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Papers by ghulam abbas

Nature Reviews Gastroenterology & Hepatology, 2010

Primary biliary cirrhosis (PBC) is a chronic, autoimmune, cholestatic liver disease with a slowly... more Primary biliary cirrhosis (PBC) is a chronic, autoimmune, cholestatic liver disease with a slowly progressive course. Without treatment, most patients eventually develop fibrosis of the liver and may need liver transplantation in the late stage of disease. Fatigue and pruritus are the most common symptoms of PBC, but the majority of patients are asymptomatic at first presentation. There is no specific treatment for fatigue in PBC, but modafinil has shown some potential beneficial effects, such as increased energy levels and decreased total sleep time. This Review article discusses the natural history and the measurement of fatigue in patients with PBC. The central and the peripheral mechanisms that have been suggested for the pathogenesis of fatigue in PBC are also discussed and treatment options are reviewed.

Journal of Gastrointestinal Cancer, 2009

Primary sclerosing cholangitis (PSC) is often complicated by the development of cholangiocarcinom... more Primary sclerosing cholangitis (PSC) is often complicated by the development of cholangiocarcinoma (CCA). Genetic variation of natural killer cell receptor G2D (NKG2D) has been associated with cancer susceptibility. An important ligand for NKG2D, major histocompatibility complex class I chain-related molecule A (MICA), serves as a marker of cellular stress. The 5.1 allele of the gene encoding MICA has been associated with PSC. In this study, we aimed to investigate the influence of genetic variations in the NKG2D-MICA receptor-ligand pair on the risk of CCA in patients with PSC. Seven single nucleotide polymorphisms (SNPs) covering the NKG2D gene were genotyped in 365 Scandinavian PSC patients and 368 healthy controls with TaqMan technology. Genotype data on the MICA 5.1 variant were available from previous studies. Forty-nine of the PSC patients (13.6%) had developed CCA at the time of study. Two of the NKG2D SNPs were associated with an increased risk of CCA: rs11053781 [odds ratio (OR) ‫؍‬ 2.08, 95% confidence interval (CI) ‫؍‬ 1.31-3.29, corrected P (P c ) ‫؍‬ 0.011] and rs2617167 (OR ‫؍‬ 2.32, 95% CI ‫؍‬ 1.47-3.66, P c ‫؍‬ 0.0020). Carriership of the MICA 5.1 allele was associated with resistance against CCA (OR ‫؍‬ 0.43, 95% CI ‫؍‬ 0.20-0.95, not corrected P ‫؍‬ 0.032). Conclusion: Our results show that genetic variants of the NKG2D receptor are associated with development of CCA in PSC patients. This suggests that interaction between NKG2D and MICA is involved in protection against CCA in PSC. Patients who are homozygous for the nonrisk alleles are unlikely to develop CCA; this finding could be helpful in identifying PSC patients with a low CCA risk. (HEPATOLOGY 2008;47:90-96.)

Medicinal Chemistry, 2012

Kaempferol-3-O--L-rhamanopyranosyl-(1 -6 )--D-glucopyranoside (1) (Nicotiflorin or kaempferol-3-O... more Kaempferol-3-O--L-rhamanopyranosyl-(1 -6 )--D-glucopyranoside (1) (Nicotiflorin or kaempferol-3-Orutinoside), isolated from the aerial parts of Osyris wightiana Wall. ex Wight, has exhibited a potent antiglycation activity in vitro. A short and efficient route to kaempferol-3-O-rutinoside (1) is also described in this paper. To study the Structure-Activity Relationship (SAR), few other derivatives of kaempferol were also evaluated for their antiglycation activity. Moreover the cytotoxicity analysis was also performed for these compounds prepared and SAR studies showed that sugar derivatives of kaempferol possess a promising antiglycation activity.

Medicinal Chemistry, 2013

Computational tools of analysis were used on a set of synthetic chromone containing sulfonamide d... more Computational tools of analysis were used on a set of synthetic chromone containing sulfonamide derivatives for evaluation of their enzyme inhibitory activity against Carbonic Anhydrase (CA) isozymes. GOLD docking software was utilized to dock the compounds against two human Carbonic Anhydrase (hCA) proteins; hCAII and hCA-IX. Differences in conformation and orientation of molecules within hCA-II and hCA-IX binding pockets were studied in detail which revealed that compounds with fluorine at R1 position and phenyl sulfonamide substituent at para position served as potent inhibitors against both proteins due to anomalous chemistry of fluorine atom. It was also noticed that the activity was decreased when sulfonamide moiety was shifted from para to meta position since it dragged the interacting specie of compounds away from Zn metal. Similarly, when substituents were replaced by F > Br > C2H5 > H, the activity declined due to the electronegativity effect. Binding interaction results against CA-IX seemed to be better than CA-II due to large binding cavity, predicting the more potent inhibitory activity against hCA-IX.

