Search PubMed⌕ Search

Biomedical subjects

R L Murphy

Publications and source records attributed to R L Murphy.

At least 55 records · Page 3Linked to original sources
PubMed1996

The concept of cardioreparation: Part 2. Medical implications of cardioreparation.

PURPOSE: Left ventricular hypertrophy (LVH) caused by systemic hypertension, myocardial infarction and congestive heart failure is associated with pathological changes in the structure of the heart, collectively described as remodelling (see part 1 of this review). The reversal of remodelling, termed cardioreparation, might restore cardiac structure and function towards normal, thereby improving the prognosis of these conditions. We aimed to explore the medical implications of this concept. DATA EXTRACTION: Clinical trials of angiotensin converting enzyme (ACE) inhibitors and other drugs in patients with hypertension, myocardial infarction and congestive heart failure were reviewed. The results showed that ACE inhibitors induce regression of LVH in hypertensive patients, reduce mortality in acute myocardial infarction, and reduce morbidity and mortality in patients with congestive heart failure or left ventricular dysfunction subsequent to myocardial infarction. These observations are consistent with cardioreparation by ACE inhibitors. CONCLUSIONS: ACE inhibitors reduce morbidity and mortality in patients with myocardial infarction or congestive heart failure. Theoretical considerations and some clinical observations suggest that these benefits might result from cardioreparation.

Antihypertensive Agents↗
PubMed1995

Key issues in the treatment of chronic lymphocytic leukaemia (CLL)

The outcome of the treatment of chronic lymphocytic leukaemia (CLL) has improved little over the past 30 years. The recent introduction of purine analogues, particularly fludarabine, may change this situation. These agents are highly effective and generally well tolerated. They raise the possibility of improved disease-free survival and allow appropriate patients to be considered for bone marrow transplantation (BMT). Randomised clinical trials are needed to establish the roles of purine analogues and other novel agents in improving the survival of CLL patients. These trials should use consistent diagnostic and assessment criteria to allow for the clinical heterogeneity of CLL.

Antibodies, Monoclonal↗
PubMed1994

Clindamycin and primaquine therapy for mild-to-moderate episodes of Pneumocystis carinii pneumonia in patients with AIDS: AIDS Clinical Trials Group 044.

The objective of this prospective, noncomparative study was to assess the safety and efficacy of clindamycin and primaquine therapy for mild-to-moderate pneumocystis pneumonia (defined as a difference of < 40 mm Hg between the alveolar and the arterial oxygen determinations) in patients with AIDS. In the first part of the study, 22 patients were treated with iv clindamycin (900 mg every 8 hours) for the first 10 days, and then their therapy was switched to oral clindamycin (450 mg every 6 hours) for an additional 11 days. In the second part of the study, 38 patients were treated entirely with oral clindamycin (600 mg every 8 hours). All patients were treated with oral primaquine base (30 mg once daily). Fifty-five (92%) of 60 patients responded to the study treatment. Forty-six (77%) of 60 patients completed a full course of therapy. Of the nine patients with treatment-limiting toxic effects, four had only a mild rash. This study indicates that the combination of clindamycin and primaquine is an effective and well-tolerated therapy for mild-to-moderate pneumocystis pneumonia in patients with AIDS. Entirely oral therapy appears to be as effective as initial therapy with iv clindamycin.

AIDS-Related Opportunistic Infections↗
PubMed1994

Phase II dose-ranging trial of foscarnet salvage therapy for cytomegalovirus retinitis in AIDS patients intolerant of or resistant to ganciclovir (ACTG protocol 093). AIDS Clinical Trials Group of the National Institute of Allergy and Infectious Diseases.

