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Biomedical subjects

Girish Mishra

Publications and source records attributed to Girish Mishra.

At least 19 recordsLinked to original sources
PubMed2006

A bifurcating pathway directs abscisic acid effects on stomatal closure and opening in Arabidopsis.

Terrestrial plants lose water primarily through stomata, pores on the leaves. The hormone abscisic acid (ABA) decreases water loss by regulating opening and closing of stomata. Here, we show that phospholipase Dalpha1 (PLDalpha1) mediates the ABA effects on stomata through interaction with a protein phosphatase 2C (PP2C) and a heterotrimeric GTP-binding protein (G protein) in Arabidopsis. PLDalpha1-produced phosphatidic acid (PA) binds to the ABI1 PP2C to signal ABA-promoted stomatal closure, whereas PLDalpha1 and PA interact with the Galpha subunit of heterotrimeric G protein to mediate ABA inhibition of stomatal opening. The results reveal a bifurcating signaling pathway that regulates plant water loss.

Abscisic Acid↗
PubMed2006

Determination of qualitative telomerase activity as an adjunct to the diagnosis of pancreatic adenocarcinoma by EUS-guided fine-needle aspiration.

BACKGROUND: Telomerase activity is up-regulated in pancreatic cancer. Hence, measurement of telomerase activity in pancreatic needle-biopsy specimens could assist in establishing a positive diagnosis in specimens that are inadequate for cytology. OBJECTIVE: To determine the sensitivity and specificity of telomerase activity for neoplasia in a series of EUS-guided fine-needle aspirate (EUS-FNA) biopsies of pancreatic mass lesions. DESIGN: Prospective, consecutive, non-randomized cohort. SETTING: Academic hospital, tertiary referral center. PATIENTS: Seventy-one patients with a pancreatic mass diagnosed by cross-sectional imaging. INTERVENTIONS: EUS-FNA of 52 solid and 18 cystic pancreatic lesions. MAIN OUTCOME MEASUREMENTS: (1) Cytologic diagnosis; (2) tissue telomerase activity by semi-quantitative polymerase chain reaction; (3) patient demographics; (4) clinical outcomes. RESULTS: Cytology results were positive for adenocarcinoma in 40 patients with a solid pancreatic mass; of these, telomerase activity was detected in 31. There were no telomerase false-positive results. Telomerase results were positive in 6 of the 7 patients (86%) who had negative cytology results and who eventually were found to have biopsy-proven adenocarcinoma. The sensitivity and specificity of telomerase activity for detecting pancreatic adenocarcinoma in solid masses was 79% (95% CI, 64%-89%) and 100% (95% CI, 55%-100%). LIMITATIONS: Extremely high sensitivity and specificity of EUS-FNA cytology in solid lesions minimized the incremental benefit of telomerase. CONCLUSIONS: Telomerase activity can be measured readily in specimens obtained at EUS-FNA and accurately predicts malignancy. Used in combination with cytology, telomerase increased the sensitivity from 85% to 98% while maintaining the specificity at 100%. Lesions with negative cytology result and positive telomerase activity should be evaluated aggressively to exclude malignancy.

Adenocarcinoma↗
PubMed2006

Predictive value of 18-fluoro-deoxy-glucose-positron emission tomography (18F-FDG-PET) in the identification of responders to chemoradiation therapy for the treatment of locally advanced esophageal cancer.

