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Biomedical subjects

S A Danner

Publications and source records attributed to S A Danner.

At least 73 records · Page 4Linked to original sources
PubMed1996

Safety and efficacy of lamivudine-zidovudine combination therapy in zidovudine-experienced patients. A randomized controlled comparison with zidovudine monotherapy. Lamivudine European HIV Working Group.

OBJECTIVE: To compare the safety and efficacy of 2 doses of lamivudine given in combination with zidovudine with continued zidovudine monotherapy. DESIGN: Double-blind, randomized, multicenter, comparative trial of 223 patients treated for 24 weeks. SETTING: Patients from 32 hospitals in Europe were enrolled throughout a 1-year period. PATIENTS: Adult human immunodeficiency virus type 1 (HIV-1)-positive, zidovudine-experienced ( > or = 24 weeks prior zidovudine) patients with CD4+ cell counts between 0.10 and 0.40 x 10(9)/L (100-400 cells/microL). INTERVENTION: Patients received either 200 mg of zidovudine every 8 hours, 150 mg of lamivudine every 12 hours plus zidovudine, or 300 mg of lamivudine every 12 hours plus zidovudine for 24 weeks. All patients were then allowed to receive zidovudine and open-label lamivudine combination therapy. Twelve patients withdrew because of adverse events during the 24-week treatment period. MAIN OUTCOME MEASURES: Efficacy was measured by evaluating immunological and viral load changes, and safety was assessed by evaluating clinical manifestations and laboratory indexes of toxic effects. RESULTS: Patients receiving low- or high-dose combination therapy had greater treatment effects compared with patients receiving continued zidovudine monotherapy during the first 24 weeks as documented by changes in CD4+ cell counts (+0.04 vs +0.03 vs -0.02 x 10(9)/L, respectively; P < .001); log10 HIV-1 RNA as measured by the Roche assay (-0.96 vs -0.77 vs +0.07 copies/mL, respectively; P < .001) or log10 HIV-1 RNA measured by the quantitative nucleic acid sequence-based amplification assay (-0.59 vs -1.06 vs -0.02 copies/mL, respectively; P < .011); and immune-complex dissociated (ICD) p24 antigen (-74% vs -68% vs +27%, respectively; P < .001). There were no statistically significant differences in viral measurements, in CD4+ cell counts, or in safety profile between the groups receiving 2 doses of lamivudine in combination with zidovudine. The effects on CD4+ cell counts and ICD p24 antigen were sustained throughout 48 weeks for patients continuing combination therapy. Patients switching to combination therapy at week 24 showed improvement. CONCLUSION: In zidovudine-experienced HIV-1-infected patients, combination treatment with lamivudine and zidovudine is well tolerated and provides greater and more sustained increases in CD4+ cell counts and decreases in viral load than continued zidovudine monotherapy.

Adult↗
PubMed1996

Severe complications of perianal sepsis in patients with human immunodeficiency virus.

Fifty human immunodeficiency virus (HIV)-infected patients with perianal sepsis were studied. Seven (14 per cent) had serious septic complications, four patients with severe necrotizing gangrene, and three with abscesses in the mediastinum, liver and brain respectively. CD4+ lymphocyte counts were significantly lower in patients with severe septic complications as compared with those with uncomplicated perianal sepsis (P < 0.05). In patients with HIV presenting with rare (metastatic) abscesses, perianal sepsis must always be kept in mind as a possible focus. Although HIV-infected patients have a limited life expectancy perianal fistulas and abscesses should be aggressively treated, because of the high risk of severe complications.

AIDS-Related Opportunistic Infections↗
PubMed1996

Increased numbers of granzyme-B-expressing cytotoxic T-lymphocytes in the small intestine of HIV-infected patients.

