Craniotomy for meningioma in the United States between 1988 and 2000: decreasing rate of mortality and the effect of provider caseload

OBJECT: The goal of this study was to determine the risk of adverse outcomes after contemporary surgical treatment of meningiomas in the US and trends in patient outcomes and patterns of care. METHODS: The authors performed a retrospective cohort study by using the Nationwide Inpatient Sample covering the period of 1988 to 2000. Multivariate regression models with disposition end points of death and hospital discharge were used to test patient, surgeon, and hospital characteristics, including volume of care, as outcome predictors. Multivariate analyses revealed that larger-volume centers had lower mortality rates for patients who underwent craniotomy for meningioma (odds ratio [OR] 0.74, 95% confidence interval [CI] 0.59-0.93, p = 0.01). Adverse discharge disposition was also less likely at high-volume hospitals (OR 0.71, 95% CI 0.62-0.80, p < 0.001). With respect to the surgeon caseload, there was a trend toward a lower rate of mortality after surgery when higher-caseload providers were involved, and a significantly less frequent adverse discharge disposition (OR 0.71, 95% CI 0.62-0.80, p < 0.001). The annual meningioma caseload in the US increased 83% between 1988 and 2000, from 3900 patients/year to 7200 patients/year. In-hospital mortality rates decreased 61%, from 4.5% in 1988 to 1.8% in 2000. Reductions in the mortality rates were largest at high-volume centers (a 72% reduction in the relative mortality rate at largest-volume-quintile centers, compared with a 6% increase in the relative mortality rate at lowest-volume-quintile centers). The number of US hospitals where craniotomies were performed for meningiomas increased slightly. Fewer centers hosted one meningioma resection annually, whereas the largest centers had disproportionate increases in their caseloads, indicating a modest centralization of meningioma surgery in the US during this interval. CONCLUSIONS: The mortality and adverse hospital discharge disposition rates were lower when meningioma surgery was performed by high-volume providers. The annual US caseload increased, whereas the mortality rates decreased, especially at high-volume centers.     

Advancing infection control in dental care settings: Factors associated with dentists' implementation of guidelines from the Centers for Disease Control and Prevention

Background and OverviewThe authors set out to identify factors associated with implementation by U.S. dentists of four practices first recommended in the Centers for Disease Control and Prevention's Guidelines for Infection Control in Dental Health-Care Settings—2003.MethodsIn 2008, the authors surveyed a stratified random sample of 6,825 U.S. dentists. The response rate was 49 percent. The authors gathered data regarding dentists' demographic and practice characteristics, attitudes toward infection control, sources of instruction regarding the guidelines and knowledge about the need to use sterile water for surgical procedures. Then they assessed the impact of those factors on the implementation of four recommendations: having an infection control coordinator, maintaining dental unit water quality, documenting percutaneous injuries and using safer medical devices, such as safer syringes and scalpels. The authors conducted bivariate analyses and proportional odds modeling.ResultsResponding dentists in 34 percent of practices had implemented none or one of the four recommendations, 40 percent had implemented two of the recommendations and 26 percent had implemented three or four of the recommendations. The likelihood of implementation was higher among dentists who acknowledged the importance of infection control, had practiced dentistry for less than 30 years, had received more continuing dental education credits in infection control, correctly identified more surgical procedures that require the use of sterile water, worked in larger practices and had at least three sources of instruction regarding the guidelines. Dentists with practices in the South Atlantic, Middle Atlantic or East South Central U.S. Census divisions were less likely to have complied.ConclusionsImplementation of the four recommendations varied among U.S. dentists. Strategies targeted at raising awareness of the importance of infection control, increasing continuing education requirements and developing multiple modes of instruction may increase implementation of current and future Centers for Disease Control and Prevention guidelines.The findings and conclusions in this report are those of the authors and do not necessarily represent the official position of the Centers for Disease Control and Prevention, Atlanta.The authors thank Jon Ruesch, who when this study was conducted was the director, Survey Center, American Dental Association, Chicago, for his effort in the collection of the data for this research project. Mr. Ruesch is now retired.     

