Biomedical subjects

S Owens

Publications and source records attributed to S Owens.

At least 55 records · Page 3Linked to original sources

PubMed1997

Effect of physical training on heart-period variability in obese children.

OBJECTIVE: The beat-to-beat variability in electrocardiogram intervals (RR, i.e., heart-period variability) provides information on cardiac autonomic activity that predicts arrhythmias and mortality rate in animals and adults. We determined the effect of physical training on heart-period variability in obese children. METHODS: Thirty-five subjects were randomly assigned to physical training and control groups. The training involved 4 months of exercise, 5 days per week, 40 minutes per day. Cardiovascular fitness was measured with submaximal heart rate during supine cycling; percentage of body fat was measured with dual-energy absorptiometry; and resting heart-period variability parameters were measured in a supine position. A pretraining to posttraining change score was computed for each variable. The effect of the training was determined by comparing the changes of the training and control groups. RESULTS: Compared with the control group, the trained group (1) reduced submaximal heart rate and percentage of body fat (p < 0.01); (2) increased in the root mean square of successive differences, a time-domain parameter reflective of vagal tone (p < 0.05); (3) decreased in low-frequency power expressed as a percentage of total power, a frequency-domain index of combined sympathetic and vagal activity (p < 0.03); and (4) decreased in the ratio of low- to high-frequency power, an index of sympathetic-parasympathetic balance (p < 0.01). CONCLUSIONS: In obese children, physical training alters cardiac autonomic function favorably by reducing the ratio of sympathetic to parasympathetic activity.

Adipose Tissue↗

PubMed1996

2'-O-aminopropyl ribonucleotides: a zwitterionic modification that enhances the exonuclease resistance and biological activity of antisense oligonucleotides.

Oligonucleotides containing 2'-O-aminopropyl-substituted RNA have been synthesized. The 2'-O-(aminopropyl)adenosine (APA), 2'-O-(aminopropyl)cytidine (APC), 2'-O-(aminopropyl)-guanosine (APG), and 2'-O-(aminopropyl)uridine (APU) have been prepared in high yield from the ribonucleoside, protected, and incorporated into an oligonucleotide using conventional phosphoramidite chemistry. Molecular dynamics studies of a dinucleotide in water demonstrates that a short alkylamine located off the 2'-oxygen of ribonucleotides alters the sugar pucker of the nucleoside but does not form a tight ion pair with the proximate phosphate. A 5-mer with the sequence ACTUC has been characterized using NMR. As predicted from the modeling results, the sugar pucker of the APU moiety is shifted toward a C3'-endo geometry. In addition, the primary amine rotates freely and is not bound electrostatically to any phosphate group, as evidenced by the different sign of the NOE between sugar proton resonances and the signals from the propylamine chain. Incorporation of aminopropyl nucleoside residues into point-substituted and fully modified oligomers does not decrease the affinity for complementary RNA compared to 2'-O-alkyl substituents of the same length. However, two APU residues placed at the 3'-terminus of an oligomer gives a 100-fold increase in resistance to exonuclease degradation, which is greater than observed for phosphorothioate oligomers. These structural and biophysical characteristics make the 2'-O-aminopropyl group a leading choice for incorporation into antisense therapeutics. A 20-mer phosphorothioate oligonucleotide capped with two phosphodiester aminopropyl nucleotides targeted against C-raf mRNA has been transfected into cells via electroporation. This oligonucleotide has 5-10-fold greater activity than the control phosphorothioate for reducing the abundance of C-raf mRNA and protein.

Exonucleases↗

PubMed1996

Pilot study of topical trifluridine for the treatment of acyclovir-resistant mucocutaneous herpes simplex disease in patients with AIDS (ACTG 172). AIDS Clinical Trials Group.

