Comparison of docetaxel/cisplatin to docetaxel/gemcitabine as first-line treatment of advanced non-small cell lung cancer: early results of a randomized trial.

The study compares docetaxel plus cisplatin (DC) and docetaxel plus gemcitabine (DG) regimens for the treatment of advanced non-small cell lung cancer (NSCLC). Patients were randomized to receive either the DC or the DG combination. They were stratified according to age, performance status (PS) and stage of disease. Three hundred seventeen patients entered the study. Of them, 162 received the DC regimen and 155 the DG regimen. There were no differences in the patients' characteristics between the two study arms. Preliminary analysis included 132 evaluable patients in the DC arm and 114 in the DG arm. Three complete responses (CR) (2.3%) and 39 partial responses (PR) (30%) were documented in the DC arm (response rate (RR) 32.3%; 95% CI 23.87-39.76%), whereas 1 CR (0.9%) and 38 PR (33%) were documented in the DG arm (RR: 33.9%; 95% CI 25.5-42.92%). No differences in the RR, response duration, time to tumor progression, overall survival and 1-year survival were observed between the two groups. Regarding toxicity, there were no significant differences in grade 3-4 anaemia and thrombocytopenia between the two arms. However, grade 3-4 neutropenia occurred in 40 patients (33%) treated with the DC regimen and in 31 patients (22%) treated with the DG regimen (P=0.01). Twenty-four (16%) patients in the DC arm and 20 (14%) in the DG arm developed febrile neutropenia. There was one death due to sepsis in each arm. Non-haematological toxicity was mild and equal in the two arms, with the exception of grade 3-4 nausea and diarrhoea, which were more frequent in the DC arm. In conclusion, preliminary results showed that the DG regimen was as effective as the DC regimen. The toxicity profile of the DG combination was relatively milder. Hence, cisplatin cannot be considered longer as a mandatory component of chemotherapy against NSCLC.

Low expression of p27 protein combined with altered p53 and Rb/p16 expression status is associated with increased expression of cyclin A and cyclin B1 in diffuse large B-cell lymphomas.

The expression of the cyclin-dependent kinase inhibitor (CDKI) p27 protein was investigated in relation to (1) the expression of the cell cycle regulators p53, Rb and p16 and (2) the proliferation profile as determined by the expression of Ki67, cyclin A, and cyclin B1 in 80 cases of de novo diffuse large B-cell lymphomas (DLBCL). P27 expression was low/null in large tumor cells in 58/80 cases and intermediate/high in 22/80 cases. Increased expression of p53 protein was observed in 39/80 cases. Decreased expression of Rb and p16 proteins was mutually exclusive and was observed in 5/80 and 14/80 cases, respectively. The analysis of the p27 expression status (low/null versus intermediate/high) with respect to the p53 and/or Rb/p16 expression status showed that low/null p27 expression was significantly correlated with increased p53 expression (P =.018) and showed a strong trend for correlation with concurrent increased p53 expression and decreased Rb or p16 expression (P =.050). These findings suggest a tendency for concurrent alterations of the cell cycle regulators p27, p53, and Rb or p16 in DLBCL, which might result in impaired tumor growth control. Indeed, the analysis of the combined p27/p53/Rb/p16 expression status with respect to the proliferation profile showed that (1) three alterations in the combined p27/p53/Rb/p16 status (i.e., low/null P27 expression, increased expression of p53, and decreased expression of Rb or p16) were significantly correlated with increased expression of cyclin B1 (P =.005) and (2) two or three alterations were significantly correlated with increased expression of cyclin A (P =.014). These findings suggest combined impairment of a complex cell-cycle control network involving the CDK inhibitor p27, the P53 pathway, and the Rb1 pathway, which exerts a cooperative effect resulting in enhanced tumor cell proliferation.

Managing Alzheimer's disease in primary care in Crete, Greece: room for improvement.

