High resolution mapping of the renal sodium-phosphate cotransporter gene (NPT2) confirms its localization to human chromosome 5q35

The precise chromosomal localization of the type II renal-specific Na+-phosphate (Pi) cotransporter (NPT2) gene (gene symbol SLC17A2) is necessary for the identification of closely linked polymorphic markers to determine whether NPT2 is a candidate gene for inherited disorders of renal Pi reabsorption. Recent studies by two different groups localized NPT2 to human chromosome 5q35 and 5q13, respectively. To resolve this discrepancy, we used three independent methods. The results using a human chromosome 5/rodent somatic cell hybrid deletion panel, fluorescence in situ hybridization with a PAC clone containing the NPT2 locus, and analysis of a chromosome 5-specific radiation hybrid panel were all consistent with the 5q35 assignment of the NPT2 gene. The radiation hybrid results placed NPT2 between polymorphic microsatellite markers D5S498 and D5S469. These findings will allow the initiation of linkage analysis to determine if NPT2 has a causative role in Mendelian disorders of renal Pi wasting.     

Monosialoganglioside (GM1) immunofluorescence in rat spinal roots studied with a monoclonal antibody

The rate of reaction of monochlorobimane with glutathione (GSH) was measured in native human mammary MCF-7 adenocarcinoma cells (MCF-7wt) and sublines displaying resistance to 4-hydroperoxycyclophosphamide (MCF-7hc) and adriamycin (MCF-7adr) prior to examination by epifluorescence and confocal microscopy. After a 60-min incubation period at 37 degrees C, essentially all GSH was conjugated in the MCF-7wt and MCF-7adr cell lines whereas only 80% of the GSH was conjugated in the MCF-7hc line. All three lines displayed significant export of the conjugate from the cell during this period, with the MCF-7adr line displaying the most rapid efflux with 85% of the conjugate exported within 60 min. Epifluorescence microscopy detected an approximately 20% increase in integrated fluorescence intensity in the nuclear region in all three lines. Confocal microscopy however, indicated that most of the cells examined showed a homogeneous fluorescence distribution. The cells grown in monolayers were found to be thicker in the nuclear region suggesting that the observed increase in fluorescence intensity in the nuclear region in the images from epifluorescence microscopy was probably derived from fluorescence from an out-of-focus plane. Cells depleted of GSH with buthionine sulfoximine followed by treatment with mBCl showed significant fluorescence intensity resulting from nonspecific binding of this probe. These studies illustrate the need for measuring the rate of GSH conjugate export and for determining probe specificity, and emphasizes the need for using confocal techniques for the quantitative evaluation of the distribution of intracellular fluorescence.     

Clinical observation of the temporal association between crack cocaine and duodenal ulcer perforation

HYPOTHESIS: To determine if a cause-effect relationship exists between crack cocaine use and duodenal ulcer perforation (DUP). PATIENTS AND METHODS: A retrospective study was conducted of all patients undergoing emergency surgical management for peptic ulcer disease over a 6-year period at a large inner-city municipal teaching hospital. The hospital records of 78 consecutive patients presenting with complications of peptic ulcer disease between April 1990 and April 1996 were reviewed. Group A (n = 24) consisted of patients with confirmation of crack cocaine usage within 8 hours of clinical presentation; group B (n = 54) consisted of patients with no antecedent history of crack cocaine use. Demographic data, timing of drug use, clinical presentation, laboratory and radiographic findings, toxicology screening, operative findings, and postoperative course were compared between the two groups. RESULTS: Both groups revealed a similar gender distribution, tobacco use, prior peptic ulcer symptoms, and laboratory findings. Group A patients were younger (t test, P = 0.01) and more likely to present with perforation, whereas patients in group B presented with a combination of symptoms (chi square, P = 0.03). Duodenal ulcer perforation was present in 75% of patients in group A compared with 46% of patients in group B (chi square, P = 0.04). Group B patients had a significantly longer hospital stay compared with those in group A (t test, P = 0.01). Both crack cocaine and alcohol are independent predictors of duodenal ulcer perforation. CONCLUSIONS: Patients with recent use of crack cocaine and/or alcohol are more likely to present with duodenal perforations. Although a temporal association between crack cocaine use and duodenal ulcer perforation was demonstrated, this study does not confirm a cause-effect relationship. A prospective cohort study is needed to clarify the pathogenesis of this potential cause-effect relationship.     

