Improved Performance of Hip DXA Using a Novel Region of Interest in the Upper Part of the Femoral Neck: In Vitro Study Using Bone Strength as a Standard of Reference

We tested the hypothesis that bone mineral density (BMD) and bone mineral content (BMC) in proximal human femur specimens in the upper neck region of interest (ROI) and femoral neck axis length (FNAL) provide a significantly better prediction of femoral bone strength than standard ROIs in vitro. BMD and BMC were measured in 110 proximal femur specimens using a standard dual-energy X-ray absorptiometry (DXA) scanner. The analysis included a new ROI in the upper neck as well as the standard ROIs. FNAL was obtained from the scan images. The specimens' failure-load was measured in a mechanical loading device, simulating a fall on the greater trochanter. For the standard ROIs, correlations between failure-load and BMD ranged from R2 = 0.64 (shaft ROI) to R2 = 0.70, p < 0.001 (femoral neck). Prediction of strength by BMD did not significantly differ from those of BMC (R2 ranging from 0.65 to 0.75, p < 0.001). In the upper neck ROI, for both BMD and BMC correlations with failure-load were higher (R2 = 0.76 and 0.81, respectively; p < 0.001). A lower, yet still significant, correlation was found between FNAL and bone strength (R2 = 0.23, p < 0.001). Normalization of failure-load with respect to FNAL did not significantly increase the correlations with densitometric measures. This study provides in vitro evidence indicating that among the ROIs of the proximal femur the newly defined upper neck ROI provides the best prediction of bone strength. Only a weak association was observed between failure load and FNAL.     

No increase in the prevalence of asthma, allergies, and atopic sensitisation among children in Germany: 1992-2001

BACKGROUND: From 1970 to 1990 increasing rates of asthma and allergic sensitisation were observed in several countries. The aim of this study was to investigate time trends in the prevalence of asthma and allergic sensitisation among school children in Germany between 1992 and 2001. METHODS: Parental reports of asthma, hay fever, and wheezing and measurements of specific serum IgE antibodies were investigated in six serial cross sectional surveys of 9-11 year old school children in three study areas in south west Germany. RESULTS: A total of 6762 school children of mean age 10 years (mean participation rate 77.9%) took part in the investigation in the three study areas. Over the 9 year study period no increase in the prevalence of current wheezing and asthma was observed. In addition, the prevalence of atopic sensitisation remained unchanged during the observation period. CONCLUSIONS: These data, using parental reports and objective measures of allergy, suggest that there has been no further increase in the prevalence of asthma and atopy since 1992. The epidemic may thus have reached a plateau.     

Is cerebral panangiography unnecessary in determining brain death?

The diagnosis of brain death, i.e. death of cortex and brainstem, can be established by neurologic examination only if there is no intoxication, sedative therapy, or hypothermia. In the latter cases, until now only cerebral panangiography can establish the diagnosis. We investigated, whether in these cases cerebral perfusion scintigraphy (CPS) in combination with brainstem auditory evoked potential (BAEP) can replace CPA for establishing the diagnosis. METHODS: 40 patients, treated in our interdisciplinary ICU because of primary or secondary brain lesions and in whom determination of brain death by neurological examination was contraindicated, were subjected to the following procedure: When coma was diagnosed, brainstem reflexes were examined. If negative, an atropine-test was done and this being negative, apnea-testing was performed. If apnea was positive, BAEP, CPS and CPA were performed. The results of BAEP and CPS were compared with the results of CPA. RESULTS: In 38 patients with suspected brain death the first examination showed complete correspondence between BAEP and CPS on one hand and CPA on the other hand (Table 3). In patient No. 39, CPS as well as CPA showed minimal supratentorial circulation, whereas BAEP were negative as was circulation in the fossa posterior. In patient No. 40 as well CPS and CPA showed minimal supratentorial circulation. Brainstem testing with BAEP was negative although CPA showed minimal brainstem perfusion.(ABSTRACT TRUNCATED AT 250 WORDS)     

Epithelial growth by rat vibrissae follicles in vitro requires mesenchymal contact via native extracellular matrix

An in vitro assay utilizing the rat vibrissa anagen follicle as a model for studying the epithelial-mesenchymal interactions (EMI) in hair growth is described. Through selective disruption of the epithelial-mesenchymal interface, we investigate whether the specialized extracellular matrix (ECM) of the dermal papilla and basement membrane zone (BMZ) serves a crucial function in hair follicle EMI. Epithelial bulbs incubated intact within their follicular sheaths incorporate thymidine primarily into cells of the hair matrix and outer root sheath, as shown by autoradiography. However, after removal of its mesenchymal associations (dermal papilla and extrabulbar connective tissue), the epithelial bulb showed no incorporation. Neither externally added collagen (type I or IV) nor the basement membrane components in Matrigel could substitute for the growth supporting influence of native surrounding stroma. Mechanical separation of the bulb from the dermal papilla in the basement membrane zone inhibited thymidine incorporation by the epithelium even though mesenchyme was still in close proximity. Enzymatic digestion of the dermal papilla ECM and the basal lamina by Dispase, a fibronectinase and type IV collagenase, also inhibited bulb growth without evidence of cytotoxicity. These experiments suggest that direct epithelial to mesenchymal contact is required for the support of follicular epithelial growth in vitro and that specific ECM components, possibly fibronectin and/or type IV collagen, rather than diffusable factors alone, play a crucial role in the mechanism of hair follicle EMI. The in vitro system described here provides an alternative to developmental EMI models and may serve as a valuable tool for studying EMI in the adult mammalian organism.     

