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Biomedical subjects

J T Cunningham

Publications and source records attributed to J T Cunningham.

At least 37 records · Page 2Linked to original sources

Endoscopic electrohydraulic lithotripsy in the management of pancreatobiliary lithiasis.

BACKGROUND: Clinical evaluation of intraoperative endoscopy with electrohydraulic lithotripsy (EHL) in the management of 13 patients with pancreatobiliary lithiasis was undertaken. METHODS: Ten patients with chronic pancreatitis with intraductal lithiasis in the head and three with biliary lithiasis (one choledochal, one cystic, one right intrahepatic) underwent intraoperative endoscopy with EHL. Shock waves were applied by visual contact with a 3-Fr gauge EHL probe until all stones were fragmented and irrigated free. All pancreatitis patients had failed ERCP attempts to stent their pancreatic ducts secondary to ductal lithiasis. Patients with pancreatic stones underwent lateral pancreatojejunostomy. Biliary stone patients underwent laparoscopic cholecystectomy with common duct exploration (two cases) and open cholecystectomy with choledochoduodenostomy (one case). RESULTS: Intraductal stone eradication was successful in all patients. Transampullary visualization of the duodenum was achieved in eight cases. Average EHL time was 65 min. There was no evidence of postoperative pancreatitis, cholangitis, or retained common duct stones. CONCLUSION: Intraoperative pancreatobiliary endoscopy with EHL is safe and effective in the eradication of pancreatic and bile duct stones. This novel technique represents a valuable adjunct in the management of chronic fibrocalcific pancreatitis with ductal lithiasis in the head region and in the open and laparoscopic management of intra- and extrahepatic bile duct stones.

Adult↗

Pancreatic stenting prevents pancreatitis after biliary sphincterotomy in patients with sphincter of Oddi dysfunction.

BACKGROUND & AIMS: Patients with sphincter of Oddi dysfunction are at high risk of developing pancreatitis after endoscopic biliary sphincterotomy. Impaired pancreatic drainage caused by pancreatic sphincter hypertension is the likely explanation for this increased risk. A prospective, randomized controlled trial was conducted to determine if ductal drainage with pancreatic stenting protects against pancreatitis after biliary sphincterotomy in patients with pancreatic sphincter hypertension. METHODS: Eligible patients with pancreatic sphincter hypertension were randomized to groups with pancreatic duct stents (n = 41) or no stents (n = 39) after biliary sphincterotomy. The primary measured outcome was pancreatitis after endoscopic retrograde cholangiopancreatography (ERCP). RESULTS: Pancreatic stenting significantly decreased the risk of pancreatitis from 26% to 7% (10 of 39 in the no stent group and 3 of 41 in the stent group; P = 0.03). Only 1 patient in the stent group developed pancreatitis after sphincterotomy, and 2 others developed pancreatitis at the time of stent extraction. Patients in the no stent group were 10 times more likely to develop pancreatitis immediately after sphincterotomy than those in the stent group (relative risk, 10.5; 95% confidence interval, 1.4-78.3). CONCLUSIONS: Pancreatic duct stenting protects significantly against post-ERCP pancreatitis in patients with pancreatic sphincter hypertension undergoing biliary sphincterotomy. Stenting of the pancreatic duct should be strongly considered after biliary sphincterotomy for sphincter of Oddi dysfunction; pancreatic sphincter of Oddi manometry identifies which high-risk patients may benefit from pancreatic stenting.

Adult↗

Prospective assessment of the ability of endoscopic ultrasound to diagnose, exclude, or establish the severity of chronic pancreatitis found by endoscopic retrograde cholangiopancreatography.

BACKGROUND: Our aim was to verify endoscopic ultrasound (EUS) accuracy to diagnose, rule out, and establish the severity of chronic pancreatitis found by endoscopic retrograde cholangiopancreatography (ERCP). METHODS: Patients undergoing ERCP for unexplained abdominal pain and/or suspected chronic pancreatitis underwent EUS. EUS was performed by experienced operators who were aware of the history but blinded to ERCP results. Chronic pancreatitis was defined using the Cambridge classification: 0 to 1 = "normal," 2 to 4 = "all chronic pancreatitis," 3 to 4 = "moderate to severe chronic pancreatitis." The number of EUS criteria required to obtain sensitivity, specificity, positive and negative predictive values > or = 85% was determined. EUS criteria for chronic pancreatitis are hyperechoic foci, hyperechoic strands, lobularity, hyperechoic duct, irregular duct, visible side-branches, ductal dilation, calcification, and cysts. RESULTS: One hundred twenty-six patients underwent EUS and ERCP. EUS was highly sensitive and specific (> 85%) depending on the number of criteria present. Chronic pancreatitis is likely (PPV > 85%) when more than two criteria (for "all chronic pancreatitis") and more than six criteria (for "moderate to severe chronic pancreatitis") are present. "Moderate to severe chronic pancreatitis" is unlikely (NPV > 85%) when fewer than three criteria are present. Independent predictors of chronic pancreatitis were "calcification" (p = 0.000001), history of alcohol abuse (p = 0.002), and the total number of EUS criteria (p = 0.008). CONCLUSIONS: EUS can accurately diagnose, rule out, and establish the severity of chronic pancreatitis found by ERCP.

