Acute flaccid paralysis: Do not forget beriberi neuropathy

We aimed to elucidate characteristics of beriberi neuropathy (BB) in a general hospital (GH) setting. Nerve conduction studies (NCS), cross‐referenced with clinical records of patients admitted to a GH (May 2011‐July 2017), were reviewed for diagnosis of BB. Thirteen patients (age range 23‐64 years; five women) were diagnosed with BB. Eleven were incarcerated (2‐24 months) at time of index event. Eleven reported prior, severe anorexia (2‐6 months); five reported significant weight loss, three had recurrent vomiting, and three reported alcohol misuse. Commonest presentation was weakness (12/13); nine had symptom evolution over ≥3 weeks. At nadir, 11/13 could not walk independently. Other features included numbness/paraesthesiae (10/13), dysautonomia (6/13), vocal cord dysfunction/dysphagia (4/13), nystagmus (3/13). Pain was not prominent. Cerebrospinal fluid, tested in five patients, was acellular; one showed mildly increased protein. NCS showed predominantly sensorimotor, axonal polyneuropathy, rarely asymmetric. Only one patient had sural‐sparing pattern. All received high dose thiamine. Two of the thirteen received intravenous immunoglobulin for suspicion of Guillain‐Barré syndrome (GBS). Eleven improved to independent ambulation. One patient died from pulmonary embolism; one was lost to follow‐up. Two of the thirteen had residual neurocognitive effects; both misused alcohol. Besides GBS, BB is an important cause of acute to subacute flaccid paralysis, especially in incarcerated patients and those with significant dietary deprivation. Features favoring BB over GBS are ≥3 weeks of symptoms, nystagmus, confusion, vocal cord dysfunction, volume overload, normal spinal fluid, elevated lactate, and absence of sural‐sparing pattern in NCS.     

18α-glycyrrhetinic acid targets prostate cancer cells by down-regulating inflammation-related genes

Glycyrrhetinic acid is an active triterpenoid metabolite of glycyrrhizin abundantly present in licorice roots. Glycyrrhetinic acid exists as α and β stereo-isomeric forms. Both stereo-isomeric forms are known to have anti-inflammatory and anticancer activity. However, the effects and anticancer mechanism of α glycyrrhetinic acid in prostate cancer cells has not yet been evaluated. Therefore, we investigated the growth inhibition, induction of apoptosis and the anticancer mechanisms of 18α-glycyrrhetinic acid (AGA), on the androgen-independent metastatic prostate cancer cell line DU-145. Our results showed that AGA inhibited proliferation and growth of these cells by inducing apoptosis as determined by Annexin V and flow cytometry analyses. Our studies also showed that HUVEC tube formation was drastically reduced when cultured in conditioned medium of AGA-treated DU-145 cells. In addition, AGA treatment prevented the invasion of DU-145 prostate cancer cells on matrigel coated transwells via down-regulation of NF-κB (p65), VEGF and MMP-9 expression. Furthermore, AGA treatment also down-regulated the expression of pro-inflammatory cytokine/growth factor genes HMGB1, IL-6 and IL-8 in DU-145 cells. Interestingly, AGA simultaneously upregulated the expression of non-steroidal anti-inflammatory gene-1 (NAG-1) in DU-145 cells suggesting its anti-inflammatory activity on prostate cancer cells. Taken together, the results of this study suggest that AGA may be a promising anticancer agent that merits further investigation for the chemoprevention and treatment of prostate cancer.     

Intraepidermal nerve fiber density as a marker of early diabetic neuropathy

The purpose of the study was to reliably identify an early stage of diabetic polyneuropathy (DPN) by measuring injury to epidermal nerve fibers. We compared intraepidermal nerve fiber density (IENFD) at the ankle and thigh of 29 diabetic subjects who had no clinical or electrophysiological evidence of small- or large-fiber neuropathy to that of 84 healthy controls. The mean ankle IENFD of diabetic subjects was 9.1+/-5.0 mm and that of controls, 13.0+/-4.8 mm (P<0.001). The thigh IENFD did not differ significantly. The IENFD ratio (thigh IENFD divided by ankle IENFD) was 2.39+/-1.30 in diabetic subjects and 1.77+/-0.58 in controls (P<0.001), indicating a length-dependent reduction of IENFD in diabetics. Ankle IENFD remained significantly lower and the IENFD ratio higher in diabetic subjects after adjusting for age. Two subjects had parasympathetic dysfunction, two had retinopathy, and two early nephropathy. Age, height, weight, duration of diabetes, and average HbA1c did not influence IENFD among diabetic subjects. We used receiver operating characteristic (ROC) curves to describe and compare the utility of various threshold values of ankle IENFD and IENFD ratio for the diagnosis of early DPN. The sensitivity and specificity of diagnosing DPN using ankle IENFD of less than 10 mm were 72.4% and 76.2%, respectively. Thus, asymptomatic diabetics have a measurable, length-dependent reduction of distal epidermal nerves. Analogous to microalbuminuria in diabetic nephropathy, reliable identification and quantitation of nascent diabetic neuropathy may have potential therapeutic implications.     

Evaluation of partial carbon dioxide rebreathing cardiac output measurement during thoracic surgery

OBJECTIVE: Noninvasive partial CO2 rebreathing (NICO; Novametrix Medical Systems, Inc, Wallingford, CT) is a relatively new alternative to thermodilution (TDCO) for measurement of cardiac output. This study compares the 2 methods during thoracic surgery and one-lung ventilation. DESIGN: A prospective, observational study. SETTING: A tertiary hospital. PARTICIPANTS: Twelve adult patients undergoing elective thoracotomy and one-lung ventilation in the lateral decubitus position. INTERVENTIONS: Paired measurements of cardiac output were performed during (1) 2-lung ventilation in the supine position (postinduction of anesthesia), (2) 10 minutes after initiation of one-lung ventilation in the lateral decubitus position with the nondependent chest open, and (3) after 30 minutes on one-lung ventilation. An average of 3 consecutive (10 mL 20 degrees C saline) TDCO measurements made during end-expiration was compared with corresponding NICO measurements. MEASUREMENTS AND MAIN RESULTS: The NICO showed a tendency to underestimate cardiac output compared with TDCO at all measurement times. Overall, bias was -0.29 L/min and limits of agreement -1.69 to 1.43 L/min. CONCLUSIONS: There was a moderate agreement between cardiac output measurements obtained with the NICO and TDCO. The present data suggest that the NICO technique may be useful during thoracic surgery.     

Long-term enhancement of skeletal muscle mass and strength by single gene administration of myostatin inhibitors

Increasing the size and strength of muscles represents a promising therapeutic strategy for musculoskeletal disorders, and interest has focused on myostatin, a negative regulator of muscle growth. Various myostatin inhibitor approaches have been identified and tested in models of muscle disease with varying efficacies, depending on the age at which myostatin inhibition occurs. Here, we describe a one-time gene administration of myostatin-inhibitor-proteins to enhance muscle mass and strength in normal and dystrophic mouse models for >2 years, even when delivered in aged animals. These results demonstrate a promising therapeutic strategy that warrants consideration for clinical trials in human muscle diseases.