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Biomedical subjects

J Feinberg

Publications and source records attributed to J Feinberg.

At least 91 records · Page 5Linked to original sources
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

Current status of HIV therapy: II. Opportunistic diseases.

Infections and malignancies account for most deaths in patients with AIDS and will continue to do so as long as HIV-induced immunosuppression is progressive and irreversible. Co-trimoxazole has emerged as the preferred agent for prevention of Pneumocystis carinii pneumonia. As appropriate broad-spectrum agents are developed, multiple opportunistic pathogen prophylaxis could become effective.

Acquired Immunodeficiency Syndrome↗
PubMed1992

Effect of the arthritis health professional on compliance with use of resting hand splints by patients with rheumatoid arthritis.

This study examined the effects of an occupational therapist's approach during the initial splinting session on the subsequent use of resting hand splints by patients with rheumatoid arthritis. Forty subjects were randomly assigned either to a standard treatment (control) group or to a compliance-enhancement (experimental) group, for whom the use of learning principles, sharing of expectations, use of a positive affective tone and behaviors by the therapist, and the assumption of responsibility by the patient were emphasized. During the 28-day period after splinting, patients in the experimental and control groups wore their splints an average of 23.3 and 18.1 days, respectively (p = 0.056). Nine subjects in the experimental group, but only four in the control group used their splints every day (p = 0.035). Knowledge of splint use correlated with actual use, regardless of the group assignment (p = 0.035). Change in the amount of wrist and hand pain was not significant in either group; however, the experimental group experienced a decrease in the duration of morning stiffness (p = 0.013). This intervention provides health professionals with a pragmatic and effective method to enhance compliance.

Arthritis, Rheumatoid↗
PubMed1992

New developments in the treatment of Pneumocystis carinii pneumonia.

Pneumocystis carinii pneumonia and therapies to treat this infection are associated with frequent and severe morbidity in patients with acquired immunodeficiency syndrome (AIDS). Mortality rates remain in the 20 to 40 percent range for severe episodes. Thus, less toxic and more effective therapies are needed. For mild-to-moderately severe episodes (PaO2 greater than 70 mm Hg or [A-a]DO2 less than 35 mm Hg), studies suggest that trimethoprim-dapsone, clindamycin-primaquine, and BW 566C80 may cause less toxicity than conventional therapy with trimethoprim-sulfamethoxazole or parenteral pentamidine. However, prospective, controlled trials are needed to establish whether the newer therapies are as effective as the existing licensed treatments. Aerosolized pentamidine is another new therapy that is better tolerated than trimethoprim-sulfamethoxazole but may not be as effective as parenteral treatment when there is extensive airspace consolidation. For severe episodes (PaO2 less than 70 mm Hg or [A-a]DO2 greater than 35 mm Hg), recent studies have established that adjunctive therapy with corticosteroids reduces mortality approximately twofold. For patients who have failed conventional treatments and are unable to ingest oral medications, trimetrexate may be tried. Other compounds being tested may further expand the therapeutic armamentarium with safer and more effective drugs.

Adrenal Cortex Hormones↗
PubMed1991

A multicenter trial of oral zidovudine in children with advanced human immunodeficiency virus disease. The Protocol 043 Study Group.