Adult↗

Endoscopic sphincterotomy for stones by experts is safe, even in younger patients with normal ducts.

OBJECTIVE: To provide current information on the risks of endoscopic sphincterotomy for stone. SUMMARY BACKGROUND DATA: In recent years (since the popularity of laparoscopic cholecystectomy), endoscopic sphincterotomy has been used increasingly for the management of bile duct stones in relatively young and healthy patients. The validity of this trend has been questioned using data on short-term complications derived from earlier decades that involved more elderly and high-risk patients. METHODS: Seven academic centers collected data prospectively using a common database. Complications within 30 days of the procedures were documented by standard criteria. RESULTS: Of 1921 patients, 112 (5.8%) developed complications; two thirds of these events were graded as mild (<3 days in hospital). There was no evidence of increased risk in younger patients or in those with smaller bile ducts. There was only one severe complication and there were no fatalities in 238 patients age <60, with bile duct diameters of <9 mm. CONCLUSION: Sphincterotomy for stones can be performed very safely by experienced endoscopists.

Age Factors↗

Angiotensin hypertension.

1. One of the most important issues in the field of hypertension research centres on the therapeutic use of inhibitors of the renin-angiotensin system (RAS). Inhibitors of the RAS have potent anti-hypertensive effects, even in experimental models of hypertension and in human essential hypertension, where the activity of the peripheral RAS is low or normal. 2. It is suggested here that determining the mechanisms by which activation of the peripheral RAS produces hypertension will help us determine the anti-hypertensive effects of these inhibitors in low/normal renin-angiotensin hypertension. 3. Three hypotheses describing the hypertensive effects of angiotensin are discussed. The first hypothesis involves the direct vasoconstrictor effects of angiotensin. The second hypothesis suggests that chronic angiotensin produces hypertension by increasing Na+ reabsorption leading to volume expansion and hypertension. The final hypothesis suggests that, in angiotensin-induced hypertension, the increased Na+ reabsorption is not associated with volume expansion but, rather, is associated with an increase in vascular tone resulting from an interaction between angiotensin and the nervous system. 4. It is also hypothesized that the interaction between angiotensin and the nervous system produces a differential activation of sympathetic outflow that spares the kidney.

Angiotensin II↗

Mechanosensitive ion channels in putative aortic baroreceptor neurons.

Cell-attached patch-clamp experiments were performed on dissociated neurons from nodose ganglia of adult rats. Putative aortic baroreceptor neurons were identified by labeling nerve endings in the adventitia of the aortic arch with the carbocyanine dye DiI. Whereas previous experiments demonstrated the presence of mechanosensitive (MS) whole cell currents, these experiments studied single MS ion channels and examined the influence of culture conditions on their expression. Single MS channels were activated by applying negative pressure through the recording pipette. Channel openings became more frequent as the negative pressure was increased, with open probability increasing significantly above 30 mmHg. MS channels had a slope conductance of 114 pS and a reversal potential of approximately 0 mV, consistent with a nonspecific cation conductance. Channels were not affected by antagonists of voltage-gated conductances but were blocked by 20 microM gadolinium, a known blocker of MS ion channels. When nodose neurons were cocultured with aortic endothelial cells, but not aortic smooth muscle cells, the percentage of patches exhibiting MS ion channels increased significantly, suggesting that aortic endothelial cells secrete a diffusible factor that increases channel expression.

Animals↗

Fos expression following isotonic volume expansion of the unanesthetized male rat.

