Giant abdominopelvic epithelioid angiomyolipoma associated with tuberous sclerosis: Report of a case

(Received for publication on July 16, 1998; accepted on Mar. 11, 1999)     

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.     

NEOPLASTIC DISEASE AND DELETION 22q11.2: A MULTICENTRIC STUDY AND REPORT OF TWO CASES

Deletion 22q11.2 is a chromosomal abnormality detected in young patients with clinical manifestations of the DiGeorge/velocardiofacial syndrome. Conotruncal heart defects are also associated with del22q11.2. An association of these cardiac malformations with neoplasias has been observed. Our series includes two cases of malignancies, a hepatoblastoma and a renal-cell carcinoma, arising in children with complex cardiac malformations. The aim of the study was to determine if the deletion at 22q11.2 was present and could be responsible for both pathological processes. Del22q11.2 was identified in both cases. Comparative genomic hybridization revealed terminal gains on chromosomes 1q and Xq and terminal loss on 1p in the hepatoblastoma, and gains in 1p, 12q, 16p, 20q, 22q, and whole chromosome 19 and loss of Xq in the renal-cell carcinoma. Our results confirm a common genetic basis for cardiac malformations, and del22q11.2 presents a risk factor for the development of pediatric tumours.     

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     

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...     

Longer duration of homelessness is associated with a lower likelihood of non-detectable plasma HIV-1 RNA viral load among people who use illicit drugs in a Canadian setting

Homelessness is common among people who use drugs (PWUD) and, for those living with HIV/AIDS, an important contributor to sub-optimal HIV treatment outcomes. This study aims to investigate the relationship between the duration of homelessness and the likelihood of plasma HIV-1 RNA viral load (VL) non-detectability among a cohort of HIV-positive PWUD. We used data from the ACCESS study, a long-running prospective cohort study of HIV-positive PWUD linked to comprehensive HIV clinical records including systematic plasma HIV-1 RNA VL monitoring. We estimated the longitudinal relationship between the duration of homelessness and the likelihood of exhibiting a non-detectable VL (i.e., <500?copies/mL plasma) using generalized linear mixed-effects modelling. Between May 1996 and June 2014, 922 highly active antiretroviral therapy-exposed participants were recruited and contributed 8188 observations. Of these, 4800 (59%) were characterized by non-detectable VL. Participants reported they were homeless in 910 (11%) interviews (median: six months, interquartile range: 6–12 months). A longer duration of homelessness was associated with lower odds of VL non-detectability (adjusted odds ratio?=?0.71 per six-month period of homelessness, 95% confidence interval: 0.60–0.83) after adjustment for age, ancestry, drug use patterns, engagement in addiction treatment, and other potential confounders. Longer durations of episodes of homelessness in this cohort of HIV-positive illicit drug users were associated with a lower likelihood of plasma VL non-detectability. Our findings suggest that interventions that seek to promptly house homeless individuals, such as Housing First approaches, might assist in maximizing the clinical and public health benefits of antiretroviral therapy among people living with HIV/AIDS.