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Biomedical subjects

T Smith

Publications and source records attributed to T Smith.

At least 451 records · Page 25Linked to original sources
PubMed1994

SPf66, a chemically synthesized subunit malaria vaccine, is safe and immunogenic in Tanzanians exposed to intense malaria transmission.

As part of the first trial of the SPf66 malaria vaccine in Africa, three randomized double-blind placebo-controlled studies of SPf66 have been conducted in a highly endemic area of Tanzania. The objectives were to confirm that the product is immunogenic and safe in highly exposed individuals. Results from ten male adult expatriates indicated that the product used in Tanzania is at least as immunogenic as that used in Colombia. No major side-effects were observed in indigenous SPf66 recipients (18 adults, and 25 children aged 1-4 years). Anti-SPf66 antibody titres in all groups showed clear responses to three doses of the vaccine.

Adolescent↗
PubMed1994

The ribosomal intergenic spacer region: a target for the PCR based diagnosis of tuberculosis.

SETTING: DNA Diagnostics, The National Diagnostics Centre and University College Hospital, Galway, Republic of Ireland. OBJECTIVE: To investigate the possibility of developing a DNA probe to distinguish the members of the Mycobacterium tuberculosis complex and develop an assay for the detection of M. tuberculosis in sputum. DESIGN: The ribosomal intergenic spacer regions from the members of the M. tuberculosis complex were sequenced and analysed for the ability of this region to provide sequence diversity for DNA probe development. RESULTS: The 100% sequence homology in this region precluded the development of a probe to distinguish the individual members of the M. tuberculosis complex. However it was possible to develop a DNA probe that could specifically detect only the members of the M. tuberculosis complex. CONCLUSION: A specific DNA probe was developed for the detection of the M. tuberculosis complex and its application to M. tuberculosis detection in sputum was demonstrated.

Base Sequence↗
PubMed1994

Relationships between Plasmodium falciparum infection and morbidity in a highly endemic area.

A total of 736 outpatients diagnosed as having malaria using clinical criteria at a health centre in a highly endemic area of Papua New Guinea were investigated parasitologically. Plasmodium falciparum-attributable fractions were determined using a logistic regression model to compare parasite densities in cases with those of healthy individuals in community surveys. Thirty-seven percent of presumptive cases were found to have raised P. falciparum parasitaemia. This corresponds to an average reporting rate for the population of 0.53 attributable episodes per annum. Whilst the maximum prevalence of parasitaemia in the community was in children aged 5-9 years, the maximum age-specific incidence of attributable cases at the outpatient clinic was 2 cases per annum in the 2- to 4-year-old age group. The procedure for estimating attributable fractions makes it possible to compare morbidity rates between age groups, and to examine how the relationship between morbidity risk and parasite density changes with age, without diagnosing individual episodes. The average tolerance of parasites in an age group was measured by considering the level of parasitaemia associated with a given risk of malaria-attributable morbidity. In contrast to anti-parasite immunity, tolerance of parasites declines with age since at parasite isodensity the probability of being symptomatic increases with age.

Adolescent↗
PubMed1994

Aggregation in schistosomiasis: comparison of the relationships between prevalence and intensity in different endemic areas.

Distributions of the intensities of helminth infections within their host populations are invariably aggregated. In the case of the intestinal nematodes, the degrees of aggregation have been shown to be species specific, and constant for any given species despite geographical variation in study sites. This species-specific aggregation can be quantified and used as a tool in planning control interventions. One practical application is that the prevalence of infection can be used to predict the prevalence of heavy infection and thus the risks of morbidity. This paper investigates the patterns of aggregation in schistosome egg counts in different endemic areas in Africa (data sets were obtained from Burundi, Cameroon, Tanzania, Zambia and Zaire). The analysis demonstrates that the degree of parasite aggregation, for both Schistosoma mansoni and S. haematobium, differs amongst the different study localities. This is probably due to area-specific differences in host exposure and immunity. This implies that for these schistosome species, it is not possible to predict egg count distributions or morbidity levels from prevalence data alone.

