Biomedical subjects

R J Fass

Publications and source records attributed to R J Fass.

At least 37 records · Page 2Linked to original sources

PubMed1994

The safety and efficacy of combination N-butyl-deoxynojirimycin (SC-48334) and zidovudine in patients with HIV-1 infection and 200-500 CD4 cells/mm3.

We conducted a double-blind, randomized phase II study to evaluate the safety and activity of combination therapy with N-butyl-deoxynojirimycin (SC-48334) (an alpha-glucosidase I inhibitor) and zidovudine versus zidovudine alone. Patients with 200 to 500 CD4 cells/mm3 who tolerated < or = 12 weeks of prior zidovudine therapy received SC-48334 (1000 mg every 8 h) and zidovudine (100 mg every 8 h) or zidovudine and placebo. Sixty patients received combination therapy and 58, zidovudine and placebo. Twenty-three patients (38%) and 15 (26%), in the combination and zidovudine groups, respectively, discontinued therapy (p = 0.15). The mean SC-48334 steady-state trough level (4.04 +/- 0.99 micrograms/ml) was below the in vitro inhibitory concentration for human immunodeficiency virus (HIV). The mean increase in CD4 cells at week 4 was 73.8 cells/mm3 and 52.4 cells/mm3 for the combination and zidovudine groups, respectively (p > 0.36). For patients with prior zidovudine therapy, the mean change in CD4 cells in the combination and zidovudine groups was 63.7 cells/mm3 and 4.9 cells/mm3 at week 8 and 6.8 cells/mm3 and -45.1 cells/mm3 at week 16, respectively. The number of patients with suppression of HIV p24 antigenemia in the combination and zidovudine groups was six (40%) and two (11%) at week 4 (p = 0.10) and five (45%) and two (14%) at week 24 (p = 0.08), respectively. Diarrhea, flatulence, abdominal pain, and weight loss were common for combination recipients.(ABSTRACT TRUNCATED AT 250 WORDS)

1-Deoxynojirimycin↗

PubMed1993

Aetiology and treatment of community-acquired pneumonia in adults: an historical perspective.

Community-acquired pneumonia is common. Most disease is mild but mortality among hospitalized patients is 5-20%. The most common aetiological pathogens are Streptococcus pneumoniae, Haemophilus influenzae, and the 'atypical' organisms, Mycoplasma pneumoniae, Legionella pneumophila and Chlamydia pneumoniae. Less common pathogens account for 10-30% of cases and the aetiology cannot be determined in one-third to one-half of cases. Classification by aetiology and initiation of specific antimicrobial therapy are difficult and treatment is often initiated empirically. Ampicillin (or amoxycillin) or erythromycin are inexpensive and effective for most patients, but their use in combination, the addition of a beta-lactamase inhibitor (e.g. amoxycillin/clavulanate) or the substitution of an expanded spectrum cephalosporin (e.g. cefuroxime) should be considered for patients with more serious illnesses or pathogens likely to be drug-resistant. Fluoroquinolones such as ciprofloxacin or ofloxacin would be acceptable if adequacy for treating pneumococcal infections were likely. New macrolides, such as azithromycin and clarithromycin, and new fluoroquinolones, such as temafloxacin and sparfloxacin, have theoretical advantages over previously available drugs, but superior efficacy has not yet been demonstrated satisfactorily. Pneumococcal resistance in various parts of the world is modifying traditional treatment. Currently, there is no drug of choice for the empirical treatment of community-acquired pneumonia.

Adult↗

PubMed1993

Neuropsychological performance in symptomatic and asymptomatic HIV infection.

OBJECTIVE: To examine cognitive function in patients at various stages of HIV infection, and to determine the nature and severity associated with stage of illness. DESIGN: Subjects were administered an extensive battery of neuropsychological tests. SUBJECTS: Two hundred and thirty-three HIV-1-infected homosexual/bisexual men and 77 HIV-negative control subjects who had been screened for previous neurological illness. All subjects were volunteers in a longitudinal study of neurobehavioral complications of HIV infection. RESULTS: Patients with symptomatic infection differed from controls on a large number of measures, and asymptomatic patients had a more circumscribed pattern of deficit. On a summary measure of cognitive impairment, there was a twofold increase in the prevalence of impairment in asymptomatic patients relative to controls, and a fourfold increase in symptomatic patients. Memory and dexterity problems appear to be early features of neurobehavioral dysfunction, and frontal lobe deficits were found in patients with symptomatic infection. CONCLUSION: These data indicate that there is a steady increase in the prevalence of neurobehavioral abnormalities associated with stage of infection. The pattern of abnormality also varies with disease stage.

