Inter Science Institute

West Menlo Park, CA, United States

Inter Science Institute

West Menlo Park, CA, United States

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Joseph S.,Louisiana State University Health Sciences Center | Li G.,University of California | Lindholm E.,Louisiana State University Health Sciences Center | Zhou Y.,University of California | And 5 more authors.
Pancreas | Year: 2010

Objectives: Octreotide long acting repeatable (LAR) is commonly used to control the symptoms of patients with functional neuroendocrine tumors. Unfortunately, most patients escape control over time and require higher LAR doses or more frequent rescue therapy to remain asymptomatic. Previous work has shown that body weight and monthly LAR dose will significantly affect circulating plasma octreotide levels in patients undergoing therapy. Methods: To determine if other parameters change circulating plasma octreotide levels, we prospectively studied 82 patients undergoing long-term LAR therapy. Results: Multivariate analysis demonstrated that the plasma octreotide levels decrease by approximately 3.4% for each unit of body mass index (BMI) increase (P = 0.03), adjusting for sex and monthly LAR dose. Plasma octreotide levels for females were approximately 47.6% higher than those for males (P = 0.045), adjusting for BMI and monthly LAR dose. Initial and subsequent octreotide LAR doses should take into consideration sex and BMI. Males are estimated to require 14.1-mg (SD, 7.25) higher monthly LAR doses than females with the same BMI. Conclusions: We have shown that plasma octreotide levels are affected by not only monthly LAR dose but also BMI and sex. We hope these observations will make choosing initial and subsequent octreotide LAR doses easier for physicians. Copyright © 2010 by Lippincott Williams & Wilkins.


O'Dorisio T.M.,University of Iowa | Krutzik S.R.,Inter Science Institute | Woltering E.A.,Health science Center | Lindholm E.,Louisiana State University Health Sciences Center | And 10 more authors.
Pancreas | Year: 2010

Objective: Pancreastatin is a fragment of the chromogranin A (CgA) molecule. Existing pancreastatin assays, which depend on antibodies that cross-react in varying percents with the larger prohormone, may lack sensitivity and specificity to detect small changes in neuroendocrine tumor volume. Methods: We developed a highly specific, sensitive pancreastatin assay. The antibody used recognizes the carboxyl terminal of the peptide hormone and was raised against a 17-amino acid porcine pancreastatin fragment with high homology with the carboxy-terminal amino acids 286-301 of the human CgA. Results: Our assay measures more than 95% of circulating pancreastatin levels; has little or no cross-reactivity with CgA, even at plasma concentrations of 1000 ng/mL; and can detect pancreastatin levels of 17 pg/mL. Interassay reproducibility for the pancreastatin radioimmunoassay was determined from results of 3 quality control pools in 15 consecutive assays. Coefficients of variation for low, medium, and high pancreastatin levels were less than 20%. The sensitivity of serial pancreastatin assays to detect early liver tumor activity was demonstrated in 2 patients with slowly progressive neuroendocrine tumors and in patients undergoing surgical cytoreduction. Conclusions: This highly specific, sensitive pancreastatin assay can detect small changes in liver tumor progression and is up to 100-fold more sensitive and specific than CgA assays in the United States. © Copyright 2010 by Lippincott Williams & Wilkins.


Mamikunian P.,Inter Science Institute | Ardill J.E.,Royal Victoria Hospital | O'Dorisio T.M.,University of Iowa | Krutzik S.R.,Inter Science Institute | And 5 more authors.
Pancreas | Year: 2011

Objectives: International cooperative group trials require specific, sensitive biomarker assays that are validated between continents. Neurokinin A (NKA) has been shown to be a powerful independent predictor of a poor prognosis in well-differentiated midgut neuroendocrine tumors. We hypothesized that NKA concentrations of clinical specimens evaluated in NKA assays in the United States and the United Kingdom would be equivalent, even though assay techniques were significantly different. Methods: Frozen clinical specimen aliquots were shipped from the United States to the United Kingdom (n = 67), and from United Kingdom to the United States (n = 50). In addition, spiked plasma standards and medium-spiked standards were exchanged. Samples from the United States were directly assayed in a radioimmunoassay, whereas the UK specimens were extracted, and the reconstituted specimens assayed in the radioimmunoassay. Neurokinin A values from the 2 studies were analyzed by regression analysis. Results: The NKA values from the US and UK laboratories were essentially identical (United States to United Kingdom, r = 0.88, P < 0.0001; and United Kingdom to United States, r = 0.96, P < 0.0001). Conclusions: Validation of biomarker assays across continents will ensure that laboratory observations made by researchers are equivalent and that prediction of clinical outcomes based on these assays is also reliable. Copyright © 2011 by Lippincott Williams & Wilkins.


