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Biomedical subjects

A Robinson

Publications and source records attributed to A Robinson.

At least 289 records · Page 16Linked to original sources

Prognostic factors in juvenile chronic granulocytic leukaemia.

A retrospective analysis of the clinical and haematological characteristics of patients diagnosed as having juvenile chronic granulocytic leukaemia between 1971 and 1986 was carried out. Thirty-three children were identified who were between the ages of 18 weeks and 8.8 years at diagnosis. The disease was more frequent in boys than girls (23:10). The most common presenting symptoms were skin rash (58%) and bleeding manifestations (45%). All patients had some degree of splenomegaly and in 88% this was more than 3 centimetres below the costal margin. Hepatomegaly and lymphadenopathy were also frequent findings. Anaemia was common and leucocytosis an invariable finding with a white cell count above 50 x 10(9) 1-1 in 42%. Monocytosis was found in 78%. Haemoglobin F measurements were available in 31 children and above 10% in 22 (67%). No child had the Philadelphia chromosome or monosomy 7. Thirty children were treated with chemotherapy, with a variable degree of symptomatic improvement. Twenty-nine patients had died with a median survival time of 5 months. The commonest cause of death was complications of bone marrow failure and no child developed acute leukaemia. Presenting characteristics associated with a longer survival period were age less than 6 months (P = 0.02), female sex (P = 0.02), HbF less than 10% (P = 0.0004) and the absence of bleeding manifestations (P = 0.03). We conclude that the prognosis for children aged over 6 months, with a raised HbF level is very poor, and that, in the absence of possible bone marrow transplantation, consideration should be given to novel treatment approaches for these patients.

Antineoplastic Agents↗

Phase II trial of whole-cell pertussis vaccine vs an acellular vaccine containing agglutinogens.

An acellular pertussis vaccine containing agglutinogens 2 and 3, pertussis toxin, and filamentous haemagglutinin was developed by the Centre for Applied Microbiology and Research in the UK. 188 infants were entered into a randomised blind trial and received either the acellular or a whole-cell vaccine, combined with diphtheria and tetanus toxoids, in a 3, 5, and 8-10 month schedule. Local reactions were similar in the two groups but significantly fewer infants had systemic symptoms after the acellular vaccine. Mean log-antibody titres to the agglutinogen and toxin components were higher with the acellular than with the whole-cell vaccine. Persistence of antibodies one year after the third dose was also better in the acellular group.

Antibodies, Bacterial↗

A comparison of fibrillation in denervated skeletal muscle of the anaesthetized rat and guinea-pig.

We have used intracellular recording in vivo to study fibrillation (spontaneous repetitive membrane activity) in extensor digitorum longus (fast twitch) and soleus (slow twitch) muscles of the anaesthetized rat and guinea-pig denervated for periods of about 10 to 60 days. The proportion of fibres fibrillating in the guinea-pig soleus was greater than 50% in most animals up to the longest period of denervation (65 days). Fibrillation was rarely found in rat soleus after three weeks of denervation. Its incidence in the extensor digitorum longus muscles of both species was intermediate. The mean frequency of fibrillation was higher in guinea-pig extensor digitorum longus (16 Hz) and soleus (8 Hz) than in the rat extensor digitorum longus (3 Hz) and soleus (2 Hz). The resting membrane potentials of the denervated muscles were less than normal and correlated inversely with the frequency of fibrillation but not with the incidence of fibrillation: in rat soleus, many fewer fibers were fibrillating at a given membrane potential than in the other three muscles. The incidence of fibrillation was compared with previously reported tensions of the four denervated muscles and was found to have the same rank order. We suggest that fibrillation may reduce atrophy (and hence tension loss) of denervated muscle, which may have implications for artificial stimulation. Fibrillation frequency was directly related to changes in twitch speed of the four muscles after denervation.

Animals↗

An exploration of family and individual profiles following father-daughter incest.

This paper presents the results of a range of psychometric assessments which attempted to identify family and individual variables associated with father-daughter incest. Psychometric self-report measures were used to examine differences between families in which incest had been confirmed and a matched comparison group. Significant differences between the members of the incest and the comparison groups included behavioral and self-esteem problems in the daughters and differences in the familial environments of the two groups. Daughters who had been sexually abused reported lower levels of self-esteem about their intellectual and school status. Mothers in the incest group reported that their daughters had more conduct problems than the comparison mothers. The incest families were generally reported to be higher in conflict and organization and lower in cohesion, expressiveness, and active recreation. No differences between groups were found for levels of marital adjustment, self-esteem in mothers, or overall level of psychopathology in the perpetrators.

Adaptation, Psychological↗

Oral immunization with bacterial polysaccharide and adjuvant enhances antigen-specific pulmonary secretory antibody response and resistance to pneumonia.