SUMMARY: Twenty-six AIDS patients were enrolled in an open label pilot study to evaluate the efficacy and toxicity of topical 1 percent ophthalmic trifluridine solution for the treatment of chronic mucocutaneous herpes simplex virus disease unresponsive to at least 10 days of acyclovir therapy. Susceptibility testing to acyclovir, trifluridine, and foscarnet was determined by plaque reduction assay. Twenty-four patients were evaluable for efficacy and 25 for toxicity analyses. Seven patients (29 percent) had complete healing of lesions. The overall estimated median time to complete healing was 7.1 weeks. An additional seven patients had > or = 50 percent reduction in lesion area. The overall estimated median time to 50 percent healing was 2.4 weeks. Ten (42 percent) patients discontinued treatment for reasons other than primary treatment failure and seven (29 percent) for failure to respond to therapy. Baseline patient characteristics associated with greater reduction in lesion area included higher Karnofsky score (p = 0.05), fewer lesions (p = 0.07), smaller lesion area (p = 0.11), and trifluridine susceptibility (p = 0.07). Eight (33 percent) patients developed new lesions outside of the treatment area while on study, reflecting the local nature of this therapy. No dose-limiting toxicity attributable to trifluridine was reported. Given the limited options for the treatment of acyclovir-resistant herpes simplex disease, topical trifluridine may be a useful alternative in selected patients.

AIDS-Related Opportunistic Infections↗

PubMed1995

A phase I trial of bryostatin 1 in patients with advanced malignancy using a 24 hour intravenous infusion.

Bryostatin 1 is a macrocyclic lactone derived from the marine invertebrate Bugula neritina. In vitro, bryostatin 1 activates protein kinase C (PKC), induces the differentiation of a number of cancer cell lineages, exhibits anti-tumour activity and augments the response of haemopoietic cells to certain growth factors. In vivo, bryostatin 1 is also immunomodulatory, but the range of tumours which respond to bryostatin 1 in xenograft tumour models is mostly the same as the in vitro tumour types, suggesting a direct mode of action. Nineteen patients with advanced malignancy were entered into a phase I study in which bryostatin 1 was given as a 24 h intravenous infusion, weekly, for 8 weeks. Myalgia was the dose-limiting toxicity and the maximum tolerated dose was 25 micrograms m-2 per week. The myalgia was cumulative and dose related, and chiefly affected the thighs, calves and muscles of extraocular movement. The mechanism of the myalgia is unknown. CTC grade 1 phlebitis affected every patient for at least one cycle and was caused by the diluent, PET, which contains polyethylene glycol, ethanol and Tween 80. Most patients experienced a 1 g dl-1 decrease in haemoglobin within 1 h of commencing the infusion which was associated with a decrease in haematocrit. Radiolabelled red cell studies were performed in one patient to investigate the anaemia. The survival of radiolabelled red cells during the week following treatment was the same as that seen in the week before treatment. However, there was a temporary accumulation of radiolabelled red cells in the liver during the first hour of treatment, suggesting that pooling of erythrocytes in the liver might account for the decrease in haematocrit. Total or activated PKC concentrations were measured in the peripheral blood mononuclear cells (PBMCs) of three patients for the first 4 h of treatment and during the last hour of the infusion. This showed that PKC activity was significantly modulated during the infusion. Bryostatin 1 is immunomodulatory in vitro, and we have confirmed this activity in vivo. An investigation of the first three cycles of treatment in seven patients showed an increased IL-2-induced proliferative response in peripheral blood lymphocytes and enhanced lymphokine-activated killer (LAK) activity. A previously reported rise in serum levels of interleukin 6 (IL-6) and tumour necrosis factor alpha (TNF 1) was not confirmed in our study; of nine patients in this study, including patients at all dose levels, none showed an increase in these cytokines.(ABSTRACT TRUNCATED AT 400 WORDS)

Adult↗

PubMed1995

Attitudes toward and knowledge of AIDS among African American social work students.

Social work students can be trained to assume critical roles in response to the acquired immune deficiency syndrome (AIDS) epidemic in the African American community. To effectively prepare social work students for these roles, educators must ascertain the knowledge and attitudes of students toward the epidemic. Although several researchers have studied the AIDS knowledge and attitudes of social work students in general, none have reported on the knowledge and attitudes of African American social work students as a group. In the present study, 48 graduate-level African American social work students responded to a questionnaire to measure these characteristics. Many students had incomplete knowledge about AIDS, felt unprepared to handle AIDS practice situations, and felt apprehensive about contact with people with AIDS. Social work educators need to take steps to ensure that African American social work students are prepared to intervene effectively in the AIDS epidemic.

