Combinations of radioprotectants spare radiation-induced damage to the physis

Radiotherapy used in the treatment of bone and soft tissue sarcomas in pediatric patients often results in undesirable growth plate damage. Radioprotectants may hold promise in the selective protection of growth plate tissue in this setting. In an animal model, the hypothesis tested was that pentoxifylline, selenium, or misoprostol, used in combination with amifostine, would significantly reduce longitudinal growth loss during one radiation dose exposure to a greater extent than the protection provided by only amifostine without increased morbidity or mortality or adverse effects on bone mineral density. Amifostine alone and in combination with each of the other radioprotectants resulted in limb discrepancy reduction to levels significantly less than radiated controls. The tibial length discrepancy in the selenium and amifostine group was 12.1 +/- 0.8%, less than the 15.5 +/- 2.6% tibial length discrepancy in the animals treated with amifostine alone, and less than the mean 18.8% tibial length discrepancy in the radiated limbs without radioprotection. There were no adverse effects on bone density in any group, but the selenium and amifostine group showed some increased mortality. Combinations of amifostine with these radioprotectants show efficacy in growth plate radioprotection and therefore warrant additional study in a clinically relevant fractionated model.     

Maternal-fetal interactions and birth order influence insulin variable number of tandem repeats allele class associations with head size at birth and childhood weight gain

Polymorphism of the insulin gene (INS) variable number of tandem repeats (VNTR; class I or class III alleles) locus has been associated with adult diseases and with birth size. Therefore, this variant is a potential contributory factor to the reported fetal origins of adult disease. In the population-based Avon Longitudinal Study of Pregnancy and Childhood birth cohort, we have confirmed in the present study the association between the INS VNTR III/III genotype and larger head circumference at birth (odds ratio [OR] 1.92, 95% CI 1.23-3.07; P = 0.004) and identified an association with higher cord blood IGF-II levels (P = 0.05 to 0.0001). The genotype association with head circumference was influenced by maternal parity (birth order): the III/III OR for larger head circumference was stronger in second and subsequent pregnancies (OR 5.0, 95% CI 2.2-11.5; P = 0.00003) than in first pregnancies (1.2, 0.6-2.2; P = 0.8; interaction with birth order, P = 0.02). During childhood, the III/III genotype remained associated with larger head circumference (P = 0.004) and was also associated with greater BMI (P = 0.03), waist circumference (P = 0.03), and higher fasting insulin levels in girls (P = 0.02). In addition, there were interactions between INS VNTR genotype and early postnatal weight gain in determining childhood BMI (P = 0.001 for interaction), weight (P = 0.005), and waist circumference (P = 0.0005), such that in the approximately 25% of children (n = 286) with rapid early postnatal weight gain, class III genotype-negative children among this group gained weight more rapidly. Our results indicate that complex prenatal and postnatal gene-maternal/fetal interactions influence size at birth and childhood risk factors for adult disease.     

Association analysis of the lymphocyte-specific protein tyrosine kinase (LCK) gene in type 1 diabetes

Prior data associating the expression of lymphocyte-specific protein tyrosine kinase (LCK) with type 1 diabetes, its critical function in lymphocytes, and the linkage of the region to diabetes in the nonobese diabetic (NOD) mouse model make LCK a premier candidate for a susceptibility gene. Resequencing of LCK in 32 individuals detected seven single nucleotide polymorphisms (SNPs) with allele frequencies >3%, including four common SNPs previously reported. These and six other SNPs from dbSNP were genotyped in a two-stage strategy using 2,430 families and were all shown not to be significantly associated with type 1 diabetes. We conclude that a major role for the common LCK polymorphisms in type 1 diabetes is unlikely. However, we cannot rule out the possibility of there being a causal variant outside the exonic, intronic, and untranslated regions studied.     

