The Impact of Insurance Status on the Outcomes after Aneurysmal Subarachnoid Hemorrhage

Investigation into the association of insurance status with the outcomes of patients undergoing neurosurgical intervention has been limited: this is the first nationwide study to analyze the impact of primary payer on the outcomes of patients with aneurysmal subarachnoid hemorrhage who underwent endovascular coiling or microsurgical clipping. The Nationwide Inpatient Sample (2001–2010) was utilized to identify patients; those with both an ICD-9 diagnosis codes for subarachnoid hemorrhage and a procedure code for aneurysm repair (either via an endovascular or surgical approach) were included. Hierarchical multivariate regression analyses were utilized to evaluate the impact of primary payer on in-hospital mortality, hospital discharge disposition, and length of hospital stay with hospital as the random effects variable. Models were adjusted for patient age, sex, race, comorbidities, socioeconomic status, hospital region, location (urban versus rural), and teaching status, procedural volume, year of admission, and the proportion of patients who underwent ventriculostomy. Subsequent models were also adjusted for time to aneurysm repair and time to ventriculostomy; subgroup analyses evaluated for those who underwent endovascular and surgical procedures separately. 15,557 hospitalizations were included. In the initial model, the adjusted odds of in-hospital mortality were higher for Medicare (OR 1.23, p<0.001), Medicaid (OR 1.23, p<0.001), and uninsured patients (OR 1.49, p<0.001) compared to those with private insurance. After also adjusting for timing of intervention, Medicaid and uninsured patients had a reduced odds of non-routine discharge (OR 0.75, p<0.001 and OR 0.42, p<0.001) despite longer hospital stays (by 8.35 days, p<0.001 and 2.45 days, p = 0.005). Variations in outcomes by primary payer–including in-hospital post-procedural mortality–were more pronounced for patients of all insurance types who underwent microsurgical clipping. The observed differences by primary payer are likely multifactorial, attributable to varied socioeconomic factors and the complexities of the American healthcare delivery system.     

New Class of Streptomycin-Resistant Mutants Incompatible with supX Suppressor Mutations in Salmonella typhimurium

Streptomycin-resistant colonies of Salmonella typhimurium appearing in platings of supX suppressors of strain leu-500 are less variegated in size than are those derived from strain leu-500 counterparts. Several of the streptomycin-resistant leu-500 clones, furthermore, yield suppressors and revertants of the leu-500 auxotrophy at unusually low rates, suggesting that they provide a genetic background inimicable to supX suppression. Two such "suppression-restrictive" leu-500 streptomycin-resistant (str) mutants, designated strains M(1) and M(4), were characterized as to their ability to receive the trp-supX-cysB linkage region by transduction. Coentry of a donor supX deletion mutation with the selected trp(+) marker was not observed even though these sites display more than 10% linkage in control experiments. This was demonstrably the result of nonviability of the combined supX mutant, M(1) or M(4) streptomycin-resistant genotype, rather than the lack of suppression of the leu-500 imparted auxotrophy. Both M(1)- and M(4)-type resistance was accompanied by pleiotropic effects resembling those caused by strB (nonribosomal)- rather than strA (ribosomal)-type resistance, but both restrictive mutants had a high upper limit of resistance corresponding to that of strA-type mutants. Transduction analyses indicated that the str character of neither the M(1) nor the M(4) strain was linked to the strA or the strB gene. These mutations define a previously undescribed locus, which we propose to designate strC, apparently related to streptomycin uptake rather than its intracellular action. Mutation at this locus is evidently incompatible with the inactivation or removal of the supX site, suggesting a functional association between products of the genes.     

Genetic variation in North Africa and Eurasia: Neolithic demic diffusion vs. paleolithic colonisation

The hypothesis that both genetic and linguistic similarities among Eurasian and North African populations are due to demic diffusion of neolithic farmers is tested against a wide database of allele frequencies. Demic diffusion of farming and languages from the Near East should have determined clines in areas defined by linguistic criteria; the alternative hypothesis of cultural transmission does not predict clines. Spatial autocorrelation analysis shows significant gradients in three of the four linguistic families supposedly affected by neolithic demic diffusion; the Afroasiatic family is the exception. Many such gradients are not observed when populations are jointly analyzed, regardless of linguistic classification. This is incompatible with the hypothesis that major cultural transformations in Eurasia (diffusion of related languages and spread of agriculture) took place without major demographic changes. The model of demic diffusion seems therefore to provide a mechanism explaining coevolution of linguistic and biological traits in much of the Old World. Archaeological, linguistic, and genetic evidence agree in suggesting a multidirectional process of gene flow from the Near East in the neolithic. However, the possibility should be envisaged that some allele frequency patterns can predate the neolithic and depend on the initial spread of Homo sapiens sapiens from Africa into Eurasia. © 1994 Wiley-Liss, Inc.     