As Greece moves during the last two decades toward a national health care system, which gives emphasis to the development of a primary care system, many worry how to ensure that the quality of care is assessed. This is more apparent in the rural populations, in which health care is served to a large extent by physicians without formal training in general practice. This article explores the level of knowledge of primary care physicians in relation to Alzheimer's disease in geographically defined areas of Crete, Greece, in comparison with that of general practitioners in Ostergötland, Sweden, and in Iceland. It emphasizes the need for better education and training for primary care physicians in Crete in both the early diagnosis and management of Alzheimer's disease.

Docetaxel-induced lymphopenia in patients with solid tumors: a prospective phenotypic analysis.

BACKGROUND: The quantitative abnormalities of the different peripheral blood lymphocyte subsets during docetaxel administration were prospectively studied. METHODS: Forty-six chemotherapy-naive patients with solid tumors were treated with docetaxel either in a 3 weekly (n = 33) or weekly (n = 13) schedule. Twenty patients with central nervous system (CNS) metastatic disease as the first clinical presentation of cancer and 35 patients with metastatic colorectal carcinoma treated with chemotherapy were enrolled as controls. The phenotype of peripheral blood lymphocytes was determined by indirect immunofluorescence using appropriate monoclonal antibodies and fluorescent-activated cell sorter analysis. RESULTS: After the administration of the first docetaxel cycle, the absolute number of peripheral blood lymphocytes (P < 0.005), CD3(+) (P < 0.01), CD4(+) (P < 0.01), CD8(+) (P < 0.01), and CD56(+) (P < 0. 01) but not CD20(+) (P < 0.3) cells was significantly decreased compared with the pretreatment values. Further treatment resulted in a further decrease of these lymphocyte subsets including CD20(+) cells (P < 0.01). Similarly, after the administration of the first weekly dose of docetaxel, the absolute number of total lymphocytes, CD3(+), CD4(+), and CD8(+) cells was decreased. The administration of the second weekly docetaxel dose resulted in a further decrease of CD56(+) (P = 0.012) and CD20(+) (P = 0.007) cells. The administration of either high dose corticosteroids in patients with CNS metastases or an irrelevant chemotherapy (CPT-11/5-FU) did not result in similar abnormalities. The discontinuation of docetaxel was associated with a recovery of CD3(+) and CD4(+) lymphocytes within a 3-month period. Eight (17%) patients developed nonneutropenic infections during docetaxel treatment. CONCLUSIONS: Docetaxel has an important but reversible nonspecific lymphopenic effect that seems to be associated with an increased risk for nonneutropenic infections.

Quantitative cytology in ovarian carcinoma ascitic fluids.

OBJECTIVE: To assess the value of quantitative methods in the differential diagnosis between ovarian carcinoma cells and mesothelial cells in ascitic fluids. STUDY DESIGN: Ninety ascitic fluid samples, previously reported as positive for ovarian carcinoma (30 cases), suspicious for malignancy (30) and negative for malignancy, containing only reactive mesothelial cells (30), were retrieved from the files. In each of these specimens the nuclear area, perimeter, roundness and shape coefficient of 100 cells were determined at 630 x magnification. Statistical analysis was performed using analysis of variance and, for multiple comparisons, the Student-Newman-Keuls technique. RESULTS: Mean values for nuclear area and perimeter were higher in malignant cells as compared to reactive mesothelial cells, whereas those for roundness and shape coefficients were lower. All differences were statistically significant, the former two at a .05 level and the latter at the .001 level. CONCLUSION: Quantitative methods can reliably support the differential diagnosis between ovarian carcinoma cells and mesothelial cells in ascitic fluid specimens.

Expression of p53, p21/waf1, bcl-2, bax, Rb and Ki67 proteins in Hodgkin's lymphomas.

