Use of vinorelbine in non-small-cell lung cancer. Provincial Lung Disease Site Group

The best known of the nation's welfare programs, Aid to Families with Dependent Children (AFDC), has from its inception reflected a tension between the desire to support children in poor, lone-parent families and the belief that parents should be held responsible for providing for themselves and their children. Against that backdrop, this article reviews the history of the AFDC program and traces the emergence of policies and programs intended to encourage employment of the parents (almost exclusively mothers) who receive benefits. The article examines in detail the Work Incentive Program (WIN) launched in 1967 and the Family Support Act of 1988, comparing these to each other and to the outlines of welfare reform signed into law in 1996. The article emphasizes the importance of sustained attention to the implementation of policy goals in concrete programs and shows that the merits of those early programs have not been fully tested because they were never funded or implemented at the scale intended. The article also outlines ways in which welfare-to-work programs can be used to assist children as well as parents, and urges that children's well-being remain the core purpose of welfare policy.     

Randomized study of paclitaxel-cisplatin versus cisplatin-teniposide in patients with advanced non-small-cell lung cancer. The European Organization for Research and Treatment of Cancer Lung Cancer Cooperative Group

PURPOSE: To compare two cisplatin based chemotherapy schedules in patients with advanced non-small-cell lung cancer (NSCLC). PATIENTS AND METHODS: A total of 332 patients with advanced NSCLC were randomized to receive cisplatin 80 mg/m2 on day 1 either in combination with teniposide 100 mg/m2 on days 1, 3, and 5 (arm A) or paclitaxel 175 mg/m2 by 3-hour infusion on day 1 (arm B); cycles were repeated every 3 weeks. RESULTS: Fifteen patients were ineligible; patient characteristics were well balanced between the two arms: 71% were male, 71% had less than 5% weight loss, 89% had a World Health Organization (WHO) performance status of 0 to 1, 51% had adenocarcinoma, and 61% had stage IV disease. Hematologic toxicity was significantly more severe in arm A (leukopenia, neutropenia, and thrombocytopenia grade 3 or 4: 66% v 19%, 83% v 55%, 36% v 2% in arms A and B, respectively), which resulted in more febrile neutropenia (27% v 3% in arms A and B, respectively), dose reductions, and treatment delays. There were a total of nine toxic deaths, six due to neutropenic sepsis: five in arm A and one in arm B. In contrast, arthralgia/myalgia (grade 2 or 3, 4% v 17%), peripheral neurotoxicity (grade 2 or 3, 6% v 29%), and hypersensitivity reactions (1% v 7%, all grades) were significantly more frequent in arm B. The frequency and severity of other toxicities were comparable between the two arms. Responses were one complete and 44 partial on arm A (28%) and two complete and 61 partial (41%) on arm B (P = .018). There was no significant difference in survival, with median and 1-year survivals 9.9 versus 9.7 months and 41% versus 43%, respectively in arm A and B. Progression-free survival was 4.9 and 5.4 months in arm A and B, respectively. Selected centers participated in a quality-of-life (QoL) assessment, which was performed by the European Organization for Research and Treatment of Cancer (EORTC) QLQ-C30 and LC-13 administered at baseline and every 6 weeks thereafter. Arm B achieved a better score at week 6 for emotional, cognitive and social functioning, global health status, fatigue, and appetite loss, which was lost at 12 weeks. In conclusion, arm B appears superior to arm A with regard to response rate, side effects, and QoL. CONCLUSION: Although survival was not improved, arm B offers a better palliation for advanced NSCLC patients than arm A.     