BACKGROUND AND METHODS: Zidovudine has been shown to be an effective antiretroviral treatment in adults with human immunodeficiency virus (HIV) infection. We examined the safety of zidovudine and the tolerance of and therapeutic response to the drug in 88 children with advanced HIV disease. During a 24-week outpatient trial, zidovudine (180 mg per square meter of body-surface area per dose) was given by mouth every six hours and serial measurements were made of clinical, immunologic, and virologic indexes. Children who completed 24 weeks of treatment were permitted to continue receiving zidovudine. RESULTS: Of the 88 children (mean age, 3.9 years; range, 4 months to 11 years), 61 completed the initial 24-week trial, and 49 continued to receive zidovudine for up to 90 weeks (median follow-up, 56 weeks). The patients generally tolerated zidovudine well. One or more episodes of hematologic toxicity occurred in 54 children (61 percent)--anemia (hemoglobin level, less than 75 g per liter) in 23 children (26 percent) and neutropenia (neutrophil count, less than 0.75 x 10(9) per liter) in 42 (48 percent). Many of these abnormalities resolved spontaneously, but 30 children required transfusions or a modification of the dose of zidovudine. Only three children had to stop receiving the drug because of hematologic toxicity. Kaplan-Meier analysis demonstrated that the probability of survival was 0.89 after 24 weeks and 0.79 after 52 weeks. There was marked improvement in weight gain, cognitive function (mainly in children less than 3 years old), serum and cerebrospinal fluid concentrations of p24 antigen, and the proportion of cerebrospinal fluid cultures negative for HIV. CD4+ lymphocyte counts (mean at base line, 0.263 x 10(9) per liter) improved during the first 12 weeks, although the improvement was not sustained through the 24th week. CONCLUSIONS: Zidovudine in a dose of 180 mg per square meter every six hours can be safely administered to children with advanced HIV disease. The resultant clinical, immunologic, and virologic improvements in children are similar to those reported with zidovudine in adults.

Acquired Immunodeficiency Syndrome↗
PubMed1991

Definition of a Ca2(+)-sensitive interface in the plasma gelsolin-actin complex.

Gelsolin is a Ca2(+)-dependent protein which severs actin filaments, caps their fast-growing ends and promotes nucleation. We report here results that delimit one of the interfaces between serum gelsolin and actin monomer. An actin-derived synthetic peptide (amino acids 305-326 of actin) coupled to a hydrophilic resin was tested for its possible interaction with gelsolin. We selected this sequence because it corresponds to a region implicated in the gelsolin-actin complex in a previous work [Boyer, Feinberg, Hue, Capony, Benyamin & Roustan (1987) Biochem. J. 248, 359-364]. We showed that this actin sequence is located at the surface of the actin molecule and observed a Ca2(+)-sensitive binding of gelsolin to this actin-derived peptide. In addition, by using a chymotryptic digest of gelsolin, we reported that only the C-terminal half of gelsolin interacts with the actin-(305-326)-peptide. These results that the Ca2(+)-sensitive interface includes both amino acids 305-326 of actin and probably amino acids 660-738 of gelsolin.

Actins↗
PubMed1991

Current status of HIV therapy: II. Opportunistic diseases.

Infections and malignancies account for most deaths in patients with AIDS--and will continue to do so as long as HIV-induced immunosuppression is progressive and irreversible. Options available for prevention and improved management of such diseases are changing as new agents emerge, new combinations of agents are developed, and new indications for available agents are identified.

Acquired Immunodeficiency Syndrome↗
PubMed1991

Localization of calmodulin in perinuclear structures of spermatids and spermatozoa: a comparison of six mammalian species.

The distribution of Calmodulin was examined during spermiogenesis and sperm epididymal maturation in rabbit, hamster, mouse, rat, monkey, and human. An affinity-purified antibody to Calmodulin was used to characterize this protein in sperm extracts by immunoblot analysis. Post-embedding immunogold procedures were used to localize Calmodulin at the ultrastructural level. The pattern of Calmodulin distribution was similar in the six species studied. A diffuse labeling was observed in round spermatids. Gold particles accumulated first in the subacrosomal layer of elongating spermatids. The perinuclear ring was also labeled. During the maturation phase of spermatids, Calmodulin labeling extended to the postacrosomal sheath. Dramatic changes occurred at spermiation so that in testicular sperm Calmodulin immunostaining was predominant in the postacrosomal sheath. Some labeling was still detected in restricted areas of the subacrosomal layer. This feature varied from species to species. Calmodulin location did not change during sperm epididymal maturation. A role for Calmodulin in the control of manchette development and regulation of subacrosomal actin aggregation state during spermiogenesis is proposed. The unique location of Calmodulin in the postacrosomal sheath of all species that have been studied in this work, together with the known presence of calcium in this area suggest a pivotal role for Calmodulin in sperm-egg fusion process.