Expert Opinion on Pharmacotherapy, 2010

Primary biliary cirrhosis is a cholestatic liver disease that at one time was the leading indicat... more Primary biliary cirrhosis is a cholestatic liver disease that at one time was the leading indication for liver transplantation. Treatment with ursodeoxycholic acid has clearly improved the natural history of primary biliary cirrhosis. The treatment of primary biliary cirrhosis with a focus on ursodeoxycholic acid is covered. Papers related to treatment of primary biliary cirrhosis and associated conditions, using a variety of drugs but with a focus on ursodeoxycholic acid, are included. The papers reviewed date from 1984 - 2009. The reader will gain an up-to-date understanding of current treatment strategies for primary biliary cirrhosis using ursodeoxycholic acid and an appreciation of what conditions are improved with this therapy and what associated conditions are not. Ursodeoxycholic acid in a dose of 13 - 15 mg/kg/day should be considered in all patients with primary biliary cirrhosis who have abnormal liver enzymes.

Bioorganic & Medicinal Chemistry, 2011

Series of chromone containing sulfonamides were prepared by the reaction of (un)substituted 3-for... more Series of chromone containing sulfonamides were prepared by the reaction of (un)substituted 3-formylchromones with 3-aminobenzenesulfonamide and 4-aminobenzenesulfonamide. Bovine carbonic anhydrase (bCA) inhibitory activity of these newly synthesized compounds was determined. All compounds were active and possessed excellent bCA inhibitory activities with IC 50 values ranged between 4.31 ± 0.001 and 29.12 ± 0.008 lmol. Compounds derived from 6-fluoro-3-formylchromones were the most active.

Seminars in Thoracic and Cardiovascular Surgery, 2005

The metaplastic change of the normal squamous epithelium of the distal esophagus into a specializ... more The metaplastic change of the normal squamous epithelium of the distal esophagus into a specialized columnar epithelium is known as Barrett's esophagus (BE) and is associated with an increased risk of adenocarcinoma of the esophagus. It is a frequent complication of gastroesophageal reflux disease (GERD) and up to 10% of patients with GERD suffer from BE. The progression to dysplasia increases the risk of cancer development and the annual risk of developing cancer in Barrett's esophagus is estimated to be 0.5% per year. The management of BE with high grade dysplasia (HGD) is controversial. Recent innovations in endoscopic therapy have allowed for the development of multiple endoscopic techniques, such as photodynamic therapy (PDT), argon plasma coagulation (APC), and endoscopic mucosal resection. In this article, we will discuss primarily photodynamic therapy, and other ablative technologies such as argon plasma coagulation in the treatment of BE. Semin Thorac Cardiovasc Surg 17:313-318

Pearson's Thoracic and Esophageal Surgery, 2008

Thoracic Surgery Clinics, 2007

RFA and SRS have been demonstrated to be safe with reasonable efficacy in the treatment of small ... more RFA and SRS have been demonstrated to be safe with reasonable efficacy in the treatment of small lung tumors. It is unclear which option is the most effective in the treatment of NSCLC, with both RFA and SRS demonstrating similar early response and progression rates. RFA can be performed in one treatment session, whereas it now seems that SRS is more effective if larger doses of radiation over two to three fractions are performed. RFA is not recommended for centrally based tumors. There are also some tumors (eg, small apical tumors, posteriorly positioned tumors close to the diaphragm, and tumors close to the scapula) where it may be difficult percutaneously to position an active electrode. Such patients are more optimally treated with SRS. In certain circumstances, a combined approach may be beneficial (RFA and SRS). At this point in time, MWA is the least well developed modality. Although treatment times and heat-sink effect may be less compared with RFA, larger trials are needed to understand better the impact of this factor on effectiveness and safety. The heat-sink effect may be protective, minimizing the necrosis of large blood vessels and the risk of subsequent fatal hemoptysis. Future studies need to address long-term outcomes using standardized assessments of treatment response between centers. Comparisons between different RFA systems and ablation modalities need to be undertaken to delineate the optimal use of these strategies in the treatment of early stage lung cancer. Until long-term data with these ablative techniques become available, surgical resection should be performed when clinically possible.

Surgical Endoscopy, 2008

Background Elderly patients with achalasia are more frequently being referred for minimally invas... more Background Elderly patients with achalasia are more frequently being referred for minimally invasive Heller myotomy (MIM). The associated morbidity and mortality of MIM in the elderly are not well defined. The objective of this study was to review our experience with MIM in the elderly. Methods We identified a total of 57 patients (32 men, 25 women) 70 years or older (mean age 78 years, range 70 to 96 years) who underwent MIM [55 laparoscopically (LAP), 2 videothoracoscopically (VATS)] for achalasia at our institution. Clinical outcomes were analyzed including postoperative surgical interventions (redo myotomy, esophagectomy), and dysphagia scores (range: 1, no dysphagia to 5, dysphagia to saliva). Results Thirty-seven (59.6%) patients had prior endoscopic therapy. There was no perioperative mortality and median hospital stay was 3 days. There were three (5.3%) conversions to open due to adhesions and concern regarding the viability of the myotomy following repair of a small perforation. A total of 11 (19.3%) patients had complications, including three (5.3%) intraoperative esophageal perforations, three pleural effusions, one (1.8%) pneumonia, one intraoperative gastric perforation, one C. difficile infection, one ileus, and one postoperative intubation. Mean follow-up was 23.5 months. Mean

