Effect of exendin (exenatide)--GLP 1 receptor agonist on the thyroid and parathyroid gland in a rat model.

Exenatide or Exendin-4 is a 39-amino acid agonist of the glucagon like peptide (GLP-1) receptor approved for the adjunctive treatment for type 2 diabetes. Recent reports suggest that GLP-1 agonists may also have distant effects including C-cell thyroid hyperplasia. The aim of this study was to evaluate the effect of exendin-4 on the thyroid and parathyroid cells in a rat model. Rat thyroids were stained for calcitonin, H&E and for carcinoembryonic antigen (CEA). Thyroid C-cell hyperplasia was graded on H&E stained slides using cell size and secretory granule numbers, morphological features of the parathyroid glands and the serum calcium concentrations of the rats were also evaluated. Counts of stained cells/high power field and intensity of staining were recorded by two pathologists. Data were analyzed by ANOVA/post-tests. C cell hypertrophy was elevated in exenatide-treated vs. untreated animals (22.5 ± 8.7 vs. 10.5 ± 2.7 cells/HPF). CEA staining failed to show effects by exendin. Calcitonin staining was significantly elevated in exenatide treated controls (P<0.001). Parathyroid glands were histologically normal in both groups, and serum calcium levels were within normal range in all animals. In summary, exenatide was associated with C cell hyperplasia and increased calcitonin staining of thyroids, but was unrelated to CEA levels. These data raise important concerns about the effects of exenatide which, given its wide clinical use, should be clarified with urgency.

Treatment with omega-3 fatty acids but not exendin-4 improves hepatic steatosis.

BACKGROUND: Nonalcoholic fatty liver disease (NAFLD) is the most common form of chronic liver disease in the Western world. The aim of this study was to evaluate the biochemical and histological effects of omega-3 fatty acid and exendin-4 treatment on NAFLD in an animal model. METHODS: Sixty-three 8-week-old outbred Sprague-Dawley male rats were used for this study. Three animals were used as procedure controls, and 30 rats were fed a methionine and choline deficient (MCD) diet and 30 were fed a regular chow diet. In each group of 30 animals, 10 served as controls, 10 received exendin-4, and 10 received omega-3 fatty acids. After 75 days of treatment, the animals were euthanized, the tissues and serum were harvested, and the livers were formalin-fixed for histology. RESULTS: The MCD diet was exceptionally efficient at producing fatty livers. The MCD control animals had a liver steatosis score of 38+/-6.7 (of 50 possible); treatment with exendin-4 was not associated with a significant reduction of steatosis (44+/-5.16, P=0.07) and the omega-3 fatty acid treatment was associated with a significant decrease in the liver steatosis score (15.6+/-13.46, P<0.001) compared with both the controls and the exendin-4 groups. The omega-3 fatty acid treatment increased serum aspartate aminotransferase significantly, whereas exendin-4 had no effect. CONCLUSION: In an animal model of NAFLD, the omega-3 fatty acid therapy was associated with significant improvement in hepatic steatosis compared with exendin-4. These data suggest that omega-3 fatty acid supplements may have a potential therapeutic role in patients with NAFLD.

Predictors of hematological abnormalities in patients with chronic hepatitis C treated with interferon and ribavirin.

Hematological abnormalities including neutropenia, anemia, and thrombocytopenia are commonly seen in patients with chronic hepatitis C treated with pegylated interferon and ribavirin. The aim of this study was to identify factors which would help to predict the development of hematological abnormalities in patients with chronic hepatitis C treated with pegylated interferon and ribavirin. During a 4-year period, all patients with chronic hepatitis C started on treatment with pegylated interferon and ribavirin were identified. Patients were defined as having hematological abnormalities if they had the presence of either anemia, neutropenia, thrombocytopenia, or a combination of the above during treatment with pegylated interferon and ribavirin. A total of 136 patients with chronic hepatitis C were included in this study. Fifty-two (38.2%) of the patients developed significant hematological abnormalities during treatment with pegylated interferon and ribavirin with 28 (20.6%), 30 (22.1%), and 11 (8.1%) developed neutropenia, anemia, and thrombocytopenia, respectively. Genotype 1, history of hypertension, low baseline platelet count, low baseline hemoglobin, as well as a raised creatinine were significant factors associated with the development of hematological abnormalities. Significant hematological abnormalities are commonly present in patients with chronic hepatitis C treated with pegylated interferon and ribavirin. This study identifies pretreatment parameters that may help identify high-risk patients who are more likely to develop hematological abnormalities during treatment for chronic hepatitis C.

Patient and physician predictors of inappropriate acid-suppressive therapy (AST) use in hospitalized patients.