The aim was to investigate the combined immunoexpression of p53, p21, bcl-2, bax, Rb and Ki67 proteins in Hodgkin's lymphomas (HL) and correlate expression patterns with the histotype and the Epstein-Barr Virus (EBV) status. Paraffin-sections from 56 cases of HL (18 nodular sclerosis and 38 mixed cellularity) and from ten "reactive" lymph nodes were investigated. P53, p21, bcl-2, bax, Rb and Ki67 proteins were detected in Hodgkin and Reed-Sternberg (HRS) cells in 35/56, 56/56, 24/56, 23/56, 56/56 and 56/56 cases of HL, respectively. No correlation was found between the expression of each protein and the EBV status or the histotype of HL. Comparison between p53 and p21 staining revealed two patterns: a) p53+/p21+ (35 cases); and b) p53-/p21+ (21 cases). The pattern p53+/p21+ suggests wild type p53 protein able to induce the expression of p21 while the p53-/p21+ pattern suggests p53-independent p21 expression. These results are consistent with the interpretation that inactivating p53 gene mutations may be rare in HL. Comparison between bcl-2 and bax staining showed a statistically significant relationship (p<0.001) for coexpression (19 cases) or absence of expression of both proteins (28 cases) in HRS cells. In contrast, bax expression was observed in most lymphoid cells in all "reactive" lymph nodes. Since the proapoptotic bax protein may act as tumour suppressor it is possible that the absence of this protein in HRS cells in a substantial proportion of HL may confer growth advantage and play a role in their pathogenesis. This could suggest bax gene alterations in some HL since in other studies acute lymphoblastic leukaemia cell lines demonstrate bax gene mutations with loss of bax immunoexpression. Another possibility is that reduced bax expression may be due to post transcriptional regulation, as was described in lymphoma cell lines. Comparison between Rb and Ki67 staining disclosed two main deviations from the normal parallel relationship in reactive lymph nodes: a) 2 cases with low Rb and high Ki67 expression possibly reflecting loss of Rb expression due to chromosome loss or to other abnormalities in the structure or the expression of Rb gene; and b) 9 cases with high RB and low Ki67 possible reflecting an attempt of Rb protein in excess to induce cell cycle arrest. Taken together, our findings provide combined immunohistological evidence for deregulated expression of cell-cycle and apoptosis-related proteins, that may play a role in the pathogenesis of HL.

Docetaxel in combination with carboplatin for the treatment of advanced non-small cell lung carcinoma: a multicentre phase I study.

Docetaxel and carboplatin have shown in vitro and in vivo activity against non-small cell lung cancer (NSCLC). A phase I study was conducted in order to determine the dose-limiting toxicities (DLTs) and the maximum tolerated doses (MTDs) of their combination. Chemotherapy-naïve patients with stage IIIB and IV NSCLC, age<75 years old, performance status (WHO) 0-2, with adequate bone marrow, renal, liver and cardiac function, were treated with docetaxel and carboplatin. Docetaxel was given at escalated doses starting from 70 mg/m(2) with increments of 10 mg/m(2) followed by carboplatin also administered at escalated doses starting from AUC 5 to 7 AUC (mg/ml. min); the regimen was administered every 3 weeks. No colony-stimulating factor or intrapatient escalation was allowed. The toxicity of the regimen was assessed during the first chemotherapy cycle. 35 enrolled patients received a total of 114 chemotherapy cycles (median 3 cycles/patient; range: 1-8). All patients were assessable for toxicity. Neutropenia was the main dose-limiting toxicity of the regimen; overall, grade 3/4 neutropenia occurred in 16 (14%) cycles; six (5%) neutropenic episodes were complicated with fever but there was no septic death. Grade 3/4 thrombocytopenia was uncommon (two cycles; 2%). Grade 3/4 diarrhoea occurred in 5 (14%) patients whilst neurotoxicity, fatigue and mucositis were extremely uncommon. Two MTDs were defined: the MTD(1) was docetaxel 80 mg/m(2) and carboplatin AUC 7 mg/ml x min whilst MTD(2) was docetaxel 100 mg/m(2) and carboplatin AUC 6 mg/ml x min. The combination of docetaxel and carboplatin is a feasible and well-tolerated outpatient regimen for the treatment of patients with locally advanced and metastatic NSCLC. This regimen merits further investigation in phase II trials.