Acquired Immunodeficiency Syndrome↗

PubMed1993

Change in neuropsychological performance in asymptomatic HIV infection: 1-year follow-up.

OBJECTIVE: To examine the stability of cognitive function in patients with asymptomatic HIV infection. DESIGN: Previous longitudinal studies of cognitive function have focused on patients who progress in terms of disease stage. The present study avoided this potential confounding factor by including only subjects who remained in the asymptomatic stage of infection over the follow-up period. METHOD: Subjects were administered an extensive neuropsychological test battery at baseline and 1 year follow-up. Overall performance was characterized as normal or abnormal based on the performance of a well-matched HIV-negative control group. RESULTS: A significantly higher proportion of HIV-positive subjects became abnormal at the follow-up examination. Comparison of the seropositive subjects who remained normal with those who became abnormal revealed no differences at baseline on age, education, depression or CD4 levels. Subjects who became abnormal had worse performance at baseline on measures of information processing, verbal learning and memory, and reaction time. CONCLUSIONS: These data indicate that cognitive function may decline in some patients who continue to be in the asymptomatic stage of infection. Patients with a pattern of cognitive abnormalities at baseline, which includes information processing and reaction time deficits, may be at increased risk for declines in function during early stages of infection.

Adult↗

PubMed1993

Erythromycin, clarithromycin, and azithromycin: use of frequency distribution curves, scattergrams, and regression analyses to compare in vitro activities and describe cross-resistance.

MICs of erythromycin, clarithromycin, and azithromycin for 852 recent clinical isolates were determined by broth microdilution methods. Frequency distribution curves, scattergrams, and regression analyses were used to compare in vitro activities and describe cross-resistance. Clarithromycin was the most active drug against Bacteroides spp. but the least active against Haemophilus influenzae. Azithromycin was most active against H. influenzae, Moraxella catarrhalis, Pasteurella multocida, and Fusobacterium spp. but the least active against Streptococcus spp. and Enterococcus spp. All three drugs had equivalent activities against Staphylococcus spp. and gram-positive anaerobes. None of the three drugs was particularly active against members of the family Enterobacteriaceae or nonfermentative gram-negative bacilli, although concentrations of 4 micrograms of azithromycin per ml inhibited some strains of the family Enterobacteriaceae (particularly Escherichia coli and Citrobacter diversus) and Acinetobacter baumannii. Although relative drug activities varied by organism, organisms relatively susceptible to one were relatively susceptible to all and organisms relatively resistant to one were relatively resistant to all; an exception was fusobacteria, which were usually susceptible only to azithromycin. Cross-susceptibility and cross-resistance were, therefore, the rule (except for Fusobacterium spp.), although the percentage of susceptible organisms could be varied considerably on the basis of the selection of breakpoints.

Azithromycin↗

PubMed1993

In vitro activity of Bay y 3118, a new quinolone.

MICs of Bay y 3118, ciprofloxacin, ofloxacin, clarithromycin, azithromycin, cefuroxime, amoxicillin-clavulanate, and trimethoprim-sulfamethoxazole for 878 recent clinical isolates were determined by broth microdilution methods. Among the three quinolones, Bay y 3118 was the most active against Haemophilus influenzae, Moraxella catarrhalis, Acinetobacter baumannii, Xanthomonas maltophilia, gram-positive cocci, and anaerobes; MICs for 50% of the strains (MIC50s) and MIC90s were < or = 0.015 and < or = 0.015, < or = 0.015 and < or = 0.015, 0.03 and 2, 0.25 and 0.5, 0.06 and 1, and 0.12 and 0.25 micrograms/ml, respectively. For gram-positive cocci and anaerobes, these values were 16- to 32-fold (4 to 5 log2 dilution steps) lower than those for ciprofloxacin and ofloxacin. Bay y 3118 was similar in activity to ciprofloxacin and more active than ofloxacin against members of the family Enterobacteriaceae and Pseudomonas aeruginosa; Bay y 3118 MIC50s and MIC90s were 0.03 and 0.25 and 0.5 and 8 micrograms/ml, respectively. Scattergrams and regression analyses comparing quinolone MICs indicated that, despite differences in activity, organisms relatively susceptible to one were relatively susceptible to all and organisms relatively resistant to one were relatively resistant to all. However, the greater in vitro activity of Bay y 3118 was most pronounced against relatively resistant organisms. Pending pharmacokinetic and safety data for Bay y 3118, there is reasonable anticipation that its enhanced activity against gram-positive cocci and anaerobes would broaden the clinical utility of the quinolone class of antimicrobial agents.