Chemotherapy in stage IV (metastatic) non-small-cell lung cancer. Provincial Lung Disease Site Group

After sciatic transection a strong decrease in immunoreactivity occurred, starting at 2 days. After 6, 10, 14, and 20 days survival only 5% of the sciatic motoneurons were strongly labeled for GluR2/3 against 80% in the control situation. From Day 20, GluR2/3 labeling started to increase again, reaching near normal levels at Day 80 after sciatic transection. In contrast, after sciatic crush, the decrease in GluR2/3 labeling in motoneurons was less pronounced and returned to normal in 30 days. In all animals, the GluR1 and GluR4 labeling of motoneurons remained unchanged after sciatic transection or crush. It is concluded that sciatic nerve injury leads to a strong, time-dependent decrease in the expression of GluR2 and 3 subunits in the corresponding motoneurons. As a consequence, AMPA receptors with a different subunit composition may be assembled, leading to a change in the functional properties of these receptors. Moreover, if they lack the GluR2 subunit, they may become calcium permeable.     

Epidermal growth factor receptors and their ligands in non-small-cell lung carcinoma

The study was carried out in 178 women without grave obstetrical or extragenital diseases. In group 1 labor pain was relieved by prolonged epidural anesthesia with 2% lidocaine solution (2-2.5 mg/kg), in group 2 prolonged epidural anesthesia with 1% lidocaine solution (1 mg/kg) and 0.01% clofelin (1 microgram/kg) was administered. Central hemodynamics, heart rhythm, external respiration function, uterine contractility, and fetal intrauterine status were assessed. The findings indicate that none of the methods had a negative impact on the vital parameters of women and newborns at any stage of anesthesia. However, a combination of epidural clofelin (1 microgram/kg) with lidocaine permits an appreciable decrease in the doses of both drugs without decreasing the efficacy of anesthesia. This method has a favorable effect on the course of labor: the mouth of the womb opens sooner at a lower uterine activity and there are no negative effects on the fetus and newborn.     

Divergent changes in survival for histological types of non-small-cell lung cancer in the southeastern area of The Netherlands since 1975

We studied the incidence and survival rates for the histological subtypes of non-small-cell lung cancer, using data from the Eindhoven Cancer Registry over the period 1975-94. The proportions with adenocarcinoma and large-cell undifferentiated carcinoma increased from 11% to 21% and from 11% to 15%, respectively, while those with squamous cell carcinoma decreased from 78% to 62%. The increase in the proportion with adenocarcinoma was only found among men. Although the overall prognosis for patients with non-small-cell lung cancer has remained unchanged, there have been divergent changes between morphological subtypes. Relative 1- and 5-year survival rates for squamous cell carcinoma have improved slightly from 48% to 51% and from 14% to 16%, respectively, because of an increase in the proportion with localized tumours, while relative 1- and 5-year survival rates for adenocarcinoma have decreased from 59% to 45% and from 28% to 18%, respectively, because of a decrease in localized tumours. The proportion with localized tumours and the relative 1-year survival for large-cell undifferentiated carcinoma (about 18% and 30% respectively) were markedly lower. The divergent trends could partly be explained by changes in the histological classification of tumours, but changes in patterns of risk and biological behaviour of adenocarcinoma cannot be excluded.     

Southwest Oncology Group phase II trial of concurrent carboplatin, etoposide, and radiation for poor-risk stage III non-small-cell lung cancer

PURPOSE: A phase II study was conducted by the Southwest Oncology Group (SWOG) to assess the efficacy and toxicity of concurrent carboplatin, etoposide, and thoracic radiation (XRT) in a defined population of poor-risk patients with stage III non-small-cell lung cancer (NSCLC). PATIENTS AND METHODS: Patients with stage III NSCLC were eligible if they were excluded from cisplatin-based protocols because of poor pulmonary or renal function, history of congestive heart failure, hearing loss, peripheral neuropathy, or weight loss. Carboplatin 200 mg/m2 daily intravenously days 1, 3, 29, and 31 and etoposide 50 mg/m2 daily intravenously days 1 through 4 and 29 through 32 were administered. Beginning day 1, XRT was delivered at 1.8 to 2.0 Gy daily to a total dose of 61 Gy. RESULTS: Within a period of 1 year, 63 patients were registered and 60 were eligible. Patient characteristics were age 47 to 79 years, performance status 0 to 1 (82%) and 2 (18%), and stages IIIA (60%) and IIIB (40%) NSCLC. The most common grades 3 and 4 toxicities included leukopenia (50%), thrombocytopenia (23%), and esophagitis (15%). There were no treatment-related deaths. The overall confirmed response rate was 29%, and median overall survival was 13 months (95% confidence interval, 11 to 14 months). The 2-year survival rate was 21%. CONCLUSION: This chemoradiotherapy regimen is well tolerated in poor-risk patients and yields a median survival similar to that of good-risk patients who received cisplatin-based chemoradiotherapy. This chemoradiotherapy regimen will be compared with XRT alone in poor-risk patients with stage III NSCLC in a randomized phase III trial.     

