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Biomedical subjects

D J Gocke

Publications and source records attributed to D J Gocke.

At least 19 recordsLinked to original sources
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

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

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

In vivo prevalence of azidothymidine (AZT) resistance mutations in an AIDS patient before and after AZT therapy.

In order to examine the in vivo prevalence of AZT resistance mutations in AID patients after long-term therapy we amplified, by polymerase chain reaction (PCR), a 654 bp pol gene fragment from peripheral blood mononuclear cell DNA samples from a patient before, and 19 months after, the start of AZT therapy. PCR products from each sample were cloned and 9 clones from each sample were sequenced. Seven of 9 clones from the post-AZT sample, but none from the pre-AZT sample, contained an amino acid substitution (Thr215 to Tyr) requiring two nucleotide changes within the same codon (ACC to TAC). This change had previously been shown by Larder and Kemp (Science, 246:1155-1158, 1989) to correlate with partial AZT resistance of virus isolates. In colony hybridizations using synthetic oligonucleotides corresponding to the mutant and wild-type sequences, 22 of 22 clones from the pre-AZT sample hybridized only to the wild-type probe while 21 of 26 clones from the post-AZT sample hybridized only to the mutant. Clinically, this patient remains well, indicating that while Tyr215 may be the first amino acid substitution leading to resistance, it alone does not appear to have significantly influenced the clinical status of this patient.

Acquired Immunodeficiency Syndrome↗
PubMed1991

In vivo sequence variation of the human immunodeficiency virus type 1 env gene: evidence for recombination among variants found in a single individual.

To assess in vivo sequence heterogeneity of the human immunodeficiency virus type 1 (HIV-1) env gene, we used the polymerase chain reaction to amplify proviral sequences present in peripheral blood mononuclear cell DNA of a patient with acquired immunodeficiency syndrome (AIDS). The amplified env gene fragment (575 bp) contains the first hypervariable region and part of the first conserved region. Eleven and twelve clones were sequenced, respectively, from specimens collected two months apart. Notable heterogeneity was observed among sequences recovered from both specimens. Also, the proviral population recovered from the first specimen varied significantly from that found in the second specimen. Both specimens contained forms with and without an 18 bp duplication. The presence or absence of this duplication, in addition to several point mutations, appear to define two molecular groups evolving in parallel within this patient. Several genotypes which had sequences characteristic of both groups occurred primarily in the second specimen; these can best be explained by multiple recombinational events between representatives of the two groups during reverse transcription. This study demonstrates that recombination may contribute significantly to the generation of diversity among HIV variants within a single individual.

Adult↗
PubMed1990

Infective endocarditis in intravenous drug users: a comparison of human immunodeficiency virus type 1-negative and -positive patients.

In a study of 34 human immunodeficiency virus (HIV)-seropositive and 12 HIV-seronegative intravenous drug users with 40 and 14 episodes, respectively, of infective endocarditis (IE), there were no differences between groups in the presentation of IE. Staphylococcus aureus was the infecting microorganism in 75% of the HIV-positive patients and 86% of the HIV-negative patients. Overall survival for the HIV-positive patients was 85% compared with 93% for the HIV-negative patients. Ninety percent of patients with asymptomatic HIV infection survived, whereas 60% of patients in CDC group IV survived (P = .052). In contrast to New Jersey seroprevalence surveys showing HIV antibody in 10%-50% of intravenous drug users, HIV antibody seroprevalence rate in this selected population was 75%. IE in the HIV-seropositive intravenous drug user is essentially the same as in the seronegative user. However, patients with symptomatic HIV infection may be more likely to die from their IE. Intravenous drug users with IE have a greater-than-expected seroprevalence of HIV; the reason remains to be determined.

Adult↗
PubMed1990

Radiologic distinction of pyogenic pulmonary infection from Pneumocystis carinii pneumonia in AIDS patients.

Thirty-four episodes of pyogenic pulmonary infection in 30 patients infected with human immunodeficiency virus (HIV) and 30 episodes of Pneumocystis carinii pneumonia (PCP) in 30 AIDS patients were reviewed to determine if the radiologic features were more helpful than clinical and laboratory findings in the differential diagnosis. The radiologic features of pyogenic pulmonary infection included lobar consolidation, nodules, infiltrates with pleural effusions, round infiltrates, and pleural effusions alone. These features are uncommon in PCP. The chest radiograph may be highly suggestive of a pyogenic process, especially when it shows local consolidation or nodules. Since bacterial pneumonias have a more favorable outcome, it is concluded that the radiologic features should be the primary guide to prompt diagnosis and treatment.

