Citations

Background—Women with congenital long-QT syndrome experience an increased risk for cardiac events after the onset of adolescence that is more pronounced among carriers of the LQT2 genotype. We hypothesized that the hormonal changes associated with menopause may affect clinical risk in this population.Methods and Results—We used a repeated-events analysis to evaluate the risk for recurrent syncope during the menopause transition and postmenopausal periods (5 years before and after the age at onset of menopause, respectively) among 282 LQT1 (n=151) and LQT2 (n=131) women enrolled in the Long-QT Syndrome Registry. Multivariate analysis showed that the risk for recurrent syncope (n=150) among LQT2 women was significantly increased during both menopause transition (hazard ratio, 3.38;P=0.005) and the postmenopausal period (hazard ratio, 8.10;P<0.001) compared with the reproductive period. The risk increase was evident among women who did or did not receive estrogen therapy. In contrast, among LQT1 women, the onset of menopause was associated with a reduction in the risk for recurrent syncope (hazard ratio, 0.19;P=0.05;P=0.02 for genotype-by-menopause interaction). Only 22 women (8%) experienced aborted cardiac arrest or sudden cardiac death during follow-up. The frequency of aborted cardiac arrest/sudden cardiac death showed a similar genotype-specific association with the onset of menopause.Conclusions—The onset of menopause is associated with a significant increase in the risk of cardiac events (dominated by recurrent episodes of syncope) in LQT2 women, suggesting that careful follow-up and continued long-term therapy are warranted in this population.

Aim: Trigeminal neuropathies are a group of clinical disorders that involve injury to primary first-order neurons within the trigeminal nerve. We review the spectrum of etiologies underlying both painful and non-painful trigeminal neuropathies, with attention to particularly dangerous processes that may elude the clinician in the absence of a meticulous evaluation. Complications and management issues specific to patients with trigeminal neuropathy are discussed. Methods: Retrospective literature review. Results: Facial or intraoral numbness, the hallmark of trigeminal neuropathy, may represent the earliest symptomology of malignancy or autoimmune connective tissue disease as sensory neurons are destroyed. Such numbness, especially if progressive, necessitates periodic evaluation and vigilance even years after presentation if no diagnosis can be made. Conclusions: In the routine evaluation of patients with facial pain, the clinician will inevitably be confronted with secondary pathology of the trigeminal nerves and nuclei. The appearance of numbness, even when pain continues to be the most pressing complaint, necessitates clinical assessment of the integrity of all aspects of the trigeminal pathways, which may also include neurophysiologic, radiographic, and laboratory evaluation.

Newly generated T cells are unable to respond to antigen/MHC. Rather, post-selection single-positive thymocytes must undergo T cell maturation to gain functional competency and enter the long-lived naive peripheral T cell pool. This process is poorly understood, as no gene specifically required for T cell maturation has been identified. Here, we demonstrate that loss of the transcriptional repressor NKAP results in a complete block in T cell maturation. In CD4-cre NKAP conditional knockout mice, thymic development including positive selection occurs normally, but there is a cell-intrinsic defect in the peripheral T cell pool. All peripheral naive CD4-cre NKAP conditional knockout T cells were found to be functionally immature recent thymic emigrants. This defect is not simply in cell survival, as the T cell maturation defect was not rescued by a Bcl-2 transgene. Thus, NKAP is required for T cell maturation and the acquisition of functional competency.

Introduction Each year, the US Antarctic Program rapidly transports scientists and support personnel from sea level (SL) to the South Pole (SP, 2835 m) providing a unique natural laboratory to quantify the incidence of acute mountain sickness (AMS), patterns of altitude related symptoms and the field effectiveness of acetazolamide in a highly controlled setting. We hypothesized that the combination of rapid ascent (3 hr), accentuated hypobarism (relative to altitude), cold, and immediate exertion would increase altitude illness risk. Methods Medically screened adults (N = 246, age = 37 ± 11 yr, 30% female, BMI = 26 ± 4 kg/m 2 ) were recruited. All underwent SL and SP physiological evaluation, completed Lake Louise symptom questionnaires (LLSQ, to define AMS), and answered additional symptom related questions (eg, exertional dyspnea, mental status, cough, edema and general health), during the 1st week at altitude. Acetazolamide, while not mandatory, was used by 40% of participants. Results At SP, the barometric pressure resulted in physiological altitudes that approached 3400 m, while T ° C averaged -42, humidity 0.03%. Arterial oxygen saturation averaged 89% ± 3%. Overall, 52% developed LLSQ defined AMS. The most common symptoms reported were exertional dyspnea-(87%), sleeping difficulty-(74%), headache-(66%), fatigue-(65%), and dizziness/lightheadedness-(46%). Symptom severity peaked on days 1-2, yet in >20% exertional dyspnea, fatigue and sleep problems persisted through day 7. AMS incidence was similar between those using acetazolamide and those abstaining (51 vs. 52%, P = 0.87). Those who used acetazolamide tended to be older, have less altitude experience, worse symptoms on previous exposures, and less SP experience. Conclusion The incidence of AMS at SP tended to be higher than previously reports in other geographic locations at similar altitudes. Thus, the SP constitutes a more intense altitude exposure than might be expected considering physical altitude alone. Many symptoms persist, possibly due to extremely cold, arid conditions and the benefits of acetazolamide appeared negligible, though it may have prevented more severe symptoms in higher risk subjects.