Surgery, 2001

The management of cytologically benign thyroid cysts is controversial. Treatment options include ... more The management of cytologically benign thyroid cysts is controversial. Treatment options include observation, chemical sclerosis, and surgery. This study was undertaken to determine the incidence of carcinoma in cytologically benign thyroid cysts that recur after complete aspiration and to determine the indications for surgery in these patients. The medical records of 1189 consecutive patients undergoing thyroid surgery between July 1995 and November 2000 were reviewed. In 34 patients the indication for surgery was a thyroid cyst with benign cytologic findings that refilled at least once after complete aspiration. These patients were selected for further study. The 26 women and 8 men had a median age of 42 years. Fine-needle aspiration cytology was consistent with a benign cyst in all these cases. Final pathologic findings revealed the nodule to be a papillary carcinoma in 4 patients (12%). In another 4 patients (12%) an incidental microscopic papillary carcinoma, separate from the cyst, was identified on final pathologic findings. In all 4 patients with papillary carcinoma the cyst size was greater than 3 cm (range, 3.4 to 5.0 cm). The incidence of malignancy in cytologically benign thyroid cysts that recur after aspiration is high enough to warrant surgical excision, especially if the cyst is greater than 3 cm in size.

Surgery, 2009

Esophageal perforation is an important therapeutic challenge. We hypothesized that patients with ... more Esophageal perforation is an important therapeutic challenge. We hypothesized that patients with minimal mediastinal contamination at the time of diagnosis could be managed successfully with nonoperative treatment modalities. We performed a retrospective review of 119 consecutive patients with esophageal perforation from 1998 to 2008. Demographics, cause of perforation, clinical presentation, diagnostic methods, and management results were evaluated. The decision to operate was based on the extent of mediastinal contamination and systemic sepsis rather than cause of perforation. Median time to diagnosis among all patients was 12 hours (range, 1-120). Spontaneous (Boerhaave's) perforation occurred in 44 (37%) patients. Iatrogenic perforations constituted the remaining patients (n = 75). After instrumental perforation, 9 patients (13%) required esophagectomy, 48 patients were managed with repair and drainage, and the remaining 18 were managed nonoperatively. All 34 patients undergoing operative therapy for spontaneous perforations were treated with esophageal repair. Overall mortality was 14%, with intrathoracic perforations having 18% mortality, cervical 8%, and gastroesophageal junction 3%. Patients undergoing nonoperative therapy had a shorter hospitalizations (13 vs 24 days), fewer complications (36% vs 62%), and less mortality (4% vs 15%) compared with those undergoing operative intervention. An approach to esophageal perforation based on injury severity and the degree of mediastinal and pleural contamination is of paramount importance. Although operative management remains the standard in the majority of patients with esophageal perforation, nonoperative management may be successfully implemented in selected patients with a low morbidity and mortality if favorable radiographic and clinical characteristics are present.

Surgery, 2010

The development of anastomotic leaks and/or strictures can be associated with considerable morbid... more The development of anastomotic leaks and/or strictures can be associated with considerable morbidity and impairment of quality of life. In the current study, we evaluated the outcomes of patients who developed anastomotic complications after esophagectomy to elucidate the impact of these events on morbidity, mortality, and subsequent need for dilation.We analyzed retrospectively the clinical course of 235 patients who underwent transhiatal esophagectomy for cancer from 2001 to 2009. Patients with confirmed anastomotic leaks were identified and classified with the following scale: class 1: Radiographic leak only, no intervention; class 2: leak requiring opening of the wound, cervical and/or percutaneous drainage; class 3: disruption of anastomosis (10–50% circumference) with perianastomotic abscess requiring video-assisted thoracoscopic surgery or thoracotomy; and class 4: gastric tip necrosis with anastomotic separation (>50% circumference).Anastomotic leaks were encountered in 30 patients (13%). Anastomotic leaks were associated with greater morbidity (70% vs 47%; P = .02) and stricture formation (57% vs 19%; P = .0001). Mortality was not different. Increasing leak class was associated with an increased need for postoperative anastomotic dilations (P = .016).Anastomotic integrity after esophagectomy has a substantial impact on perioperative course and long-term swallowing. A more formal radiographic and endoscopic leak classification system seems justified.

Journal of Surgical Oncology, 2000

Lung cancer is the most common cause of cancer-related mortality in the United States. Surgical r... more Lung cancer is the most common cause of cancer-related mortality in the United States. Surgical resection remains the standard treatment for early stage, non-small cell lung cancer, and limited pulmonary metastases. However, many patients with resectable disease have significant co-morbidities which preclude surgical resection. Radiofrequency and microwave ablation are emerging modalities of treatment for these high-risk patients. Here, we review the principles, common devices in use, and treatment results of ablative therapy for lung tumors.