Benefits of resection for metachronous lung cancer

OBJECTIVES: The benefits of resection for metachronous lung cancer are not well described. The objective of this study was to evaluate the safety and efficacy of surgical resection for metachronous lung cancers. METHODS: We reviewed the charts of all patients who underwent a second resection for a metachronous lung cancer from July 1, 1988, to December 31, 2002. Type of resection, operative morbidity, mortality, and survival by stage were analyzed. Survival was determined by using the Kaplan-Meier survival method. All patients were pathologically staged by using the 1997 American Joint Committee on Cancer standards. RESULTS: Pulmonary resections were performed in 69 patients who had undergone a previous resection. The mean interval between the first and second resection was 2.4 +/- 2.5 years. Seventy-three percent of patients presented with stage I cancers, 9% with stage II cancers, and 17% with stage III cancers. Lobectomy and wedge resection were performed with equal frequency (42% each) for the metachronous cancers. Operative mortality for the second resection was 5.8%. The mean follow-up after the second resection was 37 months. Overall 5-year actuarial survival for the entire group after the second resection was 33.4%. CONCLUSIONS: Operations for metachronous cancers provided survival that approximated the expected survival for lung cancer. Surgical intervention should be considered as a safe and effective treatment for resectable metachronous lung cancer in patients with adequate physiologic pulmonary reserve.     

Traumatic lumbar hernia: report of cases and comprehensive review of the literature

BACKGROUND: Acute lumbar hernia secondary to blunt trauma is an uncommon injury of the abdominal wall and, when encountered, is a difficult challenge for the trauma surgeon. METHODS: Three cases of lumbar hernia secondary to blunt trauma are described and a review of the literature was conducted for other such cases. Clinical, anatomic, and demographic data were extracted from these reports and analyzed. RESULTS: Sixty-three cases of lumbar hernia secondary to blunt trauma were found in the English literature and three cases are described here. Hernias occurred most commonly in the inferior lumbar triangle (70%) and were most frequently a result of a motor vehicle collision (71%). Physical examination findings were variable and reported in only a minority of cases (palpable hernia, 33%; flank hematoma, 27%) and associated intra-abdominal injuries were common (61%). Most traumatic lumbar hernias were diagnosed immediately, and computed tomography was 98% sensitive for diagnosis. Fifty-eight percent of patients were managed initially with exploratory laparotomy. Timing of hernia repair was variable. CONCLUSION: Traumatic lumbar hernias are associated with a high incidence of intra-abdominal injury and should be considered in all cases of severe blunt abdominal trauma. Computed tomography should be implemented when the diagnosis is suspected in a hemodynamically stable patient. Repair should be performed by mesh patching techniques at a time based on clinical correlation.     

Moist wound healing: a concept that changed our practice

Winter's seminal paper from 1962 showed that a moist wound environment accelerates healing. Since then, different types of dressings have been developed based on this concept. This paper describes their background and correct usage.     

Control of erythropoiesis after high altitude acclimatization

Erythropoiesis was studied in 11 subjects submitted to a 4-h hypoxia (HH) in a hypobaric chamber (4,500 m, barometric pressure 58.9 kPa) both before and after a 3-week sojourn in the Andes. On return to sea level, increased red blood cells (+3.27%), packed cell volume (+4.76%), haemoglobin (+6.55%) (P<0.05), and increased arterial partial pressure of oxygen (+8.56%), arterial oxygen saturation (+7.40%) and arterial oxygen blood content (C_aO₂) (+12.93%) at the end of HH (P<0.05) attested high altitude acclimatization. Reticulocytes increased during HH after the sojourn only (+36.8% vs +17.9%, P<0.01) indicating a probable higher reticulocyte release and/or production despite decreased serum erythropoietin (EPO) concentrations (–46%, P<0.01). Hormones (thyroid, catecholamines and cortisol), iron status (serum iron, ferritin, transferrin and haptoglobin) and renal function (creatinine, renal, osmolar and free-water clearances) did not significantly vary (except for lower thyroid stimulating hormone at sea level, P<0.01). Levels of 2,3-diphosphoglycerate (2,3-DPG) increased throughout HH on return (+14.7%, P<0.05) and an inverse linear relationship was found between 2,3-DPG and EPO at the end of HH after the sojourn only (r=–0.66, P<0.03). Inverse linear relationships were also found between C_aO₂ and EPO at the end of HH before (r=–0.63, P<0.05) and after the sojourn (r=–0.60, P=0.05) with identical slopes but different ordinates at the origin, suggesting that the sensitivity but not the gain of the EPO response to hypoxia was modified by altitude acclimatization. Higher 2,3-DPG levels could partly explain this decreased sensitivity of the EPO response to hypoxia. In conclusion, we show that altitude acclimatization modifies the control of erythropoiesis not only at sea level, but also during a subsequent hypoxia.