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Biomedical subjects

D O'Brien

Publications and source records attributed to D O'Brien.

At least 19 recordsLinked to original sources

Protective efficacy of combined live intranasal and inactivated influenza A virus vaccines in the elderly.

OBJECTIVE: To evaluate the efficacy of adding intranasal live attenuated cold-adapted influenza A vaccine to inactivated influenza vaccine to prevent influenza A in elderly residents of long-term-care institutions. DESIGN: Randomized, double-blind, placebo-controlled study conducted over 3 years. SETTING: Three large nursing homes. PARTICIPANTS: A total of 523 residents of nursing homes (mean age, 84.2 years). INTERVENTIONS: All participants received trivalent inactivated influenza vaccine parenterally and were randomly assigned to receive either live attenuated influenza A (H3N2) virus vaccine or placebo intranasally. MEASUREMENTS: Laboratory-documented influenza A was defined as a respiratory illness plus isolation of influenza A virus from nasal secretions, significant serologic response, or both. Participants were considered to have been exposed to influenza A if they resided in an institution in which cases of influenza A were documented. Outbreak-associated illnesses were defined as those occurring between the first and last isolation of influenza virus from within the institution, +/- 3 days. RESULTS: Participants who received intranasal vaccine and were subsequently exposed to influenza A had significantly lower rates of laboratory-documented influenza A (9 of 162 vaccine recipients compared with 24 of 169 placebo recipients; vaccine protective efficacy, 60.6%; 95% CI, 18% to 82%), outbreak-associated respiratory illnesses (13 of 162 vaccine recipients compared with 34 of 169 placebo recipients; vaccine protective efficacy, 56.8%; CI 23% to 76%), and outbreak-associated influenza-like illnesses (6 of 162 vaccine recipients compared with 18 of 169 placebo recipients; vaccine protective efficacy, 65.0%; CI 17% to 86%). CONCLUSIONS: Intranasal immunization with live attenuated influenza A virus vaccine provided additional protection against influenza A when added to parenteral trivalent inactivated influenza vaccine among elderly nursing home residents.

Administration, Intranasal

Silica exposure in hand grinding steel castings.

Exposure to silica dust was studied in the grinding of castings in a steel foundry that used conventional personal sampling methods and new real-time sampling techniques developed for the identification of high-exposure tasks and tools. Approximately one-third of the personal samples exceeded the National Institute for Occupational Safety and Health recommended exposure limit for crystalline silica, a fraction similar to that identified in other studies of casting cleaning. Of five tools used to clean the castings, the tools with the largest wheels, a 6-in. grinder and a 4-in. cutoff wheel, were shown to be the major sources of dust exposure. Existing dust control consisted of the use of downdraft grinding benches. The size of the casting precluded working at a distance close enough to the grates of the downdraft benches for efficient capture of the grinding dust. In addition, measurements of air recirculated from the downdraft benches indicated that less than one-half of the respirable particles were removed from the contaminated airstream. Previous studies have shown that silica exposures in the cleaning of castings can be reduced or eliminated through the use of mold coatings, which minimize sand burn-in on the casting surface; by application of high-velocity, low-volume exhaust hoods; and by the use of a nonsilica molding aggregate such as olivine. This study concluded that all these methods would be appropriate control options.

Air Pollutants, Occupational

General practice estimates of the prevalence of common chronic conditions.

This study measured the prevalence of chronic medical conditions in 4,549 middle aged persons attending three large general practices in Dublin over the course of a calender year. The prevalence of the following conditions were measured: coronary heart disease, hypertension, stroke, diabetes, asthma, chronic bronchitis, rheumatic disorders, dyspepsia, depression, anxiety disorders, psychoses, and cancer. In order to obtain a valid denominator for the study a second community based study was carried out in the same areas to determine what proportion of persons visit their general practitioner over the course of a year. Overall 40.5% of males and 44% of females suffered from a least one of the twelve conditions, with rheumatic disorders having the highest prevalence (14.5%) and psychotic disorders the lowest (0.75%).

