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Biomedical subjects

S J Sperber

Publications and source records attributed to S J Sperber.

At least 19 recordsLinked to original sources
PubMed1999

Paradoxical response to a novel influenza virus vaccine strain: the effect of prior immunization.

BACKGROUND: repeated influenza immunization does not appear to adversely affect the serum antibody response to new influenza strains. OBJECTIVE: to determine whether the immune response to a new influenza strain was inferior in persons previously vaccinated compared with persons not previously vaccinated. DESIGN: randomized, double-blind clinical trial. SETTING: university affiliated community teaching hospital. PATIENTS: 139 healthy adult men and women, mean age 38 years. INTERVENTION: subjects were vaccinated as part of another study. They received influenza vaccines containing influenza strains A/Texas/36/91 (H1N1), A/Nanchang/933/95 (H3N2) and B/Beijing/184/93. One group received a licensed influenza vaccine while the other group received a similar vaccine except the A/Nanchang strain had a diminished potency. MEASUREMENTS: serum hemagglutination inhibition (HAI) antibody titers were determined prior to vaccination and two weeks afterward. If patients had a low postvaccination titer, they were revaccinated and HAI titers were determined two weeks later. RESULTS: 68 adults received the licensed vaccine and 70 received the subpotent vaccine. The groups were similar with regards to baseline characteristics. Those previously vaccinated had significantly lower postvaccination HAI geometric mean titers (GMTs) for all three vaccine strains (A/Texas--127 vs. 359, p < 0.001, A/Nanchang--31 vs. 93, p < 0.001 and B/Beijing--140 vs. 205, p < 0.05). The percentage of subjects with a presumed protective HAI titer of > or =40 was significantly lower among the previously vaccinated groups only for the new influenza strain, A/Nanchang (55% vs. 80%, p < 0.05). For the other two vaccine strains, the percentage with an HAI titer > or =40 was greater than 90% for both groups. CONCLUSIONS: the decrease in serologic response to influenza vaccine among healthy, young adults who were previously vaccinated appears to be unique for this year's influenza vaccine. Further studies are required to determine the frequency and clinical significance of this phenomenon observed in younger healthy adults, and whether it is a general one. Based on its proven efficacy, influenza vaccine should continue to be given on an annual basis to high risk children and adults and to all those 65 years or older.

Adult↗
PubMed1998

Facial cellulitis and Pseudomonas luteola bacteremia in an otherwise healthy patient.

Pseudomonas luteola is an aerobic, Gram negative rod, formerly classified as CDC group Ve-1 and Chryseomonas luteola. It is an uncommon clinical isolate. A previously healthy 59-year-old homosexual man with facial cellulitis and Pseudomonas luteola bacteremia is reported. Previously reported cases of P. luteola bacteremia have occurred in association with pancreatic abscess, prosthetic valve endocarditis, cardiac surgery, granulomatous hepatitis, peritonitis, and indwelling vascular catheters. This case suggests that the spectrum of disease caused by this bacteria may continue to expand.

Adult↗
PubMed1997

Effectiveness of clemastine fumarate for treatment of rhinorrhea and sneezing associated with the common cold.

Limited data support the use of first-generation antihistamines for treatment of the common cold. The purpose of this study was to test the effectiveness of clemastine fumarate, a first-generation antihistamine, for treatment of sneezing and rhinorrhea associated with naturally occurring common colds. Four hundred three subjects (202 clemastine fumarate recipients and 201 placebo recipients) who reported new onset (< 24 hours) of cold symptoms that included rhinorrhea or sneezing were studied. At baseline (day 1), the mean symptom-severity scores +/- SEM for the clemastine fumarate and placebo groups were not significantly different. The mean rhinorrhea-severity score +/- SEM was not different on day 2; however, on day 3, the mean rhinorrhea-severity score +/- SEM was 1.02 +/- 0.07 for the clemastine fumarate group and 1.39 +/- 0.07 for the placebo group (P < .001). This treatment effect persisted on day 4. A significant effect on sneezing was noted on days 2-4. Sedation occurred in 14% of the clemastine fumarate-treated subjects and 1.5% of the placebo-treated subjects (P < .0001).

