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PURPOSE: To assess the negative predictive value of PSMA PET scan for lymph node staging in patients undergoing robotic radical prostatectomy and pelvic lymph node dissection. MATERIALS AND METHODS: A retrospective analysis of patients who underwent robotic-assisted radical prostatectomy with pelvic lymph node dissection and had a preoperative negative PSMA PET scan for metastasis was performed. The documented pre-operative variables studied included age, BMI, PSA at diagnosis, Gleason score, and biopsy ISUP grades. Patients were categorised as low, intermediate and high risk according to the D Amico classification. The post-op variables included were number of lymph nodes harvested, number of positive nodes, positivity rate, size of the node metastasis, T staging and ISUP grading. RESULTS: The overall negative predictive value of PSMA PET scan was 71.6%. Further sub-classification according to risk stratification demonstrated a NPV of 58.02%, 92.7% and 90% for high, intermediate and low risk, respectively. CONCLUSION: Pelvic lymph node dissection cannot be excluded based on a negative preop PSMA PET/CT scan.

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Procedimientos Quirúrgicos Robotizados , Masculino , Humanos , Valor Predictivo de las Pruebas , Estudios Retrospectivos , Tomografía Computarizada por Tomografía de Emisión de Positrones , Radioisótopos de Galio , Escisión del Ganglio Linfático , Ganglios Linfáticos/patología , Prostatectomía , Estadificación de Neoplasias

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Background: Long-term outcomes of acute pulmonary thromboembolism (PTE) have been reported. However, the immediate- and short-term outcomes have not been reported adequately. Objectives: Primary objective was to determine the patient characteristics, and immediate- and short-term outcomes of intermediate-risk PTE, and the secondary objective was to evaluate the benefit of thrombolysis in normotensive PTE patients. Material and methods: This study included patients diagnosed with acute intermediate PTE. Patient's electrocardiography (ECG) parameters along with echocardiography (echo), etc., conducted at the time of admission, during their stay in hospital, at the time of discharge, and during follow-up were recorded. The patients were treated using thrombolysis or anticoagulants depending on hemodynamic decompensation. During follow-up, they were reassessed for echo parameters-right ventricular (RV) function and pulmonary arterial hypertension (PAH). Results: Among 55 patients, 29 (52.73%) were diagnosed with intermediate high-risk PTE and 26 (47.27%) with intermediate low-risk PTE. They were normotensive and most of them had a simplified pulmonary embolism severity index (sPESI) score <2. Typical ECG pattern S1Q3T3 along with echo patterns and elevated cardiac troponin levels were observed in most of the patients. Patients treated with thrombolytic agents showed a reduction in hemodynamic decompensation as opposed to patients treated with anticoagulants who had clinical signs of right heart failure (RHF) on follow-up after 3 months. Conclusion: This study contributes to the existing literature on outcomes of intermediate-risk PTE and the effect of thrombolysis on patients with hemodynamic stability. Thrombolysis reduced the incidence and progression of RHF in patients with hemodynamic instability. How to cite this article: Mathiyalagan P, Rajangam T, Bhargavi K, Gnanaraj R, Sundaram S. Clinical Profile, Immediate- and Short-term Outcome of Patients with Intermediate-risk Acute Pulmonary Thromboembolism. Indian J Crit Care Med 2022;26(11):1192-1197.

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OBJECTIVE: To evaluate the prognostic value of amplitude-integrated EEG in term neonates with encephalopathy. METHODS: In this prospective observational study we enrolled 58 term neonates with encephalopathy from March, 2019 to March, 2020. Level of alertness was ascertained as per Volpe's classification and tone as per Amiel-Tison scale of tone assessment. Abnormal aEEG was defined as background activity other than continuous normal voltage, or immature or absent sleep-wake cycle, or presence of electrical seizure. Primary outcome was abnormal neurological examination at discharge and/or death prior to discharge. RESULTS: Out of 58 neonates, aEEG was abnormal for 50 (86.2%). There was a statistically significant association between abnormal aEEG findings and primary outcome (P=0.04). The aEEG score cut-off of >2 had satisfactory sensitivity (88.8%) and specificity (79.5%) to predict primary outcome. CONCLUSIONS: Abnormal aEEG had good sensitivity but low specificity to predict the primary outcome in term neonates with encephalopathy.

