Explosive tinnitus: an underrecognized disorder.
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Aged↗
Biomedical subjects
K Connolly
Publications and source records attributed to K Connolly.
Coeliac disease in Galway, Ireland 1971-1990.
Recent studies have reported changes in the incidence of coeliac disease and in its presentation. We carried out a retrospective study looking at the incidence and clinical features of coeliac disease in Galway children over a 20 year period. The study period was divided in two parts. (I) Patients diagnosed between 1971 and 1980 and (II) between 1981 and 1990. Comparison was made between demographic and clinical data in these two periods. There were 97 cases of coeliac disease diagnosed in children resident in Galway over the 20 year period. 71 patients were diagnosed in period I and 26 in period II. The median age at diagnosis in period I was 1.41 years and 4.95 years in period II. There were more females diagnosed in period I. Growth data, histology and enzyme levels were similar in both groups. Diarrhoea and vomiting were the major presenting symptoms in both periods but more patients presented with wasting or abdominal protuberance in the latter period. Our data support the concept that coeliac disease in childhood is declining, and is presenting at a later age.
Adolescent↗
alpha beta T cell development is abolished in mice lacking both Lck and Fyn protein tyrosine kinases.
Two families of protein tyrosine kinases (PTKs), the Src and Syk/ZAP-70 families, are required for T cell development. Lck is the major Src family member required for thymopoiesis, since there is a severe deficit of CD4+CD8+ thymocytes and mature T cells in its absence. However, some peripheral T cells are evident in these mice, suggesting that additional PTKs may contribute to T cell development. Here we show that the combined disruption of Lck and Fyn (lck(-/-)fyn(-/-)) completely arrests alpha beta T cell development at the CD4-CD8- stage. The development of V gamma 3+ dendritic epidermal T cells is also severely impaired, but natural killer cell development and cytolytic activity is unaffected in lck(-/-)fyn(-/-) mice. These findings reveal the potential for redundant functions mediated by Src family PTKs while emphasizing crucial roles for Lck and Fyn in T cell development.
Animals↗
Initial biocompatibility studies of a novel degradable polymeric bone substitute that hardens in situ.
Clinical management of osseous defects often requires bone grafts. The standard for treatment is autogenous bone harvested from sites such as either the iliac crest or the outer table of the calvaria. In addition to the problem of donor site morbidity and the limited supply of graft material, there is the additional operating time associated with harvesting procedures. A synthetic, bone graft substitute that can match the clinical performance of autogenous bone could alleviate these deficiencies. Therefore, a polymeric bone substitute was developed that consists of a four-armed star polymer of poly(dioxanone-co-glycolide) endcapped at each termini with a biocompatible lysine-based diisocyanate crosslinker. The polymer can be mixed with inorganic fillers such as either hydroxyapatite or tricalcium phosphate to form either injectable or moldable putty. The addition of a catalyst (for example, diethylaminoethanol and water) to the polymer produces a crosslinking reaction causing the combination to harden. This reaction is nontoxic, normo-thermic and can be performed in situ. During the course of the polymerization, carbon dioxide is liberated, producing an interconnected porous network within the implant, suitable for bone ingrowth. This paper will describe a preliminary biocompatibility assay of the bone substitute.
Animals↗
Acute hydrocephalus following aneurysmal subarachnoid hemorrhage.
BACKGROUND: Acute hydrocephalus is a potentially treatable cause of early neurological deterioration after aneurysmal subarachnoid hemorrhage (SAH). METHODS: A retrospective study of 105 consecutive cases of aneurysmal SAH was undertaken to determine those factors significantly related to the development of acute hydrocephalus. Acute hydrocephalus was diagnosed when the bicaudate index was greater than the 95th percentile for age on a CT scan within 72 hours of the ictus. RESULTS: Thirty-one percent of the patients developed acute hydrocephalus. Grade of SAH was a significant factor for the development of acute hydrocephalus on univariate analysis as 87% of patients with acute hydrocephalus (29/32) presented with at least grade 3 (Hunt-Hess) SAH (P < 0.05). In addition, posterior circulation aneurysms on univariate analysis were associated with acute hydrocephalus (p < 0.05). Both premorbid hypertension and intraventricular blood (p < 0.05) were predictors for acute hydrocephalus, whereas intracisternal blood, age and sex were not. On multivariate linear regression analysis, factors found to be significantly associated with acute hydrocephalus were premorbid hypertension, intraventricular blood, CSF diversion and definitive shunt procedures. External ventricular drainage was not associated with any instances of rebleeding. Thirty-seven percent (10/27) of patients with acute hydrocephalus who survived were improved by pre-operative external ventricular drainage. CONCLUSIONS: Patients with acute hydrocephalus following SAH can be safely treated with external ventricular drainage. Multiple factors can be identified to predict those patients who will develop acute hydrocephalus post aneurysmal rupture. Approximately 30% of those patients with acute hydrocephalus will require definitive shunt placement. Acute hydrocephalus occurred in 31% of aneurysmal SAH patients in this series.