Immunohistochemical expression of the p53, p21/Waf-1, Rb, p16 and Ki67 proteins in multiple myeloma.

The aim of this study was to investigate the immunohistochemical expression of the proteins p53, Waf-l/p21, Rb, p16 and Ki67 in 38 cases of multiple myelomas (MM) and 4 cases of solitary extramedullary plasmacytomas in relation to the tumor histological grade and stage. In bone marrow (BM) biopsies from MM, overexpression of p53 and p21 proteins, in comparison to plasma cell infiltrates in non-pathological bone marrow, was detected in 13 out of 38 and 21 out of 38 cases, respectively. The combined immunoexpression of p53 and p21 proteins in the 38 cases of MM showed the following patterns: a) p53+/p21+ (13 cases) b) p53-/p21+ (8 cases) and c) p53-/p21- (17 cases). Rb, p16 and Ki67 proteins were detected in tumor cells in all 38 cases and their expression increased proportionally to tumor grade. The 4 cases of solitary extramedullary plasmacytomas showed the p53+/p21+ pattern in 2 cases and the p53-/p21+ pattern in 2 cases, all of them displaying Rb, p16 and Ki67 expression in tumor cells. The pattern p53+/p21+ might represent cases with wild-type p53 able to induce p21 expression. However, in previous studies p53 mutations were reported in about 3-10% of MM, and they were strongly associated with advanced disease. Thus, in some p53+/p21+ cases associated with high p53 expression and advanced disease, p53 gene cannot be excluded and up-regulation of p21 expression may be p53- independent. P53 overexpression correlated with increased tumor grade (p < 0.005), advanced histological stage (p < 0.001) and Ki67 expression in more than 10% of tumor cells (p < 0.001). Since increase in Ki67 expression also correlated with increased tumor grade (p < 0.001) and advanced histological stage (p < 0.001), these findings suggest that impairment of the p53 growth control pathway is associated with tumor progression in MM. Thus, p53 and Ki67 immunostaining in routine BM biopsies may be helpful for the detection of MM with potentially aggressive behavior. Overexpression of p21 in MM correlated with higher Ki67 expression (p < 0.005), suggesting that the p21 function of arresting cell-cycle is impaired. Ki-67 expression in MM increased in parallel with p16 (p < 0.001) and Rb expression (p < 0.001). Rb expression could represent a growth control response which, however, might not be able to induce growth arrest in view of the parallel increase in Ki67 expression and of previous findings showing that Rb protein in MM cells is expressed mostly in its phosphorylated form.

Seroprevalence of hepatitis A, B and C markers in Greek warship personnel.

A seroepidemiological study was conducted to assess the seroprevalence of hepatitis A, B and C markers in 285 males (mean age: 24.4+/-4.4 years) aboard a Greek warship. Two hundred and sixty three serum samples were tested. None was found to be positive for HAV antibodies, three persons (1.1%) were positive for HBsAg, four persons (1.5%) were positive for anti-HBc and one person (0.4%) was positive for anti-HCV. Forty-five persons (17.1%) had developed titles anti-HBs > 10 IU/L. The establishment of a vaccination policy against hepatitis A among warship personnel is strongly recommended.

Clinical application of immunological markers as monitoring tests in celiac disease.