Journal of Cardiac Surgery, 2004

Background: Spontaneous right ventricular disruption is a rare and frequently catastrophic event ... more Background: Spontaneous right ventricular disruption is a rare and frequently catastrophic event that occurs during the treatment of mediastinitis complicating median sternotomy wound. Objective: The purpose of this study is to understand the pathogenesis of the spontaneous right ventricular disruption and to suggest strategies for the prevention and treatment of this rare but potentially fatal complication of cardiac surgery. Methods: We report three cases as an introduction to the review of 39 cases found in the English-language literature. Results: The majority of patients (71%) underwent coronary artery bypass grafting as the primary procedure prior to the development of a sternal infection. Staphylococcus Aureus and Staphylococcus Epidermidis were cultured most frequently from the sternal wound (31% and 24%, respectively). The mean interval between sternal debridement and the right ventricular disruption was 2.9 days. Most patients (24 of 42) required cardiopulmonary bypass for the repair of the right ventricular disruption. Biologic patches and adjuncts were used in 15 patients (36%). Eight patients (19%) died either preoperatively or on the operating-room table. Conclusions: Spontaneous right ventricular disruption is a potentially preventable complication. To prevent this complication we recommend: (1) avoidance of delay between diagnosis and operative treatment of mediastinitis; (2) complete lysis of adhesions between the posterior sternal edge and anterior surface of the right ventricle under general anesthesia with heart-lung machine stand-by; (3) repair of the right ventricular tear using biologic patches with heart-lung machine stand-by; (4) early (if possible immediate) closure of the chest with a myocutaneous flap

International Journal of Surgery, 2010

Esophageal cancer continues to be a lethal disease with the majority of patients presenting at an... more Esophageal cancer continues to be a lethal disease with the majority of patients presenting at an advanced stage. The incidence of adenocarcinoma is rising. Although Barrett's esophagus has been well characterized, specific pathways to the development of adenocarcinoma remain undefined. Current treatments for locoregional esophageal cancer include surgery, chemotherapy, radiation therapy, or a combination of these modalities. Optimal surgical treatment strategies include appropriate patient selection, accurate staging and risk assessment, selection of an appropriate surgical approach, and the use of multimodality treatment. This article provides an update on the myriad of options for managing esophageal cancer and outlines the surgical technique for minimally invasive esophagectomy used at our center.

Annals of Thoracic Surgery, 2009

Background. Surgical resection is the standard of care for patients with resectable non-small cel... more Background. Surgical resection is the standard of care for patients with resectable non-small cell lung carcinoma (NSCLC) or limited pulmonary metastases. Stereotactic radiosurgery (SRS) may offer an alternative option for high-risk patients who are not surgical candidates. We report our initial experience with SRS in the treatment of lung neoplasm.

Journal of Molecular Biology, 2009

Esophageal perforation is an important therapeutic challenge. We hypothesized that patients with ... more Esophageal perforation is an important therapeutic challenge. We hypothesized that patients with minimal mediastinal contamination at the time of diagnosis could be managed successfully with nonoperative treatment modalities.We performed a retrospective review of 119 consecutive patients with esophageal perforation from 1998 to 2008. Demographics, cause of perforation, clinical presentation, diagnostic methods, and management results were evaluated. The decision to operate was based on the extent of mediastinal contamination and systemic sepsis rather than cause of perforation.Median time to diagnosis among all patients was 12 hours (range, 1–120). Spontaneous (Boerhaave's) perforation occurred in 44 (37%) patients. Iatrogenic perforations constituted the remaining patients (n = 75). After instrumental perforation, 9 patients (13%) required esophagectomy, 48 patients were managed with repair and drainage, and the remaining 18 were managed nonoperatively. All 34 patients undergoing operative therapy for spontaneous perforations were treated with esophageal repair. Overall mortality was 14%, with intrathoracic perforations having 18% mortality, cervical 8%, and gastroesophageal junction 3%. Patients undergoing nonoperative therapy had a shorter hospitalizations (13 vs 24 days), fewer complications (36% vs 62%), and less mortality (4% vs 15%) compared with those undergoing operative intervention.An approach to esophageal perforation based on injury severity and the degree of mediastinal and pleural contamination is of paramount importance. Although operative management remains the standard in the majority of patients with esophageal perforation, nonoperative management may be successfully implemented in selected patients with a low morbidity and mortality if favorable radiographic and clinical characteristics are present.

Surgery, 2001

Background. The management of cytologically benign thyroid cysts is controversial. Treatment opti... more Background. The management of cytologically benign thyroid cysts is controversial. Treatment options include observation, chemical sclerosis, and surgery. This study was undertaken to determine the incidence of carcinoma in cytologically benign thyroid cysts that recur after complete aspiration and to determine the indications for surgery in these patients. Methods. The medical records of 1189 consecutive patients undergoing thyroid surgery between July 1995 and November 2000 were reviewed. In 34 patients the indication for surgery was a thyroid cyst with benign cytologic findings that refilled at least once after complete aspiration. These patients were selected for further study. Results. The 26 women and 8 men had a median age of 42 years. Fine-needle aspiration cytology was consistent with a benign cyst in all these cases. Final pathologic findings revealed the nodule to be a papillary carcinoma in 4 patients (12%). In another 4 patients (12%) an incidental microscopic papillary carcinoma, separate from the cyst, was identified on final pathologic findings. In all 4 patients with papillary carcinoma the cyst size was greater than 3 cm (range, 3.4 to 5.0 cm). Conclusions. The incidence of malignancy in cytologically benign thyroid cysts that recur after aspiration is high enough to warrant surgical excision, especially if the cyst is greater than 3 cm in size. (Surgery 2001;130:1035-8.)

Journal of Thoracic and Cardiovascular Surgery, 2009

The Annals of Thoracic Surgery CME Program is located online at http://cme.ctsnetjournals.org. To... more The Annals of Thoracic Surgery CME Program is located online at http://cme.ctsnetjournals.org. To take the CME activity related to this article, you must have either an STS member or an individual non-member subscription to the journal.