OBJECTIVE: To document response to foscarnet salvage therapy in patients with cytomegalovirus (CMV) retinitis who are intolerant of or resistant to ganciclovir. METHODS: Patients with AIDS and CMV retinitis who had documented hematologic intolerance or resistance to ganciclovir therapy received an induction course of foscarnet, 60 mg/kg every 8 h for 14 days, and subsequent chronic maintenance foscarnet therapy at a daily dose of 60, 90 or 120 mg/kg/day. The first 87 patients were randomly assigned to receive maintenance foscarnet at a dose of 60 or 90 mg/kg/day; all subsequent patients were assigned a maintenance dose of 120 mg/kg/day. RESULTS: A total of 156 evaluable patients were enrolled. Median time to retinitis progression and survival did not differ significantly among groups assigned to different maintenance foscarnet doses. Among patients with retinitis progression documented ophthalmologically occurring at < or = 2 week intervals, despite optimal doses of ganciclovir, time to progression on foscarnet therapy was a median 8 weeks at all doses studied. By dose assignment, there were no significant differences in serious drug-associated toxicity, although trends toward increased renal and hypocalcemic adverse events were observed at higher maintenance doses. CONCLUSION: In patients intolerant of ganciclovir, salvage foscarnet therapy resulted in a longer time to retinitis progression than reported previously in historic controls who terminated ganciclovir therapy. In patients who exhibited clinical resistance to ganciclovir, foscarnet appeared to have efficacy in controlling retinitis. No significant differences in either efficacy or toxicity were observed in the range of foscarnet maintenance doses studied.

AIDS-Related Opportunistic Infections↗
PubMed1994

Clinical utility of chest auscultation in common pulmonary diseases.

In this investigation we applied the techniques of lung sound mapping and time-expanded wave-form analysis to four common diseases that involve the lung: interstitial pulmonary fibrosis (IPF), chronic obstructive pulmonary disease (COPD), congestive heart failure (CHF), and pneumonia (Pn). Twenty subjects were studied in each group. We also studied 15 subjects without evidence of lung disease. Differences in timing, character, and location were observed, which allowed separation among these groups. Multiple logistic regression models were created and tested by the bootstrap method. Regression models correctly classified 68 and 79% of subjects. Area under the receiver operating curve ranged from 0.96 for IPF and CHF to 0.80 for COPD. We conclude that auscultatory differences exist among common pulmonary conditions and that statistical models based on auscultatory data perform well in predicting diagnostic categories.

Aged↗
PubMed1993

Alternating and intermittent regimens of zidovudine and dideoxycytidine in patients with AIDS or AIDS-related complex.

OBJECTIVE: To determine whether alternating regimens consisting of zidovudine and 2',3'-dideoxycytidine (ddC) reduce the toxicity and maintain or increase the antiretroviral effect associated with each drug alone. DESIGN: An unblinded, randomized (phase II) clinical trial in which seven treatment regimens were compared. SETTING: Outpatient clinics of 12 AIDS Clinical Trials Units. PATIENTS: One hundred thirty-one patients with the acquired immunodeficiency syndrome (AIDS) or AIDS-related complex and serum p24 antigenemia (> or = 70 pg/mL). INTERVENTION: Treatments included weekly or monthly alternating zidovudine (200 mg every 4 hours) and ddC (0.01 or 0.03 mg/kg body weight every 4 hours); weekly intermittent zidovudine, 200 mg every 4 hours, or ddC, 0.03 mg/kg every 4 hours; and continuous zidovudine. MEASUREMENTS: Toxicity, CD4 cell counts, serum p24 antigen levels, and clinical end points. Data were analyzed for the first 48 weeks of therapy (median follow-up, 40 weeks). RESULTS: Hematologic toxicity was significantly less frequent in patients who received zidovudine therapy every other week (11% to 15%) or every other month (11% to 14%) than in those who received continuous zidovudine therapy (33%) (P < 0.02). Weekly alternating therapy with zidovudine and ddC, 0.03 mg/kg, or intermittent therapy with ddC, 0.03 mg/kg, produced high rates of peripheral neuropathy (41% and 50%, respectively). Neuropathy occurred in 10% to 21% of patients in the other three alternating-therapy limbs and in 17% of patients receiving zidovudine alone (intermittently or continuously). Initial increases in CD4 cell counts were sustained in three alternating-therapy limbs, but counts returned to baseline by week 28 in the remaining limbs. The median weight gain at week 48 was significantly greater in patients treated with alternating regimens (0.9 to 3.8 kg) compared with those treated with continuous zidovudine therapy (-0.7 kg) (P = 0.008). Patients treated with alternating regimens and those treated with continuous zidovudine had similarly sustained decreases in p24 antigen levels. CONCLUSIONS: These findings suggest that alternating therapy with zidovudine and ddC reduces the toxicity associated with each drug alone while maintaining strong antiretroviral activity.

