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Biomedical subjects

R J O'Brien

Publications and source records attributed to R J O'Brien.

At least 55 records · Page 3Linked to original sources
PubMed1991

Talc retinopathy.

We present five case reports of the clinical manifestations of talc retinopathy. Photographs illustrate the typical intravascular location of these crystalline deposits which are evident only after repeated injections of street drugs. Discussion includes differential diagnosis, systemic complications, and ophthalmic management of this condition.

Adult↗
PubMed1990

USPHS Tuberculosis Short-Course Chemotherapy Trial 21: effectiveness, toxicity, and acceptability. The report of final results.

STUDY OBJECTIVE: To determine the effectiveness, toxicity, and acceptability of a 6-month antituberculous regimen compared with a 9-month regimen. DESIGN: A nonblinded, unbalanced, randomized, multicenter clinical trial. SETTING: Twenty-two tuberculosis clinics in public health departments and hospitals in the United States. PATIENTS: Patients were eligible if Mycobacterium tuberculosis, isolated from sputum cultures, was susceptible to study drugs. Of 1451 patients enrolled, 75% (617 of 823) assigned to the 6-month regimen and 71% (445 of 628) assigned to the 9-month regimen were eligible. INTERVENTIONS: Patients took self-administered isoniazid and rifampin daily for 24 weeks (6-month regimen) or 36 weeks (9-month regimen). In addition, patients assigned to the 6-month regimen took self-administered pyrazinamide daily during the first 8 weeks. RESULTS: Patients on the 6-month regimen converted more rapidly than patients on the 9-month regimen (94.6% compared with 89.9% after 16 weeks of therapy, with a difference of 4.7% [95% CI, 0.7% to 8.7%]); had similar rates of adverse drug reactions (7.7% compared with 6.4%, with a difference of 1.3% [95% CI, 0.0% to 4.6%]); had lower noncompliance rates (16.8% compared with 29.2%, with a difference of 12.4% [95% CI, 6.8% to 18.0%]); and had similar relapse rates 96 weeks after completing therapy (3.5% compared with 2.8%, with a difference of 0.7% [95% CI, 0.0% to 3.9%]). A significantly greater proportion of patients assigned to the 6-month regimen successfully completed therapy (61.4% compared with 50.6%; chi 2 = 11.976). CONCLUSIONS: Our results suggest that this 6-month regimen is similar in effectiveness, toxicity, and acceptability to the 9-month regimen for treating pulmonary tuberculosis.

Adult↗
PubMed1990

Rifabutin (ansamycin LM427) for the treatment of pulmonary Mycobacterium avium complex.

During the period October 1983 through January 1988, the Centers for Disease Control (CDC) provided the experimental drug rifabutin (ansamycin LM427) to 406 patients with severe, progressive Mycobacterium avium complex pulmonary disease who had been unresponsive to standard therapy. Selected patients were randomly assigned to doses of 150, 300, or 450 mg rifabutin. Choice of companion drugs was left to the treating physicians. In the analysis of data from this program, we examined the relationship between response to treatment, as measured by bacteriologic sputum conversion, survival, weight gain, improvement in respiratory symptoms, and subjective assessment of clinical improvement, and a variety of patient and treatment variables. Although in some of the analyses a higher rifabutin dose appeared to be associated with sputum conversion, survival, and clinical improvement, the drug did not have a marked effect on outcome. The role of rifabutin in the treatment of this disease will best be assessed in a controlled clinical trial.

Adolescent↗
PubMed1989

Present chemotherapy of tuberculosis.

Significant advances in the treatment of tuberculosis have occurred with the introduction of short-course therapy using isoniazid and rifampin throughout therapy. The addition of pyrazinamide to the initial phase of therapy permits shortening of the total duration of treatment to 6 months for most patients. This regimen is well tolerated, results in rapid disappearance of bacilli from the sputum, and has a low rate of relapse. Ethambutol should be added to this regimen for any patient with an increased chance of having isoniazid resistant disease. Periodic culturing of the sputum from patients with pulmonary tuberculosis is essential for monitoring response to therapy. Patient noncompliance with therapy is the most common cause of treatment failure, and any patient suspected of being noncompliant should receive directly observed therapy. For this purpose, most treatment regimens may be adapted to twice weekly administration.

Adult↗
PubMed1989

The epidemiology of nontuberculous mycobacterial disease.