Nature Reviews Gastroenterology & Hepatology, 2010

Primary biliary cirrhosis (PBC) is a chronic, autoimmune, cholestatic liver disease with a slowly... more Primary biliary cirrhosis (PBC) is a chronic, autoimmune, cholestatic liver disease with a slowly progressive course. Without treatment, most patients eventually develop fibrosis of the liver and may need liver transplantation in the late stage of disease. Fatigue and pruritus are the most common symptoms of PBC, but the majority of patients are asymptomatic at first presentation. There is no specific treatment for fatigue in PBC, but modafinil has shown some potential beneficial effects, such as increased energy levels and decreased total sleep time. This Review article discusses the natural history and the measurement of fatigue in patients with PBC. The central and the peripheral mechanisms that have been suggested for the pathogenesis of fatigue in PBC are also discussed and treatment options are reviewed.

Journal of Gastrointestinal Cancer, 2009

Primary sclerosing cholangitis (PSC) is often complicated by the development of cholangiocarcinom... more Primary sclerosing cholangitis (PSC) is often complicated by the development of cholangiocarcinoma (CCA). Genetic variation of natural killer cell receptor G2D (NKG2D) has been associated with cancer susceptibility. An important ligand for NKG2D, major histocompatibility complex class I chain-related molecule A (MICA), serves as a marker of cellular stress. The 5.1 allele of the gene encoding MICA has been associated with PSC. In this study, we aimed to investigate the influence of genetic variations in the NKG2D-MICA receptor-ligand pair on the risk of CCA in patients with PSC. Seven single nucleotide polymorphisms (SNPs) covering the NKG2D gene were genotyped in 365 Scandinavian PSC patients and 368 healthy controls with TaqMan technology. Genotype data on the MICA 5.1 variant were available from previous studies. Forty-nine of the PSC patients (13.6%) had developed CCA at the time of study. Two of the NKG2D SNPs were associated with an increased risk of CCA: rs11053781 [odds ratio (OR) ‫؍‬ 2.08, 95% confidence interval (CI) ‫؍‬ 1.31-3.29, corrected P (P c ) ‫؍‬ 0.011] and rs2617167 (OR ‫؍‬ 2.32, 95% CI ‫؍‬ 1.47-3.66, P c ‫؍‬ 0.0020). Carriership of the MICA 5.1 allele was associated with resistance against CCA (OR ‫؍‬ 0.43, 95% CI ‫؍‬ 0.20-0.95, not corrected P ‫؍‬ 0.032). Conclusion: Our results show that genetic variants of the NKG2D receptor are associated with development of CCA in PSC patients. This suggests that interaction between NKG2D and MICA is involved in protection against CCA in PSC. Patients who are homozygous for the nonrisk alleles are unlikely to develop CCA; this finding could be helpful in identifying PSC patients with a low CCA risk. (HEPATOLOGY 2008;47:90-96.)

Medicinal Chemistry, 2012

Kaempferol-3-O--L-rhamanopyranosyl-(1 -6 )--D-glucopyranoside (1) (Nicotiflorin or kaempferol-3-O... more Kaempferol-3-O--L-rhamanopyranosyl-(1 -6 )--D-glucopyranoside (1) (Nicotiflorin or kaempferol-3-Orutinoside), isolated from the aerial parts of Osyris wightiana Wall. ex Wight, has exhibited a potent antiglycation activity in vitro. A short and efficient route to kaempferol-3-O-rutinoside (1) is also described in this paper. To study the Structure-Activity Relationship (SAR), few other derivatives of kaempferol were also evaluated for their antiglycation activity. Moreover the cytotoxicity analysis was also performed for these compounds prepared and SAR studies showed that sugar derivatives of kaempferol possess a promising antiglycation activity.

Medicinal Chemistry, 2013

Computational tools of analysis were used on a set of synthetic chromone containing sulfonamide d... more Computational tools of analysis were used on a set of synthetic chromone containing sulfonamide derivatives for evaluation of their enzyme inhibitory activity against Carbonic Anhydrase (CA) isozymes. GOLD docking software was utilized to dock the compounds against two human Carbonic Anhydrase (hCA) proteins; hCAII and hCA-IX. Differences in conformation and orientation of molecules within hCA-II and hCA-IX binding pockets were studied in detail which revealed that compounds with fluorine at R1 position and phenyl sulfonamide substituent at para position served as potent inhibitors against both proteins due to anomalous chemistry of fluorine atom. It was also noticed that the activity was decreased when sulfonamide moiety was shifted from para to meta position since it dragged the interacting specie of compounds away from Zn metal. Similarly, when substituents were replaced by F > Br > C2H5 > H, the activity declined due to the electronegativity effect. Binding interaction results against CA-IX seemed to be better than CA-II due to large binding cavity, predicting the more potent inhibitory activity against hCA-IX.

