Housemaids and non-fatal occupational injuries

OBJECTIVE: To estimate the annual incidence of non-fatal work injuries according to sociodemographic and occupational variables among housemaids. METHODS: A community-based survey was conducted in a population of 1,650 women aged 10 to 65 years who reported a paid occupation randomly selected in a household sample of the city of Salvador, Brazil. Data was collected through individual questionnaires on living and work conditions and health status. Fisher Exact test was performed for frequency analysis. RESULTS: It was estimated an overall annual incidence of non-fatal work injuries in the study population of 5.0%, which was statistically significant (p<0.05) higher among housemaids (7.3%) than in the group with other occupations (4.5%). Half of the injuries among housemaids were not related with long-term disabilities, and 38.1% women referred not being able to work for two weeks on average after the injury. CONCLUSIONS: Housemaids represent a major contingent of the work force in Brazil and other Latin America countries. The high incidence of non-fatal work injuries in this working group reveals its public health relevance and the need for preventive programs.     

Non-fatal occupational injuries: gender and job contract differences

In Brazil, workers without a formal job contract comprise more than half of the labor force, a contingent formed mainly by women. This study presents estimates of the annual incidence of non-fatal work-related injuries and their distribution by gender and type of job contract in an urban area of Brazil. This was a community-based study with a random cluster area sample of the inhabitants from the city of Salvador, capital of the State of Bahia. The study population included all individuals from 18 to 65 years of age who reported having a paid job (n = 2,947). Data were obtained through individual household interviews. The overall estimated annual incidence rate was 5.80%, with a non-statistically significant difference between men (6.05%) and women (5.53%) or workers with (5.67%) and without (5.92%) a formal job contract. These similarities between work-related accidents across gender and type of job contract highlighted the need for greater attention to this problem among women and informal workers, who are largely ignored in official statistics.     

Extrathoracic obstruction and hypoxemia occurring during exercise in a competitive female cyclist

A 22-year-old competitive female cyclist complained of cough, chest tightness, and wheeze during high-intensity exercise that had previously been diagnosed as exercise-induced bronchospasm (EIB). A loud stridor, a sensation of her "throat closing," and severe dyspnea developed during maximal cycling exercise with concomitant reductions in both inspiratory and expiratory flow rates. A decrease of 25 L/min (26%) in minute ventilation and arterial hypoxemia (PaO(2) decrease, 93 to 76.5 mm Hg) resulted from this obstruction. Spontaneous tidal flow-volume loops (FVLs) during exercise exhibited a sawtooth pattern during inspiration, and substantial drops in flow rates after the stridor developed. However, maximal FVLs were unchanged from baseline following exercise, indicating that the obstruction was not EIB. We suggest that the continuous measurement of spontaneous breath-by-breath tidal FVLs may be a useful diagnostic tool for the identification of exercise-induced extrathoracic obstruction. Additionally, extrathoracic obstruction should be considered as an uncommon but potential cause of inadequate ventilation and arterial hypoxemia during exercise.     

Modulation of the molecular composition of large conductance,Ca(2+) activated K(+) channels in vascular smooth muscle during hypertension

Hypertension is a clinical syndrome characterized by increased vascular tone. However, the molecular mechanisms underlying vascular dysfunction during acquired hypertension remain unresolved. Localized intracellular Ca2+ release events through ryanodine receptors (Ca2+ sparks) in the sarcoplasmic reticulum are tightly coupled to the activation of large-conductance, Ca2+-activated K+ (BK) channels to provide a hyperpolarizing influence that opposes vasoconstriction. In this study we tested the hypothesis that a reduction in Ca2+ spark-BK channel coupling underlies vascular smooth muscle dysfunction during acquired hypertension. We found that in hypertension, expression of the beta1 subunit was decreased relative to the pore-forming alpha subunit of the BK channel. Consequently, the BK channels were functionally uncoupled from Ca2+ sparks. Consistent with this, the contribution of BK channels to vascular tone was reduced during hypertension. We conclude that downregulation of the beta1 subunit of the BK channel contributes to vascular dysfunction in hypertension. These results support the novel concept that changes in BK channel subunit composition regulate arterial smooth muscle function.     

Prognostic factors for children and adolescents with surgically resected nonrhabdomyosarcoma soft tissue sarcoma: an analysis of 121 patients treated at St Jude Children's Research Hospital.

