Post-acute care referral and inpatient rehabilitation admission criteria for persons with brain injury across two Canadian provinces

Purpose: Investigate health care providers’ perceptions of referral and admission criteria to brain injury inpatient rehabilitation in two Canadian provinces.

Methods: Health care providers (n?=?345) from brain injury programs (13 acute care and 16 rehabilitation facilities) participated in a cross-sectional web-based survey. The participants rated the likelihood of patients (traumatic brain injury and cerebral hypoxia) to be referred/admitted to rehabilitation and the influence of 19 additional factors (e.g., tracheostomy). The participants reported the perceived usefulness of referral/admission policies and assessment tools used.

Results: Ninety-one percent acute care and 98% rehabilitation participants reported the person with traumatic brain injury would likely or very likely be referred/admitted to rehabilitation compared to respectively 43% and 53% for the patient with hypoxia. Two additional factors significantly decreased the likelihood of referral/admission: older age and the combined presence of minimal learning ability, memory impairment and physical aggression. Some significant inter-provincial variations in the perceived referral/admission procedure were observed. Most participants reported policies were helpful. Similar assessment tools were used in acute care and rehabilitation.

Conclusions: Health care providers appear to consider various factors when making decisions regarding referral and admission to rehabilitation. Variations in the perceived likelihood of referral/admission suggest a need for standardized referral/admission practices.

• Implications for Rehabilitation

• Various patient characteristics influence clinicians’ decisions when selecting appropriate candidates for inpatient rehabilitation.

• In this study, acute care clinicians were less likely to refer patients that their rehabilitation counter parts would likely have admitted and a patient with hypoxic brain injury was less likely to be referred or admitted in rehabilitation than a patient with a traumatic brain injury.

• Such discrepancies suggest that policy-makers, managers and clinicians should work together to develop and implement more standardized referral practices and more specific admission criteria in order to ensure equitable access to brain injury rehabilitation services.

     

Systemic ventricular function in patients with transposition of the great arteries after atrial repair: a tissue Doppler and conductance catheter study

OBJECTIVES: The aim of this study was to assess the utility of tissue Doppler echocardiography in the setting of repaired transposition of the great arteries when the right ventricle (RV) functions as the systemic ventricle. BACKGROUND: Myocardial acceleration during isovolumic contraction, "isovolumic myocardial acceleration" (IVA), has been validated as a sensitive non-invasive method of assessing RV contractility. Although traditional indexes may be less valid for the abnormal RV, the relative insensitivity of IVA to an abnormal load makes it a potentially powerful clinical tool for the assessment of RV disease. METHODS: We examined 55 controls and 80 patients (mean age 22 years) with transposition, who had undergone atrial repair at age 8 (0.3 to 72) months. A subgroup of 12 underwent cardiac catheterization. The RV systolic function was derived by analysis of pressure-volume relationships and IVA both at rest and during dobutamine stress. In all 80, myocardial velocities were sampled in the RV free wall. RESULTS: During dobutamine (10 microg/kg/min for 10 min), the increase of IVA mirrored the increase in end-systolic elastance (r = 0.69, p < 0.02). In the group as a whole, IVA was reduced compared with the subpulmonary RV and the systemic left ventricle of controls. There was abnormal wall motion in 44 patients, which was associated with reduced IVA. Diastolic myocardial velocities were also abnormal but unrelated to the presence of wall motion abnormalities. CONCLUSIONS: The IVA can accurately assess changes in RV contractile function in patients with an RV as the systemic ventricle. Global long-axis RV function is reduced in patients with transposition, and this is associated with abnormal regional function.     