AIDS-Related Complex↗
PubMed1992

Salvage therapy with clindamycin/primaquine for Pneumocystis carinii pneumonia.

Clindamycin/primaquine is effective for treating mild-to-moderate cases of Pneumocystis carinii pneumonia (PCP) in patients with AIDS. We retrospectively reviewed our experience with this combination among patients in whom conventional therapy had failed or was not tolerated. Twenty-six patients who experienced 28 episodes of PCP received salvage therapy with clindamycin/primaquine at two university-affiliated medical centers. Clindamycin was administered intravenously, (usually 900 mg every 8 hours), after which oral therapy was instituted. Primaquine (30 mg) was given orally to all patients except three; two of these patients received 15 mg of the drug daily and another 30 mg of drug on alternate days. In 11 of the episodes, the patients received clindamycin/primaquine as initial therapy for PCP because of previous intolerance of conventional therapy. In 13 of the episodes, conventional therapy had failed or the patients were unable to tolerate the regimen, while in four episodes conventional therapy failed and the patients were unable to tolerate their therapeutic regimens. Twenty-four (86%; 95% confidence interval, 73%-99%) of 28 episodes were successfully treated with clindamycin/primaquine. The most common adverse effect was the development of an erythematous rash. Clindamycin/primaquine appears to be an attractive alternative for patients in whom standard therapy for PCP has failed or cannot be tolerated.

Administration, Oral↗
PubMed1992

Concurrent bacterial lung infection in patients with AIDS, PCP, and respiratory failure.

STUDY OBJECTIVES: To determine and compare the incidence of concurrent bacterial lung infection in intubated and nonintubated patients with the acquired immunodeficiency syndrome (AIDS) and Pneumocystis carinii pneumonia (PCP) requiring medical intensive care unit (MICU) admission for support of their respiratory function. DESIGN: Retrospective review of medical records. SETTING: A large university hospital and AIDS treatment center. PATIENTS: All AIDS/PCP patients admitted to the MICU for support of oxygenation and/or ventilation between 1985 and 1989. Survival was defined as discharge from the hospital; nonsurvival was defined as death any time during the hospitalization. Patients with acute spinal cord injury (SCI) were used as controls to determine the incidence of nosocomial pneumonia in ICU patients of similar age without AIDS. MEASUREMENTS AND RESULTS: Twenty-nine AIDS/PCP patients met study criteria; eight (28 percent) were survivors and 21 (72 percent) were nonsurvivors. There was no significant difference in duration of intubation or duration of ICU stay between survivors and nonsurvivors with or without intubation. The incidence of bacterial concurrent lung infection (CLI) in AIDS/PCP patients overall was 7 percent and in intubated AIDS/PCP patients it was 10 percent. There was no statistically significant difference in the incidence of bacterial CLI between the survivors and nonsurvivors or between intubated and nonintubated patients with AIDS/PCP. The incidence of nosocomial pneumonia in SCI overall was 17 percent and in intubated SCI patients it was 30 percent. CONCLUSIONS: The incidence of bacterial lung infections in our retrospective study of AIDS patients with PCP is remarkably less than in the general ICU population with respiratory failure and in our control patients with SCI, although the differences did not attain statistical significance. This finding may be related to antimicrobial therapy directed against P carinii. Endotracheal intubation in patients with AIDS and PCP, who were undergoing appropriate antimicrobial therapy, did not result in a significantly higher incidence of bacterial lung infections than in those who were not intubated. There was no significant difference in the incidence of bacterial lung infections between those AIDS/PCP patients who survived episodes of severe respiratory failure and those who did not. Endotracheal intubation should not be delayed or withheld from this patient population due to concerns of pulmonary bacterial superinfection.