As the prevalence of tuberculosis has decreased, diseases due to nontuberculous mycobacteria have assumed a greater importance, and the common occurrence of disseminated M. avium complex disease in AIDS patients has stimulated interest in these organisms. Skin test surveys indicate that infection by these mycobacteria is common, but disease is infrequent, with an estimated prevalence in the United States of approximately 2 per 100,000. The most common forms of disease are chronic pulmonary disease resembling tuberculosis, benign cervical adenopathy in children, skin and soft-tissue infection, and disseminated disease in immunocompromised persons. Recent studies have increased our understanding of the ecology of these organisms, which are found in water, soil, and aerosols. However, much remains to be learned about transmission of infection and pathogenesis of disease. Increased understanding in these areas will be important in the prevention of nosocomially acquired disease and disseminated disease in immunocompromised patients.

Acquired Immunodeficiency Syndrome↗
PubMed1987

The epidemiology of nontuberculous mycobacterial diseases in the United States. Results from a national survey.

During the 2-yr period 1981-83, demographic, clinical, and laboratory information was collected for 5,469 patients from whom nontuberculous mycobacteria (NTM) had been isolated. Among the potential NTM pathogens, isolates of Mycobacterium avium complex were most frequent, followed by M. kansasii, M. fortuitum, M. scrofulaceum, and M. chelonae. Almost 90% of the isolates were obtained from respiratory specimens. Prevalence rates for NTM disease, as calculated by a diagnostic algorithm, were highest for M. avium complex (1.3/10(5)), M. fortuitum-M. chelonae (0.2/10(5)). The data suggest a changing epidemiologic picture of NTM disease due perhaps to the decreasing incidence of tuberculosis, the increasing prevalence of chronic lung disease, and increased culturing of diagnostic specimens, as well as possibly a change in the ecology of these organisms.

Adolescent↗
PubMed1986

Characterization of excitatory amino acid receptors expressed by embryonic chick motoneurons in vitro.

We have examined the effect of L-glutamate and other excitatory amino acids on embryonic chick motoneurons maintained in cell culture along with other types of spinal cord cells. When the motoneuron membrane is clamped at -50 mV, glutamate induces a dose-dependent inward current. Although the dose-response curve is hyperbolic with an ED50 of 78 microM, glutamate apparently activates 2 types of receptors on motoneurons. The first, G1, is activated by N-methyl-D-aspartate (NMDA) and aspartate and inhibited by 2-amino-5-phosphonovaleric acid (2-APV). The second, G2, is activated by kainate and quisqualate and is not inhibited by 2-APV. At -50 mV, 38% of the glutamate current is due to activation of G1 receptors and the remaining 62% to G2 activation. In contrast to motoneurons grown with other spinal cord cells, sorted motoneurons grown in isolation apparently exhibit only G2 receptor-mediated currents. Both G1 and G2 currents reverse polarity between -10 and -5 mV. However, they could be distinguished when the membrane was hyperpolarized. G2 currents increased but G1 currents decreased when the membrane potential was increased beyond -50 mV. Consistent with the mixed agonist action of glutamate, glutamate currents remained nearly constant on hyperpolarization. No evidence was obtained that the G2 class of receptors on motoneurons could be subdivided: Quisqualate and kainate apparently compete for the same sites; gamma-glutamylglycine blocked quisqualate as effectively as it blocked kainate currents when the different potencies of the 2 agonists were taken into account.(ABSTRACT TRUNCATED AT 250 WORDS)

2-Amino-5-phosphonovalerate↗
PubMed1986

Excitatory synaptic transmission between interneurons and motoneurons in chick spinal cord cell cultures.

We have examined the development of synaptic transmission between interneurons and motoneurons in spinal cord cell cultures. Unitary excitatory synaptic currents and complex bursts of excitatory currents develop rapidly: EPSCs (excitatory postsynaptic currents) were detected in 100% of the motoneurons by the 4th day after plating. Inhibitory synaptic currents develop more slowly: IPSCs (inhibitory postsynaptic currents) were detected in only 10% of the motoneurons on day 5 and 40% on day 8. During the 1st and 2nd days in vitro, 24% of the motoneurons tested were dye (Lucifer Yellow) coupled to nearby interneurons. The incidence of dye coupling declined during the first week in culture. No coupling was observed between motoneurons. Our data imply that both G1 and G2 receptors are activated at each synapse. The amplitude of spontaneous excitatory synaptic currents did not change when the motoneuron was hyperpolarized from -50 to -80 mV. This behavior is similar to that of currents induced by glutamate, an agonist that activates 2 types of receptors (G1 and G2) on motoneurons. In addition, a concentration of 2-amino-5-phosphonovaleric acid sufficient to inhibit all G1 receptors only partially inhibited the excitatory synaptic currents. Given the conductance of G1 and G2 channels and the ratio of channels activated during unitary EPSCs, we estimate that as few as 25 G1 channels and 5 G2 channels may mediate excitatory interaction between interneurons and motoneurons during the first week in culture.

Animals↗
PubMed1986

Modulation of embryonic chick motoneuron glutamate sensitivity by interneurons and agonists.