Adenomatous polyposis coli protein contains two nuclear export signals and shuttles between the nucleus and cytoplasm

Mutational inactivation of the adenomatous polyposis coli (APC) tumor suppressor initiates most hereditary and sporadic colon carcinomas. Although APC protein is located in both the cytoplasm and the nucleus, the protein domains required to maintain a predominantly cytoplasmic localization are unknown. Here, we demonstrate that nuclear export of APC is mediated by two intrinsic, leucine-rich, nuclear export signals (NESs) located near the amino terminus. Each NES was able to induce the nuclear export of a fused carrier protein. Both APC NESs were independently able to interact with the Crm1 nuclear export factor and substitute for the HIV-1 Rev NES to mediate nuclear mRNA export. Both APC NESs functioned within the context of APC sequence: an amino-terminal APC peptide containing both NESs interacted with Crm1 and showed nuclear export in a heterokaryon nucleocytoplasmic shuttling assay. Also, mutation of both APC NESs resulted in the nuclear accumulation of the full-length, approximately 320-kDa APC protein, further establishing that the two intrinsic APC NESs are necessary for APC protein nuclear export. Moreover, endogenous APC accumulated in the nucleus of cells treated with the Crm1-specific nuclear export inhibitor leptomycin B. Together, these data indicate that APC is a nucleocytoplasmic shuttle protein whose predominantly cytoplasmic localization requires NES function and suggests that APC may be important for signaling between the nuclear and cytoplasmic compartments of epithelial cells.     

Fibroblast growth factor-23 mutants causing familial tumoral calcinosis are differentially processed

Familial tumoral calcinosis (TC, OMIM 211900) is a heritable disorder characterized by hyperphosphatemia, normal or elevated serum 1,25-dihydroxyvitamin D, and often severe ectopic calcifications. Two recessive mutations in fibroblast growth factor-23 (FGF23), serine 71/glycine (S71G) and serine 129/phenylalanine (S129F), were identified as causing TC. Herein, we undertook comprehensive biochemical analyses of an extended TC family carrying the S71G FGF23 mutation, which revealed that heterozygous (serine/glycine, S/G) individuals had elevated serum FGF23 C-terminal fragments compared with wild-type (serine/serine, S/S) family members (P < 0.025). To understand the differential processing of FGF23 in TC patients, we transiently expressed S71G as well as S129F FGF23. FGF23 ELISA in tandem with Western analyses revealed increased proteolytic cleavage of mutant FGF23 and a limited secretion of intact protein. Furthermore, S71G and S129F FGF23 carrying mutations that disrupt the furin-like protease RXXR motif in FGF23 rescued the secretion of the intact protein, and both TC mutant proteins harboring the R176Q mutation revealed no altered sensitivity to trypsin compared with the native (R176Q)FGF23. Finally, S71G, but not S129F mutant FGF23, is rescued by temperature. In summary, FGF23 mutations causing TC lead to increased intracellular proteolysis of FGF23, most likely by furin-like proteases, due to conformational changes of the mutant protein. The destabilizing nature of these mutations provides new insight into the pathophysiology of TC and exemplifies the physiological importance of FGF23 in phosphate and vitamin D metabolism.     

Role of the ATP-binding cassette transporter Abcg2 in the phenotype and function of cardiac side population cells

Recently, the side population (SP) phenotype has been introduced as a reliable marker to identify subpopulations of cells with stem/progenitor cell properties in various tissues. We and others have identified SP cells from postmitotic tissues, including adult myocardium, in which they have been suggested to contribute to cellular regeneration following injury. SP cells are identified and characterized by a unique efflux of Hoechst 33342 dye. Abcg2 belongs to the ATP-binding cassette (ABC) transporter superfamily and constitutes the molecular basis for the dye efflux, hence the SP phenotype, in hematopoietic stem cells. Although Abcg2 is also expressed in cardiac SP (cSP) cells, its role in regulating the SP phenotype and function of cSP cells is unknown. Herein, we demonstrate that regulation of the SP phenotype in cSP cells occurs in a dynamic, age-dependent fashion, with Abcg2 as the molecular determinant of the cSP phenotype in the neonatal heart and another ABC transporter, Mdr1, as the main contributor to the SP phenotype in the adult heart. Using loss- and gain-of-function experiments, we find that Abcg2 tightly regulates cell fate and function. Adult cSP cells isolated from mice with genetic ablation of Abcg2 exhibit blunted proliferation capacity and augmented cell death. Conversely, overexpression of Abcg2 is sufficient to enhance cell proliferation, although with a limitation of cardiomyogenic differentiation. In summary, for the first time, we reveal a functional role for Abcg2 in modulating the proliferation, differentiation, and survival of adult cSP cells that goes beyond its distinct role in Hoechst dye efflux.     