Adolescent↗
PubMed1994

Interferon-alpha 2 produced by normal human leukocytes is predominantly interferon-alpha 2b.

Peripheral blood leukocytes, isolated from the buffy coats of greater than 10,700 normal healthy donors, were induced with Sendai virus to produce biologically active interferon alpha (IFN-alpha). The IFN-alpha was purified to near homogeneity by immunoaffinity chromatography, followed by size-exclusion chromatography. The resultant product, IFN-alpha n3, is reproducibly > or = 98% pure (to be reported elsewhere). The different IFN-alpha proteins in IFN-alpha n3 were separated by reverse-phase high performance liquid chromatography (RP-HPLC) and the identity of the IFN-alpha 2 isolated by HPLC was determined by amino-terminal sequencing. IFN-alpha 2 was found to migrate as two closely eluting peaks on RP-HPLC, and they have been designated as peaks 1.1 and 1.2. Distinction among the three possible variants of IFN-alpha 2, i.e., IFN-alpha 2a, IFN-alpha 2b, and IFN-alpha 2c, was determined by amino-terminal sequencing of the first 35 amino acids in peaks 1.1 and 1.2. Protein sequence data showed that the discriminating amino acids found at positions 23 and 34 are Arg and His, respectively. The presence of Arg and not Lys at amino acid position 23 and His at amino acid position 34 argues that IFN-alpha 2b is the major component in the Sendai virus-induced leukocyte IFN-alpha 2 and that IFN-alpha 2a is not present. These findings were verified by subjecting RP-HPLC peaks 1.1 and 1.2 to CNBr cleavage, followed by separation of the fragments by RP-HPLC and sequencing.(ABSTRACT TRUNCATED AT 250 WORDS)

Amino Acid Sequence↗
PubMed1994

Foscarnet-resistant herpes simplex virus infection in patients with AIDS.

Six human immunodeficiency virus-infected patients had clinical lesions of herpes simplex virus (HSV) type 2 that showed in vitro resistance to foscarnet. In each patient, lesions were unresponsive to foscarnet therapy or developed during daily suppressive foscarnet. Five patients had a history of intermittent or chronic foscarnet use for the management of acyclovir-resistant HSV infection, and 1 was receiving daily foscarnet for suppression of cytomegalovirus retinitis. Seven of 10 foscarnet-resistant isolates from 6 patients were susceptible to acyclovir in vitro, and 1 was of borderline susceptibility. In 3 patients, the administration of acyclovir, either alone or in combination with foscarnet, resulted in healing. Clinically significant resistance to foscarnet may occur in immunosuppressed patients with prior foscarnet exposure. Addition or substitution of acyclovir to foscarnet therapy may be a useful strategy for patients in whom foscarnet resistance is suspected, pending the results of in vitro susceptibility testing.

AIDS-Related Opportunistic Infections↗
PubMed1994

Client flow analysis: a practical management technique for outpatient clinic settings.

Client flow analysis (CFA) is a practical technique to help address one of the most frequently cited causes of patient disquiet with quality of health services--waiting times. It allows clinic managers and workers to look at the way that clients and patients move through the clinic. It gives information on waiting times, time spent in contact with different service providers, bottle-neck areas in services and staff utilization patterns. It is a technique which is simple, quickly performed, cost effective, easy to learn and easily transferrable. This paper gives two illustrative examples of sites where CFA has been initiated in Africa--a free-standing family planning clinic and a provincial hospital outpatient clinic. Waiting times were reduced by over one-half and by one-third, respectively. By reducing waiting times for clients and patients and addressing some of the problems of staff time allocation, the quality of clinic operations can be improved for both providers and clients.

Ambulatory Care Facilities↗
PubMed1994

Attaining The Health of the Nation targets for ischaemic heart disease: the contribution of a clinical outcome measure.