Nosocomial pneumonia, often due to Pseudomonas aeruginosa, occurs frequently after haemorrhage and trauma, and contributes to the increased incidence of morbidity and mortality in this clinical setting. In order to determine if enhancement of bacterial antigen-specific secretory IgA (sIgA) titres in the lungs can increase resistance to P. aeruginosa pneumonia following haemorrhage, we investigated oral immunization strategies, using bacterial polysaccharides (levan, from Aerobacter levanicum, and P. aeruginosa polysaccharide type I) and adjuvant (cholera toxin and the B-subunit of cholera toxin), capable of increasing bacterial polysaccharide-specific pulmonary secretory antibody titres. Oral co-administration of 1000 micrograms levan and 10 micrograms cholera toxin resulted in increased titres of levan-specific sIgA in lung lavages and increased numbers of levan-specific pulmonary plasma cells, but no changes in serum anti-levan titres. Similarly, oral co-administration of 1000 micrograms P. aeruginosa polysaccharide and 10 micrograms cholera toxin produced increased anti-P. aeruginosa polysaccharide titres in lung lavages. Significant decreases in anti-levan pulmonary sIgA titres and in numbers of levan-specific pulmonary plasma cells were found when oral immunization with levan and cholera toxin was performed 4 days following haemorrhage, but not if the mice were immunized 8 h after blood loss. Although haemorrhage markedly increased the susceptibility of mice to P. aeruginosa pneumonia, significant protection from mortality could be achieved through oral immunization with 1000 micrograms P. aeruginosa polysaccharide and 10 micrograms cholera toxin 8 h after haemorrhage. These results demonstrate that haemorrhage induces marked alterations in bacterial antigen-specific pulmonary B-cell responses, which contribute to the increased susceptibility to infection in this setting.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Oral↗

Noscapine-induced polyploidy in vitro.

The conditions under which noscapine causes high levels of polyploidy in vitro in human lymphocytes were investigated to try to determine its mode of action and to assess whether it was likely to be a genotoxic hazard when used as an antitussive agent. Irrespective of duration of treatment or type of medium, there seemed to be a threshold for polyploidy induction between 15.0 and 30.0 micrograms/ml and a maximum between 100.0 and 150.0 micrograms/ml noscapine. High levels (10.0-20.0%) of noscapine-induced polyploidy were never found with 4 h treatments or with RPMI 1640 medium plus 15% (v/v) foetal calf serum; the use of Iscove's modified Dulbecco's medium and 24 h treatments were needed. The reasons for these observations seemed to be the faster cell division and greater sensitivity of cells grown in Iscove's medium. There was conflicting evidence about the mechanism of polyploidy induction by noscapine; either spindle damage or cell fusion remain as possibilities. The need for prolonged exposure and the precise nutritional requirements suggest that a short exposure, albeit at high concentration, in the upper gastro-intestinal tract is unlikely to be a hazard for humans. Furthermore, evidence of a threshold at approximately 20 micrograms/ml plus the virtual elimination of noscapine-induced polyploidy by microsomal metabolism (S9 mix) together with published metabolic data imply that the low-level systemic exposure after absorption may well not be hazardous. We conclude that the use of noscapine in cough mixtures does not pose a significant potential hazard for humans.

Bromodeoxyuridine↗

Effects of hemorrhage and resuscitation on bacterial antigen-specific pulmonary plasma cell function.

BACKGROUND AND METHODS: Nosocomial pneumonia is frequent after hemorrhage and trauma, and often contributes to multiple organ system failure, morbidity, and mortality in this setting. Although the percentages and numbers of resting pulmonary B cells (clonal precursors) able to be stimulated to produce antibodies to bacterial antigens are markedly decreased after hemorrhage, the effects of hemorrhage on the pulmonary plasma cells actually producing antibody to bacterial antigens have not been examined. To investigate this question, mice were bled 30% blood volume, then resuscitated with the shed blood 1 hr later. At predetermined times after hemorrhage, the mice were intranasally immunized with liposomes containing the bacterial polysaccharide antigen levan (from Aerobacter levanicum). One week later, lung lavages were performed to measure bacterial antigen-specific secretory immunoglobulin A (sIgA) titers and the numbers of intraparenchymal pulmonary plasma cells producing antibody against the bacterial antigen were determined. RESULTS: Reduced numbers of pulmonary plasma cells producing antibody against the immunizing bacterial polysaccharide antigen were found between 1 and 14 days after blood loss, and titers of bacterial antigen-specific secretory IgA were decreased for greater than 2 wks after hemorrhage. The importance of these abnormalities in pulmonary B-cell function was demonstrated by an increased susceptibility to Pseudomonas aeruginosa pneumonia in mice infected 4 days after hemorrhage, when bacterial antigen-specific pulmonary plasma cell numbers were at their lowest point. Resuscitated mice showed the same increased susceptibility to P. aeruginosa pneumonia as did hemorrhaged but unresuscitated animals. CONCLUSIONS: Hemorrhage, even if resuscitated, results in alterations in bacterial antigen-specific pulmonary B-cell function and secretory IgA production that are profound, long lasting, and associated with increased susceptibility to infection at this mucosal surface. Because these effects on pulmonary B-cell function do not occur immediately after hemorrhage, immunization techniques able to enhance bacterial antigen-specific secretory IgA titers at pulmonary surfaces may be able to increase resistance to nosocomial pneumonia if administered shortly after injury and blood loss.