Acrosome↗
PubMed1991

Co-distribution of annexin VI and actin in secretory ameloblasts and odontoblasts of rat incisor.

Annexin VI and actin were detected by immunoblot analysis in the enamel- and dentin-related portions of dental tissues. Annexin VI was found mainly in the particulate fraction whereas actin was detected in both the soluble and particulate fractions. By immunoelectron microscopy, annexin VI antibodies conjugated with colloidal gold were seen to label the mitochondria, the cytosol and the nucleus of secretory ameloblasts and odontoblasts of rat incisor. In the processes of these cells, the plasmalemmal undercoat was labeled. Anti-actin antibodies labeled the desmosome-like junctions, the cytosol, and the mitochondria of the cell bodies. Extensive labeling was seen at the periphery of the Tomes' processes and odontoblast processes. These results suggest that annexin VI may play a role in Ca2(+)-regulation in the cell bodies, especially as a calcium receptor protein in the mitochondria. Moreover, annexin VI and actin seem to be co-distributed in secretory processes. Thus, these proteins might be both involved in exocytotic and endocytotic events.

Actins↗
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

Foscarnet therapy for ganciclovir-resistant cytomegalovirus retinitis in patients with AIDS.

Infections caused by cytomegalovirus (CMV) resistant in vitro to ganciclovir, defined as requiring greater than 6 mumols of ganciclovir for ED50 have developed in some AIDS patients with progressive CMV retinitis despite chronic ganciclovir therapy. Two such patients (CMV isolates ED50, 9.5-14.5 mumols) were treated with foscarnet, an antiviral pyrophosphate analogue to which both patients' isolates demonstrated in vitro susceptibility (ED50, less than or equal to 300 mumols). Each patient had documented retinitis progression, at 2- and 1- to 5-week intervals, respectively, despite high-dose intravenous ganciclovir therapy. Both patients responded to foscarnet therapy with cessation of viral shedding in urine and blood. After foscarnet therapy was started, retinitis stabilized in the two patients for 12 and 25 weeks, respectively, before progression recurred. Therefore, foscarnet may be effective in immunocompromised patients with rapidly progressive CMV retinitis whose CMV isolates have developed in vitro resistance to ganciclovir.

Acquired Immunodeficiency Syndrome↗
PubMed1990

Interferon-alpha in patients with asymptomatic human immunodeficiency virus (HIV) infection. A randomized, placebo-controlled trial.

STUDY OBJECTIVE: To evaluate the toxicity and clinical efficacy of interferon-alpha 2b (IFN-alpha) in patients with asymptomatic human immunodeficiency virus (HIV) infection. DESIGN: Randomized, placebo-controlled, and double-blind study. SETTING: Outpatient clinic of a government referral-based research hospital. PATIENTS: Volunteer sample of 34 patients with asymptomatic HIV infection who had CD4 counts of 400 cells/mm3 or more, positive peripheral blood mononuclear cell cultures for HIV, or p24 antigenemia. INTERVENTIONS: Patients were randomly assigned to receive either IFN-alpha or placebo, 35 x 10(6) units per day subcutaneously. Doses of IFN-alpha or placebo were modified according to predefined laboratory and clinical criteria. Therapy lasted at least 12 weeks. MEASUREMENTS AND MAIN RESULTS: Seventeen patients were randomly assigned to each group. The two groups had similar mean CD4 counts at study entry. Thirty-five percent of patients assigned to receive IFN-alpha withdrew from the study because of toxicity. The average daily dose of IFN-alpha was 17.5 x 10(6) units. All patients receiving IFN-alpha reported flu-like symptoms; other toxicities included granulocytopenia (55%) and elevated liver enzyme levels (45%). While receiving IFN-alpha, 7 patients (41%) became HIV culture negative (three or more consecutive negative peripheral blood mononuclear cell cultures taken at least 2 weeks apart). In contrast, 2 patients in the placebo group (13%) became culture negative while on study (P = 0.05). During the treatment period, CD4 lymphocyte percentages were sustained at or above the baseline level in patients receiving IFN-alpha and declined slightly in patients receiving placebo. Of the 32 study patients followed after study (range, 5 to 33 months), no patients in the IFN-alpha group developed an acquired immunodeficiency syndrome (AIDS)-defining opportunistic infection, compared with 5 patients in the placebo group (P = 0.02). CONCLUSIONS: Treatment of early-stage HIV infection with IFN-alpha can result in a decrease in frequency of viral isolation. Although its use may be accompanied by dose-dependent toxicities, IFN-alpha may have a role in slowing progression of HIV disease.