Anti-Infective Agents↗

PubMed1993

Restriction endonuclease analysis of clinical Pseudomonas aeruginosa strains: useful epidemiologic data from a simple and rapid method.

Newer genetic techniques have replaced phenotypic methods of subtyping Pseudomonas aeruginosa strains. Widespread application of newer methodologies, however, may be limited by technologic complexity and the cost of equipment. We conducted restriction endonuclease analysis (REA) of sheared genomic DNAs from 48 clinical P. aeruginosa strains using the enzyme SalI and electrophoresis in horizontal, low-concentration (0.3 to 0.6%) agarose gels. Each REA profile consisted of a smear of lower-molecular-mass bands as well as a countable number of well-resolved bands in the 8.3- to 48.5-kbp range which could easily be compared when isolates were run side-by-side on the same gel. In general, the REA patterns of strains recovered from different patients differed by at least seven bands, and those of serial isolates from individual patients were identical or differed by, at most, two bands over this 8.3- to 48.5-kbp range. REA of strains already subtyped by field inversion gel electrophoresis revealed that the two techniques generally paralleled each other. Overall, some unrelated strains had similar REA profiles, but the relative simplicity and low cost of the approach coupled with the ability to demonstrate differences between most unrelated strains should make this type of REA an attractive first step in the investigation of institutional P. aeruginosa problems.

Adult↗

PubMed1993

Depression and neuropsychological performance in asymptomatic HIV infection.

OBJECTIVE: The authors examined the effect of depression on neuropsychological performance in HIV-infected men. Previous studies have suggested that depression may account for the neuropsychological abnormalities observed in some patients with HIV infection, but few studies have specifically examined this question. METHOD: An extensive neuropsychological test battery was administered to 121 HIV-seropositive asymptomatic men and 42 HIV-seronegative comparison subjects. The seropositive subjects were grouped into depressed and non-depressed groups on the basis of scores on the Beck Depression Inventory, Hamilton Rating Scale for Depression, and Structured Clinical Interview for DSM-III-R. RESULTS: Statistical comparisons revealed very few measures on which the depressed seropositive subjects scored significantly worse than either of the nondepressed comparison groups. The nondepressed seropositive group differed consistently from the seronegative comparison subjects on measures of verbal memory and dexterity. CONCLUSIONS: These data indicate that the subtle neuropsychological abnormalities observed in some asymptomatic HIV-seropositive subjects cannot be attributed to depression. These data also indicate the advantages of a multifaceted approach to assessment of depression.

Adult↗

PubMed1993

Drug and alcohol use and neuropsychological performance in asymptomatic HIV infection.

The effect of drug and alcohol abuse on neuropsychological performance was examined in 132 human immunodeficiency virus-seropositive gay or bisexual men. Syndromal (diagnostic) criteria of alcohol/drug abuse based on DSM-III-R were used, and quantitative estimates of alcohol consumption were obtained. Very few differences appeared between substance abuse subgroups formed on the basis of recency or severity of drug use. There were some correlations with the quantitative estimate of alcohol use, but not on the measures previously found to differentiate seronegative and asymptomatic seropositive gay men. These data indicate that alcohol use does affect neuropsychological performance but does not account for the differences observed in studies of seronegative and seropositive subjects.

Acquired Immunodeficiency Syndrome↗

PubMed1992

A controlled trial of trimethoprim-sulfamethoxazole or aerosolized pentamidine for secondary prophylaxis of Pneumocystis carinii pneumonia in patients with the acquired immunodeficiency syndrome. AIDS Clinical Trials Group Protocol 021.