Adult

An explanation for the difference in general practitioner consultation rates between GMS and non-GMS patients.

This study compares annual consultation rates between 3,111 General Medical Services and private patients, and their family doctors in three large general practices in Dublin. Visiting rates were substantially different between practices and between GMS and private patients. However, GMS patients were older and had 50% more chronic illnesses. When the effects of age and illness were controlled in a multiple regression model, GMS status accounted for less than 5% of the variation in visiting rates. GMS patients consult their practitioners in proportion to their medical need.

Adult

Fibrinolytic activity in patients with idiopathic and secondary deep venous thrombosis.

Decreased fibrinolytic activity (FA) is considered a risk factor in the development of deep venous thrombosis (DVT). The purpose of this study was to test the hypothesis that an abnormally low FA is more likely in idiopathic DVT as opposed to DVT in the presence of other predisposing risk factors. 156 patients were studied three months after an acute DVT confirmed by venography. In 82 patients a predisposing factor such as trauma, surgery or malignancy was present. In 74, DVT was idiopathic. Fibrinolytic activity was measured in all patients using the following tests: 1. Euglobulin Lysis Time (ELT, in minutes). 2. Global Fibrinolytic activity (FA in mg fibrin lysed per hour). ELT measures plasminogen activator activity (PAA) while FA which is a more global test measures the net effect of the PAA, the plasminogen activator inhibitor (PAI) and the clot structure. PAI was measured in 67 patients from both groups using an Enzyme-Linked immunosorbent assay (ELISA). The results obtained show a significant increase in the incidence of abnormal FA and ELT in the idiopathic group. This supports the hypothesis that low FA is an aetiological factor in the development of idiopathic DVT. The results also demonstrate the importance of associating the FA test to the classical tests such as ELT, PA and PAI for the detection of hypofibrinolysis.

Fibrinolysis

Prediction of the course of pre-type I diabetes.

To increase knowledge on the predictability of the onset of insulin-dependent diabetes mellitus (IDDM; type I), we followed 38 subjects less than 18 years of age who had positive results on two or more islet-cell antibody tests and one identical twin who had positive results on one islet-cell antibody test. All 39 patients had longitudinal intravenous glucose tolerance tests to determine the first-phase insulin response (FPIR). Insulin dependence has developed in 10 untreated subjects less than 18 years of age. Of the 10 subjects, insulin dependence developed in eight a mean of 4.6 months after their FPIR fell to less than 30 microU/ml and a mean of 14 months after it fell to less than 46 microU/ml. Nine of the untreated subjects had an FPIR less than 67 microU/ml on at least two occasions and became insulin dependent a mean of 19 months after the value first fell below this level (95% confidence limit = 66.4% to 100%). All but one of the 10 subjects in whom IDDM developed initially had islet-cell antibody levels of greater than 80 JDF units. Insulin autoantibody values at onset were available for 9 of the 10 subjects and were positive (greater than 39 nU/ml) in six. We conclude that the combination of positive results on two islet-cell antibody tests and two diminished FPIRs (less than 67 microU/ml) in subjects less than 18 years of age reliably predicts the onset of IDDM. These data should permit intervention studies to be planned.

Adolescent

10 year review of invasive aspergillosis detected at necropsy.

Between 1980 and 1989, 32 cases of invasive aspergillosis were identified out of 2315 consecutive necropsies, an incidence of 1.4%. The incidence in immunosuppressed "high risk" patients was 10.7%. Twenty out of 32 cases showed spread beyond the lungs, with the brain the most common site. There was an increase in cases in the second half of the decade, attributable to the start of a liver transplantation programme. Liver transplant recipients and patients with haematological malignancies were at significantly greater risk of acquiring aspergillosis than kidney transplant recipients or those with solid malignancies treated with chemotherapy. There was also a greater risk of haematogenous dissemination in liver transplant recipients than in all other groups, and this was significantly associated with the use of high dose steroids as anti-rejection treatment. Aspergillus was isolated during life in only eight cases, which indicates a continuing need for and emphasises the value of necropsy.