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Encefalopatías , Electroencefalografía , Encefalopatías/diagnóstico , Humanos , Recién Nacido , Valor Predictivo de las Pruebas , Pronóstico , Sensibilidad y Especificidad

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Dietary nutrients absorbed in the proximal small intestine and assimilated in different tissues have a profound effect on overall energy homeostasis, determined by a balance between body's energy intake and expenditure. In obesity, altered intestinal absorption and consequently tissue assimilation of nutrients may disturb the energy balance leading to metabolic abnormalities at the cellular level. The absorption of nutrients such as sugars, amino acids and fatty acids released from food digestion require high-capacity transporter proteins expressed in the intestinal epithelial absorptive cells. Furthermore, nutrient sensing by specific transporters/receptors expressed in the epithelial enteroendocrine cells triggers release of gut hormones involved in regulating energy homeostasis via their effects on appetite and food intake. Therefore, the intestinal epithelial cells play a pivotal role in the pathophysiology of obesity and associated complications. Over the past decade, gut microbiota has emerged as a key factor contributing to obesity via its effects on digestion and absorption of nutrients in the small intestine, and energy harvest from dietary fiber, undigested component of food, in the large intestine. Various mechanisms of microbiota effects on obesity have been implicated. However, the impact of obesity-associated microbiota on the intestinal nutrient transporters needs extensive investigation. This review marshals the limited studies addressing the altered structure and function of the gut epithelium in obesity with special emphasis on nutrient transporters and role of diet and microbiota. The review also discusses the thoughts and controversies and research gaps in this field.

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Dieta , Mucosa Intestinal/fisiopatología , Microbiota , Nutrientes/metabolismo , Obesidad/patología , Animales , Humanos , Obesidad/etiología

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In mammalian small intestine, glucose is primarily absorbed via Na-dependent glucose co-transporter (SGLT1) on the brush border membrane (BBM) of absorptive villus cells. Malabsorption of nutrients (e.g., glucose) leads to malnutrition, a common symptom of inflammatory bowel disease (IBD), where the mucosa is characterized by chronic inflammation. Inducible nitric oxide (iNO) is known to be elevated in IBD mucosa. SAMP1/YitFc (SAMP1) mouse is a spontaneous model of chronic ileitis that develops lesions in its terminal ileum, very similar to human IBD. How SGLT1 may be affected in SAMP1 model of chronic ileitis is unknown. Ten-week-old SAMP1 mice with AKR mice as control were treated with N6-(1-iminoethyl)-L-lysine dihydrochloride (L-NIL) to inhibit iNO production. Intracellular NO levels were found to be increased in villus cells from SAMP1 mice. Moreover, SGLT1 and Na+/K+-ATPase activities and BBM SGLT1 expression were significantly decreased. However, L-NIL treatment reduced the intracellular iNO production, and reversed both downregulated SGLT1 and Na+/K+-ATPase activities in SAMP1 mice. Inhibition of iNO by L-NIL treatment also significantly reversed the BBM SGLT1 protein expression in SAMP1 mice. L-NIL reversed the inflammation mediated downregulation of SGLT1 activity by restoring the BBM SGLT1 expression. Thus, regulation of SGLT1 in chronic ileitis is likely mediated by iNO.

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Transporte Biológico/efectos de los fármacos , Enfermedad de Crohn/metabolismo , Glucosa/metabolismo , Íleon/metabolismo , Óxido Nítrico/fisiología , Sodio/metabolismo , Animales , Enfermedad Crónica , Modelos Animales de Enfermedad , Expresión Génica , Proteínas de la Membrana , Ratones Transgénicos , Microvellosidades/metabolismo , Óxido Nítrico/metabolismo , Proteínas Nucleares , Transportador 1 de Sodio-Glucosa/genética , Transportador 1 de Sodio-Glucosa/metabolismo , Transportador 1 de Sodio-Glucosa/fisiología , ATPasa Intercambiadora de Sodio-Potasio/metabolismo

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INTRODUCTION: The glossopharyngeal nerve lies posterior to the internal carotid artery at the submandibular region. The primary objective of this study was to compare ultrasound-guided glossopharyngeal nerve block (UGPNB) and landmark glossopharyngeal nerve block (GPNB). MATERIALS & METHODS: Inclusion criteria were patients with unilateral Eagle syndrome and ear pain. Group UGPNB (N = 25) received three UGPNBs at weekly intervals with 1.5 mL of 0.5% ropivacaine and 20 mg of methylprednisolone. Group GPNB (N = 26) received landmark GPNB. Pain intensity was evaluated with the numerical rating scale (NRS) before every block, 30 minutes after every block, and at one, three, and five weeks after the third block. Quality of life, assessed using the Brief Pain Inventory (BPI), and satisfaction scores were noted. RESULTS: NRS scores before the second and third blocks and a week after were significantly lower in group UGPNB and comparable at weeks 3 and 5. NRS scores 30 minutes after every block were significantly decreased from the preblock values but were comparable between groups. In 68% of patients, a curvilinear probe delineated the internal carotid artery (ICA). Out-of-plane needle trajectory was required in 64% of patients. BPI and satisfaction scores were significantly better in the UGPNB group in the "block" weeks. CONCLUSIONS: UGPNB with 1.5 mL of 0.5% ropivacaine and 20 mg of methylprednisolone injected posterior to the ICA in the submandibular region provides better pain relief for at least a week compared with an extraoral landmark technique when three weekly consecutive blocks are given. In most patients, a curvilinear probe and out-of-plane needle trajectory are most suitable for ultrasound block.

