RESULTS: Three hundred patients were studied over a 4-month period. They averaged 35 years of age with an average injury severity score of 12. The time required to perform the US examination averaged less than 3 minutes. Standard diagnostic evaluation included computed tomographic scan (21%), diagnostic peritoneal lavage (45%), and observation (34%). US examinations resulted in 277 true negatives, 17 true positives, two false positives, and four false negatives for a sensitivity of 81.0%, a specificity of 99.3%, and an accuracy of 98.0%. Annualized cost savings with the use of US evaluation versus standard diagnostic evaluation would amount to over $100,000.00. CONCLUSIONS: This experience with the de novo implementation of a trauma US program suggests that the training and credentialing requirements in this study are sufficient to provide surgeon ultrasonographers with acceptable competence in US diagnosis of blunt abdominal trauma.

Abdominal Injuries↗
PubMed1994

Approaches to maximizing stable expression of alpha 1-antitrypsin in transformed CHO cells.

A variety of approaches to maximizing the production of recombinant human alpha 1-antitrypsin (AAT) in Chinese hamster ovary (CHO) cells have been investigated. The highly active and inducible human cytomegalovirus immediate early (IE) promoter/enhancer was used to drive transcription of a recombinant AAT gene in transiently transfected and stably transformed CHO cells. The AAT gene was modified to incorporate highly efficient 3'RNA processing signals from the herpes simplex virus type 2 IE gene 5, and optimal translational initiation signals were created by site-directed mutagenesis. The effect of flanking the recombinant gene with matrix attachment regions was investigated. Combinations of these modifications allowed secretion of up to 44 micrograms AAT/ml per day by cell lines growing in serum-rich medium. This could be increased to up to 100 micrograms AAT/ml per day upon chemical induction of expression by propionate, butyrate or hexamethylene bisacetamide. Cell lines adapted to grow in protein-free medium produced less AAT but still responded to chemical induction to secrete up to 14 micrograms/ml per day of readily purified AAT.

Animals↗
PubMed1993

Retained intraocular foreign body simulating choroidal melanoma. A report of two cases.

Many different lesions can be difficult to distinguish from malignant melanomas of the choroid. With the use of modern diagnostic facilities the misdiagnosis rate has been greatly reduced. In a recent report from the Collaborative Ocular Melanoma Study Group the incidence of misdiagnosis was only 0.48%. The presence of a retained intraocular foreign body presenting as a raised pigmented choroidal mass similar to a uveal melanoma is rare. We report two cases in which retained intraocular foreign bodies presented clinically as raised pigmented intraocular lesions. Retained intraocular foreign bodies should be considered in the differential diagnosis of ocular tumours, especially if there are any atypical features.

Aged↗
PubMed1990

Genetic differences in maternal behaviour patterns in mice administered phenobarbital during pregnancy.

In a study designed to examine the role of the genotype on sensitivity to drug-induced behavioural changes, pregnant C57BL/6J and CBA mice were administered 60 mg/kg phenobarbital (PHB) intraperitoneally during days 10-16 of gestation. Following a balanced intrastrain fostering procedure, the behaviour of lactating dams was observed in their home cage at 2, 3, 5, 7 and 14 days postpartum. As the pups became older, maternal behaviour declined in control groups, whereas PHB dams of the CBA strain persisted in nursing their pups. C57 dams were generally affected in an opposite way by PHB exposure. For example, treated dams spent significantly less time in licking behaviour. Nest quality score was especially elevated in PHB dams of the CBA strain, while in C57 dams, nest-building was inhibited and nest quality unaffected by the previous PHB exposure. These results indicate that specific items of maternal behaviour can be differently affected by PHB exposure, and that the responses are affected by the genotype. To summarise, pups raised by treated dams may receive either exaggerated or insufficient maternal attention, as a result of changes in neurotransmitter systems and behavioural regulation following phenobarbital exposure. These results point to the need for a better understanding of mother/pup interactions in studies aimed at characterizing drug and toxicant effects on postnatal development.

Animals↗
PubMed1990

Specific lysis of mycobacterial antigen-bearing macrophages by class II MHC-restricted polyclonal T cell lines in healthy donors or patients with tuberculosis.

