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Biomedical subjects

R L Murphy

Publications and source records attributed to R L Murphy.

At least 73 records · Page 4Linked to original sources

Indwelling central venous catheter infections in patients with acquired immune deficiency syndrome.

Indwelling central venous catheters are increasingly useful in the clinical management of patients with acquired immune deficiency syndrome (AIDS). To evaluate the risk of catheter infection in this group of patients, we reviewed the records of 299 patients with Hickman and Port-a-cath catheters. Patients were stratified into three groups: (a) AIDS (n = 54), (b) non-AIDS immunodeficiencies (n = 102), and (c) immunocompetent (n = 98). The rate of infection per 1,000 catheter days was 2.02, 0.41 (p less than 0.002), and 0.23 (p less than 0.002), respectively. Gram-positive cocci were the predominant isolate. Previous catheter infection and advanced AIDS (as determined by positive p24 antigen and low CD4+ number) were associated with increased risk of infection. Exit, tunnel, and fungal infections required catheter removal. The risk of infection and management were similar in Hickman and Port-a-cath catheters. The mortality was extremely low in all groups. However, the risk of infection associated with indwelling catheters was significantly higher in AIDS patients compared to patients with other immunodeficiencies.

Acquired Immunodeficiency Syndrome↗

Prospective comparative trial of short course (four day) and continuous tobramycin in combination with cefoperazone or mezlocillin in febrile, granulocytopenic patients.

In a prospective, randomized trial of 195 febrile episodes in granulocytopenic patients short course aminoglycoside treatment (initial tobramycin and cefoperazone followed by tobramycin discontinuation at day four of therapy) was compared with two regimens (tobramycin plus cefoperazone and tobramycin plus mezlocillin) in which both drugs were continued for up to 26 days. All regimens were successful as empirical therapy with comparable response rates of just over seventy per cent. Fifty-three per cent of the initial episodes of fever were related to documented infections which responded less well (P = 0.007) than unexplained fever. Patients with bacteraemia, pneumonia or Gram-positive aerobic or Pseudomonas aeruginosa infections responded poorly to all regimens. The recovery from granulocytopenia was the most important determinant of successful response. Aminoglycoside discontinuation followed by cefoperazone monotherapy after day four was statistically as effective as the combination regimens. Short course tobramycin therapy eliminated the nephrotoxicity seen in the combination limbs. The use of cefoperazone was not associated with an increased incidence of hypoprothrombinemia; however, the only three bleeding episodes occurred in patients given cefoperazone but not vitamin K. Short course aminoglycoside therapy will reduce cost and nephrotoxicity when compared with prolonged combination therapy and should be further explored in this setting, with use of different agents and comparison with monotherapy.

Adolescent↗

Cytoplasmic calcium as the messenger for light adaptation in salamander rods.

1. In order to study the role of cytoplasmic calcium concentration (Ca2+i) in rod photoreceptor light adaptation, we have attempted to prevent light-induced changes in Ca2+i by minimizing calcium fluxes across the outer segment plasma membrane. This was achieved by exposing the outer segment to a low-Ca2+, 0-Na+ solution, in which sodium was replaced with either guanidinium or lithium and the external calcium concentration (Ca2+o) was reduced to micromolar levels. 2. With guanidinium and 1-3 microM-Ca2+o, the circulating current in darkness was maintained for a period of at least 15 s, consistent with approximate stability of Ca2+i. With Li+ rather than guanidinium most of the initial current was suppressed, but the residual current was again relatively stable. 3. During prolonged exposures (greater than 30 s) to low-Ca2+, 0-Na+ solution followed by dim illumination, the circulating current did not remain constant but slowly increased. Incorporation of calcium buffer into the cytoplasm greatly reduced the rate of change of current, consistent with the idea that the increase arose from a gradual decrease in Ca2+i. 4. Light responses of rods exposed to low-Ca2+, 0-Na+ solution in darkness were altered in a characteristic manner. Although the initial rising phase of the light response was little changed, the peak amplitude of the response was larger and occurred later, and the response decayed more slowly than in control. The response-intensity relation was steepened and was shifted towards lower intensities both for flashes and for steps of light. The normal sag in the response to steps disappeared, and the waveform of the step response could be predicted to a close approximation from the integral of the dim flash response. 5. Presentation of background illumination in Ringer solution produced a marked acceleration of the response to a subsequent bright flash. No such acceleration was observed if the background was given in low-Ca2+, 0-Na+ solution. 6. The results described in paragraphs 4 and 5 indicate that, under conditions expected to minimize changes in Ca2+i, all manifestations of light adaptation disappear, and the rod simply sums the effects of incident photons with an invariant integration time. 7. Exposure of a light-adapted rod to low-Ca2+, 0-Na+ solution altered the responses to superimposed test flashes in much the same way as for rods in darkness. The initial rising phases in low-Ca2+, 0-Na+ solution were unchanged, but the responses were larger, reached peak later and decayed more slowly.(ABSTRACT TRUNCATED AT 400 WORDS)

Adaptation, Ocular↗

Validation of an automatic crackle (rale) counter.