Adolescent↗
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↗
PubMed1993

Anti-rhinoviral activity of recombinant and hybrid species of interferon alpha.

To define further differences in antiviral activity as well as to identify candidate interferons for study in the prevention of rhinovirus colds, the antiviral activities of nine species of recombinant interferon alpha (IFN-alpha A, IFN-alpha B, IFN-alpha C, IFN-alpha D, IFN-alpha J, [Ser-116]IFN-alpha J1, IFN-alpha K, IFN-alpha J/C(Fnu4HI), and IFN-alpha A/D(BglII)) were evaluated against rhinovirus types 39 (RV 39) and 1A (RV 1A). WI-38 cells were exposed to various concentrations of each interferon and were then infected with RV 39, RV 1A, or VSV. Efficacy was determined by protection from cytopathic effect using a tetrazolium dye assay. The 50% inhibitory concentrations ranged from 4 +/- 3 pg/ml for IFN-alpha C to > 3000 pg/ml for IFN-alpha D against RV 39, and from 6 +/- 4 pg/ml for IFN-alpha J/C(Fnu4HI) to > 3000 pg/ml for IFN-alpha D against RV 1A. IFN-alpha J/C(Fnu4HI), [Ser-116]IFN-alpha J1, and IFN-alpha C were the most active of the interferons, and were all more active than IFN-alpha A, against RV 39, RV 1A, and VSV. These interferons warrant further study against rhinoviruses and other viruses.

Amino Acid Sequence↗
PubMed1993

In vitro activities of nucleoside analog antiviral agents against salmonellae.

Zidovudine (ZDV) has antibacterial activity against many members of the family Enterobacteriaceae, including Salmonella species, and may be responsible for a decrease in the frequency of salmonellosis in persons infected with human immunodeficiency virus (HIV). Other nucleoside analogs, such as didanosine (2',3'-dideoxyinosine [ddI]) and zalcitabine (2',3'-dideoxycytidine [ddC]), which have undefined anti-salmonella activity, increasingly are being used in the treatment of HIV infection. To evaluate the anti-Salmonella activity of the antiviral agents ZDV, ddI, ddC, and acyclovir (ACV), we determined MICs for 39 nontyphoidal Salmonella blood isolates. ZDV (MIC for 50% of strains tested [MIC50], 0.5 microgram/ml; MIC range, 0.125 to 4 micrograms/ml) and ddI (MIC50, 8 micrograms/ml; MIC range, 2 to 125 micrograms/ml) had concentration-dependent activity. Anti-Salmonella activity was not observed for ddC or ACV. Nine Escherichia coli blood isolates were inhibited by ZDV (MIC50, 0.125 microgram/ml; MIC range, 0.031 to 1 microgram/ml) to a greater degree than they were by ddI (MIC50, 62.5 micrograms/ml; MIC range, 31 to > 62.5 micrograms/ml). Inoculum size affected susceptibility to ZDV and ddI for Salmonella and E. coli isolates. Resistance to ZDV or to ddI could be induced in vitro in Salmonella isolates, but cross-resistance was not observed. These results indicate that at concentrations achieved during the treatment of HIV infection, ZDV has activity against nontyphoidal salmonellae, although resistance can develop. ddI, ddC, and ACV at currently used dosages would not be expected to be effective in the prevention or treatment of Salmonella infections.

Antiviral Agents↗
PubMed1993

Human immunodeficiency virus type 1 pol gene mutations in an AIDS patient treated with multiple antiretroviral drugs.

Multiple mutations were found in the human immunodeficiency virus pol gene following treatment of an AIDS patient with antiretroviral drugs. After approximately 2.5 years of monthly alternating therapy with 3'-azido-3'-deoxythymidine (AZT) and 2',3'-dideoxycytidine (ddC), most of the pol sequences amplified from the patient's peripheral blood mononuclear cell DNA contained known AZT resistance mutations at codons 41, 67, and 215 and a putative ddC resistance mutation at codon 69 as well as other novel mutations. These mutations persisted for 6 months after the patient was switched to 2',3'-dideoxyinosine monotherapy. Mutations known to be associated with 2',3'-dideoxyinosine resistance did not occur during this time. Antiviral susceptibility testing of point mutants, introduced into the genetic background of laboratory strain NL4-3, showed that the codon 41 mutation antagonized ddC resistance when present with the codon 69 mutation. However, this antagonism was not found with a chimeric mutant containing the patient's pol gene sequence from codons 25 to 218, implying that other mutations compensated for the antagonism. Thus, alternating therapy with AZT and ddC resulted in the selection of viruses resistant to both drugs.

