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Biomedical subjects

S J Olsen

Publications and source records attributed to S J Olsen.

At least 37 records · Page 2Linked to original sources

Evidence against KSHV infection in the pathogenesis of multiple myeloma.

Kaposi's sarcoma-associated herpesvirus (KSHV) is likely to play a pathogenic role in Kaposi's sarcoma, body cavity-based primary effusion lymphoma and a subset of Castleman's disease. A recent polymerase chain reaction (PCR)-based study reported an association between KSHV and multiple myeloma (MM). We searched for KSHV infection in MM patients by serology, PCR and immunohistochemistry. In addition, we cultured dendritic and stromal cells from MM patients. KSHV antibodies were universally absent from MM patients (0/25) whereas EBV antibodies were nearly ubiquitous (24/25). All of the bone marrow biopsies (0/16) and negative controls (0/4) were vIL-6 negative. None of the bone marrow aspirates (0/6) or biopsies (0/3), peripheral blood mononuclear cells (0/8), mononuclear apheresis cells (0/5) or dendritic cell cultures (0/5) were positive by PCR. One of the MM stromal cell cultures (1/7) was positive for KSHV DNA by PCR and weakly positive on direct southern hybridization using a probe to the terminal repeat region. However, this same patient was PCR negative using another primer set, KSHV seronegative, and negative for vIL-6 immunostaining. Our results suggest that the KSHV DNA positivity rate among MM patients is much lower than previously reported.

Antibodies, Viral↗

Risk of Kaposi's sarcoma-associated herpes virus transmission from donor allografts among Italian posttransplant Kaposi's sarcoma patients.

Kaposi's sarcoma-associated herpesvirus (KSHV) is a newly discovered herpes virus found in all forms of Kaposi's sarcoma (KS) including KS among immunosuppressed transplant patients. It is unknown whether this virus is transmitted by organ transplantation or is reactivated during immunosuppression among those patients infected before transplantation. To investigate the risk of KSHV transmission during organ transplantation, we conducted a case-control study of transplant recipients with and without KS matched to their respective donors. Sera were collected at time of transplantation and tested in a randomized and blinded fashion using four KSHV serologic assays testing for antibodies to both latent and lytic phase antigens. Ten (91%) of 11 organ recipients who developed KS were seropositive prior to transplantation by one or more of the assays compared with two (12%) of 17 control organ recipients (OR = 75, 95% CI = 4.7, 3500). KS cases were more likely to have been born in southern Italy where KS is endemic than the recipient controls or either donor group. Only four (36%) of 11 donors to case patients and three (18%) of 17 donors to control patients were seropositive (P = .38, two-tailed Fisher's exact test). KSHV transmission could not be ruled out for the single KS patient seronegative at transplantation and clear evidence for organ-related transmission was found for another KS patient outside of the case-control study. Antibodies to KSHV are detectable in the sera from most transplant recipients before initiation of immunosuppressive treatment suggesting that KS among immunosuppressed transplant patients is primarily due to virus reactivation. KSHV transmission, however, from an infected allograft can occur, and our study reports the first documented case of person-to-person transmission of KSHV.

Adult↗

The effect of sorivudine on dihydropyrimidine dehydrogenase activity in patients with acute herpes zoster.

OBJECTIVE: Bromovinyl-uracil (BVU) is the principal metabolite of sorivudine, a potent anti-zoster nucleoside. BVU binds to, and irreversibly inhibits, the enzyme dihydropyrimidine dehydrogenase (DPD). The objective of this study was to assess the time course of recovery of DPD activity after oral administration of sorivudine in patients with herpes zoster and to correlate restoration of DPD activity and levels of uracil with the elimination of sorivudine and its metabolite BVU from the circulation. METHODS: Sorivudine was given orally as 40 mg once-daily doses for 10 consecutive days to a total of 19 patients with herpes zoster. Serum sorivudine, BVU, and circulating uracil and DPD activity in peripheral blood mononuclear cells (PBMCs) were determined before, during, and after administration of sorivudine. RESULTS: BVU was eliminated from the circulation within 7 days after the last sorivudine dose. DPD activity in PBMCs, which was completely suppressed in 18 of the 19 subjects and markedly suppressed in the remaining subject during administration of sorivudine, recovered to baseline levels within 19 days after the last dose of sorivudine in all subjects and within 14 days in all but one of the subjects. The restoration of DPD activity was temporally associated with elimination of BVU from the circulation. The elevated uracil concentrations produced by inhibition of DPD activity fell rapidly after cessation of sorivudine administration and also were temporally associated with elimination of BVU from the circulation. The time course of recovery of DPD activity in three patients with renal impairment was similar to that of the other subjects. CONCLUSIONS: This study indicates that sorivudine therapy is associated with a profound depression of DPD activity. Recovery of DPD activity occurred within 4 weeks of the completion of sorivudine therapy, which indicates that fluorinated pyrimidines may be safely administered 4 weeks after completion of sorivudine therapy.

