Clinical and neuropathological parameters affecting the diagnostic yield of nerve biopsy

The value of nerve biopsy in the investigation of peripheral neuropathies is an important and controversial issue, partially obscured by the large variations in the diagnostic yield routinely reported for this procedure. The aim of this study was to evaluate the clinical and neuropathological parameters affecting the yield of nerve biopsy. We compared the experience of two independent neuropathology laboratories with different patient recruitment and neuropathological methods over 11 years (01/1987-12/1997). Clinicopathological correlations were studied retrospectively in 355 patients. Using the same criteria of evaluation, contributive biopsies accounted for 35.5% in one laboratory, and 47.3% in the other. Clinical parameters affecting the yield of nerve biopsy were: (a) the presumptive diagnosis at time of referral for biopsy; (b) the distribution of symptoms; and (c) the interval between disease onset and biopsy. Greater yield was associated with clinically suspected vasculitis, inflammatory demyelinating neuropathy or hereditary sensorimotor neuropathies. Contributive findings were more often reported with multifocal or asymmetrical presentations, and onset-to-biopsy interval of less than 6 months. The contribution of nerve biopsy varied according to neuropathological techniques: (a) serial sections on frozen. paraffin-embedded and resin-embedded material improved sensitivity for interstitial pathology: (b) combined muscle biopsy increased sensitivity in the detection of vasculitis; and (c) teasing of nerve fibers added critical information to other classical techniques in only 4/102 cases.     

Clinical And Neuropathological Parameters Affecting The Diagnostic Yield Of Nerve Biopsy

Insulin-like growth factors (IGFs) are important trophic factors during development as well as in the adult or damaged nervous system. Their trophic actions are modulated by interactions with six distinct IGF binding proteins. The mRNA expression profiles of binding proteins 2, 4 and 5 in the normal developing and adult CNS are well characterized and are shown to have distinctive, non-overlapping distributions. The IGF binding protein-6 (BP6) is also expressed in the CNS, however, details regarding its mRNA expression distribution in the developing and adult nervous system is limited. BP6 has the unique property of preferentially binding the IGF-II ligand. Coupled with the fact that this ligand is the most abundantly expressed IGF in the adult CNS, this suggests that the IGF-II/BP6 complex has a unique role in modulating IGF-II function in the adult brain. In this report the anatomical distribution of BP6 messenger RNA in the developing and adult rat nervous system is presented. In the embryonic animal the CNS expression is tightly restricted to trigeminal ganglia and, relative to the rest of the embryo, this structure has the highest expression. The expression in the forebrain and cerebellum does not occur until after postnatal day 21 and then is primarily associated with GABAergic interneurons, The highest levels of expression in the adult animal are in the hindbrain, spinal cord, cranial ganglia, and dorsal root ganglia. These nuclei in the hindbrain and periphery that express BP6 are all associated with the coordination of sensorimotor function in the cerebellum, which indicates an important role for the BP6/IGF-II complex in the function and maintenance of these systems.     

Surgical safety checklist and operating room efficiency: results from a large multispecialty tertiary care hospital

Background

The Surgical Safety Checklist (SSC) improves patient safety and outcomes; however, barriers to effective use include the perceived negative impact on operating room (OR) efficiency. The purpose of this study was to determine the effect of SSC implementation on OR efficiency.

Methods

All operations at our large multispecialty tertiary care hospital were reviewed for 1-year pre- and 1-year post-SSC implementation. OR efficiency included operating room time, operation time, first starts on time, same-day cancellations, and OR disposable cost.

Results

A total of 35,570 operations were reviewed: 17,204 pre-SSC and 18,366 post-SSC. There was no difference between groups for operating room time (P = .93), operation time (P = .66), first starts on time (P = .15), and same-day cancellations (P = .57). The mean OR disposable cost was significantly lower ($70/operation) for the post-SSC group (P < .01).

Conclusions

The implementation of an SSC does not negatively impact OR efficiency and should not be considered a barrier to effective use. Our data suggest that SSC use can reduce overall cost per surgical procedure.     