OBJECTIVE: To evaluate the utility of F-FDG-PET in predicting response to concomitant chemoradiation in locally-advanced esophageal cancer. SUMMARY BACKGROUND DATA: Approximately 25% of esophageal cancer patients experience a pathologic complete response (pCR) to preoperative chemoradiation therapy. Computed tomography, endoscopy, and endoscopic ultrasound are unable to identify patients experiencing a pCR. Growing evidence supports the use of F-FDG-PET in the staging of esophageal cancer in its ability to detect occult metastatic and lymph nodal disease. The identification of patients with a pCR to chemoradiation could potentially spare those patients the morbidity associated with a resection. METHODS: Eligibility criteria included T3-T4N0M0 or T1-T4N1M0 esophageal cancer. Patients underwent an initial F-FDG-PET before treatment and then repeated 4 to 6 weeks after chemoradiation, prior to the esophagectomy. Chemoradiation consisted of: cisplatinum, 5-fluorouracil, and radiation to a median dose of 50.4 Gy. Pathologic response was determined from a systematic review of the esophagectomy specimens. RESULTS: Sixty-four patients have completed therapy to date. Response was as follows: pCR 27%, pathologic residual microscopic (pCRmicro) 14.5%, partial response 19%, and stable or progressive disease 39.5%. A pretreatment standardized uptake value (SUVmax1hour) > or = 15 was associated with an observed 77.8% significant response (pCR + pCRmicro) compared with 24.2% for patients with a pretreatment SUVmax1hour < 15 (P = 0.005). Significant response was observed in 71.4% of patients with a decrease in SUVmax1hour > or = 10 compared with 33.3% when the SUVmax1hour decreased <10 (P = 0.004). CONCLUSIONS: Pretreatment and posttreatment F-FDG-PET can be useful for predicting significant response to chemoradiation in esophageal cancer. These data should be considered in evaluation of patients for esophagectomy after chemoradiation.

Adenocarcinoma↗
PubMed2005

A prospective evaluation of the impact of 18-F-fluoro-deoxy-D-glucose positron emission tomography staging on survival for patients with locally advanced esophageal cancer.

PURPOSE: To determine the impact of 18-F-fluoro-deoxy-D-glucose positron emission tomography (FDG-PET) in the staging and prognosis of patients with locally advanced esophageal cancer (LAEC). METHODS AND MATERIALS: Between January 2000 and October 2004, all patients with LAEC evaluated in the Department of Radiation Oncology were considered for enrollment into a Phase II trial of preoperative chemoradiation. Entry required a staging whole-body FDG-PET scan. RESULTS: One hundred ten consecutive patients were evaluated; 38 were ineligible for reasons including treatment elsewhere, prior malignancy, or refusal of treatment. After conventional staging (clinical examination, endoscopic ultrasound, and chest/abdominal computerized tomography), 33 patients were ineligible because of metastatic disease or poor performance status. Of the remaining 39 patients, 23 were confirmed to have LAEC after FDG-PET staging and were treated in the Phase II trial (Cohort I). Sixteen patients, however, had FDG-PET findings consistent with occult metastatic disease and were deemed ineligible for the trial but were treated with curative intent (Cohort II). The 2-year survival rate for the 23 patients in Cohort I was 64%, compared with 17% (p=0.003) for patients in Cohort II (FDG-PET positive). CONCLUSIONS: More than one-third of patients determined to have LAEC with conventional staging were upstaged with the use of FDG-PET. Despite comparable therapy, upstaging with FDG-PET predicts poor 2-year survival.

Adult↗
PubMed2005

Colchicine treatment of alcoholic cirrhosis: a randomized, placebo-controlled clinical trial of patient survival.

BACKGROUND & AIMS: Colchicine improved survival and reversed cirrhosis in several small clinical trials. We compared the efficacy and safety of long-term colchicine, as compared with placebo, in patients with advanced alcoholic cirrhosis. METHODS: Five hundred forty-nine patients with advanced (Pugh B or C) alcoholic cirrhosis were randomized to receive either colchicine 0.6 mg twice per day (n = 274) or placebo (n = 275). Treatment lasted from 2 to 6 years. The primary outcome was all-cause mortality. Secondary outcomes were liver-related morbidity and mortality. Liver biopsy was requested prior to entry and after 24 months of treatment. RESULTS: Attendance at scheduled clinic visits and adherence with study medication were similar in colchicine and placebo groups. Alcohol intake was less than 1 drink per day in 69% of patients. In an intention-to-treat analysis, all-cause mortality was similar in colchicine (49%) and placebo (45%) patients (P = .371). Mortality attributed to liver disease was 32% in colchicine and 28% in placebo patients (P = .337). Fewer patients receiving colchicine developed hepatorenal syndrome. In 54 patients with repeat liver biopsies after 24 or more months of treatment, cirrhosis improved to septal fibrosis in 7 patients (3 colchicine, 4 placebo) and to portal fibrosis in 1 patient (colchicine). CONCLUSIONS: In patients with advanced alcoholic cirrhosis, colchicine does not reduce overall or liver-specific mortality. Liver histology improves to septal fibrosis in a minority of patients after 24 months of treatment, with similar rates of improvement in patients receiving placebo and colchicine. Colchicine is not recommended for patients with advanced alcoholic cirrhosis.