The objective of this study was to determine whether granzyme B-expressing cells, which identify activated cytotoxic lymphocytes, are present in the small intestinal mucosa of human immunodeficiency virus (HIV)-infected patients with and without diarrhea. Therefore, duodenal biopsy specimens from 29 HIV-infected patients (11 with diarrhea and 18 without diarrhea) and 15 control patients were stained for the presence of granzyme B expressing cells. In HIV-infected patients, a significantly increased expression of granzyme B in the lamina propria was observed (p = 0.00001): In 22 of 29 patients, at least 5-10 cells per high-power field were counted. In contrast, in 13 of 15 control patients, granzyme B was not expressed or minimally so, and in two others a maximum of five granzyme-B-expressing cells could be detected per high-power field. No significant difference was found between the HIV-infected patients with and without diarrhea. Double staining revealed that the granzyme-B-expressing cells were mainly CD3 positive. These data show that activated cytotoxic T lymphocytes (CTLs) are present in the duodenal mucosa of HIV-infected patients. No relation between the number of CTLs and the presence of diarrhea was demonstrated. CTLs are known to be involved in the pathogenesis of HIV infection and in the production of tissue injury, but their functional role in intestinal HIV-related pathology has yet to be elucidated.

Adult↗
PubMed1996

Serological and polymerase chain reaction-based analysis of aqueous humour samples in patients with AIDS and necrotizing retinitis.

OBJECTIVE: To evaluate the measurement of intraocular antibody production and detection of DNA by the polymerase chain reaction (PCR) for diagnosis of the causative microorganism in patients with AIDS and necrotizing retinitis. METHODS: Paired serum and aqueous humour samples obtained from 28 patients with AIDS and necrotizing retinitis, seen between January 1987 and March 1992, were analysed for intraocular antibody production against cytomegalovirus (CMV), varicella zoster virus, herpes simplex virus, Epstein-Barr virus, and Toxoplasma gondii. Specific antibody titres in the inflamed eye and in the circulation were related to total immunoglobulin G content in the aqueous humour and serum. In addition, PCR analysis was performed in 15 samples. Results were compared to the final diagnosis, which was based on the subsequent clinical course. Results were also related to parameters describing the immune state of the patients: CD4 count, time between diagnosis of an AIDS-defining illness and retinitis, and time of survival following the diagnosis of retinitis. RESULTS: In 11 (39%) out of 28 patients we found local intraocular antibody production which correlated with the final diagnosis (one out of two cases with acute retinal necrosis, three out of five cases with toxoplasma retinitis, and eight out of 21 patients with CMV retinitis). In all 13 patients with CMV retinitis PCR analysis detected CMV DNA. In one patient with the clinical diagnosis of Toxoplasma retinitis, Toxoplasma DNA could be determined, whereas in the same sample CMV DNA was also found. In yet another patient with Toxoplasma retinitis only CMV DNA could be detected. A relationship between results of local antibody determination with either CD4 counts, or the time interval between AIDS-defining illness and retinitis, or survival time after diagnosis of retinitis could not be established. CD4 counts were higher than 50 x 10(6)/l in eight out of 19 patients with CMV retinitis. No complications of paracentesis were seen. CONCLUSIONS: Detection of intraocular antibody production and PCR analysis are quick and safe procedures and helpful tools for diagnosis of the involved pathogen in AIDS patients with a necrotizing retinitis. Negative results of local antibody production, even in the presence of detectable viral DNA, could not be related to the parameters of a more deteriorated immune status of these patients.

Acquired Immunodeficiency Syndrome↗
PubMed1996

Cytomegalovirus retinitis in AIDS patients: a comparative study of intravenous and oral ganciclovir as maintenance therapy.

OBJECTIVES: To compare the safety and efficacy or oral ganciclovir with intravenous ganciclovir for the maintenance therapy of cytomegalovirus (CMV) retinitis in AIDS patients. DESIGN: Multicenter, randomized, open-label study, with both masked and unmasked ophthalmic assessments. METHODS: Patients with AIDS and stable CMV retinitis were randomized after an induction course of intravenous ganciclovir (5 mg/kg twice daily) to receive maintenance therapy with oral ganciclovir (500 mg six times daily) or intravenous ganciclovir (5 mg/kg once daily). MAIN OUTCOME MEASURE: The primary endpoint of the study was time to progression of CMV retinitis from the start of maintenance therapy. RESULTS: The mean time to progression, evaluated by funduscopy was 109 days for the intravenous group, and 86 days for the oral group (P = 0.02). The masked photographic assessment revealed shorter time to progression for both oral and intravenous groups, as compared with funduscopy data, and showed no significant difference between the two treatment groups: 62 days for intravenous ganciclovir and 51 days for oral ganciclovir (P = 0.15). Diarrhea and neutropenia were the most frequent reported events in both groups, with the incidence of sepsis more than double in the intravenous compared with the oral ganciclovir group (3 versus 8.5%). CONCLUSIONS: Oral ganciclovir offers a reasonable alternative to intravenous ganciclovir for the maintenance therapy of CMV retinitis in AIDS patients.