BACKGROUND: Pneumocystis carinii pneumonia (PCP) continues to be the most common index diagnosis in the acquired immunodeficiency syndrome (AIDS), but it is not clear which of several available agents is the most effective in preventing a recurrence of PCP. METHODS: We conducted a comparative, open-label trial in 310 adults with AIDS who had recently recovered from an initial episode of PCP and had no treatment-limiting toxic effects of trimethoprim-sulfamethoxazole or pentamidine. All the patients were treated with zidovudine and were randomly assigned to receive either 800 mg of sulfamethoxazole and 160 mg of trimethoprim once daily or 300 mg of aerosolized pentamidine administered every four weeks by jet nebulizer. The participants were followed for a median of 17.4 months. RESULTS: In the trimethoprim-sulfamethoxazole group (n = 154) there were 14 recurrences of PCP, as compared with 36 recurrences (including 1 extrapulmonary recurrence) in the aerosolized-pentamidine group (n = 156). The estimated recurrence rates at 18 months were 11.4 percent with trimethoprim-sulfamethoxazole and 27.6 percent with pentamidine (P < 0.001). The risk of a recurrence (adjusted for initial CD4 cell count) was 3.25 times higher in the pentamidine group (P < 0.001, 95 percent confidence interval, 1.72 to 6.16). There were no significant differences between the groups in survival or in hematologic or hepatic toxicity. Crossovers from trimethoprim-sulfamethoxazole to aerosolized pentamidine were more common than the reverse (27 vs. 4 percent), partly because of the study protocols for the management of leukopenia. There were 19 serious bacterial infections in the trimethoprim-sulfamethoxazole group and 38 in the pentamidine group. The time to a first bacterial infection was significantly greater for those assigned to trimethoprim-sulfamethoxazole (P = 0.017). CONCLUSIONS: In patients with AIDS who are receiving zidovudine, trimethoprim-sulfamethoxazole is more effective than aerosolized pentamidine in conventional doses for the prevention of recurrent pneumocystis infection.

AIDS-Related Opportunistic Infections↗

PubMed1992

Quantitation of antigen-specific immune responses in human immunodeficiency virus (HIV)-infected individuals by limiting dilution analysis.

The lymphocyte proliferative response to recall antigens is lost following HIV infection. We sought to devise a means by which the functional immune status of persons in the early stages of HIV infection could be monitored quantitatively. The response to tetanus toxoid was examined in 45 HIV-infected individuals and 11 controls using conventional lymphocyte proliferative assays concurrently with limiting dilution analysis utilizing the secretion of interleukin-2 as the measure of a response. Our data show that the limiting dilution analysis detects tetanus toxoid-reactive T cells in 80% of those tested, as compared to only 44% by proliferation. However, the frequency of tetanus-reactive T cells in HIV-infected individuals (median frequency = 1/59,156) is decreased five-fold as compared to seronegative controls (median frequency = 1/11,599). Longitudinal studies demonstrated a time-dependent decrease in the frequency of tetanus-specific T cell responses in the HIV-infected individuals. Thus, the limiting dilution analysis is a quantitative approach for detecting antigen-specific T cells in HIV-infected individuals, and may be used to monitor changes in T cell function in HIV infection.

CD4-Positive T-Lymphocytes↗

PubMed1992

Magnetic resonance imaging of white matter lesions in HIV infection.

Previous studies of the frequency of high-signal lesions in human immunodeficiency virus (HIV) infection have had methodological weaknesses regarding lack of control groups, differing machine strengths, and biased subject selection. To obtain a more accurate estimate of prevalence, MRI scans were performed on 243 HIV-positive and HIV-negative homosexual or bisexual men with no history of intravenous drug use. Axial T2-weighted (long TR/TE, spin-echo) MRI scans were rated blindly for presence of focal white matter high-signal lesions. Incidence of hyperintensities was low in all groups, although slightly higher in patients with AIDS, and was not associated with neuropsychological performance. The lower incidence of hyperintensities appears to relate to elimination of methodological problems in previous studies.

AIDS Dementia Complex↗

PubMed1992

Neuropsychological performance in asymptomatic HIV infection.

This study compared 74 human immunodeficiency virus (HIV)-negative and 131 HIV-positive asymptomatic homosexual or bisexual men on an extensive neuropsychological test battery. HIV-positive subjects' performance was significantly worse on verbal memory and psychomotor skills. The prevalence of mild but persistent neurobehavioral impairment in the HIV-positive group was approximately twice that in HIV-negative patients, consistently across several criteria for impairment. There was evidence that degree of neuropsychological impairment was related to patients' perceptions of dysfunction in daily life. Findings were not related to degree of depression or to medication effects. These data suggest that approximately 10% to 20% of HIV-positive asymptomatic men suffer mild neuropsychological impairment that influences their daily lives.

AIDS Dementia Complex↗

PubMed1991

Rate of CD4 decline and neuropsychological performance in HIV infection.