Colchicine↗
PubMed2005

Phase II trial of induction gemcitabine/CPT-11 followed by a twice-weekly infusion of gemcitabine and concurrent external beam radiation for the treatment of locally advanced pancreatic cancer.

PURPOSE: This phase II trial of induction irinotecan/gemcitabine followed by twice-weekly gemcitabine and upper abdominal radiation was initiated to determine the activity of this regimen in patients with unresectable pancreatic cancer. METHODS: Patients with locally advanced, nonmetastatic adenocarcinoma of the pancreas received 2 cycles of induction irinotecan (100 mg/m2 IV) and gemcitabine (1000 mg/2 IV) on days 1 and 8 of each 3-week cycle. Following the induction, patients without disease progression received gemcitabine administered twice weekly (40 mg/m2/day) for 5 weeks concurrent with upper abdominal radiation (50.4 Gy over 5.5 weeks). RESULTS: From April 2000 to August 2003, 20 patients were entered into this study, 17 of whom were evaluable for treatment response. Characteristics included a median age of 67 years (range, 44-87 years) and 14 men (70%). Grades III and IV hematologic toxicity occurred in 25% and 5% of patients respectively and was primarily thrombocytopenia. No grade IV gastrointestinal toxicities or deaths due to therapy were observed. All therapy was completed in 8 patients, 7 patients were removed due to progression, 2 due to toxicity, 2 refused further treatment, and 1 was removed per the treating physician. The median time to progression and median survival was 5.1 months (95% CI, 3.2-6.7) and 8.8 months (95% CI, 6.4-10.1) respectively. Four patients (20%) were alive at 12 and 18 months. CONCLUSION: Induction irinotecan/gemcitabine followed by twice-weekly gemcitabine and upper abdominal radiation is feasible in patients with locally advanced pancreatic cancer. This regimen, however, has only modest activity and should not be explored further.

Adenocarcinoma↗
PubMed2005

Comparative analysis of direct pancreatic function testing versus morphological assessment by endoscopic ultrasonography for the evaluation of chronic unexplained abdominal pain of presumed pancreatic origin.

OBJECTIVES: The diagnosis of "minimal change" chronic pancreatitis (MCCP) is often considered when conventional imaging studies are unrevealing in a patient population with abdominal pain of presumed pancreatic origin. Direct pancreatic function testing using secretin as a secretagogue (ST) has been considered the most sensitive method to diagnose MCCP but is not widely available to clinicians. Endoscopic ultrasound (EUS) allows detailed imaging of pancreatic architecture, but the sensitivity and specificity for MCCP remain to be determined. We sought to compare the accuracy of EUS and ST in patients with presumed MCCP. METHODS: Seventy-four patients referred to our pancreas clinic with unexplained abdominal pain and previously negative imaging studies underwent an ST for evaluation of possible MCCP. Twenty-one of these also underwent EUS. EUS images were read by 1 of 2 experts blinded to ST results. RESULTS: Using ST as the "gold standard," EUS had a maximum sensitivity of 71% when the cut-off for diagnosis was set at at least 3 EUS features. Conversely, maximum specificity (92%) was seen when the cut-off value was set at at least 6 EUS criteria. Diagnostic certainty was only 50% (positive predictive value = 0.5) when at least 6 criteria were used as the cut-off. MCCP was excluded with greater than 70% certainty when less than 3 criteria were present. At the best cut-off value of at least 4 features, EUS had a sensitivity of 57% and a specificity of 64%. CONCLUSIONS: In this patient population with abdominal pain of presumed pancreatic origin, EUS and standard pancreatic function testing are often discordant. If ST is assumed to be the reference against which other tests are compared, EUS is less accurate than ST in diagnosing MCCP.

