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Biomedical subjects

J G Wheeler

Publications and source records attributed to J G Wheeler.

At least 55 records · Page 3Linked to original sources
PubMed1995

Inter-observer variability in the assessment of nerve function in leprosy patients in Ethiopia.

One of the major problems in leprosy is to detect any change in nerve function early enough so as to increase the chances of recovery and prevent disability. Several tests have been developed to assess nerve function and are used in leprosy control programs worldwide, but they are frequently performed by different workers on different occasions and under variable conditions. In this study we investigated the variability between different groups of observers in the assessment of nerve function in leprosy patients in Ethiopia. Sensory function was assessed by using a set of nylon monofilaments (NF) and a ball-point pen (BP), and motor function was assessed by using voluntary motor testing (VMT). We also studied the variability between observers in the assessment of the clinical signs of neuritis. Duplicate measurements were performed in random order on 50 leprosy patients by two physio-technicians and on 50 other patients by two health assistants. The percent agreement between observers was calculated for each single nerve, and weighted kappa statistics were used to assess whether agreement was better than expected due to chance alone. Systematic differences between observers were evaluated using the Wilcoxon signed rank test. On sensory testing, inter-observer variability was found to be related to the training and experience of the observer, to the nerve tested, and to the neurological status of the patient. When tests were performed by physio-technicians, we observed 32% to 58% agreement with the NF test and 71% to 84% agreement with the BP test, measured on different scales. After weighting for the scale difference, the agreement seemed comparable with these methods but the differences in measurements with the BP test were found to be dependent upon the neurological status of the patient. The variability between observers differed according to the nerve tested, and there was some evidence of systematic differences between observers with both methods. When performed by the health assistants, agreement was between 34% and 46% with the NF and between 66% and 82% with the BP tests. After weighting for the scale difference, the agreement seemed comparable but the BP was not liable to the systematic differences seen in the NF results. These differences could be attributed to the differences in the experience of the workers with these tests. With the VMT, small variability between observers was found for all nerves tested, except the facial nerve, when performed by both the physio-technicians and by the health assistants (72% to 98% agreement).(ABSTRACT TRUNCATED AT 400 WORDS)

Adult↗
PubMed1994

Serum sickness-like reactions associated with cefprozil therapy.

Four patients had serum sickness-like reactions during treatment with cefprozil, a new cephalosporin. Two patients had had previous mild reactions associated with cephalosporin therapy. It remains uncertain whether cefprozil-associated serum sickness-like reaction represents a unique or a class-related adverse drug reaction.

Adult↗
PubMed1994

Does clinical experience with a treatment regimen affect survival of lung cancer patients? An analysis based on consecutive randomized trials of the Medical Research Council in small cell and non-small cell tumours. Medical Research Council Lung Cancer Working Party.

This paper investigates the influence on patient survival of an individual clinician's experience with a particular treatment regimen and the collective experience of the centre through which the patient is recruited to a particular clinical trial. Data were available from two series of randomized trials, one series in small cell and the other in non-small cell lung cancer, which were conducted by the Medical Research Council Lung Cancer Working Party. Successive small cell trials used the same chemotherapy regimen and successive non-small cell trials the same radiotherapy regimen. We found no evidence that either the degree of experience of individual clinicians with the regimen or the participation in terms of number of patients recruited to centres influenced patient survival. There is a strong suggestion, in non-small cell lung cancer that, as clinicians' experience with the regimen extended, they became increasingly likely to admit patients in poor condition to the trials. We stress how important it is to take account of patient prognostic characteristics in such an analysis, as we found that unadjusted comparisons suggested negative influences of increasing experience with the regimen. The implications for routine audit are self evident, in particular that it is not a substitute for the randomized controlled trial.

Aged↗
PubMed1994

Comparison of colony stimulation factors on in vitro rat and human neutrophil function.