Acute Disease↗
Larval foraging behaviour and competition in Drosophila melanogaster.
Populations of Drosophila melanogaster derived by bidirectional selection for high (HA) and low (LA) aggregated oviposition behaviour differ significantly in the duration of the larval period and adult size because of differences in the developmental profiles for feeding rate over successive phases of larval growth. Feeding rates of HA larvae are significantly lower than those of LA larvae during the flexible period of growth which precedes attainment of critical mass for pupation. Consequently the HA larvae have a slower mean rate of development. In the fixed postcritical period of development the feeding rates of HA larvae are significantly higher than those of LA larvae. This causes a greater postcritical growth increment and larger adult flies. HA and LA larvae respond adaptively by changing the expression of components of their foraging behaviour depending on whether they are in or out of food. LA larvae exhibit a more flexible pattern of response and are also more successful competitors when food resources are limiting.
Animals↗
School breakfast improves verbal fluency in undernourished Jamaican children.
School feeding programs exist in many countries, but few have been properly evaluated. In this study, the short-term effects of breakfast on children's cognitive functions were examined. The subjects were 97 undernourished (weight-for-age < or = -1 SD of reference) and 100 adequately nourished (weight-for-age > -1 SD) children in four primary schools in rural Jamaica. The children were randomly assigned to a group provided with breakfast or a group given a quarter of an orange as a placebo, and then given a battery of four cognitive function tests. After a few weeks the treatments were reversed and the tests repeated. Undernourished children's performance improved significantly on a test of verbal fluency when they received breakfast, whereas that of the adequately nourished children did not change (breakfast x group interaction, P < 0.05). There were no other effects of breakfast on test scores. The findings extend those of a previous Jamaican study conducted under more controlled conditions, and support the targeting of school meals to undernourished children.
Child↗
Behavioural correlates of selection for oviposition by Drosophila melanogaster females in a patchy environment.
The behaviour of females from lines selected for high (H) and low (L) aggregated oviposition was compared in an environment consisting of discrete patches of resource available for larval development. Oviposition behaviour was influenced by the conformation and by the texture of the substrate, but this does not account for the selective differences in levels of aggregation which are under genetic control. The distribution of males of both selected populations tends to be overdispersed across resource patches. This observation is consistent with male territorial behaviour. The dispersal patterns of females of the two selected populations differ significantly. H females show a contagious distribution whereas the distribution for L females is more nearly random. Differences in adult female dispersion are likely to be a significant factor contributing to aggregated oviposition. The level of aggregated oviposition affects the pattern of progeny survival when the unit of resource in each patch is small.
Animals↗
Disruption of the structure of larval foraging behaviour in interspecific hybrids in Drosophila.
Larval foraging behaviour in two sibling species, Drosophila pavani and Drosophila gaucha belonging to the mesophragmatica species group, is described. Interspecific hybrid larvae derived from both reciprocal crosses of the parent species show disruption in the organization of their behaviour, leading to lower mean feeding rates. This, together with interactions involving biotic residues, described elsewhere, is likely under competitive conditions to contribute to reduced fitness of the hybrids relative to the parent species.
Animals↗
Darwin and disability.
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Adaptation, Physiological↗
Development of murine lupus in CD4-depleted NZB/NZW mice. Sustained inhibition of residual CD4+ T cells is required to suppress autoimmunity.