Abdominal Pain↗
PubMed2005

Long-term results of local excision with and without chemoradiation for adenocarcinoma of the rectum.

The role of local excision for rectal carcinoma remains controversial. We reviewed 285 patients undergoing curative resection for rectal cancer between 1984 and 2001. Surgical procedures were local excision (LE; n = 49), abdominoperineal resection (APR; n = 124), and low anterior resection (LAR; n = 112). Median follow-up for all patients was 6.2 years. For patients undergoing local excision, postoperative tumor stages were Tis (22%), T1 (41%), T2 (18%), and T3 (18%). Twelve patients received postoperative radiation >/= 45 Gy, and 4 patients received adjuvant chemotherapy. Of the 49 patients who underwent LE, the 5- and 10-year overall survival rates were 76% and 42%, respectively. The 5- and 10-year disease-free survival rates were 69% and 58%, respectively. The incidence of local recurrence was 16% and the incidence of distant recurrence was 6%. For the 11 patients who experienced disease recurrence, the median time to recurrence was 13 months (range, 1-59 months). Of the 8 patients who developed local recurrence, 4 refused salvage treatment, 2 underwent salvage APR, and 2 underwent repeat excision. Of the 4 who underwent salvage surgery, one is alive with no evidence of disease, one developed distant disease, and 2 died with unknown disease status. Adjuvant therapy did not affect survival or recurrence rates in patients undergoing LE compared with other surgeries. The rate of local failure (16%) is comparable to that observed in the Cancer and Leukemia Group B (CALGB) 8984 prospective study and suggests that highly selected patients undergoing local excision can expect good local control of rectal cancer.

Adenocarcinoma↗
PubMed2004

ACBP4 and ACBP5, novel Arabidopsis acyl-CoA-binding proteins with kelch motifs that bind oleoyl-CoA.

In plants, fatty acids synthesized in the chloroplasts are exported as acyl-CoA esters to the endoplasmic reticulum (ER). Cytosolic 10-kDa acyl-CoA-binding proteins (ACBPs), prevalent in eukaryotes, are involved in the storage and intracellular transport of acyl-CoAs. We have previously characterized Arabidopsis thaliana cDNAs encoding membrane-associated ACBPs with ankyrin repeats, designated ACBP1 and ACBP2, which show conservation to cytosolic ACBPs at the acyl-CoA-binding domain. Analysis of the Arabidopsis genome has revealed the presence of three more genes encoding putative proteins with acyl-CoA-binding domains, designated ACBP3, ACBP4 and ACBP5. Homologues of ACBP1 to ACBP5 have not been reported in any other organism. We show by reverse-transcriptase polymerase chain reaction (RT-PCR) analysis that ACBP3 , ACBP4 and ACBP5 are expressed in all plant organs, like ACBP1 and ACBP2 . ACBP4 and ACBP5 that share 81.4 identity and which contain kelch motifs were further investigated. To demonstrate their function in binding acyl-CoA, we have expressed them as (His)6-tagged recombinant proteins in Escherichia coli for in vitro binding assays. Both (His)6-ACBP4 and (His)6-ACBP5 bind [14C]oleoyl-CoA with high affinity, [14C]palmitoyl-CoA with lower affinity and did not bind [14C]arachidonyl-CoA. Eight mutant forms of each protein with single amino acid substitutions within the acyl-CoA-binding domain were produced and analyzed. On binding assays, all mutants were impaired in oleoyl-CoA binding. Hence, these novel ACBPs with kelch motifs have functional acyl-CoA-binding domains that bind oleoyl-CoA. Their predicted cytosol localization suggests that they could maintain an oleoyl-CoA pool in the cytosol or transport oleoyl-CoA from the plastids to the ER in plant lipid metabolism.

Acyl Coenzyme A↗
PubMed2004

Infectious complications of pancreatitis: diagnosis and management.

