Biomedical subjects
Publications and source records attributed to J Mills.
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Hospital acquired infections caused by enterococci are increasing in incidence. This increase has been attributed, in part, to widespread use of cephalosporin antibiotics which lack activity against enterococci. To test this hypothesis, we compared patients having nosocomial enterococcal pulmonary and wound infections with those patients having nosocomial staphylococcal infections for antecedant cephalosporin use. In a six month period, we found 14 instances of nosocomial enterococcal wound and respiratory infections; 13 were superinfections (occurring during or up to one week after administration of antimicrobials). Seven had coexisting pathogens noted. In the same six month period, 30 instances of Staphylococcus aureus nosocomial respiratory tract and wound infections were found and only 13 were superinfections (p less than 0.002 compared with enterococcal superinfections). Nine had coexisting pathogens noted. The mean age, gender distribution and underlying illnesses in the Staphylococcus aureus and enterococcal superinfection groups were comparable. Of the 14 instances of enterococcal nosocomial infections, 11 were associated with administration of a cephalosporin compared with seven of 30 for staphylococcal infections (p less than 0.002). Nosocomial enterococcal infections are commonly associated with antimicrobial therapy and the use of cephalosporins may selectively predispose patients to increased risk of enterococcal superinfections.
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Current therapy for condylomata acuminata (genital warts) is not consistently effective. Therefore, we conducted a randomized, double-blind trial to compare interferon alpha-2b with placebo in the treatment of this disorder. Our rationale was that interferon has both antiproliferative and antiviral properties. The placebo or interferon (1 X 10(6) IU) was injected directly into one to three warts three times weekly for three weeks. The injections were well tolerated by both groups of patients. The side effects of fever, chills, myalgia, headache, fatigue, and leukopenia occurred more commonly in the interferon group than in the placebo group, but such effects rarely disrupted daily routines. Only 13 of 296 patients (4 percent) discontinued therapy because of side effects (11 in the interferon group and 2 in the placebo group). Twenty-six other patients were excluded from analysis because of a loss to follow-up or other deviations from protocol, thus leaving 257 patients in the final evaluation. At one week after the completion of therapy, interferon had produced a large and significantly greater reduction in mean wart area (a 62.4 percent decrease), as compared with placebo (a 1.2 percent increase in mean area) (P less than 0.001). At the conclusion of the study (13 weeks after the completion of therapy), the mean wart area was still decreased 39.9 percent below the initial size in the interferon group, whereas it had increased by 46 percent over base-line measurements in the placebo group (P less than 0.001). At the same time, all treated warts had completely cleared in 36 percent of the interferon recipients and in 17 percent of the placebo recipients (P less than 0.001), whereas treated warts progressed in 13 percent of the interferon recipients and in 50 percent of the placebo recipients (P less than 0.001). We conclude that injection of interferon alpha-2b directly into genital warts appears to be an effective and fairly well-tolerated form of therapy.
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pH-Dependent bactericidal activity on four gram-negative bacilli that are mainly responsible for gastric to airway colonisation has been investigated. Organisms studied were Escherichia coli, Enterobacter cloacae, Klebsiella pneumoniae and Serratia marcescens. At pH of the medium adjusted to 2.7 or lower all four organisms were killed in 1.5 h. At pH 3.1 or greater, no reduction in viable bacterial number was noted over 2 h. Even when pH of the medium was adjusted to 6.8, no increase in bacterial count was observed in 4 h. Relevance of these findings in relation to airway colonisation and prophylaxis of acid aspiration and stress ulcer syndromes is discussed. It is suggested to maintain pH of the gastric contents above 4.0 by H2 antagonists and prevent growth of gram-negative organisms in the stomach by keeping it empty.
