Biomedical subjects
C O'Brien
Publications and source records attributed to C O'Brien.
An outpatient eating disorders program in a CMHC.
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Single night studies in obstructive sleep apnea.
The role of single night studies and the determinants of effective nasal continuous positive airway (CPAP) pressures were determined in 412 consecutive patients between 1984 and 1989. Patients chosen for analysis had an apnea index (AI) of greater than or equal to 20 hr-1 prior to CPAP. The AI was 67 +/- 30 hr-1, the body mass index (BMI) was 36 +/- 9 kg/m2, the age was 51 +/- 13 yr and the lowest oxygen saturation was 72 +/- 14%. Effective CPAP (9 +/- 3 cm H2O) was documented in 320 patients on single night studies and resulted in a 99% reduction in the frequency of obstructive events and improvement in the lowest O2 saturation to 94 +/- 5%. Only 18% of the variability in effective CPAP could be explained by AI and BMI. Single night studies are sufficient to establish effective CPAP in 78% of patients and offer considerable conservation of resources compared to routine multiple night studies. Effective CPAP pressures are variable and must be determined by incremental CPAP trials.
Prediction of the exercise-heat tolerance of soldiers wearing protective overgarments.
The purpose of this investigation was to see whether subject characteristics and physiologic measurements predicted exercise-heat tolerance (EHT) and voluntary tolerance time in young soldiers. A total of 18 unacclimatized males attempted six 50-min periods of treadmill walking (4.0 km.h-1, 0% grade, 33 degrees C db, 20% rh) while wearing protective overgarments. Two post hoc groups of soldiers were defined: high EHT (H) and low EHT (L), having mean (+/- S.E.) tolerance times of 360 +/- 0 and 222 +/- 12 min, respectively. Significant (p less than 0.05) H vs. L differences were observed in pretrial body mass, percent fat, and mass-to-surface area ratio (M/SA), as well as 170 min HR, Tsk and heat storage. The first three of these factors indicated that preexercise anthropomorphic characteristics may be used to distinguish H from L. The HR and Tsk differences were interpreted to mean that L experienced greater cardiovascular strain in protective overgarments because of a higher Tsk, which resulted in increased pooling of blood in cutaneous vessels, decreased cardiac filling pressure, and increased fatigue. Because HR variables were the strongest correlates of exercise tolerance time (r2 = 0.60 for HR at 170 min, r2 = 0.83 for time to reach HR of 160 beats.min-1) a novel HR monitoring technique was proposed which uses a wrist-mounted cardiotachometer to predict tolerance time.
Employment Contracts Bill.
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A randomized, controlled trial of interferon alfa-2b alone and after prednisone withdrawal for the treatment of chronic hepatitis B. The Hepatitis Interventional Therapy Group.
BACKGROUND AND METHODS: Chronic hepatitis B is a common and often progressive liver disorder for which there is no accepted therapy. To assess the efficacy of treatment with interferon, we randomly assigned patients with chronic hepatitis B to one of the following regimens: prednisone for 6 weeks followed by 5 million units of recombinant interferon alfa-2b daily for 16 weeks; placebo followed by 5 million units of interferon daily for 16 weeks; placebo followed by 1 million units of interferon daily for 16 weeks; or observation with no treatment. RESULTS: Hepatitis B e antigen and hepatitis B viral DNA disappeared from serum significantly more often in the patients given prednisone plus interferon (16 of 44 patients, or 36 percent) or 5 million units of interferon alone (15 of 41; 37 percent) than in the untreated controls (3 of 43; 7 percent; P less than 0.001); the difference between those given 1 million units of interferon (7 of 41; 17 percent) and the controls was not significant. The strongest independent predictor of a response to treatment was the amount of hepatitis B viral DNA in serum at entry (P less than 0.0001). Of the 38 patients who responded to interferon, 33 (87 percent) had normal serum aminotransferase levels after therapy; 11 patients who responded (29 percent), but no controls, lost the hepatitis B surface antigen. Blinded histologic assessment revealed a significant improvement in periportal necrosis in the treated patients (P = 0.03). CONCLUSIONS: In chronic hepatitis B, treatment with interferon alfa-2b (5 million units per day for 16 weeks) was effective in inducing a sustained loss of viral replication and achieving remission, assessed biochemically and histologically, in over a third of patients. Moreover, in about 10 percent of the patients treated with interferon, hepatitis B surface antigen disappeared from serum.
The seroepidemiology of human herpesvirus-6 (HHV-6) from a case-control study of leukaemia and lymphoma.
