Levels and causes of maternal mortality in Senegal

OBJECTIVES: To report the findings of a direct, community-based, assessment of maternal mortality and medical causes of death using verbal autopsy in three unique cohorts in rural Senegal. METHODS: Methods from ongoing demographic surveillance systems. We obtained records of all deaths and births in women of age 15-49 over a period of 14 years in Niakhar, 10 years in Bandafassi and 13 years in Mlomp. Relatives of all women who died were interviewed using a standard questionnaire. Causes of death were assigned by three physicians independently. Maternal deaths were defined according to the ninth and tenth revisions of the International Classification of Diseases. RESULTS: The maternal mortality ratio was similar in Mlomp [436 per 100 000 live births (95% confidence interval 209-802)] and Niakhar [516 per 100 000 (413-636)] but significantly higher in the more remote area of Bandafassi [852 (587-1196)] [relative risk compared with Niakhar 1.6 (1.0-2.4)]. Two-thirds of the maternal deaths were from direct obstetric causes, haemorrhage being the most common. Abortion was rare. CONCLUSIONS: Demographic surveillance systems are useful tools for the measurement of maternal mortality provided special studies are carried out to arrive at the levels and causes of maternal death. The estimates of maternal mortality reported here are lower than those published by the WHO and UNICEF but remain extremely high, particularly in the very remote areas with very limited health infrastructure, where as many as one in 19 women may be expected to die as a consequence of childbirth.     

In vitro skin irritation testing on reconstituted human epidermis: reproducibility for 50 chemicals tested with two protocols.

Since it is of high importance to establish the skin irritation potential of industrial chemicals, toxicologists developed tests on various skin models. Most test data come from the rabbit Draize test, but its reproducibility is questionable. Some human in vivo test data exist, but they concern only few compounds. The emergence of new tools such as reconstituted human skin tissues offers a promising future to alternative methods. We describe here two in vitro skin irritation test protocols performed on reconstituted human epidermis. One is a direct topical application test and the other an in vitro patch test. Both protocols were performed using multiple endpoint analysis including cell viability (MTT reduction), histology, and IL-1alpha release. Fifty chemicals were tested: 20 compounds were used in the ECVAM pre-validation study and 30 products were previously tested in a human in vivo patch test. These in vitro skin irritation tests have not only the advantages of enhanced convenience and of reduced costs, but a good reproducibility is observed by endpoint, and by compound. A prediction model is proposed to classify the chemicals as irritant or non-irritant, and the results are compared to available rabbit and human data. We do not wish to overgeneralize from these 50 compounds; but, instead suggest that this data set be extensively extended to include chemicals of varying physico-chemical properties.     

Detection and characterization of primary liver cancer in rats by MS-264-enhanced MRI

A new MR contrast agent, MS-264 (Gd(1 RS)-1-(p-butylbenzyl)-DTPA), was developed to achieve hepatobiliary specificity and its potential evaluated for detecting and characterizing liver tumors in rats with chemically induced hepatocellular carcinoma (HCC). In seven rats with 66 HCC lesions, enhancements of different abdominal organs and tumors were compared on T₁-weighted images after intravenous administration of Gd-DTPA (0.3 mmol/kg) and MS-264 (0.05 mmol/kg). MR images were correlated with postmortem microangiographic and histological findings. An overall enhancement of different organs, which normalized within 24 h, was observed after Gd-DTPA and MS-264 injection. MS-264 caused a higher relative enhancement (RE) in liver (60%), compared with that of Gd-DTPA (40%), which resulted in a prompt negative contrast enhancement in 59 of 66 HCCs. All were moderately to poorly differentiated (Grades II–IV) tumors. Six of these 59 negative contrast-enhancing lesions showed a positively enhanced peritumoral rim, which corresponded histologically to malignant infiltration (n = 2) or compression (n = 4). On the other hand, six well differentiated HCCs showed prolonged positive enhancement. However, one well differentiated HCC was not positively enhanced by MS-264, probably due to poor access of the agent to the lesion. In comparison to that of the pre-contrast images, enhancement with Gd-DTPA and MS-264 increased the number of detected lesions by 22 and 42%, respectively. In this animal study, MS-264 proved to be useful in detection and characterization of primary liver cancers.     