Acquired Immunodeficiency Syndrome↗
PubMed1993

Low-dose oral recombinant interferon-alpha A in patients with HIV-1 infection: a blinded pilot study.

OBJECTIVE: To evaluate the efficacy of low-dose oral recombinant interferon-alpha (IFN-alpha A) on clinical parameters, body weight, CD4+ lymphocyte counts and natural killer cell cytolytic activity in HIV-infected patients. DESIGN: Blinded crossover trial with controls for the protein and diluent components of the drug preparation. SETTING: Medical school outpatient referral center. PATIENTS, PARTICIPANTS: Eight patients with HIV-1 infection and a CD4+ lymphocyte count between 150 and 600 x 10(6)/l. Concurrent use of zidovudine was permitted. INTERVENTIONS: Patients received (daily, by mouth) 10 ml of a study solution of 2.5% albumin for 6 weeks, 150 IU IFN-alpha A for 6 weeks, and normal saline for 6 weeks. MAIN OUTCOME MEASURES: After two baseline visits, clinical assessments, vital signs, body weight, and laboratory tests, including enumeration of number and percentage of CD4+ and CD8+ lymphocytes and natural killer cell cytolytic activity, were performed every 3 weeks. Complete physical examinations were conducted every 6 weeks. RESULTS: No significant clinical or laboratory changes were observed during treatment with IFN-alpha A. Peak CD4+ lymphocyte counts were achieved at baseline in one patient, during albumin treatment in two patients, during IFN-alpha A treatment in one patient, and during saline treatment in four patients. All patients remained HIV-seropositive. Treatments were well-tolerated. CONCLUSION: This blinded pilot study of orally administered IFN-alpha A (150 IU daily for 6 weeks) did not demonstrate clinical benefit in HIV-infected patients.

Administration, Oral↗
PubMed1992

Effects of naproxen on experimental rhinovirus colds. A randomized, double-blind, controlled trial.

OBJECTIVE: To determine whether naproxen, a propionic acid inhibitor of cyclooxygenase, alters the course of experimental rhinovirus colds. DESIGN: A randomized, double-blind, controlled trial. SETTING: Rhinovirus challenge model in volunteers cloistered in individual hotel rooms. VOLUNTEERS: Eighty-seven healthy young adults with serum neutralizing antibody titers of less than or equal to 1:2 to the challenge virus; 79 were evaluable. INTERVENTION: Thirty-nine participants received naproxen (loading dose, 400 mg or 500 mg followed by 200 mg or 500 mg three times daily for 5 days). Forty participants received placebo. Treatment was started 6 hours after viral challenge. MEASUREMENTS: Daily measurement of viral titers, symptoms, nasal mucus production, and nasal tissue use; incidence of infection and illness; and measurement of homotypic serum neutralizing antibody responses. RESULTS: Viral titers and serum homotypic antibody responses were similar in the naproxen and placebo groups. Significant reductions in headache, malaise, myalgia, and cough occurred in the naproxen group. A 29% reduction was noted in the total (5-day) symptom score in the naproxen group (95% CI, 16% to 42%). CONCLUSION: Naproxen treatment did not alter virus shedding or serum neutralizing antibody responses in participants with experimental rhinovirus colds, but it had a beneficial effect on the symptoms of headache, malaise, myalgia, and cough. Prostaglandins may be among the inflammatory mediators that play a role in the pathogenesis of rhinovirus colds.

Adult↗
PubMed1992

Otologic effects of interferon beta serine in experimental rhinovirus colds.

