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Biomedical subjects

S D Shafran

Publications and source records attributed to S D Shafran.

At least 19 recordsLinked to original sources
PubMed1996

Dapsone- and primaquine-induced methemoglobinemia in HIV-infected individuals.

Clinically significant methemoglobinemia can develop as a result of medications. Although dapsone and primaquine are known to produce methemoglobinemia in susceptible individuals, methemoglobinemia has been reported only rarely in the human immunodeficiency virus (HIV) population. We describe five cases of methemoglobinemia caused by either primaquine or dapsone alone or in combination. The initial methemoglobin level ranged from 15.3% in the patient whose methemoglobinemia was caused by primaquine alone to 33.1%. Five patients developed symptomatic methemoglobinemia requiring hospitalization for 1 to 12 days. Two cases resulted from intentional overdoses of dapsone, and three developed within several days of commencing primaquine while dapsone remained present in the bloodstream. The four severe cases required intravenous methylene blue, supplemental oxygen, plus erythrocyte transfusions, whereas the mild case responded to oxygen therapy plus discontinuation of the precipitating drugs. Blood gases and pulse oximetry do not aid in the diagnosis, which requires cooximetry. Our study indicates that dapsone and primaquine alone or in combination can produce clinically significant methemoglobinemia in HIV-infected individuals, either in the setting of an overdose or when primaquine is instituted before dapsone has been cleared from the bloodstream.

AIDS-Related Opportunistic Infections↗
PubMed1996

A comparison of two regimens for the treatment of Mycobacterium avium complex bacteremia in AIDS: rifabutin, ethambutol, and clarithromycin versus rifampin, ethambutol, clofazimine, and ciprofloxacin. Canadian HIV Trials Network Protocol 010 Study Group.

BACKGROUND: Bacteremia with the Mycobacterium avium complex is common in patients with the acquired immunodeficiency syndrome (AIDS), but the most effective treatment for this infection remains unclear. METHODS: We randomly assigned 229 patients with AIDS and M. avium complex bacteremia to receive either rifampin (600 mg daily), ethambutol (approximately 15 mg per kilogram of body weight daily), clofazimine (100 mg daily), and ciprofloxacin (750 mg twice daily) (the four-drug group) or rifabutin (600 mg daily), ethambutol (as above), and clarithromycin (1000 mg twice daily) (the three-drug group). In the three-drug group the dose of rifabutin was reduced by half after 125 patients were randomized, because 24 of 63 patients had uveitis. RESULTS: Among 187 patients who could be evaluated, blood cultures became negative more often in the three-drug group than in the four-drug group (69 percent vs. 29 percent, P<0.001). Among patients treated for at least four weeks, the bacteremia resolved more frequently in the three-drug group (78 percent vs. 40 percent, P<0.001). In the three-drug group, bacteremia resolved more often with the 600-mg dose of rifabutin than with the 300-mg dose (P=0.025), but the latter regimen was more effective than the four-drug regimen (P<0.05). The median survival was 8.6 months in the three-drug group and 5.2 months in the four-drug group (P = 0.001). The median Karnofsky performance score was higher in the three-drug group than in the four-drug group from week 2 to week 16 (P<0.05). Mild uveitis developed in 3 of the 53 patients receiving the 300-mg dose of rifabutin, an incidence about one quarter that observed with the 600-mg dose (P<0.001). CONCLUSIONS: In patients with AIDS and M. avium complex bacteremia, treatment with the three-drug regimen of rifabutin, ethambutol, and clarithromycin leads to resolution of the bacteremia more frequently and more rapidly than treatment with rifampin, ethambutol, clofazimine, and ciprofloxacin, and survival rates are better.

AIDS-Related Opportunistic Infections↗
PubMed1996

Patient-initiated, twice-daily oral famciclovir for early recurrent genital herpes. A randomized, double-blind multicenter trial. Canadian Famciclovir Study Group.

