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Biomedical subjects

P Reiss

Publications and source records attributed to P Reiss.

At least 91 records · Page 5Linked to original sources
PubMed1996

Tolerability and activity of a new recombinant interferon-alpha B/D hybrid in patients with HIV-1 infection.

The maximum tolerated dose (MTD) and toxicity profile of a new recombinant interferon-alpha B/D hybrid (IFN-alpha B/D) in HlV-1-infected patients were determined in an outpatient, dose-escalating study with dose groups of three patients: 16, 32, 48, 64, 96 and 112 million international units (MIU) three times weekly subcutaneously during 12 weeks. The MTD was the last dose level just below the dose level at which more than one patient experienced > or = grade 3 toxicity. The study also searched for preliminary evidence of efficacy of IFN-alpha B/D. Sixteen HIV-1-infected patients with CD4 cell counts > or = 200/mm3 were enrolled: eight were asymptomatic and eight had symptomatic disease. Two patients were excluded as a result of protocol violations. Five patients (36 per cent; one at each tested dose level) discontinued prematurely due to side effects. One patient was lost to follow-up. Twelve patients (87 per cent) experienced > or = grade 2 toxicity. Toxicity > or = grade 3 occurred in none of three patients assigned to 16 MIU, one of five assigned to 32 MIU (fatigue), one of three assigned to 48 MIU (haemorrhagic colitis) and two of three assigned to 64 MIU (fatigue). One patient (48 MIU) had reversible cardiomegaly. Progressive weight loss was experienced by 12 of 14 participants. Serum HIV-1 p24 antigen declined in nine of 11 antigenaemic patients (seven persistently > 50 per cent) without a clear dose-response relationship. CD4 percentages showed no consistent pattern and T cell reactivity diminished. The tolerability and toxicity profile of IFN-alpha B/D appear to be fairly similar to that of other types of IFN-alpha.

Administration, Cutaneous↗
PubMed1995

Photodynamic therapy in AIDS-related cutaneous Kaposi's sarcoma.

For evaluating the role of photodynamic therapy (PDT) in the local treatment of acquired immune deficiency syndrome (AIDS)-related cutaneous Kaposi's sarcoma (KS), nine treatments were performed in eight human immunodeficiency virus-positive homosexual men. The patients received 2 mg Photofrin/kg and either 120 J/cm2 (n = 5) or 70 J/cm2 (n = 4) laser light (630 nm). A total of 83 lesions were evaluable for response with a follow-up of 3-8 months. The overall response rates by patient for all treated lesions were 50-100% (120 J/cm2) and 83.3-90.3% (70 J/cm2), with a median duration of 3 months (range, 2-6 months). Tumors located at the head had higher response rates than those at the trunk or extremities (p = 0.005 and p - 0.015 respectively). The size of the KS showed a negative relationship with the probability of complete response (p = 0.047). Local and general side effects occurred, including pain, blisters, temperature increase, muscle stiffness, and severe edema. The cosmetic result was unsatisfactory because of a high prevalence of scars and long-lasting hyperpigmentation. Although the response rates of PDT are high, light dose of 70-120 J/cm2 cannot be recommended in the treatment of cutaneous KS in combination with 2 mg/kg Photofrin because of severe side effects and unsatisfactory cosmetic result.

Acquired Immunodeficiency Syndrome↗
PubMed1995

Sound-induced displacement responses in the plane of the organ of Corti in the isolated guinea-pig cochlea.

Sound-induced displacement responses in the plane of the organ of Corti were studied in the apical turn in the isolated temporal-bone preparation of the guinea-pig cochlea. Swept sinusoidal sound stimuli (100-500 Hz) were delivered closed-field to the external auditory meatus. The surface of the organ of Corti was continuously monitored using a CCD video camera. Displacement responses in the plane of the organ of Corti were determined by analyzing the change of the location of the cells (pixel-by-pixel) within the visual field of the microscope. Displacement responses followed the stimulus amplitude and were observable at Hensen's cells, three rows of outer hair cells and inner hair cells. The most prominent displacement responses were over the outer hair cells; the maximum amplitude was 0.6-1.7 microns at 100 dB SPL. Tuned displacement responses were found; the Q10 dB was 1.3 +/- 0.6. The best frequency was tonotopically organized, decreasing toward the apex with a space constant of 0.4-0.9 mm/oct. The motion was directed either strial-apically or strial-basally in a frequency dependent manner. With the aid of laser interferometric measurements of the transverse displacement, it was concluded that sound stimulation does not induce slow DC motion in the organ of Corti for the isolated temporal-bone preparation.