Cardiopulmonary afferents, baroreceptor afferents, or atrial natriuretic peptide binding to circumventricular organs may mediate the central response to volume expansion, a condition common to pregnancy, exercise training, and congestive heart failure. This study used Fos immunocytochemistry to examine brain regions activated by volume expansion. Male Sprague-Dawley rats were infused with isotonic saline equal to 10% of their body weight in 10 min followed by a maintenance infusion of 0.5 ml/min for 110 min. Control animals received 2-h infusions at 0.01 ml/min. Five minutes after the start of volume expansion, central venous pressure of expanded animals was significantly greater than control animals. The volume-expanded group exhibited significantly greater Fos activation (P < 0.05) in the area postrema, nucleus of the solitary tract, caudal ventrolateral medulla, paraventricular nucleus, supraoptic nucleus, and perinuclear zone of the supraoptic nucleus. Double labeling indicates that oxytocinergic neurons in the supraoptic nucleus are activated. Neurons in brain regions known to inhibit both sympathetic activity and vasopressin release show increased Fos expression following isotonic volume expansion.

Animals↗

Outcome after laparoscopic cholecystectomy for chronic acalculous cholecystitis.

Patients with typical symptoms of biliary tract disease but no gallstones on ultrasonography may benefit from cholecystectomy for presumed chronic acalculous cholecystitis. We retrospectively analyzed the outcome of 50 patients with a preoperative diagnosis of chronic acalculous cholecystitis based upon history (chronic or recurrent, postprandial right upper quadrant abdominal pain), the absence of acid-peptic disease, and normal biliary sonography treated with laparoscopic cholecystectomy (LC) and transcholecystic cholangiography from 1991 to 1996. All patients had preoperative cholecystokinin-stimulated hepatobiliary scintigraphy (CCK-HBS). There were 42 women and 8 men with a mean age of 43 years. CCK-HBS was abnormal in 45 patients (< or = 35 per cent gallbladder ejection fraction or nonfilling of the gallbladder). There was no postoperative mortality and one morbidity (urinary retention). All patients had microscopic evidence of chronic cholecystitis. At mean follow-up of 30 months, (range, 7-62 months) 39 patients (78%) were free of abdominal pain. Thirty-five of 45 patients with abnormal CCK-HBS were pain free (positive predictive value, 0.78). Four of five patients with normal CCK-HBS were pain free (negative predictive value, 0.20). The positive and negative likelihood ratios for CCK-HBS were 0.99 and 1.13, respectively, confirming that this test was not useful for predicting benefit from LC. Seven patients with persistent right upper quadrant pain had abnormal postoperative sphincter of Oddi manometry; they improved after endoscopic sphincterotomy. Patients with symptoms typical of biliary colic with normal gallbladder sonography and absence of acid-peptic disease benefit from LC in the majority of cases. Those who remain symptomatic after LC may benefit from endoscopic retrograde cholangiopancreatography with sphincter of Oddi manometry and endoscopic sphincterotomy when manometry is abnormal.

Adult↗

Fos-like immunoreactivity in the medulla after acute and chronic angiotensin II infusion.

Acute and chronic angiotensin (Ang) II hypertension are reported to have different mechanisms that involve differential contributions of the peripheral vasculature and the nervous system. Acute Ang II hypertension is mediated primarily by Ang acting at vascular smooth muscle, whereas chronic Ang II hypertension appears to have a neural component. In our experiments, the transition from a peripheral to a neural effect occurs over 10 hr of Ang II infusion in rats. To identify the role of the central nervous system in this transition, we measured Fos immunoreactivity, an indicator of neural activity, in the nucleus of the solitary tract (NTS), caudal ventrolateral medulla (CVL) and rostral ventrolateral medulla (RVL) in normal, sinoaortic denervated (SAD) and sham SAD rats after 2- or 18-hr Ang II infusion (50 ng/kg/min intravenously). Vehicle (5% dextrose) was infused in normal rats as control. Comparable increases in arterial pressure were produced by 2- and 18-hr Ang II infusion in all groups. Fos was increased in the NTS in sham SAD rats by 2- and 18-hr Ang II infusion (P < .05 vs. vehicle control). In the CVL, only 2-hr Ang II infusion was associated with increased Fos in normal and sham SAD rats (P < .05 vs. vehicle control) but not in SAD rats. In the RVL, 18-hr Ang II infusion elevated Fos in all groups (P < .05 vs. vehicle control). Activation of NTS during Ang II infusion is baroreceptor mediated and independent of infusion duration. Acute Ang II infusion produced a baroreceptor-mediated activation of the CVL, a region associated with baroreflex sympathoinhibition. Chronic Ang II infusion produced a baroreceptor-independent activation of the RVL, a brain area associated with sympathoexcitation, suggesting a centrally mediated increase in sympathetic outflow that may be associated with chronically infused Ang II.

Angiotensin II↗

Mechanical stimulation of neurites generates an inward current in putative aortic baroreceptor neurons in vitro.