AIDS-Related Opportunistic Infections↗
PubMed1995

A short-term study of the safety, pharmacokinetics, and efficacy of ritonavir, an inhibitor of HIV-1 protease. European-Australian Collaborative Ritonavir Study Group.

BACKGROUND: Reverse-transcriptase inhibitors have only moderate clinical efficacy against the human immunodeficiency virus type 1 (HIV-1). Ritonavir is an inhibitor of HIV-1 protease with potent in vitro anti-HIV properties and good oral bioavailability. METHODS: We evaluated the antiviral activity and safety of ritonavir in a double-blind, randomized, placebo-controlled phase 1 and 2 study of 84 HIV-positive patients with 50 or more CD4+ lymphocytes per cubic millimeter. The patients were randomly assigned to one of four regimens of ritonavir therapy, or to placebo for four weeks and then (by random assignment) to one of the ritonavir regimens. RESULTS: During the first 4 weeks, increases in CD4+ lymphocyte counts and reductions in the log number of copies of HIV-1 RNA per milliliter of plasma were similar among the four dosage groups, but in the three lower-dosage groups there was a return to base-line levels by 16 weeks. After 32 weeks, in the seven patients in the highest-dosage group (600 mg of ritonavir every 12 hours), the median increase from base line in the CD4+ lymphocyte count was 230 cells per cubic millimeter, and the mean decrease in the plasma concentration of HIV-1 RNA (as measured by a branched-DNA assay) was 0.81 log (95 percent confidence interval, 0.40 to 1.22). In a subgroup of 17 patients in the two higher-dosage groups, RNA was also measured with an assay based on the polymerase chain reaction, and after eight weeks of treatment there was a mean maximal decrease in viral RNA of 1.94 log (95 percent confidence interval, 1.37 to 2.51). Adverse events included nausea, circumoral paresthesia, elevated hepatic aminotransferase levels, and elevated triglyceride levels. Ten withdrawals from the study were judged to be related to ritonavir treatment. CONCLUSIONS: In this short-term study, ritonavir was well tolerated and had potent activity against HIV-1, but its clinical benefits remain to be established.

Adult↗
PubMed1995

Local excision and mucosal advancement for anorectal ulceration in patients infected with human immunodeficiency virus.

In patients infected with human immunodeficiency virus (HIV) no effective surgical procedure has been described for anorectal ulceration that is resistant to medical therapy. This study was designed to determine the effectiveness of surgical excision of anorectal ulcers, with or without mucosal advancement. The medical records of patients with HIV and anorectal pathology diagnosed between 1984 and 1994 were reviewed. Patients with anorectal ulcers were divided into group A which was treated only with excision and group B in which excision was combined with mucosal advancement. Surgical treatment was considered successful if relief of symptoms was achieved within 4 weeks of the operation. Excision of anorectal ulcers was successful in seven of 16 patients (44 per cent) in group A. Relief of symptoms was achieved in 12 of 13 patients (92 per cent) in group B when surgical excision was combined with mucosal advancement, which is significantly better than the results in group A (P = 0.02). This non-randomized study indicates that after unsuccessful medical treatment persistent symptomatic ulcers should be treated operatively by excision with mucosal advancement.

AIDS-Related Opportunistic Infections↗
PubMed1995

Anorectal surgery in human immunodeficiency virus-infected patients. Clinical outcome in relation to immune status.