The effects of rhCSFs on in vitro polymorphonuclear leukocyte (PMN) function were studied in Sprague-Dawley neonatal and adult rats and adult and umbilical cord derived human PMN to compare species response. Following in vitro exposure to buffer or rhCSFs (50-100 micrograms/ml), PMN oxidative burst, chemotactic activity and adherence protein expression were measured. RhG-CSF increased the oxidative burst of adult rat PMN as measured by chemiluminescence and altered CD11b/CD18 in resting neonatal rat but not adult rat cells. RhGM-CSF had no effect on adult rat PMN function in vitro, but led to modest changes in adult rat PMN diapedesis across rat peritoneum. No responses were noted to rhM-CSF. Human PMN responded best to GM-CSF (particularly in the neonate), intermediately to G-CSF and none to M-CSF. These experiments show that the profile of cytokine effects is not similar in adult and neonatal rat PMN when compared to human cells. The diversity of actions in other species must be considered when using rhCSFs in animal models.

Animals↗
PubMed1994

Serum sickness-like reactions to cefaclor: role of hepatic metabolism and individual susceptibility.

In an effort to explain the increased incidence of serum sickness-like reactions (SSLR) in patients receiving cefaclor, we used an in vitro murine microsomal system as a surrogate for in vivo hepatic drug biotransformation. Lymphocytes from three groups of subjects were exposed to a nonselective mixture of cefaclor metabolites. After an 18-hour incubation of lymphocytes with these metabolites, cells were examined for viability by trypan blue exclusion. The subject groups consisted of patients with a previous history of SSLR after cefaclor therapy (n = 19), patients who experienced adverse reactions to cefaclor suggestive of immediate hypersensitivity (n = 11), and control subjects who had previously tolerated at least two courses of cefaclor therapy without adverse effect (n = 9). Additionally, immediate family members of six subjects with cefaclor-associated SSLR were studied. Lymphocyte killing was 100% greater than baseline (i.e., a non-drug-containing control) in subjects with SSLR compared with those with immediate hypersensitivity reactions (4% cell death above baseline; p < 0.001) and nonaffected control subjects (6% cell death above baseline; p < 0.001). Family studies were consistent with a pattern of maternal inheritance; five of six mothers who had not received cefaclor had a positive (i.e., > or = 35% cell death above baseline) in vitro cytotoxic response. Other studies confirmed the requirement for biotransformation of the parent drug to elicit cell death, demonstrated specificity of the reaction to cefaclor, illustrated a lack of cross-reactivity to cephalexin in subjects with SSLR to cefaclor, and verified the reproducibility of the reaction over time in an affected subject. Our findings indicate that cefaclor associated SSLR may be a unique adverse drug reaction that requires biotransformation of the parent drug and may result from inherited defects in the metabolism of reactive intermediates. Furthermore, this condition can be retrospectively confirmed with an in vitro lymphocyte-based cytotoxicity assay.

Acetaminophen↗
PubMed1993

Gene specific assay to differentiate strains of pseudorabies virus.

The need for compatibility between Pseudorabies vaccination and disease eradication measures has caused the production and release of diverse Pseudorabies virus (PRV) vaccine strains with altered genetic makeups due to the deletion of specific genes. These genes code for antigens used as differential serologic markers. By use of polymerase chain reaction (PCR), it is possible to determine, in a rapid and sensitive way, if a given PRV strain has a "wildtype" genotype, or if instead it carries a deletion for a specific gene. A sequence of 217 bp was selected as an amplification target within the gene of the essential glycoprotein 50 (gp50). Another sequence of 173 bp was selected in the joint area of glycoprotein 63 (gp63) and glycoprotein I (gI) genes. Under optimal amplification conditions, the simultaneous use of both PCR tests allowed us to differentiate specifically gI negative strains from several other wild type PRV strains, utilizing cell culture-propagated virus, acutely and latently infected neural tissue of mice and pigs as source of DNA targets. This kind of test will be useful for the rapid identification of PRV strains detected in tissues from individual animals, especially in cases of single reactors occurring in vaccinated herds. At the same time, the gene-defined PCR test will be useful for the evaluation of vaccines in their ability to prevent latency, by permitting unequivocal differentiation between vaccine and challenge virus strains.

Animals↗
PubMed1993

Protective effect of BCG against tuberculous meningitis and miliary tuberculosis: a meta-analysis.

