Numb chin syndrome associated with vertical root fracture and odontogenic infection.

Numb chin syndrome (NCS) is a multifactorial neuropathic disorder associated with paresthesia to the chin, lip, and oral mucosa, particularly arising as a sequela to various dental-related procedures or infections in the mandible. Timely elucidation of the underlying etiology is of paramount importance as the presentation of NCS could serve as a harbinger of malignancy or metastatic disease. This report describes an unusual case of NCS developing synchronously with a vertical root fracture and odontogenic infection in a mandibular first molar. Clinicians should consider the inclusion of a vertical root fracture as plausible cofactor for the development of NCS.

2015 Recommendations for the management of polymyalgia rheumatica: a European League Against Rheumatism/American College of Rheumatology collaborative initiative

Therapy for polymyalgia rheumatica (PMR) varies widely in clinical practice as international recommendations for PMR treatment are not currently available. In this paper, we report the 2015 European League Against Rheumatism (EULAR)/American College of Rheumatology (ACR) recommendations for the management of PMR. We used the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) methodology as a framework for the project. Accordingly, the direction and strength of the recommendations are based on the quality of evidence, the balance between desirable and undesirable effects, patients' and clinicians' values and preferences, and resource use. Eight overarching principles and nine specific recommendations were developed covering several aspects of PMR, including basic and follow-up investigations of patients under treatment, risk factor assessment, medical access for patients and specialist referral, treatment strategies such as initial glucocorticoid (GC) doses and subsequent tapering regimens, use of intramuscular GCs and disease modifying anti-rheumatic drugs (DMARDs), as well as the roles of non-steroidal anti-rheumatic drugs and non-pharmacological interventions. These recommendations will inform primary, secondary and tertiary care physicians about an international consensus on the management of PMR. These recommendations should serve to inform clinicians about best practices in the care of patients with PMR.(AU)

Towards more efficient burn care: Identifying factors associated with good quality of life post-burn.

BACKGROUND: As minor burn patients constitute the vast majority of a developed nation case-mix, streamlining care for this group can promote efficiency from a service-wide perspective. This study tested the hypothesis that a predictive nomogram model that estimates likelihood of good long-term quality of life (QoL) post-burn is a valid way to optimise patient selection and risk management when applying a streamlined model of care. METHOD: A sample of 224 burn patients managed by the Burn Service of Western Australia who provided both short and long-term outcomes was used to estimate the probability of achieving a good QoL defined as 150 out of a possible 160 points on the Burn Specific Health Scale-Brief (BSHS-B) at least six months from injury. A multivariate logistic regression analysis produced a predictive model provisioned as a nomogram for clinical application. A second, independent cohort of consecutive patients (n=106) was used to validate the predictive merit of the nomogram. RESULTS AND DISCUSSION: Male gender (p=0.02), conservative management (p=0.03), upper limb burn (p=0.04) and high BSHS-B score within one month of burn (p<0.001) were significant predictors of good outcome at six months and beyond. A Receiver Operating Curve (ROC) analysis demonstrated excellent (90%) accuracy overall. At 80% probability of good outcome, the false positive risk was 14%. The nomogram was validated by running a second ROC analysis of the model in an independent cohort. The analysis confirmed high (86%) overall accuracy of the model, the risk of false positive was reduced to 10% at a lower (70%) probability. This affirms the stability of the nomogram model in different patient groups over time. An investigation of the effect of missing data on sample selection determined that a greater proportion of younger patients with smaller TBSA burns were excluded due to loss to follow up. CONCLUSION: For clinicians managing comparable burn populations, the BSWA burns nomogram is an effective tool to assist the selection of patients to a streamlined care pathway with the aim of improving efficiency of service delivery.

Analysis of sequence and haemagglutinin activity of the HN glycoprotein of Newcastle disease virus.

Reverse transcription-polymerase chain reaction (RT-PCR) was used to generate sequence data for recent Taiwanese strains of Newcastle disease virus (NDV) isolated from 1999 to 2003, covering the full length of the haemagglutinin-neuraminidase (HN) gene and protein. Nucleotide sequence analysis of the HN gene of these recent isolates revealed that the whole HN gene carries an open reading frame encoding 571 amino acids and possesses a shorter C-terminal extension. Six amino acid substitutions in epitopes on the HN glycoprotein of the recent Taiwanese NDV isolates were also found. All the recent Taiwanese NDV isolates have the amino acid sequence (112)RRQKRF(117) for the F protein. A phylogenetic tree analysis based on the nucleotide sequences of the F gene revealed that all recent Taiwanese isolates were related to genotype VII viruses. Since the recent Taiwanese NDV isolates exhibited a low level of haemagglutination (HA) activity, we generated two sets of mutants to elucidate whether mutations in the heptad repeat region of the HN protein could affect the HA activity. To demonstrate the presence of the viruses used in the HA test, a real-time RT-PCR was established to determine the copy number of NDV isolates. From sequence analysis, site-directed mutagenesis, and haemadsorption assays, it was found that the HN glycoprotein of recent Taiwanese NDV isolates carrying a substitution at the amino acid residue 81 (I to M) in the heptad repeat region in the stalk domain showed a dramatic decrease in the activity of HA. We infer from these results that a specific amino acid sequence within the heptad repeat region of the stalk is important for the HA activity of the HN glycoprotein.