Infected pancreatic necrosis is the leading cause of death in patients with severe acute pancreatitis. Early prophylactic antibiotic treatment is effective in preventing conversion of sterile necrosis to pancreatic infection, but its effect on mortality remains unproven. Fungal infections may predict a worse outcome, but no evidence supports the use of antifungal prophylaxis. Because infection of pancreatic necrosis by enteric bacteria can develop despite prophylaxis, a high index of suspicion should allow early detection followed by aggressive management.

Humans↗
PubMed2004

Quantitative analysis of endosonographic parenchymal echogenicity in patients with chronic pancreatitis.

BACKGROUND AND AIM: The aim of the study was to develop a method of quantitation of endoscopic ultrasonography (EUS) changes of chronic pancreatitis (CP). METHODS: Twenty-three patients with chronic pancreatitis by EUS were compared with nine normal subjects. Hyperechogenicity was evaluated as the size of the hyperechoic area that was over a threshold echogenicity level. Mean echo density was expressed using the average gray-scale value within the region of interest. The quantitative data were compared with the diagnosis using conventional EUS criteria. RESULTS: The size of the hyperechoic area over the threshold level was 0.86 +/- 0.67 mm2 (mean +/- SD) in the normal pancreas using EUS criteria. In chronic pancreatitis, the size of the hyperechoic area was 7.28 +/- 2.98 mm2 in patients with mild CP, 18.12 +/- 2.56 mm2 in patients with moderate CP, and 18.02 +/- 10.81 mm2 in patients with severe CP, respectively. These changes in hyperechoic size area were statistically significant in all patients having mild to severe CP when compared with normal controls. CONCLUSION: Computer analysis of EUS images may provide objective information for the diagnosis of CP and may be useful in quantitating the severity of disease and overcoming interobserver variability in analyzing individual echo features supporting the diagnosis of CP.

Aged↗
PubMed2004

A descriptive analysis of EUS-FNA for mediastinal lymphadenopathy: an emphasis on clinical impact and false negative results.

OBJECTIVES: Endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) has been shown to accurately diagnose mediastinal lymph node pathology. We investigated the clinical impact of EUS-FNA in the management of patients with mediastinal lymphadenopathy, and determined the nature and clinical consequences of false negative results. METHODS: We analyzed a cohort of patients who were found to have mediastinal lymph nodes by EUS and underwent FNA. The diagnostic standard included FNA cytology, histopathology, and clinical follow-up. RESULTS: Sixty EUS-FNAs of mediastinal lymph nodes were performed on 59 patients (mean age 61 years old, 74.5% men) over a 24-month period. Prior to EUS, 20 (34%) patients had known malignancy. The most frequent indication for EUS was failed diagnosis by bronchoscopy (54%). EUS-FNA of lymph nodes showed malignant cells in 38%. The diagnostic accuracy of EUS-FNA was 84%. Among the 47 patients who were available for follow-up, EUS-FNA provided new information by changing the clinical diagnosis, and subsequently changed the management in 18 (38%) patients. The false negative rate was 20% (95% exact CI, 8.4-31.6%). Two of the 7 false negative cases received empiric chemoradiation without tissue diagnosis, and 4 received palliative treatment for advanced malignancy. CONCLUSION: The most common indication for EUS-FNA of the mediastinum in our institution is nondiagnostic transbronchial FNA. EUS-FNA is a valuable diagnostic method for sampling mediastinal lymph nodes and affecting management. False negative results do not appear to delay appropriate treatment or adversely affect clinical outcome.

Biopsy, Fine-Needle↗
PubMed2003

Angiotensin-converting enzyme inhibitor-induced isolated visceral angioedema in a liver transplant recipient.

Isolated visceral angioedema is an extremely rare complication of angiotensin-converting enzyme inhibitors (ACEIs). We report the first known case of ACEI-associated visceral angioedema occurring in a liver transplant recipient who presented with acute-onset abdominal pain, nausea, vomiting, diarrhea, radiologic findings of small bowel edema, and ascites. Heightened awareness of the phenomenon of isolated ACEI-associated visceral angioedema is necessary given the increasing use of these medications for treating hypertension related to calcineurin inhibitors and the need to avoid unnecessary surgical or diagnostic interventions in solid-organ transplant recipients.