Acquired Immunodeficiency Syndrome↗
PubMed1989

Chronic constrictive pericarditis. A case report and review of the literature.

Actinomycosis is typically a chronic infection of the cervicofascial, thoracic, or abdominal region. Involvement of the heart occurs but is unusual. We present a case of chronic constrictive pericarditis caused by actinomycetes. The actinomycosis infection was present for 20 years, thereby representing the longest duration reported in the literature, to our knowledge.

Actinomycosis↗
PubMed1989

Immunochemical specificity of human antibodies to lipopolysaccharide from the J5 rough mutant of Escherichia coli O111:B4.

Antibody to the core region of lipopolysaccharide (LPS) of Escherichia coli O111:B4 (J5) is reported to cross-react with LPS from other gram-negative bacteria. We used an enzyme-linked immunosorbent assay to test various LPSs and their constituents for their ability to inhibit binding of human IgG antibody to J5 LPS to J5 LPS. Results were expressed as the concentration of inhibitor required to cause 50% inhibition of binding (I50). I50 values of antibody to J5 LPS for J5 LPS ranged from 5 x 10(-7) M to 8 x 10(-9) M. I50 values for Salmonella minnesota (Rc) were higher (2 x 10(-4) M to 2 x 10(-7) M). Other rough LPS failed to inhibit to 50% (up to 2 x 10(-4) M). J5 lipid A and core oligosaccharide inhibited, with I50 values ranging from 2 x 10(-5) M to 3 x 10(-8) M. Fifty percent inhibition was not achieved by smooth LPS (8 x 10(-5) M), heterologous lipid A (3 x 10(-4) M), or core LPS constituents (5 x 10(-3) M). These data suggest that IgG J5 LPS antibodies are specific for the Rc chemotype of the core of LPS.

Antibodies, Bacterial↗
PubMed1988

Toxic shock syndrome associated with use of a nasal tampon.

Toxic shock syndrome has been noted to occur with nasal surgery, both with and without packing. A new synthetic sponge, described as a nasal tampon, has become available for use as packing after surgery. Herein is reported the first case of toxic shock syndrome associated with the use of this nasal tampon.

Adult↗
PubMed1987

Natural history of acquired immunodeficiency syndrome in hemophilic patients.

During the 5-year period from 1981 to 1985, we have observed 8 cases of acquired immunodeficiency syndrome (AIDS) among our 85 patients with hemophilia A. Thus, the prevalence of AIDS with hemophilia A is 9.4% in our patient population. By utilizing stored serum or plasma samples dating back to 1978, antibody against HTLV-III was detected in all 8 cases with AIDS. Based on the time interval from the appearance of antibody to HTLV-III to the diagnosis of AIDS in these patients, the incubation period ranged from 27 months to 60 months, with a median of 36 months. Before the diagnosis of full-blown AIDS, all patients exhibited a variety of prodromal manifestations of non-specific nature, including weight loss, oral candidiasis, unexplained non-productive chronic cough, generalized lymphadenopathy, and thrombocytopenia lasting several months to several years. Serial T-lymphocyte subset studies were available in some patients during the HTLV-III seropositive period and showed progressive lymphopenia, depletion of T4 cells with an average absolute count of 94 +/- 128 per mm3 (mean +/- 1 S.D.), and a markedly reversed T4/T8 ratio of 0.26 +/- 0.19 (mean +/- 1 S.D.). These findings suggest that the incubation period of AIDS is considerably long and that prospective study of serial immunologic markers and HTLV-III markers may be warranted in hemophilic patients at risk.

Acquired Immunodeficiency Syndrome↗
PubMed1985

In vitro studies of the killing of clinical isolates by povidone-iodine solutions.

Two-hundred-and-thirty clinical isolates were surveyed for susceptibility to povidone-iodine (PVP-I) ('Betadine'). Of 95 staphylococcal isolates tested, only 18 (19%) were completely killed by exposure to 10% PVP-I (the usual stock concentration) for 15 s. Seventy-seven staphylococcal isolates (81%) exhibited varying degrees of apparent 'resistance' under these conditions. However, of 39 other Gram-positive isolates and 96 Gram-negative isolates tested (including 20 Pseudomonas aeruginosa and four Ps. cepacia), only one strain of Escherichia coli exhibited significant lack of killing. However, this apparent 'resistance' was completely lost by prolonging the contact time to as little as 30 s in 60% of the isolates, and all isolates were completely killed by 120 s. A paradoxical increase in killing by lower concentrations of PVP-I was observed (maximal killing about 0.1% PVP-I). A new PVP-I formulation ('SP-Betadine') was completely cidal for all isolates tested after only a 15-s contact time.

Anti-Bacterial Agents↗