The hydroxylation, dechlorination, and glucuronidation of 4,4'-dichlorobiphenyl (4-DCB) by human hepatic microsomes

Since chlorine placement and the degree of chlorination of the biphenyl nucleus play an important role in the metabolism and ultimate elimination of polychlorinated biphenyls (PCBs), we have studied the metabolism of 4,4'-dichlorobiphenyl (4-DCB) by human hepatic microsomes. This low molecular weight PCB congener is substituted at the preferred site of metabolism (para-position). 4-DCB was metabolized by human microsomes with a Km of 0.43 microM and a Vmax of 1.2 pmoles/mg microsomal protein/min. Six metabolites were identified: 4,4'-dichloro-3,3'-biphenyldiol, 4'-chloro-3-biphenylol, 4'-chloro-4-biphenylol, 4,4'-dichloro-2-biphenylol, 4,4'-dichloro-3-biphenylol (most abundant), and 3,4'-dichloro-4-biphenylol. [14C]-4-DCB equivalents were found to covalently bind to microsomal protein. Addition of a 1 mM concentration of reduced glutathione decreased the degree of covalent binding. These data suggest that human microsomes metabolize this PCB through an arene oxide and that an "NIH shift" occurs. When UDPGA was added to the incubation, human microsomal glucuronosyltransferase catalyzed the formation of the glucuronide of the major metabolite, 4,4'-dichloro-3-biphenylol. These and previous in vitro results show that the biotransformation of PCBs by humans is governed by the same principles established for the in vivo biotransformation of PCBs by the rat, mouse and monkey. That is, PCBs without two adjacent unsubstituted carbon atoms are poorly metabolized and that an unsubstituted para-position facilitates metabolism.     

Increasing physician involvement In cholesterol-lowering practices: The role of knowledge,attitudes and perceptions

The study evaluated a multifaceted educational intervention systematically designed to increase physician involvement in cholesterol-lowering practices. We hypothesized that knowledge, perceptions and behaviours would be enhanced in participating physicians, compared with controls. Method: Fifty-one family physicians were assigned randomly to three groups; the two experimental groups attended a training workshop, received physician and patient education materials and ongoing consultant support. One experimental group also received a “cuing” intervention. The control group received no interventions. Outcome measures included knowledge and attitude scores, self-efficacy perceptions, and physician dietary counselling behaviour. Measures were taken at pretest, 6 weeks and 15 months later. Results: Intervention group physicians achieved significantly higher knowledge scores than the control group at the six-week test; the differences disappeared at 15 months. Attitudes, self-reported practices and overall self-efficacy scores were similar across groups. Within group variation was highly significant. Physician dietary counselling scores were significantly higher in the intervention groups (p = 0.0001). Some associations were seen among knowledge, attitude, self-efficacy and dietary counselling scores. Conclusion: Physician behaviour change in cholesterol reduction may not depend entirely upon knowledge, attitudes and perceptions. This revised version was published online in June 2006 with corrections to the Cover Date.     

Memory performance of geriatric and nongeriatric chronic schizophrenic patients: a cross-sectional study.

Memory functioning has been studied extensively in nongeriatric schizophrenic patients, leading to the suggestion that schizophrenic patients manifest a "subcortical" pattern of memory deficits. Few previous studies examined very poor outcome patients with a chronic course of hospitalization. This study examined the association of age and global cognitive dysfunction with verbal and spatial learning and delayed recall, as well as examining differential impairments in delayed recall as compared to delayed recognition memory. Sixty-six chronic schizophrenic patients were studied, with 30 of these patients over the age of 65. Verbal (California Verbal Learning Test) and spatial (Biber Figure Learning Test) serial learning and delayed memory tests were administered. All aspects of memory functioning were correlated with estimates of global cognitive status. When global cognitive status was controlled, age effects were still found for the majority of the memory measures. Delayed recognition memory was not spared, being performed as poorly as delayed recall. In contrast to previous studies of better-outcome patients with schizophrenia, geriatric patients with chronic schizophrenia performed more poorly than nongeriatric patients. The lack of sparing of delayed recognition memory suggests that previous findings of specific recall memory deficit and a subcortical profile of memory impairments may apply to schizophrenic patients with less severe global cognitive impairments. These data suggest that poor-outcome patients may have a pattern of memory impairments that has some features in common with cortical dementia.     