To evaluate the efficacy and otologic effects of recombinant interferon beta serine for experimental rhinovirus colds, 38 healthy adults received nasal drops of recombinant interferon beta serine, 12 x 10(6) U, or placebo three times daily for 4.3 days beginning 36 hours after infection. Illness rates and severity did not differ between the groups, but the frequency of virus shedding was reduced on the fourth (37% vs 74%) and sixth (11% vs 42%) postchallenge days in recipients of recombinant interferon beta serine. Abnormal eustachian tube function in at least one ear was identified by the inflation-deflation test during 44% of observations in 13 infected recipients of recombinant interferon beta serine compared with 62% of observations in five placebo recipients. Tympanometry revealed middle-ear pressure abnormalities (less than -50 or greater than 20 mm H2O) in at least one ear during 18% of observations in recipients of recombinant interferon beta serine compared with 38% of observations in placebo recipients. These results suggest that antiviral therapy may alter the course of middle-ear dysfunction associated with experimental colds.

Administration, Intranasal↗
PubMed1992

Serologic response and reactogenicity to booster immunization of healthy seropositive adults with live or inactivated varicella vaccine.

The immunogenicity and reactogenicity of live and heat-inactivated varicella vaccine were evaluated in 95 healthy seropositive adults (mean age, 32 yrs). Live-attenuated vaccine containing 28,000 pfu, 2800 pfu, or 280 pfu of Oka/Merck strain virus (8.4, 0.84, and 0.08 antigen units, respectively) or heat-inactivated vaccine with comparable antigen content (7.1, 0.71, and 0.07 antigen units) was administered subcutaneously to 15 to 16 adults per group in a randomized, single-blind study. ELISA antibody responses were dose-dependent but independent of whether the vaccine was live or inactivated. Mean titers reached a peak on day 14 and remained elevated through day 42 in recipients of the highest dosages but declined by followup at eleven months. A minority of vaccinees developed a four-fold or greater increase in antibody titer on day 14 (25 to 31 percent in the high-dose groups [greater than or equal to 7.1 antigen units], less than or equal to 7 percent of other groups). The vaccine was generally well tolerated. Localized erythema and swelling occurred at the injection site in 44 to 56 percent of the high- and middle dose recipients [greater than or equal to 0.71 antigen units], compared with 0 to 6 percent of those receiving the lowest dose. Although statistically significant increases in varicella antibody titer were observed after immunization with high doses of live or inactivated vaccine, the duration and clinical significance of this booster effect remains to be determined.

Adolescent↗
PubMed1992

Anti-HIV-1 activity of recombinant and hybrid species of interferon-alpha.

To identify candidate interferons (IFNs) for the treatment of human immunodeficiency virus type 1 (HIV-1) infection and to investigate sequence-function relationships, the antiviral activities of nine species of recombinant IFN-alpha [IFN-alpha A, IFN-alpha B, IFN-alpha C, IFN-alpha D, IFN-alpha J, [Ser116]IFN-alpha J1, IFN-alpha K, IFN-alpha J/C(Fnu4HI), and IFN-alpha A/D(BglII)] were evaluated against HIV-1. MT-2 cells were exposed to various concentrations of each IFN and were then infected with HIV. Protective effect was determined by cell viability using a tetrazolium dye assay. Activity against vesicular stomatitis virus (VSV) was assessed on MDBK and WISH cells. The 50% inhibitory concentration against HIV was 37 +/- 14 pg/ml for IFN-alpha A, and ranged from 15 +/- 3 pg/ml for IFN-alpha J/C(Fnu4HI) to > 90,000 pg/ml for IFN-alpha D. In general, relative activity against HIV was similar to relative activity against VSV on WISH cells. IFN-alpha D was notable for its decreased activity on human cells. The observations suggest that it may be possible to produce IFNs-alpha with more favorable therapeutic indices than currently available IFNs. Furthermore, the anti-HIV activity of IFNs-alpha is not determined solely by their linear amino acid sequence.

Acquired Immunodeficiency Syndrome↗
PubMed1992

Human immunodeficiency virus type 1 pol gene mutations which cause decreased susceptibility to 2',3'-dideoxycytidine.