Increased erythrocyte stearic acid desaturation in rats with chemically induced colorectal carcinomas

Our previous studies have demonstrated a desaturation of stearic acid related to oleic acid in the lipid layer of erythrocytes in patients with malignancies. This study investigated the stearic acid desaturation in red blood cell membranes of rats during the induction of colorectal tumours. Male Sprague-Dawley rats were injected weekly with dimethylhydrazine (DMH) and sacrificed at 4-week intervals. Blood was withdrawn via heart puncture, collected in EDTA bottle and erythrocytes separated by centrifugation. Total lipid extraction was carried out and analysed with gas liquid chromatography. In the control rats (injected with normal saline) the mean of the stearic to oleic acid ratio in erythrocyte membranes was 2.0±0.3 (n=28, range 1.51–2.62) compared to a mean of 0.94±0.16 (n=0.5–1.23) in tumour bearing rats (p< 0.001). The increased desaturation occurred in parallel with appearance of tumours. These data suggest the regulation of stearic acid desaturation is an important adaptive mechanism of membrane fluidity and could be a useful chemical marker for malignancy.     

Physical and functional interactions between Stat5 and the tyrosine- phosphorylated receptors for erythropoietin and interleukin-3

Erythropoietin (Epo) and interleukin-3 (IL-3) stimulate activation of the Jak2 tyrosine kinase and induce tyrosine phosphorylation and activation of Stat5. In the present study, we have shown that Epo or IL- 3 stimulation induces binding of Stat5 to the tyrosine-phosphorylated Epo receptor (EpoR) or IL-3 receptor beta subunit (betaIL3), respectively, in IL-3-dependent 32D cells expressing the EpoR. The binding of Stat5 to these cytokine receptors was shown to be rapid and transient, occurring within 1 minute of stimulation of cells and significantly decreasing after 5 minutes of cell treatment. In vivo binding experiments in COS cells showed that binding of Stat5 to the EpoR was mediated through the Stat5 Src homology 2 (SH2) domain. In vitro binding studies further showed that Stat5, but not other Stats examined, bound specifically to tyrosine-phosphorylated recombinant EpoR fusion proteins. In these in vivo and in vitro binding studies, Stat5 bound, albeit to a lesser degree, to truncated EpoR mutants in which all the intracellular tyrosines except Y-343 were removed. Furthermore, EpoR-derived synthetic phosphotyrosine peptides corresponding to Y-343, Y-401, Y-431, and Y-479 inhibited the in vitro binding of Stat5. When expressed in 32D cells, a mutant EpoR in which all the intracellular tyrosines were removed by carboxy-terminal truncation showed a significantly impaired ability to induce tyrosine phosphorylation of Stat5, particularly at low concentrations of Epo, but exhibited an increased sensitivity to Epo for growth signaling as compared with the wild-type EpoR. These results indicate that Stat5 specifically and transiently binds to the EpoR through the interaction between the Stat5 SH2 domain and specific phosphorylated tyrosines, including Y-343, in the EpoR cytoplasmic domain. It was implied that betaIL3 may also have similar Stat5 docking sites. The Stat5 docking sites in the EpoR were shown to facilitate specific activation of Stat5, which, however, may not be required for the EpoR-mediated growth signaling.     

Low birth weights contribute to high rates of early-onset chronic renal failure in the Southeastern United States

BACKGROUND: The southeastern United States is a region in which rates of cardiovascular and renal diseases are excessive. Within the Southeast, South Carolina has unusually high rates of end-stage renal disease (ESRD) in young people, with more than 70% of cases attributed to hypertension and diabetes. OBJECTIVE: To determine whether the increased vulnerability to early-onset ESRD might originate through impaired renal development in utero as measured by low birth weight. METHODS: Patients who were diagnosed with renal failure and undergoing dialysis from 1991 through 1996 were identified from the ESRD registry maintained by the Southeastern Kidney Council, Raleigh, NC. Birth weights reported on birth certificates were selected for the ESRD cases and non-ESRD controls who were born in South Carolina in 1950 and later. Birth weights were compared for 1230 cases and 2460 controls who were matched for age, sex, and race. RESULTS: Low birth weight was associated with ESRD among men and women as well as blacks and whites. Among people whose birth weight was less than 2.5 kg, the odds ratio for ESRD was 1.4 (95% confidence interval, 1.1-1.8) compared with people who weighed 3 to 3.5 kg. This association was present for renal failure resulting from diabetes, hypertension, and other causes. CONCLUSIONS: Low birth weights, which reflect adverse effects on development in utero, contribute to the early onset of ESRD in South Carolina. Since low birth weight increases the risk of ESRD from multiple causes, the data suggest that an adverse environment in utero impairs kidney development and makes it more vulnerable to damage from a range of pathological processes.     