Gene expression in thyroid autonomous adenomas provides insight into their physiopathology

The purpose of this study was to use the microarray technology to define expression profiles characteristic of thyroid autonomous adenomas and relate these findings to physiological mechanisms. Experiments were performed on a series of separated adenomas and their normal counterparts on Micromax cDNA microarrays covering 2400 genes (analysis I), and on a pool of adenomatous tissues and their corresponding normal counterparts using microarrays of 18,000 spots (analysis II). Results for genes present on the two arrays corroborated and several gene regulations previously determined by Northern blotting or microarrays in similar lesions were confirmed. Five overexpressed and 24 underexpressed genes were also confirmed by real-time RT-PCR in some of the samples used for microarray analysis, and in additional tumor specimens. Our results show: (1) a change in the cell populations of the tumor, with a marked decrease in lymphocytes and blood cells and an increase in endothelial cells. The latter increase would correspond to the establishment of a close relation between thyrocytes and endothelial cells and is related to increased N-cadherin expression. It explains the increased blood flow in the tumor; (2) a homogeneity of tumor samples correlating with their common physiopathological mechanism: the constitutive activation of the thyrotropin (TSH)/cAMP cascade; (3) a low proportion of regulated genes consistent with the concept of a minimal deviation tumor; (4) a higher expression of genes coding for specific functional proteins, consistent with the functional hyperactivity of the tumors; (5) an increase of phosphodiesterase gene expression which explains the relatively low cyclic AMP levels measured in these tumors; (6) an overexpression of antiapoptotic genes and underexpression of proapoptotic genes compatible with their low apoptosis rate; (7) an overexpression of N-cadherin and downregulation of caveolins, which casts doubt about the use of these expressions as markers for malignancy.     

Repeated injections of 131I-rituximab show patient-specific stable biodistribution and tissue kinetics

Purpose It is generally assumed that the biodistribution and pharmacokinetics of radiolabelled antibodies remain similar between dosimetric and therapeutic injections in radioimmunotherapy. However, circulation half-lives of unlabelled rituximab have been reported to increase progressively after the weekly injections of standard therapy doses. The aim of this study was to evaluate the evolution of the pharmacokinetics of repeated ¹³¹I-rituximab injections during treatment with unlabelled rituximab in patients with non-Hodgkins lymphoma (NHL).Methods Patients received standard weekly therapy with rituximab (375 mg/m²) for 4 weeks and a fifth injection at 7 or 8 weeks. Each patient had three additional injections of 185 MBq ¹³¹I-rituximab in either treatment weeks 1, 3 and 7 (two patients) or weeks 2, 4 and 8 (two patients). The 12 radiolabelled antibody injections were followed by three whole-body (WB) scintigraphic studies during 1 week and blood sampling on the same occasions. Additional WB scans were performed after 2 and 4 weeks post ¹³¹I-rituximab injection prior to the second and third injections, respectively.Results A single exponential radioactivity decrease for WB, liver, spleen, kidneys and heart was observed. Biodistribution and half-lives were patient specific, and without significant change after the second or third injection compared with the first one. Blood T_1/2, calculated from the sequential blood samples and fitted to a bi-exponential curve, was similar to the T_1/2 of heart and liver but shorter than that of WB and kidneys. Effective radiation dose calculated from attenuation-corrected WB scans and blood using Mirdose3.1 was 0.53+0.05 mSv/MBq (range 0.48–0.59 mSv/MBq). Radiation dose was highest for spleen and kidneys, followed by heart and liver.Conclusion These results show that the biodistribution and tissue kinetics of ¹³¹I-rituximab, while specific to each patient, remained constant during unlabelled antibody therapy. RIT radiation doses can therefore be reliably extrapolated from a preceding dosimetry study.     

Peripheral block of the hyperpolarization-activated cation current (Ih) reduces mechanical allodynia in animal models of postoperative and neuropathic pain

BACKGROUND AND OBJECTIVES: Block of the hyperpolarization-activated inward current (I h) reduces excitability of peripheral axons during stimulation and decreases ectopic discharges in axotomized sensory neurons. Changes in I h expression in DRG neurons have been suggested to partially underlie sensitization after nerve injury and inflammation. We hypothesized that peripheral block of I h on axons would produce an antiallodynic effect in postoperative as well as neuropathic conditions, and we tested perineural administration of ZD 7288, a specific blocker of I h , on pain-associated behavior in animal models of neuropathic and postoperative pain. METHODS: Under halothane anesthesia, partial sciatic nerve injury or hind-paw incision were performed on adult male rats as previously described. Mechanical allodynia was inferred by demonstration of a decrease in paw withdrawal threshold by application of calibrated von Frey filaments. After surgery, animals received either a saline or a ZD 7288 solution either by sciatic perineural injection or by intraplantar injection. RESULTS: Perineural administration of ZD 7288 (100 microM) significantly reduced mechanical allodynia induced by partial sciatic nerve injury and hind-paw incision. Saline and 10 microM of ZD 7288 had no significant effect on mechanical allodynia. Contralateral administration of ZD 7288, 100 microM, did not affect ipsilateral paw withdrawal threshold after nerve injury. Intraplantar injection of ZD 7288 failed to reduce mechanical allodynia after nerve injury. Sedation and motor effects were not observed. CONCLUSIONS: The current study shows that peripheral block of I h produces an antiallodynic effect, which suggests that I h channels represent a novel target for nerve block treatment of postoperative and neuropathic pain.     