The aim of this study was to investigate anti-gliadin (IgA-AGA and IgG-AGA), endomysial (IgA-EmA), and anti-reticulin (Ig-ARA) antibodies for monitoring celiac disease (CD) patients while on gluten-free and gluten-containing diets. Sera from 30 confirmed CD patients (13 boys, 17 girls), 1-24 years old, were examined for antibodies using ELISA (AGA) and Immunofluorescence (EmA, ARA) at 1, 3, 6, 9, and 12 months following institution of gluten-free diet and also at 3 and 6 months after challenge with gluten. One month following the exclusion of gluten from the diet, most antibodies are still positive. Twenty-three to 43% of antibodies remained positive by the end of the third month. At 6 and 9 months, 17% and 10% were positive, respectively. At 12 months no positive antibodies were detected. After gluten challenge, positive IgA-AGA and IgA-EmA titers were already demonstrated at 3 months (90% and 86%, respectively), while Ig-ARA titers showed a slow increase. Finally IgG-AGA responded with a slow decrease of titers to gluten-free diet levels and a fast increase upon provocation. The morphology of the intestine at diagnosis and during the periods of gluten-free diet and gluten challenge corresponds with the antibody titers. On the basis of these results, immunological markers may be applied to follow-up CD patients. IgA-AGA and IgA-EMA appear to be the most sensitive to dietary changes in gluten and correlate best with intestinal mucosal morphology.

Is there room for general practice in penitentiary institutions: screening and vaccinating high-risk groups against hepatitis.

OBJECTIVE: The purpose of this study was to determine the prevalence of hepatitis markers in inmates and staff of the Penitentiary of Neapolis on Crete and discuss the role of GPs in identifying and vaccinating susceptible subjects. METHOD: Forty-five prisoners and 20 house workers were invited to participate in the study. Hepatitis B (HBV) markers (HBsAg and anti-HBc) and hepatitis C antibodies (anti-HCV) were tested. Vaccination against hepatitis B was administered to all susceptible subjects. RESULTS: Hepatitis B carriage was found in 10 people, six of whom were prisoners. Fifteen of the subjects tested were found to be positive for anti-HBc, six of whom were house workers. Anti-HCV were found to be positive in seven prisoners and one worker. A vaccination programme against hepatitis B was introduced in 27 susceptible subjects (58.7% of unexposed subjects) and was completed in 22. CONCLUSION: Prisoners and staff at Neapolis Prison constitute a high-risk group for hepatitis B and C. Compliance rate in screening was high and GPs were successful in having a desirable response rate in the administration of vaccines.

Bringing community involvement into a Cretan primary/hospital care center: an evaluation of population habits and attitudes toward health care.

In a small Cretan township hospital combining secondary and primary care, a questionnaire was distributed to a consecutive visitor sample. The questionnaire requested information on the participants' personal smoking and other life habits, perceptions and expectations of the delivery of the health care services, and attitudes toward their own doctors and others who provide various health services. Three hundred and one individuals of both sexes who were 15 years and older participated in the study (participation rate, more than 97%). An interesting and varied response was recorded, covering a wide range of perceptions, opinions, and attitudes not only toward the services, but also toward the staff. Although a high confidence in and appreciation of both the primary care and hospital sections appeared in the study results, these attitudes should not be allowed to deteriorate. Therefore, specific actions should be undertaken: constant upgrading of the existing organizational context, implementation of promotional and educational programs, and use of the questionnaire as an effective tool for periodically assessing the population's attitudes, experiences, and expectations.

Expression of p53, p21/waf, bcl-2, bax, Rb and Ki67 proteins in colorectal adenocarcinomas.

