The effect of moderate sedation on exocrine pancreas function in normal healthy subjects: a prospective, randomized, cross-over trial using the synthetic porcine secretin stimulated Endoscopic Pancreatic Function Test (ePFT)

BACKGROUND: We have developed a purely endoscopic collection method for the assessment of pancreatic secretory function (ePFT). The pancreatic secretory effects of sedation medications utilized during endoscopic procedures are not completely known. AIMS: To study the effect of moderate sedation on the exocrine pancreas gland in a prospective, randomized trial. METHODS: Healthy volunteers were randomized by computers to one of two treatments (A-no sedation, B-sedation) in period 1 and crossed-over to the other treatment in period 2 with a minimal washout interval of 7 days. Sedation dosage was standardized for each patient based on age, gender and weight from a previously published dosing nomogram. Synthetic porcine secretin (ChiRhoClin, Inc., Burtonsville, Maryland) was used as the pancreatic stimulant. Duodenal fluid samples were aspirated via the endoscope every 5 min for 1 h and sent on ice to our hospital laboratory for the measurement of pancreatic secretory electrolyte concentrations by autoanalyzer. RESULTS: A total of 17 healthy volunteers were enrolled. Sixteen subjects (8 males and 8 females) completed the randomized prospective trial. Median intravenous meperidine and midazolam sedation dose was 62.5 mg and 2.5 mg, respectively. Maximum pancreatic juice flow occurred during the early phase of secretion and maximum bicarbonate concentration occurred during the late phase of secretion. Analysis of the electrolyte composition of the endoscopically collected duodenal drainage fluid revealed a constant cation concentration for both sodium and potassium over the 1 h collection period. The anions, chloride and bicarbonate, exhibited a reciprocal relationship identical to that seen in traditional gastroduodenal tube collection studies. There was no statistical difference observed between the sedation and no sedation groups. The estimated total bicarbonate output (area under curve, AUC) for the sedated and non-sedated groups were 5,017 meq + 724 (range 3,663-6,173) and 5,364 meq +/- 583 (range 4,323-6563) respectively (p= 0.0656). The mean peak bicarbonate concentrations for sedated (n = 8) versus non-sedated (n = 8) groups were 103 +/- 11 meq/L (range 78-125) and 106 +/- 11 meq/L (range 87-138), respectively (p= 0.1346). There was excellent correlation of peak bicarbonate concentrations when sedation and no sedation groups were compared (r= 0.744, p < 0.05; Spearman rank correlation). There were no episodes of pancreatitis. CONCLUSIONS: (a) Moderate sedation used for upper endoscopy does not effect the clinical diagnostic parameters (peak bicarbonate concentration or total bicarbonate output) utilized to diagnose pancreatic insufficiency. (b) Analysis of duodenal drainage fluid collected endoscopically after synthetic secretin stimulation produces an identical pancreatic secretory curve described with traditional gastroduodenal tube collection methods.     

Comparison of Endoscopic Ultrasound and Endoscopic Retrograde Pancreatography for the Prediction of Pancreatic Exocrine Insufficiency

Endoscopic retrograde pancreatography (ERP) is a sensitive test for the early ductal changes of chronic pancreatitis. More recently, endoscopic ultrasound (EUS) has also been proposed as a sensitive structural test for chronic pancreatitis. Few studies have compared EUS and ERP using an external reference standard. Direct pancreatic function tests (PFT) are an acceptable reference standard for chronic pancreatitis since they detect mild exocrine insufficiency. Our aim was to compare structural abnormalities as revealed by ERP and EUS for the prediction of exocrine insufficiency. Eight-three patients who underwent EUS, ERP, and secretin PFT for the evaluation of pancreatitis were identified from our database. Exocrine insufficiency was defined as a secretin PFT peak bicarbonate concentration <80 mEq/l. Based on the number of abnormal sonographic criteria observed, EUS findings were categorized as normal (<2 criteria), mild (3–5 criteria) or severe (6–9 criteria or calcifications). ERP findings were categorized based on the Cambridge classification. ERP and EUS did not differ significantly in either sensitivity (72% vs 68%, P = 0.52) or specificity (76% vs 79%, P = 0.40). ERP and EUS were similarly associated with exocrine insufficiency both in the presence of minimal (OR 3.4 and 4.9, respectively) and severe structural changes (OR 12 and 24, respectively). We consider EUS to have a diagnostic accuracy for the structural diagnosis of early- and late-stage chronic pancreatitis similar to that of ERP.     