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Nervio Glosofaríngeo , Bloqueo Nervioso , Anestésicos Locales , Humanos , Osificación Heterotópica , Dolor Postoperatorio , Calidad de Vida , Hueso Temporal/anomalías , Ultrasonografía Intervencional

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In obesity, increased absorption of dietary fat contributes to altered lipid homeostasis. In turn, dyslipidemia of obesity leads to many of the complications of obesity. Bile acids are necessary for the absorption of dietary fat. In the mammalian intestine, apical sodium-dependent bile acid cotransporter (ASBT; SLC10A2) is exclusively responsible for the reabsorption of bile acids in the terminal ileum. In rat and mice models of obesity and importantly in obese humans, ASBT was increased in ileal villus cells. The mechanism of stimulation of ASBT was secondary to an increase in ASBT expression in villus cell brush border membrane. The stimulation of ASBT was not secondary to the altered Na-extruding capacity of villus cells during obesity. Further, increased Farnesoid X receptor (FXR) expression in villus cells during obesity likely mediated the increase in ASBT. Moreover, enhanced FXR expression increased the expression of bile-acid-associated proteins (IBABP and OSTα) that are responsible for handling bile acids absorbed via ASBT in villus cells during obesity. Thus, this study demonstrated that in an epidemic condition, obesity, the dyslipidemia that leads to many of the complications of the condition, may, at least in part, be due to deregulation of intestinal bile acid absorption.

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Dislipidemias/metabolismo , Íleon/citología , Obesidad/complicaciones , Transportadores de Anión Orgánico Sodio-Dependiente/metabolismo , Receptores Citoplasmáticos y Nucleares/metabolismo , Simportadores/metabolismo , Animales , Ácidos y Sales Biliares/metabolismo , Células Cultivadas , Modelos Animales de Enfermedad , Dislipidemias/etiología , Homeostasis , Humanos , Íleon/metabolismo , Masculino , Ratones , Microvellosidades/metabolismo , Obesidad/metabolismo , Ratas , Regulación hacia Arriba

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During obesity, diabetes and hypertension inevitably coexist and cause innumerable health disparities. In the obesity, diabetes, and hypertension triad (ODHT), deregulation of glucose and NaCl homeostasis, respectively, causes diabetes and hypertension. In the mammalian intestine, glucose is primarily absorbed by Na-glucose cotransport 1 (SGLT1) and coupled NaCl by the dual operation of Na-H exchange 3 (NHE3) and Cl-HCO3 [down-regulated in adenoma (DRA) or putative anion transporter 1 (PAT1)] exchange in the brush border membrane (BBM) of villus cells. The basolateral membrane (BLM) Na/K-ATPase provides the favorable transcellular Na gradient for BBM SGLT1 and NHE3. How these multiple, distinct transport processes may be affected in ODHT is unclear. Here, we show the novel and broad regulation by Na/K-ATPase of glucose and NaCl absorption in ODHT in multiple species (mice, rats, and humans). In vivo, during obesity inhibition of villus-cell BLM, Na/K-ATPase led to compensatory stimulation of BBM SGLT1 and DRA or PAT1, whereas NHE3 was unaffected. Supporting this new cellular adaptive mechanism, direct silencing of BLM Na/K-ATPase in intestinal epithelial cells resulted in selective stimulation of BBM SGLT1 and DRA or PAT1 but not NHE3. These changes will lead to an increase in glucose absorption, maintenance of traditional coupled NaCl absorption, and a de novo increase in NaCl absorption from the novel coupling of stimulated SGLT1 with DRA or PAT1. Thus, these novel observations provide the pathophysiologic basis for the deregulation of glucose and NaCl homeostasis of diabetes and hypertension, respectively, during obesity. These observations may lead to more efficacious treatment for obesity-associated diabetes and hypertension.-Palaniappan, B., Arthur, S., Sundaram, V. L., Butts, M., Sundaram, S., Mani, K., Singh, S., Nepal, N., Sundaram, U. Inhibition of intestinal villus cell Na/K-ATPase mediates altered glucose and NaCl absorption in obesity-associated diabetes and hypertension.

