Biomedical subjects
Publications and source records attributed to E Ramsey.
Nucleic acid extraction and human immunodeficiency virus type 1 (HIV-1) genotyping using the NucliSens miniMAG platform and the TruGene HIV-1 genotyping kit gave HIV-1 sequence data from HIV-1-negative plasma spiked with 100 copies/ml reference HIV-1 RNA and from low-viremia clinical samples (<500 copies/ml) without the need for ultracentrifugation or nested second-round PCR.
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OBJECTIVES: Chronic nonbacterial prostatitis/chronic pelvic pain syndrome (CPPS) has clinical and perhaps etiologic characteristics similar to interstitial cystitis. Pentosan polysulfate sodium (PPS), an oral medication indicated for the treatment of interstitial cystitis, has shown moderate benefit in reducing chronic pelvic pain and voiding symptoms in patients with interstitial cystitis. We undertook a prospective open-label, multicenter Phase II pilot study to examine the potential efficacy of PPS in the treatment of CPPS in men, using outcome tools validated for CPPS in men. METHODS: Patients with a diagnosis consistent with National Institutes of Health (NIH) CPPS category IIIA (inflammatory) were treated with PPS, 100 mg three times daily, for 6 months. The evaluation at baseline, 3 months, and 6 months consisted of the Symptom Severity Index, a Symptom Frequency Questionnaire, the NIH-Chronic Prostatitis Symptom Pain Index (NIH-CPSI), a quality-of-life assessment, and a subjective global assessment. RESULTS: Thirty-two patients (mean age 45.5 +/- 11 years; duration of symptoms 9.2 +/- 12 years) were enrolled in five centers; 28 patients were available for evaluation. Seven patients experienced drug-related side effects, including hair loss (n = 2), headache (n = 2), mild nausea (n = 1), mild weight gain (n = 1), and skin flushing (n = 1). The decrease in frequency (Symptom Frequency Questionnaire 28.1 to 17.9), severity (Symptom Severity Index 53.6 to 36.3), and combined location/frequency/severity of pain (NIH-CPSI pain 14.5 to 9.2) symptom scores at 6 months compared with baseline was significant. The decrease was associated with a significant improvement in patients' quality of life (quality-of-life assessment 5.3 to 3.8). Forty-three percent of the patients had a greater than 50% improvement in the Symptom Frequency Questionnaire, Symptom Severity Index, and NIH-CPSI (rated as clinically significant improvement). At 6 months, mild, moderate, and marked improvement was noted (subjective global assessment) by 33%, 19%, and 15% of the patients, respectively. CONCLUSIONS: PPS is well tolerated and appears to have efficacy in reducing the severity and frequency of general symptoms, reducing specific pain symptoms, and improving the quality of life in many male patients with CPPS. The results of this study justify the initiation of a randomized controlled trial comparing the safety and efficacy of PPS to placebo.
OBJECTIVES: To describe the initial experience of a newly designed temporary urethral catheter, ContiCath, as an aid in the management of postoperative or temporary outflow obstruction. In patients with normal detrusor and sphincter function, this catheter allows volitional voiding while maintaining an open prostatic urethra. METHODS: In a pilot study, 64 nonconsecutive patients with postoperative or temporary urinary retention, at eight clinical trial sites, were enrolled for the placement of this temporary catheter. Three patients did not have the catheter placed because of placement failure because of either a large median lobe or a urethral stricture. The remaining 61 patients were divided into three groups: those with non-neuropathic causes of retention and retention for 1 week or less (37 patients), those with non-neuropathic causes of retention and retention for longer than 1 week (19 patients), and those with neuropathic causes of retention and retention for longer than 1 week (5 patients). The ContiCath is placed in the office setting, in the same fashion as a Foley catheter. A blue prolene tether extends from the bulbar urethra to the meatus to assist in the removal of the device. Patients were then reassessed at 3 hours, and at 7, 14, 21, and 28 days, at which point the device was removed. RESULTS: In patients with a neuropathic cause for their retention (5 patients) and those with non-neuropathic causes of retention and retention for longer than 1 week (19 patients), only 3 patients were able to void after the catheter was placed. Of the 37 patients with a non-neuropathic cause and retention 1 week or less, controlled voiding was seen in 33 patients (89%). Controlled voiding was defined as the patient's volitional ability to initiate and stop his urinary stream. There were no complications with catheter placement; however, 8 patients (24.2%) had minor adverse experiences of frequency/urgency (n = 3), incontinence (n = 3), migration of the catheter (n = 1), and pain (n = 1). CONCLUSIONS: ContiCath offers an alternative to an indwelling Foley catheter in men with temporary bladder outlet obstruction and urinary retention.