Acoustic Stimulation↗
PubMed1995

The proteolytic specificity of the natural enediyne-containing chromoproteins is unique to each chromoprotein.

BACKGROUND: Enediyne chromoproteins are potent antitumor antibiotic agents. They consist of a labile nine-membered enediyne chromophore non-covalently associated with a stabilizing acidic polypeptide. Studies in vitro on three members of this superfamily of natural products--kedarcidin, maduropeptin and neocarzinostatin--demonstrated that their chromophores cleave DNA at sites specific to each chromophore. Recently, we showed that these chromoproteins possess proteolytic activity against histones in vitro, with histone H1 as a preferred substrate. Based on these results, we speculated that this selective proteolytic activity may be important in vivo in the delivery of the enediynes intact to the DNA in chromatin. RESULTS: We show here that each chromoprotein generates a unique set of H1 fragments as revealed by gel analyses of the H1 cleavage reaction products. To probe the observed cleavage specificity, we synthesized a 24-amino-acid peptide representing a basic region of histone H1. This model peptide was incubated individually with similar concentrations of the kedarcidin, neocarzinostatin and maduropeptin chromoproteins as well as the kedarcidin apoprotein. The reaction products were analyzed by electrospray liquid chromatography/mass spectrometry. Our results indicate that all proteins cleave the peptide at selected backbone amides, and that these sites vary according to the chromoprotein used. Moreover, the kedarcidin apoprotein appears to be less specific than the kedarcidin chromoprotein complex. CONCLUSIONS: The small size, unique architecture and very acidic nature of the enediyne chromoproteins are highly unusual. These natural products exhibit the dual functionalities of specific DNA cleavage and selective proteolytic activity. This observation adds to the fascinating properties of these molecules and suggests that it is possible not only to design small moieties to cleave DNA but also to conceive of small proteins to deliver these moieties intact to defined areas of chromatin.

Alkynes↗
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↗
PubMed1994

Activation of the cytokine network in a patient with AIDS and the recalcitrant erythematous desquamating disorder.

An AIDS patient with the recalcitrant erythematous desquamating (RED) disorder, a presumed variant of the Staphylococcus aureus toxic shock syndrome that is characterized by relapses, skin involvement, and variable multiple-organ involvement, is described. A strain of S. aureus producing toxic shock syndrome toxin 1 was isolated from the patient, but no antibodies to this exotoxin were detectable before and during the most severe episode of the RED disorder. Levels of cytokines were measured during episodes and at other times. Tumor necrosis factor and interleukin 6 were detectable only during the most severe exacerbation of the disorder; this finding suggests a pathogenetic role for these cytokines.

Acquired Immunodeficiency Syndrome↗
PubMed1993

[HIV-related non-Hodgkin lymphoma in 45 patients; a retrospective analysis].

Non-Hodgkin lymphoma is seen in approximately 5% of patients with AIDS. In recent years, the incidence has increased due to an extension of the average lifespan of HIV-infected individuals. In this article we describe the histological and clinical features of 45 patients with HIV-related non-Hodgkin lymphoma seen at the Academic Medical Centre between 1984 and 1991. There were 43 men and 2 women with a median age of 40 years. Most patients had high-grade B-cell lymphoma; 85% had extranodal sites. Prognosis was poor: overall median survival was only 3.8 months. Twelve patients were treated with 3 or more courses of chemotherapy: their median survival was 8 months. In 7 of 12 patients a complete remission was obtained; their median survival was 18 months. A history of AIDS was a poor prognostic factor.

Adult↗
PubMed1993

Use of competitive polymerase chain reaction to determine HIV-1 levels in response to antiviral treatments.