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Glucosa/metabolismo , Intestinos/citología , Microvellosidades/metabolismo , Obesidad/tratamiento farmacológico , Obesidad/metabolismo , Cloruro de Sodio/metabolismo , Animales , Western Blotting , Línea Celular , Técnica del Anticuerpo Fluorescente , Hipertensión/tratamiento farmacológico , Hipertensión/metabolismo , Absorción Intestinal/fisiología , Mucosa Intestinal/efectos de los fármacos , Mucosa Intestinal/metabolismo , Masculino , Interferencia de ARN , Ratas , ATPasa Intercambiadora de Sodio-Potasio/metabolismo

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Na-amino acid co-transporters (NaAAcT) are uniquely affected in rabbit intestinal villus cell brush border membrane (BBM) during chronic intestinal inflammation. Specifically, Na-alanine co-transport (ASCT1) is inhibited secondary to a reduction in the affinity of the co-transporter for alanine, whereas Na-glutamine co-transport (B0AT1) is inhibited secondary to a reduction in BBM co-transporter numbers. During chronic intestinal inflammation, there is abundant production of the potent oxidant peroxynitrite (OONO). However, whether OONO mediates the unique alteration in NaAAcT in intestinal epithelial cells during chronic intestinal inflammation is unknown. In this study, ASCT1 and B0AT1 were inhibited by OONO in vitro. The mechanism of inhibition of ASCT1 by OONO was secondary to a reduction in the affinity of the co-transporter for alanine, and secondary to a reduction in the number of co-transporters for B0AT1, which were further confirmed by Western blot analyses. In conclusion, peroxynitrite inhibited both BBM ASCT1 and B0AT1 in intestinal epithelial cells but by different mechanisms. These alterations in the villus cells are similar to those seen in the rabbit model of chronic enteritis. Therefore, this study indicates that peroxynitrite may mediate the inhibition of ASCT1 and B0AT1 during inflammation, when OONO levels are known to be elevated in the mucosa.

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Sistemas de Transporte de Aminoácidos Neutros/metabolismo , Enterocitos/metabolismo , Proteínas de Transporte de Glutamato en la Membrana Plasmática/metabolismo , Microvellosidades/metabolismo , Simportadores/metabolismo , Animales , Línea Celular , Enterocitos/efectos de los fármacos , Enterocitos/patología , Inflamación/metabolismo , Ácido Peroxinitroso/toxicidad , Ratas

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During chronic intestinal inflammation in rabbit intestinal villus cells brush border membrane (BBM) Na-glucose co-transport (SGLT1), but not Na/H exchange (NHE3) is inhibited. The mechanism of inhibition is secondary to a decrease in the number of BBM co-transporters. In the chronic enteritis mucosa, inducible nitric oxide (iNO) and superoxide production are known to be increased and together they produce abundant peroxynitrite (OONO), a potent oxidant. However, whether OONO mediates the SGLT1 and NHE3 changes in intestinal epithelial cells during chronic intestinal inflammation is unknown. Thus, we determined the effect of OONO on SGLT1 and NHE3 in small intestinal epithelial cell (IEC-18) monolayers grown on trans well plates. In cells treated with 100 µM SIN-1 (OONO donor) for 24 h, SGLT1 was inhibited while NHE3 activity was unaltered. SIN-1 treated cells produced 40 times more OONO fluorescence compared to control cells. Uric acid (1mM) a natural scavenger of OONO prevented the OONO mediated SGLT1 inhibition. Na⁺/K⁺-ATPase which maintains the favorable trans-cellular Na gradient for Na-dependent absorptive processes was decreased by OONO. Kinetics studies demonstrated that the mechanism of inhibition of SGLT1 by OONO was secondary to reduction in the number of co-transporters (Vmax) without an alteration in the affinity. Western blot analysis showed a significant decrease in SGLT1 protein expression. Further, p38 mitogen-activated protein (MAP) kinase pathway appeared to mediate the OONO inhibition of SGLT1. Finally, at the level of the co-transporter, 3-Nitrotyrosine formation appears to be the mechanism of inhibition of SGLT1. In conclusion, peroxynitrite inhibited BBM SGLT1, but not NHE3 in intestinal epithelial cells. These changes and the mechanism of SGLT1 inhibition by OONO in IEC-18 cells is identical to that seen in villus cells during chronic enteritis. Thus, these data indicate that peroxynitrite, known to be elevated in the mucosa, may mediate the inhibition of villus cell BBM SGLT1 in vivo in the chronically inflamed intestine.