Adolescent

The role of aspiration cytologic examination in the diagnosis of carcinoma of the breast.

A study of 2,000 patients who had undergone fine needle aspiration of a solid lump of the breast was conducted to determine the accuracy of this technique. During the period 1982 to 1989, all patients with a solid mammary mass, presenting to a specialized breast unit were initially investigated by fine needle aspiration cytologic examination (FNAC). To date, we present data on 2,000 consecutive aspirations with matching histologic diagnosis on the excised pathologic specimens. In particular, the relationship between tumor histologic factors and the accuracy of cytologic diagnosis was examined. The sensitivity of FNAC in the diagnosis of a malignant growth was 84 per cent; this represents first aspiration results only. The specificity was more than 99 per cent. The rate of acellular or unsatisfactory aspirations was 12 per cent. We had a positive predictive rate for diagnosis in carcinoma of the breast of almost 95 per cent. The diagnosis of lobular and in situ patterns of disease was questioned, with three of three in situ lesions and ten of 23 lobular lesions missed by FNAC. We do not recommend that FNAC replace excision biopsy and frozen section in the diagnosis of carcinoma of the breast.

Biopsy, Needle

A trial of nicotinamide in newly diagnosed patients with type 1 (insulin-dependent) diabetes mellitus.

Various agents have been tried in subjects with newly diagnosed Type 1 (insulin-dependent) diabetes mellitus in an attempt to preserve Beta-cell function. In this double-blind study, nicotinamide or placebo were given for one year to 35 children and adolescents with newly-diagnosed Type 1 diabetes. All subjects were within six weeks of diagnosis and were between the ages of 6 and 18 years. Nicotinamide, a poly-(ADP-ribose) synthetase inhibitor, was given in a dose of 100 mg/year of age up to a maximum of 1.5 g/day. There were no initial differences between the 17 control and the 18 test subjects in relation to mean age, sex distribution, or severity at onset. Mean insulin dosages and HbA1 values were similar for the two groups during the year of study. Fasting and glucagon-stimulated C-peptide levels were similar for the control and nicotinamide treated groups at the beginning and after 4 and 12 months. There were no differences in remission rates between the two groups. Nicotinamide, at this dosage, does not preserve residual insulin secretion in subjects with newly diagnosed Type 1 diabetes.

Adolescent

Zinc status and peripheral nerve function in guinea pigs.

Guinea pigs fed a diet low in zinc develop clinical signs of apparent neurological origin. The signs include abnormal posture and locomotion as well as hypersensitivity to touch. In this study, electrophysiological and biochemical measurements were made on sciatic nerves from zinc-deficient and repleted animals as well as on controls fed either ad libitum or restricted to maintain weight comparable to those consuming the deficient diet. Both in vivo and in vitro measurements showed decreased motor nerve conduction velocity (NCV) in nerves of deficient animals. A longitudinal study showed excellent correlation of NCV and severity of clinical signs. Nerves from zinc-deficient guinea pigs had decreased Na,K-ATPase activity, but the number of sodium channels, as determined by saxitoxin binding, was not affected. It was concluded that the clinical signs of neuropathy in zinc deficiency are associated with impaired NCV and decreased Na,K-ATPase activity of peripheral nerves. The zinc-deficient guinea pig provides a useful model to study the biochemical defect in a peripheral neuropathy.

Amphibian Proteins

Evoked potentials induced by transcranial stimulation in dogs.