BACKGROUND: Deaths occurring within 30 days of admission as a percentage of all admissions with acute myocardial infarction' was recently defined by the Scottish Office Clinical Resource and Audit Group as a clinical outcome measure for inclusion in service contracts between purchaser health authorities and provider NHS trusts. The aim of this study was to determine the extent to which improvements in the clinical outcome measure have already contributed and may continue to contribute to attaining the Health of the nation targets for ischaemic heart disease (IHD). METHODS: Information was obtained from the computerized discharge summaries of patients treated in Tayside hospitals and the death registrations provided by the Registrar General for Scotland. RESULTS: In Tayside between 1980-1982 and 1990-1992, the number of death outside hospital from acute myocardial infarction (AMI) in the under-65s fell by 33 per cent, and the proportion of patients admitted as emergencies with AMI who died within 30 days fell by 40 per cent. The proportion of diagnosed heart attacks which proved fatal fell by a third over the period. CONCLUSION: As 75 per cent of deaths from IHD in the under-75s still take place before hospital admission, not more than 25 per cent of the overall fall in deaths from IHD can be accounted for by improvements in the clinical outcome measure. Most of the fall was apparently unrelated to immediate medical intervention after an attack, long-term nutritional and behavioural changes possibly having reduce the severity of diagnosed attacks. The Health of the nation targets cannot therefore be met by improvements in the clinical outcome measure alone.

Aged↗
PubMed1994

Pressure and volume control for local drug-delivery catheters: development of a new microprocessor-controlled system.

BACKGROUND: Local drug delivery is a potential solution to postintervention restenosis. Most catheters developed for local delivery depend upon control of pressure and of delivered volume for optimal performance. The present study was designed to assess the accuracy of current methods for inflation of local delivery catheters compared with a new microprocessor-controlled system specifically designed for this application. METHODS: An in vitro gravimetric testing system was constructed to record developed pressure and delivered volume using a variety of inflation devices and a microporous infusion catheter. Experienced catheterization laboratory personnel were given commercial angioplasty indeflators and a pressure-driven syringe and asked to quickly apply 5 atm and deliver 2.0 ml. A new microprocessor-controlled system was then tested using the same protocol. RESULTS: The time required to reach a plateau pressure was lowest with the pressure-driven syringe (0.164 +/- 0.017 s) and much higher with standard indeflators (2.94 +/- 2.54, 4.64 +/- 2.98, 7.69 +/- 4.89, 8.28 +/- 6.31 s). The corresponding microprocessor-controlled value was much lower than that of the manual systems (0.84 +/- 0.37 s). The variability of plateau pressure, as measured by the standard deviation, was lowest with the pressure-driven syringe (0.029 +/- 0.014 atm) and highest with the manual systems (0.37 +/- 0.26, 0.40 +/- 0.18, 0.44 +/- 0.31, 0.32 +/- 0.10 atm). The microprocessor-controlled system also produced very little variability in pressure (0.08 +/- 0.004 atm). The volume delivered varied significantly with all manual devices (1.77 +/- 0.64, 1.74 +/- 0.66, 1.36 +/- 0.45, 1.80 +/- 0.33 ml) as well as with the pressure-driven syringe (1.86 +/- 0.32 ml), but the volume delivered by the microprocessor-controlled system was highly accurate (1.99 +/- 0.06 ml). CONCLUSIONS: Manual inflation devices do not allow precise control of pressure or volume when used with local delivery catheters. Use of a pressure-driven syringe minimizes pressure error, but does not deliver an accurate volume. The microprocessor-controlled system minimizes pressure and volume error and should maximize transfer efficiency for local delivery catheter systems.

Angioplasty, Balloon, Coronary↗
PubMed1994

Acute lymphocytic leukaemia in the elderly: characteristics and outcome with the vincristine-adriamycin-dexamethasone (VAD) regimen.