Chaetomella acutiseta produces chaetomellic acids A and B which are reversible inhibitors of farnesyl-protien transferase

Chaetomellic acids A and B, isolated from Chaetomella acutiseta, are specific inhibitors of farnesyl-protein transferase that do not inhibit geranylgeranyl transferase type 1 or squalene synthase. Chaetomellic acids A and B are reversible inhibitors, resemble farnesyl diphosphate and probably inhibit FPTase by substituting for farnesyl diphosphate. Chaetomellic acid production appears to be widespread within the genus Chaetomella. Correspondence to: R. B. Lingham     

Why are some genetic diseases common?

Various processes (selection, mutation, migration and genetic dirft) are known to determine the frequency of genetic disease in human populations, but so far it has proved almost impossible to decide to what extent each is responsible for the presence of a particular genetic disease. The techniques of gene and haplotype analysis offer new hope in addressing this issue, and we review relevant studies of three haemoglobinopathies: sickle cell anaemia, and and thalassaemia. We show how for each disease it is possible to recognize a pattern of regionally specific mutations, found in association with one or a few haplotypes, that is best explained as the result of selection; other patterns are due to population migration and genetic drift. However, we caution that such conclusions can be drawn in special circumstances only. In the case of the haemoglobinopathies it is possible because a selective agent (malaria) was already suspected, and the investigations could be carried out in relatively genetically homogenous populations whose migratory histories are known. Moreover, some data reviewed here suggest that gene conversion and the haplotype composition of a population may affect the frequency of a mutation, making interpretation of gene frequencies difficult on the basis of standard population genetics theory. Hence attempts to use the same approaches with other genetic diseases are likely to be frustrated by a lack of suitably untrammelled populations and by difficulties accounting for poorly understood genetic processes. We conclude that although this combination of molecular and population genetics is successful when applied to the study of haemoglobinopathies, it may not be so easy to apply it to the study of other genetic diseases.     

Reliability and stability of mothers' reports about their pregnancies with twins.

The objective of this study was to determine if mothers' retrospective reports about events in their pregnancies with twins are reliable and stable. Six hundred and twenty-four mothers completed psychiatric interviews about their twins. These interviews also contained questions about the mothers' pregnancies, the perinatal period, and the child's early development. The mothers reported first on one twin and then on the other with interviews spaced from 3 days to 2 weeks apart. Thus mothers reported on the same pregnancy twice. Of these mothers, 47 were re-interviewed 6 to 18 months later by raters blind to the results of the initial interview. The twin design allowed us to compare the short-term reliability of the 624 mothers' reports of the same pregnancy. The re-interview of the 47 mothers enabled us to compare the stability of reports over a longer time period. Agreement between the reports was measured with the kappa statistic. Kappas were good to excellent for the short-term reports of pregnancy for each twin for the 624 mothers. Kappas were equally high for the 47 mothers that were re-interviewed 6 to 18 months later. Mothers show good reliability and stability of reporting about events during pregnancy.     

Sequential processing of epidermal growth factor in early and late endosomes of rat liver.

We have used isolated perfused rat livers to examine the intracellular processing of 125I-epidermal growth factor (EGF) and to determine where in the endocytic pathway the hydrolases which degrade EGF are acting. Following uptake of 125I-EGF at 37 or 16 degrees C, subcellular fractions enriched in endosomes and lysosomes were isolated, and their 125I-EGF content was examined by reverse-phase high performance liquid chromatography. Three forms of EGF processed at their carboxyl termini are generated in endosomes. At 37 degrees C, EGF is first processed in early endosomes by a carboxypeptidase B-like protease and is further processed in late endosomes by a trypsin-like protease and then a carboxypeptidase B-like protease. At 16 degrees C, entry of EGF into late endosomes is slowed, and only the first processed form is generated over 60 min. Longer perfusions (180 min) at 16 degrees C result in some processing (7%) by proteases found in late endosomes. EGF-horseradish peroxidase cytochemistry confirmed that the additional processing detected at 180 min correlated with movement of EGF from tubulovesicular to multivesicular endosomes. These results, combined with in vitro incubations of EGF in isolated endosomal and lysosomal fractions, suggest that different proteases are active at selective points in the endocytic pathway and that the full complement of proteases needed for complete degradation of EGF is active only in lysosomes.