PURPOSE: The rarity and heterogeneity of pediatric nonrhabdomyosarcoma soft tissue sarcoma (NRSTS) has precluded meaningful analysis of prognostic factors associated with surgically resected disease. To define a population of patients at high risk of treatment failure who might benefit from adjuvant therapies, we evaluated the relationship between various clinicopathologic factors and clinical outcome of children and adolescents with resected NRSTS over a 27-year period at our institution. PATIENTS AND METHODS: We analyzed the records of 121 consecutive patients with NRSTS who underwent surgical resection between August 1969 and December 1996. Demographic data, tumor characteristics, treatment, and outcomes were recorded. Univariate and multivariate analyses of prognostic factors for survival, event-free survival (EFS), and local and distant recurrence were performed. RESULTS: At a median follow-up of 9.2 years, 5-year survival and EFS rates for the entire cohort were 89% +/- 3% and 77% +/- 4%, respectively. In univariate models, positive surgical margins (P =.004), tumor size > or = 5 cm (P <.001), invasivene (P =.002), high grade (P =.028), and intra-abdominal primary tumor site (P =.055) adversely affected EFS. All of these factors except invasiveness remained prognostic of EFS and survival in multivariate models. Positive surgical margins (P =.003), intra-abdominal primary tumor site (P =.028), and the omission of radiation therapy (P =.043) predicted local recurrence, whereas tumor size > or = 5 cm (P <.001), invasiveness (P <.001), and high grade (P =.004) predicted distant recurrence. CONCLUSION: In this largest single-institution analysis of pediatric patients with surgically resected NRSTS, we identified clinicopathologic features predictive of poor outcome. These variables should be prospectively evaluated as risk-adapted therapies are developed.     

Phase I dose escalation and pharmacokinetic study of oral gefitinib and irinotecan in children with refractory solid tumors

Purpose

This phase I study endeavored to estimate the maximum tolerated dose and describe the dose-limiting toxicities (DLTs) of oral irinotecan with gefitinib in children with refractory solid tumors.

Methods

Oral irinotecan was administered on days 1–5 and 8–12 with oral gefitinib (fixed dose, 150 mg/m²/day) on days 1–12 of a 21-day course. The escalation with overdose control method guided irinotecan dose escalation (7 dose levels, range 5–40 mg/m²/day).

Results

Sixteen of 19 patients were evaluable, with serial pharmacokinetic studies in ten patients. Diagnoses included osteosarcoma (N = 5), neuroblastoma (N = 3), sarcoma (N = 3), and others (N = 5). Patients received a median of two courses (range 1–20), with at least two patients treated on dose levels 2–7. Three patients had five DLTs; the most common being metabolic (hypokalemia, N = 2 and hypophosphatemia, N = 1) at dose levels two (10 mg/m²) and four (20 mg/m²). One patient experienced grade 3 diarrhea (40 mg/m²). Irinotecan bioavailability was 2.5-fold higher when co-administered with gefitinib, while the conversion rate of irinotecan to SN-38 lactone was unaffected. The study closed due to poor accrual before evaluation of the next recommended irinotecan dose level (35 mg/m²). Of 11 patients receiving at least two courses of therapy, three had stable disease lasting two to four courses and one patient maintained a complete response through 18 courses.

Conclusions

The combination of oral gefitinib and irinotecan has acceptable toxicity and anti-tumor activity in pediatric patients with refractory solid tumors. Pharmacokinetic analysis confirms that co-administration of gefitinib increases irinotecan bioavailability leading to an increased SN-38 lactone systemic exposure.     

Effectiveness of Thalidomide and Tamoxifen in Preventing Neointimal Hyperplasia in Experimental Vascular Injury in Rats

Introduction

Chronic allograft vasculopathy is an important cause of graft loss. Considering the inflammatory response in the development of chronic vascular lesions, therapeutic approaches to target the inflammatory process may be useful. We sought to investigate the possible protective effects on balloon catheter-induced vascular injury of thalidomide and tamoxifen, 2 drugs with powerful anti-inflammatory, immunomodulatory, and antifibrotic effects, using an animal model that mimics the morphologic features of chronic allograft vasculopathy.

Methods

Male Wistar rats subjected to balloon catheter carotid injury (INJ) were treated with thalidomide (100 mg/kg), or tamoxifen (10 mg/kg), or vehicle. Contralateral right carotid arteries were used as uninjured controls. Morphometric and immunohistochemical analyses were performed at 14 days postinjury.

Results

Injured carotid arteries showed marked neointimal hyperplasia, which was significantly inhibited among animals treated with thalidomide or tamoxifen: neointimal/media ratios of 1.4 ± 0.4 versus 0.2 ± 0.1 versus 0.4 ± 0.2, for INJ, INJ + Thalid, and INJ + Tamox; respectively (P < .001). The endothelial cell loss was significantly less pronounced among animals subjected to carotid balloon injury that were treated with thalidomide (24 ± 14 vs 1 ± 1 cells per section in INJ, respectively (P < .05). Therapy with either thalidomide or tamoxifen effectively maintained α-smooth muscle actin expression in the media, similar to uninjured arteries. In this setting, tamoxifen was additionally effective to prevent the migration of myofibroblasts in to the intima.

Conclusion

Thalidomide and tamoxifen were effective to reduce neointimal hyperplasia secondary to vascular damage. The vasculoprotective effects of thalidomide were more pronounced to preserve endothelial cells, whereas tamoxifen inhibited smooth muscle cell migration and proliferation. A possible beneficial effect of combined therapy with thalidomide plus tamoxifen should be addressed in future studies.