Crackles are commonly used in clinical decision-making, and in certain diseases the number of crackles reflects the severity of the illness. Auditory crackle estimations are subjective; crackle counting from time amplitude plots of sound (called time-expanded waveforms) is more objective but is cumbersome. We devised a computer-based system to count crackles automatically. One hundred samples of lung sounds from 41 subjects were recorded using an electret microphone air-coupled to the chest wall. Interobserver agreement in estimating the number of crackles per breath was high (r = 0.88, p less than 0.001), and these counts were significantly correlated with counts made of spikelike deflections seen on time-expanded waveform analysis (r = 0.78, p less than 0.001). The automatic crackle counting correlated with the physician counts (r = 0.74, p less than 0.001). The average number of crackles counted per breath was greater by visual inspiration (8.8) and by automatic analysis (7.8) than it was by the physician observers (5.8). Reasons for the discrepancies include the fact that there are no absolute criteria for crackles and that rapidly occurring crackles are difficult to count by ear. Counting crackles by computer-based methods is feasible and can improve noninvasive cardiopulmonary diagnosis.

Asbestosis↗

Predictors of outcome in AIDS patients receiving zidovudine.

Fifty-eight AIDS patients who previously had Pneumocystis carinii pneumonia (PCP) were enrolled in an open trial of zidovudine therapy. We analyzed baseline clinical and laboratory parameters to identify predictors of outcome. Fifty-eight patients were followed for a mean of 26.5 weeks. There were 17 deaths; the probability of survival at 24 weeks was 0.81. Forty-one participants had unsuccessful outcomes, which included new opportunistic infections (24), progressive neurologic deterioration (2), and drug toxicity, excluding anemia, necessitating discontinuation of zidovudine (15). Only 24 subjects (41%) were receiving zidovudine at the end of the study period including 17 who had neither opportunistic infection nor toxicity. Low baseline hemoglobin level (p less than 0.001) and poor performance status as measured by the Karnofsky scale (p less than 0.01) independently predicted unsuccessful outcome and early death. Low hemoglobin (p = 0.001), low platelet count (p = 0.016), and increased time since PCP (p = 0.008) predicted development of drug toxicity. Neither CD4 lymphocyte count nor p24 antigenemia correlated with outcome.

Acquired Immunodeficiency Syndrome↗

Photoreceptor light adaptation is mediated by cytoplasmic calcium concentration.

The vertebrate visual system can operate over a large range of light intensities. This is possible in part because the sensitivity of photoreceptors decreases approximately in inverse proportion to the background light intensity. This process, called photoreceptor light adaptation, is known to be mediated by a diffusible intracellular messenger, but the identity of the messenger is still unclear. There has been considerable speculation that decreased cytoplasmic Ca2+ concentration (Cai2+) may play a role in light adaptation, and recent experiments in which Ca2+ buffer was incorporated into rod-cells have supported this notion. The extent of the contribution of calcium, however, remains unresolved. We now show that light-dependent changes in sensitivity in amphibian photoreceptors can be abolished by preventing movements of Ca2+ across the outer-segment plasma membrane. These experiments demonstrate that light adaptation in photoreceptors is mediated in cones primarily, and in rods perhaps exclusively, by changes in Cai2+.

Adaptation, Ocular↗

AIDS.

AIDS is a syndrome that represents the most severe form of infection with the retrovirus HIV. Opportunistic infections, uncommon malignant neoplasms, and intractable immunologic deficiency are hallmarks of AIDS. To date, the syndrome in the U.S. is seen mainly in epidemiologically restricted populations. It appears to be transmitted in a manner analogous to hepatitis B. There is no available means of reversing the immune deficit. Therapy is restricted to treating the complicating infections and tumors. Those having been diagnosed with P. carinii pneumonia may benefit from therapy with AZT. The spread of HIV and the syndrome can only be reduced by preventive measures until an effective and safe vaccine can be developed.