Validation of an oscillometric home blood pressure monitor in an end-stage renal disease population and the effect of arterial stiffness on its accuracy

OBJECTIVES: Increased arterial stiffness, common in end-stage renal disease patients, has been shown to affect the correspondence between oscillometric and mercury sphygmomanometer blood pressure readings. The purpose of this study was to validate an oscillometric home blood pressure monitor in an end-stage renal disease population and to determine the effect of arterial stiffness on its accuracy. METHODS: Blood pressure measurements were taken with the Microlife 3AC1-1PC (Microlife; Taipei, Taiwan), an oscillometric home blood pressure monitor, and a mercury sphygmomanometer in 33 patients as specified by the European Society of Hypertension Validation Protocol. Radial pulse wave analyses were also performed. RESULTS: On the basis of European Society of Hypertension criteria, the Microlife 3AC1-1PC received a passing score for systolic and diastolic blood pressures. On average, the oscillometric monitor overestimated diastolic blood pressure by 2.4 mmHg (P=0.005, SD=4.5 mmHg) and there was a trend towards overestimation of systolic blood pressure as well (1.3 mmHg, P=0.09, SD=4.4 mmHg). A positive correlation was found between arterial stiffness, as assessed by augmentation index and pulse pressure, and the diastolic blood pressure difference between the device and the mercury sphygmomanometer (r=0.54, P=0.003; and r=0.65, P=0.001, respectively). Diastolic blood pressure was negatively correlated with the diastolic blood pressure difference (r=-0.49, P=0.003). No significant relationship was found between the systolic blood pressure difference and augmentation index, pulse pressure or systolic blood pressure. CONCLUSION: The Microlife 3AC1-1PC was shown to accurately measure blood pressure in patients with end-stage renal disease. As arterial stiffness increased and diastolic blood pressure fell, diastolic blood pressure was increasingly overestimated.     

Efficacy of two telemonitoring systems to improve glycaemic control during basal insulin initiation in patients with type 2 diabetes: The TeleDiab-2 randomized controlled trial

TeleDiab-2 was a 13-month randomized controlled trial evaluating the efficacy and safety of two telemonitoring systems to optimize basal insulin (BI) initiation in subjects with inadequately controlled type 2 diabetes (HbA1c, 7.5%-10%). A total of 191 participants (mean age 58.7 years, mean HbA1c 8.9%) were randomized into three groups: group 1(G1, standard care, n = 63), group 2 (G2, interactive voice response system, n = 64) and group 3 (G3, Diabeo-BI app software, n = 64). The two telemonitoring systems proposed daily adjustments of BI doses, in order to facilitate the achievement of fasting blood glucose (FBG) values targeted at ~100 mg/dL. At 4 months follow-up, HbA1c reduction was significantly higher in the telemonitoring groups (G2: −1.44% and G3: −1.48% vs. G1: −0.92%; P < 0.002). Moreover, target FBG was reached by twice as many patients in the telemonitoring groups as in the control group, and insulin doses were also titrated to higher levels. No severe hypoglycaemia was observed in the telemonitoring groups and mild hypoglycaemia frequency was similar in all groups. In conclusion, both telemonitoring systems improved glycaemic control to a similar extent, without increasing hypoglycaemic episodes.     

The effect of age,body mass index,and fasting triglyceride level on postprandial lipemia is dependent on apolipoprotein E polymorphism in subjects with non-insulin-dependent diabetes mellitus

The aim of this study was to evaluate in non-insulin-dependent diabetes mellitus (NIDDM) subjects the respective influence of apolipoprotein (apo) E polymorphism, age, gender, weight, fasting triglyceride (TG) status, and glycemic status on postprandial lipemia. Apo E genotyping was performed in consecutive NIDDM hospitalized patients in order to recruite size-adjusted groups of each apo E genotype. In 57 NIDDM including 22 E3/3 (E3), 18 E2/3 (E2), and 17 E4/3 (E4) subjects, an 8-hour vitamin A-fat loading test was performed and TG and retinyl palmitate (RP) measured. Fasting TG level correlated with the TG area under the incremental curve (AUIC) (r = 0.512, P <.001) but not with RP AUIC. Despite not different fasting and postprandial TG concentrations, E2 and E4 carriers exhibited a 2- to 3-fold higher RP AUIC than E3 carriers (P =.01). Multivariate analysis indicated an age x apo E interaction on postprandial TG (P <.01), since the unfavorable effect of E2 and E4 allele on TG AUIC was unmasked by aging. In addition, a fasting TG x apo E interaction on postprandial TG was shown (P <.01), and the correlation between fasting TG and TG AUIC was actually restricted to E2 or E4 carriers. Finally, the negative correlation between BMI and postprandial TG observed in the experimental group was actually restricted to E4 carriers (r = -0.77, P <.001). Our results indicate interactions between apo E polymorphism and aging, fasting TG level and BMI that may be important for analyzing postprandial TG clearance in NIDDM.     

