A randomized,double-blind trial of the effect of metronidazole on pain after closed hemorrhoidectomy

PURPOSE: Patients consider hemorrhoidectomy to be a painful operation. Attempts to reduce the length of inpatient stay have concentrated mainly on a reduction in postoperative pain. Metronidazole has been shown to reduce pain after open hemorrhoidectomy. The aim of this study was to evaluate the effect of metronidazole after closed hemorrhoidectomy. METHODS: Thirty-eight patients undergoing closed hemorrhoidectomy were randomly allocated to receive metronidazole 400 mg (n = 18) or placebo (n = 20) three times daily for seven postoperative days. All patients received a stool softener and analgesics perioperatively. Linear analog scales were used to assess expected pain, actual pain and patient satisfaction. Time to first bowel movement, return to normal activity, complications, and use of additional analgesics were recorded. RESULTS: Both groups of patients experienced less pain than expected. Patients in the metronidazole group required fewer additional analgesics postoperatively (6.3 vs. 26.3 percent), and satisfaction scores in the placebo group were higher at one week (0.5 vs. 2.5), although these differences were not statistically significant. There were no differences in pain actually experienced, time to first bowel movement, return to normal activity, or complications between the two groups. Satisfaction scores at six weeks for all patients were relatively high, with no significant difference between the groups. CONCLUSION: Closed hemorrhoidectomy results in high patient satisfaction and low pain scores. The use of postoperative metronidazole did not reduce postoperative pain.     

Neurologic manifestations in primary Sjögren syndrome: a study of 82 patients

Neurologic involvement occurs in approximately 20% of patients with primary Sj?gren syndrome (SS). However, the diagnosis of SS with neurologic involvement is sometimes difficult, and central nervous system (CNS) manifestations have been described rarely. We conducted the current study to describe the clinical and laboratory features of SS patients with neurologic manifestations and to report their clinical outcome. We retrospectively studied 82 patients (65 women and 17 men) with neurologic manifestations associated with primary SS, as defined by the 2002 American-European criteria. The mean age at neurologic onset was 53 years. Neurologic involvement frequently preceded the diagnosis of SS (81% of patients). Fifty-six patients had CNS disorders, which were mostly focal or multifocal. Twenty-nine patients had spinal cord involvement (acute myelopathy [n = 12], chronic myelopathy [n = 16], or motor neuron disease [n = 1]). Thirty-three patients had brain involvement and 13 patients had optic neuropathy. The disease mimicked relapsing-remitting multiple sclerosis (MS) in 10 patients and primary progressive MS in 13 patients. We also recorded diffuse CNS symptoms: some of the patients presented seizures (n = 7), cognitive dysfunction (n = 9), and encephalopathy (n = 2). Fifty-one patients had peripheral nervous system involvement (PNS). Symmetric axonal sensorimotor polyneuropathy with a predominance of sensory symptoms or pure sensory neuropathy occurred most frequently (n = 28), followed by cranial nerve involvement affecting trigeminal, facial, or cochlear nerves (n = 16). Multiple mononeuropathy (n = 7), myositis (n = 2), and polyradiculoneuropathy (n = 1) were also observed. Thirty percent of patients (all with CNS involvement) had oligoclonal bands. Visual evoked potentials were abnormal in 61% of the patients tested. Fifty-eight patients had magnetic resonance imaging (MRI) of the brain. Of these, 70% presented white matter lesions and 40% met the radiologic criteria for MS. Thirty-nine patients had a spinal cord MRI. Abnormalities were observed only in patients with spinal cord involvement. Among the 29 patients with myelopathy, 75% had T2-weighted hyperintensities. Patients with PNS manifestations had frequent extraglandular complications of SS. Anti-Ro/SSA or anti-La/SSB antibodies were detected in 21% of patients at the diagnosis of SS and in 43% of patients during the follow-up (mean follow-up, 10 yr). Biologic abnormalities were more frequently observed in patients with PNS involvement than in those with CNS involvement (p < 0.01). Fifty-two percent of patients had severe disability, and were more likely to have CNS involvement than PNS involvement (p < 0.001). Treatment by cyclophosphamide allowed a partial recovery or stabilization in patients with myelopathy (92%) or multiple mononeuropathy (100%). The current study underlines the diversity of neurologic complications of SS. The frequency of neurologic manifestations revealing SS and of negative biologic features, especially in the event of CNS involvement, could explain why SS is frequently misdiagnosed. Screening for SS should be systematically performed in cases of acute or chronic myelopathy, axonal sensorimotor neuropathy, or cranial nerve involvement. The outcome is frequently severe, especially in patients with CNS involvement. Our study also underlines the efficacy of cyclophosphamide in myelopathy and multiple neuropathy occurring during SS.     