Lieb D.C.,Eastern Virginia Medical School | Parson H.K.,Eastern Virginia Medical School | Mamikunian G.,Inter Science Institute | Vinik A.I.,Eastern Virginia Medical School
Experimental Diabetes Research | Year: 2012

Introduction. Diabetics die from cardiovascular disease at a much greater rate than nondiabetics. Cardiac autonomic imbalance predicts increased cardiovascular risk and mortality. We studied the relationship between cardiac autonomic imbalance and adipose tissue-derived inflammation in newly diagnosed and established type 2 diabetes. Materials and Methods. Non-diabetics, newly diagnosed diabetics, and established diabetics were included. Anthropomorphic and biochemical measurements were obtained, and insulin resistance was approximated. Cardiac autonomic function was assessed using conventional measures and with power spectral analysis of heart rate. Results and Discussion. Heart rate variability was reduced in all diabetics. Interleukin-6 was higher in diabetics, as was the high molecular weight adiponectin-to-leptin ratio. Interleukin-6 correlated negatively with measures of autonomic balance. Ratios of adiponectin to leptin correlated positively with measures of autonomic balance. Cardiac autonomic imbalance and inflammation occur early in diabetes and are interrelated. Conclusions. Cardiac autonomic imbalance correlates with the adipose tissue-derived inflammation seen early in type 2 diabetes. Copyright © 2012 David C. Lieb et al.


Tellez M.R.,Inter Science Institute | Mamikunian G.,Inter Science Institute | O'Dorisio T.M.,University of Iowa | Vinik A.I.,Eastern Virginia Medical School | Woltering E.A.,Louisiana State University Health Sciences Center
Pancreas | Year: 2013

OBJECTIVES: 5-Hydroxyindoleacetic acid (5-HIAA) is used for the evaluation of neuroendocrine tumors (NETs) but currently requires a 24-hour urine collection. METHODS: We developed a gas chromatography mass spectroscopy-based plasma 5-HIAA assay. We compared 24-hour urine 5-HIAA values against plasma 5-HIAA values in 115 mixed-variety patients with NETs and in a subset of 72 patients with only small bowel NETs. We also compared the information gained from urinary and plasma 5-HIAA values with other biomarkers of midgut NET activity to determine the plasma assay's clinical implications. RESULTS: In a group of 115 patients with all types of NETS, in a subset of patients with midgut NET and in a subgroup of midgut NETS with liver metastasis, the correlation between the urine and fasting plasma 5-HIAA values were statistically significant (P ≤ 0.0001). Comparison of the proportion of normal or abnormal urinary and plasma 5-HIAA values to the proportion of chromogranin, serotonin, neurokinin, or pancreastatin values that were in the normal or abnormal range yielded essentially identical information. CONCLUSIONS: Plasma fasting 5-HIAA values are proportional to urinary 5-HIAA values and yielded identical clinical correlation with other biomarkers. Copyright © 2013 by Lippincott Williams & Wilkins.


Raines D.,Louisiana State University Health Sciences Center | Chester M.,Louisiana State University Health Sciences Center | Diebold A.E.,Louisiana State University Health Sciences Center | Mamikunian P.,Inter Science Institute | And 3 more authors.
Pancreas | Year: 2012

Objective: Proton pump inhibitors (PPIs) are used primarily to treat gastroesophageal reflux disease. Proton pump inhibitor-induced achlorhydria increases circulating gastrin and chromogranin A (CGA). Chromogranin is a widely used biomarker for the diagnosis and follow-up for gut-based neuroendocrine tumors (NETs). Proton pump inhibitor-induced increases in CGA or gastrin may falsely suggest the presence of a NET when none exists. Pancreastatin, a fragment of CGA, is also commonly used to diagnose and follow NETs. We hypothesized that chronic PPI use would increase circulating plasma gastrin, CGA, and pancreastatin levels. Methods: Thirty patients who used PPIs for 6 months or more (mean ± SD duration, 3.1 ± 2.5 years) and a separate control group of 30 patients who never used antacid medications were prospectively evaluated with plasma gastrin, CGA, and pancreastatin determinations. Results: Chronic PPI use resulted in significant increases in CGA (15.1 ± 11 vs 131 ± 207 ng/mL; P=0.005) and significant increases in gastrin (34.8 ± 22.3 vs 167.8 ± 136.2 pg/mL; P=0.001) compared to controls. In contrast, pancreastatin level in nonusers and chronic PPI users were identical (81.6 ± 36.4 vs 89.4 ± 43.4 pg/mL; P=0.46). Conclusions: Pancreastatin levels do not change with chronic PPI use and normal pancreastatin levels may be used to distinguish between drug-induced changes in biomarkers and tumor-related increases in circulating biomarkers. © 2012 by Lippincott Williams & Wilkins.