This is the first case-control study to determine whether smoking is associated with cervical dysplasia, after adjustment for human papillomavirus (HPV) infection, among a group of non-Hispanic black women. Subjects were interviewed and asked questions about smoking and other risk factors for cervical cancer. HPV infection was determined by hybrid capture. Thirty-two women with histologically confirmed incident dysplasia and 113 control women with normal cytologic smears were enrolled; all women were HIV negative. Smoking was more strongly associated with dysplasia among women with high-grade lesions than among all case women combined. After adjustment, women with high-grade lesions were roughly four times more likely to be ever (odds ratio [OR]: 3.8; 95% confidence interval [CI]: 0.76-18.4) or current (OR: 4.3; 95% CI: 0.83-21.9) smokers, compared with control women. Larger studies among black women that control for HPV infection are needed to confirm these findings and to explore associations among black women with low-grade lesions.
We examined whether elevated levels of retinoids, carotenoids, folate, and vitamin E protected against cervical dysplasia among non-Hispanic, black women. We enrolled 32 women with incident cervical dysplasia, including cervical intraepithelial neoplasia (CIN) I, CIN II, and CIN III/carcinoma in situ, and 113 control women with normal cervical cytology in case-control study. Micronutrient levels were estimated from a food-frequency questionnaire (FFQ) and measured from blood samples. Information on risk factors for cervical neoplasia was elicited by interview. Hybrid capture was used to determine infection with human papillomavirus. After adjustment for potential confounders, analysis of micronutrient levels estimated from the FFQ suggested that women in the upper tertile of lycopene and vitamin A intake were one-third (odds ratio = 0.32, 95% confidence interval = 0.8-1.3) and one-fourth (odds ratio = 0.24, 95% confidence interval = 0.05-1.2) as likely, respectively, to have dysplasia as women in the lower tertile. Borderline protective trends (p < or = 0.10) were apparent. Elevated levels of serum lycopene also suggested some protection against dysplasia. Results were not significant at alpha = 0.05 because of the small number of case women enrolled. Overall, correlations between estimates from the FFQ and serum levels were poor. This study indicates that, among black women, lycopene and perhaps vitamin A may play a protective role in the early stages of cervical carcinogenesis.
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Enhanced expression of the epidermal growth factor receptor (EGFR) or its ligands, epidermal growth factor (EGF) and transforming growth factor alpha (TGF-alpha) can increase signalling via receptor-mediated pathways which may lead to excessive proliferation and cellular transformation. Such autocrine regulation of growth has been demonstrated for prostate cancer cell lines in culture but its role in prostate cancer in vivo has not been established. To assess the potential of such a mechanism, we have examined the pathway components in prostate carcinomas (CaP) in comparison with non-malignant benign prostatic hyperplasias (BPH). In the present study, we investigate the dosage, structure and expression of EGF, TGF-alpha and EGFR genes in a series of 34 human prostate samples and 3 prostate cancer cell lines. All of the samples contained transcripts from each of the genes. The expression of pre-pro-TGF-alpha mRNA and pre-pro-EGF mRNA were significantly higher in CaP (n = 13) than BPH (n = 21) specimens (p < 0.05). The androgen-responsive prostatic carcinoma cell line, LNCaP, expressed high levels of EGF mRNA while the androgen-independent DU145 and PC-3 cell lines expressed high levels of TGF-alpha mRNA and EGFR mRNA. In general, overexpression of these mRNAs was not associated with amplification or detectable gene rearrangement; only DU145 cells demonstrated any alteration in these genes, with apparent amplification of the TGF-alpha gene. Relative to BPH, all prostate carcinomas and cell lines studied had elevated levels of mRNA for one or both mRNA coding for the ligands for EGFR.(ABSTRACT TRUNCATED AT 250 WORDS)
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NCT is a binary system, in which 10B is physiologically targeted to tumor and then allowed to interact with thermal neutrons generated in the treatment volume by an externally applied neutron beam. Consequently, an unusually large number of parameters are obtained, which bear on the resultant Therapeutic Gain (TG). However, a perusal of these data, as illustrated in Figure 7, indicates that the TG would increase significantly beyond values projected in this paper if the absolute amount of 10B could be increased above 30 ppm. For example, increasing 10B concentration in tumor to 45 ppm would increase TG by approximately 33% (with a T/N of 5). A similar increase in TG would follow an increase in T/N from 5 to 10. Those associated with the development of boron compounds for NCT feel that such developments are within reach.
