A Decade of Advances in Military Trauma Care.

BACKGROUND: While combat casualty care shares many key concepts with civilian trauma systems, its unique features mandate certain practices that are distinct from the civilian ones. METHODS: This is a review of the most current literature on combat casualty care, based on computer database searches for studies on combat casualty care and military medicine. Studies were selected for inclusion in this review based on their relevance and contribution. RESULTS: Over the last decade, meticulous, international data collection and research efforts have led to significant improvements in military trauma care. Combat medicine has focused on the causes of preventable deaths and targeted on bleeding control and resuscitation strategies, as well as improved evacuation. En route care and forward surgical interventions have resulted in unprecedented low fatality rates and the saving of more lives. CONCLUSION: This overview of the developments in combat casualty care in recent years emphasizes medical practices that are characteristic of combat medicine, yet with the potential to save lives in other scenarios, as well.

Clinical manifestations in Israeli cystinuria patients and molecular assessment of carrier rates in Libyan Jewish controls.

BACKGROUND: Cystinuria is an autosomal recessive disease that is manifested by the development of kidney stones. Mutations in SLC3A1 cause type I disease, while mutations in SLC7A9 are associated with non-type I disease. In Israel, cystinuria is especially common among Libyan Jews who suffer from non-type I disease. OBJECTIVES: To compare clinical manifestations of patients with mutations in SLC3A1 to those with mutations in SLC7A9, and to assess the carrier rate among unaffected Libyan Jewish controls. METHODS: Clinical manifestations were evaluated in patients with mutations in SLC3A1 and in patients with mutations in SLC7A9. Carrier rates for two SLC7A9 mutations were assessed in 287 unaffected Libyan Jewish controls. RESULTS: Twelve patients with mutations in SLC3A1 were compared to 15 patients with mutations in SLC7A9. No differences were detected between the patients with mutations in SLC3A1 and those with mutations in SLC7A9 in relation to the age of disease onset, the estimated number of stones, the number of invasive procedures, the number of patients receiving drug therapy, or the patients' urinary pH. Eleven of the unaffected Libyan Jewish controls were found to be heterozygotes for the V170M mutation, establishing a carrier rate of 1:25. The 1584 + 3 del AAGT mutation was not found in any of the Libyan Jewish controls. CONCLUSION: Mutations in SLC3A1 and SLC7A9 cystinuria patients result in indistinguishable disease manifestations. The high carrier rate among Libyan Jews is a result of a single missense mutation, V170M.

Functional analysis of mutations in SLC7A9, and genotype-phenotype correlation in non-Type I cystinuria.

Cystinuria (OMIM 220100) is a common recessive disorder of renal reabsorption of cystine and dibasic amino acids that results in nephrolithiasis of cystine. Mutations in SLC3A1, which encodes rBAT, cause Type I cystinuria, and mutations in SLC7A9, which encodes a putative subunit of rBAT (b(o,+)AT), cause non-Type I cystinuria. Here we describe the genomic structure of SLC7A9 (13 exons) and 28 new mutations in this gene that, together with the seven previously reported, explain 79% of the alleles in 61 non-Type I cystinuria patients. These data demonstrate that SLC7A9 is the main non-Type I cystinuria gene. Mutations G105R, V170M, A182T and R333W are the most frequent SLC7A9 missense mutations found. Among heterozygotes carrying these mutations, A182T heterozygotes showed the lowest urinary excretion values of cystine and dibasic amino acids. Functional analysis of mutation A182T after co-expression with rBAT in HeLa cells revealed significant residual transport activity. In contrast, mutations G105R, V170M and R333W are associated to a complete or almost complete loss of transport activity, leading to a more severe urinary phenotype in heterozygotes. SLC7A9 mutations located in the putative transmembrane domains of b(o,+)AT and affecting conserved amino acid residues with a small side chain generate a severe phenotype, while mutations in non-conserved residues give rise to a mild phenotype. These data provide the first genotype-phenotype correlation in non-Type I cystinuria, and show that a mild urinary phenotype in heterozygotes may associate with mutations with significant residual transport activity.

Aspergillus niger endocarditis in an immunocompetent patient: an unusual course.

Aspergillus is an opportunistic nosocomial fungus generally associated with a high mortality rate. A niger has been rarely associated with infection, and most cases have occurred in patients who have recently undergone heart surgery or in immunocompromised patients. We present a case of an immunocompetent patient with A niger endocarditis which illustrates the difficulties in diagnosis and the possible insidious course of fungal endocarditis.