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CONTEXT: Papillary thyroid carcinoma with tall cell histology (PTC-TCH) is an aggressive subtype in terms of clinicopathological features and outcome. Even 10% of tall cells can show aggressive features. AIMS: The aim of this study is to investigate the behavior of PTC-TCH, to compare with classic PTC (cPTC), and evaluate the short-term outcome. SETTINGS AND DESIGN: This is a retrospective analysis of patients with cPTC and those with TCH (PTC-TCH) seen from January 2010 to May 2017 seen in our Thyroid Cancer Clinic. MATERIALS AND METHODS: A total of 40 patients with TCH were compared with 352 cPTC and evaluated for age, gender, tumor size, presence of multifocality, capsular, vascular invasion, extrathyroid extension, and appearance of metastases. Short-term response to therapy was assessed using the 2015 American Thyroid Association guidelines. STATISTICAL ANALYSIS: P < 0.05 was considered statistically significant. All analyses were performed with SPSS software (Version 21.0, Chicago, IL, USA). RESULTS: PTC with TCH presented at a younger age, had larger tumors, and more extrathyroid extension. Seven out of 40 cases developed lung metastases, (17.5% vs. 4.5% in cPTC), within a year of diagnosis. CONCLUSION: PTC-TCH irrespective of percentage of tall cells showed aggressive features and early metastases. They should be recognized early as an aggressive subtype and treated intensively. Close follow-up must be instituted to look for metastases, especially to the lungs.

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INTRODUCTION: Balloon Mitral Valvuloplasty (BMV) with inoue balloon is the most common technique being followed worldwide. Over the wire BMV is a modified technique with Joseph Mitral Valvuloplasty (JOMIVA) balloon and is being followed in certain centres. We hypothesized that, the incidence and mechanism of Mitral Regurgitation (MR) is likely to be different from that of inoue balloon. AIM: To assess the mechanism and immediate clinical outcome of significant MR following BMV with JOMIVA balloon retrospectively. MATERIALS AND METHODS: We retrospectively analyzed the outcome of 48 patients who developed moderate to severe MR out of 249 patients who underwent BMV in our institute. We analyzed the echocardiographic and clinical parameters of these patients. RESULTS: Nineteen (7.6%) patients developed severe MR and 29 (11.2%) patients developed moderate MR. Commisural separation resulting in MR was the most common cause which was contributing to 73.6 % and 85.7% of patients with moderate and severe MR respectively. Leaflet tear was the second most common cause which contributed to 15.7% and 14.2% of patients with severe and moderate MR respectively. Chordal rupture contributed to 10.5% of patients with severe MR. Six (31.6%) patients with severe MR developed worsening breathlessness among them one had to be referred for mitral valve replacement during index hospitalization and the rest could be managed medically. Patients with moderate MR remained asymptomatic and stable. CONCLUSION: Severe MR following JOMIVA BMV results most commonly due to wide separation of commisures. JOMIVA balloon is less likely to cause damage to subvalvular structures than inoue balloon. Most patients who develop severe MR will not require emergency mitral valve replacement. Moderate MR is well tolerated clinically.

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OBJECTIVES: Diabetic cardiomyopathy (DCM) is an established complication of diabetes mellitus. In West Virginia, the especially high incidence of diabetes and heart failure validate the necessity of developing new strategies for earlier detection of DCM. Since most DCM patients remain asymptomatic until the later stages of the disease when the fibrotic complications become irreversible, we aimed to explore biomarkers that can identify early-stage DCM. METHODS: The patients were grouped into 4 categories based on clinical diabetic and cardiac parameters: Control, Diabetes (DM), Diastolic dysfunction (DD), and Diabetes with diastolic dysfunction (DM+DD), the last group being the preclinical DCM group. RESULTS: Echocardiography images indicated severe diastolic dysfunction in patients with DD+DM and DD compared to DM or control patients. In the DM and DM+DD groups, TNFα, isoprostane, and leptin were elevated compared to control (p<0.05), as were clinical markers HDL, glucose and hemoglobin A1C. Fibrotic markers IGFBP7 and TGF-ß followed the same trend. The Control group showed higher beneficial levels of adiponectin and bilirubin, which were reduced in the DM and DM+DD groups (p<0.05). CONCLUSION: The results from our study support the clinical application of biomarkers in diagnosing early stage DCM, which will enable attenuation of disease progression prior to the onset of irreversible complications.

