Axonal dysfunction,dysmyelination, and conduction failure in hereditary neuropathy with liability to pressure palsies

Introduction: Patients with hereditary neuropathy with liability to pressure palsies (HNPP) manifest with episodes of focal paresis when exposed to mechanical stress, although the basis for vulnerability to conduction block remains relatively unexplained. Methods: Axonal excitability techniques were utilized to provide insights into pathophysiological mechanisms in 13 HNPP patients, stimulating median motor and sensory axons at the wrist. Results: In HNPP, distal latencies were prolonged, and motor and sensory amplitudes were reduced. Threshold was increased. Depolarizing and hyperpolarizing electrotonus was greater, and resting current–threshold slope was reduced. There were greater threshold changes in superexcitability, and refractoriness was decreased. Conclusions: Taken together, excitability testing in patients with HNPP established axonal hyperpolarization in both motor and sensory axons that may be attributable to changes in nerve architecture. In turn, the hyperpolarized resting membrane potential in HNPP may be a major predisposing factor for development of conduction block with mechanical stresses. Muscle Nerve 49 : 858–865, 2014     

Effect of a Cooling Vest on Core Temperature in Athletes With and Without Spinal Cord Injury

Background:

It is well accepted that persons with spinal cord injury (SCI) have impaired ability to regulate core temperature due to impaired vasomotor and sudomotor activity below their level of injury. Impaired heat dissipation puts SCI athletes at great risk of exercise-induced hyperthermia (EIH) (>37.8°C). There is minimal evidence for efficacy of any specific cooling method in SCI athletes in a thermoneutral sport-specific setting.

Objective:

To evaluate the extent of EIH in persons with and without SCI and subsequently examine the effect of a cooling vest to attenuate rise in core body temperature (T_c).

Methods:

SCI (n = 17) and able-bodied (AB; n = 19) athletes participated in a 60-minute intermittent sprinting exercise in a thermoneutral (21.1°C-23.9°C) environment. Participants were separated according to their level of injury: tetraplegia defined as above T1 (TP; n = 6), high paraplegia defined as T5 through T1 (HP; n = 5), low paraplegia defined as T6 and below (LP; n = 6), and AB (n = 19). T_c was recorded at 15-minute intervals using an ingestible thermometer pill. This protocol was completed with a cooling vest (V) and without a cooling vest (NV).

Results:

All SCI and most AB athletes experienced EIH. After 60 minutes, T_c of TP athletes was significantly increased compared to HP (P = .03) and AB athletes (P = .007). There was no significant effect of the vest on T_c over time for any group.

Conclusions:

TP athletes have the highest risk of exercise-induced hyperthermia. The cooling vest does not significantly attenuate rise in T_c in SCI or AB athletes.Key words: body temperature, hyperthermia, spinal cord injury, thermoregulationInjury to the spinal cord results in impairment of vasomotor and sudomotor function at and below the level of injury (LOI).¹ In non–spinal-cord-injured individuals, internal heat gain from metabolically active muscles (eg, during exercise) and external heat gain from the ambient air is mitigated through processes regulated by the hypothalamus. The afferent input of heat gain results in neurological efferent signals that regulate vasomotor tone (convective cooling) and sudomotor activation (evaporative cooling). In persons with spinal cord injury (SCI), the output from the hypothalamus is blocked due to lesions within the spinal cord. Furthermore, the loss of skeletal muscle pump activity from the paralyzed limbs further impairs blood circulation and thus core temperature regulation. As a result, persons with SCI have difficulty dissipating heat during exercise compared to their able-bodied (AB) counterparts.^1–3 The extent of such thermal impairment has been shown to be directly related to level and completeness of injury, with higher and complete lesions having more impairment than lower, incomplete lesions.^4,5 Specifically, the vessels of the face and neck are sympathetically mediated from levels T1-4, upper extremity vessels mediated from T5-7, and vessels of the lower extremity from T10 to L3.⁶ Therefore, persons with complete tetraplegia have essentially no vasomotor control, whereas persons with high paraplegia have vasomotor control of face and neck and persons with low paraplegia have control of upper limbs and potentially some control of lower limb vessels depending on the LOI.In the AB athlete, is it well accepted that elevated core temperature (T_c) due to internal and external heat gain during exercise can impair endurance and performance.^7,8 Extreme elevations in T_c can result in exercise-induced hyperthermia (EIH) (>37.8°C-38.3°C) that that can lead to heat exhaustion (<40°C) or heat stroke (>40°C) as defined by American College of Sports Medicine (ACSM).⁹ For this reason, cooling methods such as whole body cooling, cooling vests, and hand/foot cooling are utilized before and during exercise in AB athletes.^10–13 These devices have been shown to reduce thermal strain, increase endurance capacity, and improve performance.^14–17Due to the increased risk of EIH and heat-related illness from thermoregulatory dysfunction in persons with SCI, a number of commercially available cooling devices have been tested in a controlled laboratory setting in attempts to attenuate rise in T_c. Foot cooling garments, hand cooling garments, head and neck cooling garments, misting devices, and a cooling vest have been tested in SCI populations.^18–22 This study sought to test the efficacy of the cooling device in a sport-specific environment. The cooling vest interferes minimally with wheelchair propulsion during sporting activities and was thus chosen for this study.While the efficacy of the cooling vest in normalizing T_c in the AB population has been clearly documented, the efficacy of the vest in SCI populations has variable results from 3 small studies.^14,23,24 Armstrong et al¹⁸ found that cooling (ice) vests worn during 30 minutes of wheelchair roller exercise in a hot-humid environment (~33°C and ~75% relative humidity) did not significantly decrease T_c in an SCI group (4 with paraplegia, 1 with tetraplegia). Webborn et al evaluated the effect of cooling vests in 2 studies of 8 persons with tetraplegia during an arm crank ergometry intermittent sprint protocol (defined as 14 two-minute exercise periods each consisting of 10 seconds passive rest, 5 seconds maximum sprint, and 105 seconds of active recovery). The first study reported a significant decrease in T_c and rate of perceived exertion when vests were used before (pre-cooling) or during 28 minutes of exercise in the heat.¹⁹ The second study also reported a significant decrease in T_c and time to exhaustion during 60 minutes in the heat when wearing the vest.²⁵ Webborn recommended that tetraplegic athletes performing intermittent sprint exercise in hot conditions should wear a cooling vest before or during exercise to attenuate rise in T_c. This study tested Webborn’s recommendation to examine whether these findings translate to a nonlaboratory field-based environment of athletes engaging in intermittent sprint exercise during play of wheelchair basketball and rugby. This concept of testing has recently been recommended, as testing of athletes in their normal sports wheelchair and their natural environment may yield results that are more relevant than laboratory testing.²⁶The objectives of this study are 2-fold: (1) to evaluate the extent of EIH in persons with and without SCI, and (2) to examine the ability of a cooling vest to attenuate the rise in T_c of SCI and AB athletes during intermittent sprinting exercise.     

Management of Positive Sub‐areolar/Nipple Duct Margins in Nipple‐Sparing Mastectomies

We evaluated management of positive sub‐areolar/nipple duct margins in nipple‐sparing mastectomies (NSM) at our institution. Retrospective chart review of all NSM from January 2007 to April 2012 was performed and patient, tumor, and treatment information was collected. Sub‐areolar/nipple duct margins included ductal tissue from within the nipple. Of 438 NSM, 22 (5%) had positive sub‐areolar/nipple duct margins; 21 of 220 cancer‐bearing breasts (10%) and 1 of 218 prophylactic mastectomies (0.5%). Positive margins included four with invasive lobular carcinoma and 18 with ductal carcinoma in situ (DCIS). Management included removal of eight nipples and nine nipple areola complexes (NAC). Four of 17 nipple/NAC specimens had evidence of residual DCIS and none had residual invasive cancer. The majority of nipple/NAC specimens excised for a positive margin had no residual malignancy. Future studies are needed to determine the extent of NAC tissue removal required for positive margins.     

Pharmacologic Prophylaxis,Postoperative INR,and Risk of Venous Thromboembolism after Hepatectomy

Introduction

Pharmacologic prophylaxis (PP) is recommended for patients undergoing general surgical procedures with at least moderate risk of venous thromboembolism (VTE). The role of PP in patients undergoing hepatectomy is controversial, however, due to concerns regarding postoperative liver dysfunction and bleeding.

Methods

We conducted a retrospective analysis of a prospectively maintained institutional database in order to clarify the relationship between PP, postoperative INR, and risk of VTE.

Results

Postoperative VTE occurred in 55 of 2,147 patients (2.6 %) and was independently associated with advanced age, higher BMI, longer procedure time, and development of a major complication, as well as higher postoperative INR (≥1.5 versus <1.5: OR 2.50, P?=?0.006). Patients undergoing more extensive liver resection with higher postoperative INR were less likely to receive PP, but receipt of PP demonstrated no relationship with either VTE incidence or hemorrhagic complications.

Conclusions

In this large single-institution study, incidence of VTE was not associated with PP but was associated with higher postoperative INR, contrary to the notion that postoperative liver dysfunction is protective against VTE. The interplay between prothrombotic and antithrombotic mechanisms in posthepatectomy patients must be more completely characterized before broad recommendations can be made regarding PP use in these patients.     