The protective effect of BCG against tuberculosis (TB) estimated in randomized controlled trials and observational studies ranges from negative to close to a 100%. One of the many explanations offered for this is that different immunological mechanisms may be associated with protective effect against different forms and sites of disease. In this investigation, we recalculated vaccine protective effect separately for pulmonary disease and for meningeal/miliary disease in randomized controlled trials and case-control studies, tested for heterogeneity in site-specific estimates of protective effect and calculated a summary measure when appropriate. We found protective effect against pulmonary disease to be heterogeneous to a statistically significant degree, and thus we did not calculate a summary measure of protection. Protective effect against meningeal and miliary TB was higher than against pulmonary disease and, except for a single study with two cases only, appeared to be homogenous. Summary BCG protective effect against miliary or meningeal TB in randomized controlled trials was 86% (95% confidence interval [CI] 65, 95) and in case-control studies 75% (95% CI: 61, 84). The fact that protective effect appeared to be homogeneous against meningitis and miliary TB but not against pulmonary disease may result from the fact that patients with meningitis are on average younger and thus less likely to have been exposed to atypical bacteria; to a waning of the protective effect of BCG; or from the diversity of mechanisms of pathogenesis of pulmonary disease, which can originate from reinfection, reactivation or primary progression.

BCG Vaccine↗
PubMed1993

Historical cohort evaluation of ribavirin efficacy in respiratory syncytial virus infection.

Evaluation of ribavirin therapy for respiratory syncytial virus infection of the lower respiratory tract is problematic because of multiple risk factors and variable severity of illness in respiratory syncytial virus-infected patients. To address these difficulties we used multivariate analysis and performed a historical concurrent cohort study in two children's hospitals one of which had used ribavirin since licensing and one that had not utilized ribavirin therapy. The medical records of 158 patients who satisfied the American Academy of Pediatrics inclusion criteria for receiving ribavirin were analyzed for three seasons (1988 to 1991). No significant benefit of ribavirin therapy could be appreciated for the whole group in length of stay (median, 5.0 vs. 6.5 days), days on oxygen therapy (median, 5 vs. 3), progression to ventilator status (3.8 vs. 3.9%) or mortality (1.9% vs. 1.9%) for ribavirin treatment vs. supportive care. Multivariate analysis failed to uncover a beneficial effect of ribavirin when all risk factors were considered. No significant differences were noted when ventilated and nonventilated patients were examined separately. Our data raise questions about the efficacy of ribavirin when used in common practice and suggest that further prospective study, with appropriate analysis, is needed to justify the continued widespread use of this drug.

Cohort Studies↗
PubMed1993

Response of early lactation cows to fat supplementation in diets with different nonstructural carbohydrate concentrations.

Twenty-four high producing (36.7 kg/d, initially) Holstein cows in early lactation were used in a 63-d lactation trial to study the effects of low (28%), medium (31%), and high (37%) nonstructural carbohydrate concentrations in diets with added fat. Diets with isonitrogenous (17% CP) and fed as TMR with 41% sorghum silage. Nonstructural carbohydrate concentrations were altered by substitution of corn gluten feed and soybean hulls (50:50) for wheat and corn in the concentrate portion of the diet. Fat was added at 3% of DM in the form of yellow grease. Production of milk (38.5, 38.9, and 40.4 kg/d) and 3.5% FCM (38.2, 37.0, and 37.6 kg/d) was not significantly different for the cows fed low, medium, and high nonstructural carbohydrate diets, respectively. Milk fat percentages (3.47, 3.22, and 3.10%) decreased, and milk output per unit of DMI (1.5, 1.6, and 1.7) increased, as nonstructural carbohydrate concentration increased. Increasing nonstructural carbohydrate concentrations of the diet increased digestibilities of DM (58.4, 60.6, and 61.5%) and nonstructural carbohydrates (76.5, 79.6, and 80.4%) and decreased digestibilities of NDF (44.3, 43.7, and 40.6%) and ADF (46.3, 45.2, and 38.8%). Altering nonstructural carbohydrate content of the diet had no effect on AA supply to or uptake by the mammary gland or efficiency of utilization of AA for milk protein synthesis.

Animal Feed↗
PubMed1992

Transneuronal labeling of spinal interneurons and sympathetic preganglionic neurons after pseudorabies virus injections in the rat medial gastrocnemius muscle.