Expert Opinion on Pharmacotherapy, 2010

Primary biliary cirrhosis is a cholestatic liver disease that at one time was the leading indicat... more Primary biliary cirrhosis is a cholestatic liver disease that at one time was the leading indication for liver transplantation. Treatment with ursodeoxycholic acid has clearly improved the natural history of primary biliary cirrhosis. The treatment of primary biliary cirrhosis with a focus on ursodeoxycholic acid is covered. Papers related to treatment of primary biliary cirrhosis and associated conditions, using a variety of drugs but with a focus on ursodeoxycholic acid, are included. The papers reviewed date from 1984 - 2009. The reader will gain an up-to-date understanding of current treatment strategies for primary biliary cirrhosis using ursodeoxycholic acid and an appreciation of what conditions are improved with this therapy and what associated conditions are not. Ursodeoxycholic acid in a dose of 13 - 15 mg/kg/day should be considered in all patients with primary biliary cirrhosis who have abnormal liver enzymes.

Bioorganic & Medicinal Chemistry, 2011

Series of chromone containing sulfonamides were prepared by the reaction of (un)substituted 3-for... more Series of chromone containing sulfonamides were prepared by the reaction of (un)substituted 3-formylchromones with 3-aminobenzenesulfonamide and 4-aminobenzenesulfonamide. Bovine carbonic anhydrase (bCA) inhibitory activity of these newly synthesized compounds was determined. All compounds were active and possessed excellent bCA inhibitory activities with IC 50 values ranged between 4.31 ± 0.001 and 29.12 ± 0.008 lmol. Compounds derived from 6-fluoro-3-formylchromones were the most active.

Seminars in Thoracic and Cardiovascular Surgery, 2005

The metaplastic change of the normal squamous epithelium of the distal esophagus into a specializ... more The metaplastic change of the normal squamous epithelium of the distal esophagus into a specialized columnar epithelium is known as Barrett's esophagus (BE) and is associated with an increased risk of adenocarcinoma of the esophagus. It is a frequent complication of gastroesophageal reflux disease (GERD) and up to 10% of patients with GERD suffer from BE. The progression to dysplasia increases the risk of cancer development and the annual risk of developing cancer in Barrett's esophagus is estimated to be 0.5% per year. The management of BE with high grade dysplasia (HGD) is controversial. Recent innovations in endoscopic therapy have allowed for the development of multiple endoscopic techniques, such as photodynamic therapy (PDT), argon plasma coagulation (APC), and endoscopic mucosal resection. In this article, we will discuss primarily photodynamic therapy, and other ablative technologies such as argon plasma coagulation in the treatment of BE. Semin Thorac Cardiovasc Surg 17:313-318

Pearson's Thoracic and Esophageal Surgery, 2008

Thoracic Surgery Clinics, 2007

RFA and SRS have been demonstrated to be safe with reasonable efficacy in the treatment of small ... more RFA and SRS have been demonstrated to be safe with reasonable efficacy in the treatment of small lung tumors. It is unclear which option is the most effective in the treatment of NSCLC, with both RFA and SRS demonstrating similar early response and progression rates. RFA can be performed in one treatment session, whereas it now seems that SRS is more effective if larger doses of radiation over two to three fractions are performed. RFA is not recommended for centrally based tumors. There are also some tumors (eg, small apical tumors, posteriorly positioned tumors close to the diaphragm, and tumors close to the scapula) where it may be difficult percutaneously to position an active electrode. Such patients are more optimally treated with SRS. In certain circumstances, a combined approach may be beneficial (RFA and SRS). At this point in time, MWA is the least well developed modality. Although treatment times and heat-sink effect may be less compared with RFA, larger trials are needed to understand better the impact of this factor on effectiveness and safety. The heat-sink effect may be protective, minimizing the necrosis of large blood vessels and the risk of subsequent fatal hemoptysis. Future studies need to address long-term outcomes using standardized assessments of treatment response between centers. Comparisons between different RFA systems and ablation modalities need to be undertaken to delineate the optimal use of these strategies in the treatment of early stage lung cancer. Until long-term data with these ablative techniques become available, surgical resection should be performed when clinically possible.

Surgical Endoscopy, 2008

Background Elderly patients with achalasia are more frequently being referred for minimally invas... more Background Elderly patients with achalasia are more frequently being referred for minimally invasive Heller myotomy (MIM). The associated morbidity and mortality of MIM in the elderly are not well defined. The objective of this study was to review our experience with MIM in the elderly. Methods We identified a total of 57 patients (32 men, 25 women) 70 years or older (mean age 78 years, range 70 to 96 years) who underwent MIM [55 laparoscopically (LAP), 2 videothoracoscopically (VATS)] for achalasia at our institution. Clinical outcomes were analyzed including postoperative surgical interventions (redo myotomy, esophagectomy), and dysphagia scores (range: 1, no dysphagia to 5, dysphagia to saliva). Results Thirty-seven (59.6%) patients had prior endoscopic therapy. There was no perioperative mortality and median hospital stay was 3 days. There were three (5.3%) conversions to open due to adhesions and concern regarding the viability of the myotomy following repair of a small perforation. A total of 11 (19.3%) patients had complications, including three (5.3%) intraoperative esophageal perforations, three pleural effusions, one (1.8%) pneumonia, one intraoperative gastric perforation, one C. difficile infection, one ileus, and one postoperative intubation. Mean follow-up was 23.5 months. Mean

