Effect of amiodarone on non-deiodinative pathway of thyroid hormone metabolism

Amiodarone, an iodine containing anti-arrhythmic drug, causes a significant decrease in molar ratio of daily production rates of T3 and T4 from 0.75 in controls to 0.36 in amiodarone-treated rabbits. A model was constructed from the above data which showed that metabolism of T4 via non-deiodinative pathways (e.g. tetraiodothyroacetic acid and/or conjugates) increased from 29% in untreated controls to 66% in amiodarone-treated rabbits. In this study, we have examined the metabolic clearance rate of tetraiodothyroacetic acid in rabbits given amiodarone (20 mg.kg-1.day-1 ip for 3 weeks) or saline (controls). Serum amiodarone and desethylamiodarone levels under the above experimental conditions were 0.20 +/- 0.067 and 0.17 +/- 0.058 mg/l, respectively, which were in the near-therapeutic range observed in humans. Control and amiodarone-treated rabbits were administered [125I]-tetraiodothyroacetic acid (10 muCi/rabbit) iv and blood was collected at 0.5, 1, 2, 4, 6, 10, 32 and 48 h. Serum tetraiodothyroacetic acid radioactivity was determined by trichloroacetic acid precipitation and ethanol extraction and metabolic clearance rates were calculated from the area under the curve of computer fits to tetraiodothyroacetic acid radioactivity data. Amiodarone treatment decreased metabolic clearance rates significantly from 0.107 +/- 0.008 in controls to 0.074 +/- 0.009 l/day in amiodarone-treated rabbits (p less than 0.05). However, when expressed per unit body weight (1.day-1.kg-1), the metabolic clearance rates were not significantly different between the controls and amiodarone-treated rabbits. The terminal serum elimination half-life in the two groups were similar (32.0 +/- 6.7 h in controls vs 49.2 +/- 12.4 h in amiodarone-treated).(ABSTRACT TRUNCATED AT 250 WORDS)     

CENTRAL PANCREATECTOMY FOR BENIGN PANCREATIC PATHOLOGY/TRAUMA: IS IT A REASONABLE PANCREAS‐PRESERVING CONSERVATIVE SURGICAL STRATEGY ALTERNATIVE TO STANDARD MAJOR PANCREATIC RESECTION?

BACKGROUND: The aim of this study was to assess the technical feasibility, safety and outcome of central pancreatectomy (CP) with pancreaticogastrostomy or pancreaticojejunostomy in appropriately selected patients with benign central pancreatic pathology/trauma. Benign lesions/trauma of the pancreatic neck and proximal body pose an interesting surgical challenge. CP is an operation that allows resection of benign tumours located in the pancreatic isthmus that are not suitable for enucleation. METHODS: Between January 2000 and December 2005, eight central pancreatectomies were carried out. There were six women and two men with a mean age of 35.7 years. The cephalic pancreatic stump is oversewn and the distal stump is anastomosed end-to-end with a Roux-en-Y jejunal loop in two and with the stomach in six patients. The indications for CP were: non-functional islet cell tumours in two patients, traumatic pancreatic neck transection in two and one each for insulinoma, solid pseudopapillary tumour, splenic artery pseudoaneurysm and pseudocyst. Pancreatic exocrine function was evaluated by a questionnaire method. Endocrine function was evaluated by blood glucose level. RESULTS: Morbidity rate was 37.5% with no operative mortality. Mean postoperative hospital stay was 10.5 days. Neither of the patients developed pancreatic fistula nor required reoperations or interventional radiological procedures. At a mean follow up of 26.4 months, no patient had evidence of endocrine or exocrine pancreatic insufficiency, all the patients were alive and well without clinical and imaging evidence of disease recurrence. CONCLUSION: When technically feasible, CP is a safe, pancreas-preserving pancreatectomy for non-enucleable benign pancreatic pathology/trauma confined to pancreatic isthmus that allows for cure of the disease without loss of substantial amount of normal pancreatic parenchyma with preservation of exocrine/endocrine function and without interruption of enteric continuity.     

Mild Renal Artery Stenosis Can Induce Renovascular Hypertension and is Associated with Elevated Renal Vein Renin Secretion

Renovascular hypertension is a syndrome which encompasses the physiological response of the kidney to changes in renal blood flow and renal perfusion pressure. Such physiological changes can occur with renal artery occlusion irrespective of the severity of the lesion. We have analyzed hypertensive patients with mild renal artery stenosis and compared them to patients with no stenosis. Renal vein renin sampling from catheterization of the renal vein was performed in all these patients. Patients with mild stenosis had higher renal vein renin ratio (3.01 ± 1.5) than the patients with no stenosis (1.10 ± 0.29; p = 0.002). Patients with mild stenosis were also found to have higher diastolic blood pressure and renal artery resistive indices when compared to patients with no stenosis. We therefore conclude that mild stenosis can precipitate renin‐mediated hypertension in renovascular stenosis and also emphasis that parameters pertinent to renal physiology need to be evaluated before considering treatment options in patients with renal artery stenosis and medical management with RAAS blockade is the preferred modality of therapy for patients with renin‐mediated hypertension.     

