Continuous infusion cisplatin and etoposide chemotherapy for cancer of unknown primary site (CUPS) in Taiwan, a region with a high prevalence of endemic viral infections

BACKGROUND: To evaluate the efficacy and toxicity of cisplatin/etoposide continuous infusion chemotherapy for cancer of unknown primary site in Taiwan, a region with a high prevalence of endemic viral infections. METHOD: Between April 1994 and February 1996, 20 patients with a diagnosis of CUPS were treated, including 15 males and five females, of average age 63.3 years (range 41-83 years). Continuous intravenous infusion of etoposide 80 mg/m2 and cisplatin 25 mg/m2 was given for 3 days every 3 weeks. Pretreatment tumor marker and viral serology studies were performed for baseline evaluation. Nearly two-thirds of the patients had poorly differentiated carcinoma. The average number of metastatic sites was 2.65 (range 1-4), with liver and lymph node involvement predominating. RESULTS: The overall response rate was 25% (95% CI 17.7-32.3%); 30.7% for poorly differentiated cancers and 25% for well differentiated cancers. Median survival was 4 months (range 1-12 months), 4.8 months for patients attaining partial response. Toxicity was moderate, grade 3 and 4 neutropenia occurred in 55% and grade 3 and 4 thrombocytopenia in 40%; other toxicities were mild. CA125 and CA199 were elevated in more than 50% of patients. Viral serology studies were not significantly different from those of the indigenous population. CONCLUSION: Etoposide and cisplatin combination chemotherapy has modest activity in patients with extensive CUPS and, at the schedule and dosage given, it is associated with moderate toxicity.      

Dental caries and erosion status of 12-year-old Hong Kong children

Background

We examined the association of alcohol use disorders (AUD) with adherence to and health-related quality of life (HRQOL) outcomes of antiretroviral treatment (ART) for HIV/AIDS patients.

Methods

A cross-sectional multi-site survey was conducted in 468 drug users and 648 non-drug users (age: 35.4 ± 7.0 years; 63.8% male) in 3 epicentres of Vietnam. AUD, ART adherence, and HRQOL were measured using the Alcohol Use Disorders Identification Test - Consumption (AUDIT-C), the self-reported Visual Analogue Scale (VAS), and the World Health Organization Quality of Life instrument (WHOQOL-HIV BREF).

Results

35.0% of drug users were hazardous drinkers, compared to 25.9% of non-drug users. 22.3% of drug users engaged in binge drinking, and 25.9% reported suboptimal ART adherence. Adjusting for propensity scores of AUD, patients who had either at-risk or binge drinking behaviour were about twice as likely to be treatment non-adherent as those who did not have AUD. Hazardous drinkers reported small to medium decrements in the Performance, Physical, Social, Spirituality, and Environment quality of life domains. Binge drinkers had a slightly higher score in Social dimension.

Conclusion

AUD is prevalent and negatively affecting adherence to and HRQOL outcomes of ART services in injection-driven HIV epidemics. Screening and intervention are recommended for AUD, especially during the stable periods of ART. Other social and psychological interventions might also enhance patients’ responses to and outcomes of ART in Vietnam.     

Effect of fumonisin B(1) on rat hepatic P450 system

The effects of the mycotoxin fumonisin B(1) (FB(1)) on the hepatic cytochrome P450 system were investigated in male rats dosed daily by oral gavage with 3 mg FB(1) per kg body weight for 9 consecutive days. FB(1) treatment resulted in a reduced weight gain. At the same time, CYP2E activity was increased, which is considered to mark the metabolic changes inherent to growth retardation in young rats. Treatment with FB(1) also resulted in a selective inhibition of CYP2C11 and to a lesser extent, CYP1A2 in liver microsomes obtained from treated animals, whereas it did not affect significantly the activity of CYP2A1/2A2, CYP2B1/2B2, CYP3A1/3A2 and CYP4A. The significant inhibition of CYP2C11 is considered to reflect a suppressed activity of protein kinase activity resulting from the inhibition of sphingolipid biosynthesis caused by FB(1).     