The founder mutations in the BRCA1, BRCA2, and ATM genes in Moroccan Jewish women with breast cancer.

To gain insight into the molecular mechanisms underlying the inherited predisposition to breast cancer in non-Ashkenazi Jews, we genotyped 54 Jewish Moroccan women with breast cancer, unselected for family history of cancer, for the predominant Jewish mutations in BRCA1, BRCA2, and ATM. One patient (2%) was found to have the 185de1AG BRCA1 mutation, none was a carrier of the 6174delT BRCA2 mutation, and 2/54 (4%) were heterozygous for the ATM mutation. These rates were not significantly different from the rates in the general non-Ashkenazi population. These preliminary data may indicate that the predominant Jewish mutations in BRCA1, BRCA2, and ATM genes contribute little, if any, to breast cancer predisposition and risk among Moroccan Jews.

Efficacy and safety of intravenous amiodarone in recent-onset atrial fibrillation: experience in patients admitted to a general internal medicine department.

We examined the efficacy and safety of intravenous amiodarone in 20 unselected patients with recent-onset atrial fibrillation who were admitted to a general internal medicine department during a 6-month period. The treatment protocol included a loading dose of 1200 mg intravenous amiodarone in 24 hours, after which amiodarone treatment was continued orally. Eleven of the 20 patients (55%) converted to sinus rhythm within 48 hours of intravenous amiodarone treatment and were discharged in sinus rhythm, while 9/20 (45%) patients failed to convert during hospitalisation. Six patients (30%) failed to convert to sinus rhythm even after one further month of oral treatment. There was one death and a high frequency (25%) of thrombophlebitis during hospitalisation. The in-hospital non-convertors had a significantly lower ejection fraction and initial low ventricular response rate than the convertors. In conclusion, the acute conversion rate by intravenous amiodarone was at best modest. It is suggested that intravenous amiodarone is probably more effective in patients with rapid recent-onset atrial fibrillation and good left ventricular function.

Non-type I cystinuria caused by mutations in SLC7A9, encoding a subunit (bo,+AT) of rBAT.

Cystinuria (MIM 220100) is a common recessive disorder of renal reabsorption of cystine and dibasic amino acids. Mutations in SLC3A1, encoding rBAT, cause cystinuria type I (ref. 1), but not other types of cystinuria (ref. 2). A gene whose mutation causes non-type I cystinuria has been mapped by linkage analysis to 19q12-13.1 (Refs 3,4). We have identified a new transcript, encoding a protein (bo, +AT, for bo,+ amino acid transporter) belonging to a family of light subunits of amino acid transporters, expressed in kidney, liver, small intestine and placenta, and localized its gene (SLC7A9) to the non-type I cystinuria 19q locus. Co-transfection of bo,+AT and rBAT brings the latter to the plasma membrane, and results in the uptake of L-arginine in COS cells. We have found SLC7A9 mutations in Libyan-Jews, North American, Italian and Spanish non-type I cystinuria patients. The Libyan Jewish patients are homozygous for a founder missense mutation (V170M) that abolishes b o,+AT amino-acid uptake activity when co-transfected with rBAT in COS cells. We identified four missense mutations (G105R, A182T, G195R and G295R) and two frameshift (520insT and 596delTG) mutations in other patients. Our data establish that mutations in SLC7A9 cause non-type I cystinuria, and suggest that bo,+AT is the light subunit of rBAT.

Refined mapping of the CSNU3 gene to a 1.8-Mb region on chromosome 19q13.1 using historical recombinants in Libyan Jewish cystinuria patients.

Cystinuria is a genetic disease manifested by the development of kidney stones. In some patients, the disease is caused by mutations in the SLC3A1 gene located on chromosome 2p. In others, the disease is caused by a gene that maps to chromosome 19q, but has not yet been cloned. Cystinuria is very common among Jews of Libyan ancestry living in Israel. Previously we have shown that the disease-causing gene in Libyan Jews maps to an 8-cM interval on chromosome 19q between the markers D19S409 and D19S208. Several markers from chromosome 19q showed strong linkage disequilibrium, and a specific haplotype was found in more than half of the carrier chromosomes. In this study we have analyzed Libyan Jewish cystinuria families with eight markers from within the interval containing the gene. Seven of these markers showed significant linkage disequilibrium. A common haplotype was found in 16 of the 17 carrier chromosomes. Analysis of historical recombinants placed the gene in a 1.8-Mb interval between the markers D19S430 and D19S874. Two segments of the historical carrier chromosome used to calculate the mutation's age revealed that the disease-causing mutation was introduced into this population 7-16 generations ago.