Fetal programming of coronary heart disease.

People who develop coronary heart disease grow differently from other people both in utero and during childhood. Slow growth during fetal life and infancy is followed by accelerated weight gain in childhood. Two disorders that predispose to coronary heart disease, type 2 diabetes and hypertension, are preceded by similar paths of growth. Mechanisms underlying this are thought to include the development of insulin resistance in utero, reduced numbers of nephrons associated with small body size at birth and altered programming of the micro-architecture and function of the liver. Slow fetal growth might also heighten the body's stress responses and increase vulnerability to poor living conditions in later life. Coronary heart disease appears to be a developmental disorder that originates through two widespread biological phenomena, developmental plasticity and compensatory growth.     

Multilocus mapping of the X-linked hypophosphatemic rickets gene.

X-linked hypophosphatemic rickets (HYP), the most common form of familial hypophosphatemic (vitamin D-resistant) rickets, is an X-linked dominant disorder characterized by decreased renal tubular phosphate reabsorption and consequent hypophosphatemia. Despite the application of a wide variety of biochemical and cell biology techniques, controversy exists regarding whether a primary renal abnormality underlies the abnormal phosphate transport or if this defect is secondary to the effects of a hormonal/metabolic factor. Thus localization of the HYP gene and its ultimate cloning may be necessary to elucidate the pathophysiology of the disorder. In order to map the human HYP gene we investigated several new polymorphic probes for linkage to HYP and constructed a map of markers around the gene. The database used to ascertain linkage and perform mapping included 5 large HYP kindreds, 40 Centre d'Etudie Polymorphisms Humain reference pedigrees, and 19 kindreds which had been obtained for other disease linkage studies. Two point LOD scores (odds of linkage, log10) indicate that the probes DXS365, DXS257, DXS451, and DXS41 are tightly linked to the HYP locus. Indeed, there were no cross-overs between DXS365 and HYP with a peak LOD score of 13.98 [recombination fraction (theta) = 0.00]. Moreover, multipoint analysis reveals a probable locus order of: Xtel-DXS315-DXS43-DXS257-HYP-DXS41-DXS4 51-Xcen. The likelihood of HYP occurring between DXS257 and DXS41 is 407:1 over the next most likely position. DXS365 is located between DXS41 and DXS43 but could not be located with respect to HYP and DXS257. Regardless, we have located the HYP gene between the flanking markers DXS257 (telomeric) and DXS41 (centromeric) which are 3.5 centiMorgans apart. Thus, the results of this study will facilitate attempts to further localize and eventually clone the gene.     

The roles of the glycosylphosphatidylinositol anchor on the production and immunogenicity of recombinant ookinete surface antigen Pbs21 of Plasmodium berghei when prepared in a baculovirus expression system

Malarial ookinetes express an immunodominant surface protein (P28) that is a priority candidate for the development of transmission-blocking vaccines. The full length P28 gene from Plasmodium berghei [Pbs21(1-213)] and a deletion construct [Pbs21(1-188)] encoding a protein that lacks the 25 C-terminal amino acids, including the glycosylphosphatidylinositol (GPI) anchor signal, were expressed in insect cells using baculovirus vectors. Pbs21(1-213) protein is strongly hydrophobic, found in the cytoplasm and on the surface of Spodoptera Sf21 cells, and in the culture medium. Pbs21(1-188) protein was largely found in the aqueous phase of the medium and in the cytoplasm of Sf21 cells, but was not detected on the cell surface. The presence of 25 C-terminal amino acids is therefore critical to the attachment of recombinant Pbs21 to the parasite plasma membrane. Mice were immunized subcutaneously or intramuscularly with affinity purified recombinant Pbs21(1-213), Pbs21(1-188) or native Pbs21 proteins. Following two immunizations, native Pbs21 induces higher titres when administered by either route, than the recombinant protein bearing an insect GPI anchor, which in turn is markedly more immunogenic than the recombinant polypeptide lacking a GPI anchor. When specific anti Pbs21 antibody titres exceeded 1 mg/ml all three antigens were capable of inducing transmission blockade > or = 90%, below 1 mg/ml blockade did not correlate with antibody concentration.