Utility of thromboelastography and/or thromboelastometry in adults with sepsis: a systematic review

Introduction

Coagulation abnormalities are frequent in sepsis. Conventional coagulation assays, however, have several limitations. A surge of interest exists in the use of point-of-care tests to diagnose hypo- and hypercoagulability in sepsis.We performed a systematic review of available literature to establish the value of rotational thromboelastography (TEG) and thromboelastometry (ROTEM) compared with standard coagulation tests to detect hyper- or hypocoagulability in sepsis patients. Furthermore, we assessed the value of TEG/ROTEM to identify sepsis patients likely to benefit from therapies that interfere with the coagulation system.

Methods

MEDLINE, EMBASE, and the Cochrane Library were searched from 1 January 1980 to 31 December 2012. The search was limited to adults, and language was limited to English. Reference lists of retrieved articles were hand-searched for additional studies. Ongoing trials were searched on http://www.controlled-trials.com and http://www.clinicaltrials.gov. Studies addressing TEG/ROTEM measurements in adult patients with sepsis admitted to the ICU were considered eligible.

Results

Of 680 screened articles, 18 studies were included, of which two were randomized controlled trials, and 16 were observational cohort studies. In patients with sepsis, results show both hyper- and hypocoagulability, as well as TEG/ROTEM values that fell within reference values. Both hyper- and hypocoagulability were to some extent associated with diffuse intravascular coagulation. Compared with conventional coagulation tests, TEG/ROTEM can detect impaired fibrinolysis, which can possibly help to discriminate between sepsis and systemic inflammatory response syndrome (SIRS). A hypocoagulable profile is associated with increased mortality. The value of TEG/ROTEM to identify patients with sepsis who could possibly benefit from therapies interfering with the coagulation system could not be assessed, because studies addressing this topic were limited.

Conclusion

TEG/ROTEM could be a promising tool in diagnosing alterations in coagulation in sepsis. Further research on the value of TEG/ROTEM in these patients is warranted. Given that coagulopathy is a dynamic process, sequential measurements are needed to understand the coagulation patterns in sepsis, as can be detected by TEG/ROTEM.     

Immediate food hypersensitivity reactions on the first known exposure to the food

We report 8 infants with immediate hypersensitivity reactions to foods (milk, egg, or peanut), occurring at the first-known exposure. Each developed symptoms within the first hour, but these generally settled within 2 hours. Sensitisation to the food concerned was demonstrated by positive immediate allergen skin prick tests in every case. Symptoms experienced included irritability, erythematous rash, urticaria, angio-oedema, vomiting, rhinorrhoea, and cough. Five infants were being followed prospectively and 4 were clinically tolerant of the food by age 16 months. The most likely route of sensitisation was via breast milk. None of the infants experienced similar reactions while being breast fed, suggesting that the reaction was dose dependent. As 5 out of a group of 80 infants being followed prospectively developed an immediate reaction at their first known exposure to a food, this appeared to be a not uncommon presentation of food hypersensitivity in infancy.     

Growth hormone resistance in uremia

Growth retardation is a major complication in children with uremia. Protein restriction, calorie deficit, metabolic acidosis, renal osteodystrophy, and endocrinologic disturbances contribute to the growth failure. The effect of these factors on growth retardation can be attenuated in part by therapy with vitamin D metabolites, adequate nutrition, alkalization, and dialysis. Linear growth in children with uremia is markedly retarded despite normal or increased levels of circulating serum growth hormone. An increased growth hormone level in children with uremia is due to normal growth hormone secretion from the pituitary gland and impaired growth hormone clearance in the kidney. However, the elevated growth hormone level does not lead to a commensurate rise in serum insulin-like growth factor I (IGF-I); the serum IGF-I level is decreased or normal in relation to the degree of renal failure. This discrepancy suggests growth hormone resistance in the liver in uremia. Recent molecular techniques open a new era in studying the gene expression for growth hormone or IGF-I. There is no doubt today that growth hormone treatment has the beneficial effect of growth promotion in children with uremia, which also suggests endogenous growth hormone resistance in target organs or target cells in uremia.