Acquired Immunodeficiency Syndrome↗
PubMed1992

Pneumocystis carinii choroiditis in patients with AIDS: clinical features, response to therapy, and outcome.

To further characterize the clinical features, response to therapy, and outcome of Pneumocystis carinii choroiditis in patients with AIDS, we retrospectively reviewed the course of choroiditis for eight patients identified from two institutions through April 1991. Seven patients had prior Pneumocystis carinii pneumonia and had received aerosolized pentamidine prophylaxis for a median of 10 months; one patient had no prior history of pneumonia or prophylaxis. The median CD4+ lymphocyte count for six patients was 11 cells/mm3. Choroiditis was a preterminal diagnosis for three patients--two with associated disseminated pneumocystosis. Ocular manifestations improved or resolved with therapy for five of the six treated patients. All five subsequently received prophylaxis with dapsone (n = 2), dapsone/trimethoprim (n = 2), or aerosolized pentamidine (n = 1). Choroiditis recurred at 15 months in the one patient receiving aerosolized pentamidine. The median survival from time of diagnosis was 44 weeks. A literature review including an additional 40 cases support the conclusions that (a) Pneumocystis choroiditis is a rare complication of advanced HIV disease, occurring often in the context of systemic pneumocystosis; (b) ocular signs and symptoms may improve or resolve with specific antipneumocystis therapy; and (c) relapse may occur, particularly in those not receiving systemic prophylaxis.

AIDS-Related Opportunistic Infections↗
PubMed1991

The effects of a diacylglycerol kinase inhibitor at mammalian and amphibian neuromuscular junctions in vitro.

Miniature endplate potentials were studied in mouse phrenic nerve-hemidiaphragm and frog pectoris-cutaneous neuromuscular preparations. The diacylglycerol kinase inhibitor R59022 increased the frequency of miniature endplate potentials in both preparations. The results indicate that endogenous diacylglycerol regulates acetylcholine release via activation of protein kinase C. Continuous monitoring of miniature endplate potential frequency in the frog preparation showed that higher doses of the inhibitor caused a large rise in release rate, which subsequently settled at a lower, though still augmented, level. It is suggested that a negative feedback may occur in response to high protein kinase C activity, possibly to inhibit diacylglycerol generation.

Animals↗
PubMed1991

Clindamycin and primaquine as primary treatment for mild and moderately severe Pneumocystis carinii pneumonia in patients with AIDS.

The combination of clindamycin and primaquine was investigated as primary treatment for mild or moderately severe Pneumocystis carinii pneumonia (alveolar-arterial oxygen gradient less than 40 torr) in 36 AIDS patients. All patients were treated with primaquine 30 mg (base) orally for 21 days. The first 22 patients were treated with clindamycin 900 mg i.v. q8h for the first 10 days, followed by clindamycin 450 mg q6h orally for 11 days. Twenty of these 22 patients (91%) showed a marked clinical response by day 7. Four patients were later withdrawn from the study due to toxicity. An additional 14 patients were treated with an entirely oral regimen of clindamycin and primaquine. Thirteen of the 14 patients (93%) showed a marked therapeutic response and 12 (86%) successfully completed treatment. The combination of clindamycin and primaquine appears to be an effective and well-tolerated treatment for mild to moderately severe Pneumocystis carinii pneumonia in AIDS patients.

