Typhlitis in patients with HIV-1 infection.
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Adult↗
Biomedical subjects
R L Murphy
Publications and source records attributed to R L Murphy.
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↗
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↗
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↗
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↗
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↗
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↗
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↗
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↗
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↗
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↗
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↗
Acute pancreatitis associated with aerosolized pentamidine.
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Acute Disease↗
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↗
Megestrol acetate for treatment of cachexia associated with human immunodeficiency virus (HIV) infection.
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Acquired Immunodeficiency Syndrome↗