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Biomarcadores/sangre , Cardiomiopatías Diabéticas/sangre , Cardiomiopatías Diabéticas/diagnóstico , Adiponectina/sangre , Bilirrubina/sangre , Estudios de Casos y Controles , Electrocardiografía , Humanos , Proteínas de Unión a Factor de Crecimiento Similar a la Insulina/sangre , Interleucina-6/sangre , Isoprostanos/sangre , Leptina/sangre , Factor de Crecimiento Transformador beta/sangre , Factor de Necrosis Tumoral alfa/sangre , West Virginia

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Na-K-ATPase located on the basolateral membrane (BLM) of intestinal epithelial cells provides a favorable intracellular Na+ gradient to promote all Na dependent co-transport processes across the brush border membrane (BBM). Down-regulation of Na-K-ATPase activity has been postulated to alter the absorption via Na-solute co-transporters in human inflammatory bowel disease (IBD). Further, the altered activity of a variety of Na-solute co-transporters in intact villus cells has been reported in animal models of chronic enteritis. But the molecular mechanism of down-regulation of Na-K-ATPase is not known. In the present study, using a rabbit model of chronic intestinal inflammation, which resembles human IBD, Na-K-ATPase in villus cells was shown to decrease. The relative mRNA abundance of α-1 and ß-1 subunits was not altered in villus cells during chronic intestinal inflammation. Similarly, the protein levels of these subunits were also not altered in villus cells during chronic enteritis. However, the BLM concentration of α-1 and ß-1 subunits was diminished in the chronically inflamed intestinal villus cells. An ankyrin-spectrin skeleton is necessary for the proper trafficking of Na-K-ATPase to the BLM of the cell. In the present study, ankyrin expression was markedly diminished in villus cells from the chronically inflamed intestine resulting in depolarization of ankyrin-G protein. The decrease of Na-K-ATPase activity was comparable to that seen in ankyrin knockdown IEC-18 cells. Therefore, altered localization of Na-K-ATPase as a result of transcriptional down-regulation of ankyrin-G mediates the down-regulation of Na-K-ATPase activity during chronic intestinal inflammation.

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Ancirinas/genética , Membrana Celular/metabolismo , Células Epiteliales/metabolismo , Enfermedades Inflamatorias del Intestino/genética , Microvellosidades/metabolismo , Subunidades de Proteína/genética , ATPasa Intercambiadora de Sodio-Potasio/genética , Actinas/genética , Actinas/metabolismo , Animales , Ancirinas/metabolismo , Membrana Celular/química , Polaridad Celular , Enfermedad Crónica , Modelos Animales de Enfermedad , Células Epiteliales/química , Células Epiteliales/patología , Regulación de la Expresión Génica , Humanos , Enfermedades Inflamatorias del Intestino/metabolismo , Enfermedades Inflamatorias del Intestino/patología , Intestino Delgado/química , Intestino Delgado/metabolismo , Intestino Delgado/patología , Masculino , Microvellosidades/química , Microvellosidades/patología , Isoformas de Proteínas/genética , Isoformas de Proteínas/metabolismo , Subunidades de Proteína/metabolismo , Conejos , ATPasa Intercambiadora de Sodio-Potasio/metabolismo

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AIM: The aim of this study was to assess and compare the response to two forms of treatment-immobilization with zoledronic acid injection and immobilization with oral weekly Alendronate, in patients with diabetes mellitus and acute Charcot arthropathy (CA) of foot in terms of clinical and radiological parameters. MATERIAL AND METHODS: Patients attending the endocrinology and podiatry clinic with history of diabetes mellitus and Acute CA were taken for study. The patients were randomized into two treatment groups. Group Z-zoledronic acid injection along with total contact cast (TCC). Group A-Tab. Alendronate 70 mg. once a week till the complete clinical resolution of acute CA along with TCC. Forty-five patients were randomized and 40 of them completed the study. The primary end point was complete clinical resolution of acute CA-defined as temperature difference between normal and affected foot <1°F. RESULTS: Among the 40 patients, 30 (75%) had complete clinical resolution. The mean number of days taken for complete clinical resolution since the initiation of treatment (either Zoledronic acid or Alendronate) was approximately 122 days. There was no significant difference in a number of days required for complete clinical resolution, between the two forms of therapy. There was more than 50% reduction in the visual score between the baseline and the final scan. The target to non-target ratio in the skeletal phase also showed an average of 40% reduction from the baseline to the final skeletal scintigraphy. CONCLUSION: Both Intravenous Zoledronic acid and oral alendronate had comparable efficacy with respect to the time taken for attaining complete clinical resolution of acute CA of foot. However, Alendronate therapy was cost effective among the two. (99m)Tc MDP bone scan can be used as an adjuvant to the clinical parameters in assessing the response to therapy.