Acquired Immunodeficiency Syndrome↗
PubMed1991

Prevalence of measles antibodies in asymptomatic human immunodeficiency virus-infected adults.

One hundred five asymptomatic human immunodeficiency virus-seropositive adults were screened for measles antibody. Ages ranged from 21 to 59 years (mean, 35.7). CD4+ lymphocyte counts (range, 76-1137/mm3), percentage of CD4+ cells (6-42), CD4:CD8 ratio (0.08-1.3), measles antibody titers by EIA, and undocumented history of prior measles or immunization were obtained. Forty-six patients gave a history of measles but no immunization, 18 of immunization but no measles, 26 of immunization and measles, and 15 of neither measles nor vaccination. Only one patient (less than 1%) lacked levels of antibody considered protective. Neither the presence nor the level of antibody were predictable from patient age, history of measles or immunization, CD4+ lymphocyte count, percentage of CD4+ cells, or CD4:CD8 ratio. Nearly all subjects had antibody to measles, regardless of immunization or measles history. Whether these antibodies are truly protective is unknown.

Adult↗
PubMed1991

Aerosol pentamidine prophylaxis following Pneumocystis carinii pneumonia in AIDS patients: results of a blinded dose-comparison study using an ultrasonic nebulizer.

PURPOSE: To compare the efficacy and safety of three different doses of prophylactic aerosol pentamidine in patients with one prior episode of Pneumocystis carinii pneumonia (PCP) and the acquired immunodeficiency syndrome. PATIENTS AND METHODS: The design of the study was a double-blind, randomized, dose-comparison clinical trial conducted at 13 medical centers within the United States. In stage I of the trial, patients were randomized to receive either 5 mg, 60 mg, or 120 mg of aerosol pentamidine delivered biweekly with the Fisoneb (Fisons, Inc., Rochester, New York) ultrasonic nebulizer. After 24 weeks of therapy, patients entered stage II of the trial, where the 5-mg group was re-randomized to either the 60-mg or 120-mg group. RESULTS: One hundred seventy-five patients entered stage I of the trial and received prophylaxis for a mean of 123.6 days. Seven assigned to the 5-mg biweekly dosing schedule had a confirmed recurrence of PCP, compared with none in the 60-mg group (p = 0.007) and three in the 120-mg group (p = 0.304). During stage II of the trial, eight patients in the 60-mg group and one additional patient in the 120-mg group had recurrent PCP. After 52 weeks of observation, the likelihood of being PCP-free was 88.0% in the 60-mg group and 93% in the 120-mg group (p = 0.712). Minor adverse events related to aerosol pentamidine administration included cough, taste perversion, chest pain, bronchospasm, and dyspnea. These side effects were more common in the 60-mg and 120-mg treatment groups and resulted in withdrawal from the study by one patient. Serious events were more common after 24 weeks of therapy and included asymptomatic hypoglycemia (five), pancreatitis (two), pneumothorax (one), and extrapulmonary pneumocystosis (one). CONCLUSIONS: These results demonstrate that biweekly administration of 60 mg or 120 mg of aerosol pentamidine significantly decreases PCP recurrence when compared with a 5-mg regimen or findings in historic controls and is generally well tolerated. There is no significant difference in effect or safety between these two dosing regimens in patients followed for at least 52 weeks of therapy.

Adult↗
PubMed1990

Light adaptation in cone photoreceptors of the salamander: a role for cytoplasmic calcium.