Evoked potentials were induced by transcranial stimulation and recovered from the spinal cord, and the radial and sciatic nerves in six dogs. Stimulation was accomplished with an anode placed on the skin over the area of the motor cortex. Evoked potentials were recovered from the thoracic and lumbar spinal cord by electrodes placed transcutaneously in the ligamentum flavum. Evoked potentials were recovered from the radial and sciatic nerves by surgical exposure and electrodes placed in the perineurium. Signals from 100 repetitive stimuli were averaged and analyzed. Waveforms were analyzed for amplitude and latency. Conduction velocities were estimated from wave latencies and distance traveled. The technique allowed recovery of evoked potentials that had similar characteristics among all dogs. Conduction velocities of potentials recovered from the radial and sciatic nerves suggested stimulation of motor pathways; however, the exact origin and pathway of these waves is unknown.

Animals

Limiting dilution analysis of ontogeny of self- and allo-reactive thymocytes of C57BL/6J mouse.

In the present study, functional development of mouse fetal through neonatal to adult thymocytes was analyzed by limiting dilution assay (LDA) in terms of allo-reactivity and self-reactivity. Self-reactive PTL-p were always much less than those of allo-reactive PTL-p at all ages examined in this study. These results imply that thymocyte proliferation is not predominantly driven by responses to self antigens in the thymus, and that self-reactive thymocytes do not develop prior to allo-reactive thymocytes during thymic ontogeny. It is unlikely that most of such proliferating, murine early fetal thymocytes are self-reactive; allo-reactive cells are unlikely to have been derived from self-reactive cells during T cell development.

Animals

Cyclosporine A for the treatment of new-onset insulin-dependent diabetes mellitus.

It is not known whether early immunosuppressive treatment can preserve long-term endogenous insulin secretion in subjects with insulin-dependent diabetes mellitus. In the present study, clinical remissions during the first year and C-peptide production for 3 years were followed after 43 subjects with newly diagnosed insulin-dependent diabetes mellitus were randomly assigned to a cyclosporine A treatment group for 4 months or to a control group. Of the six cyclosporine A-treated subjects who had remissions, five were 19 years of age or younger, compared with two of the four in the control group. C-peptide production was present in 98% of all subjects after 4 months, in 88% after 1 year, and in 43% after 3 years. There were no significant differences in numbers of subjects with C-peptide production or in mean hemoglobin A1 levels, between cyclosporine A-treated and control subjects after 3 years. Cyclosporine A treatment of subjects with newly diagnosed insulin-dependent diabetes mellitus for a period of 4 months does not have the ability to preserve residual beta-cell function.

Adolescent

Movement disorders during sleep in cats and dogs.

Spontaneous sleep movement disorders in 5 cats and 3 dogs were studied. Objective abnormalities during sleep were confirmed by electrographic or behavioral monitoring techniques in all animals. The cause of the disorder was CNS disease in 3 animals. A cause was not discovered in the other 5 animals, although at necropsy, 2 were found to have thyroid tumors. Many pharmacologic treatments were ineffectual, but trials with the benzodiazepine tranquilizer, clonazepam, suggested it will prove useful in controlling violent movements during rapid-eye-movement sleep.

Animals

Glucose control and the renal and retinal complications of insulin-dependent diabetes.

Two hundred thirty subjects with insulin-dependent diabetes were followed up longitudinally by measuring glycohemoglobin values to relate glucose control with renal and retinal complications. Subjects with long-term poor control (glycohemoglobin values greater than 1.5 times the upper limit of normal) had 3.6 times the prevalence of microalbuminuria and 2.5 times the prevalence of level 3 to 6 retinopathy than that found in subjects with long-term good control (glycohemoglobin values within 1.33 times the upper limit of normal). Variables related to kidney damage were glucose control and, to a lesser degree, duration of diabetes. Variables related to eye disease were, in descending order of significance, duration of diabetes, glucose control, and age. No subject whose mean glycohemoglobin value was consistently within 1.1 times the upper limit of normal had retinopathy or microalbuminuria. In contrast, when the mean glycohemoglobin value was more than 1.5 times the upper limit of normal, 24 (29%) of 82 subjects had microalbuminuria and 30 (37%) of 82 had level 3 to 6 retinopathy.

Adolescent