This study investigated the combined immunoexpression of p53, p21, bcl-2, bax, Rb and Ki67 proteins in colorectal adenocarcinomas and correlated expression patterns with tumour stage and grade. Paraffin sections from 98 cases of colorectal adenocarcinomas were stained by immunohistochemistry for p53, p21, bcl-2, bax, Rb and MIB-1 (Ki67) proteins. In addition, 12 cases of colorectal adenomas and normal colorectal mucosa were studied in parallel. P53, p21, bcl-2, bax, Rb and Ki67 proteins were detected in at least 5% of tumour cells in 63/98, 72/98, 52/98, 96/98 and 98/98 adenocarcinomas, respectively. Comparative study of the normal-adenoma-carcinoma tissues revealed abrogation of the normal immunotopography in adenomas and adenocarcinomas, and considerable modifications, increase or reduction, of the expression of p53, p21, bcl-2, bax, Rb and Ki67 proteins in adenocarcinomas when compared with normal mucosa and adenomas. Statistically significant correlations were found between low bax expression and Dukes C stage of carcinomas, Ki67 expression and carcinoma grade, and Ki67 and Rb expression. P53, p21, bcl-2 and Rb immunoexpression did not correlate with tumour stage or grade. Our findings show that low bax immunoexpression is frequently related to colorectal adenocarcinomas with lymph node metastases suggesting that low levels of bax expression play a role in late stage colorectal cancer. The correlation between Ki67 and Rb expression, in view of previous data that the hyperphosphorylated inactive Rb protein is frequently increased in colorectal adenocarcinomas, suggests that Rb protein is somewhat ineffective in inhibiting the cell-cycle progression in these malignancies. Furthermore, our findings provide immunohistochemical evidence that the abrogation of the normal immunotopography and the modifications of the expression of p53, p21, bcl-2, bax, Rb and Ki67 proteins reflect important events in colorectal oncogenesis.

Dose-escalation study of docetaxel in combination with mitoxantrone as first-line treatment in patients with metastatic breast cancer.

PURPOSE: To define the maximum-tolerated dose (MTD) and the dose-limiting toxicities (DLTs) of docetaxel in combination with mitoxantrone in patients with metastatic breast cancer (MBC). PATIENTS AND METHODS: Forty-one chemotherapy-naive patients with MBC (median age, 61 years) were enrolled. Thirty-eight (93%) had performance status (World Health Organization [WHO]) 0, 29 (71%) were postmenopausal, and 21 (51%) had estrogen receptor-negative tumors. Patients received escalated doses of docetaxel (75 to 100 mg/m2) on day 1 and mitoxantrone (8 to 22 mg/m2) on day 8. Treatment was repeated every 3 weeks. RESULTS: A total of 217 chemotherapy cycles were administered. Without recombinant human granulocyte colony-stimulating factor (rhG-CSF) support, the MTD1 occurred at the first dose level (docetaxel 75 mg/m2 and mitoxantrone 8 mg/m2); DLTs were febrile neutropenia, grade 4 neutropenia lasting more than 5 days, and grade 3 diarrhea. With prophylactic rhG-CSF, the MTD2 was docetaxel 100 mg/m2 and mitoxantrone 20 mg/m2; DLTs were febrile neutropenia and grade 4 neutropenia. Nine (22%) patients developed neutropenia after the first cycle of treatment. A total of 19 episodes of febrile neutropenia (9% of the cycles) occurred during the whole period of the study; there were no toxic deaths. At high docetaxel (100 mg/m2) and mitoxantrone (> 12 mg/m2) dose levels, a significant decrease of the absolute lymphocyte number was observed; immunophenotyping revealed that all lymphocyte subpopulations were reduced. Grades 2 and 3 neurosensory toxicity occurred in six patients (15%) and one patient (2%), respectively. No cardiac toxicity was observed. Nine complete responses (22%) and 23 partial responses (56%) were achieved (overall response rate, 78%; 95% confidence interval, 62.5% to 88.8%). The median duration of response was 12.5 months, and the median time to tumor progression was 14.5 months. CONCLUSION: The reported combination of docetaxel and mitoxantrone with G-CSF support is a safe, intensified, well-tolerated, and effective regimen as first-line treatment in patients with MBC.

Combination chemotherapy with docetaxel, vinorelbine and cisplatin as first-line treatment of advanced non-small-cell lung cancer: a multicenter phase II study of the Greek Cooperative Group for Lung Cancer.