BACKGROUND: The use of acid suppressive therapy (AST) in prevention of stress ulcers has been well defined in critical care patients, though its use has become increasingly common in general medicine patients, with little to no supportive evidence. None of the previous studies has examined the patient and physician characteristics of inappropriate AST initiation and use in hospitalized patients. The aim of our study was to identify: (1) the appropriateness of AST in hospitalized patients and the cost associated with inappropriate use; and (2) patient and physician characteristics predicting inappropriate initiation and use of AST. METHODS: All discharges over a period of 8 consecutive days were selected. RESULTS: There were 207 patients discharged over a period of 8 days. AST was inappropriately initiated in 92 of 133 (69.2%) patients included in our study. On univariate analysis, higher hemoglobin value, postgraduate year 1 (PGY-1) residents, physicians with an MD degree, international medical graduates (IMGs), and internal medicine physicians were more likely to prescribe AST inappropriately. On multivariate analysis, a higher hemoglobin value, PGY-1 residents, and MD physicians were factors associated with inappropriate AST use. The total direct patient cost for this inappropriate use was $8026, with an estimated annual cost of approximately $366,000. CONCLUSIONS: AST was inappropriately initiated in 69.2% of patients with increased direct costs of $8026. Residents in their first year of training as well physicians with a MD degree are more likely to initiate AST inappropriately. Curtailing the inappropriate use of AST therapy may reduce overall costs for the patient and institution.

Predictors of community-acquired methicillin resistant Staphylococcus aureus in the inpatient population.

The predictors of community-acquired methicillin resistant Staphylococcus aureus (CA-MRSA) in hospitalized patients based on their clinical presentation are limited. The aim of our study was identification of predictors of CA-MRSA infections based on clinical features in patients admitted to the hospital for skin and soft tissue infections. We retrospectively collected data over a period of two years at a single tertiary teaching institution. Younger age and presence of fever may be significant predictors of CA-MRSA.

Megestrol acetate-associated adrenal insufficiency.

BACKGROUND: Megestrol acetate (MA) is commonly used to promote weight gain in malnourished elderly patients. Although adrenal insufficiency has been reported as an adverse effect of MA, this association is not well recognized in clinical practice. CASE SUMMARY: An 80-year-old woman with worsening dyspnea was transferred to our university-affiliated community medical center from an inpatient psychiatric facility, where she was being treated for major depressive disorder with psychotic features. She had undergone a general decline in physical function accompanied by some weight loss and anorexia consistent with failure to thrive and, 1 month earlier, had been started on MA 400 mg/d to stimulate her appetite and improve her nutrition. During hospitalization at our center, the patient's dyspnea worsened and she was transferred to the intensive care unit, where she was intubated. While in the intensive care unit, the patient developed hypotension. Infectious, cardiac, and neurologic causes of hypotension having been ruled out, a cosyntropin stimulation test was performed to rule out adrenal insufficiency. Cortisol levels before, 30 minutes after, and 60 minutes after administration of cosyntropin were 1.6, 7.1, and 9.8 microg/dL, respectively, indicating a suboptimal response. The adrenocorticotropic hormone level was 8 pg/mL (normal, 10-60 pg/mL). Based on these findings suggesting adrenal insufficiency, MA was discontinued and steroid replacement was initiated. The patient's blood pressure normalized and she improved slowly. She was weaned from the ventilator several weeks later and was discharged to a skilled nursing facility. At 2-month follow-up, the patient's strength and respiratory function were improved, and the results of a repeat cosyntropin stimulation test were normal (cortisol response before, 30 minutes after, and 60 minutes after cosyntropin administration: 15.4, 22.6, and 25.2 microg/dL, respectively). The Naranjo score for this case was 7, indicating a probable correlation between MA use and adrenal insufficiency. CONCLUSIONS: This case of adrenal insufficiency in an elderly woman was probably related to MA use. Clinicians should be alert to the possibility of this adverse effect when considering use of MA therapy.

Predictors of nonalcoholic steatohepatitis in patients undergoing bariatric surgery: when is liver biopsy indicated?