Sera from an epidemiological case-control study of leukaemias and lymphomas conducted between 1980 and 1986 were examined for reactivity to human herpesvirus-6 (HHV-6) by an indirect immunofluorescence assay. Statistical analyses of the data revealed higher HHV-6 seroprevalence and antibody titres in the cases, particularly evident in the disease subtypes acute myeloid leukaemia, Hodgkin's disease (HD), and low-grade non-Hodgkin's lymphoma. Within the control group alone, HHV-6 seroprevalence was placed at 55% at a serum dilution of 1:40. The controls also displayed higher seropositivity in females as compared with males. Further analyses suggest an association of increased HHV-6 seropositivity and geometric mean titre ratio with HD among young adults lacking social contact in the family group. This finding might indicate late exposure to HHV-6 in such persons and could possibly signify late exposure to a number of viruses, including those hypothesized as playing a role in the aetiology of HD. Previous reports have nominated Epstein-Barr virus as a possible candidate. Our results suggest that HHV-6 should be included in further investigations of the aetiology of HD.
A monoclonal antibody reactive with a 15-kDa cytoplasmic granule-associated protein defines a subpopulation of CD8+ T lymphocytes.
We have recently described a novel method for the production and characterization of mAb reactive with T cell-restricted intracellular antigens. From a panel of antibodies that react specifically with permeabilized T lymphocytes but not with permeabilized B lymphocytes or native T cells, we have selected one, designated TIA-1, that reacts with 20 to 36% of digitonin permeabilized peripheral blood T lymphocytes. Flow cytometric analysis of purified CD4+ and CD8+ subsets showed TIA-1 to recognize a subpopulation of 49 to 64% of CD8+ lymphocytes. Little or no reactivity with CD4+ resting T lymphocytes was observed. TIA-1 did not react with any of a panel of T cell lines, B cell lines, or monocytoid cell lines. TIA-1 reacted strongly with NK cell clones and CD8+ cytolytic T cell clones, and less strongly with CD4+-activated T cell clones, suggesting a preferential expression in cells possessing cytolytic potential. Cell fractionation experiments showed TIA-1 to be membrane associated. Furthermore, Percoll gradient fractionation of a cytolytic T cell clone (T4T8C1) showed the majority of TIA-1 to be contained in a low density membrane fraction that also contained serine protease activity. Immunoelectron microscopy showed TIA-1 to decorate the membranes of electron lucent and electron dense cytoplasmic granules in this same cytolytic T cell clone. Biochemical analysis showed TIA-1 to be a 15-kDa protein in unstimulated T cells. Upon activation with Con A or anti-CD3 antibodies. TIA-1 was induced to form disulfide linked dimers, trimers, and tetramers of the basic 15-kDa unit. Taken together, our data suggest that TIA-1 is a cytolytic granule associated protein that may define a subpopulation of resting CD8+ T lymphocytes possessing cytolytic potential.
The growth-associated protein GAP-43 appears in dorsal root ganglion cells and in the dorsal horn of the rat spinal cord following peripheral nerve injury.
When adult dorsal root ganglion cells are dissociated and maintained in vitro, both the small dark and the large light neurons show increases in the growth-associated protein GAP-43, a membrane phosphoprotein associated with neuronal development and plasticity. Immunoreactivity for GAP-43 appears in the cytoplasm of the cell bodies as early as 3.5 h post axotomy and is present in neurites and growth cones as soon as they develop. At early stages of culture (4 h to eight days) satellite/Schwann cells are also immunoreactive for GAP-43. Neurons in isolated whole dorsal root ganglion maintained in vitro become GAP-43-immunoreactive between 2 and 3 h after axotomy. It takes three days however, after cutting or crushing the sciatic nerve in adult rats in vivo, for GAP-43 immunoreactivity to appear in the axotomized dorsal root ganglion cells. GAP-43 immunoreactivity can be detected in the central terminals of primary afferent neurons in the superficial laminae of the dorsal horn of the lumbar enlargement four days after sciatic cut or crush. The intensity of the GAP-43 staining reaches a peak at 21 days and becomes undetectable nine weeks following crush injury and 36 weeks following sciatic nerve cut. The pattern of GAP-43 staining is identical to the distribution of sciatic small-calibre afferent terminals. Little or no staining is present in the deep dorsal horn, but GAP-43 does appear in the ipsilateral gracile nucleus 22 days after sciatic injury. In investigating the mechanism of GAP-43 regulation, blockade of axon transport in the sciatic nerve with vinblastine (10(-5) M-10(-4) M) or capsaicin (1.5%) was found to produce a pattern of GAP-43 immunoreactivity in the dorsal horn identical to that found with crush, while electrical stimulation of the sciatic nerve had no effect. Axotomy of primary sensory neurons or the interruption of axon transport in the periphery therefore acts to trigger GAP-43 production in the cell body. The GAP-43 is transported to both the peripheral and the central terminals of the afferents. In the CNS the elevated GAP-43 levels may contribute to an inappropriate synaptic reorganization of afferent terminals that could play a role in the sensory disorders that follow nerve injury.
The visual field in chronic open angle glaucoma: the rate of change in different regions of the field.