Dipyridamole-Atropine-Induced Myocardial Infarction in a Patient with Patent Epicardial Coronary Arteries

BACKGROUND: The diagnostic accuracy of the physical and pharmacological stress echocardiography tests is higher than routine exercise electrocardiography. They have an acceptable safety profile and have been rarely associated with severe adverse effects. CASE REPORT: We present a case of acute anterior myocardial reinfarction immediately after exercise and pharmacological (dipyridamole-atropine) stress echocardiography testing 1 month after successful stent implantation in LAD. Our patient was a 43-year-old man with a history of heavy smoking and hypertension. Remarkably, the stress echocardiogram was non-diagnostic few hours before the infarction occurred. Angiography performed 4 months after the reinfarction revealed neither a culprit lesion nor stent thrombosis. CONCLUSION: Aggressive "last generation" pharmacological stress testing may provide optimal diagnostic accuracy, but as in our case, complications may occur, even after negative stress testing. To our knowledge, this is the first reported case of an acute myocardial infarction as a severe complication of stress testing, which developed in a patient after stent implantation.     

Inhibition of Calpain Prevents N-Methyl-D-aspartate-Induced Degeneration of the Nucleus Basalis and Associated Behavioral Dysfunction

N-Methyl-D-aspartate (NMDA) receptor-mediated excitotoxicity is thought to underlie a variety of neurological disorders, and inhibition of either the NMDA receptor itself, or molecules of the intracellular cascade, may attenuate neurodegeneration in these diseases. Calpain, a calcium-dependent cysteine protease, has been identified as part of such an NMDA receptor-induced excitotoxic signaling pathway. The present study addressed the question of whether inhibition of calpain can prevent neuronal cell death and associated behavioral deficits in a disease-relevant animal model, which is based on excitotoxic lesions of the cholinergic nucleus basalis magnocellularis of Meynert. Excitotoxic lesions of the nucleus basalis with NMDA induced a markedly impaired performance in the novel object recognition test. Treatment with the calpain inhibitor, N-(1-benzyl-2-carbamoyl-2-oxoethyl)-2-[E-2-(4-diethlyaminomethylphenyl) ethen-1-yl]benzamide (A-705253), dose-dependently prevented the behavioral deficit. Subsequent analysis of choline acetyltransferase in the cortical mantle of the lesioned animals revealed that application of A-705253 dose-dependently and significantly attenuated cholinergic neurodegeneration. Calpain inhibition also significantly diminished the accompanying gliosis, as determined by immunohistochemical analysis of microglia activation. Finally, inhibition of calpain by A-705253 and the peptidic calpain inhibitor N-acetyl-Leu-Leu-Nle-CHO did not impair long-term potentiation in hippocampal slices, indicating that calpain inhibition interrupts NMDA excitotoxicity pathways without interfering with NMDA receptor-mediated signaling involved in cognition. We conclude that inhibition of calpains may represent a valuable strategy for the prevention of excitotoxicity-induced neuronal decline without interfering with the physiological neuronal functions associated with learning and memory processes. Thus, calpain inhibition may be a promising and novel approach for the treatment of various neurodegenerative disorders.     

Mycophenolate mofetil and neurological diseases

We describe experience with the use of mycophenolate mofetil (MMF) in neurological diseases. Although only small series of patients or case reports were described, MMF is promising in immune-mediated neuromuscular disorders. MMF has been used for the treatment of polymyositis, chronic inflammatory demyelinating polyradiculoneuropathy, and multifocal motor neuropathy. These studies showed that MMF is well tolerated and may be useful in some patients. MMF can be effective alone but mainly as an adjuvant therapy by reducing steroid requirements or the frequency of infusions of IVIg. MMF has also been tested alone as a single drug treatment or in combination with immunomodulatory drugs in multiple sclerosis in open surveillance trials or in phase II studies. None of these studies have been designed to demonstrate a clinical efficacy but preliminary results are very promising.     