Intravenous Mesenchymal Stem Cells Prevented Rejection of Allogeneic Corneal Transplants by Aborting the Early Inflammatory Response

Mesenchymal stem/progenitor cells (MSCs) were reported to enhance the survival of cellular and organ transplants. However, their mode of action was not established. We here used a mouse model of corneal allotransplantation and demonstrated that peri-transplant intravenous (i.v.) infusion of human MSCs (hMSCs) decreased the early surgically induced inflammation and reduced the activation of antigen-presenting cells (APCs) in the cornea and draining lymph nodes (DLNs). Subsequently, immune rejection was decreased, and allograft survival was prolonged. Quantitative assays for human GAPDH revealed that <10 hMSCs out of 1 × 10⁶ injected cells were recovered in the cornea 10 hours to 28 days after i.v. infusion. Most of hMSCs were trapped in lungs where they were activated to increase expression of the gene for a multifunctional anti-inflammatory protein tumor necrosis factor-α stimulated gene/protein 6 (TSG-6). i.v. hMSCs with a knockdown of TSG-6 did not suppress the early inflammation and failed to prolong the allograft survival. Also, i.v. infusion of recombinant TSG-6 reproduced the effects of hMSCs. Results suggest that hMSCs improve the survival of corneal allografts without engraftment and primarily by secreting TSG-6 that acts by aborting early inflammatory responses. The same mechanism may explain previous reports that MSCs decrease rejection of other organ transplants.     

Marrow stromal cells migrate throughout forebrain and cerebellum, and they differentiate into astrocytes after injection into neonatal mouse brains

Stem cells are a valuable resource for treating disease, but limited access to stem cells from tissues such as brain restricts their utility. Here, we injected marrow stromal cells (MSCs) into the lateral ventricle of neonatal mice and asked whether these multipotential mesenchymal progenitors from bone marrow can adopt neural cell fates when exposed to the brain microenvironment. By 12 days postinjection, MSCs migrated throughout the forebrain and cerebellum without disruption to the host brain architecture. Some MSCs within the striatum and the molecular layer of the hippocampus expressed glial fibrillary acidic protein and, therefore, differentiated into mature astrocytes. MSCs also populated neuron rich regions including the Islands of Calleja, the olfactory bulb, and the internal granular layer of the cerebellum. A large number of MSCs also were found within the external granular layer of the cerebellum. In addition, neurofilament positive donor cells were found within the reticular formation of the brain stem, suggesting that MSCs also may have differentiated into neurons. Therefore, MSCs are capable of producing differentiated progeny of a different dermal origin after implantation into neonatal mouse brains. These results suggest that MSCs are potentially useful as vectors for treating a variety of central nervous system disorders.     

Ethnic Origin of Alcoholics Admitted to an Israeli Treatment Center

Jews have a low rate of alcohol use and abuse as reported in several different countries. In Israel over the last 10 years there has been a rising rate of alcoholism. We studied consecutive new admissions to our inpatient alcohol center, and an age and sex matched comparison group of patients consecutively admitted with schizophrenia for whether each of their four grandparents was Jewish, or non-Jewish. A significantly higher percentage of alcohol-related admissions were immigrants from the Former Soviet Union (FSU) than among schizophrenics. Among the alcohol-related admissions from the FSU, there were significantly fewer Jewish grandparents than among schizophrenia patients from the FSU. These data could support the concept that biological Jewish ethnicity has a protective effect against alcohol abuse, but are also consistent with cultural transmission of Jewish attitudes toward alcohol use.     

Phytochemical analysis and in vitro antimicrobial activity of Illicium griffithii Hook. f. & Thoms extracts

ObjectiveTo evaluate the antimicrobial activity of hexane, ethyl acetate and methanol extracts of seeds and fruits of Illicium griffithii (I. griffithii)(Family: Schisandraceae).MethodsThe antimicrobial activity of the organic extracts were determined using disc diffusion assay against Gram-positive bacterial strains (three reference cultures and three clinical isolates), Gram-negative bacterial strains (nine reference cultures and six clinical isolates), and six fungi. The primary phytochemical and chemical compositions were analyzed using qualitative chemical analysis and gas chromatography-mass spectrometry respectively.ResultsEthyl acetate extract of fruits was effective against most of the tested reference cultures such as Staphylococcus aureus, Yersinia enterocolitica, Vibrio parahaemolyticus, Bacillus subtilis, Salmonella paratyphi, Enterococcus feacalis, Xanthomonas oryzae and Pseudomonas aerugenosa, whereas methanol extract showed activity only against Staphylococcus aureus, Bacillus subtilis and Xanthomonas oryzae. The hexane and ethyl acetate extracts of fruits were more effective against most of the clinical isolates, whereas methanol extract was effective only against Klebsiella pneumoniae ESBL. The extracts of fruits and seeds did not show any significant antifungal activity against tested fungi. The presence of phenols, tannins, flavonoids, triterpenoids, steroids, alkaloids, saponis and carbohydrates in the different extracts was established. Gas chromatography-mass spectrometry studies on hexane and ethyl acetate extract of fruits resulted in the identification of 31 and 39 compounds respectively.ConclusionsPotent antibacterial phytochemicals are present in ethyl acetate extract of I. griffithii fruits. Further studies are needed to investigate activities of I. griffithii against multidrug resistant bacteria.