Acquired Immunodeficiency Syndrome↗

PubMed1994

Phase II dose-ranging trial of foscarnet salvage therapy for cytomegalovirus retinitis in AIDS patients intolerant of or resistant to ganciclovir (ACTG protocol 093). AIDS Clinical Trials Group of the National Institute of Allergy and Infectious Diseases.

OBJECTIVE: To document response to foscarnet salvage therapy in patients with cytomegalovirus (CMV) retinitis who are intolerant of or resistant to ganciclovir. METHODS: Patients with AIDS and CMV retinitis who had documented hematologic intolerance or resistance to ganciclovir therapy received an induction course of foscarnet, 60 mg/kg every 8 h for 14 days, and subsequent chronic maintenance foscarnet therapy at a daily dose of 60, 90 or 120 mg/kg/day. The first 87 patients were randomly assigned to receive maintenance foscarnet at a dose of 60 or 90 mg/kg/day; all subsequent patients were assigned a maintenance dose of 120 mg/kg/day. RESULTS: A total of 156 evaluable patients were enrolled. Median time to retinitis progression and survival did not differ significantly among groups assigned to different maintenance foscarnet doses. Among patients with retinitis progression documented ophthalmologically occurring at < or = 2 week intervals, despite optimal doses of ganciclovir, time to progression on foscarnet therapy was a median 8 weeks at all doses studied. By dose assignment, there were no significant differences in serious drug-associated toxicity, although trends toward increased renal and hypocalcemic adverse events were observed at higher maintenance doses. CONCLUSION: In patients intolerant of ganciclovir, salvage foscarnet therapy resulted in a longer time to retinitis progression than reported previously in historic controls who terminated ganciclovir therapy. In patients who exhibited clinical resistance to ganciclovir, foscarnet appeared to have efficacy in controlling retinitis. No significant differences in either efficacy or toxicity were observed in the range of foscarnet maintenance doses studied.

AIDS-Related Opportunistic Infections↗

PubMed1993

Prevention of relapse of histoplasmosis with itraconazole in patients with the acquired immunodeficiency syndrome.

OBJECTIVE: To assess the efficacy and safety of itraconazole in preventing relapse of histoplasmosis after induction therapy with amphotericin B in patients with the acquired immunodeficiency syndrome (AIDS) and disseminated histoplasmosis. DESIGN: A prospective, multicenter, open-label clinical trial, with follow-up for at least 52 weeks. SETTING: Tertiary care hospitals participating in a clinical investigation sponsored by the National Institutes of Allergy and Infectious Diseases (AIDS Clinical Trial Group and Mycoses Study Group). PATIENTS: Forty-two patients with AIDS who had successfully completed induction therapy for disseminated histoplasmosis amphotericin B, at least 15 mg/kg body weight given over 4 to 12 weeks. INTERVENTIONS: Itraconazole, 200 mg given orally twice daily. MAIN OUTCOME MEASURES: Response to therapy, specifically prevention of histoplasmosis relapse, was the main outcome measure. Secondary end points were survival and the effect of therapy on Histoplasma capsulatum variety capsulatum antigen levels in urine and serum. Plasma itraconazole concentrations were measured to document drug absorption and compliance with therapy. RESULTS: The median follow-up was 109 weeks, and median survival was 98 weeks. Two relapses occurred (5%; 95% CI, 0.5% to 16%), one in a patient withdrawn from the study 18 weeks earlier and one in a patient who did not comply with the study therapy. Patients with elevated antigen levels at study entry showed clearance of antigen from urine and serum; urine specimens became negative in 43% of patients (CI, 26% to 59%), and serum specimens became negative in 75% of patients (CI, 56% to 94%). Only one patient discontinued treatment because of itraconazole toxicity (hypokalemia). CONCLUSIONS: Itraconazole, 200 mg twice daily, is safe and effective in preventing relapse of disseminated histoplasmosis in patients with AIDS. Antigen clearance from blood and urine correlates with clinical efficacy.

AIDS-Related Opportunistic Infections↗

PubMed1991

Williams' vulvovaginoplasty after supralevator total pelvic exenteration.