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BACKGROUND CONTEXT: Laminoplasty aims to decompress the spinal cord and stabilize the cervical spine in patients with multilevel cervical lesions. Not every patient with cervical compressive myelopathy is a good candidate for laminoplasty. Most studies recommend that neutral or kyphotic alignments are contraindications for laminoplasty. However, cervical sagittal alignment does not have a strong and consistent effect on the clinical outcomes of laminoplasty. Moreover, many reports on the effect of cervical sagittal alignment did not designate the ideal definition of alignment and used different definitions of lordosis. PURPOSE: To identify the effect of preoperative cervical alignment according to two different definitions after midline splitting double-door laminoplasty. STUDY DESIGN: Retrospective cohort study. PATIENT SAMPLE: From August 2008 to September 2010, 58 patients were diagnosed with cervical myelopathy and treated with midline splitting double-door laminoplasty. OUTCOME MEASURES: The clinical results were assessed with the modified Japanese Orthopedic Association (JOA) score, neck disability index (NDI), and visual analog scale (VAS) and were compared to analyze the rate of change between preoperative and postoperative values. Postoperative radiological results at the final follow-up examinations were compared between groups to obtain the change in range of motion and sagittal alignment. METHOD: The effect of cervical alignment on JOA, NDI, and VAS scales and also on change of alignment and change of range of motion (ROM) at the final follow-up examinations was analyzed statistically between two groups according to two different definitions such as Toyama classification and Cobb angle. RESULTS: No difference was found between the two groups according to Toyama classification in terms of the postoperative improvement rate of the modified JOA score (p=.086), decreasing rate of the VAS (p=.940) or NDI (p=.211), postoperatively. Additionally, no difference was found for the decreasing rate of ROM (p=.427) or sagittal alignment (p=.864) based on the radiological evaluation results. Also, there was no difference between two groups according to Cobb angle in terms of the modified JOA score (p=.743), VAS (p=.548), or NDI (p=.32), postoperatively. Additionally, no difference was found for the ROM (p=1.000) or sagittal alignment (p=.440) based on the radiological evaluation results. CONCLUSIONS: Despite nonlordosis cervical sagittal alignment, double-door laminoplasty would be effective for patients with cervical myelopathy because of cervical spondylotic myelopathy or ossification of the posterior longitudinal ligament. Furthermore, sagittal alignment is not the absolute and sole factor that surgeons should consider when determining the optimal treatment strategy.

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Vértebras Cervicales/cirugía , Descompresión Quirúrgica/métodos , Laminectomía/métodos , Lordosis/cirugía , Rango del Movimiento Articular , Compresión de la Médula Espinal/cirugía , Adulto , Anciano , Anciano de 80 o más Años , Vértebras Cervicales/diagnóstico por imagen , Evaluación de la Discapacidad , Femenino , Humanos , Lordosis/diagnóstico por imagen , Masculino , Persona de Mediana Edad , Periodo Posoperatorio , Radiografía , Estudios Retrospectivos , Compresión de la Médula Espinal/diagnóstico por imagen , Resultado del Tratamiento