The cytolytic capacity of mycobacterial antigen-stimulated peripheral blood mononuclear cells, from healthy Mantoux-positive volunteers and from patients with tuberculosis was investigated. Polyclonal T cell lines induced by 7 days of stimulation in vitro with PPD or a sonicate of Mycobacterium tuberculosis lysed both autologous macrophages and Epstein-Barr virus (EBV) transformed B cell lines which had been pulsed with mycobacterial antigens, to a greater extent than unpulsed target cells or target cells pulsed with an irrelevant antigen (streptokinase/streptodornase). The killing of mycobacterial antigen-pulsed macrophages and EBV-transformed B cell line targets was inhibited by monoclonal antibodies to MHC class II antigens but not by antibodies directed against MHC class I antigens. PPD-pulsed EBV-transformed lymphoblastoid cell lines (LCL) competitively inhibited the killing of mycobacterial antigen-pulsed macrophages, whereas natural killer (NK) sensitive K562 cells (with or without antigen pulsing) did not inhibit mycobacterial antigen-dependent cytolysis of macrophages. Patients with tuberculosis showed a spectrum of mycobacterial antigen-induced cytolytic capacity. Those with extensive tissue necrosis (e.g. cavitatory pulmonary tuberculosis or caseous, extrathoracic tuberculosis) had high levels while patients with disseminated (miliary) tuberculosis or disease refractory to treatment showed little evidence of mycobacterial antigen induced cytotoxicity. The ability of mycobacterial antigen-stimulated lymphoblasts to kill specific antigen-pulsed autologous macrophages was not significantly different between healthy donors and patients with tuberculosis. However, the 'mycobacterial antigen-specific' component of this cytolysis was significantly deficient (P less than 0.01) in patients. We conclude that mycobacterial antigen-specific cytotoxic T cell responses may play a significant part in the immune response to mycobacterial infection.

Adult↗
PubMed1989

Differential effects of prenatal exposure to phenobarbital on the behaviour and neurochemistry of CBA and C57BL/6J mice.

Pregnant C57BL/6J and CBA mice were administered 60 mg/kg phenobarbital intraperitoneally from days 10 to 16 of gestation. On day 18 of pregnancy half of the control and drug-treated mice were killed and the embryonic brains removed for cell cultures. The remaining mice were allowed to have their litter. After cross-fostering the mice were used for behavioural studies. Pups born to drug-treated CBA mice had birth-weights similar to controls, but their weights had fallen behind controls by day 18 after birth. They were slower at attaining mature responses in tests for sensory motor development and became progressively more hyperactive (three times more active at day 18) compared to controls. Drug-exposed C57 pups also had birth weights similar to controls. After cross-fostering, 19% of control and 31% of drug-exposed pups died, but the remaining drug-exposed pups showed no deficits in weight gain. In contrast to drug-treated CBA pups, drug-exposed C57 pups were slightly quicker in attaining mature responses in some tests. There was no difference in activity between them and their controls. In neurochemical analyses, uptake of neurotransmitters by cerebral cultures from CBA showed that uptake of GABA was increased by 5%, choline by 95%, dopamine 120%, serotonin 165% and noradrenaline by 160% in cultures from drug exposed embryos compared to controls. In cerebral cultures from C57, GABA uptake was reduced by 18%, choline 33%, dopamine 35% and noradrenaline by 25%. Only serotonin uptake was increased by 182% compared to controls. Differences between C57 and CBA were also apparent in the uptake of neurotransmitters by neuronal cultures from the mesencephalon.(ABSTRACT TRUNCATED AT 250 WORDS)

Aging↗
PubMed1986

Persistence of bone marrow lymphocytosis after induction treatment in common acute lymphoblastic leukemia. Marker analysis and significance.

In a series of 22 adult acute lymphoblastic leukemias expressing the common acute lymphoblastic leukemia antigen (cALLA +), eight had marrow lymphocytosis greater than 30% (43 +/- 12%) with disappearance of marrow lymphoblasts and correction of bone marrow insufficiency at the end of the induction treatment. Four of these patients were studied for the cALL antigen at this time and had persistence of this immunological marker (62 +/- 15% of the mononuclear bone marrow cells). The evolution of these patients suggests that these patients were not in complete remission and emphasizes the usefulness of cALLA determination in cases with borderline excess of marrow lymphocytes.

Acute Disease↗
PubMed1986

The vasoactive properties of ascitic fluid in acute pancreatitis in a porcine model.

The hemodynamic effect of pancreatic ascitic fluid was studied in a porcine model. Pancreatitis was induced by a low-pressure infusion of trypsin and taurocholate sodium into the pancreatic duct. The ascitic fluid that accumulated was then injected into the inferior vena cava of five pigs, with each pig receiving five infusions at 40-minute intervals. Mean arterial blood pressure and peripheral vascular resistance fell with each infusion, while pulmonary artery pressure increased. The magnitude of the drop in arterial blood pressure decreased with subsequent infusions, suggesting tachyphylaxis. The rise in pulmonary artery pressure increased with successive infusions. Anesthesia artifact and decay of the pancreatic ascitic fluid were ruled out as causes of the tachyphylaxis. Filtration separated the substances producing pulmonary effects and systemic blood pressure effects (0.2 to 11 microns vs 10,000 daltons to 0.2 micron). These data suggest that two mediators may produce the hemodynamic effects of pancreatic ascitic fluid.

Animals↗