Animals↗

Construction and characterization of Bordetella pertussis mutants lacking the vir-regulated P.69 outer membrane protein.

The Bordetella pertussis P.69 protein is an immunogen with vaccine potential. The role of this protein in pathogenesis is unclear; it has been associated with the toxic adenylate cyclase and adhesion to eukaryotic cells. For further analysis of the role of P.69 in the biology of B. pertussis, we have constructed strains which specifically lack P.69. The cloned P.69 (prn) gene of B. pertussis was insertionally inactivated with a kanamycin-resistance cassette. This inactivated gene was used to construct P.69- mutants of B. pertussis by allelic exchange using plasmid pRTP1. B. pertussis P.69- strains produced normal levels of other vir-regulated factors, including adenylate cyclase. The serotype of B. pertussis, determined by Eldering and Preston typing sera and monoclonal antibodies, was also unaffected by the presence or absence of P.69. The ability of a prn mutant to adhere to and invade HEp2 cells was not significantly different from that of its parent strain. A strain containing a mutation in fhaB was significantly less adhesive and invasive than its parent, and a prn fhaB double mutant exhibited an even greater reduction in adhesiveness and invasiveness down to levels comparable with a Vir- strain. However, strains harbouring mutations in FHA and/or P.69 were able to colonize or multiply in the murine respiratory tract, although a Vir- strain was unable to survive and proliferate in the same infection model.

Adenylyl Cyclases↗

Seminal white blood cells in men with urethral tract infection. A monoclonal antibody study.

Monoclonal antibodies were used to detect seminal leucocytes in 19 men with urethritis. A wide range in the number and type of leucocytes between individuals was documented (median 2.06 x 10(6)/ml, range 0.6-29.89 x 10(6)/ml); 22% of the men had less than 1 x 10(6) leucocytes/ml. The results suggest that the threshold of greater than or equal to 1 x 10(6)/ml proposed by the World Health Organisation to indicate genital tract infection is unsuitable for men with urethritis.

Antibodies, Monoclonal↗

Dieting concerns have a functional effect on the behaviour of nine-year-old girls.

The eating patterns of restrained and unrestrained nine-year-old girls were compared. Prospective seven-day food diary records showed the restrained girls to eat significantly less energy and dietary fibre than the unrestrained. Their ratings of hunger were also significantly higher. Most nutritional indicators, however, showed their diet to be of adequate quality. The translation of dieting concerns into dieting behaviour by nine-year-olds may increase their susceptibility to future clinical eating problems.

Child↗

Parasuicide and alcohol: a 20 year survey of admissions to a regional poisoning treatment centre.

The relationship between alcohol dependence, alcohol consumption and parasuicide was studied among patients admitted over a twenty year period (1968-87) to a regional poisoning treatment centre in Edinburgh. Both alcohol dependence and consumption of alcohol at the time of the parasuicidal act were reported more commonly by men than by women. An examination of temporal trends showed little change among male patients, while the proportion of females diagnosed as alcohol dependent or consuming alcohol at the time of the act tended to increase over time. A comparison of alcohol dependent (AD) and non-alcohol dependent (non-AD) parasuicides over the period 1982-87 revealed differences in respect of sociodemographic characteristics (the AD group containing more unemployed, especially long term) clinical variables (the AD group being more likely to have acted suicidally and to have received psychiatric treatment in the past, yet less likely to be currently diagnosed psychiatrically ill), family features and social problems. The implications of the study findings for research and service delivery are mentioned.

Adjustment Disorders↗

Reconstruction of the anterior cruciate ligament with an intra-articular patellar tendon graft and an extra-articular tenodesis. Results after six years.