Acute Disease↗

Validity of hospital discharge data regarding intentionality of fatal pediatric injuries.

This study of hospitalized fatal injuries to children in New York City (1991-1992) compares the classification of injury intention on hospital discharge data with that on death certificates in 302 injuries for which records could be linked. Using death certificates as the criterion, the sensitivity of hospital data for identifying intentional injuries ranged from 0.50 for children under age 5 years confidence interval (CI) = 0.27-0.73] to 0.85 for adolescents (95% CI = 0.80-0.90), and from 0.75 for white children (95% CI = 0.65-0.83) to 0.89 for nonwhite children (95% CI = 0.82-0.93). Hospital discharge data for this population appear to understate both the incidence and the proportion of fatal injuries due to intentional causes, particularly those occurring to very young children and to white children.

Adolescent↗

Assessing breast self-examination.

BACKGROUND: Women practice breast self-examination (BSE) according to their own schedule and skill. This variation in how BSE is performed has complicated the interpretation of studies of BSE efficacy and utilization. METHODS: We compared two methods commonly used to assess BSE competency, self-report of practice and ability to detect lumps in a model, among 81 women participating in a controlled toxicity trial of tamoxifen. Subjects were postmenopausal, were under 65 years of age, and had a history of breast cancer within the past 10 years but were currently free of disease. Women were asked to describe their usual BSE practice and were assigned a score (0-10) based on the number of recommended techniques and positions mentioned. Subjects were then instructed to examine a silicone breast model embedded with lumps (HealthEdCo) and to report any abnormalities. RESULTS: Overall proficiency was low by both measures. No significant correlation (r = 0.16, P = 0.15) was found between the two measures of proficiency. Higher correlations were observed among older women and among those practicing BSE monthly. CONCLUSIONS: This study suggests that the two techniques are not comparably evaluating BSE proficiency. Further, both of these methods are likely to be poor measures of true BSE practice.

Aged↗

Cancer prevention and screening activities reported by African-American nurses.

PURPOSE/OBJECTIVES: To describe the cancer prevention and screening activities of African-American nurses prior to their participation in a national workshop on cancer prevention and screening. The hypothesis tested was that African-American nurses would describe few prevention and screening behaviors. DESIGN: 18-month, longitudinal, descriptive study. SETTING: National survey. SAMPLE: 360 African-American nurses who applied for participation in a National Cancer Institute/Oncology Nursing Society workshop received study questionnaires. One hundred forty-six questionnaires were returned. The final sample was 64 nurses citing involvement in prevention/screening activities. METHODS: Self-administered quantitative/qualitative questionnaire mailed to nurses two weeks prior to the workshop. Quantitative data analyzed using descriptive statistics; a clustering technique was used to categorize responses emerging from qualitative data. MAIN RESEARCH VARIABLE: Cancer prevention and screening activities of African-American nurses six months prior to the workshop. FINDINGS: Respondents reported involvement in 11 categories (618 prevention/screening activities), predominantly in those of life-style (86%), education (77%), and clinical screening (58%). Respondents practiced 64% of the activities on a voluntary basis. Respondents provided prevention/screening education to more than 8,900 community members. CONCLUSION: African-American nurses favorably influence cancer prevention and screening beliefs and practices of clients in their communities. IMPLICATIONS FOR NURSING PRACTICE: A survey approach can describe cancer prevention/screening behaviors of African-American nurses. These nurses are an effective resource for community education.

Adult↗

Cancer prevention and early detection in ethnically diverse populations.

Providing cancer screening to the diverse minority subgroups of the United States is a challenge. In order to effectively screen the African American, Hispanic, Asian/Pacific Islander, Native American, Native Alaskan, and Native Hawaiian populations, cancer screening methods must be ethically and culturally based. Nurses must also strive make preventive care accessible to the underserved.

Black or African American↗

Tissue distribution of amphotericin B lipid complex in laboratory animals.

Amphotericin B lipid complex (ABLC), under development for the treatment of serious fungal disease, is not a true liposome but a complex of amphotericin B, dimyristoyl phosphatidylcholine and dimyristoyl phosphatidylglycerol with a particle size range of 1.6-6.0 microns. Tissue distribution of ABLC was determined in mice and rats after i.v. or i.p. administration. ABLC resembles typical liposomal preparations with amphotericin B concentrating in the reticuloendothelial system. After a single i.v. treatment with ABLC, amphotericin B was present in high concentrations in liver, lung and spleen of mice and rats while plasma levels were consistently low. Mouse liver contained 48% of the administered dose 1 h after treatment and always contained the largest amount of amphotericin B after ABLC treatment. In mice treated once daily for 7 consecutive days with 10 mg kg-1 ABLC, liver amphotericin B concentration reached 377 micrograms g-1. Tissue concentrations of amphotericin B were substantially lower when ABLC was given i.p. instead of i.v. with reticuloendothelial tissues containing 2- to 7-fold more after i.v. treatment. Animals treated with 10 mg kg-1 ABLC for 14 consecutive days showed no overt signs of toxicity and had only transient changes in liver and kidney function after treatment.