Chronic administration of anti-CD4 mAb prevents autoimmune disease in NZB/NZW F1 (B/W) mice. This may be due either to CD4 cell depletion or to inhibition of CD4 cell function. To evaluate the relative importance of these mechanisms, we devised a system in which the consequences of cell depletion could be analyzed independent of the inhibitory effects of chronic mAb therapy. This was accomplished by performing adult thymectomy before mAb administration. Specifically, female B/W mice underwent thymectomy or sham thymectomy at age 6 wk, followed at age 3 mo by a short course of either anti-CD4 (2 mg/wk for 3 wk) or saline. Treatment with anti-CD4 depleted 90% of circulating CD4 cells, but a small subpopulation (10%) of CD4 cells was refractory to depletion. In non-thymectomized mice, the CD4 population gradually reconstituted after cessation of therapy. In contrast, in thymectomized mice, recovery of CD4 cells was prevented by the absence of the thymus. Despite the striking reduction in CD4 cells in thymectomized mice, severe autoimmune disease developed, with autoantibody levels, proteinuria, and mortality comparable with non-thymectomized, nondepleted controls. The unexpected development of lupus nephritis in thymectomized, CD4-depleted B/W mice suggested that the thymus might be required to achieve the benefits of therapy with anti-CD4. To exclude this possibility, we demonstrated that chronic therapy with anti-CD4 prevents autoimmunity in thymectomized B/W mice. These findings imply that: 1) substantial depletion of CD4 T cells is not sufficient to suppress autoimmunity; 2) suppression of autoimmunity requires sustained functional inhibition of CD4 T cells; and 3) a small subpopulation of CD4 cells that is refractory to depletion by anti-CD4 is sufficient to promote the full expression of murine lupus in B/W mice.
Age Factors↗
Effect of successful treatment with amphotericin B on Histoplasma capsulatum variety capsulatum polysaccharide antigen levels in patients with AIDS and histoplasmosis.
PURPOSE: The purpose of this study was to establish the effect of induction and maintenance treatment with amphotericin B on levels of Histoplasma capsulatum var. capsulatum polysaccharide antigen (HPA) in the urine and blood of patients with acquired immunodeficiency syndrome (AIDS) and disseminated histoplasmosis. PATIENTS AND METHODS: This was a retrospective study of the effect of amphotericin B treatment on levels of HPA in the urine or serum from 70 patients with AIDS and disseminated histoplasmosis. All patients received initial intensive induction treatment with amphotericin B, and a subset continued to receive amphotericin B at less frequent intervals for maintenance therapy to prevent relapse. Treatment regimens varied in intensity and duration and specimens were obtained at irregular intervals. Urine and serum specimens were stored and retested for HPA in the same radioimmunoassay. RESULTS: HPA levels in serum decreased by at least 2 units during induction therapy in all 19 (100%) patients with initial levels of greater than or equal to 2.6 units and reverted to negative in 40.9% of those with initial levels of greater than or equal to 1.0 unit. HPA in urine decreased by at least 2 units in 84.8% and reverted to negative in 17.3% of patients. During induction treatment, HPA cleared more rapidly from serum than from urine. During maintenance treatment, HPA levels in serum decreased by at least 2 units in 100% and became negative in 66.7%. HPA in urine decreased by at least 2 units in 54.5% and reverted to negative in 20.0%. Rates of clearance of HPA from the serum and urine were similar, 0.01 unit/week compared with -0.04 unit/week, respectively, but less than rates during induction treatment. CONCLUSIONS: Successful therapy of histoplasmosis with amphotericin B is associated with reduction of HPA in body fluids. Periodic measurement of HPA levels offers a method for monitoring the response to therapy and for comparing new treatments for histoplasmosis.
Acquired Immunodeficiency Syndrome↗
Diagnosis of histoplasmosis in patients with the acquired immunodeficiency syndrome by detection of Histoplasma capsulatum polysaccharide antigen in bronchoalveolar lavage fluid.