Vinorelbine, docetaxel and cisplatin have documented single-agent activity in non-small-cell lung cancer (NSCLC); a multicenter phase II trial was initiated in order to evaluate the tolerance and efficacy of their combination. A total of 24 chemotherapy-naive patients with measurable stage IIIB or IV NSCLC and performance status (PS; WHO) 0-2 entered the study. Vinorelbine (20 mg/m2 i.v.) was given on days 1 and 15, cisplatin (60 mg/m2) on day 1, and docetaxel (100 mg/m2) on day 16, in cycles of 28 days. Recombinant human granulocyte colony-stimulating factor (150 microg/m2 s.c.) was administered prophylactically from day 17 to day 27. One pathological complete (4%) and six partial responses (25%) were documented (overall response 29%; 95% CI 11.6-49.2%). A total of five patients (21%) had stable and 12 (50%) progressive disease. The median duration of response was 28 weeks and the median time to tumor progression 36 weeks; the median survival was 20 weeks. Grade 3-4 neutropenia occurred in 16 patients (67%) while 13 of them (54%) developed febrile neutropenia. Grade 4 mucositis occurred in two patients (8%) and one of them also presented grade 4 diarrhea. There were four treatment-related deaths: two from sepsis, one from massive hemoptysis due to a pulmonary abscess and one from acute myocardial ischemia 7 days post-chemotherapy. In conclusion, the high incidence of neutropenic episodes and treatment-related deaths led to an early discontinuation of patient enrollment. This combination, in the schedule and the doses used, could not be recommended for off protocol treatment of patients with advanced NSCLC.

First-line treatment of advanced nonsmall cell lung carcinoma with docetaxel and vinorelbine.

BACKGROUND: Docetaxel and vinorelbine are active agents in the treatment of nonsmall cell lung carcinoma (NSCLC). The efficacy and toxicity of this combination was evaluated in a Phase II study in patients with advanced NSCLC. METHODS: Forty-six chemotherapy-naive patients (44 men and 2 women with a median age of 64 years) with NSCLC (11 with Stage IIIB and 35 with Stage IV disease) were entered into the study; the World Health Organization (WHO) performance status was 0, 1, and 2 in 32, 11, and 3 patients, respectively. Patients received vinorelbine (25 mg/m2) on Day 1 and docetaxel (100 mg/m2) on Day 2 in cycles repeated every 3 weeks. Granulocyte-colony stimulating factor was given to all patients from Day 3 to Day 10. RESULTS: One hundred and seventy-seven courses of chemotherapy were administered. Adverse events included WHO Grade 4 neutropenia (15 patients), Grade 3/4 thrombocytopenia (3 patients), Grade 3 anemia (2 patients), Grade 2 and 3 neurotoxicity (7 patients and 1 patient, respectively), and Grade 3 fatigue (2 patients). Twenty patients (43%) required hospitalization: 11 (24%) for neutropenic fever (2 deaths from sepsis), and 9 (20%) for nonneutropenic pulmonary infections (2 deaths from cardiopulmonary insufficiency). The median overall survival was 5 months and the 1-year survival was 24%. Four complete responses (9.8%) and 11 partial responses (26.8%) (overall response rate of 36.6%; 95% confidence interval, 21.8-51.3%) were documented in 41 evaluable patients (intent-to-treat: 32.6%). Stable and progressive disease occurred in 13 patients each (31.7%). The median duration of response was 5 months and the median time to progression was 3 months (6 months for the responders). CONCLUSIONS: This schedule of docetaxel and vinorelbine combination is effective but its relatively high incidence of complicated neutropenia precludes its general use in patients with advanced NSCLC.

Does draining the neck affect morbidity following thyroid surgery?