We describe 74 patients with disabling instability of the knee due to isolated anterior cruciate deficiency. None responded to conservative measures or correction of internal derangements. All patients were treated by replacement of the anterior cruciate ligament with the medial third of the patellar tendon as a free graft, supplemented by an extra-articular MacIntosh lateral reconstruction. A satisfactory outcome was found in 93% of knees after an average of 70 months follow-up. Cast immobilisation after operation, the interval between injury and reconstruction, the age of the patient and the severity of symptoms before reconstruction had no significant effect on the final outcome.

Activities of Daily Living↗

Proteolysis of interleukin-2, interferon and immunoglobulin by venoms.

Limited proteolysis by venoms was analysed by the cleaved peptide band(s) in SDS-polyacrylamide gel electrophoresis. The venom from Crotalus atrox degraded interferon, interleukin-2, IgG, IgM, and a crude form of acetyl cholinesterase but had no effect on IgA. Although the venom from Androctonus australis did not exert appreciable proteolysis on any of the immunoglobulins it had potent proteolytic activities against interferon and interleukin-2. The venom from Vespula maculifrons had only a minor proteolytic effect on interferon. The proteolysis by venoms was not effectively inhibited by alpha 1-antitrypsin or a2-macroglobulin. Moreover, no appreciable proteolytic activity was detected in the venoms from Bufo arenarum, Apis mellifera and Heloderma suspectrum.

Animals↗

Genetic aspects of familial multiple myeloma.

To elucidate the role of genetics in familial multiple myeloma, two sisters having plasma cell dyscrasia were studied. The women were 58 and 56 years old, and the diagnoses were made 22 months apart. Specific antisera for patient 1's lambda light chains produced in rabbits had no cross-reactivity with her sister's lambda light chains. Karyotypic analysis by G.T.G. banding revealed abnormalities in both patients, but no common abnormalities. HLA typing disclosed identical tissue types (AW24, A26, B13, BW55). An immunologic epidemiologic study performed on 26 family members, encompassing four generations, disclosed no additional cases of paraproteinemia.

Female↗

Role of gastric colonization in the development of pneumonia in critically ill trauma patients: results of a prospective randomized trial.

Critically ill trauma patients were entered in a prospective, randomized trial to determine the role of gastric colonization in the development of pneumonia. Trauma patients admitted to the SICU were randomized to receive antacids (n = 27), continuous IV cimetidine (n = 32), or sucralfate (n = 30). Quantitative nasogastric tube (NGT) cultures were obtained biweekly and correlated with gastric pH, the incidence of pneumonia, and the incidence of pneumonia caused by an organism previously isolated from the stomach (percentage of gastric source of pneumonia--% GSP). Patients receiving antacids had a significantly greater pH than those receiving cimetidine (5.6 +/- 1.03 vs. 4.7 +/- 1.03; p = 0.006). However, there was no significant difference between the overall incidence of pneumonia, the percentage of NGT isolates greater than 10(6)/ml, or the % GSP. The gastric bacteriology of the three subgroups was nearly identical, with Candida albicans, Enterococci, and beta-hemolytic Streptococci being the most frequently isolated organisms. Gastric growth of organisms preceding their appearance in the blood occurred in 5 of 89 (5.6%) patients. These results suggest that 1) in trauma patients, the incidence of pneumonia is not increased by the use of stress ulcer prophylactic agents that elevate gastric pH; 2) increases in gastric pH progressively increased the number of intragastric bacteria but this did not correlate with an increased incidence of % GSP; and 3) while organisms in the upper intestinal tract may be pathogens for pneumonia, they are uncommonly a source of bacteremia in seriously injured patients.

Adolescent↗

Hemorrhage in mice produces alterations in pulmonary B cell repertoires.

Nosocomial pneumonia occurs frequently after hemorrhage and trauma and contributes to the increased incidence of morbidity and mortality after severe injury. The production of secretory antibodies by mucosally associated B cells is an important component of pulmonary host defense mechanisms. To determine the effects of hemorrhage on pulmonary B cell function, we examined hemorrhage induced alterations in pulmonary B cell repertoires. There were no changes in the relative distribution of T or B cells among intraparenchymal pulmonary lymphocytes after blood loss. Hemorrhage induced decreases of between 5- and 10-fold in the frequencies and numbers of pulmonary B cell clonal precursors specific for the bacterial Ag levan and Pseudomonas aeruginosa polysaccharide. These decreases in numbers and frequencies of bacterial Ag-specific pulmonary B cell clonal precursors were present between 3 and 10 days after blood loss. Similar decreases in numbers and frequencies were found among pulmonary clonal precursors specific for the autoantigen mouse transferrin, but not for the autoantigen dsDNA or the external antigens OVA and keyhole limpet hemocyanin. These results demonstrate that hemorrhage produces marked alterations in pulmonary B cell repertoires, which may contribute to postinjury abnormalities in host defenses.

Animals↗