Clinical genetics in The Netherlands. I. Organization, activities and laboratory diagnosis]

The main feature of clinical genetics is the involvement of close relatives in the diagnostics of a hereditary disorder, and the possible consequences of the findings for future generations. Complex genetic counseling is required in cases with different, possibly hereditary disorders or congenital anomalies in the family or by a syndrome with variable risks of recurrence, depending on the exact nature of the disorder; also the difficult, often emotionally charged choices with which counselees are faced demands the expertise of a clinical genetic centre. Results of follow-up studies after genetic counseling show that experience with a handicap or disease in the own environment and the presence of healthy issue are the main determinants for the decision about reproduction of persons with an enhanced genetic risk who request counseling. Because of the great variety in perception of risks and of the severity of a disorder, and because of the marked clinical heterogeneity, rigid legislation should be avoided in the field of prenatal diagnosis. In the future, the training of the clinical geneticist has to be adapted to the rapid progress in human genetics. Increasingly, the clinical geneticist will function in collaboration with other disciplines such as oncology, obstetrics and gynaecology, paediatrics and neurology; in connection with family testing and counseling, there will also be more collaboration with primary health care.     

Randomized study of chemotherapy and surgery versus radiotherapy for stage IIIA non-small-cell lung cancer: a National Cancer Institute of Canada Clinical Trials Group Study

We treated two children with the unusual complication of ulnar nerve palsy after closed both-bone forearm fractures. Both patients developed an ulnar claw-hand deformity within 7 weeks of injury that resolved spontaneously by 20 weeks postinjury with nonoperative treatment. No patient showed any signs or symptoms of an ischemic compartment syndrome. Both nerve injuries were identified immediately at the time of fracture by a careful neurologic examination. This avoids confusion with a postreduction nerve entrapment injury or ischemic injury after a localized compartment syndrome, which may have considerably different treatments and outcomes. We recommend that a careful neurologic examination be recorded before any manipulative reduction of forearm fractures in children. If an ulnar nerve palsy is detected, it is probably a result of nerve contusion and should resolve without the need for surgical exploration.     

Adjuvant radiotherapy and chemotherapy for stage II or IIIA non-small-cell lung cancer after complete resection. Provincial Lung Cancer Disease Site Group