Mamikunian G.,Inter Science Institute
Endocrinology and Metabolism Clinics of North America | Year: 2011

Modern medicine, and specifically clinical diagnosis, relies, among other diagnostic procedures, on the measurements of the biogenic analytes for elucidation and correlation of specific neuroendocrine markers. Tremendous advances have been made in imaging and radioactive uptake procedures to elucidate tumor presence and characterization. However, such advances only partially provide the fundamental degree of tumor activity and clinical confirmational validity. The author points out in some detail the problems that may arise when the methodological differences presented by each investigational study and investigators are not standardized. This variation causes a concern with the specific objectives of the investigator and the specific aims of the research project at hand, and ultimately for the validity of the published results. © 2011 Elsevier Inc.


PubMed | Childrens Hospital New Orleans, Inter Science Institute and Louisiana State University Health Sciences Center
Type: | Journal: Journal of clinical anesthesia | Year: 2016

The prophylactic use of a preoperative, intraoperative, and postoperative high-dose continuous octreotide acetate infusion was evaluated for its ability to minimize the incidence of carcinoid crises during neuroendocrine tumor (NET) cytoreductive surgeries.A retrospective study was approved by the institutional review boards at Ochsner Medical Center-Kenner and Louisiana State University Health Sciences Center.Ochsner Medical Center-Kenner operating room and multispecialty NET clinic.One hundred fifty consecutive patients who underwent a total of 179 cytoreductive surgeries for stage IV, small bowel NETs.All patients received a 500-g/h infusion of octreotide acetate preoperatively, intraoperatively, and postoperatively.Anesthesia and surgical records were reviewed. Carcinoid crisis was defined as a systolic blood pressure of less than 80mm Hg for greater than 10minutes. Patients who experienced intraoperative hypertension or hypotension, profound tachycardia, or a crisis according to the operative note were also reviewed.One hundred sixty-nine (169/179; 94%) patients had normal anesthesia courses. The medical records of 10 patients were further investigated for a potential intraoperative crisis using the aforementioned criteria. Upon review, 6 patients were determined to have had a crisis. The final incidence of intraoperative crisis was 3.4% (6/179).A continuous high-dose infusion of octreotide acetate intraoperatively minimizes the incidence of carcinoid crisis. We believe that the low cost and excellent safety profile of octreotide warrant the use of this therapy during extensive surgical procedures for midgut and foregut NETs.


5-Hydroxyindoleacetic acid (5-HIAA) is used for the evaluation of neuroendocrine tumors (NETs) but currently requires a 24-hour urine collection.We developed a gas chromatography mass spectroscopy-based plasma 5-HIAA assay. We compared 24-hour urine 5-HIAA values against plasma 5-HIAA values in 115 mixed-variety patients with NETs and in a subset of 72 patients with only small bowel NETs. We also compared the information gained from urinary and plasma 5-HIAA values with other biomarkers of midgut NET activity to determine the plasma assays clinical implications.In a group of 115 patients with all types of NETS, in a subset of patients with midgut NET and in a subgroup of midgut NETS with liver metastasis, the correlation between the urine and fasting plasma 5-HIAA values were statistically significant (P 0.0001). Comparison of the proportion of normal or abnormal urinary and plasma 5-HIAA values to the proportion of chromogranin, serotonin, neurokinin, or pancreastatin values that were in the normal or abnormal range yielded essentially identical information.Plasma fasting 5-HIAA values are proportional to urinary 5-HIAA values and yielded identical clinical correlation with other biomarkers.


PubMed | Inter Science Institute
Type: Journal Article | Journal: Endocrinology and metabolism clinics of North America | Year: 2011

Modern medicine, and specifically clinical diagnosis, relies, among other diagnostic procedures, on the measurements of the biogenic analytes for elucidation and correlation of specific neuroendocrine markers. Tremendous advances have been made in imaging and radioactive uptake procedures to elucidate tumor presence and characterization. However, such advances only partially provide the fundamental degree of tumor activity and clinical confirmational validity. The author points out in some detail the problems that may arise when the methodological differences presented by each investigational study and investigators are not standardized. This variation causes a concern with the specific objectives of the investigator and the specific aims of the research project at hand, and ultimately for the validity of the published results.

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