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As part of an ongoing effort to evaluate alternative treatments for benign prostatic hyperplasia, we compared the outcomes of transurethral resection of the prostate with those of open prostatectomy. Men undergoing prostatectomy in Denmark (n = 36,703), Oxfordshire, England (n = 5284), and Manitoba, Canada (n = 12,090), were identified retrospectively through administrative data and followed for up to eight years. The cumulative percentage of patients undergoing a second prostatectomy was substantially higher after transurethral than after open prostatectomy (12.0 vs. 4.5 percent in Denmark, 12.0 vs. 1.8 percent in Oxfordshire, and 15.5 vs. 4.2 percent in Manitoba). The long-term age-specific mortality rates associated with transurethral prostatectomy as compared with open prostatectomy were also elevated in each country. The data on 1650 Canadian patients were used to investigate the contribution of coexisting morbid conditions to the elevated risk of death. The relative risk was 1.45 (95 percent confidence interval, 1.15 to 1.83) before risk adjustment and 1.45 (95 percent confidence interval, 1.15 to 1.84) after adjustment; the higher mortality was seen among low-risk as well as high-risk patients. These findings suggest that transurethral prostatectomy is less effective in overcoming urinary obstruction than the open operation. Our data also raise the possibility that transurethral prostatectomy may result in higher long-term mortality, although we cannot rule out potential confounding effects of unmeasured characteristics of patients.
A developmental model of antisocial behavior is outlined. Recent findings are reviewed that concern the etiology and course of antisocial behavior from early childhood through adolescence. Evidence is presented in support of the hypothesis that the route to chronic delinquency is marked by a reliable developmental sequence of experiences. As a first step, ineffective parenting practices are viewed as determinants for childhood conduct disorders. The general model also takes into account the contextual variables that influence the family interaction process. As a second step, the conduct-disordered behaviors lead to academic failure and peer rejection. These dual failures lead, in turn, to increased risk for depressed mood and involvement in a deviant peer group. This third step usually occurs during later childhood and early adolescence. It is assumed that children following this developmental sequence are at high risk for engaging in chronic delinquent behavior. Finally, implications for prevention and intervention are discussed.
1. Renal transplantation can be performed at small regional centers as successfully as at large centers. 2. Immunosuppression should be individualized for the patient thereby avoiding the use of costly and often clinically complicated immunosuppressive regimens. 3. Small centers need to participate in large regional pools in order to give highly presensitized patients a reasonable chance of successful transplantation. 4. Long-term patient compliance is a major problem and requires careful surveillance of patients' adherence to their prescribed therapy. Frequent follow-up also allows for the detection of late rejection episodes which can often be reversed.
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We have examined the level of c-myc transcripts in prostate tissue obtained from patients with both benign prostatic hyperplasia and adenocarcinoma of the prostate. A significantly higher level of c-myc transcripts is observed in patients with adenocarcinoma (P less than 0.05). In addition, a subset of patients with adenocarcinoma had levels of c-myc transcripts 2-fold higher than the mean level for this group. These preliminary results indicate that the investigation of c-myc levels as a prognostic indicator in prostatic carcinoma is warranted.
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An immunosuppressive regimen consisting of azathioprine (AZ), prednisone, and intermittent i.v. infusions of 400 mg of cyclophosphamide (CY) in the first post-transplant month was prospectively compared with a no CY regimen. There were no significant differences in patient or graft survival, graft function, or infectious complications between the two regimens.