Surgery, 2001

The management of cytologically benign thyroid cysts is controversial. Treatment options include ... more The management of cytologically benign thyroid cysts is controversial. Treatment options include observation, chemical sclerosis, and surgery. This study was undertaken to determine the incidence of carcinoma in cytologically benign thyroid cysts that recur after complete aspiration and to determine the indications for surgery in these patients. The medical records of 1189 consecutive patients undergoing thyroid surgery between July 1995 and November 2000 were reviewed. In 34 patients the indication for surgery was a thyroid cyst with benign cytologic findings that refilled at least once after complete aspiration. These patients were selected for further study. The 26 women and 8 men had a median age of 42 years. Fine-needle aspiration cytology was consistent with a benign cyst in all these cases. Final pathologic findings revealed the nodule to be a papillary carcinoma in 4 patients (12%). In another 4 patients (12%) an incidental microscopic papillary carcinoma, separate from the cyst, was identified on final pathologic findings. In all 4 patients with papillary carcinoma the cyst size was greater than 3 cm (range, 3.4 to 5.0 cm). The incidence of malignancy in cytologically benign thyroid cysts that recur after aspiration is high enough to warrant surgical excision, especially if the cyst is greater than 3 cm in size.

Surgery, 2009

Esophageal perforation is an important therapeutic challenge. We hypothesized that patients with ... more Esophageal perforation is an important therapeutic challenge. We hypothesized that patients with minimal mediastinal contamination at the time of diagnosis could be managed successfully with nonoperative treatment modalities. We performed a retrospective review of 119 consecutive patients with esophageal perforation from 1998 to 2008. Demographics, cause of perforation, clinical presentation, diagnostic methods, and management results were evaluated. The decision to operate was based on the extent of mediastinal contamination and systemic sepsis rather than cause of perforation. Median time to diagnosis among all patients was 12 hours (range, 1-120). Spontaneous (Boerhaave's) perforation occurred in 44 (37%) patients. Iatrogenic perforations constituted the remaining patients (n = 75). After instrumental perforation, 9 patients (13%) required esophagectomy, 48 patients were managed with repair and drainage, and the remaining 18 were managed nonoperatively. All 34 patients undergoing operative therapy for spontaneous perforations were treated with esophageal repair. Overall mortality was 14%, with intrathoracic perforations having 18% mortality, cervical 8%, and gastroesophageal junction 3%. Patients undergoing nonoperative therapy had a shorter hospitalizations (13 vs 24 days), fewer complications (36% vs 62%), and less mortality (4% vs 15%) compared with those undergoing operative intervention. An approach to esophageal perforation based on injury severity and the degree of mediastinal and pleural contamination is of paramount importance. Although operative management remains the standard in the majority of patients with esophageal perforation, nonoperative management may be successfully implemented in selected patients with a low morbidity and mortality if favorable radiographic and clinical characteristics are present.

Surgery, 2010

The development of anastomotic leaks and/or strictures can be associated with considerable morbid... more The development of anastomotic leaks and/or strictures can be associated with considerable morbidity and impairment of quality of life. In the current study, we evaluated the outcomes of patients who developed anastomotic complications after esophagectomy to elucidate the impact of these events on morbidity, mortality, and subsequent need for dilation.We analyzed retrospectively the clinical course of 235 patients who underwent transhiatal esophagectomy for cancer from 2001 to 2009. Patients with confirmed anastomotic leaks were identified and classified with the following scale: class 1: Radiographic leak only, no intervention; class 2: leak requiring opening of the wound, cervical and/or percutaneous drainage; class 3: disruption of anastomosis (10–50% circumference) with perianastomotic abscess requiring video-assisted thoracoscopic surgery or thoracotomy; and class 4: gastric tip necrosis with anastomotic separation (>50% circumference).Anastomotic leaks were encountered in 30 patients (13%). Anastomotic leaks were associated with greater morbidity (70% vs 47%; P = .02) and stricture formation (57% vs 19%; P = .0001). Mortality was not different. Increasing leak class was associated with an increased need for postoperative anastomotic dilations (P = .016).Anastomotic integrity after esophagectomy has a substantial impact on perioperative course and long-term swallowing. A more formal radiographic and endoscopic leak classification system seems justified.

Journal of Surgical Oncology, 2000

Lung cancer is the most common cause of cancer-related mortality in the United States. Surgical r... more Lung cancer is the most common cause of cancer-related mortality in the United States. Surgical resection remains the standard treatment for early stage, non-small cell lung cancer, and limited pulmonary metastases. However, many patients with resectable disease have significant co-morbidities which preclude surgical resection. Radiofrequency and microwave ablation are emerging modalities of treatment for these high-risk patients. Here, we review the principles, common devices in use, and treatment results of ablative therapy for lung tumors.