Seven patients had delayed Williams' vulvovaginoplasty after supralevator total pelvic exenteration. Of the three patients who died of carcinoma of the cervix (at 2, 5, and 15 months after vulvovaginoplasty), the first died before having a chance to attempt intercourse, but the other two had reported intercourse on at least two occasions after the reconstruction. One of the patients described the experiences as neither pleasant nor unpleasant but stated that her husband seemed satisfied. The other patient described the experience as satisfactory to both herself and her husband. The remaining four patients are alive with no evidence of recurrent disease at 28, 42, 56, and 106 months after operation. Two of these patients have reported entirely satisfactory sexual relations approximating pre-exenteration frequency, but the remaining two have not had sexual relations since surgery. Both give the main reason for this as lack of opportunity. The Williams' vulvovaginoplasty appears to be a reasonable alternative for vaginal reconstruction in patients who will have and especially who have had exenteration. To improve results, other methods of vaginal reconstruction should continue to be evaluated.

Adult↗

PubMed1991

Laparoscopic treatment of painful perihepatic adhesions in Fitz-Hugh-Curtis syndrome.

This report illustrates a case of Fitz-Hugh-Curtis syndrome associated with pelvic inflammatory disease in which the clinical symptom of right upper quadrant pain was severe and persistent despite appropriate antibiotic therapy. Because of the atypical course, an extensive work-up was performed to rule out other possible etiologies for the pain. In this context, a laparoscopy was performed and identified dense adhesions between the liver and the anterior abdominal wall. These adhesions were safely and successfully lysed using a KTP/532 laser through a second puncture site. After surgery the pain was completely resolved, with no further recurrence after 6 months of follow-up.

Abdominal Pain↗

PubMed1990

Locomotion, active choice, and spatial memory in children.

In two studies, children between 4 and 6 years old were tested on a radial search task requiring nonredundant sampling of eight identically labeled positions in a room. In the training phase (5 days), children made free choices by walking between positions, were passively transported in a pushchair, actively directed their own route from a pushchair, or were led on foot to positions selected by the experimenter. When tested (whether walking or directing while seated in a pushchair), children who had either walked independently or directed the experimenter while being pushed performed competently; those led on foot without spatial choice performed almost as well. Only the children who had neither independent locomotor experience nor autonomous choice performed very poorly. The results are related to neurobiological models of spatial cognition and may have implications for the transportation of children with mobility problems.

Child, Preschool↗

PubMed1989

Enhancement of primary and secondary immune responses by interferon-gamma.

We have investigated the effects of interferon-gamma (IFN-gamma) administered with "G" glycoprotein of vesicular stomatitis virus (VSV), on the neutralizing antibody response. Treatment of mice or cattle with recombinant DNA-derived IFN-gamma at the time of primary immunization with "G" glycoprotein enhanced the secondary virus-neutralizing antibody response that followed a booster administration of the same antigen without IFN-gamma treatment. Enhancement was statistically significant, and occurred at relatively low doses of IFN-gamma in the absence of any additional adjuvants. Cattle treated with IFN-gamma at the time of primary immunization were also more resistant to VSV challenge than those immunized without IFN-gamma treatment. Such treatment in conjunction with primary immunization may therefore provide a practical means of enhancing protection from viral challenge without inflammatory adjuvants or boosters.

Adjuvants, Immunologic↗

PubMed1989

Ovarian management at the time of radical hysterectomy for cancer of the cervix.

Ovarian management at the time of radical hysterectomy for cervical cancer was reviewed retrospectively over a 7-year period. All patients had early-stage cancer except three who had stage IIB disease. Approximately 80% of patients had squamous cancer and 20% adenocarcinoma or adenosquamous carcinoma. The mean age was 44, and 24% of patients were 35 or younger. Ninety-nine patients had their ovaries removed. None of the ovaries contained metastatic disease including 22 patients with adenocarcinoma or adenosquamous carcinoma. Of the 17 patients with retained ovaries 14 had transposition into the paracolic gutters. Only one of the 14 patients with transposed ovaries developed symptoms of ovarian failure. No patients with retained ovaries developed metastatic disease or required reoperation secondary to new ovarian pathology. It is our opinion that normal ovaries can be preserved in young women at the time of radical hysterectomy for early cervical cancer regardless of histologic type.