The motivations for self-injury in psychiatric inpatients

Nonsuicidal self-injurious behavior (SIB) occurs in both culturally appropriate and culturally inappropriate forms. It is one of the diagnostic criteria for borderline personality disorder, but it occurs in several psychiatric and neurological populations. The personal intent of SIB in psychiatric populations is incompletely understood. A self-report scale (Self-Injury Motivation Scale; SIMS) to assess motivation for self-injury was developed. Relationships among motivation for SIB, characteristics of SIB, and psychopathology were explored. A semistructured interview and the SIMS, Dissociative Experiences Scale, Beck Depression Inventory, Davidson Trauma Scale, and Millon Clinical Multiaxial Inventory-II were given to 99 consecutively admitted inpatients. The SIMS had good reliability and validity. A high SIMS score suggested distinct psychopathology. Several factors on the SIMS differentiated motivations for SIB. Patients with different SIMS factor profiles had different psychopathology.     

Resection of lung metastases: long-term results and prognostic analysis based on 5206 cases--the International Registry of Lung Metastases

The International Registry of Lung Metastases was established in 1991 to asses the long-term results of pulmonary metastasectomy. The Registry has accrued 5206 cases of lung metastasectomy, from 18 departments of thoracic surgery in Europe (n = 13), USA (n = 4) and Canada (n = 1). Of these patients 4572 (88%) underwent complete surgical resection. The primary tumor was epithelial in 2260 (43%), sarcoma in 2173 (42%), germ cell in 363 (7%), and melanoma in 328 (6%) patients. The disease-free interval was 0 to 11 months in 1729 (33%) cases, 12 to 35 months in 1857 (36%) and more than 36 months in 1620 (31%). Single metastases accounted for 2383 (46%) cases and multiple lesions for 2726 (52%). Mean follow up was 46 months. Analysis was performed by Kaplan-Meier estimates of survival, relative risk of death and multivariate Cox model. The actuarial survival after complete metastasectomy was 36% at 5 years, 26% at 10 years and 22% at 15 years (median 35 months); the corresponding values for incomplete resection were 13% at 5 years and 7% at 10 years (median 15 months). Among complete resections, the 5-year survival was 33% for patients with a disease free-interval of 0 to 11 months and 45% for those with a disease-free interval of more than 36 months; 43% for single lesions and 27 for four or more lesions. Multivariate analysis showed a better prognosis for patients with germ cell tumors, disease-free interval of 36 months and more and single metastases. These results confirm that lung metastasectomy is a safe and potentially curative procedure.     

Distal radial metaphyseal forces in an extrinsic grip model: implications for postfracture rehabilitation

The purpose of this study was to establish the relationship between force at the distal radius and power grip force of the hand, a common functional and rehabilitation maneuver. This information will provide limits of allowable grip forces during postfixation rehabilitation and guide design requirements for fixation systems. By designing a model of power grip using the extrinsic hand musculotendinous units, we were able to compare grip force with force at the distal radius. Our results show that to obtain 10 N of grip force, approximately 26.3 N of force is transmitted through the distal radius, 52.4 N is transmitted through the radius and ulna combined, and 30.0 N needs to be applied to the flexor tendons. Fifty-one percent of the total forearm force was transmitted through the distal radius in this model. If all forearm forces were transmitted through the radius, 52 N of force would be transmitted through the distal radius to obtain 10 N of grip force. The clinical application of this model suggests that since failure forces of tested distal radius fixation systems range from 55 to 825 N, rehabilitation grip force should not exceed 10 to 159 N, depending on the type of fixation.     