PURPOSE: Anorectal disease is commonly found in human immunodeficiency virus (HIV)-infected patients. The aim of this study was to determine the spectrum of anorectal disease, its surgical treatment, clinical outcome, and its relation to immune status. METHODS: Medical records of all HIV-infected patients with anorectal pathology that required surgical treatment from January 1984 to January 1994 were retrospectively reviewed. Patients were divided into five different groups: common anorectal pathology (hemorrhoids, polyps, Group A); condylomata acuminata (Group B); perianal sepsis (abscesses, fistulas, Group C); anorectal ulcers (Group D); malignancies (Group E). RESULTS: Eighty-three patients needed 204 surgical consultations (13 percent conservative, 87 percent operative) for 170 anorectal diseases. Fifty-one patients had multiple anorectal pathology. Operative intervention resulted in adequate wound healing and symptom relief in 59 percent of patients, adequate wound healing without relief of symptoms in 24 percent of patients, and disturbed wound healing was related to type of anorectal disease (P < 0.001) and to preoperative CD4(+)-lymphocyte counts (P < 0.01). Disturbed wound healing and most insufficient immune status were encountered in Groups C, D, and E. Within these groups low CD4(+)-lymphocyte counts were a risk factor for disturbed wound healing (P = 0.004). Median postoperative survival was highest (4.7 years) in Group A, lowest (0.6 years) in Groups D and E, and related to type of anorectal disease (P = 0.0001). CONCLUSIONS: The spectrum of anorectal disease is complex. Type of anorectal disease is strongly related to immune status, wound healing, and postoperative survival.

Adult↗
PubMed1995

Treatment of poor prognosis epidemic Kaposi's sarcoma with doxorubicin, bleomycin, vindesine and recombinant human granulocyte-monocyte colony stimulating factor (rh GM-CSF).

The efficacy and toxicity of doxorubicin, bleomycin and vindesine in epidemic Kaposi's sarcoma, and the role of rh GM-CSF in chemotherapy-induced neutropenia were evaluated in this Phase II study. Patients with progressive Kaposi's sarcoma were eligible, and were staged according to ACTG criteria. Treatment consisted of 20 mg/m2 doxorubicin, and a fixed dose of 15 mg bleomycin and 4 mg vindesine every 2 weeks. All patients continued antiretroviral medication with severe myelosuppression, patients received subcutaneous 5 micrograms/kg rh GM-CSF (Leucomax) from days 2-12. Response and toxicity were measured according to ACTG and WHO criteria. 27 patients were evaluable, 25 patients classified as having a poor prognosis. The response rate was 70% (3 CR, 16 PR), the duration of response was 18 weeks (range 8-25) and the median survival 30 weeks (range 4-63+). The cause of death was mostly opportunistic infection. 4 patients died of pulmonary Kaposi's sarcoma. The toxicity of this regimen was mainly myelosuppression and 13 patients were treated with rh GM-CSF. Complete recovery of the white blood cells occurred in seven of the 27 courses of rh GM-CSF (26%). No bacterial infections were recorded, but 5 patients (19%) developed an opportunistic infection during treatment. Peripheral neuropathy occurred in 16% of patients. Combination chemotherapy is effective in poor prognosis Kaposi's sarcoma but has a shortlasting effect. The main toxicity of this treatment is severe myelosuppression which can be ameliorated by rh GM-CSF. It remains to be established whether rh GM-CSF is also able to reduce the incidence of opportunistic infections.

Adult↗
PubMed1995

Rapid changes in human immunodeficiency virus type 1 RNA load and appearance of drug-resistant virus populations in persons treated with lamivudine (3TC).

The effect of the appearance of drug-resistant human immunodeficiency virus type 1 (HIV-1) on viral RNA load was studied in patients treated with the reverse transcriptase inhibitor lamivudine. During the first 12 weeks of treatment, HIV-1 RNA concentrations and amino acid changes in codon 184, causing high-level resistance to lamivudine, were determined in longitudinal serum samples from HIV-1 p24 antigen-positive and -negative patients. A marked decline in the amount of HIV-1 RNA (approximately 95% below baseline) and HIV-1 p24 antigen was observed within 2 weeks, followed by a rise that coincided with the appearance of lamivudine-resistant viruses in serum (isoleucine mutants initially, which were subsequently replaced by valine variants). After 12 weeks, a partial antiviral effect was observed despite the presence of a complete codon 184 mutant virus population in serum. This study shows that the rapid appearance of drug-resistant virus in serum is followed by an increase in viral RNA load.

