Docetaxel and oxaliplatin combination in second-line treatment of patients with advanced gastric cancer

Background In advanced gastric cancer few data are available on the efficacy or safety of new drug combination regimens after progression following first-line chemotherapy. Methods Patients with histologically confirmed advanced gastric cancer and Eastern Cooperative Oncology Group (ECOG) performance status (PS) less than 2, progressing after first-line chemotherapy, were eligible. Patients were treated with docetaxel 75 mg/m² on day 1 and oxaliplatin 80 mg/m² on day 2, every 3 weeks, until progression or unacceptable toxicity. Results Between May 2002 and April 2005, 38 patients were enrolled. Men accounted for 73.7% of the patients and the median age was 59 years. The primary tumor was not resected in 47.4% of the patients; the peritoneum was the most frequent metastatic site (60.5%). The first-line treatment was cisplatin, epirubicin, and infusional 5-fluorouracil (ECF) in 81.5% of the patients and cisplatin and infusional 5-fluorouracil (CF) in 15.7%. The median number of cycles was 4.3. The treatment was well tolerated, with no toxic deaths. National Cancer Institute (NCI) grade III-IV neutropenia was frequent (26.3%), but no febrile neutropenia was reported. Severe asthenia (15.7%) and severe nausea (15.7%) required dose reductions in 2 patients and treatment discontinuation in another. The overall response rate was 10.5%, and 18 patients (47.3%) experienced disease stabilization (7 of them with significant clinical benefit). Median time to progression was 4.0 months (range, 2–8 months) and median overall survival was 8.1 months (range, 3–26 months). Thirteen patients (34.2%) also received third-line chemotherapy, with an irinotecan-containing regimen, and their median overall survival was higher than that of the other patients (16.3 vs 6.0 months) Conclusion The combination of oxaliplatin and docetaxel shows only marginal activity as second-line treatment, but it has a good tolerability profile. This suggests that there is room for optimizing the schedule as well as for planning sequential treatments in gastric cancer.     

Effect of cholecystokinin analogue caerulein and cholecystokinin antagonist lorglumide on pancreatic carcinogenesis in the rat

The effects of the cholecystokinin (CCK)-analogue, caerulein, and CCK-receptor antagonist lorglumide (CR-1409) on pancreatic carcinogenesis induced by 7,12-dimethylbenz(a)anthracene (DMBA) were studied. One hundred thirty rats were divided into the following 10 treatment groups: group 1, DMBA (2–3 mg); group 2, DMBA + caerulein (5 μg/kg); group 3, DMBA + caerulein + CR-1409 (12 mg/kg); group 4, caerulein + DMBA; group 5, caerulein + CR-1409 + DMBA; group 6, DMBA + CR-1409; group 7, CR-1409 + DMBA; group 8, caerulein; group 9, CR-1409; and group 10, sham operation + saline. DMBA was surgically implanted into the pancreas. Caerulein and/or CR-1409 was administered twice daily for 15 days after (in groups 2, 3, and 6) or before (in groups 4, 5, and 7) DMBA implantation. Six months after carcinogen administration, all rats were sacrificed and autopsied. The incidence of pancreatic cancer appeared significantly (P < 0.001) increased when caerulein was administered following DMBA implantation. CR-1409 significantly inhibited (P < 0.02) caerulein effects and reduced tumor growth when injected after carcinogen exposure. © 1994 Wiley-Liss, inc.     

Suicidal ideation and aggressiveness in school-aged youths

This study set out to explore the frequency and correlates of suicidal ideation in a community sample of school-aged adolescents living in a northeastern area of Italy. The study involved a mixed male–female sample of 1000 adolescents, corresponding to 10% of the young population aged 15–19 in the district. We investigated psychological distress through the revised Symptom Checklist (SCL-90-R), from which we also derived our indicators on suicidality (items concerning hopelessness and suicidal ideation). Propensity to aggression was measured with an Italian version of the Aggression Questionnaire. Females scored significantly higher than males on all SCL-90-R subscales, with the exception of the hostility subscale. In our sample, 30.8% of females and 25.3% of males reported having thought about suicide; one adolescent out of 20 reported suicidal ideation of high intensity (5% out of the total sample in both genders). Males scored significantly higher than females on the Aggression Questionnaire. Both males and females who reported suicidal feelings had significantly higher scores on the Aggression Questionnaire than did those who denied suicidal ideation. Suicidal ideation is a rather widespread occurrence among adolescents and correlates with other indicators of psychological distress. Psychological distress in adolescence might also be expressed through turbulent behaviors and conduct disorders. Identification of the mental disorders underlying a higher propensity to aggression might help to prevent other negative outcomes such as suicide.     