Amphotericin B↗

Amphotericin B lipid complex therapy of experimental fungal infections in mice.

The amphotericin B lipid complex (ABLC), which is composed of amphotericin B and the phospholipids dimyristoyl phosphatidylcholine and dimyristoyl phosphatidylglycerol, was evaluated for its acute toxicity in mice and for its efficacy in mice infected with a variety of fungal pathogens. ABLC was markedly less toxic to mice when it was administered intravenously; it had a 50% lethal dose of greater than 40 mg/kg compared with a 50% lethal dose of 3 mg/kg for Fungizone, the desoxycholate form of amphotericin B. ABLC was efficacious against systemic infections in mice caused by Candida albicans, Candida species other than C. albicans, Cryptococcus neoformans, and Histoplasma capsulatum. ABLC was also efficacious in immunocompromised animals infected with C. albicans, Aspergillus fumigatus, and H. capsulatum. Against some infections, the efficacy of ABLC was comparable to that of Fungizone, while against other infections Fungizone was two- to fourfold more effective than ABLC. Against several infections. Fungizone could not be given at therapeutic levels because of intravenous toxicity. ABLC, with its reduced toxicity, could be administered at drug levels capable of giving a therapeutic response. ABLC should be of value in the treatment of severe fungal infections in humans.

Amphotericin B↗

Evaluation of SQ 34,514: pharmacokinetics and efficacy in experimental herpesvirus infections in mice.

The new antiviral nucleoside SQ 34,514 [(1R-1 alpha, 2 beta, 3 alpha)-2-amino-9- [2,3-bis(hydroxymethyl)cyclobutyl]-6H-purin-6-one], the active R isomer of racemic SQ 33,054 (cyclobut-G), was evaluated for efficacy in the treatment of herpesvirus infections in mice. SQ 34,514 was orally efficacious in a herpes simplex virus type 1 (HSV-1) systemic infection, an intracerebral HSV-2 infection, a vaginally induced HSV-2 infection in ovariectomized mice, and in a systemic murine cytomegalovirus infection. SQ 34,514 compared favorably with acyclovir and ganciclovir in the treatment of these experimental infections. In mice, SQ 34,514 had an oral bioavailability of 80% based on urinary excretion. SQ 34,514 may have potential value in the therapy of HSV and cytomegalovirus infections in humans.

Animals↗

In vivo evaluation of tigemonam, a novel oral monobactam.

Tigemonam, a new monobactam with excellent activity against gram-negative bacteria, was evaluated for in vivo efficacy and absorption after oral administration to laboratory animals. Tigemonam is absorbed when administered orally to mice and dogs. In a variety of gram-negative systemic infections in mice, orally administered tigemonam was efficacious in all infections studied. Comparison drugs such as amoxicillin, cephalexin, and cefaclor were less efficacious, especially in infections caused by beta-lactamase-producing organisms. In localized infections, tigemonam also demonstrated excellent in vivo activity. In acute pyelonephritis in mice caused by Escherichia coli or Proteus sp., tigemonam was very effective. In a rat lung model with Klebsiella pneumoniae, tigemonam was active with a median effective dose of 46 mg/kg compared with 160 mg/kg for cefaclor and over 200 mg/kg for amoxicillin. Tigemonam was well absorbed in laboratory animals and with its excellent gram-negative spectrum of activity should prove of value in oral antibiotic therapy in humans.

Acute Disease↗

Herd incidence of bovine mastitis in four danish dairy districts. III. Relation between frequency of mastitis and cell counts on bulk molk samples.

The correlations between monthly bulk milk cell counts and the actual frequency of mastitis was investigated in 399 Danish dairy farms with a total of about 7000 cows. The correlation coefficients varied from 0.3 to 0.5. Correlations were improved by using more than one cell count, but not further improved by using more than two cell counts. The correlations were higher for large than for small herds. It was not possible by combining cell counts in different ways, as indicated in (Table IV, to point out every heavily mastitis-affected herd without also pointing out some not so heavily affected ones. Table IV shows what infection levels can be expected when different criteria based on bulk milk cell counts are applied. The figures cannot be transferred directly from Danish conditions to conditions in other countries, but similar tendencies can probably be found anywhere.

Animals↗