The distribution of retrogradely and transneuronally labeled neurons was studied in CNS of rats 4 days after injections of the Bartha strain of pseudorabies virus (PRV) into the medial gastrocnemius (MG) muscle. Tissue sections were processed for immunohistochemical detection of PRV. Retrogradely labeled cells were identified in the ipsilateral MG motor column in the caudal L4 and the L5 spinal segments. In order to evaluate the efficacy of PRV retrograde cell body labeling, the number of PRV retrogradely labeled neurons in the MG motor column was compared to the number labeled with two conventional retrograde cell body markers--Fluoro-Gold and cholera toxin-HRP. A ratio of 1:3 representing medium-sized (less than 30 microns) versus large neurons (greater than 30 microns) was found in the Fluoro-Gold dye experiments; a 1:2 ratio was seen in the PRV experiments. In contrast, when cholera toxin-HRP was used as a retrograde marker, mainly large neurons were labeled; the medium-to-large cell body ratio was 1:10 suggesting cholera toxin-HRP may have a greater affinity for the terminals of alpha-motoneurons as opposed to gamma-motoneurons. Transneuronally labeled cells were identified in the L1-L6 spinal gray matter, intermediolateral cell column (T11-L2), lateral spinal nucleus and medial part of lamina VII in C4 and C5 spinal segments, brainstem (caudal raphe nuclei, rostral ventrolateral medulla, A5 cell group, paralemniscal nucleus, locus coeruleus, subcoeruleus nucleus, red nucleus) and paraventricular hypothalamic nucleus. In the L5 spinal cord, transneuronally labeled neurons were seen in the ipsilateral spinal laminae I and II and bilaterally in spinal laminae IV-VIII, and X. Similar results were obtained in rats that had chronic unilateral L3-L6 dorsal rhizotomies indicating most of the labeling was due to retrograde transneuronal cell body labeling. In order to determine whether PRV was transported into the spinal cord by the dorsal root axons, the ipsilateral dorsal root ganglia (DRGs) were examined for PRV immunoreactivity; none was found. However, using the polymerase chain reaction, viral DNA was shown to be present in the ipsilateral DRGs indicating that some of spinal cord cell body labeling may have resulted from anterograde transneuronal labeling, as well.

Animals↗
PubMed1992

Therapeutic use of recombinant human granulocyte-macrophage colony-stimulating factor in neonatal rats with type III group B streptococcal sepsis.

The use of recombinant human granulocyte-macrophage colony-stimulating factor (rhGM-CSF) as therapy in neonatal sepsis has been proposed because of observed defects in polymorphonuclear leukocyte (PMNL) production and function in infected neonates. Newborn rats were infected intraperitoneally (ip) with type III group B streptococcus (III-GBS) and effects of treatment with rhGM-CSF given ip 7-19 h after infection were studied. Overall mortality was 67% in controls and 37% in animals treated with rhGM-CSF (P = .003). No changes in peripheral blood PMNL number or oxidative metabolic function were found in infected or uninfected animals given rhGM-CSF compared with controls. In uninfected animals, there was an increase in the oxidative burst of peritoneal cells at 3.5 h (P = .043) and in the numbers of peritoneal cells at 3 h (P = .001) in animals receiving ip rhGM-CSF compared with controls. Phagocyte priming, cellular influx into the peritoneum, or both appear to contribute to the decreased mortality observed in this model of rhGM-CSF therapy of III-GBS disease in neonates.

Animals↗
PubMed1992

Naturally acquired cellular and humoral immune responses to the major merozoite surface antigen (PfMSP1) of Plasmodium falciparum are associated with reduced malaria morbidity.

