Enteral Bioavailability of Human Granulocyte Colony Stimulating Factor Conjugated with Poly(ethylene glycol)

Purpose. The focus of this paper is to demonstrate that pegylation of a therapeutic protein, recombinant human granulocyte colony stimulating factor (PEG-G-CSF), results in an increase in stability and in retention of in vivo bioactivity when administered by the intraduodenal route and may, therefore, be a suitable form of the protein for inclusion in an oral delivery formulation. Methods. The ability of PEG-G-CSF to elicit a therapeutic response from the enteral route was investigated by two methods of intraduodenal dosing in an in vivo model to determine the optimal dosing method: by slow, constant infusion, or by a single bolus administration. Results. Circulating levels of the proteins confirmed that PEG-G-CSF was delivered into the systemic circulation from the enteral route and that biological activity was retained. Bioavailability from the enteral route by the constant infusion method was calculated from the intravenous administration of the proteins to be between 1.8 and 3.5% while un-modified G-CSF failed to elicit a quantifiable response by this method. Bolus administration of PEG-G-CSF also resulted in biological activity although responses were short lived and significantly lower than with the pegylated formulation. Conclusions. The possible mechanisms of enteral delivery of PEG-G-CSF are discussed. Our results indicate that oral delivery of pegylated G-CSF may be possible and in fact, preferable to using the un-modified form of the therapeutic.     

Pay Status as a Predictor of Outcome in Surgical Treatment of Obesity

Background: Higher complication rates and lower success in surgery for severe obesity have been reported for patients with government pay status. We examined the effect of pay status upon outcome in surgical treatment of obesity. Methods: This was an observational study from an aggregate data set of individual patient information. Government pay status (G) was defined as full or partial medical care payment through Medicare, Medicaid, or Veterans Administration. Payment entirely by private insurance was defined as private (P). Operations were classified as either simple (S, gastric restriction) or complex (C, gastric restriction with small bowel bypass). Two measures of outcome, perioperative complication rate and weight loss success (≤50% excess weight), were examined to determine pay status effect. Results: More G than P patients were treated with simple procedures (79% vs 51%, p < 0.05). Perioperative complication rates were more common for G than P patients (14.4% vs 9.1%, p < 0.05). One-year weight loss success was higher for P than G, regardless of operation type. Conclusion: Pay status should be included in characterization of patient groups and in the analysis of results when effectiveness of surgical treatment for severe obesity is reported.     

Cervical epithelial abnormalities are significantly associated with non-HPV lower genital tract infection in female contacts of warts*

Objectives

• 1 To assess the prevalence of cervical epithelial abnormalities in female sexual partners of men with anogenital warts.
• 2 To examine the possible association between non-HPV lower genital tract infection, and cervical epithelial abnormalities.

Design Retrospective review of the medical records of all female sexual partners of men with anogenital warts attending the GUM clinic in 1990. Setting and patients The department of Genito-Urinary Medicine (GUM), Royal Victoria Hospital, Belfast. Sixty-two female sexual partners of men with anogenital warts. Methods Cervical cytology and colposcopy was performed on all patients. Biopsies were taken of colposcopically identified cervical epithelial abnormalities, Non-HPV lower genital tract infection was detected by routine genito-urinary screening. Demographic data and sexual history were obtained by questionnaire. Outcome measured Overall prevalence of cervical epithelial abnormalities and correlation to the presence of non-HPV lower genital tract infection in the female. Results The overall prevalence of cervical epithelial abnormalities detected with colposcopy and biopsy was 46.8%. The prevalence of koilocytosis and cervical intraepithelial neoplasia (CIN) was 69.6% when non-HPV lower genital tract infection was detected by routine genito-urinary screening. When no infection was detected the prevalence was 33.3% (P < 0.05).     