BACKGROUND: Nonalcoholic fatty liver disease is a frequent accompaniment of morbid obesity. A component of nonalcoholic fatty liver disease, steatosis, can, on occasion, lead to nonalcoholic steatohepatitis (NASH). Bariatric surgery has been shown to alter the course of this disease. Intraoperative liver biopsies might identify patients with NASH for more careful follow-up. We sought to determine noninvasive preoperative indicators of NASH. METHODS: The patients scheduled for bariatric surgery underwent a preoperative assessment. The study variables included age, gender, race, body mass index, diabetes mellitus, hypertension, and the results of serum liver function tests and triglyceride, cholesterol, iron, and prealbumin measurements. Univariate and multivariate analyses were performed to identify significant variables associated with NASH as determined by subsequent core liver biopsies taken during open Roux-en-Y gastric bypass. RESULTS: A total of 139 patients were entered into the study. NASH or NASH-associated fibrosis was found in 57 patients (41%). On univariate analyses, male gender (odds ratio [OR] 2.46, P = .06), diabetes mellitus (OR 2.60, P = .009), elevated serum triglyceride levels (OR 1.003, P = .02), elevated gamma glutamyl transferase (OR 1.015, P = .01), and decreased prealbumin (OR 0.94, P = .04) correlated with the presence of NASH. On multivariate analysis, only increased triglycerides (OR 1.004, P = .04) and decreased prealbumin (OR 0.88, P = .005) correlated with the presence of NASH. CONCLUSION: NASH is a frequent accompaniment of morbid obesity in patients undergoing bariatric surgery. Univariate and multivariate analyses of the clinical parameters studied could not identify strong predictors of biopsy-verified NASH. Therefore, intraoperative biopsy remains instrumental in diagnosing NASH and providing information for additional follow-up.

Acquired pure megakaryocytic aplasia: report of a single case treated with mycophenolate mofetil.

Acquired pure megakaryocytic aplasia (APMA) is a rare disorder in the field of hematological diseases. We report the case of a patient with APMA treated with mycophenolate mofetil and review the literature associated with this. Until today, very few cases of APMA have been reported and the disease etiology still seems to be unclear. There have been no reported cases of treatment of APMA treated with mycophenolate mofetil.

Clinicopathological predictors to predict sustained viral response rates in patients with chronic hepatitis C infection.

BACKGROUND: Treatment of patients with chronic hepatitis C virus (HCV) infection remains suboptimal, with the current pegylated interferon (PEG-IFN) and ribavirin combination therapy providing sustained viral response (SVR) rates of 54 - 63%. The aim of this study was to identify clinical, laboratory and histological findings that can predict non-response to this treatment. METHODS: Medical records of patients who had completed PEG-IFN and ribavirin therapy for chronic HCV infection between December 2002 and November 2005 and had undergone a liver biopsy prior to starting treatment were retrospectively reviewed. Data on various clinical and biochemical parameters were extracted and liver biopsy slides were reviewed by a pathologist who was blinded to the clinical and laboratory findings. RESULTS: Of 67 patients studied (mean [SD] age 46.3 [6.3] years; 36 men), 42/57 (74%) had an early viral response (EVR) and 37/64 (58%) had an SVR. On univariate analysis, absence of EVR (p=0.0002), non-white race (p=0.008), AST/ALT ratio > or = 1.0 (p=0.008), INR > or = 1.0 (p=0.02) and presence of steatosis > or = 5% on liver biopsy (p=0.03) were associated with lack of SVR. In multivariate analysis, all of these except INR were significant independent predictors of SVR. CONCLUSIONS: Absence of EVR, non-white race, AST/ALT ratio > or = 1.0 and presence of steatosis > or = 5% on liver biopsy are independent predictors of absence of SVR in patients with chronic HCV infection receiving PEG-IFN and ribavirin combination treatment.

Polyneuropathy complicating the diagnosis of normal pressure hydrocephalus: case report and review of literature.

Polyneuropathy is a rare association of normal pressure hydrocephalus (NPH) and may complicate the diagnosis of both diseases. We describe a patient with NPH who presented with acute polyneuropathy. The patient was initially thought to have Guillain-Barré disease (GBS). Early consideration of NPH in patients presenting with acute polyneuropathy could result in prompt diagnosis and treatment of NPH.

Pre-operative prediction of difficult laparoscopic cholecystectomy using clinical and ultrasonographic parameters.

BACKGROUND: Pre-operative prediction of a difficult laparoscopic cholecystectomy (LC) can help the patient as well as the surgeon prepare better for the intra-operative risk and the risk of conversion to open cholecystectomy. METHODS: In 105 eligible patients who underwent LC during May 2001 to January 2003, patient characteristics, clinical history, laboratory data, ultrasonography results and intra-operative details were prospectively analyzed to determine predictors of difficult LC. RESULTS: Of 105 patients, 12 (11.4%) required conversion to open cholecystectomy. Significant predictors of conversion were body mass index> 30 Kg/m2, male gender, past history of acute cholecystitis or acute pancreatitis, past history of upper abdominal surgery, and gall bladder wall thickness exceeding 3 mm. CONCLUSION: Clinical and ultrasonograpic factors can help predict difficult LC and likelihood of conversion of LC to open surgery.