Hospital ownership, reimbursement systems and mortality rates

This paper analyses the effect of ownership and system of reimbursement on mortality rates. From the statistical results we could conclude that the incentive created by fee-for-service reimbursement yields a four-point reduction in the mortality rate. However, this ranking of hospital quality is completely dependent on the characteristics and illness severity of patients. To take this difficulty into account, we use an innovative duration model applied to panel data: a duration model with both patient and hospital unobserved heterogeneity. No distributional assumptions are made regarding the latter. By this way, we control the fact that patients admitted to the private sector can be different in terms of disease severity from patients admitted to the public sector.The capacity to perform innovative procedures has more effect on the mortality than the system of reimbursement and/or ownership. As such, private sector hospitals that perform more innovative procedures provide a better quality of care, measured by the probability of dying. Nevertheless, heterogeneity within hospitals is greater in for-profit hospitals than in other types of hospital. This suggests that, by choosing a for-profit hospital, patients have on average a lower instantaneous probability of dying but are less sure about the quality of the hospital.     

The relative influence of individual and contextual socio-economic status on consumption of fruit and soft drinks among adolescents in Europe

BACKGROUND: The number of studies among children and adolescents that focus on socio-economic differences in food habits is limited. Moreover, most are done in only one country and often include a non-representative sample. The present study examines whether socio-economic differences in the consumption of fruit and soft drinks can be found among young adolescents in a wide range of European countries. METHODS: Multilevel statistical analysis of 114 558 school-pupils aged 11, 13 and 15 from 28 countries participating in the WHO collaborative cross-national study of Health Behaviours among School-aged Children 2001-2002. The individual outcomes were daily fruit and soft drink consumption and the socio-economic predictors at the individual level were occupation of the head of household and family material wealth. Family material wealth was aggregated at the country level to operationalize country-level socio-economic status. RESULTS: In general, girls and younger pupils consumed fruit more often and soft drinks less often. Significant between-school, between-country and between-region differences were found. Fruit consumption increased with family material wealth and higher parental occupational status. Soft drink consumption was lower among pupils of higher parental occupational status in Northern, Southern and Western European countries, but not in Central and Eastern European countries. Only in Central and Eastern European countries was a significant increase in soft drink consumption with increasing family affluence found. The country level of family affluence did not seem to have an effect on either outcome variable. CONCLUSION: The findings underscore the importance of socio-economic factors in relation to the food habits of young adolescents.     

Malignancies, prothrombotic mutations, and the risk of venous thrombosis

Context  Venous thrombosis is a common complication in patients with cancer, leading to additional morbidity and compromising quality of life. Objective  To identify individuals with cancer with an increased thrombotic risk, evaluating different tumor sites, the presence of distant metastases, and carrier status of prothrombotic mutations. Design, Setting, and Patients  A large population-based, case-control (Multiple Environmental and Genetic Assessment [MEGA] of risk factors for venous thrombosis) study of 3220 consecutive patients aged 18 to 70 years, with a first deep venous thrombosis of the leg or pulmonary embolism, between March 1, 1999, and May 31, 2002, at 6 anticoagulation clinics in the Netherlands, and separate 2131 control participants (partners of the patients) reported via a questionnaire on acquired risk factors for venous thrombosis. Three months after discontinuation of the anticoagulant therapy, all patients and controls were interviewed, a blood sample was taken, and DNA was isolated to ascertain the factor V Leiden and prothrombin 20210A mutations. Main Outcome Measure  Risk of venous thrombosis. Results  The overall risk of venous thrombosis was increased 7-fold in patients with a malignancy (odds ratio [OR], 6.7; 95% confidence interval [CI], 5.2-8.6) vs persons without malignancy. Patients with hematological malignancies had the highest risk of venous thrombosis, adjusted for age and sex (adjusted OR, 28.0; 95% CI, 4.0-199.7), followed by lung cancer and gastrointestinal cancer. The risk of venous thrombosis was highest in the first few months after the diagnosis of malignancy (adjusted OR, 53.5; 95% CI, 8.6-334.3). Patients with cancer with distant metastases had a higher risk vs patients without distant metastases (adjusted OR, 19.8; 95% CI, 2.6-149.1). Carriers of the factor V Leiden mutation who also had cancer had a 12-fold increased risk vs individuals without cancer and factor V Leiden (adjusted OR, 12.1; 95% CI, 1.6-88.1). Similar results were indirectly calculated for the prothrombin 20210A mutation in patients with cancer. Conclusions  Patients with cancer have a highly increased risk of venous thrombosis especially in the first few months after diagnosis and in the presence of distant metastases. Carriers of the factor V Leiden and prothrombin 20210A mutations appear to have an even higher risk.