To investigate whether human immunodeficiency virus type 1 pol gene mutations are selected during prolonged 2',3'-dideoxycytidine (ddC) therapy, we used the polymerase chain reaction to amplify a portion of the reverse transcriptase segment of the pol gene from the peripheral blood mononuclear cell DNA of a patient with AIDS before and after an 80-week course of ddC therapy. The consensus sequence from the second sample contained a unique double mutation (ACT to GAT) in the codon for reverse transcriptase amino acid 69, causing substitution of aspartic acid (Asp) for the wild-type threonine (Thr). A mutation (ACA to ATA) also occurred in the codon for position 165, causing substitution of isoleucine (Ile) for Thr. The GAT (Asp) codon was introduced into the pol gene of a molecular clone of human immunodeficiency virus via site-directed mutagenesis. Following transfection, mutant and wild-type viruses were tested for susceptibility to ddC by a plaque reduction assay. The mutant virus was fivefold less susceptible to ddC than the wild type; cross-resistance to 3'-azido-3'-deoxythymidine or 2'3'-dideoxyinosine was not found. The Ile-165 mutation did not confer additional ddC resistance. The Asp-69 substitution may have contributed to the generation of resistant virus in this patient.

Acquired Immunodeficiency Syndrome↗
PubMed1991

Recovery of drug-resistant influenza A virus during therapeutic use of rimantadine.

The therapeutic activity of rimantadine and its relationship to the shedding of drug-resistant influenza A virus were assessed in two randomized, double-blind, placebo-controlled trials involving patients with laboratory-documented influenza A virus (H3N2 subtype) illness of 2 days' duration or less. In a family-based study, rimantadine treatment for 10 days (24 children and adults) was associated with significant decreases in the number of days to a 50% reduction in symptoms (mean difference, 2.5 days), days of fever (1.6 days), and days of restricted activity (1.5 days) compared with the results obtained with placebo-treated patients (32 children and adults). Drug-resistant virus was recovered from eight (33%) of the rimantadine recipients on day 5. No differences in patient demographics or illness severity at the time of enrollment in the study were apparent between those who shed resistant virus and those who did not. Illness resolution tended to be slower in those who shed resistant virus compared with that in those who did not. In a study of adults treated for 5 days (six treated with rimantadine, six treated with placebo), resistant virus was recovered in three rimantadine recipients by day 3 of treatment. The results indicate that drug-resistant influenza A virus (H3N2) can be recovered from rimantadine-treated children and adults as early as 2 days after starting treatment, but that rimantadine retains a net therapeutic benefit compared with that of placebo.

Adolescent↗
PubMed1989

Protective effect of rhinovirus receptor blocking antibody in human fibroblast cells.

Infection of HeLa cells by human rhinoviruses (RV) of the major receptor group is inhibited by a HeLa-derived rhinovirus receptor murine monoclonal antibody (RRMA). In yield reduction studies in human embryonic lung fibroblast cells, pretreatment with 1.0 or 10 micrograms/ml of RRMA partially protected (greater than 90% titer reduction) against infection by RV 39 or coxsackie A21 (members of the major receptor family), but not by RV 1A (member of the minor receptor family). The protection afforded by RRMA persisted at least 72 h after a 2-h exposure. These results suggest that RV receptors can be effectively blocked for prolonged periods in cultured fibroblast cells.

Antibodies, Monoclonal↗
PubMed1989

Comparative susceptibility of respiratory viruses to recombinant interferons-alpha 2b and -beta.

Intranasal recombinant interferon-alpha 2b (rIFN-alpha 2b) protects against natural colds due to rhinoviruses, but apparently not against those caused by viruses. Because rIFN-beta serine17 (rIFN-beta ser) appears less active than rIFN-alpha 2b in preventing natural rhinovirus colds, we compared the two IFNs in two in vitro assays against selected respiratory viruses. In a yield reduction assay, both IFNs had comparable activity against rhinovirus types 39 and 1A and coronavirus 229E, which were inhibited by 90% or more at IFN concentrations of 10(-11) to 10(-10) gram of protein/ml (approximately 2-20 IU/ml). Similar activities were observed with rIFN-beta ser against rhinoviruses isolated from clinical specimens. At concentrations of 10(-9) gram protein/ml, both IFNs inhibited the growth of influenza A and parainfluenza viruses, but not of adenovirus or respiratory syncytial virus in the cell culture systems tested. Thus, the different clinical protection conferred by rIFN-alpha 2b and rIFN-beta ser in studies of natural rhinovirus colds are not accounted for by differences in their in vitro activity against these viruses, and other explanations must be found.

Biological Assay↗