OBJECTIVE: To compare the efficacy and safety of episodic patient-initiated oral famciclovir with placebo in recurrent genital herpes. DESIGN: Randomized, double-blind, frequent-observation, dose-ranging study comparing twice-daily 125-mg, 250-mg, or 500-mg oral famciclovir with placebo. Patients initiated therapy after self-culturing, reported to the clinic within 12 hours, and were assessed twice daily for at least 5 days. SETTING: Fifteen Canadian university, private practice, or public outpatient clinics. PATIENTS: A total of 692 patients with culture-proven recurrent genital herpes were randomized; 467 patients experienced a symptomatic episode and commenced treatment. MAIN OUTCOME MEASURE: Time to complete healing of all lesions. RESULTS: Famciclovir (all doses) was significantly more effective than placebo in reducing time to healing, time to cessation of viral shedding, and durations of lesion edema, vesicles, ulcers, and crusts. Times to cessation of all symptoms and of moderate to severe lesion tenderness, pain, and burning were also reduced. Patients who initiated famciclovir prior to viral shedding were more likely to not shed virus throughout. All doses were equally effective, safe, and well tolerated. CONCLUSIONS: Oral famciclovir reduced the onset and duration of viral shedding, lesion persistence, and uncomfortable symptoms. Several individual symptoms and lesion stages were also reduced in duration by this episodic therapy. Additionally, our twice-daily observation trial design proved to be a helpful tool for studying recurrent disease. Episodic oral famciclovir provides a convenient and effective alternative for those patients with recurrent genital herpes whose frequency rates do not require continuous antiviral suppression.

2-Aminopurine↗
PubMed1996

Infective endocarditis: review of 135 cases over 9 years.

One hundred thirty-five cases of infective endocarditis in adults at the University of Alberta Hospital from 1985 to 1993 were reviewed and the von Reyn and Duke criteria were compared. There were 80 cases of native valve endocarditis, 15 cases of endocarditis in intravenous drug users, 7 cases of early prosthetic valve endocarditis, and 33 cases of late prosthetic valve endocarditis. Valve replacement or repair was performed in 33% of all cases. The overall mortality was 19%. The mortality among patients treated surgically was significantly lower than that among those treated medically (9% vs. 24%, respectively; P = .037). However, when patients who were too medically unstable for surgery or who refused surgery were excluded, the mortality among the medically treated group decreased to 15%, which was not significantly different from that among the surgically treated group. The 33 patients transferred from other hospitals were infected with similar pathogens; however, the rate of surgical intervention among these patients was much higher than that among other patients (64% vs. 24%, respectively; P < .0001), and the mortality was slightly lower (12.1% vs. 21.6%, respectively; P = .31). The 54 surgical and autopsy-proven cases were classified by the von Reyn and the Duke criteria without knowledge of the operative and autopsy results: 15% of these cases were rejected by the von Reyn criteria, and none were rejected by the Duke criteria.

Adolescent↗
PubMed1995

Disseminated Mycobacterium genavense infection in Canadian AIDS patients.

Mycobacterium genavense is a recently described mycobacterial species which thus far has been identified only in persons with advanced HIV disease. It appears to be a rare pathogen with an undefined reservoir. We describe the first two cases of M. genavense infection in Canadian AIDS patients. The clinical presentation of fever and wasting with extremely low CD4 lymphocyte counts was indistinguishable from disseminated M. avium complex (MAC) infection. However, blood cultures in BACTEC 13A medium required a mean of 58 days (range 41-87) to detect growth of M. genavense in contrast to a mean of 10 days for MAC in our laboratory. M. genavense infection is underdiagnosed due to the lack of universal use of BACTEC liquid medium and the use of relatively short incubation times (only 6 weeks) by some laboratories. The value of antimycobacterial therapy for M. genavense is unknown, but anecdotal data suggest that treatment with a regimen appropriate for MAC may be beneficial.

Acquired Immunodeficiency Syndrome↗
PubMed1993

Treatment of acute uncomplicated urinary tract infections with 3 days of lomefloxacin compared with treatment with 3 days of norfloxacin.