Disease Activity Score 28-ESR bears a similar relationship to treatment decisions across different rheumatologists, but misclassification is too frequent to replace physician judgement.

OBJECTIVES: To determine whether physician factors are associated with disease activity status in RA, independently of 28-joint disease activity score (DAS28)-ESR and to re-evaluate DAS28-ESR misclassification rates for identifying active disease in usual practice. METHODS: A prospective observational study of outpatients with RA seen by 17 rheumatologists across New Zealand. Active disease was defined by an increase in therapy together with a reason of 'active disease'; very low disease activity was defined by a decrease in therapy together with a reason of 'patient well'. The independent physician effect was assessed using logistic regression. Sensitivity and specificity of current DAS28-ESR thresholds were calculated. RESULTS: In 511 patients, 178 had active disease, 220 had low disease activity, 37 had very low disease activity and 76 had uncertain disease activity status. There was no independent effect of physician upon active disease status (P = 0.16) with DAS28-ESR [(OR) 3.7] explaining around 50% of the variability in active disease status. There was a trend towards an independent effect of physician upon very low disease activity status (P = 0.06) and greater variability in the distribution of DAS28-ESR for patients in very low disease activity. DAS28-ESR thresholds showed a significant risk of misclassification for active disease. CONCLUSIONS: DAS28-ESR discriminates satisfactorily between groups of patients with active and non-active disease, with no evidence of additional physician-specific factors to explain disease activity status. However, DAS28-ESR is not as good for discriminating remission from non-remission status. There are appreciable probabilities of misclassification error, which make DAS28-ESR inappropriate as a sole guide for treatment decisions.

Successful intravenous thrombolysis in ischemic stroke caused by infective endocarditis.

INTRODUCTION: Infective endocarditis can lead to serious neurological complications including ischemic stroke and intracranial hemorrhage. Treatment with intravenous thrombolysis within 3 h of symptom onset has become the standard of care in acute ischemic stroke, but the safety and efficacy of this intervention in patients with infective endocarditis is unknown. SUMMARY OF CASE: We report the case of a patient with ischemic stroke who experienced substantial neurological improvement after being treated with intravenous thrombolysis (NIH stroke scale score of 15 on admission and 4 after treatment) and was subsequently found to have acute infective mitral endocarditis. CONCLUSION: Favorable response to thrombolysis may occur in patients with stroke due to infectious endocarditis. The safety of this therapy remains to be established.

Avian reovirus-induced apoptosis related to tissue injury.

Apoptosis plays an important role in pathogenesis of many viral infections. Infection of chicken with avian reovirus S1133 causes tissue injury related to virus-induced apoptosis. To determine whether avian reovirus (ARV) induced apoptosis in chicken tissues, six 3-week-old specific pathogen free White Leghorn chicks were inoculated with ARV S1133. Tissues were dual-labelled for the simultaneous detection of viral antigen containing and apoptotic cells. DNA laddering was detected in ARV-infected but not mock-infected chicken tissues. Dual-labelling assay revealed that the majority of antigen-expressing cells were not apoptotic. Surprisingly, some apoptotic but non-antigen-expressing cells were frequently located in the vicinity of antigen-expressing cells. Syncytium formation in ARV-infected chicken tissues undergoing apoptosis was apparent, suggesting a correlation between virus replication and apoptosis in chicken tissues.

Storage and microencapsulation of islets for transplantation.

Microencapsulation is an effective means of immunoisolation for pancreatic islet transplants. However, the process of isolating, purifying, encapsulating, and transplanting islets in a single day is labor intensive and difficult for routine use. There is an apparent need for reliable methods of islet storage, and cryopreservation has emerged as an attractive system of islet banking. While studies have shown that cryopreserved islets are viable when tested unencapsulated after thawing, it is not clear if the combination of freezing and encapsulation would affect islet function. The purpose of the present study was to determine the in vitro function of cryopreserved islets following thawing and microencapsulation. Islets were isolated from the pancreata of Sprague-Dawley rats and cryopreserved under liquid nitrogen for either 1 week or 1 month, following an overnight culture at 37 degrees C. Upon thawing, the islets were tested either unencapsulated or after encapsulation in polylysine-alginate membrane. In all experiments islets were preperifused for 1 h at 37 degrees C with a modified Krebs-Ringer bicarbonate buffer containing 3.3 mM (60 mg/dl) glucose and maintained at pH 7.4 by continuous gassing with 95% air/5% CO2. Following basal effluent sample collection on ice, the glucose concentration was raised to 16.7 mM (300 mg/dl). It was found that, within 10 min of high glucose stimulation, an average of twofold increase in insulin secretion (p < 0.01) was obtained in islets within or without microcapsules. We conclude that islets cryopreserved for 1 month prior to thawing and microencapsulation retained functional viability as determined in in vitro experiments.