GUIDELINE QUESTIONS: 1) Does the use of postoperative, adjuvant radiotherapy or chemotherapy, alone or in combination, improve survival rates among patients with completely resected, pathologically confirmed stage II or IIIA non-small-cell lung cancer (NSCLC)? 2) Does the use of radiotherapy reduce the risk of local recurrence among patients with completely resected stage II or IIIA NSCLC? OBJECTIVE: To make recommendations about the use of postoperative adjuvant radiotherapy and chemotherapy in the treatment of patients with completely resected stage II or IIIA NSCLC. OUTCOMES: Overall survival and disease-free survival are the primary outcomes of interest. A secondary outcome of interest is local disease control. PERSPECTIVES (VALUES): Evidence was collected and reviewed by 4 members of the Lung Cancer Disease Site Group (Lung Cancer DSG) of the Cancer Care Ontario Practice Guidelines Initiative. The evidence-based recommendation resulting from this review was approved by the Lung Cancer DSG, which comprises medical oncologists, radiation oncologists, pathologists, surgeons and a medical sociologist. A community representative was present at 1 meeting during which the recommendation was discussed. QUALITY OF EVIDENCE: One meta-analysis and 22 randomized controlled trials (RCTs) were published between 1962 and 1996. The RCTs compared surgery plus radiotherapy with surgery alone; surgery plus adjuvant chemotherapy with surgery alone; surgery plus radiotherapy with surgery plus both chemotherapy and radiotherapy. Many studies included patients with stage IIIB NSCLC; some included patients with incompletely resected stage I NSCLC or with small cell lung cancer (maximum 10%). Older studies used chemotherapy or radiation that would now be considered inferior according to current standards of practice. BENEFITS: There was no survival benefit with adjuvant radiotherapy alone, although 3 RCTs reported a reduction in the rate of local recurrence among patients treated with adjuvant radiotherapy. The meta-analysis showed that postoperative, cisplatin-based chemotherapy alone reduced the relative risk of death by 13% (hazard ratio [HR] 0.87, 95% confidence interval [CI] 0.74 to 1.02); in combination with radiotherapy it resulted in a 6% reduction in the relative risk of death (HR 0.94, 95% CI 0.79 to 1.11). HARMS: Postoperative adjuvant chemotherapy with alkylating agents was found in the meta-analysis to increase the relative risk of death by 15%. A study involving prolonged adjuvant chemotherapy (busulfan or cytoxan daily for 2 years) reported that 4 of 726 patients had hematologic malignancies. In 1 study, only 53% of patients received all 4 cycles of chemotherapy with cyclophosphamide-doxorubicin-cisplatin (CAP); in another, 22% of patients refused therapy with CAP because of nausea and vomiting. PRACTICE GUIDELINE: There is evidence from RCTs that postoperative radiotherapy reduces rates of local recurrence by 11% to 18% (or 1.6 to 19-fold) among patients with completely resected, pathologically confirmed stage II or IIIA NSCLC. Therefore, if the outcome of interest is a reduction in the frequency of local tumour recurrence, radiotherapy is recommended. However, there is no evidence of a survival benefit from postoperative radiotherapy alone. In a meta-analysis, postoperative chemotherapy with or without radiotherapy resulted in a slightly reduced (statistically nonsignificant) risk of death among patients with surgically resected stage II or IIIA NSCLC. The survival benefit was small and achieved only with chemotherapy regimens that produced substantial toxic effects and that are no longer used. Newer chemotherapy regimens are currently being evaluated as adjuvant therapy, but there is insufficient evidence of benefit at this time to recommend them. Therefore, if the outcome of interest is survival, there is insufficient evidence to recommend current chemotherapy regimens with or without radiotherapy as postoperative, adjuvant the     

Guidelines of the National Heart, Lung, and Blood Institute Working Group on Blood Drawing, Processing, and Storage for Genetic Studies

The sphingomyelin cycle is activated to accumulate ceramides in the process of epidermal differentiation. We found that sphingomyelin in the epidermis of 4 different murine strains gave three bands on TLC, the lower band containing alpha-hydroxypalmitic acid (C16h:0(alpha)). However, in the papillomas induced in the skin of SENCAR and SSIN mice by initiation with 7,12-dimethylbenz[a]anthracene followed by promotion with 12-O-tetradecanoylphorbol acetate, the concentration of C16h:0(alpha)-containing sphingomyelin was selectively diminished with a concomitant increase in the concentrations of the ceramides containing alpha-hydroxy fatty acids. These findings indicate a possible involvement of the selective hydrolysis of alpha-hydroxy fatty acid-containing sphingomyelin in the process of tumorigenesis in mouse skin.     

The College of American Pathologists, 1946-1996. Quality Assurance Service

Since its creation in 1970, the College of American Pathologists Quality Assurance Service Committee has provided important and highly respected interlaboratory programs for daily quality control. In 1988, this committee extended its domain by announcing Q-Probes, a unique benchmarking program for laboratory quality assurance. Because of the success and rapid growth of this program during the next 2 years, the Quality Assurance Service Committee expanded into two committees, namely, QAS-QC and QAS-QA, with expertise concentrated, respectively, in quality control and quality assurance. These committees have compiled a history of significant scientific and educational contributions to members, the international laboratory community, other physicians, and patients. New directions for both committees are now underway so that their contributions can continue in the rapidly changing field of pathology and laboratory medicine.     