The increase in human plasma antioxidant capacity after red wine consumption is due to both plasma urate and wine polyphenols

By using red wine, dealcoholized red wine, polyphenols-stripped red wine, ethanol-water solution and water, the role of wine polyphenols and induction of plasma urate elevation on plasma antioxidant capacity was examined in humans (n=9 per beverage). Healthy males randomly consumed each beverage in a cross-over design. Plasma antioxidant capacity (measured by ferric reducing antioxidant power, FRAP), ethanol, catechin and urate concentrations were determined before and 30, 60, 90, 120 and 180 min after beverage intake. Dealcoholized red wine and polyphenols-stripped red wine induced similar increase in FRAP values which represented nearly half the effect of the original red wine. This indicates that consumption of red wine involves two separate mechanisms in elevation of plasma FRAP values and both wine phenols and plasma urate contribute to that effect.     

Radial artery spasm during transradial coronary procedures

Although transradial access (TRA) for coronary procedures has many advantages over the transfemoral approach, it's still not the dominant route used in coronary interventions. Radial artery spasm (RAS) is an important limitation of TRA. We performed a search of published literature to estimate the prevalence and possible risk factors of RAS in patients undergoing transradial coronary procedure. Nineteen published papers including 7197 patients were identified as relevant; reported incidence of RAS was 14.7% altogether. It varies depending upon the criteria used, on applied premedications, and on sheath or catheter selection. Use of hydrophilic coated sheaths and catheters can reduce the incidence of RAS to 1%, while intra-arterial application of verapamil (1.25-5 mg) and nitroglycerin (100-200 μg) can reduce the incidence of RAS up to 3.8%. We concluded that RAS is still problematic in transradial access, and that besides hydrophilic materials, the use of intra-arterial vasodilators remains mandatory in RAS prevention. However, the optimal spasmolytic cocktail is yet to be confirmed by valid spasm criteria.     

Impaired endothelium-derived hyperpolarizing factor-mediated dilations and increased blood pressure in mice deficient of the intermediate-conductance Ca2+-activated K+ channel

The endothelium plays a key role in the control of vascular tone and alteration in endothelial cell function contributes to several cardiovascular disease states. Endothelium-dependent dilation is mediated by NO, prostacyclin, and an endothelium-derived hyperpolarizing factor (EDHF). EDHF signaling is thought to be initiated by activation of endothelial Ca(2+)-activated K(+) channels (K(Ca)), leading to hyperpolarization of the endothelium and subsequently to hyperpolarization and relaxation of vascular smooth muscle. In the present study, we tested the functional role of the endothelial intermediate-conductance K(Ca) (IK(Ca)/K(Ca)3.1) in endothelial hyperpolarization, in EDHF-mediated dilation, and in the control of arterial pressure by targeted deletion of K(Ca)3.1. K(Ca)3.1-deficient mice (K(Ca)3.1(-/-)) were generated by conventional gene-targeting strategies. Endothelial K(Ca) currents and EDHF-mediated dilations were characterized by patch-clamp analysis, myography and intravital microscopy. Disruption of the K(Ca)3.1 gene abolished endothelial K(Ca)3.1 currents and significantly diminished overall current through K(Ca) channels. As a consequence, endothelial and smooth muscle hyperpolarization in response to acetylcholine was reduced in K(Ca)3.1(-/-) mice. Acetylcholine-induced dilations were impaired in the carotid artery and in resistance vessels because of a substantial reduction of EDHF-mediated dilation in K(Ca)3.1(-/-) mice. Moreover, the loss of K(Ca)3.1 led to a significant increase in arterial blood pressure and to mild left ventricular hypertrophy. These results indicate that the endothelial K(Ca)3.1 is a fundamental determinant of endothelial hyperpolarization and EDHF signaling and, thereby, a crucial determinant in the control of vascular tone and overall circulatory regulation.     