To analyse the pretreatment characteristics, response to therapy, and overall prognosis of elderly patients with acute lymphocytic leukaemia (ALL), 268 consecutive adults with newly-diagnosed ALL who received the vincristine-adriamycin-dexamethasone (VAD) regimens were reviewed. Pretreatment characteristics, response to VAD therapy, and overall outcome were analysed in patients 60 years or older, and compared to younger patients. Fifty-two patients (19%) were 60 years or older. Compared with younger patients, elderly patients with ALL had a significantly worse performance status at presentation (P < 0.001); higher incidences of FAB L2 morphology (P = 0.03), thrombocytopenia (P < 0.01), hypoalbuminaemia (P < 0.001) and renal dysfunction (P = 0.03); and trends for worse anaemia (P = 0.06) and a higher rate of myeloid markers positivity (P = 0.06). With VAD induction therapy, elderly patients had a lower CR rate than younger patients following two induction courses (CR rate 58% v 82%; P < 0.01), and overall (CR rates 65% v 90%; P < 0.01). The response rate to VAD chemotherapy, however, appeared superior to the 30-35% CR rates reported from other series in elderly ALL patients. The lower CR rate was due to both higher induction mortality (P = 0.02) and more resistant disease (P < 0.01). The long-term CR rate was 20% in elderly patients achieving CR, but the overall survival was poor (< 10% at 3 years). There were strong associations between older age and other poor prognostic features. However, multivariate analyses identified older age to be an independent poor prognostic factor for response to chemotherapy. In summary, elderly patients with ALL have an appreciable CR rate with the VAD regimens. Patients achieving CR may have durable remissions. The myelosuppression-associated mortality in both remission induction and maintenance may be reduced with the addition of growth factors in both treatment phases, and by using standard maintenance therapy without consolidation-intensification phases.

Age Factors↗
PubMed1994

Neuroendocrine-immune interactions in homeostasis and autoimmunity.

Recent experimental evidence confirms the interrelationships between the central nervous, neuroendocrine and immune systems. Indeed, extensive duality exists in the use of neurotransmitters, hormones and receptors each system displays. In the present annotation, the effect of cytokines, soluble mediators of immune function, on the CNS and neuroendocrine systems is addressed and conversely, we discuss the modification of the immune compartment by the sympathetic nervous and neuroendocrine systems, with particular reference to the role of noradrenaline and corticosterone. Dysfunction between the systems is considered in the context of autoimmune conditions, with emphasis on experimental allergic encephalomyelitis and the contribution of corticosterone-driven T-cell apoptosis to recovery from the disease. Finally, we speculate on the relevance of neuroimmune interactions in the pathogenesis of multiple sclerosis.

Animals↗
PubMed1994

Cardiorespiratory reflexes, vibratory and thermal thresholds, sensory and motor conduction in diabetic patients with end-stage nephropathy.

The neuropathic profile was studied in 26 patients with long-standing, insulin-dependent diabetes mellitus and end-stage nephropathy using tests to evaluate large and small nerve fibres and autonomic function. Clinically, 18 patients (69%) has symptoms and signs of peripheral neuropathy, 9 (35%) had symptoms of autonomic involvement. Vibratory sensation was impaired in 20 patients (77%) in the lower limbs and in 6 (22%) in the upper limbs; cold and warm sensation was equally often impaired in the feet and in the hands with no significant difference between patients with and without neuropathy. Heart rate variation was abnormal in 23 patients at rest (88%), in 24 (92%) during deep breathing and during the orthostatic test. Conduction studies revealed abnormalities in two or more nerves in all patients regardless of whether or not they had overt neuropathy clinically. Thus, the applied multimodal tests revealed evidence of impaired function in large or small nerve fibres or both in all patients independent of clinical findings.

Adult↗
PubMed1994

Effect of pancreas and kidney transplantation on the neuropathic profile in insulin-dependent diabetics with end-stage nephropathy.

From a series of 26 diabetics selected for combined pancreas and kidney transplantations 9 died before surgery was scheduled, one died after surgery and 4 rejected the transplants. The effect of pancreas or kidney transplantation or both on vibratory perception and thermal thresholds, various motor and sensory conduction parameters were studied in 9 of the remaining 12 patients. In 6 both the pancreatic and renal grafts were functioning, in 2 the pancreas was rejected, and in 1 the kidney. At an average follow-up of 41 months after surgery, the mean total score of clinical and electrophysiological improvement in 6 patients with successful combined transplantation was 5.5 +/- 1.6 compared with -4.3 +/- 2.5 in 3 patients with one surviving transplant (P < 0.001). Similarly, the average increase in nerve conduction velocity was 5.8 +/- 1.1 m/s in patients with two functioning grafts whereas it decreased 2.9 +/- 0.7 m/s in those with only one (P < 0.001). The quality of life was considered improved in patients with successful outcome of the two organ transplantations in contrast to the statements of those with only one.