Personality, Interpersonal, and Motivational Predictors of the Working Alliance in Group Cognitive-Behavioral Therapy for Partner Violent Men.

Recent studies have demonstrated that the working alliance predicts treatment outcome for partner violent men. This study examined the influence of personality and interpersonal characteristics, motivational readiness to change, and demographic factors on working alliance formation among a sample of men (N = 107) participating in a cognitive-behavioral group treatment program for partner violence. Motivational readiness to change was the strongest predictor of the working alliance. Psychopathic personality characteristics also emerged as a strong (negative) predictor of the working alliance. Lower levels of borderline personality characteristics and interpersonal problems, self-referred status, married status, and higher age and income predicted higher working alliance ratings. The results support recent clinical efforts to address motivational readiness in programs for partner violent men. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Single agent activity of rhizoxin in non-small-cell lung cancer: a phase II trial of the EORTC Early Clinical Trials Group

In a multicentre trial of the EORTC-Early Clinical Trials Group (ECTG) we treated 31 chemotherapy-naive patients with advanced non-small-cell lung cancer (NSCLC) with rhizoxin, a novel tubulin-binding agent. The drug was given as an i.v. bolus injection at 2 mg m-2 once every 3 weeks in an outpatient setting. Prophylactic antiemetics were not routinely given. Of the 29 eligible patients, nine had been treated surgically and three had received radiotherapy. The main toxic effects observed were stomatitis (34% of cycles) and neutropenia (41% of cycles). Neutropenic fever was rare (3% of cycles). Twenty-seven patients were evaluable for response. There were four partial responses (15%), while 13 patients (48%) showed stabilisation of their disease. The median duration of response was 7 months (range 6.0-10.7 months) and median survival from the start of rhizoxin treatment was 6 months (range 2-14.7 months). Rhizoxin as single agent shows activity in patients with advanced NSCLC.     

Diagnostic criteria for degenerative, inflammatory, proliferative nonneoplastic and neoplastic liver lesions in medaka (Oryzias latipes): consensus of a National Toxicology Program Pathology Working Group

Women residing in villages in three districts of Pakistan were recruited, trained to deliver primary care and mobilize their communities for health, assigned to limited catchment areas, provided with supervisory and managerial support, and remunerated. Their comprehensive activities substantially reduced infant, child and maternal mortality within a year and generated positive perceptions of family planning in the communities. The programme was cost-effective and appeared suitable as a model for reforming the organization and provision of health care services.     

Variance components analysis of carotid and femoral intima-media thickness measurements. REGRESS Study Group, Interuniversity Cardiology Institute of The Netherlands, Utrecht, The Netherlands. Regression Growth Evaluation Statin Study

B-mode ultrasound intima-media thickness (IMT) measurements of carotid and femoral arterial walls are used in atherosclerosis studies. In this study, the components contributing to IMT measurement variability in males with coronary artery disease were investigated by means of repeated B-mode ultrasound scans and repeated off-line video image analyses. For statistical analysis, a mixed-model analysis of variance was used. From sonographer data, it was shown that human subjects and their arterial wall segments contributed 75% of the total IMT measurement variability in this population. Inter-sonographer variance contributed 25%. The intra-sonographer variance was negligible (<1%). In off-line image analysis, variance components due to subjects and segments, inter-analyst variance, and residual fluctuation were 88%, < 1% and 11%, respectively. Intra-analyst variance was negligible (<1%). The major source of B-mode ultrasound IMT measurement variability finds its origin in subjects and their arterial walls. Although sonographers proved a lesser source of variability, in comparative studies they should enter a study well trained and should be randomly assigned to subjects. Follow-up examinations should preferably be done by the same sonographer. Off-line image analysis contributed little to IMT measurement variability.