The bacteriologic and clinical efficacies of 3 days of lomefloxacin therapy were compared with those of 3 days of norfloxacin therapy for the treatment of acute uncomplicated urinary tract infections in a prospective, randomized, double-blind study. One hundred sixty-four subjects were enrolled at five Canadian centers; 84 received lomefloxacin, and 80 received norfloxacin. Escherichia coli (84%) and Staphylococcus saprophyticus (11%) were the most common organisms isolated. Forty subjects (24%) had low quantitative counts in their pretherapy urine specimens. In the intent-to-treat analysis, 76 lomefloxacin subjects (91%) and 76 norfloxacin subjects (95%) were cured or improved at follow-up 5 to 9 days posttreatment and 73 (87%) and 71 (89%) subjects from the lomefloxacin and norfloxacin groups, respectively, were cured or improved at 4 to 6 weeks posttreatment. Bacteriologic eradication occurred in 61 of 63 lomefloxacin subjects (97%) with > or = 10(8) CFU/liter in their pretherapy specimens and 56 of 59 norfloxacin subjects (95%) at 5 to 9 days and 55 (87%) and 53 (90%) subjects from the lomefloxacin and norfloxacin groups, respectively, at 4 to 6 weeks. There were no statistically significant differences in outcome. Adverse effects which were potentially related to the study medications were reported by 26% of the subjects who received lomefloxacin and 25% of the subjects who received norfloxacin. There were no severe adverse events, and only one subject discontinued therapy. These data suggest that 3 days of therapy with either lomefloxacin or norfloxacin is effective in the treatment of acute uncomplicated urinary tract infections.

Acute Disease↗
PubMed1993

Treatment of the chronic fatigue syndrome. A review and practical guide.

The chronic fatigue syndrome (CFS) was formally defined in 1988 to describe a syndrome of severe and disabling fatigue of uncertain aetiology associated with a variable number of somatic and/or psychological symptoms. CFS has been reported in most industrialised countries and is most prevalent in women aged between 20 and 50 years. Despite occasional claims to the contrary, the aetiology of CFS remains elusive. Although abnormalities in tests of immune function and cerebral imaging have been described in variable numbers of CFS patients, such findings have been inconsistent and cannot be relied upon, either to establish or exclude the diagnosis. Thus, diagnosis rests on fulfillment of the Centers for Disease Control case definition which was revised in 1992. This case definition remains somewhat controversial, largely due to its subjectiveness. The mainstay of treatment is establishing the diagnosis and educating the patient about the illness. An empathetic clinician can stop further consultations elsewhere ('doctor shopping') and subsequent excessive investigations, which frequently occur in such patients. Most patients should undertake a trial of antidepressant therapy, even if major depression is not present. The choice of antidepressant drug should tailor the tolerability profile to relief of particular CFS symptoms, such as insomnia or hypersomnia. Failure to improve within 12 weeks warrants an alternative antidepressant agent of another class. Many other drugs have been reported anecdotally to be beneficial, but no therapy has been demonstrated to be reproducibly useful in double-blind, placebo-controlled clinical trials with an adequate duration of follow-up.

Fatigue Syndrome, Chronic↗
PubMed1992

A multicenter, open comparative study of parenteral cefotaxime and ceftriaxone in the treatment of nosocomial lower respiratory tract infections.

A multicenter Canadian study enrolled 74 persons to compare low-dose cefotaxime at 1 g every 8 hr to ceftriaxone 1 g every 12 hr in patients with nosocomial pneumonia. Of 57 evaluable patients (30 cefotaxime and 27 ceftriaxone) in this preliminary report, 93% responded to therapy in both groups. Ceftriaxone patients tended to have more side effects (14.2%). This study is continuing to accrue patients to achieve 100 evaluable patients. Interim data, however, support the continued use of low-dose cefotaxime as an appropriate alternative for clinically effective and cost-effective management of nosocomially acquired pneumonia.

Adult↗
PubMed1992

Herpes simplex esophagitis in the immunocompetent patient: report of four cases and review.

Esophagitis due to herpes simplex virus is a well-recognized entity in immunocompromised patients but has only rarely been described in apparently immunocompetent hosts. We report four cases and review 27 additional cases identified in the English-language literature. Odynophagia, retrosternal chest pain, and fever are the most common symptoms. Single-contrast esophagography is insensitive and nonspecific, but double-contrast esophagography may be of more diagnostic value. Esophagoscopy with biopsy or collection of aspirate for cytologic examination and culture are required to make a definitive diagnosis. Patients are predominantly male, and most cases are associated with primary infection. Viral isolates were typed in 13 cases and were always type 1. Herpes simplex esophagitis in the immunocompetent patient is a self-limited infection; however, therapy with acyclovir may attenuate infection and hasten resolution of symptoms.

Adult↗
PubMed1992

Norfloxacin is inferior to chloroquine for falciparum malaria in northwestern Zambia: a comparative clinical trial.