The effect of staged decompression while breathing 100% oxygen on altitude decompression sickness

INTRODUCTION: Space Shuttle extravehicular activity (EVA) requires decompression from sea level pressure (14.7 psia) to a 4.3 psia (30,300 ft) pressure suit. The transition currently involves altering the shuttle atmosphere to allow shirt-sleeve denitrogenation to occur during a 12 to 36-h staged decompression (SD) at 10.2 psia (9,800 ft) with an oxygen-enriched breathing gas (26.5% oxygen, 73.5% nitrogen). The denitrogenation provides protection from decompression sickness (DCS) during EVA in a 4.3 psia pressure suit. Our goal was to determine the highest altitude at which SD while breathing 100% oxygen (SD100) could provide effective protection from development of DCS symptoms after further decompression to 29,500 ft (4.5 psia). METHODS: There were 30 male subjects exposed to at least 6 of 11 conditions in random order on successive months to 29,500 ft for 4 h while performing mild exercise and being monitored for venous gas emboli (VGE) with an echo-imaging system. The subjects received 15 min of ground-level (GL) preoxygenation and an additional 60 or 120 min of SD100 at one of four altitudes between 8,000 ft (10.9 psia) and 18,000 ft (7.3 psia). Control exposures followed a 75- or 135-min ground-level preoxygenation. RESULTS: During SD100, one case of DCS occurred at 18,000 ft, but not at lower staging altitudes. Higher levels of VGE were observed during SD100 at 18,000 ft than during SD100 at any lower altitude. CONCLUSION: Staged decompression at 16,000 ft and below results in decompression risk during subsequent decompression to 29,500 ft similar to that following equivalent periods of ground-level preoxygenation.     

The median palmar cutaneous nerve in normal subjects and CTS.

OBJECTIVE: The neurophysiological confirmation of carpal tunnel syndrome (CTS) relies on detecting abnormal median nerve transcarpal conduction in the presence of unaffected comparator nerves. We compare the palmar cutaneous median branch (PCBm) with the ulnar sensory nerve conduction to digit 5 (US(5)) as comparator nerves for diagnosing CTS. METHODS: In a prospective case control study of patients with clinically defined carpal tunnel syndrome and normal subjects, we determined and compared the PCBm and US(5) conduction velocity. RESULTS: We examined 57 hands with clinically defined CTS and 59 control hands. Comparison showed highly significantly slowed PCBm conduction (p<0.0001) but not for US(5) conduction (p=0.488). Using a 3 percentile cut-off for abnormality derived from controls, PCBm conduction velocity was abnormal in 46% of CTS hands. CONCLUSIONS: The high frequency of PCBm nerve conduction abnormality in CTS suggests that this nerve should not be used as a comparator nerve for the neurophysiological diagnosis of CTS. This finding may help explain some of the extension of sensory symptoms outside the median nerve distribution in CTS. SIGNIFICANCE: In CTS frequent abnormality of PCBm conduction makes this a poor comparator nerve and may explain extension of sensory symptoms beyond the median nerve.     

Familial cortical dysplasia caused by mutation in the mammalian target of rapamycin regulator NPRL3

We describe first cousin sibling pairs with focal epilepsy, one of each pair having focal cortical dysplasia (FCD) IIa. Linkage analysis and whole‐exome sequencing identified a heterozygous germline frameshift mutation in the gene encoding nitrogen permease regulator‐like 3 (NPRL3). NPRL3 is a component of GAP Activity Towards Rags 1, a negative regulator of the mammalian target of rapamycin complex 1 signaling pathway. Immunostaining of resected brain tissue demonstrated mammalian target of rapamycin activation. Screening of 52 unrelated individuals with FCD identified 2 additional patients with FCDIIa and germline NPRL3 mutations. Similar to DEPDC5, NPRL3 mutations may be considered as causal variants in patients with FCD or magnetic resonance imaging–negative focal epilepsy. ANN NEUROL 2016;79:132–137     

Multilevel Correlates of Satisfaction with Neighborhood Availability of Fresh Fruits and Vegetables

Background  

Little is known about influences on perceptions of neighborhood food environments, despite their relevance for food-shopping behaviors and food choices.