The pharmacokinetics of ketanserin (R 41 468), a novel serotonin S2-receptor blocking agent widely investigated for its effect on acute and chronic hypertension, has been studied in 10 healthy male subjects. They received single 10 mg doses i.v. and i.m., and 20, 40 and 60 mg solutions of ketanserin by mouth, in a five-way cross-over design. The model-independent kinetics of i.v. ketanserin were characterized by a terminal half-life of 14.3 +/- 4.4 h, a moderate plasma clearance (CL = 565 +/- 57 ml/min) and a large tissue distribution (Vss = 268 +/- 71 l, Vz = 703 +/- 204 l; mean +/- SD). Following i.m. administration, peak levels of nearly 200 ng/ml were attained within 10 minutes and the absolute bioavailability was 112 +/- 23%. After oral dosing, peak levels of ketanserin were reached within 1 h. The peak level and AUC increased in proportion to the dose. The absolute bioavailability was 46.8, 50.4 and 55.5% for 20, 40 and 60 mg doses and they conformed to the predicted bioavailability based on i.v. clearance data. The terminal half-life of 17 h and the urinary excretion of parent drug (about 0.7% of the dose) were similar after oral and parenteral dosing. The kinetics of ketanserin-ol, the major metabolite of ketanserin formed by ketone reduction, was also studied. Because of its negligible pharmacological activity, the contribution of ketanserin-ol to the overall therapeutic effect of ketanserin is small, in spite of its 1.6-times (parenteral) to 3.2-times (oral) higher plasma level than that of ketanserin.(ABSTRACT TRUNCATED AT 250 WORDS)
Keeping track of needs in communal and exchange relationships was investigated in two experiments. In both, subjects could check to see if another person needed help. The first experiment tested the hypotheses that When there is no opportunity for the other to reciprocate in kind, keeping track of the other's needs will be greater if the person desires a communal relationship with the other than if the person desires an exchange relationship with the other. If the person desires an exchange relationship with the other, keeping track of the other's needs will be greater when an opportunity for the other to reciprocate in kind exists than when it does not. If a communal relationship is desired, the existence of an opportunity for the other to reciprocate in kind will not influence keeping track of the other's needs. The results of the first experiment supported all three hypotheses. The second experiment tested and found support for the hypothesis that even when nothing can be done to help the other, keeping track of the other's needs will be greater if a communal relationship is desired with the other than if an exchange relationship is desired.
Oral cefuroxime axetil (1 g) plus probenecid cured 29 of 30 urethral and 6 of 6 rectal gonococcal infections in men; alone the drug cured 22 of 23 urethral and 4 of 6 rectal infections. No toxicity was observed. Cefuroxime axetil alone is effective for urethral gonorrhea in males; rectal gonorrhea probably requires additional probenecid.
There are two major problems remaining for the successful assessment of left-ventricular regional wall motion (RWM) using nuclear cardiology. These are as follows. Which technique should be used: first pass or equilibrium? Secondly, which views should be used to give full information about the RWM of the left ventricle? This paper specifically considers each of these questions and concludes that equilibrium blood pool imaging in both the right anterior oblique and left anterior oblique projections is currently the best option.
All patients with the acquired immunodeficiency syndrome and a first episode of Pneumocystis carinii pneumonia seen at the San Francisco General Hospital between November 1984 and April 1985 were evaluated for oral treatment with dapsone (100 mg/d) plus trimethoprim (20 mg/kg body weight X d). All 15 patients who met the entry criteria improved clinically and radiographically within 3 to 10 days after starting treatment. Repeat pulmonary function tests and gallium lung scans after 3 weeks of therapy also showed improvement. Although side effects occurred in 14 patients, in only 2 were they severe enough to require stopping therapy. Both of these patients had worsening skin rash, and dapsone-trimethoprim therapy was stopped after 10 days. When compared with trimethoprim-sulfamethoxazole or pentamidine used to treat P. carinii pneumonia in similar patients, oral dapsone-trimethoprim is at least as effective, seems to be better tolerated, and may have a lower frequency of serious side effects.