Recent studies proposed that mechanical inactivity of the human diaphragm during mechanical ventilation rapidly causes diaphragm atrophy and weakness. However, conclusive evidence for the notion that diaphragm weakness is a direct consequence of mechanical inactivity is lacking. To study the effect of hemidiaphragm paralysis on diaphragm muscle fiber function and structure in humans, biopsies were obtained from the paralyzed hemidiaphragm in eight patients with hemidiaphragm paralysis. All patients had unilateral paralysis of known duration, caused by en bloc resection of the phrenic nerve with a tumor. Furthermore, diaphragm biopsies were obtained from three control subjects. The contractile performance of demembranated muscle fibers was determined, as well as fiber ultrastructure and morphology. Finally, expression of E3 ligases and proteasome activity was determined to evaluate activation of the ubiquitin-proteasome pathway. The force-generating capacity, as well as myofibrillar ultrastructure, of diaphragm muscle fibers was preserved up to 8 wk of paralysis. The cross-sectional area of slow fibers was reduced after 2 wk of paralysis; that of fast fibers was preserved up to 8 wk. The expression of the E3 ligases MAFbx and MuRF-1 and proteasome activity was not significantly upregulated in diaphragm fibers following paralysis, not even after 72 and 88 wk of paralysis, at which time marked atrophy of slow and fast diaphragm fibers had occurred. Diaphragm muscle fiber atrophy and weakness following hemidiaphragm paralysis develops slowly and takes months to occur.

The authors present the case of a 56-year-old right hand–dominant woman who was referred for chronic neck pain and a second opinion regarding a cervical lesion. The patient's pain was localized to the subaxial spine in the midline. She reported a subjective sense of intermittent left arm weakness manifesting as difficulty manipulating small objects with her hands and fingers. She also reported paresthesias and numbness in the left hand. Physical and neurological examinations demonstrated no abnormal findings except for a positive Tinel sign over the left median nerve at the wrist. Electromyography demonstrated bilateral carpal tunnel syndrome with no cervical radiculopathy. Cervical spine imaging demonstrated multilevel degenerative disc disease and a pneumatocyst of the C-5 vertebral body. The alignment of the cervical spine was normal. A review of the patient's cervical imaging studies obtained in 1995, 2007, 2008, and 2010 demonstrated that the pneumatocyst was not present in 1995 but was present in 2007. The lesion had not changed in appearance since 2007. At an outside institution, multilevel fusion of the cervical spine was recommended to treat the pneumatocyst prior to evaluation at the authors' institution. The authors, however, did not think that the pneumatocyst was the cause of the patient's neck pain, and cervical pneumatocysts typically have a benign course. As such, the authors recommended conservative management and repeated MR imaging in 6 months. Splinting was used to treat the patient's carpal tunnel syndrome.

Background: Invasive leg compartment testing may be performed to diagnose chronic exertional compartment syndrome. No prior study has assessed the accuracy of leg compartment needle tip access. Purpose: This study was undertaken to describe and determine the accuracy of palpation-guided and ultrasound-guided techniques for needle tip placement into the deep and superficial posterior leg compartments by a less experienced clinician and a more experienced clinician using a cadaveric model. Study Design: Controlled laboratory study. Methods: Twenty unembalmed adult lower limb cadaveric specimens were used for the study. Two investigators, a sports medicine fellow with 10 months of musculoskeletal ultrasound experience and a staff physiatrist with 3 years of musculoskeletal ultrasound experience, each performed 1 palpation-guided and 1 ultrasound-guided colored latex dye injection into the deep and superficial posterior leg compartments of each cadaveric specimen. A blinded investigator dissected the specimens and graded them for accuracy. Results: The accuracy rates of palpation-guided (accuracy rate, 90%; 95% confidence interval [CI], 76%-97%) and ultrasound-guided (accuracy rate, 88%; 95% CI, 73%-95%) deep posterior compartment injections were statistically equivalent ( P = 1.000). All 80 injections performed into the superficial posterior compartment were accurate (accuracy rate, 100%; 95% CI, 89%-100%). The accuracy of the less experienced investigator (total injection accuracy rate, 88%; 95% CI, 73%-95%) and the more experienced investigator (total injection accuracy rate, 90%; 95% CI, 76%-97%) were not significantly different ( P = 1.000). Conclusion: Needle tip placement into the deep and superficial posterior leg compartments is relatively accurate with palpation guidance regardless of level of experience, and does not improve with the use of ultrasound guidance. Clinical Relevance: Ultrasound guidance does not appear to be indicated for routine deep or superficial posterior leg compartment pressure testing. However, this does not preclude the need for ultrasound guidance in selected clinical scenarios.

Calcific aortic valve stenosis (CAVS) is a major health problem facing aging societies. The identification of osteoblast-like and osteoclast-like cells in human tissue has led to a major paradigm shift in the field. CAVS was thought to be a passive, degenerative process, whereas now the progression of calcification in CAVS is considered to be actively regulated. Mechanistic studies examining the contributions of true ectopic osteogenesis, nonosseous calcification, and ectopic osteoblast-like cells (that appear to function differently from skeletal osteoblasts) to valvular dysfunction have been facilitated by the development of mouse models of CAVS. Recent studies also suggest that valvular fibrosis, as well as calcification, may play an important role in restricting cusp movement, and CAVS may be more appropriately viewed as a fibrocalcific disease. High-resolution echocardiography and magnetic resonance imaging have emerged as useful tools for testing the efficacy of pharmacological and genetic interventions in vivo. Key studies in humans and animals are reviewed that have shaped current paradigms in the field of CAVS, and suggest promising future areas for research.