Adult↗
PubMed2003

Risk factors for hepatitis C virus infection among patients receiving health care in a Department of Veterans Affairs hospital.

A cross-sectional, seroepidemiological study was conducted to determine the prevalence and risk factors for hepatitis C virus (HCV) infection among veterans receiving health care from the VA. Among 274 evaluated outpatients, anti-HCV was found in 27 (9.9%). The prevalence of anti-HCV was 3.7% among 190 individuals who reported no illicit drug use compared to 24.7% among 81 subjects who had used drugs (P < 0.001). The prevalence of anti-HCV was 4.8% among 208 veterans who had never been incarcerated compared to 27.9% among 61 veterans who had been incarcerated (P < 0.001). A multivariate model found the following factors to be independently associated with anti-HCV; having used illicit drugs [odds ratio (OR) = 3.7, 95% CI 1.3-11.8; P = 0.001), having been incarcerated (OR = 4.4, 95% CI 1.7-10.9; P = 0.001), and a yearly income less than 10,000 US dollars (OR = 3.5, 95% CI 1.3-9.4; P = 0.002). Because HCV infection was most strongly associated with illicit drug use, incarceration, and low income, these risk factors should be utilized to develop screening strategies among VA patients.

Adult↗
PubMed2003

Recombinant toxin DAB389EGF is cytotoxic to human pancreatic cancer cells.

Few malignancies have frustrated the persistent efforts of the oncologist like pancreatic cancer. Pancreatic cancer is usually unresectable at the time of diagnosis because of metastasis or local extension. Despite the aggressive nature of this deadly disease, systemic treatment options are limited. Even the recent introduction of the deoxycytidine analogue gemcitabine does not extend median survival of responders beyond a year. Clearly, alternative, more effective regimens are needed for treating pancreatic carcinoma. In pancreatic cancer, there is overexpression of growth factors and growth factor receptors, including epidermal growth factor receptor (EGFR). Targeted toxins consist of a targeting polypeptide covalently linked to a peptide toxin. DAB(389)EGF is a fusion protein composed of the catalytic and translocation domains of diphtheria toxin fused via a His-Ala linker to human epidermal growth factor (EGF). The authors have previously shown that DAB(389)EGF is selectively toxic to EGFR-overexpressing cells, including human brain tumour and lung carcinoma cell lines. Pancreatic adenocarcinoma should be responsive to this fusion protein based on its EGFR overexpression. However, the cytotoxic effect of DAB(389)EGF on human pancreatic carcinoma cell lines has yet to be explored. The authors describe preliminary data showing the potent cytotoxicity of DAB(389)EGF to human pancreatic carcinoma cell lines. Because of the nonspecific toxicity to liver and kidney (which possess EGFR) of systemic administration, they also propose a potential novel drug delivery system for direct toxin implantation into pancreatic tumours using endoscopic ultrasound guided fine-needle injection (EUS-FNI). Hopefully, the use of these targeted therapeutic approaches in combination with other modalities may further extend survival and quality of life in patients with pancreatic adenocarcinoma.

Adenocarcinoma↗
PubMed2002

Ectopic pancreatic tissue presenting as submucosal gastric mass.

BACKGROUND: Ectopic pancreas is pancreatic tissue found outside its usual anatomic location without connection to the normal pancreas. We describe the presentation and minimally invasive management of four patients with ectopic pancreatic tissue in the stomach. METHODS: Data were collected from a retrospective chart review of four patients undergoing laparoscopic resection of gastric pancreatic rests. RESULTS: Four patients underwent laparoscopic resection of gastric pancreatic tissue. All patients were discharged on postoperative day 3. No complications developed. CONCLUSION: Laparoscopic gastric wedge resection is a safe and effective treatment for symptomatic pancreatic rests located in the stomach.

Aged↗