Clinical ease of using doxazosin in BPH patients with and without hypertension

Clinical studies have demonstrated that doxazosin therapy reduced blood pressure (BP) in patients with benign prostatic hyperplasia (BPH) who were hypertensive at baseline but not in patients who were physiologically or pharmacologically normotensive at baseline. In patients with BPH and uncontrolled hypertension, despite treatment with other antihypertensive drugs, the addition of doxazosin resulted in improved control with significant reductions in BP. The new formulation, doxazosin gastrointestinal therapeutic system (GITS), is initiated at a therapeutic dose, simplifying dose titration. Based on its efficacy and pharmacokinetic and tolerability profiles, doxazosin GITS is an effective and well-tolerated treatment for normotensive and hypertensive patients with BPH.     

Safety and tolerability of the dual 5alpha-reductase inhibitor dutasteride in the treatment of benign prostatic hyperplasia

OBJECTIVE: The objective of this paper is to examine safety and tolerability data from a number of recently completed clinical trials with the novel, dual 5alpha-reductase inhibitor, dutasteride.METHODS: Intent-to-treat analyses were conducted on data for dutasteride 0.5 mg/day for drug-related adverse events, clinical laboratory test results, and prostate-specific antigen (PSA) levels derived from four large, randomised, double-blind clinical trials (n=5655). Further data were derived from a randomised, double-blind combination study of dutasteride 0.5 mg/day and tamsulosin 0.4 mg/day (n=327), and several safety studies conducted in healthy volunteers. RESULTS: Data from two-year blinded clinical studies demonstrate that dutasteride is well tolerated, with a profile comparable with that of placebo. The exception is a modestly elevated incidence of impotence, decreased libido, ejaculation disorders, and gynaecomastia. Clinical laboratory test abnormalities were reported by <1% of patients treated with dutasteride, and abnormal values occurred with similar frequency versus placebo-treated patients. In a healthy volunteer study, when dutasteride was administered daily for 1 year, it did not significantly affect bone metabolism markers, bone mineral density or lipid profiles. Dutasteride reduced total serum PSA concentrations by approximately 50% following 6, 12, and 24 months of treatment but had no effect on free-to-total PSA levels. The safety profile of dutasteride did not differ from that of finasteride in a large, parallel-group, comparator trial. Additionally, when dutasteride was used in combination with an alpha(1)-blocker, the drug-related adverse event profiles were as would be expected for the individual agents. CONCLUSIONS: Considered together, these data demonstrate dutasteride to be well-tolerated.     

The Prognosis of T3N0 Colon Cancer Is Dependent on the Number of Lymph Nodes Examined

Background: T3N0 colon cancer is the target of many adjuvant studies. Very few studies have examined the relationship of the number of lymph nodes examined to the prognosis of this stage. We examined data from the National Cancer Data Base (NCDB) to determine whether the number of examined lymph nodes is prognostic for T3N0 colon cancer.Methods: A total of 35,787 prospectively collected cases of T3N0 colon cancer that were surgically treated and pathologically reported from 1985 to 1991 to the NCDB as T3N0M0 were analyzed.Results: The 5-year relative survival rate for T3N0M0 colon cancer varied from 64% if 1 or 2 lymph nodes were examined to 86% if >25 lymph nodes were examined. Three strata of lymph nodes (1–7, 8–12, and 13) distinguished significantly different observed 5-year survival rates.Conclusions: These results demonstrate that the prognosis of T3N0 colon cancer is dependent on the number of lymph nodes examined. A minimum of 13 lymph nodes should be examined to label a T3 colon cancer as node negative. These data suggest that adjuvant trials for T3N0 colon cancer should stratify according to the number of lymph nodes examined.Presented at the 54th Annual Meeting of the Society of Surgical Oncology, Washington, DC, March 17, 2001     

Parent-child dyadic mutuality and child behavior problems: an investigation of gene-environment processes

BACKGROUND: Parent-child mutuality is comprised of emotional reciprocity, co-responsiveness, and cooperation, which together represent aspects of co-regulation of emotion and behavior that may be important in the etiology of children's behavior problems. Furthermore, individual differences in children's mutuality and behavior problems involve transactions between genetic and environmental influences. Behavioral genetic designs are useful for elucidating these processes. METHODS: The sample included 396 children in adoptive families (53% female, age M = 8.16 years), of whom 244 were siblings (122 pairs). All of the siblings were genetically unrelated. In some families, one child was adopted but the other child was a biological child of the adoptive parents. We observed mother-child dyadic mutuality (a composite score including responsiveness, interaction reciprocity, and cooperation) during videotaped in-home observations. In addition, child behavior problems were assessed and represented as a composite score including observers' ratings of noncompliance, and parents' ratings of aggression and conduct problems. RESULTS: Greater mutuality was associated with lower levels of child behavior problems, both between families and within families (i.e., sibling differences). The sibling intra-class correlation for mutuality with the same parent was near zero in this sample of genetically unrelated siblings. The correlation between child behavior problems and dyadic mutuality did not vary as a function of mother-child genetic similarity. CONCLUSIONS: Mother-child mutuality is child specific within families, a finding that is consistent with theories regarding bi-directional parent and child effects in socialization. In addition, there was no evidence of passive gene-environment correlation, suggesting that the link between lower levels of maternal mutuality and higher levels of child behavior problems is not only reflecting overlapping genetic influences on parent and child behavior.