Autonomic Nervous System↗
PubMed1994

Do high levels of C-reactive protein in Tanzanian children indicate malaria morbidity.

Children under 6 years of age living in an area of Tanzania highly endemic for malaria were tested for C-reactive protein (CRP) in order to determine how the acute-phase response is related to malaria in children of different ages and to investigate whether serum CRP concentrations might be useful in the qualification of morbidity in such children. The median CRP level in the 629 finger-prick blood samples measured, 6.0 mg/liter, was much higher than that reported in the blood of children in Europe. The CRP concentration was correlated with recent illness reported by the parents. High CRP levels were most strongly associated with Plasmodium falciparum parasitemia in children under 1 year of age. In older children, lower levels of CRP were associated with parasitemia, and fewer children had increased CRP levels attributable to parasitemia. The levels of malaria-attributable CRP appear to track the acquisition of parasitological and clinical tolerance in this area with very high levels of P. falciparum transmission. Determination of CRP levels should be useful in the rapid assessment of the overall burden of morbidity, especially in infants. In areas where malaria is endemic, CRP associated with increased parasite densities provides an objective measure of malaria-specific morbidity. This would be an efficient approach to estimating malaria morbidity risks from small-scale serological surveys.

Animals↗
PubMed1994

Hypothalamic PGE2 and cAMP production and adrenocortical activation following intraperitoneal endotoxin injection: in vivo microdialysis studies in Lewis and Fischer rats.

Inflammatory disease-susceptible Lewis (LEW) rats exhibit reduced glucocorticoid release in response to inflammatory and neurotransmitter stimuli, compared to histocompatible Fischer (F/344) rats. This compromised hypothalamo-pituitary-adrenal (HPA) axis activity has been ascribed to a primary defect in hypothalamic corticotrophin-releasing factor-41 (CRF) secretion, possibly caused by abnormal signal transduction in the CRF neuron. In the present study, we have used in vivo microdialysis to asses the role of hypothalamic prostaglandin E2 (PGE2) and cyclic adenosine monophosphate (cAMP) in endotoxin-mediated HPA axis activation in adult hyporesponsive LEW and hyperresponsive F/344 rats. Basal plasma corticosterone concentration was significantly higher in F/344 relative to LEW rats; however, the basal levels of PGE2 and cAMP, recovered from microdialysis probes in the anterior hypothalamus, were significantly greater in the LEW rat. Lipopolysaccharide (LPS) (200 micrograms/kg) caused a time-dependent increase in corticosterone secretion, the magnitude of which was markedly greater in the F/344 rat. Both LEW and F/344 rats displayed a similar PGE2 profile in response to LPS, although in absolute terms the response was more pronounced in LEW rats. LPS caused a dose-related increase in cAMP production in the LEW rat and comparison with F/344 animals, following the 200 micrograms/kg dose of LPS, revealed a larger and more prolonged cAMP response in the LEW strain. Simultaneous administration of indomethacin (50 mg/kg) with LPS (200 micrograms/kg) in the LEW rat completely blocked the PGE2 and cAMP responses to the toxin and whilst the corticosterone response to LPS was significantly attenuated at 140 min, no difference was apparent by 240 min. Hence, PGE2 and cAMP participate in the hypothalamic response to endotoxin-mediated adrenocortical activation in both LEW and F/344 adult rats but the steroid and second messenger profiles are strain-specific. The cAMP response to LPS appears to depend on products of arachidonic acid metabolism, such as PGE2, and hence basal and stimulated production of these mediators may be effected by the steroid milieu.

Adrenal Cortex↗