CD4 Lymphocyte Count↗
PubMed1995

Diarrhoea in HIV-infected patients: no evidence of cytokine-mediated inflammation in jejunal mucosa.

OBJECTIVE: To determine whether a mucosal cytokine-mediated inflammatory response is involved in cryptosporidial or microsporidial diarrhoea, as well as in diarrhoea of unknown origin in HIV-infected patients. DESIGN: Prospective study. METHODS: Jejunal biopsies were obtained from HIV-infected patients with diarrhoea. Controls were HIV-infected and HIV-seronegative patients without diarrhoea. Two biopsies were homogenized immediately and two other biopsies were first cultured for 20 h. Cytokines [tumour necrosis factor (TNF), interleukin (IL)-1 beta, IL-6, IL-8, IL-10], soluble TNF receptors (sTNFR) p55 and p75, and soluble IL-2 receptor (sIL-2R) were assessed in the homogenates and in the supernatants by sandwich enzyme-linked immunosorbent or enzyme-linked binding assays. The cytokine receptors were also measured in serum. RESULTS: Six HIV-infected patients with cryptosporidiosis, six with microsporidiosis, seven with diarrhoea of unknown origin, seven without diarrhoea, and seven HIV-seronegative patients were eligible. Four patients were excluded because of the presence of other pathogens. No cytokines were detected in immediately homogenized jejunal tissue. Following culture, IL-6 and IL-8 levels were higher in HIV-infected patients with diarrhoea of unknown origin than in HIV-seronegative controls without diarrhoea, although this was not statistically significant. No differences in serum or post-culture supernatant sTNFR p55 and p75 levels existed between the HIV-infected patients with or without diarrhoea. sTNFR, IL-1 beta, IL-10 and the sIL-2R were only detected in low amounts or not at all, and were equally distributed among all patient groups. CONCLUSIONS: This study indicates that mucosal cytokine-mediated inflammatory responses do not play an important role in the pathogenesis of different types of diarrhoea in HIV-infected patients. These results do not support the use of immunomodulatory therapy in these patients.

AIDS-Related Opportunistic Infections↗
PubMed1995

Management of cytomegalovirus disease.

AIM: To review the estimated incidence of cytomegalovirus (CMV) disease, its diagnosis and currently accepted treatments and those under investigation. CMV DISEASE IN PATIENTS WITH HIV INFECTION: The most frequently occurring manifestation of CMV disease is retinitis, occurring in approximately 20-40% of patients. Oesophagitis and generalized infection are also common. DIAGNOSIS: At present, diagnosis relies on specific histopathology as serology is unreliable and CMV culture lacks sensitivity and specificity. Assessment of the presence of CMV-specific proteins and polymerase chain reaction assays of CMV DNA may prove useful. TREATMENT: Intravenous ganciclovir and foscarnet are equally effective for the treatment of CMV disease, but ganciclovir is generally regarded as the primary treatment option due to its relative ease of administration. Combination therapy with these agents is also effective in the treatment of CMV retinitis. As well as patients with sight-threatening retinitis, patients with peripheral retinitis benefit from immediate treatment. Local treatment with a ganciclovir implant or intravitreal injection is effective, but does not provide protection against ocular complications, infection of the contralateral eye and extraocular disease. Oral ganciclovir is virtually as effective as intravenous administration for secondary prophylaxis versus maintenance treatment for CMV retinitis with the advantage of a more favourable adverse-effect profile. CONCLUSIONS: Intravenous ganciclovir and foscarnet are equally effective in the treatment of CMV disease. Oral ganciclovir is effective in secondary prophylaxis and provides a welcome alternative to intravenous maintenance treatment.

Antiviral Agents↗