AIDS-Related Complex↗

Action of phospholipase C at the neuromuscular junction in rodent skeletal muscles.

The isometric tension developed in response to diffuse application of acetylcholine was recorded in intact soleus muscles of the rat. Purified bacterial phospholipases of the C type, which hydrolyse either phosphatidylinositol or phosphatidylcholine, increased the acetylcholine contracture responses of the muscles. Sciatic nerve cytosol which had been purified over 8-fold with respect to phosphatidylinositol phospholipase C activity also increased these responses. The effect of phospholipase C on the miniature endplate potentials and neurally evoked endplate potentials was investigated in mouse diaphragm in vitro. The amplitude of both the miniature endplate potentials and the evoked endplate potentials was increased by the enzyme. The resting membrane potential, the effective input resistance and the frequency of miniature endplate potentials were not significantly altered by concentrations of the enzyme which increased the endplate responses. It is suggested that phospholipase C could have a trophic role at the neuromuscular junction.

Animals↗

Effects of diacylglycerol and phorbol ester on acetylcholine release and action at the neuromuscular junction in mice.

Miniature endplate potentials and nerve-evoked endplate potentials were studied in a phrenic nerve-diaphragm preparation of the mouse. A phorbol ester, phorbol-12 beta, 13 alpha-dibutyrate, and a diacylglycerol, 1-oleyl-2-acetyl-sn-glycerol, both increased the frequency of miniature endplate potentials. The effect of the phorbol ester on the frequency was still significant when the preparation was incubated in a calcium-deficient solution. The phorbol ester, but not the diacylglycerol, caused a significant increase in the amplitude of the miniature potentials. The phorbol ester also increased the amplitude of the endplate potentials in the presence of (+)-tubocurarine. The mechanisms of action of phorbol ester and diacylglycerol are discussed in relation to the control of acetylcholine release and action at the neuromuscular junction.

Animals↗

Observer agreement, chest auscultation, and crackles in asbestos-exposed workers.

Investigators cite observer variability as a problem in using crackles to diagnose asbestosis. We measured agreement on the presence or absence of crackles noted during auscultation of 64 asbestos-exposed workers in order to clarify this question. There was 89 percent agreement between two observers who simultaneously examined subjects breathing from functional residual capacity (FRC). Kappa (kappa), a statistic accounting for chance agreement, was 0.73. Unanimous agreement between four observers who listened to tape recordings of the breath sounds was 81 percent (kappa = 0.69). When the subjects breathed from residual volume (RV) there was 78 percent (kappa = 0.53) and 67 percent (kappa = 0.60) agreement, respectively. Comparing direct to tape-playback auscultation, there was 90 percent (kappa = 0.77) and 84 percent (kappa = 0.58) intraobserver agreement when the subjects breathed from FRC and 90 percent (kappa = 0.79) and 75 percent (kappa = 0.39) when they breathed from RV. We conclude that observer variability is sufficiently low to allow trained observers to monitor asbestos-exposed workers for crackles directly and during tape-playback auscultation.

Adult↗

Crackles in the early detection of asbestosis.

We studied 386 workers exposed to asbestos to assess the value of chest auscultation by a trained technician in detecting asbestosis as defined by previously reported clinical, physiologic, and roentgenologic criteria. The presence and degree of crackles were assessed at preselected basilar lung sites by a technician whose performance was validated by comparison with computer-generated time-expanded waveforms of tape recordings of lung sounds. Asbestosis was present in only 2.8% of the total population, but it was present in 8.6% of those with over 25 yr or more of employment. The technician correctly identified all the workers in whom the diagnosis was most certain, that is, those with all criteria positive. The overall true positive rate was 55%. The majority (94.8%) of those with no abnormal criteria were correctly classified. Auscultation by an objectively validated technician can be a useful noninvasive method for screening industrial populations exposed to asbestos.

Allied Health Personnel↗

Lung sounds.

A resurgence of interest in clinical auscultation is in progress. Recent technical advances permit more objective observations than were previously possible. Quantified lung sounds are being correlated with clinical, physiologic, and roentgenologic information. The purpose of this article is to summarize current knowledge on the production, transmission, and clinical significance of lung sounds. The complex sonic signals arising in the lung during respiration reflect its mechanical state. More precise understanding of pulmonary sounds and their clinical correlations could lead to powerful diagnostic tools, which have particular appeal because of their noninvasive nature.

Asthma↗