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U.S. Army hypobaric chamber operations over a 63-month period were retrospectively reviewed, and incidence rates for decompression sickness were calculated. The overall incidence rate was 1.38/1000 exposures. The rate for interior technicians monitoring chamber operations was 6.16/1000 exposures. The rate for students was 0.64/1000 exposures. The increased incidence of decompression sickness for technicians was especially pronounced for the 10,668-m and 13,106-m flight profiles. Rapid decompression after the 7,620-m flight profile did not appear to increase the incidence of decompression sickness.
Acquired-immunodeficiency-syndrome (AIDS)-associated retroviruses (ARV) have been isolated from the cerebrospinal fluid and brain of homosexual men presenting with neurological symptoms. Most of these patients also met the clinical criteria for AIDS. The viruses grew readily in peripheral mononuclear cells and were identified by their induction of cytopathic effects and ARV antigens in culture. The results suggest that ARV could be the cause of the neurological syndromes in AIDS patients and indicate that the virus can infect cells other than T lymphocytes.
We studied the clinical features and course (average follow-up time, 18 months) of 27 patients with acute dilated cardiomyopathy (symptoms for less than 6 months) who were referred for endomyocardial biopsy. Almost 40 per cent of the patients subsequently had a rise in left ventricular ejection fraction (on average, from 0.21 to 0.41) and substantial improvement in heart failure; the remainder died or had chronic dilated cardiomyopathy. Biopsy revealed myocarditis in 18 patients, and this finding was especially common (89 per cent) in patients who had been ill for less than four weeks. But the biopsy specimen was negative in four patients whose clinical features and later course were diagnostic of myocarditis. Nine patients received immunosuppressive drugs, and four improved--a rate that did not differ from the rate of spontaneous improvement. Neither the histologic features of the biopsy specimen nor the clinical features at presentation were clearly correlated with subsequent improvement, whether or not immunosuppressive drugs were given. We conclude that many cases of unexplained dilated cardiomyopathy result from myocarditis. Definitive histologic confirmation depends on the duration of illness. The efficacy of immunosuppressive treatment must still be established.
Within a 5-month period, 2 homosexual men with persistent lymphadenopathy developed clinical findings consistent with herpes simplex virus (HSV) encephalitis. These signs included abrupt change in mental status, seizures, cerebrospinal fluid pleocytosis, and localized electroencephalographic abnormalities showing temporal lobe involvement. Initial computed tomographic scans were unremarkable. Treatment with adenine arabinoside was instituted and temporal lobe biopsies were performed. Although virus-specific antigens were detectable in only 1 patient, cultures of biopsy tissue from both patients yielded HSV type 2 organisms. Spiking fevers persisted and the patients failed to improve, prompting administration of acyclovir. Both patients recovered gradually after their second course of antiviral therapy and survived with severe neurological deficits. These patients should raise concerns about an increased incidence of type 2 encephalitic illness among homosexual men with persistent lymphadenopathy or acquired immune deficiency syndrome. In addition, the importance of using HSV type 2 antibody in the immunofluorescence test of brain biopsy tissue for rapid diagnosis of the disease is emphasized.
Over a one-year period the cerebrospinal fluid (CSF) obtained from a series of homosexual men immunocompromised with either Hodgkin's disease or acquired immune deficiency syndrome (AIDS) was cultured to assess the frequency with which infectious viruses could be recovered. Of 58 patients examined, 4 (6.9%) had CSF cultures that showed a cytopathology consistent with a virus infection. All isolates proved to be herpesviruses. Cytomegalovirus (CMV) and varicella-zoster virus were isolated from CSF obtained from 2 patients with neurological features consistent with a subacute encephalitis common among AIDS patients. CMV was also recovered from the CSF of an AIDS patient who developed an ascending myelitis of herpesvirus origin. Finally, a CSF sample obtained from an immunodeficient homosexual man who showed no detectable neurological abnormalities consistently yielded herpes simplex virus type 1 in culture. These results suggest that seeding of the CSF with infectious virus is an uncommon event in this patient population. However, our experience should not dissuade attempts to culture viruses from CSF in similar cases. Successful isolations may prove beneficial in the diagnosis of an accompanying neurological illness and facilitate treatment with antiviral therapy when indicated.