OBJECTIVE: To develop a competitive polymerase chain reaction technique with which to evaluate the usefulness of HIV-1 level as a marker of response to antiviral treatment. DESIGN: HIV-1 sequences were assessed by competitive polymerase chain reaction in four subjects participating in a double-blind study of monotherapy versus combination therapy with nucleoside analogues. METHODS: We inserted a mutant construct of the HIV-1 pol sequence into a commercial vector, enabling us to generate known amounts of mutant DNA and RNA for competitive polymerase chain reaction. To measure HIV-1 DNA copies in cells, the mutant DNA fragments were allowed to compete in a 10-fold dilution series with a constant amount of nucleic acid from the subject. To measure HIV-1 RNA copies in plasma, in vitro synthesized mutant RNA was added in a 10-fold dilution series to a constant amount of subject RNA and copy DNA was synthesized. DNA and copy DNA were used as the input for nested pol polymerase chain reaction. Mutant and wild-type amplimers were discriminated by size. RESULTS: The competitive polymerase chain reaction technique has been validated in model experiments and can be used over a broad range (at least 6 logs) of levels. Three of the four subjects showed a decline of 1 log in proviral DNA levels in cells after beginning antiviral treatment. All four showed a decline of at least 1 log in viral RNA levels in plasma, but this decline was transient in one subject. CONCLUSION: The HIV-1 sequence level is a useful marker in antiviral treatment studies.

Antiviral Agents↗
PubMed1993

Diagnosis of intestinal and disseminated microsporidial infections in patients with HIV by a new rapid fluorescence technique.

AIMS: To assess the value of a new rapid fluorescence method for the diagnosis of microsporidiosis in HIV seropositive patients. METHODS: Microsporidian spores in stools were demonstrated by using the fluorochrome stain Uvitex 2B. The new technique was evaluated in three groups of HIV seropositive patients with diarrhoea. Group 1: 19 patients with biopsy confirmed E bieneusi infection (186 stool samples); group 2: 143 consecutive patients from whom faeces were submitted for routine investigation of diarrhoea (318 samples); group 3: 16 patients with small intestinal biopsy specimens negative for microsporidia (55 samples). The new method was used to monitor spore shedding during experimental treatment with paromomycin and albendazole in four patients. RESULTS: Brightly fluorescent spores were detected in all stool samples of patients in group 1. In group 2 16 (11%) patients had spores in their stool samples. E bieneusi was found in 11 patients; in the other five another genus of microsporidia, Encephalitozoon, was recognised. Encephalitozoon spores were also found in the urine of three of these patients and in the maxillary sinus aspirate of two of them, suggesting disseminated infection. The results were confirmed by electron microscopic examination. In group 3 negative biopsy specimens were confirmed by negative stool samples in all cases. Treatment with albendazole and paromomycin did not affect the spore shedding in three patients with E bieneusi infection. By contrast, in a patient with Encephalitozoon sp infection albendazole treatment resulted in clinical improvement together with complete cessation of spore excretion in the stool. CONCLUSION: The Uvitex 2B fluorescence method combines speed, sensitivity, and specificity for the diagnosis and treatment evaluation of intestinal and disseminated microsporidiosis.

Albendazole↗
PubMed1992

Pyrimethamine alone as maintenance therapy for central nervous system toxoplasmosis in 38 patients with AIDS.

We retrospectively assessed the efficacy of maintenance therapy with pyrimethamine alone in 38 patients with AIDS and central nervous system (CNS) toxoplasmosis. The diagnosis was based on clinical presentation and compatible CT scan abnormalities with subsequent response to therapy. Survival analysis was performed by the product limit method of Kaplan-Meier. Fourteen patients received maintenance therapy with 25 mg pyrimethamine per day (group 1), and 24 patients were treated with 50 mg per day (group 2). The median survival from initiation of maintenance therapy until death or end of the study for the entire study population was 32 weeks. Median survival in group 1 was 28 weeks, as compared with 36 weeks in group 2 (p = 0.34). Relapses occurred in 12 patients, six in group 1 and six in group 2. There was no significant difference in failure-free survival between the two treatment groups (p = 0.09). One patient in group 1 and two patients in group 2 experienced severe toxicity, requiring discontinuation of therapy. All three patients relapsed and died. Two patients in group 2 who stopped treatment on their own initiative also had relapses. Thus, all five patients who discontinued therapy had relapses. Five of 13 patients in group 1 and two of 20 patients in group 2 relapsed during continuous therapy with pyrimethamine (p = 0.13); these seven patients responded to reintroduction of combination therapy (n = 6) or treatment with 50 mg pyrimethamine per day (n = 1). The results of our retrospective analysis suggest that maintenance therapy with oral pyrimethamine, 50 mg per day, in AIDS patients with CNS toxoplasmosis is effective.

Acquired Immunodeficiency Syndrome↗