Journal of Cardiac Surgery, 2004

Background: Spontaneous right ventricular disruption is a rare and frequently catastrophic event ... more Background: Spontaneous right ventricular disruption is a rare and frequently catastrophic event that occurs during the treatment of mediastinitis complicating median sternotomy wound. Objective: The purpose of this study is to understand the pathogenesis of the spontaneous right ventricular disruption and to suggest strategies for the prevention and treatment of this rare but potentially fatal complication of cardiac surgery. Methods: We report three cases as an introduction to the review of 39 cases found in the English-language literature. Results: The majority of patients (71%) underwent coronary artery bypass grafting as the primary procedure prior to the development of a sternal infection. Staphylococcus Aureus and Staphylococcus Epidermidis were cultured most frequently from the sternal wound (31% and 24%, respectively). The mean interval between sternal debridement and the right ventricular disruption was 2.9 days. Most patients (24 of 42) required cardiopulmonary bypass for the repair of the right ventricular disruption. Biologic patches and adjuncts were used in 15 patients (36%). Eight patients (19%) died either preoperatively or on the operating-room table. Conclusions: Spontaneous right ventricular disruption is a potentially preventable complication. To prevent this complication we recommend: (1) avoidance of delay between diagnosis and operative treatment of mediastinitis; (2) complete lysis of adhesions between the posterior sternal edge and anterior surface of the right ventricle under general anesthesia with heart-lung machine stand-by; (3) repair of the right ventricular tear using biologic patches with heart-lung machine stand-by; (4) early (if possible immediate) closure of the chest with a myocutaneous flap

International Journal of Surgery, 2010

Esophageal cancer continues to be a lethal disease with the majority of patients presenting at an... more Esophageal cancer continues to be a lethal disease with the majority of patients presenting at an advanced stage. The incidence of adenocarcinoma is rising. Although Barrett's esophagus has been well characterized, specific pathways to the development of adenocarcinoma remain undefined. Current treatments for locoregional esophageal cancer include surgery, chemotherapy, radiation therapy, or a combination of these modalities. Optimal surgical treatment strategies include appropriate patient selection, accurate staging and risk assessment, selection of an appropriate surgical approach, and the use of multimodality treatment. This article provides an update on the myriad of options for managing esophageal cancer and outlines the surgical technique for minimally invasive esophagectomy used at our center.

Annals of Thoracic Surgery, 2009

Background. Surgical resection is the standard of care for patients with resectable non-small cel... more Background. Surgical resection is the standard of care for patients with resectable non-small cell lung carcinoma (NSCLC) or limited pulmonary metastases. Stereotactic radiosurgery (SRS) may offer an alternative option for high-risk patients who are not surgical candidates. We report our initial experience with SRS in the treatment of lung neoplasm.

Journal of Molecular Biology, 2009

Esophageal perforation is an important therapeutic challenge. We hypothesized that patients with ... more Esophageal perforation is an important therapeutic challenge. We hypothesized that patients with minimal mediastinal contamination at the time of diagnosis could be managed successfully with nonoperative treatment modalities.We performed a retrospective review of 119 consecutive patients with esophageal perforation from 1998 to 2008. Demographics, cause of perforation, clinical presentation, diagnostic methods, and management results were evaluated. The decision to operate was based on the extent of mediastinal contamination and systemic sepsis rather than cause of perforation.Median time to diagnosis among all patients was 12 hours (range, 1–120). Spontaneous (Boerhaave's) perforation occurred in 44 (37%) patients. Iatrogenic perforations constituted the remaining patients (n = 75). After instrumental perforation, 9 patients (13%) required esophagectomy, 48 patients were managed with repair and drainage, and the remaining 18 were managed nonoperatively. All 34 patients undergoing operative therapy for spontaneous perforations were treated with esophageal repair. Overall mortality was 14%, with intrathoracic perforations having 18% mortality, cervical 8%, and gastroesophageal junction 3%. Patients undergoing nonoperative therapy had a shorter hospitalizations (13 vs 24 days), fewer complications (36% vs 62%), and less mortality (4% vs 15%) compared with those undergoing operative intervention.An approach to esophageal perforation based on injury severity and the degree of mediastinal and pleural contamination is of paramount importance. Although operative management remains the standard in the majority of patients with esophageal perforation, nonoperative management may be successfully implemented in selected patients with a low morbidity and mortality if favorable radiographic and clinical characteristics are present.

Surgery, 2001

Background. The management of cytologically benign thyroid cysts is controversial. Treatment opti... more Background. The management of cytologically benign thyroid cysts is controversial. Treatment options include observation, chemical sclerosis, and surgery. This study was undertaken to determine the incidence of carcinoma in cytologically benign thyroid cysts that recur after complete aspiration and to determine the indications for surgery in these patients. Methods. The medical records of 1189 consecutive patients undergoing thyroid surgery between July 1995 and November 2000 were reviewed. In 34 patients the indication for surgery was a thyroid cyst with benign cytologic findings that refilled at least once after complete aspiration. These patients were selected for further study. Results. The 26 women and 8 men had a median age of 42 years. Fine-needle aspiration cytology was consistent with a benign cyst in all these cases. Final pathologic findings revealed the nodule to be a papillary carcinoma in 4 patients (12%). In another 4 patients (12%) an incidental microscopic papillary carcinoma, separate from the cyst, was identified on final pathologic findings. In all 4 patients with papillary carcinoma the cyst size was greater than 3 cm (range, 3.4 to 5.0 cm). Conclusions. The incidence of malignancy in cytologically benign thyroid cysts that recur after aspiration is high enough to warrant surgical excision, especially if the cyst is greater than 3 cm in size. (Surgery 2001;130:1035-8.)

Journal of Thoracic and Cardiovascular Surgery, 2009

The Annals of Thoracic Surgery CME Program is located online at http://cme.ctsnetjournals.org. To... more The Annals of Thoracic Surgery CME Program is located online at http://cme.ctsnetjournals.org. To take the CME activity related to this article, you must have either an STS member or an individual non-member subscription to the journal.