New fish-killing alga in coastal Delaware produces neurotoxins

Ten fish mortality events, involving primarily Atlantic menhaden, occurred from early July through September 2000 in several bays and creeks in Delaware, USA. Two events involved large mortalities estimated at 1-2.5 million fish in Bald Eagle Creek, Rehoboth Bay. Samples from Indian Inlet (Bethany Beach), open to the Atlantic, as well as from an enclosed area of massive fish kills at nearby Bald Eagle Creek and Torque Canal were collected and sent to our laboratory for analysis. Microscopic examination of samples from the fish kill site revealed the presence of a single-cell Raphidophyte alga Chattonella cf. verruculosa at a maximum density of 1.04 x 10(7) cells/L. Naturally occurring brevetoxins were also detected in the bloom samples. Besides the Chattonella species, no other known brevetoxin-producing phytoplankton were present. Chromatographic, immunochemical, and spectroscopic analyses confirmed the presence of brevetoxin PbTx-2, and PbTx-3 and -9 were confirmed by chromatographic and immunochemical analyses. This is the first confirmed report in the United States of brevetoxins associated with an indigenous bloom in temperate Atlantic estuarine waters and of C. cf. verruculosa as a resident toxic organism implicated in fish kills in this area. The bloom of Chattonella continued throughout September and eventually declined in October. By the end of October C. cf. verruculosa was no longer seen, nor was toxin measurable in the surface waters. The results affirm that to avoid deleterious impacts on human and ecosystem health, increased monitoring is needed for brevetoxins and organism(s) producing them, even in areas previously thought to be unaffected.     

Domiciliary clinics II: a cost minimisation analysis

OBJECTIVES: We compare the cost of assessing new referrals to an old age psychiatry service at the patient's home or a hospital-based clinic. METHOD: An old age psychiatry service in Liverpool where routine referrals were assessed at home (domiciliary clinic) was compared to an adjacent service which assessed people in an outpatient clinic. Activity levels for four years of the service were collected and analysed. A cost-minimization analysis was done using an algorithm which allowed all direct costs to the service to be taken into account. A sensitivity analysis changed key values of the algorithm allowing their relative contribution to be considered. RESULT: The domiciliary clinic was marginally cheaper than outpatient assessment (48 pounds sterling compared to 50 pounds sterling per successful assessment). The most important variables in determining the cost effectiveness of the service were non-attendance rates, the grade of doctor seeing the patient and the time spent traveling for the home assessment. CONCLUSIONS: Domiciliary initial assessments were comparable in cost to clinic assessments in this study but in other situations the cost will vary, depending on the key local variables.     

Further evidence of the validity and reliability of the Skindex-29: an Italian study on 2,242 dermatological outpatients

BACKGROUND: Quality of life is increasingly recognized as an important measure in dermatology. The Skindex-29 is a self-administered questionnaire recently developed to measure comprehensively the complex effects of skin diseases on patients' quality of life. OBJECTIVE: We aimed to provide further evidence of the reliability and validity of the Skindex-29 in a large sample of patients affected by a wide variety of skin diseases. METHODS: An Italian version of the Skindex-29 was produced following accepted guidelines for the cross-cultural adaptation of questionnaires. All adult outpatients attending a dermatological hospital on predetermined days were given the Skindex-29 and the 12-item General Health Questionnaire (GHQ-12). RESULTS: A total of 2,242 complete questionnaires were analyzed. The internal consistency and test-retest reliability of each scale were high. The factor structure of the Skindex-29 was strikingly similar to the one originally observed in American patients. The pattern of correlation with the GHQ-12 provided evidence of convergent validity of the Skindex-29. CONCLUSION: The instrument seems to measure three fundamental dimensions of skin health-related quality of life.     

Nonocclusion and spontaneous recanalization rates in acute ischemic stroke: a review of cerebral angiography studies

BACKGROUND: Spontaneous recanalization is an understudied phenomenon in stroke. It is often overestimated by nonocclusion rates. The heterogeneity of the causes and manifestations of stroke and of the studies assessing vascular patency has created difficulties in assigning accurate rates of its incidence. METHODS: Systematic review of published articles about cerebral angiography in stroke. RESULTS: Lack of anticipated occlusions (nonocclusion rates) was noted in 28% of patients in suspected vessels 6 hours after stroke onset, whereas documented occlusions were noted in 17% of patients who underwent spontaneous lysis at 6 to 8 hours. At 3 to 4 days, the nonocclusion rate was 50% of studied vessels. CONCLUSIONS: In the first 6 to 8 hours from stroke onset, spontaneous recanalization occurs in approximately 17% of patients, whereas nonocclusion exists in about 28% of patients and up to 50% by 4 days after stroke.     

Meta-analysis of risk factors for cutaneous melanoma: II. Sun exposure

A systematic revision of the literature was conducted in order to undertake a comprehensive meta-analysis of all published observational studies on melanoma. An extensive analysis of the inconsistencies and variability in the estimates was performed to provide some clues about its Epidemiology. Following a systematic literature search, relative risks (RRs) for sun exposure were extracted from 57 studies published before September 2002. Intermittent sun exposure and sunburn history were shown to play considerable roles as risk factors for melanoma, whereas a high occupational sun exposure seemed to be inversely associated to melanoma. The country of study and adjustment of the estimates adjuste for phenotype and photo-type were significantly associated with the variability of the intermittent sun exposure estimates (P = 0.024, 0.003 and 0.030, respectively). For chronic sun exposure, inclusion of controls with dermatological diseases and latitude resulted in significantly different data (P = 0.05 and 0.031, respectively). Latitude was also shown to be important (P = 0.031) for a history of sunburn; studies conducted at higher latitudes presented higher risks for a history of sunburns. Role of country, inclusion of controls with dermatological diseases and other study features seemed to suggest that "well conducted" studies supported the intermittent sun exposure hypothesis: a positive association for intermittent sun exposure and an inverse association with a high continuous pattern of sun exposure.