RESUMEN

BACKGROUND CONTEXT: Despite significant advances in the development of diagnostic technology, the diagnosis of cervical myelopathy (CM) still remains based on the clinical findings, which do not provide the means for a sufficiently accurate diagnosis. Furthermore, conventional magnetic resonance imaging (MRI) using T1- and T2-weighted sequences lacks sensitivity to detect and characterize spinal cord lesions. Considering these uncertainties, several investigators have assessed the diagnostic value of diffusion tensor imaging (DTI), an advanced MRI technique that measures the diffusion of water molecules. PURPOSE: To determine the diagnostic value of DTI in CM in reliably characterizing spinal lesions and in associating them with the clinical findings. STUDY DESIGN/SETTING: Prospective cohort study. PATIENT SAMPLE: Fifteen CM patients and five healthy volunteers without a history of neurological disorders or of symptoms as controls. OUTCOME MEASURES: Symptoms and signs of CM were evaluated by the use of a modified Japanese Orthopedic Score and the other clinical findings. T2-weighed MRI was used to note the number of compressed levels. Diffusion tensor imaging results were measured according to two parameters, fractional anisotropy (FA) and apparent diffusion coefficient (ADC), at anterior, lateral, and posterior regions of interest (ROIs) in each of five cervical vertebrae, C3-C7. METHODS: On diagnosis of CM by clinical evaluation and findings from T2-weighted MRI, the 15 subjects were assigned to two subgroups based on complaints, symptoms, and signs. The nine subjects who had typical CM symptoms such as motor weakness, gait disturbance, clumsiness of the hands, and unilateral hypesthesia were assigned to the paralysis subgroup. The other six subjects, whose main symptom was pain and who had vague signs of upper motor neuron injury despite a definitive finding of CM by T2-weighted MRI, were assigned to the pain subgroup. Once assignments had been made, subjects underwent DTI done by the use of the same scanner as for T2-weighted MRI. Results of DTI for each subgroup and controls were averaged, and the mean was used for comparisons. Diffusion tensor imaging results from the paralysis subgroup were sorted into affected and unaffected sides according to the presence or the absence of symptoms. RESULTS: The paralysis subgroup and the pain subgroup had similar findings from T2-weighted MRI on presentation. The paralysis subgroup had statistically significantly decreased FA values in the anterior and lateral ROIs on the affected side and in the anterior ROIs on the unaffected side, compared with controls. The paralysis subgroup also had statistically significantly increased ADC values in the anterior ROIs of the affected side, compared with controls. The pain subgroup showed significantly increased ADC values in anterior, lateral, and posterior ROIs. CONCLUSIONS: Use of DTI to quantitatively compare compression in the cervical spinal cords of CM subjects and healthy controls explained individual differences in the clinical findings in the subjects. These findings even applied to CM subjects whose compressed spinal cords looked similar on conventional T2-weighted MRI. Therefore, DTI provided more accurate and reliable information than did conventional T2-weighted MRI about the relationship between spinal cord structure and clinical presentation of CM. Based on our DTI findings, we hypothesized that different clinical findings in CM are attributable to the stage of progression and the severity of pathologic change at presentation. We anticipate that the use of DTI to quantify the extent of myelopathological changes in CM could be more reliable than any other existing diagnostic tools and might provide invaluable information about selecting the optimal treatment for CM and predicting surgical outcomes and prognosis.

Asunto(s)

Imagen de Difusión Tensora , Compresión de la Médula Espinal/diagnóstico , Médula Espinal/patología , Adulto , Anciano , Anciano de 80 o más Años , Vértebras Cervicales/patología , Femenino , Humanos , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Compresión de la Médula Espinal/patología

RESUMEN

Previously studies have demonstrated that Cl(-)/HCO(3)(-) exchange was inhibited during chronic intestinal inflammation secondary to decrease in the affinity of the exchanger for Cl(-) rather than the number of transporters. Arachidonic acid metabolites (AAM) are elevated in the mucosa of the chronically inflamed small intestine. However, their role in the alteration of Cl(-)/HCO(3)(-) during chronic enteritis was unknown. Inhibition of AAM formation with arachidonyl trifluoro methylketone (ATMK) in chronically inflamed rabbit intestine reversed the diminished Cl(-)/HCO(3)(-) exchange activity. Kinetics studies showed that the reversal was secondary to restoration of the altered affinity of transporter. Downstream regulation of Cl(-)/HCO(3)(-) inhibition by AAM was determined to be by the cyclooxygenase pathway since only inhibition of cyclooxygenase with piroxicam treatment reversed the inhibited Cl(-)/HCO(3)(-) exchange. Further, DRA was shown to be the primary Cl(-)/HCO(3)(-) exchanger in villus cells. Kinetics and molecular studies indicated that the mechanism of inhibition of Cl(-)/HCO(3)(-) exchange by cyclooxygenase pathway metabolites was secondary to diminished affinity of the transporter for Cl(-) without a change in DRA BBM expression. Thus our data indicated that cyclooxygenase pathway metabolites mediate the inhibition of DRA during chronic intestinal inflammation.

Asunto(s)

Antiportadores de Cloruro-Bicarbonato/metabolismo , Íleon/metabolismo , Leucotrienos/metabolismo , Prostaglandinas/metabolismo , Animales , Ácido Araquidónico/metabolismo , Relación Dosis-Respuesta a Droga , Inmunohistoquímica/métodos , Indoles/farmacología , Inflamación/metabolismo , Mucosa Intestinal/metabolismo , Cetonas/metabolismo , Cinética , Masculino , Microvellosidades/metabolismo , Conejos