This study examined the relationship between performance on a battery of neuropsychologic tasks and rate of CD4 lymphocyte decline in 47 gay or bisexual men infected with the human immunodeficiency virus type 1. Subjects were volunteers for a longitudinal study of the human immunodeficiency virus infection and were not selected because of neuropsychiatric symptoms. Subjects were at all stages of illness, although most were asymptomatic. Faster rates of decline in percent CD4 lymphocyte were related to poorer performance on measures of memory and reaction time. This relationship was independent of stage of illness and CD4 level at the time of neuropsychologic examination, and was not due to medication effects. The rate of percent CD4 lymphocyte cell loss is associated with and may represent a risk factor for the development of the human immunodeficiency virus-related neurobehavioral deficit.

Adult↗

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

In vitro activity of RP 59500, a semisynthetic injectable pristinamycin, against staphylococci, streptococci, and enterococci.

The in vitro activity of RP 59500, a semisynthetic pristinamycin, was compared with the activities of vancomycin, oxacillin, ampicillin, gentamicin, ciprofloxacin, and rifampin against five Staphylococcus species, five Streptococcus species, and four Enterococcus species. For staphylococci, MICs were 0.13 to 1 microgram/ml and the MICs for 90% of the strains tested (MIC90s) were 0.13 to 0.5 microgram/ml; there were no differences between oxacillin-susceptible and -resistant strains. For streptococci, MICs were 0.03 to 4 micrograms/ml and MIC90s were 0.25 to 2 micrograms/ml; viridans group streptococci were the least susceptible streptococci. For enterococci, MICs were 0.25 to 32 micrograms/ml and MIC90s were 2 to 4 micrograms/ml; Enterococcus faecalis was the least susceptible. Vancomycin was the only comparative drug with consistent activity against all species of gram-positive cocci. With RP 59500, raising the inoculum 100-fold, lowering the pH of cation-adjusted Mueller-Hinton broth to 5.5, or omitting cation supplementation had little effect on MICs, but 50% serum increased MICs 2 to 4 dilution steps. The differences between MBCs and MICs were greater for staphylococci and enterococci than for streptococci. Time-kill studies with 24 strains indicated that RP 59500 concentrations 2-, 4-, and 16-fold greater than the MICs usually killed bacteria of each species at similar rates; reductions in CFU per milliliter were less than those observed with oxacillin or vancomycin against staphylococci and less than those observed with ampicillin against enterococci. RP 59500 antagonized the bactericidal activities of oxacillin and gentamicin against Staphylococcus aureus ATCC 29213 and that of ampicillin against E. faecalis ATCC 29212. Against the latter, combination with gentamicin was indifferent. RP 59500 has a broad spectrum of in vitro activity against gram-positive cocci; combining it with other drugs is not advantageous.

Anti-Bacterial Agents↗

PubMed1990

Ciprofloxacin. Best use of this new broad-spectrum antibiotic.

Resistance to traditional antibiotics is an increasing problem. The introduction of ciprofloxacin (Cipro) has been welcome, because it is safe and effective against many organisms (including drug-resistant ones), can be taken orally, and is well tolerated. Dr Fass provides a complete description of the drug, including its use for infections of the urinary, respiratory, and gastrointestinal tracts; skin and skin structures; and bones and joints.

Bacterial Infections↗

PubMed1990

In vitro activities of cefoperazone and sulbactam singly and in combination against cefoperazone-resistant members of the family Enterobacteriaceae and nonfermenters.

Among 28,000 isolates of the family Enterobacteriaceae and nonfermenters isolated at multiple medical centers, 1,084 (4%) were resistant to cefoperazone (MIC, greater than or equal to 64 micrograms/ml) and 1,711 (6%) exhibited cefoperazone MICs of 2 to 32 micrograms/ml. Ninety-six percent of these 2,795 isolates produced beta-lactamase, as determined by the nitrocefin test. Sulbactam alone (8 micrograms/ml) was inactive against 99.6% of the isolates other than Acinetobacter calcoaceticus and Pseudomonas cepacia. Sulbactam enhanced the activity of cefoperazone against 56% of the isolates of the family Enterobacteriaceae and 44% of the nonfermenters. In the presence of sulbactam concentrations of less than or equal to 8 micrograms/ml, 65% of the cefoperazone-resistant isolates had reductions in cefoperazone MICs of greater than or equal to 2 log2 dilution steps and were susceptible to less than or equal to 32 micrograms/ml. Antagonism was not observed.

Bacteria↗