Requirement for Ras and phosphatidylinositol 3-kinase signaling uncouples the glucocorticoid-induced junctional organization and transepithelial electrical resistance in mammary tumor cells.

In Con8 rat mammary epithelial tumor cells, the synthetic glucocorticoid dexamethasone stimulates the remodeling of the apical junction (tight and adherens junctions) and the transepithelial electrical resistance (TER), which reflects tight junction sealing. Indirect immunofluorescence revealed that dexamethasone induced the recruitment of endogenous Ras and the p85 regulatory subunit of phosphatidylinositol (PI) 3-kinase to regions of cell-cell contact, concurrently with the stimulation of TER. Expression of dominant-negative RasN17 abolished the dexamethasone stimulation in TER, whereas, dexamethasone induced the reorganization of tight junction and adherens junction proteins, ZO-1 and beta-catenin, as well as F-actin, to precise regions of cell-cell contact in a Ras-independent manner. Confocal microscopy revealed that RasN17 and the p85 regulatory subunit of PI 3-kinase co-localized with ZO-1 and F-actin at the tight junction and adherens junction, respectively. Treatment with either of the PI 3-kinase inhibitors, wortmannin or LY294002, or the MEK inhibitor PD 098059, which prevents MAPK signaling, attenuated the dexamethasone stimulation of TER without affecting apical junction remodeling. Similar to dominant-negative RasN17, disruption of both Ras effector pathways using a combination of inhibitors abolished the glucocorticoid stimulation of TER. Thus, the glucocorticoiddependent remodeling of the apical junction and tight junction sealing can be uncoupled by their dependence on Ras and/or PI 3-kinase-dependent pathways, implicating a new role for Ras and PI 3-kinase cell signaling events in the steroid control of cell-cell interactions.

Glucocorticoid down-regulation of fascin protein expression is required for the steroid-induced formation of tight junctions and cell-cell interactions in rat mammary epithelial tumor cells.

Glucocorticoid hormones, which are physiological regulators of mammary epithelium development, induce the formation of tight junctions in rat Con8 mammary epithelial tumor cells. We have discovered that, as part of this process, the synthetic glucocorticoid dexamethasone strongly and reversibly down-regulated the expression of fascin, an actin-bundling protein that also interacts with the adherens junction component beta-catenin. Ectopic constitutive expression of full-length mouse fascin containing a Myc epitope tag (Myc-fascin) in Con8 cells inhibited the dexamethasone stimulation of transepithelial electrical resistance, disrupted the induced localization of the tight junction protein occludin and the adherens junction protein beta-catenin to the cell periphery, and prevented the rearrangement of the actin cytoskeleton. Ectopic expression of either the carboxyl-terminal 213 amino acids of fascin, which includes the actin and beta-catenin-binding sites, or the amino-terminal 313 amino acids of fascin failed to disrupt the glucocorticoid induction of tight junction formation. Mammary tumor cells expressing the full-length Myc-fascin remained generally glucocorticoid responsive and displayed no changes in the levels or protein-protein interactions of junctional proteins or the amount of cytoskeletal associated actin filaments. However, a cell aggregation assay demonstrated that the expression of Myc-fascin abrogated the dexamethasone induction of cell-cell adhesion. Our results implicate the down-regulation of fascin as a key intermediate step that directly links glucocorticoid receptor signaling to the coordinate control of junctional complex formation and cell-cell interactions in mammary tumor epithelial cells.

Hemiparesis and altered mental status in a child after glyburide ingestion.

A normally healthy 6-year-old woke in an agitated state, limp, and moving only her left extremities. Upon arrival at the emergency department, a blood glucose measurement was 34 mg/dL. The child was lethargic, not responding to questions appropriately, and not moving her right extremities. The right arm was flexed, and the right leg was flexed and abducted. Pupils were equal and reactive, and eyes were deviated to the left. Six loose tablets of the grandmother's glyburide were found at home in the child's outdoor playhouse. Administration of glucose produced no change in the child's clinical condition. Intravenous glucose was begun at 4 mg glucose/kg/min, and the blood glucose level did not fall below 74 mg/dL after that. Over the next 48 h, the hemiparesis and mental status changes resolved without sequelae. The events of the case suggest a hypoglycemia-induced seizure with subsequent Todd's paralysis. Early direct medical evaluation in suspected glyburide ingestions in children is suggested.