Cranial Tumor Surgical Outcomes at a High-Volume Academic Referral Center

Objective

To determine adverse event rates for adult cranial neuro-oncologic surgeries performed at a high-volume quaternary academic center and assess the impact of resident participation on perioperative complication rates.

Low individualized growth hormone (GH) dose increased renal and cardiac growth in young adults with childhood onset GH deficiency

OBJECTIVE: In childhood onset GH deficiency (GHD) a reduction in left ventricular mass (LV-mass) and impairment of systolic function as well an impairment in glomerular filtration rate (GFR) has been shown. The aim of the present study was to assess if a low GH dose resulted in an improvement in morphological and functional parameters of these organs. DESIGN AND PATIENTS: Eleven patients with childhood onset GHD were investigated before and after 10 months of GH treatment at a dose of 1.5 IU/day (range 1-2), corresponding to 0.02 IU/kg/day or 7 microg/ kg/day. The GH dose resulted in a serum IGF-I level in the normal range in all but one patient. MEASUREMENTS: Doppler echocardiography of the heart and ultrasound examination of the kidneys was performed. Glomerular filtration rate (GFR) was estimated with iohexol clearance and urinary proteinuria was measured with 24-h urinary samples collected for analyses of albumin, alpha-1-microglobulin, IgG and albumin/creatinine clearance ratio. Body composition was measured by bioelectric impedance analysis. RESULTS: L V-mass index increased significantly after GH treatment (P = 0.04), and there was a clear trend for a positive correlation between the increase in serum IGF-I and the increase in LV-mass index, although it did not reach significance (r= 0.57, P = 0.07). GH treatment did not increase cardiac fractional shortening. Kidney length increased significantly (P = 0.02) with an average increase of 1 cm (range - 0.5-1.5 cm). No significant changes in median GFR or serum creatinine were recorded. Three patients with subnormal GFR before GH treatment normalized after 10 months of treatment. Urine analysis showed no abnormalities before or after GH treatment. A significant decrease in percentage fat mass was recorded (P = 0.03). CONCLUSION: A low individualized GH dose to adults with childhood onset GHD resulted in an increase in LV-mass index and kidney length. Re-establishing GH treatment with a low dose in this patient group can lead to a further somatic maturation of these organs, probably not accomplished previously.     

Identification of somatic JAK1 mutations in patients with acute myeloid leukemia

Somatic mutations in JAK2 are frequently found in myeloproliferative diseases, and gain-of-function JAK3 alleles have been identified in M7 acute myeloid leukemia (AML), but a role for JAK1 in AML has not been described. We screened the entire coding region of JAK1 by total exonic resequencing of bone marrow DNA samples from 94 patients with de novo AML. We identified 2 novel somatic mutations in highly conserved residues of the JAK1 gene (T478S, V623A), in 2 separate patients and confirmed these by resequencing germ line DNA samples from the same patients. Overexpression of mutant JAK1 did not transform primary murine cells in standard assays, but compared with wild-type JAK1, JAK1^T478S, and JAK1^V623A expression was associated with increased STAT1 activation in response to type I interferon and activation of multiple downstream signaling pathways. This is the first report to demonstrate somatic JAK1 mutations in AML and suggests that JAK1 mutations may function as disease-modifying mutations in AML pathogenesis.     

Extraction of Buried P Waves from Printed Electrocardiograms

Background: Morphologic identification of ectopic P‐waves from surface ECGs can be challenging, particularly when the P‐wave is buried in the QRST wave complex. Because ECGs are often available on paper and not digitally, we developed a method of subtracting the T‐wave from the buried P‐wave complex on paper ECGs. Methods: To validate our system, an atrial extrastimulus was introduced during and following the T‐wave. The ECGs were scanned and then transformed from an image format to a digital format. A computer algorithm digitally subtracted a QRST with no buried P‐wave from one with a buried P‐wave, thus resulting in an extracted P‐wave. The extracted P‐waves were compared to the nonburied P‐wave by determining correlation coefficients and by visual grading by two independent reviewers. Results: Visual grading comparing the buried P‐wave with the exposed paced P‐wave was 94%. The median correlation coefficient was 85%. Conclusions: An ectopic atrial P‐wave obscured by a coincident QRST wave complex can be accurately derived from printed ECG using this PC‐based system. Addition of this technique to the existing methods may aid in the localization and ablation of ectopic atrial foci.