A prospective randomized study questioning the benefit of neck drainage in thyroid surgery is presented. Two hundred consecutive patients, candidates for elective thyroid surgery, were randomized into Group A (no drain) and Group B (drain). Reoperation for bleeding was necessary for two patients of Group A and for one patient in Group B. Minor hematomas occurred in seven patients from Group A and five patients from Group B; wound infection occurred in two and four patients in Groups A and B, respectively; and lymphatic discharge occurred in two patients from Group B. These differences were not statistically different. The present study failed to demonstrate any protective value from the use of drains. However, the hospital stay was shorter and pain scores were smaller in the non-drain Group A.

Heart disease risk-factor status and dietary changes in the Cretan population over the past 30 y: the Seven Countries Study.

A follow-up study was conducted to identify the heart disease risk-factor status and dietary changes of surviving elderly subjects in Crete who took part in the Seven Countries Study in 1960. In 1991, data were obtained from 245 of the 686 original male participants (169 of the original 40-49-y age group and 76 men 50-59 y age group). In 1991, the men were 70-79 and 80-89 y old. There was a significant (11.5%) increase in serum total cholesterol concentrations between 1960 and 1991. Body mass index and systolic and diastolic blood pressures also increased significantly, and all age groups were characterized by central obesity. A representative subsample of 21 men took part in a 3-d weighed food record study. Dietary data indicated increases in the intake of saturated fat and decreases in monounsaturated fat over the 30-y period. Comparison with a 1962 representative Cretan sample indicated a significantly increased concentration of adipose palmitic acid (16:0) in our surviving sample. The observed changes occurred during a period when many developed countries were observing a decline in most heart disease risk factors.

Quantitative pathology in uterine smooth muscle tumours: the case for the standard histologic classification criteria.

A number of nuclear morphometric factors (longest and shortest axis, perimeter, area, roundness coefficient) as well as the number of mitoses per 20 high power fields with an x40 objective (mitotic index) and the volume corrected mitotic index (VCMI) have been assessed in 33 uterine smooth muscle tumours (14 leiomyomata, 5 leiomyosarcomata, 9 atypical leiomyomata and 5 tumours of uncertain malignant potential). Multivariate analysis showed the VCMI and nuclear roundness coefficient to be the two most significant prognostic factors achieving, by means of Fisher's linear discriminant function, a high percentage of correct reclassification of the tumours into their respective groups. Furthermore, VCMI was shown to be a more accurate prognostic factor than the simple mitotic index. The results uphold the traditional classification histologic criteria and demonstrate the significance of VCMI as a reliable index of mitotic activity.

Morphologic differences between latent membrane protein-1 (LMP-1)-positive and negative tumour cells in Epstein-Barr virus (EBV)-related childhood Hodgkin's disease. A morphometric study.

The values of five cellular morphometric parameters (longest and shortest cytoplasmic axis, cellular circumference, area and roundness coefficient) were compared between 20 Latent Membrane Protein 1 (LMP-1)-positive and an equal number of LMP-1-negative Reed-Sternberg and Hodgkin (HRS) cells for each of 13 cases of Hodgkin's disease (HD) occurring in children (aged 3-15 years); the presence of Epstein-Barr virus (EBV) encoded EBER mRNAs had previously been detected in all cases using RNA in situ hybridisation (RISH), while the presence of LMP-1 was immunohistochemically detected using the alkaline phosphatase-antialkaline phosphatase (APAAP) method. The longest and shortest axis, circumference and area were larger in LMP-1-positive than in LMP-1 negative HRS cells, while the roundness coefficient of LMP-positive HRS cells was smaller than that of LMP-1 negative cells. All differences were statistically highly significant when univariate (paired comparisons) t-test were used. Multivariate analysis (Hotelling's T2 test) showed all differences (except the roundness coefficient) to be significant both at the 5% and 1% level of significance. These results provide a numerical basis for the alteration brought by the expression of LMP-1 in the cellular skeleton of tumour (HRS) cells in EBV-related childhood HD cases.