Beta2-chimaerin is a high affinity receptor for the phorbol ester tumor promoters.

Beta2-chimaerin, a member of the GTPase-activating proteins for the small GTP-binding protein p21Rac, possesses a single cysteine-rich domain with high homology to those implicated in phorbol ester and diacylglycerol binding in protein kinase C (PKC) isozymes. We have expressed beta2-chimaerin in Sf9 insect cells using the baculovirus expression system and determined that, like PKCs, beta2-chimaerin binds phorbol esters with high affinity in the presence of phosphatidylserine as a cofactor. Scatchard plot analysis using the radioligand [3H]phorbol 12,13-dibutyrate revealed a dissociation constant of 1.9 +/- 0.2 nM for beta2-chimaerin. Likewise, beta2-chimaerin is a high affinity receptor for the bryostatins, a class of atypical PKC activators. A detailed comparison of structure-activity relations using several phorbol ester analogs revealed striking differences in binding recognition between beta2-chimaerin and PKCalpha. Although the diacylglycerol 1-oleoyl-2-acetylglycerol binds with similar potency to both beta2-chimaerin and PKCalpha, the mezerein analog thymeleatoxin has 56-fold less affinity for binding to beta2-chimaerin. To establish whether beta2-chimaerin responds to phorbol esters in cellular systems, we overexpressed beta2-chimaerin in COS-7 cells and monitored its subcellular distribution after phorbol ester treatment. Interestingly, as described previously for PKC isozymes, beta2-chimaerin translocates from cytosolic to particulate fractions as a consequence of phorbol ester treatment. Our results demonstrate that beta2-chimaerin is a novel target for the phorbol ester tumor promoters. The expansion of the family of phorbol ester receptors strongly suggests a potential for the "non-kinase" receptors as cellular mediators of the phorbol ester responses.

Gowning does not affect colonization or infection rates in a neonatal intensive care unit.

OBJECTIVE: To study the effect of gowning in a neonatal intensive care unit on colonization patterns, necrotizing enterocolitis, respiratory syncytial virus and other infections, mortality, and traffic and handwashing patterns. METHODS: Alternate 2-month gowning and no-gowning cycles were established in a 24-bed level III neonatal intensive care unit for 8 months, with respiratory site, umbilical, and stool surveillance cultures done weekly on all patients. Traffic flow and handwashing compliance were evaluated by direct observation. RESULTS: Demographic data did not differ between periods. There were no significant differences between the gowning and no-gowning periods in the rates of bacterial colonization, any type of infection, or mortality. There was no effect on traffic flow or handwashing compliance. CONCLUSION: Gowning in the neonatal intensive care unit is an unnecessary custom without benefit in neonatal colonization, infection rates, mortality, traffic patterns, and handwashing behavior.

Injection therapy of superficial rheumatoid nodules.

Although intralesional corticosteroid injection of subcutaneous rheumatoid nodules was mentioned in 1968, this simple procedure is not commonly practised. A placebo-controlled, double-blind trial of intralesional corticosteroid injection using 24 rheumatoid nodules from 11 patients was carried out to determine the efficacy and safety of the procedure. Nodules injected with methylprednisolone and lignocaine regressed significantly more than nodules injected with placebo (lignocaine alone). This was consistently shown in all modalities of assessments which included patients' assessments (P < 0.001) and investigator's assessments (P < 0.001) of the percentage change in nodule size, and gross measurements of nodule volumes using a pincer (P < 0.001). Nine of 12 active injections produced > or = 50% loss in nodular volume with complete disappearance of two nodules. This compares with only one out of 12 placebo injections which resulted in > or = 50% loss in nodular volume. The patients found all 12 active injections to be worthwhile compared to only two of 12 placebo injections being worthwhile. The only complication of injection therapy observed was that of pain during the procedure.

Once-daily ceftriaxone to complete therapy of uncomplicated group B streptococcal infection in neonates. A preliminary report.

Newborn infants minimally symptomatic with non-central nervous system (CNS) infections due to Streptococcus agalactiae (group B streptococcus [GBS]) and other pathogens may not require skilled nursing care during the entire course of parenteral antibiotic therapy. In 1985, treatment guidelines were made available to private practitioners in Oregon for therapy of newborn infants at low risk of complications from their infections. In 1988, patient data were collected and analyzed retrospectively. Outpatient management during convalescence of 51 infants (21 with culture-positive infections due to GBS) was accomplished with once-daily physician follow-up examinations and IM injection of ceftriaxone. Long-term (greater than or equal to two months) follow-up data were available for 67% of GBS-infected infants, with no complication of infection or significant complication of therapy reported. Outpatient parenteral antibiotic management of selected, low-risk infants may offer the clinician an alternative to hospitalization for a portion of the duration of parenteral antibiotic therapy.