Diagnosis of histoplasmosis in patients with Acquired Immunodeficiency Syndrome (AIDS) may be established by detection of the organism in lung tissue or bronchoalveolar lavage fluid. In this report we have evaluated the utility of Histoplasma capsulatum polysaccharide antigen (HPA) detection in bronchoalveolar lavage fluid for diagnosis of histoplasmosis. HPA was detected in bronchoalveolar lavage fluid of 19 of 27 cases (70.3%). Of 122 controls with a variety of underlying diseases, HPA was detected in none. Eight of the negative specimens from patients with histoplasmosis were retested after fivefold concentration, and HPA was detected in five. Fivefold concentration of 10 control samples had no effect on HPA level. H. capsulatum was seen by methenamine silver or Giemsa stain in 19 of the 27 (70.3%) and isolated by culture in 24 of 27 (88.9%) cases. Twenty-four of 26 (92.3%) cases had positive cultures from extrapulmonary sites as well. HPA was detected in the urine of 25 (92.6%) and the serum of 23 (88.5%) of the 26 cases. We conclude that HPA detection offers a rapid method for identification of pulmonary histoplasmosis in patients with AIDS and could be a helpful addition to the battery of tests performed on bronchoalveolar lavage fluids in areas where histoplasmosis is endemic.
Acquired Immunodeficiency Syndrome↗
Histoplasmosis relapse in patients with AIDS: detection using Histoplasma capsulatum variety capsulatum antigen levels.
OBJECTIVE: To assess the accuracy of Histoplasma capsulatum variety capsulatum polysaccharide antigen testing for the identification of histoplasmosis relapse in patients with the acquired immunodeficiency syndrome (AIDS). DESIGN: A retrospective study using stored specimens. SETTING: A referral center and several private hospitals. PATIENTS: Twenty episodes of histoplasmosis relapse were evaluated in 17 patients with AIDS from November 1987 to August 1990. Controls included 30 patients with AIDS and histoplasmosis who did not have a relapse during maintenance therapy and who were initially tested during the same week as the patients with relapse. A second control group included seven patients with AIDS and histoplasmosis who were evaluated for relapse on 23 occasions; relapse, however, was excluded on each occasion. MEASUREMENTS: To avoid interassay variability, specimens were tested for H.c. var. capsulatum polysaccharide antigen with the same radioimmunoassay. MAIN OUTCOME MEASURE: The change in the H.c. var. capsulatum polysaccharide antigen level during successful as opposed to unsuccessful maintenance therapy for the prevention of histoplasmosis relapse. MAIN RESULTS: For the 20 episodes of relapse (17 patients), H.c. var. capsulatum antigen levels increased by at least 2 radioimmunoassay units in 12 of 14 serum specimens tested (85.7%; 95% Cl, 57.2% to 98.2%) and in 17 of 18 urine specimens tested (94.4%; Cl, 72.7% to 99.9%). Antigen levels increased in the urine or serum in 1 of 83 specimens (1.2%; CI, 0.03% to 6.6%) obtained on 56 occasions (1.8%; CI, 0.04% to 9.6%) from controls (specificity, 98.2%; CI, 90.4% to 99.96%). In three cases of relapse, antigen levels increased before clinical relapse, antigen levels increased before clinical relapse was suspected. Complement fixation titers increased by at least 2 dilutions in 4 of 11 cases (36.4%; CI, 10.9% to 69.2%) but in 0 of 9 control patients (CI, 0% to 28.3%). CONCLUSION: An increase in H.c. var. capsulatum polysaccharide antigen levels of 2 units or more strongly suggests histoplasmosis relapse. The presence of increasing titers of anti-H.c. var. capsulatum antibodies by complement fixation is less accurate for the diagnosis of relapse.
Acquired Immunodeficiency Syndrome↗
Correlation of Histoplasma capsulatum polysaccharide antigen with the severity of infection in murine histoplasmosis.
We sought to determine if Histoplasma capsulatum polysaccharide antigen (HPA) levels correlate with the extent of infection in murine of histoplasmosis. Separate groups of mice were inoculated intratracheally with varying numbers of H. capsulatum yeast cells. After 1 week, HPA levels and fungal burden (quantitative culture of lung and spleen and histopathologic stain of lung) were determined in lung and spleen, and HPA levels in serum. HPA levels, cultures and histopathological stain results of lung and spleen tissue showed a direct correlation with increasing inoculum size. HPA levels in serum also correlated with the size of inoculum. H. capsulatum antigen in lung correlated with silver stain scores of lung tissue, (R = 0.948, P less than 0.001) and with quantitative culture scores of lung, (R = 0.929, P less than 0.001). HPA levels in spleen tissue also correlated with spleen culture scores, (R = 0.724, P less than 0.001). These results indicate that determination of HPA level in serum and tissue may be a useful test in evaluating the severity of diseases as well as efficacy of antifungal therapy in histoplasmosis.
Animals↗