Fluoroquinolones are active against Plasmodium falciparum in vitro. In a prospective, randomized, comparative trial, norfloxacin, 400 mg twice a day for 3 days, was compared with a standard course of chloroquine in semiimmune adults with symptomatic falciparum malaria in northwestern Zambia, where chloroquine resistance is uncommon. Patients were followed for 28 days. The trial was terminated after 38 patients were studied because chloroquine was markedly more effective, curing all 18 patients (100%) compared with only 8 (40%) of 20 who received norfloxacin (P less than .001). Of the 12 norfloxacin failures, 6 had clearing of trophozoites but recurrence during the study period (RI), 4 had incomplete clearance of trophozoites with later recurrence (RII), and 2 had no improvement (RIII). The mean parasite clearance time was significantly shorter with chloroquine (30.4 vs. 52.7 h; P = .02). The mean defervescence time was also shorter with chloroquine (16.9 vs. 24.5 h; not significant). In contrast to its inferior efficacy, norfloxacin caused fewer adverse effects than did chloroquine (33% vs. 0; P less than .001).

Adult↗
PubMed1991

The chronic fatigue syndrome.

The chronic fatigue syndrome (CFS) was formally defined in 1988 to describe disabling fatigue of at least 6 months' duration of uncertain etiology. Reports of CFS have emerged from the United States, Canada, the United Kingdom, Australia, New Zealand, Israel, Spain, and France. The disease primarily affects individuals between 20 and 50 years of age, and there is a preponderance of females. Although a triggering infectious illness is reported by most patients with CFS, there is no convincing evidence causally linking any currently recognized infectious agent to CFS. Multiple minor immunologic aberrations are frequent but inconsistent and of uncertain significance. There is no consistent evidence for myopathy or physical deconditioning. Depression is found in approximately 50% of CFS patients, with depression preceding the physical symptoms in half of the cases. No therapy has been proved effective in controlled clinical trials with prolonged follow-up, although antidepressants have not been formally evaluated. The long-term prognosis of patients with CFS has not been well studied, but CFS appears to be a disease of prolonged duration with considerable morbidity but no mortality. Further research into the pathogenesis and treatment of CFS is necessary.

Adolescent↗
PubMed1990

Polymicrobial endocarditis with eight pathogens in an intravenous drug abuser.

A 17-year-old intravenous drug abuser with tricuspid endocarditis required valvulectomy for refractory infection due to 8 different bacterial pathogens. Only one organism was isolated from blood cultures in the first 48 h, and subsequent organisms were not isolated until 9-13 days after hospitalization. The spectrum of pathogens in this patient strengthens previous clinico-bacteriologic observations made in the literature, and emphasizes the need for empiric coverage of oropharyngeal flora in addition to the usual skin flora involved in drug-addict associated endocarditis.

Adolescent↗
PubMed1990

The basis of antibiotic resistance in bacteria.

The ability of bacteria to resist the inhibitory and lethal actions of antibiotics is a major clinical problem, and has been observed with every antimicrobial agent. In this article, the major mechanisms of antibiotic resistance are reviewed, and the clinical relevance of such resistance in selected bacteria is discussed.

Biochemical Phenomena↗
PubMed1989

Branhamella catarrhalis bronchopulmonary isolates in PICU patients.

Branhamella catarrhalis is commonly considered a respiratory commensal but has recently been implicated as a pathogen, particularly in adults. Over a 28 month period, B. catarrhalis was isolated from bronchopulmonary secretions of 14 PICU patients with acute respiratory infections. Twelve patients had pneumonia and two had tracheitis. The mean age was 3.5 years. Seven patients had chronic cardiopulmonary disease including two who were immunosuppressed. Three had an acute underlying condition and four had no complicating medical problem. Polymorphs and Gram-negative diplococci on Gram stain were found in respiratory secretions of all patients. Twelve of 14 isolates produced beta-lactamase, and six patients had a second potentially pathogenic bronchopulmonary isolate. All patients were treated for B. catarrhalis infection and none died. When isolated in pure culture from bronchopulmonary secretions in symptomatic patients, B. catarrhalis should be considered a pathogen. When isolated in mixed culture, its pathogenic role is uncertain. We conclude that B. catarrhalis can be a bronchopulmonary pathogen in critically ill children with otherwise normal cardiopulmonary function as well as in those with chronic cardiopulmonary dysfunction. When administering antibiotics the high frequency of beta-lactamase-producing strains must be taken into consideration.

Adolescent↗