Adolescent↗
PubMed1990

Trimetrexate-leucovorin dosage evaluation study for treatment of Pneumocystis carinii pneumonia.

To determine the maximal tolerable dosage of trimetrexate for treatment of pneumocystis pneumonia, 25 patients were treated each day with 45 mg/m2 of trimetrexate and 80 mg/m2 of leucovorin; 10 received 60 mg/m2 and 80 mg/m2; 12 received 60 mg/m2 and 160 mg/m2; and 6 received 90 mg/m2 and 160 mg/m2, respectively. Leucovorin was increased twofold and trimetrexate reduced by 50% or suspended briefly for various levels of neutropenia and thrombocytopenia until blood counts increased. Dosage-modifying hematologic toxicity occurred in 12 (46%), 8 (80%), 9 (75%), and 4 (67%) patients with the respective groups. Cytopenias were in each case reversible and other toxicities were well tolerated. All survivors but one were able to receive a full 21 doses of trimetrexate. Twenty-four (92%), 10 (100%), 7 (58%), and 4 (80%) of patients in the respective groups survived. Thus, the 45 mg/m2/day dosage of trimetrexate with 80 mg/m2/day of leucovorin resulted in the least dosage-modifying toxicity and excellent efficacy. This combination should be selected for studies to compare trimetrexate with other therapies for pneumocystis pneumonia.

Acquired Immunodeficiency Syndrome↗
PubMed1990

The relationship between admission criteria and practice preferences.

A continual decline in the number of occupational therapists selecting mental health as their practice area has resulted in a personnel shortage. This study aimed at examining admission criteria to one occupational therapy program and the relationship of these criteria to practice preferences at admission. The question of whether current admission criteria are biased against those applicants preferring mental health practice is pertinent if the personnel shortage in mental health is to be alleviated. An analysis of the differences in practice preferences between accepted, alternate, and rejected groups of applicants indicated that such a bias did not exist. When admission was recalculated with only grade point average instead of the current procedure of a weighted combination of grade point average and interview, it was found that the admitted class would have contained more students preferring mental health practice. Additional research is recommended to further examine admission criteria and their relationship to practice.

Attitude↗
PubMed1990

Annexins I-VI in secretory ameloblasts and odontoblasts of rat incisor.

Immunoblot analyses and ultrastructural immunogold studies have been conducted on annexins in the secretory ameloblasts and odontoblasts of the rat incisor. Annexins I and II were seen in the soluble and particulate fractions of the enamel-related portion but not in the dentin-related portion. These proteins were visualized in the cytosol, near to the plasma membrane of Tomes' processes and in secretory vesicles in the ameloblasts. The forming enamel was also labeled. Annexins III, VI an V were detected in both the soluble and particulate fractions of the enamel-and dentin-related portions. Annexin IV was mainly localized in the proximal and distal areas of the secretory ameloblasts and virtually absent from in the supranuclear area. Annexin V was mainly detected in the cytosol of the cells and to a lesser extent near the plasma membrane. Annexin VI was mainly detected in the particulate fraction of enamel- and dentin-related portions. It was seen in the mitochondria and in the subplasmalemmal undercoat. All these proteins may play a role in exocytosis and endocytosis. They are implied in the regulation of cell calcium, but not in the transfer of calcium through the cells in the direction of the forming enamel and dentin, except annexins I and II since they are both present in the secretory vesicles and in the forming enamel.

Ameloblasts↗