We have investigated the pattern of acquired immune responses to the major surface protein of Plasmodium falciparum merozoites (gp 190, PfMSP1) in a malaria endemic population in West Africa. A prospective longitudinal study in 3- to 8-year-old children was conducted to examine the relationship between naturally acquired immune responses to PfMSP1 and subsequent susceptibility to malaria infection and clinical disease. A population cross-sectional survey was performed to investigate changes in immune response with age. The prevalence and concentration of antibodies to all regions of the molecule increased with age with the highest prevalence of antibodies being detected against regions of the molecule which are highly conserved between parasite isolates. In vitro lympho-proliferation and interferon-gamma production in response to recombinant proteins representing polymorphic regions of the molecule also increased with age. Interestingly, proliferative responses to some regions of the molecule, including some highly conserved sequences, were highest in young children and decreased markedly with increasing age. Significant associations were observed between antibody and lymphoproliferative responses to proteins from the C terminus of the molecule and resistance to episodes of fever associated with high parasitaemia in partially immune children. In addition, high concentrations of antibodies to a conserved region close to the N terminus of PfMSP1 were also significantly associated with protection.

Africa, Western↗
PubMed1992

Evaluation of humoral responsiveness in children.

The evaluation of postvaccine antibody responses can provide a reasonably convenient and useful adjunct to the evaluation of possible humoral immune dysfunction syndromes. In patients whose clinical history is suspicious for an antibody deficiency syndrome, such studies can document normal antibody responsiveness. On the other hand the wide age-dependent variation in antibody responses makes careful interpretation necessary in concluding that a patient falls outside the "normal" pattern of antibody responsiveness. Finding a patient well below the mean values for age for multiple vaccines in concert with an appropriate clinical history would strongly suggest an abnormality of immune regulation. At this time the finding of abnormal antibody responses does not always imply that intervention with immunoglobulin therapy is indicated or that it would lead to improvement in clinical symptoms. It might help justify prophylactic antibiotic programs, however, similar to those used for recurrent otitis media. Interpretation of antibody responses in children younger than 2 years of age is probably hazardous since many patients may have relative retardation in their normal development of polysaccharide antibody responsiveness. Such patients usually develop a normal response as they grow older and do not need long term therapy. Until new technologies for measuring immune competence are developed, the above-mentioned measures of humoral immunity, when combined with clinical judgment, should be adequate to guide clinical decision-making in most cases.

Adolescent↗
PubMed1992

The diagnosis of intra-abdominal abscesses in patients with severe Crohn's disease.

A series of 24 patients with severe relapses of Crohn's disease responding poorly to conventional treatment with corticosteroids was studied to determine the incidence of intra-abdominal abscesses and the best means to detect them. Ultrasound scans proved to be difficult to interpret and unreliable. Computed tomography demonstrated abnormal bowel thickening in most cases, and showed seven of the eight intraabdominal abscesses. 111In leucocyte scintigraphy always demonstrated inflamed areas of bowel, but underestimated the extent of disease in three patients and overestimated it in five. All eight abdominal abscesses were detected, and there were no false-positive results. It was always possible to distinguish the abscess from inflamed bowel wall. Intra-abdominal abscess is not uncommon in patients with severe relapses of Crohn's disease which are not responsive to corticosteroid therapy, being present in about one-third of patients. 111In leucocyte scintigraphy is a simple and helpful test for differentiating between active inflammatory bowel disease and complicating abscesses, contributing significantly to the management of patients with severe Crohn's disease.

Abscess↗
PubMed1991

Immune response to soluble exoantigens of Plasmodium falciparum may contribute to both pathogenesis and protection in clinical malaria: evidence from a longitudinal, prospective study of semi-immune African children.

Some soluble exoantigens of Plasmodium have lipopolysaccharide (LPS)-like properties and are believed to contribute to the pathogenesis of acute malaria. We have studied cellular and humoral immune responses to several purified exoantigens of Plasmodium falciparum in a cohort of children and compared these responses with their subsequent susceptibility to malaria infection and clinical disease. We found no evidence that either lymphoproliferative or interferon-gamma (IFN-gamma) responses to these antigens were associated with protective immunity. On the contrary, children whose cells produced IFN-gamma after in vitro activation with one of the soluble antigens (Ag7) were more likely to experience clinical manifestations of malaria infection (fever and malaise) than were children whose cells did not produce IFN-gamma. It is possible that exoantigen-induced IFN-gamma may exacerbate the LPS-like effects of these antigens. However, serum antibodies to another antigen (Ag2) were more prevalent in children with asymptomatic infections or low parasitemia than in children with fever and higher parasitemia (confirmed clinical malaria), suggesting that these antibodies may contribute to the development of protective immunity.

Animals↗