Adenocarcinoma↗

PubMed1989

Epidemiology and diagnosis of acute conjunctivitis at an inner-city hospital.

Chlamydia has been found to be the cause of a high percentage of cases of neonatal and chronic conjunctivitis in an inner-city population. To assess the etiology and epidemiology of acute conjunctivitis in this population, conjunctival scrapings were sampled from 45 patients presenting to an ocular emergency room; and replicate chlamydial, viral, and bacterial cultures and cytology tests were done. No cases of chlamydial conjunctivitis were diagnosed, although a viral etiology was established in 36% of the cases and a bacterial etiology in 40%. Twenty-four percent of the cases were not diagnosed. The authors recommend limiting the initial laboratory workup of patients with acute conjunctivitis to obtaining conjunctival smears for Gram and Giemsa staining. Chlamydial direct immunofluorescent monoclonal antibody (DFA) should be done if the patient is sexually active. Hyperacute conjunctivitis or acute conjunctivitis refractory to treatment mandates a more complete set of laboratory tests.

Acute Disease↗

PubMed1989

The kinetics of human granulopoiesis following treatment with granulocyte colony-stimulating factor in vivo.

Cell proliferation in the bone marrow and blood of two patients with metastatic breast cancer who were treated with granulocyte colony-stimulating factor was studied by using [3H]thymidine labeling and autoradiography. Additionally, the fate of neutrophils labeled with 99mTc-hexamethylpropyleneamineoxime was observed following granulocyte colony-stimulating factor infusion. Proliferation increased in all stages of granulopoiesis, but a significant amount of the increased production stemmed from a greater input to the myeloblast compartment. Changes in the myelogram combined with the increased labeling indicated a faster throughput of cells, which resulted in labeled cells appearing in the circulation within 1 day compared to the normal 4 or 5 days. The 99mTc studies demonstrated no sequestration of circulating neutrophils by spleen, lungs, or liver. The half-life of the circulating neutrophils was not significantly changed, and calculations from the flow of labeled cells to the peripheral blood indicated an increase of 3.2 extra amplification divisions during neutrophil development. The dramatic neutrophil response to granulocyte colony-stimulating factor can therefore be accommodated by a relatively modest increase in granulopoietic activity.

Adult↗

PubMed1989

Ocular melanoma.

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Adult↗

PubMed1988

Protection of cattle against rinderpest with vaccinia virus recombinants expressing the HA or F gene.

Rinderpest is a highly contagious ruminant viral disease manifested by a rapid course and greater than 90% mortality. Infectious vaccinia virus recombinants were constructed that express either the hemagglutinin or the fusion gene of rinderpest virus. All cattle vaccinated with either recombinant or with the combined recombinants produced neutralizing antibodies against rinderpest virus and were protected against the disease when challenged with more than 1000 times the lethal dose of the virus.

Animals↗

PubMed1988

High levels of interferon in synovial fluid of retrovirus-infected goats.

A high level of interferon (IFN) was found in the synovial fluid of goats with naturally acquired caprine arthritis-encephalitis (CAE), a disease caused by caprine arthritis-encephalitis virus (CAEV), a nononcogenic retrovirus of the lentivirus group. Intraarticular injection of CAEV or control inoculum in the joints of affected goats caused increased amounts of IFN production in synovial fluid.

Animals↗

PubMed1985

Preliminary characterization of a serum viral inhibitor in goats.

A serum viral inhibitor (SVI) was isolated from goats and partially characterized. The inhibitor prevented the cytopathic effects of vesicular stomatitis virus, encephalomyocarditis virus, and a caprine herpesvirus, indicating broad antiviral activity. The SVI was distinct from interferon because SVI did not induce an antiviral state in cells (ie, lack of protection of SVI-treated cells from virus challenge). The SVI had activity on heterologous cells, including human, bovine, and ovine cells. The lack of antiviral activity in mouse cells indicated that SVI was not an antibody. Like fibroblast interferon, however, SVI was sensitive to trypsin, was acid stable at pH 2 and 4 C for 4 days, was heat stable at 56 C for 1 hour, and could not be sedimented by centrifugation at 100,000 X g for 4 hours.

Animals↗