Role of positron emission tomography and bone scintigraphy in the evaluation of bone involvement in metastatic pheochromocytoma and paraganglioma: specific implications for succinate dehydrogenase enzyme subunit B gene mutations

We performed a retrospective analysis of 71 subjects with metastatic pheochromocytoma and paraganglioma (30 subjects with mutation of succinate dehydrogenase enzyme subunit B (SDHB) gene and 41 subjects without SDHB mutation). Sixty-nine percent presented with bone metastases (SDHB +/-: 77% vs 63%), 39% with liver metastases (SDHB +/-: 27% vs 47%), and 32% with lung metastases (SDHB +/-: 37% vs 29%). The most common sites of bone involvement were thoracic spine (80%; SDHB+/-: 83% vs 77%), lumbar spine (78%; SDHB +/-: 78% vs 75%), and pelvic and sacral bones (78%; SDHB +/-: 91% vs 65%, P=0.04). Subjects with SDHB mutation also showed significantly higher involvement of long bones (SDHB +/-: 78% vs 30%, P=0.007) than those without the mutation. The best overall sensitivity in detecting bone metastases demonstrated positron emission tomography (PET) with 6-[(18)F]-fluorodopamine ([(18)F]-FDA; 90%), followed by bone scintigraphy (82%), computed tomography or magnetic resonance imaging (CT/MRI; 78%), 2-[(18)F]-fluoro-2-deoxy-d-glucose ([(18)F]-FDG) PET (76%), and scintigraphy with [(123/131)I]-metaiodobenzylguanidine (71%). In subjects with SDHB mutation, imaging modalities with best sensitivities for detecting bone metastases were CT/MRI (96%), bone scintigraphy (95%), and [(18)F]-FDG PET (92%). In subjects without SDHB mutations, the modality with the best sensitivity for bone metastases was [(18)F]-FDA PET (100%). In conclusion, bone scintigraphy should be used in the staging of patients with malignant pheochromocytoma and paraganglioma, particularly in patients with SDHB mutations. As for PET imaging, [(18)F]-FDG PET is highly recommended in SDHB mutation patients, whereas [(18)F]-FDA PET is recommended in patients without the mutation.     

TWIK-related two-pore domain potassium channel TREK-1 in carotid endothelium of normotensive and hypertensive mice

AIMS: Potassium channels are essential elements of endothelial function. Recently, evidence emerged that the TWIK (tandem of P domains in a weak inwardly rectifying K+ channel)-related K+ channel (TREK-1) of the two-pore domain potassium channel gene family (K2P) may be involved in the regulation of vascular tone. However, the functional and molecular characterization of vascular TREK-1 is incomplete. In this study, we therefore analysed the functional expression of TREK-1 in the endothelium. Moreover, we hypothesized that changes in channel expression may contribute to altered endothelial vasodilator response under conditions of elevated blood pressure. METHODS AND RESULTS: Gene expression and function of endothelial TREK-1 were analysed by single-cell RT-PCR, the patch-clamp technique and pressure myography in murine carotid arteries (CA). K+ outward currents displaying the characteristics of TREK-1 were observed following various TREK-1-activating stimuli such as membrane stretch, intracellular acidosis, polyunsaturated fatty acids, isoflurane (ISOFL), riluzole, and acetylcholine (ACh). In K(Ca)3.1(-/-) mice exhibiting elevated blood pressure, endothelial TREK-1 currents and TREK-1 mRNA expression were enhanced as compared with normotensive control mice. TREK-1-mediated vasodilator responses to alpha-linolenic acid, ISOFL, or ACh were increased. A similar up-regulation of endothelial TREK-1 was observed in spontaneously hypertensive rats. CONCLUSION: We have found that TREK-1 is an endothelial K+ channel capable of producing hyperpolarization and vasodilation. A correlation between hypertension and up-regulation of TREK-1 was observed in two different animal models of elevated blood pressure. Thus, TREK-1 may play a protective role in the cardiovascular system by providing a novel type of endothelial hyperpolarization-mediated vasodilator response.