Embryonic chick motoneurons grown in culture together with other spinal cord cells are more sensitive to L-glutamate than are sorted motoneurons grown in isolation. After 6 d in vitro, the difference in peak sensitivity reached 6-fold. Comparable increases in aspartate and kainate currents were observed, indicating that both G1 and G2 amino acid receptors were affected. Elimination of proliferating non-neuronal cells from mixed spinal cord cell cultures by addition of cytosine arabinoside (ara C) did not prevent the increase in motoneuron chemosensitivity, so the induction is probably due to the presence of interneurons. In contrast to their effect on glutamate response, interneurons did not affect the sensitivity of motoneurons to the inhibitory neurotransmitters GABA and glycine. Glutamate receptors expressed by sorted and unsorted motoneurons are identical in terms of their ED50, reversal potential, mean channel open time, and conductance, implying that the increased sensitivity of motoneurons in mixed cultures is due to an increase in the number of open channels. In addition to an increase in the number of channels, the distribution of glutamate sensitivity over the surface of individual motoneurons was altered in interneuron-containing cultures. The sensitivity of isolated motoneurons was greatest at the soma and decreased with distance along major processes, but the sites of highest sensitivity on motoneurons in mixed cultures occurred along their processes. Sharp peaks identified by focal iontophoresis of glutamate were separated by areas of lower sensitivity. The inductive effect of interneurons cannot be due to glutamate, the most likely excitatory interneuron-motoneuron transmitter in 6 d chick cultures.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1986

Isolation of embryonic chick motoneurons and their survival in vitro.

This is the first of a series of 4 papers in which we describe the regulation of excitatory amino acid receptors on embryonic chick motoneurons dissociated from the lateral motor column and maintained in cell culture. Techniques are described for labeling embryonic chick motoneurons in vivo with Lucifer Yellow or fluorescein isothiocyanate conjugates of wheat germ agglutinin (Fl-WGA). We estimate that 65-95% of the motoneurons in the lateral motor column survive tissue dissociation and settle on an appropriate culture surface. The number of fluorescent motoneurons observed in heterogeneous spinal cord cell cultures decreases with a half-life of 2 d. The decline is due to fading of the fluorescent tracer rather than to loss of cells. Techniques are also described for separating motoneurons from other spinal cord cells with a fluorescence-activated cell sorter. Approximately 24% of the motoneurons in the lateral motor column can be isolated, and motoneurons comprise more than 90% of the population in cultures seeded with sorted cells. The survival of sorted and unsorted motoneurons in vitro is enhanced in the presence of skeletal myotubes or muscle conditioned medium, but the survival of non-motoneurons is not influenced by muscle. Electrophysiologic properties of sorted and unsorted motoneurons determined with patch-clamp techniques are similar. Both differ from mature motoneurons in their lower resting membrane potential (-50 mV), larger input resistance (450 M omega), and longer time constant (39 msec). Also they do not exhibit anomalous rectification or a calcium-activated potassium after hyperpolarization. Motoneurons grown in the absence of interneurons differ from motoneurons in heterogeneous spinal cord cell cultures in that their neurites (dendrites) are shorter and they branch less often.

Animals↗
PubMed1985

The mechanism of action of ethanolamine ammonia-lyase, an adenosylcobalamin-dependent enzyme. Evidence that the hydrogen transfer mechanism involves a second intermediate hydrogen carrier in addition to the cofactor.

Ethanolamine ammonia-lyase catalyzes the adenosylcobalamin (AdoCbl)-dependent conversion of ethanolamine to acetaldehyde and ammonia. During this reaction, a hydrogen atom migrates from the carbinol carbon of ethanolamine to the methyl carbon of acetaldehyde. Previous studies have shown that this migrating hydrogen equilibrates with the hydrogens on the 5'-(cobalt-linked) carbon of the cofactor. On the basis of those studies, a two-step mechanism for hydrogen transfer has been postulated in which the migrating hydrogen is first transferred from the substrate to the cofactor, then in a subsequent step is returned from the cofactor to the product. We now show that this migrating hydrogen is transferred not only to the cofactor, but also to a second acceptor at the active site. Hydrogens on this acceptor do not exchange with water during the course of the reaction, but are released to water when the enzyme is denatured. The catalytic significance of this second hydrogen acceptor was demonstrated by the findings that the transfer of hydrogen to this acceptor required both AdoCbl and active enzyme and that hydrogen at the second acceptor site could be washed out by unlabeled ethanolamine. On the basis of these results, we propose an expanded hydrogen transfer mechanism in which AdoCbl and the second acceptor site serve as alternative intermediate hydrogen carriers during the course of ethanolamine deamination.

Ammonia-Lyases↗