Overexpression Of GPR7 In Schwann Cells From Patients With Peripheral Neuropathies

The identification of regulated gene products that play a role in Schwann cell-axon contact after nerve injuries may have important implications for pain mechanisms and nerve repair processes. Schwann cell-intrinsic defects have been recently shown to cause neuropathies associated with pain (Gillespie et al., 2000). The 7TM GPR7, originally described by O'Dowd et al. (1995) as a likely G-protein coupled receptor, is a human orphan receptor expressed in the nervous system with sequence similarity to both somatostatin and opioid receptors. Using real time quantitative PCR^TM we evaluated the expression of GPR7 in sural nerve biopsies from patients with different kinds of peripheral neuropathies. We observed that GPR7 expression was significantly (p < 0.001) increased in sural nerves when an epineurial and endoneurial perivascular inflammatory infiltration was present. The overexpression was particularly noted in patients with painful peripheral neuropathies with an inflammatory, immuno and vasculitic etiology. In order to confirm changes in GPR7 expression at the protein level, we performed immunofluorescence staining on sections of neuropathic human sural nerves. A comparative analysis of rat injured sciatic nerves was also performed. We observed that GPR7 receptor is expressed by Schwann cells and that the amount of Schwann cell-staining in both human and rat nerve is increased in conditions of inflammatory neuropathy. In addition, we observed that the expression of GPR7 was significantly decreased in severe axonal neuropathies, suggesting that GPR7 expression is axon dependent. Immunofluorescence staining in rat cultured Schwann cells suggested that the expression GPR7 increased during Schwann-axon interaction. Taken together these results suggest that molecules such as GPR7 whose expression in Schwann cells varies under pathological conditions may play a role in the pathogenesis of human neuropathies. Altered GPR7 expression may disrupt myelination leading to progression of the neuropathy. Alternatively, GPR7 may play a role in Schwann cell-axon signaling and thereby influence axonal function in neuropathies leading to a painful phenotype.     

Duodenal hematoma: the ring sign in MR imaging

Proper management of duodenal hematoma requires that an accurate diagnosis be made using noninvasive radiological methods. Conventional imaging may be nonspecific if there is no history of trauma or coagulopathy. Two cases of duodenal hematoma that were imaged by magnetic resonance (MR) and computed tomography (CT) are described. In both cases the hematoma had a well-defined concentric ring configuration on MR images, a finding which helped establish the diagnosis. MR imaging may provide tissue-specific characterization of duodenal hematomas.     

Cloning of glycoprotein IIIa cDNA from human erythroleukemia cells and localization of the gene to chromosome 17

Platelet aggregation requires the binding of adhesive proteins such as fibrinogen to the heterodimer of membrane glycoproteins IIb (GPIIb) and IIIa (GPIIIa). Human erythroleukemia (HEL) cells synthesize both GPIIb and GPIIIa. Using poly(A+) RNA purified from HEL cells, we constructed a cDNA library in the lambda gt10 phage vector. This library was screened with a 38mer oligonucleotide derived from a platelet GPIIIa peptide, and three overlapping cDNAs were isolated. The three inserts encompassed 3.5 kilobases (kb), including the entire coding region of mature GPIIIa (2,286 basepairs, bp) and 1.3 kb of 3' untranslated sequence. All 222 residues determined directly from platelet GPIIIa tryptic peptides exactly matched the HEL cell-deduced amino acid sequence. The HEL cell sequence matched a previously reported endothelial cell cDNA sequence except for eight nucleotides. Five of these nucleotide differences were silent changes consistent with genetic polymorphisms. The other three differences resulted in changes in the deduced amino acid sequence of GPIIIa; reexamination of the endothelial cell cDNA sequence in these three areas revealed that it is actually identical to the HEL cell sequence. The virtual identity of the endothelial and HEL cell cDNA sequences provides direct evidence that GPIIIa is a subunit common to cell-adhesion receptors present in more than one cell type. We localized the gene for GPIIIa to chromosome 17, the same chromosome to which we had previously mapped the gene for GPIIb.     

Chest radiography: a survey of techniques and exposure levels currently used

In diagnostic radiology, the routine measurement of exposure levels for a reference patient is an important part of an effective quality assurance program. In the United States, chest radiography is the most frequent examination and has the lowest exposure level of all radiologic examinations. We estimated the amount of exposure an average patient received from both manual and automatic exposure-controlled radiographic techniques by using a "patient-equivalent" chest phantom during measurements. A densitometric procedure was used to assess processor performance. The mean exposure from 194 chest systems was 20 mR (5.16 X 10(-5) C/kg); the mean film density, 1.38; and the mean processing speed, 108. It is interesting to note that a wide range of radiographic techniques, processing conditions, and screen-film speeds are currently being used. With the information given in our study, investigators can begin to identify the problems that lead to unusual exposure levels and, perhaps, poor image quality.     

Short-term effects of an educational intervention on physical restraint use: a cluster randomized trial

Background

Hospitalization for older patients with community-acquired pneumonia (CAP) is associated with functional decline. Little is know about the relationship between inflammatory markers and determinants of functional status in this population. The aim of the study is to investigate the association between tumor necrosis factor (TNF)-α, C-reactive protein (CRP) and Activities of Daily Living, and to identify risk factors associated with one year mortality or hospital readmission.

Methods

301 consecutive patients hospitalized for CAP (mean age 73.9 ± 5.3 years) in a University affiliated hospital over 18 month period were included. All patients were evaluated on admission to identify baseline demographic, microbiological, cognitive and functional characteristics. Serum levels for TNF-α and CRP were collected at the same time. Reassessment of functional status at discharge, and monthly thereafter till 3 months post discharge was obtained and compared with preadmission level to document loss or recovery of functionality. Outcome was assessed by the composite endpoint of hospital readmission or death from any cause up to one year post hospital discharge.

Results

36% of patients developed functional decline at discharge and 11% had persistent functional impairment at 3 months. Serum TNF-α (odds ratio [OR] 1.12, 95% CI 1.08–1.15; p < 0.001) and the Charlson Index (OR = 1.39, 95% CI 1.14 to 1.71; p = 0.001) but not age, CRP, or cognitive status were independently associated with loss of functionality at the time of hospital discharge. Lack of recovery in functional status at 3 months was associated with impaired cognitive ability and preadmission comorbidities. In Cox regression analysis, persistent functional impairment at 3 months, impaired cognitive function, and the Charlson Index were highly predictive of one year hospital readmission or death.

Conclusion

Serum TNF-α levels can be useful in determining patients at risk for functional impairment following hospitalization from CAP. Old patients with impaired cognitive function and preexisting comorbidities who exhibit delay in functional recovery at 3 months post discharge may be at high risk for hospital readmission and death. With the scarcity of resources, a future risk stratification system based on these findings might be proven helpful to target older patients who are likely to benefit from interventional strategies.