Electroconvulsive Therapy in Adolescents

Because of the limited number of case reports on the use of electroconvulsive therapy (ECT) in adolescent psychiatric patients, we retrospectively reviewed the medical records of 20 young patients who underwent ECT. They constituted all the patients 相似文献   

The effects of Δ9-tetrahydrocannabinol alone and in combination with cannabidiol on fixed-interval performance in rhesus monkeys

It has been reported that cannabidiol (CBD) antagonizes the effects of ⁹-tetrahydrocannabinol (THC) on operant behavior in rats and pigeons. We have replicated this finding with rhesus monkeys. Four rhesus monkeys were trained to lever press on a fixedinterval 5-min schedule of food presentation with a 1-min limited hold and 1-min time out between successive intervals. The effects of 0.3 and 1.0 mg/kg THC alone were determined three times during the experiment; before the CBD-THC interaction, after the CBD-THC interaction and once with the CBD vehicle. A dose of 30 mg/kg CBD, which alone resulted in a 24% reduction in responding, completely antagonized the response rate reduction produced by 0.3 mg/kg THC. The effects of THC revealed a rate-dependent effect that did not conform to the log-linear rate-dependency plots described for most other drugs.This research was reported at the FASEB Meeting in Atlantic City, NJ in 1978 [Fed. Proc. 37: 739 (Abs.) 1978]     

Comparing the Self-Image of Prepubescent Girls Before and After Four Sessions on Body Awareness

The purpose of this research was to determine whether increasing the knowledge of prepubescent girls concerning emotional and physiological changes would result in a more positive self-image. Eleven Junior Girl Scouts comprised the sample. The procedure consisted of pretesting with the "How I See Myself Scale" and the "Sex Knowledge Test," teaching a four-session Body Awareness Course and posttesting with pretest instruments. Body awareness of the participants was significantly increased following the course. Self-image was improved, although not significantly. Each participant indicated a strong interest in body awareness and her developing sexuality. This study demonstrates that prepubescent females need and desire factual information about their physical and emotional concerns.     

Predicting genitourinary toxicity in patients receiving cisplatin-based combination chemotherapy: a cancer and leukemia group B study

Summary Assessment of renal function prior to cisplatin chemotherapy has long been based on measurement of creatinine clearance by 24-hour urine collection (CrC _meas). Estimated creatinine clearance (CrC _est) as calculated from the patient's age, weight, and serum creatinine level has been suggested as an adequate surrogate for CrC _meas, as it provides advantages of improved convenience, decreased cost, and possibly increased accuracy. We studied 847 patients receiving cisplatin-based chemotherapy on Cancer and Leukemia Group B (CALGB) protocols to determine whether the CrC _meas, CrC _est, or serum creatinine value or the age of the patient would predict the subsequent genitourinary (GU) toxicity. Both CrC _meas (P=0.001) and CrC _est (P=0.02) were predictive of subsequent grade 2+GU toxicity, with CrC _meas being a slightly better predictor. Patient age also influenced subsequent GU toxicity, with the risk increasing with age (P=0.0008). When patients were classified by age group and by CrC _meas, distinct subgroups were identified, with differences in the risk for grade 2+GU toxicity ranging from 14% to 32%. Using a logistic model to assess the probability of grade 2+GU toxicity, we found that an age of60 years (P=0.005), a CrC _meas value of <75 ml/min (P=0.004), and the risk characteristics of the individual cisplatin trial were important, whereas CrC _est was not. Furthermore, CrC _est proved to be a poor predictor of a CrC _meas value of <75 ml/min, misclassifying nearly half of the patients to a lower-risk subgroup. In summary, both CrC _meas and the patient's age independently provided predictive information concerning cisplatin GU toxicity. Our data support the continued clinical usefulness of determining the CrC _meas value prior to the administration of cisplatin-based chemotherapy to most patients.This study is supported by the following NIH grants: CA 26806, CA 33601, CA 11789, CA 31983, USAThe opinions or assertations contained herein are the private views of the authors and are not to be construed as official or as reflecting the views of the Department of the Army or the Department of Defense of the United States of America     

Brainstem maturation after antenatal steroids exposure in premature infants as evaluated by auditory brainstem-evoked response.

OBJECTIVE: Antenatal steroids result in fetal lung maturation, but may retard brain development. Auditory brainstem-evoked response (ABR) is a noninvasive assessment of brainstem maturation. The objective of this study was to determine if antenatal steroids affect brainstem maturation in infants 相似文献