Blood Kidney Injury Molecule-1 Is a Biomarker of Acute and Chronic Kidney Injury and Predicts Progression to ESRD in Type I Diabetes

Currently, no blood biomarker that specifically indicates injury to the proximal tubule of the kidney has been identified. Kidney injury molecule-1 (KIM-1) is highly upregulated in proximal tubular cells following kidney injury. The ectodomain of KIM-1 is shed into the lumen, and serves as a urinary biomarker of kidney injury. We report that shed KIM-1 also serves as a blood biomarker of kidney injury. Sensitive assays to measure plasma and serum KIM-1 in mice, rats, and humans were developed and validated in the current study. Plasma KIM-1 levels increased with increasing periods of ischemia (10, 20, or 30 minutes) in mice, as early as 3 hours after reperfusion; after unilateral ureteral obstruction (day 7) in mice; and after gentamicin treatment (50 or 200 mg/kg for 10 days) in rats. In humans, plasma KIM-1 levels were higher in patients with AKI than in healthy controls or post-cardiac surgery patients without AKI (area under the curve, 0.96). In patients undergoing cardiopulmonary bypass, plasma KIM-1 levels increased within 2 days after surgery only in patients who developed AKI (P<0.01). Blood KIM-1 levels were also elevated in patients with CKD of varous etiologies. In a cohort of patients with type 1 diabetes and proteinuria, serum KIM-1 level at baseline strongly predicted rate of eGFR loss and risk of ESRD during 5–15 years of follow-up, after adjustment for baseline urinary albumin-to-creatinine ratio, eGFR, and Hb1Ac. These results identify KIM-1 as a blood biomarker that specifically reflects acute and chronic kidney injury.     

Impact of single immunosuppressive drug withdrawal on lymphocyte immunoreactivity

Background

Chronic rejection is a major cause of graft loss in kidney transplant recipients. Nonadherence to drug therapy is a well-recognized cause of chronic rejection leading to long-term graft dysfunction and failure for transplant recipients. Immunosuppressive medications with short half-lives that require frequent dosing, such as tacrolimus, complicate transplant regimens and may increase noncompliance. Regimens could be simplified using drugs with long half-lives requiring once-daily administration, such as sirolimus. The impact of missing doses of single agents has not been studied extensively. Erratic compliance or temporary discontinuation of immunosuppressive drugs may have significant implications for chronic rejection.

Methods

Our study evaluated the impact of single drug withdrawal of commonly used immunosuppressive agents (sirolimus and tacrolimus) on lymphocyte responses. We analyzed lymphocyte proliferation, cytokine secretion, and adenosine triphosphate generation using a crossover study design with normal healthy patients. Lymphocyte proliferation was assessed using 5-bromo-2-deoxyuridine incorporation, and T cell function was analyzed by examining adenosine triphosphate generation.

Results

Our results indicate that sirolimus exerts prolonged suppression of lymphocyte proliferation and decreased interleukin 17A that lasts up to 48 h after drug withdrawal. In comparison, tacrolimus did not have a similar effect on lymphocyte proliferation or interleukin 17A secretion.

Conclusion

Future analysis of sirolimus in diverse transplantation populations merits investigation.     

Isolation and characterization of 8 polymorphic microsatellite markers from the Greater Short-horned Lizard (Phrynosoma hernandesi)

The Greater Short-horned Lizard (Phrynosoma hernandesi) is a small reptile endemic to western North America that is classified as endangered in Canada. Here, we describe the development of 8 microsatellite markers for P. hernandesi. Observed allelic diversity varied from 2 to 11 while observed heterozygosity and expected heterozygosity ranged from 0.370–0.852 to 0.486–0.856, respectively. These markers will facilitate studies that address conservation of the species, such as levels of genetic diversity and population structure.     

Neuroimaging and facial affect processing: implications for traumatic brain injury

The ability to recognize others’ emotions is critical to successful interpersonal interactions. Given its importance, there has been an extensive amount of research using functional magnetic resonance imaging (fMRI) to investigate the neurobiological mechanisms associated with facial affect recognition in healthy individuals, and some in patient populations with affective disorders. Findings from these studies reveal that the underlying mechanisms involve a distributed neural network, engaging structures within limbic and subcortical regions, prefrontal cortex, temporal and parietal lobes, and occipital cortex. In the last several decades, researchers have become increasingly interested in how emotion recognition is affected after a traumatic brain injury (TBI), which often involves damage to these structures, as well as the neural circuitry connecting them. Not surprisingly, research has reliably demonstrated that facial affect recognition deficits are common after TBI. To date, however, no neuroimaging studies have investigated facial affect recognition deficits in the TBI population. Consequently, the purpose of this paper is to consider how functional magnetic resonance imaging (fMRI) might inform our knowledge about affect recognition deficits after TBI, and potentially enhance treatment approaches.