The formation and control of Laves phase in superalloy 718 welds

Weld heat input/cooling rate (affected by welding process, parameters, technique, tooling, etc.) was found to influence the microstructural characteristics and segregational features in alloy 718 welds, with low heat inputs proving beneficial. Laves phase formed in the interdendritic regions of the weld metals as a result of segregation. The morphology and composition of Laves phase depended strongly on heat input/cooling rate and influenced its response to subsequent homogenization post-weld heat treatment. The various factors affecting the formation and control of Laves phase in alloy 718 welds are highlighted. This revised version was published online in November 2006 with corrections to the Cover Date.     

The functional outcome of lower-extremity fractures with vascular injury

Salvage of lower-extremity Gustilo type IIIC fractures is difficult, time-consuming for the patients and physicians, and not universally successful because of poor functional outcomes. Even if successful with limb salvage, the functional result may be unsatisfactory because of mutilating injuries to muscle and nerve, bone loss, and the presence of chronic infection. From July 1991 until July 1994, revascularizations of open IIIC fractures were attempted for wounds with Mangled Extremity Severity Score (MESS) < or = 10. The functional results were evaluated at 2 years after injury. Thirty-six lower-extremity revascularizations were performed on 34 patients, including 1 patient with bilateral distal tibial IIIC fractures and a child with IIIC femoral fracture accompanied by ipsilateral distal tibial amputation. Excluded were patients with below-ankle IIIC fractures as well as patients who underwent immediate amputation at admission. After the revascularization, seven patients with IIIC fractures (7 of 36, 19.4%) underwent secondary amputation within 1 week. At the 2-year follow-up, the overall secondary amputation rate was 25% (9 of 36) and the salvage rate was 75% (27 of 36). Those were no deaths. Of the 29 salvaged limbs among these 27 patients, 23 limbs (23 of 29, 79.3%) required secondary coverage procedures that included 12 free flap transfers (12 of 29, 41.4%). Every patient needed subsequent reconstructive surgery to achieve an acceptable functional result. In this series, MESS was able to predict the secondary amputation rate and the functional result. Sixteen of the 17 limb-salvaged patients with MESS < or = 7 were able to achieve minimal functional requirements, whereas 3 of the 10 patients with MESS = 8 to 10 failed to achieve minimal functional requirements at the 2-year follow-up. Using statistical analysis, we found that the salvaged limbs with MESS < or = 9 exhibited a significant difference in achieving adequate function compared with limbs with MESS > 9. Using our protocol for treatment for IIIC fractures, the threshold for immediate amputation can be raised from MESS = 7 to MESS = 9. Our conclusions are (1) more severely injured limbs have poor functional results, (2) every patient needs subsequent reconstructive surgery, and (3) the MESS may be helpful in decision-making.     

OTR-COTA collaboration in home health: roles and supervisory issues

Previous neuroimaging research has contributed insights regarding the neural substrates of specific psychiatric disorders. The purpose of this study was to determine the shared mediating neuroanatomy of anxiety symptoms across three different anxiety disorders. Data were pooled from 23 right-handed adult outpatients meeting criteria for obsessive-compulsive disorder, simple phobia, or posttraumatic stress disorder. Relative regional cerebral blood flow (rCBF) was measured using positron emission tomography in the context of symptom provocation paradigms. Symptom severity was measured via self-reports. The analysis of pooled imaging data indicated activation in right inferior frontal cortex, right posterior medial orbitofrontal cortex, bilateral insular cortex, bilateral lenticulate nuclei, and bilateral brain stem foci during the symptomatic versus control conditions. A positive correlation was found between rCBF at one brain stem locus and subjective anxiety scores (r = .744, p < .001). These findings suggest that elements of the paralimbic belt together with right inferior frontal cortex and subcortical nuclei mediate symptoms across different anxiety disorders. In addition, activation at one brain stem locus appears to be associated with the subjective severity of anxiety. Further studies are warranted to determine whether these same brain systems mediate normal anxiety states as well.