Successful immune tolerance induction by FVIII in hemophilia A patients with inhibitor may occur without deletion of FVIII‐specific T cells

Summary. Background: The development of an inhibitor is the major complication facing patients with hemophilia A treated by administration of factor (F) VIII concentrates. Restoration of tolerance to FVIII can be achieved by prolonged administration of FVIII (immune tolerance induction, ITI). Although ITI has been used for more than 30 years in patients with hemophilia A and inhibitor, its mechanism of action is still poorly understood. Objectives: As administration of high doses of antigen can induce the apoptosis of the T cells recognizing the antigen, a potential mechanism of action of ITI may be the deletion of FVIII‐specific T cells. Patients/Methods: We studied the CD4+ T‐cell response to FVIII in five (one mild, one moderate and three severe) patients successfully desensitized by administration of FVIII and in control subjects. Results: Following repeated stimulation with autologous dendritic cells loaded with FVIII, FVIII‐specific T oligoclonal cell lines were expanded from the blood of one of the successfully desensitized patients. The FVIII‐specific T cells produced IL‐5, IL‐13 and IL‐2. By contrast, FVIII‐specific T‐cell lines could not be derived from three patients with mild hemophilia A without inhibitor or from four normal control subjects. Conclusions: These data represent the first analysis of the cellular mechanisms regulating the induction of tolerance to FVIII. They demonstrate that successful tolerance induction may occur without deletion of FVIII‐specific T cells.     

Patients' attitudes about rapid oral HIV screening in an urban, free dental clinic

The 2006 Centers for Disease Control recommendations for routine HIV screening in all health care settings could include dental clinics an important testing venue. However, little is known about patients' attitudes regarding the routine use of rapid oral HIV screening at an urban free dental clinic. This pilot study seeks to evaluate the patient perspective on rapid HIV screening in this setting. In June 2007, patients at a free dental clinic in Kansas City, Missouri, were provided an attitude assessment survey prior to their dental visit. This dental clinic serves a diverse patient population consisting of approximately 37% white, 47% black, 6% Hispanic, 4% Asian, and 1% Native American uninsured patients. Results were analyzed for acceptance of testing and potential barriers. Of the 150 respondents, 73% reported they would be willing to take a free rapid HIV screening test during their dental visit. Overall, 91% of Hispanics, 79% of Caucasians, and 73% of African American patients reported they would be willing to be screened. Patients with a history of multiple prior screening tests for HIV were more likely to agree to oral rapid HIV screening in the dental clinic. The majority (62%) reported that it did not matter who provided them with the screening result, although some (37%) preferred their dentist above any other provider. Low self-perception of risk (37%) and having already received screening elsewhere (24%) were the main reasons for not accepting a free, rapid HIV screening. Overall, dental clinic patients widely accepted the offer of rapid oral HIV screening. Rapid HIV screening in the dental clinic setting is a viable option to increase the number of individuals who know their HIV status.     

Effect of nibentan on dispersion of repolarization of ventricular myocardium in the rabbit

Among factors determining development of polymorphic ventricular tachycardia torsades de pointes under influence of class III antiarrhythmic drugs great value is attributed to enhanced heterogeneity of repolarization of ventricular myocardium which can cause functional conduction blocks and development of re-entry of excitation. In this work with the help of optical mapping of electrical activity of the heart we investigated effect of nibentan (0.3 and 1 mM) on chronotopography of repolarization of epicardial surface of ventricles of isolated after Langendorf rabbit heart (n=5). For assessment of heterogeneity of repolarization we measured the following parameters: standard deviation of mean action potential duration (APDm) along mapped region (SD-APD), dispersion index (DI=1000 SD-APDm), maximal dispersion (Dmax=APDmax-APDmin). Nibentan in concentrations 0.3 and 1 mM increased APD at the level of 90% repolarization (APD90%) from 231 +/- 12 to 277 +/- 7 ms (p < 0.05) 318 +/- 7 ms (p < 0.001), respectively, but in concentration 1 mM it practically did not affect parameters of heterogeneity of repolarization (SD-APD: from 4.4 +/- 0.9 to 5.7 +/- 1.1 ms, p=0.4; DI: from 19.1 +/- 4.2 to 18.0+3.5, p=0.8; Dmax: from 16.6 +/- 2.5 to 24.8 +/- 4.3 ms, < 0.05). These results show that nibentan in the range of clinically used doses does not effect heterogeneity of ventricular myocardium. This can explain low proarrhythmic effect of nibentan.