Isosexual precocious pseudopuberty secondary to a feminizing adrenal tumor

We report a 2 10/12-yr-old girl with precocious pseudopuberty due to a feminizing adrenal carcinoma without Cushing's syndrome. The patient had marked elevation of plasma concentrations of the delta 5 adrenal steroids dehydroepiandosterone and dehydroepiandrosterone sulfate and increased levels of androstenedione, estrone, estradiol, and testosterone. Adrenal microsomal 3 beta-hydroxysteroid dehydrogenase-isomerase 17-hydroxylase, 17,20-desmolase, and 21-hydroxylase activities in the tumor and adjacent normal adrenal gland were measured. The tumor had approximately normal levels of 17-hydroxylase and 17,20-desmolase activity, with low levels of 21-hydroxylase and 3 beta-hydroxysteroid dehydrogenase-isomerase activities. This combination of enzyme activity may explain the absence of Cushing's syndrome and the high levels of delta 5 adrenal steroids. This patient demonstrates that adrenal neoplasms arising in girls may mimic isosexual true precocious puberty and should be included in the differential diagnosis of precocious puberty.     

An audit of the investigation and initial management of adults presenting with possible bacterial meningitis

OBJECTIVES: This study was carried out to determine local levels of compliance with guidelines from the British Infection Society (BIS) for the early management and investigation of adult patients presenting with possible bacterial meningitis [J Infect 39 (1999) 1; J Infect 46 (2003) 75]. METHODS: Patients investigated for possible bacterial meningitis at Wythenshawe Hospital, Manchester were identified retrospectively by a computer search of microbiology requests. The clinical presentation, laboratory investigations and early antibiotic management were reviewed. RESULTS: Only two of 26 patients who presented over a 9-month period were confirmed to have bacterial meningitis. Basic laboratory investigations were carried out on all patients. Samples for more specific investigations to determine the aetiological agent such as polymerase chain reaction, serology or throat swab culture, were frequently omitted by the clinicians. The choice of antibiotic therapy was generally appropriate for the treatment of bacterial meningitis with large variation in the dosage prescribed. Both patients with confirmed bacterial meningitis received appropriate doses. CONCLUSIONS: Compliance with BIS guidelines was incomplete in a group of patients presenting with possible bacterial meningitis. Access to a simplified outline of recommendations for early investigation and management of adult patients with possible bacterial meningitis may optimise guideline compliance and patient outcome. SUMMARY: Appropriate early investigation and management of bacterial meningitis in adults can optimise the outcome of this high mortality disease. Guidelines published by the BIS in 1999 detailed the recommended initial management of such patients [J Infect 39 (1999) 1]. In this study, the level of adherence to these guidelines was investigated for patients with possible bacterial meningitis who presented to a hospital in Manchester. The results showed that basic investigations such as peripheral blood count and blood cultures were almost invariably carried out, whereas, more specific investigations such as meningococcal PCR, serology and throat swab were frequently omitted. The choice of antibiotic was in agreement with the guidelines for the majority of cases but highlighted a considerable variability in dosage prescribed. The availability of a simple flow-chart outlining the early management of suspected bacterial meningitis and meningococcal septicaemia in adults produced by the BIS in 2003 may raise awareness of and compliance with their guidelines, thus optimising patient outcome.