Induction chemotherapy before surgery for early-stage lung cancer: A novel approach. Bimodality Lung Oncology Team

OBJECTIVE: This phase II trial assessed the feasibility, as measured by response rate, toxicity, resectability rate, and surgical morbidity and mortality rates, of perioperative paclitaxel and carboplatin chemotherapy in patients with early-stage non-small cell lung carcinoma. METHODS: All patients required negative mediastinoscopy results and adequate medical parameters to undergo induction chemotherapy and an operation. Superior sulcus patients were excluded. Chemotherapy consisted of paclitaxel 225 mg/m(2) over 3 hours and carboplatin (area under the curve = 6) every 21 days for 2 cycles preoperatively. Three postoperative cycles of chemotherapy were planned for patients undergoing complete resection. RESULTS: Between June 1996 and July 1998, 94 patients were entered into the study. Sixty-five (69%) were men, and the median age was 64 years (range, 34-79 years). After induction chemotherapy, 53 of 94 (56%; 95% confidence interval, 46%-67%) had a major objective response, 88 (94%) underwent surgical exploration, and 81 (86%; 95% confidence interval, 78%-92%) underwent complete resection. Reasons for not undergoing an operation included disease progression (n = 3), clinically unresectable status (n = 1), death (n = 1), and patient lost to follow-up (n = 1). Two postoperative deaths occurred. Six (6%; 95% confidence interval, 0%-13%) pathologic complete responses were observed. Ninety (96%) patients received the planned preoperative chemotherapy versus 45% receiving postoperative chemotherapy. No unexpected chemotherapy or surgical morbidity occurred. The 1-year survival is currently estimated at 85%, and the median survival has not yet been reached. CONCLUSIONS: Induction chemotherapy with paclitaxel and carboplatin is feasible and produces a high response rate with acceptable morbidity and mortality rates in early-stage non-small cell lung carcinoma. A prospective randomized trial comparing 3 cycles of induction chemotherapy and surgery with surgery alone in early-stage non-small cell lung carcinoma is planned.     

18F]fluorodeoxyglucose uptake by positron emission tomography predicts outcome of non-small-cell lung cancer.

PURPOSE: To determine whether the standardized uptake value (SUV) of [(18)F]fluorodeoxyglucose uptake by positron emission tomography could be a prognostic factor for non-small-cell lung cancer (NSCLC). PATIENTS AND METHODS: One hundred sixty-two patients with stage I to IIIb NSCLC were analyzed. Overall survival (OS), disease-free survival (DFS), distant metastasis-free survival (DMFS), and local-regional control (LRC) were calculated by the Kaplan-Meier method and evaluated with the log-rank test. The prognostic significance was assessed by univariate and multivariate analyses. RESULTS: There were 93 patients treated with surgery and 69 patients treated with radiotherapy. A cutoff of 5 for the SUV for the primary tumor showed the best discriminative value. The SUV for the primary tumor was a significant predictor of OS (P = .02) in both groups. Low SUVs ( 5.0; surgery group, P = .02; radiotherapy group, P = .0005). Low SUVs ( 5.0; stage I or II, P = .02; stage IIIa or IIIb, P = .004). However, using the same cutoff point of 5, the SUV for regional lymph nodes was not a significant indicator for DFS (P = .19), LRC (P = .97), or DMFS (P = .17). The multivariate analysis showed that the SUV for the primary tumor was a significant prognostic factor for OS (P = .03) and DFS (P = .001). CONCLUSION: The SUV of the primary tumor was the strongest prognostic factor among the patients treated by curative surgery or radiotherapy.     

Clinical imaging of macular pigment optical density and spatial distribution

Clinical research continues to provide an increasing number of studies that reveal an association between macular pigment optical density (MPOD) and both visual function and ocular health. As a result, there is a growing need for repeatable, accurate measures of MPOD that can describe peak optical density as well as spatial distribution. Measurement of MPOD in a research setting has an established history encompassing a number of both objective and subjective techniques. Transition of these techniques to a clinical setting has produced an array of commercial devices using three primary methods: heterochromatic flicker photometry, fundus autofluorescence and fundus reflectometry. The inherent differences among the techniques create difficulty in making direct comparisons between MPOD measurement devices. Understanding the limitations of each technique is critical in the clinical interpretation of MPOD results. Here, both the objective and subjective methods of MPOD measurement are reviewed with emphasis on the commercially available devices used in clinical settings.