1. Light adaptation has been studied in isolated red-sensitive cone photoreceptors of the salamander, using suction pipette recordings of circulating current. 2. In the presence of background illumination, the response to incremental dim flashes became desensitized according to the Weber-Fechner law. The recovery phase of the flash response was accelerated significantly, although the time-to-peak was reduced only slightly, and for dim backgrounds the rising phase was unaltered. 3. The role of cytoplasmic calcium concentration, Cai2+, in mediating cone adaptation was investigated by minimizing light-induced changes in Cai2+, either by incorporating calcium buffer into the cytoplasm or by exposing the outer segment to low-Ca2+, 0-Na+ solution. Both treatments appeared to slow dramatically or even to eliminate the onset of light adaptation in the cone. 4. When the low-Ca2+, 0-Na+ solution was presented in darkness, responses to subsequent illumination were affected in a characteristic manner: (i) the response-intensity relation was steepened and shifted to lower intensities, (ii) the response to a step of light could be predicted by integration and compression of the flash response, and (iii) the flash sensitivity declined steeply as a function of background intensity. 5. After extended exposure of the cone to bright backgrounds, the sensitivity in darkness failed to return to its original level. The flash response kinetics were faster and more biphasic than for dark-adapted responses or for responses desensitized to a comparable degree by exposure to steady background illumination. 6. The results indicate that, in cones isolated from the pigment epithelium, the primary factor influencing the adaptational state of the cell is the cytoplasmic concentration of free calcium, but that at high intensities the effects of pigment bleaching are likely to be significant.

Action Potentials↗
PubMed1990

Lung sound nomenclature survey.

We report the terms used by 223 pulmonary physicians and 54 physicians in other specialties to describe eight recorded examples of lung sounds. The participants listened to the lung sounds at the 1988 American College of Chest Physicians annual convention and wrote "free form" answers. Pulmonary physicians used the terms "crackles" and "rales" with equal frequency to describe discontinuous adventitious lung sounds (ALS) and not at all to describe continuous ALS. Other physicians preferred the term "rales" in describing discontinuous ALS. The terms "wheeze" and "stridor" were used only in describing continuous ALS; however, the term "rhonchi" was frequently used to describe continuous and discontinuous ALS. The majority of participants recognized the normal breath sounds but not the pleural friction rub. Most did not use a qualifying adjective to describe ALS, and there was little agreement among those who did. The lung sound terminology used by physicians is not well standardized and the recommendations of the ATS/ACCP nomenclature subcommittee are not widely accepted.

Data Collection↗
PubMed1990

Megestrol acetate for treatment of anorexia and cachexia associated with human immunodeficiency virus infection.

Cachexia is a common problem in persons infected with the human immunodeficiency virus (HIV). Megestrol acetate, an agent used for the treatment of metastatic breast cancer, is associated with appetite stimulation and weight gain. To determine whether this drug might benefit HIV-positive patients, 22 such subjects (14 previously reported) were treated with oral megestrol acetate, beginning at a dose of 80 mg four times daily. All patients had lost at least 10% of their preillness weight prior to treatment; the median loss was 11.4 kg (range, 5.5 to 26.8). Preliminary data from patients observed during therapy from 2 to 72 weeks showed that 21 of the 22 patients gained weight; the average weight gain was 7.3 kg (range, -4.1 to 17.3). Three patients failed to gain weight on 320 mg per day of megestrol acetate; both appetite stimulation and weight gain were achieved with 460 mg per day in one and 640 mg per day in another. One patient continued to lose weight despite 480 mg per day megestrol acetate. The median time to peak weight during megestrol acetate treatment was 14 weeks. Seven patients returned to within 1 kg of their normal body weight. In three of the 22 patients treated, megestrol acetate and zidovudine were started simultaneously. For these three patients, weight gain was potentially due to the recognized weight gain associated with the initiation of zidovudine. For the remaining 18 patients, however, appetite stimulation and weight gain were a result of megestrol acetate. All patients tolerated the drug well. One patient developed a deep vein thrombosis. No patient developed peripheral edema or drug-related impotence. The appetite improvement and weight gain seen in this initial series are encouraging. The true effectiveness of megestrol acetate for HIV-related cachexia and the effects of treatment on quality of life are currently being assessed in a national prospective, randomized, double-blind, placebo-controlled trial.

Acquired Immunodeficiency Syndrome↗