Screening for alcohol problems in primary care

Alcohol problems are common among patients seen in primary care settings, yet they are often missed by physicians. This article offers a model for alcohol screening designed to facilitate early identification of alcohol problems. This approach emphasizes the heterogeneity of alcohol problems and looks at alcohol use along a spectrum, with different risks depending on where in the spectrum a patient falls. The authors provide practical suggestions on integrating alcohol screening and early intervention into routine care.     

Flattening the organization: implementing self-directed work groups

In response to tremendous growth of managed care and threats to financial stability and job security, the Greater Baltimore Medical Center (GBMC) restructured itself into independent business units. The radiology department at GBMC resolved to reduce cost per unit-of-service, improve service, determine optimal staffing levels and reduce the number of layers of organization. It was decided to achieve those goals by implementing self-directed work groups. Staff buy-in was critical to success of the project. To begin, the staff was educated intensively about current trends in healthcare, managed care and potential changes in the job market. The radiology department was allowed to reduce the size of its staff through attrition and worked hard to focus staff concern on the impact each individual could have on the bottom line and the resultant effect on job security. Self-directed work groups were designed on a matrix that used small "service teams" in combinations to form larger "work groups." Actual work and daily activities occur at the service team level; information exchange and major decisions occue at the work group level. Seventeen months after beginning the project and 10 months after implementation, the organization has flattened, staff members have adjusted well to new roles, there have been no lay-offs, and the matrix system of small and large groups have proved particularly valuable.     

Psychological adjustment in adult adoptees: assessment of distress, depression, and anger

Psychological adjustment was assessed in a sample of 525 female and 191 male adoptees. Analyses were conducted by gender; by search status, i.e., those who had never searched, those who were searching, and those who had made contact with their biological parents; and by history of mental health service utilization. Compared to normative data, the sample reported significantly higher levels of psychological maladjustment; only women adoptees scored higher on a scale measuring anger. Overall, adoptees' scores were elevated but did not approach levels typical of outpatient populations.     

Preclinical pharmacology of the natural product anticancer agent 10-hydroxycamptothecin, an inhibitor of topoisomerase I

Purpose: 10-Hydroxycamptothecin (HCPT) is an indole alkaloid isolated from a Chinese tree, Camptotheca acuminata, and has a wide spectrum of anticancer activity in vitro and in vivo mainly through inhibitory effects on topoisomerase I. HCPT has been shown to be more potent and less toxic than camptothecin and has recently undergone clinical trials. To determine how HCPT might be best used as an anticancer agent, preclinical studies of the pharmacokinetics, tissue distribution, metabolism and elimination of HCPT in rats were undertaken. Methods: HCPT was administered to rats by i.v. bolus injection at doses of 1, 3, and 10 mg/kg body weight. HCPT (lactone and carboxylate) and its metabolites in plasma, urine, feces, and various tissues were quantitated by reversed-phase HPLC. Pharmacokinetic parameters were then estimated. Results: Following i.v. administration at doses of 3 or 10 mg/kg, the plasma concentration-time profile for lactone HCPT could be best described by a three-compartment model, with terminal elimination half-lives of 140.4 and 428.6 min, respectively. A two-compartment model was used to fit the plasma concentration-time curve at 1 mg/kg, with a terminal elimination half-life of 30.5 min. Carboxylate HCPT had a longer half-life than the lactone form of HCPT. During the initial 6 h after dosing, urinary excretion was the major route of elimination, and fecal excretion became the major route of elimination thereafter. HCPT was widely distributed to various tissues including the enterohepatic system, kidney, and bone marrow. The lactone form of HCPT was detectable in various tissues examined up to 72 h after dosing at all the three test doses. HCPT glucuronides were present in plasma, urine, feces and various tissues. No significant toxicity was observed at doses of 1 or 3 mg/kg. Polyuria and hematuria were observed only during the initial 3 h after dosing at 10 mg/kg. Conclusions: Prolonged elimination of HCPT in vivo may have a significant impact on its therapeutic effects. HCPT is metabolized to its carboxylate form and glucuronides. Dose-dependent toxicity was observed with i.v. administration of HCPT. The results of this study should be useful in the design of future human trials with this anticancer drug. Received: 6 September 1996 / Accepted: 15 July 1997     

Impact of Varying Stages of Endometriosis on the Outcome of In Vitro Fertilization–Embryo Transfer

Purpose: The impact of severity of endometriosis on the outcome of in vitro fertilization (IVF) was analyzed in an uncontrolled, retrospective study in an academic IVF program. Methods: Sixty-one patients with a primary diagnosis of endometriosis undergoing 85 cycles of IVF were included in the study. Patients were divided according to the severity of disease based on the revised American Fertility Society (AFS) classification into groups A (stages I/II, or minimal/mild) and B (stages III/IV, or moderate/severe). Group A included 32 patients undergoing 45 IVF-embryo transfer (ET) cycles; group B included 29 patients undergoing 40 IVF cycles. Exclusion criteria were age older than 40 years, basal day 3 follicle stimulating hormone (FSH) greater than 20 IU/L, male-factor infertility, assisted hatching, and gamete intrafallopian transfer cases. Stimulation for IVF cycles was standard using pituitary down-regulation with gonadotropin-releasing hormone agonist in a midluteal protocol. Controlled ovarian hyperstimulation (COH) was achieved using a combination of FSH and human menopausal gonadotropin. Outcomes assessed included response to COH and number, maturity, and quality of oocytes retrieved. Fertilization, implantation, and pregnancy rates after IVF-ET were also analyzed. Results: The response to COH and the number, maturity, and quality of the oocytes was comparable between patients with varying severity of endometriosis. Fertilization rates for oocytes of patients in group B (stages III/IV) were significantly impaired compared to those in group A (stages I/II) (P = 0,004). The rates for implantation, clinical pregnancy, and miscarriage were comparable between the two groups. Conclusions: The reduced fertilization potential of the oocytes obtained from patients with severe endometriosis in the absence of male-factor infertility suggests an adverse biological impact of the advanced disease on the oocytes. The outcome of IVF-ET, however, is unaffected by increasing severity of endometriosis. This suggests that IVF may compensate for or overcome this reduction in the biological potential of the oocytes associated with severe disease, thus accounting for a comparable outcome irrespective of the severity of endometriosis.     

Demonstration of ATP-Dependent,Transcellular Transport of Lipid Across the Lymphatic Endothelium Using an In Vitro Model of the Lacteal

Pharmaceutical Research - The lymphatic system plays crucial roles in tissue fluid balance, trafficking of immune cells, and the uptake of dietary lipid from the intestine. Given these roles there...