Using automated perimetry the distribution of visual field loss in 40 chronic open angle glaucoma eyes (40 patients) was found to be predominantly in the nasal, supranasal, and superotemporal regions. The rate of change of visual field threshold values in seven regions of the field was measured by trend analysis over 44.9 +/- 17.9 months. Seventeen eyes had a significant rate of field loss in one or more regions of the field with the remaining eyes either showing improvement or stability. Seven of the 17 eyes with significant regional field loss had stable overall fields. The greatest rate of field loss occurred in the temporal and superotemporal regions. The correlation between the mean threshold value of the initial field test and the rate of change of field over time was significant in the temporal region and of borderline significance in the superotemporal region. The relationship was such that the greater the initial threshold value, the greater the subsequent rate of field loss.
Neodymium: YAG transscleral cyclocoagulation: a clinical study.
Thirty-seven eyes of 35 patients with uncontrolled glaucoma on maximum medication and after previous failed glaucoma surgery, were treated by transscleral cyclocoagulation using the free running mode of the Lasag Microrupter II Neodymium: YAG (Nd:YAG) laser. The indications, technique and results are discussed in this group of complicated glaucomatous eyes and suggests that Nd:YAG laser cyclocoagulation is a safe and effective method of lowering the intraocular pressure (IOP) and improving glaucoma control. The mean pre-treatment IOP was 41 mmHg, and the mean post-operative IOP was 22.5 mmHg. The post-operative IOP was 25 mmHg or less in 27 of 37 eyes (73%) after an average follow-up of eight months.
Fc gamma receptor type III (CD16) is included in the zeta NK receptor complex expressed by human natural killer cells.
We recently reported that CD3- natural killer (NK) cells express the zeta chain of the T-cell receptor complex (zeta NK) in association with higher molecular weight structures whose expression differs between individual NK cell clones. Because NK cell cytolytic activity is known to be triggered by perturbation of the type III Fc gamma receptor (CD16), we sought to determine whether this activating molecule is included in the zeta NK molecular complex. Biochemical evidence for a physical association between CD16 and zeta NK was obtained by comparing immunoprecipitates formed using monoclonal antibodies reactive with each of these molecules by SDS/polyacrylamide gel electrophoresis, immunoblotting, and peptide mapping. In both clonal and polyclonal populations of CD3- NK cells, CD16 and zeta NK specifically associated with one another. Functional evidence for a specific association between CD16 and zeta NK in intact cells was obtained by demonstrating a coordinate down-modulation of both of these molecules induced by either phorbol 12-myristate 13-acetate or monoclonal antibodies reactive with CD16. Our results suggest that Fc gamma receptor type III (CD16) is included in the zeta NK complex and that this complex is likely to play an important role in NK cell activation.
Productivity, stress and the person in the middle.
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Chronic myeloid leukaemia in Yorkshire: a case control study.
The results of a case-control study of chronic myeloid leukaemia in adults are reported. 122 cases and 241 controls were interviewed. Excess risks associates with heart disease and related drugs were revealed. In addition a weak association with occupational and/or hobby exposure to irradiation emerged.
Striatonigral degeneration: clinical, MRI, and pathologic correlation.
We report a patient with striatonigral degeneration in whom T2-weighted MRI imaging revealed low signal and atrophy in the putamen. Neuropathologic studies confirmed putaminal atrophy and iron deposition in the MRI low signal regions.
Effects of antimalignancy therapy as seen in the oral cavity of children and young adults--a review.
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Monoclonal antibodies reactive with the T cell receptor zeta chain: production and characterization using a new method.
We have developed a novel method for the production and characterization of monoclonal antibodies reactive with lineage-restricted intracellular Ag. Using this technique, we have produced a panel of antibodies that react specifically with permeabilized T lymphocytes but not with permeabilized B lymphocytes or native T cells. One of these antibodies, designated TIA-2, was found to react with greater than 98% of peripheral blood T lymphocytes. Immunoblotting experiments showed TIA-2 to recognize a 32 kd protein that was reduced to 16 kDa in the presence of 2-mercaptoethanol. Immunoprecipitates analyzed on non-reducing/reducing diagonal polyacrylamide gels showed the homodimeric structure recognized by TIA-2 to be associated with additional structures whose pattern closely resembled that of the T cell receptor complex. When immunoprecipitates formed using antibodies reactive with CD3 epsilon were immunoblotted with TIA-2, the homodimeric TCR zeta chain was specifically recognized. Using TIA-2 as a TCR zeta specific reagent, we show that whole cell expression of this TCR subunit is dramatically reduced following exposure to mAb reactive with CD3. mAb reactive with activating epitopes of CD2 were also capable of down-modulating the expression of TCR zeta, but to a lesser degree. Exposure to Con A or IL-2, on the other hand, did not reduce the whole cell expression of TCR zeta. Given the central importance of TCR zeta in the expression of a functionally competent Ag receptor, its reduced expression in response to certain activating stimuli is likely to play an important role in regulating T cell responsiveness.
Epstein-Barr virus infection and thyroid dysfunction.
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