We investigated the responses of putative aortic baroreceptor neurons to mechanical stimulation of their processes. Putative aortic baroreceptor neurons were identified by applying the carbocyanine dye DiI to the adventitia of the aortic arch of anesthetized rats. After at least 1 week, the nodose ganglia were removed and the neurons were cultured. Within 2-3 days, neurite outgrowth was evident on many neurons. The soma was voltage-clamped using whole cell patch clamp techniques while the neurites were deformed with pneumatic ejection of bath solution at 5-15 psi using a glass pipette (7-15 microm) positioned at least 50 microm from the neurite. Mechanical stimulation induced an inward current in 15 out of 17 putative aortic baroreceptor neurons. The magnitude of the current was related to the intensity of stimulation. The current was blocked by 20 microM gadolinium (n = 11), a reported blocker of mechanically sensitive ion channels, or by incubating the cells overnight in 10 microM phalloidin, which binds to actin filaments (n = 5). We conclude that mechanical deformation of neurites of putative baroreceptor neurons activates a mechanosensitive inward current in the soma and that the cytoskeletal actin filaments are involved in the generation of this current.

Animals↗

Magnetic resonance cholangiopancreatography: a novel approach to the evaluation of suspected pancreaticobiliary neoplasms.

BACKGROUND: Magnetic resonance cholangiopancreatography (MRCP) is a new noninvasive diagnostic method for pancreaticobiliary (PB) imaging without endoscopy, sedation, or iodinated contrast. The purpose of this study was to evaluate the ability of MRCP to depict pancreatic and biliary ductal anatomy compared to that of endoscopic retrograde cholangiopancreatography (ERCP) and to evaluate the ability of MRCP to accurately diagnose PB neoplasms. METHODS: Twenty patients had MRCP, and 17 also had ERCP. All studies were read prospectively by experienced reviewers blinded to other imaging data. Pathologic diagnosis was made in all patients. RESULTS: Bile duct dilatation seen by ERCP in 14 of 17 patients was correctly identified by MRCP in all 14 patients, and normal ducts were correctly identified by MRCP in the other 3 patients. The pancreatic duct was visible on MRCP in the pancreatic head in 17 of 20 patients, the body in 17 of 20 patients, and the tail in 15 of 20 patients. At ERCP, pancreatic duct dilatation was present in 11 cases and was identified by MRCP in 10 of them. Eighteen of 20 patients had malignant PB neoplasms. MRCP indicated PB neoplasm in 19 patients. Seventeen of these 19 patients had histologically confirmed malignant neoplasms pathologically, whereas 2 had benign pathology (both chronic pancreatitis). Among the 17 patients who also had ERCP, MRCP and ERCP correctly agreed on a final diagnosis of malignant neoplasm in 14 cases. In the three cases in which MRCP and ERCP disagreed on a final diagnosis, MRCP was correct in one and incorrect in two. CONCLUSIONS: MRCP can accurately and noninvasively delineate PB ductal anatomy and diagnose PB neoplasms comparably to ERCP. MRCP is an interesting new noninvasive method for evaluating patients with suspected PB neoplasms.

Bile Ducts↗

Differentiation of benign from malignant pancreatic masses by endoscopic ultrasound.

BACKGROUND: It is often difficult to determine whether a mass in the pancreas is benign or malignant. The goal was to evaluate whether endoscopic ultrasound (EUS) can reliably establish whether a mass is benign or malignant. METHODS: One hundred five patients with possible pancreatic tumors were referred for EUS. Those who were found to have a lesion suspicious for carcinoma and did not have a known malignancy also underwent EUS-guided FNA. RESULTS: A mass suspicious for cancer was identified in 73 patients, whereas inflammatory changes or a normal pancreas was noted in 32 patients. Four of the latter 32 patients were subsequently found to have cancer. EUS-guided FNA was performed on 47 of the 73 patients with a suspicious mass and was read as cancer in 27 patients, atypia in 10 patients, and benign in 10 patients. All 10 patients with atypia were subsequently confirmed to have cancer, and 6 of the 10 patients with a benign FNA were proved to have a tumor at surgery. EUS could differentiate the lesion as malignant with a sensitivity of 95%, specificity 88%, positive predictive value 95%, and negative predictive value 88%. CONCLUSIONS: Radial array EUS is helpful in supporting or refuting a diagnosis of cancer in a patient with a pancreatic mass. Although EUS-guided FNA can confirm the diagnosis, a negative FNA should not preclude exploration when clinically indicated.

Adenocarcinoma↗

Transpapillary stenting of proximal biliary strictures: does biliary sphincterotomy reduce the risk of postprocedure pancreatitis?

BACKGROUND: Pancreatitis after biliary stenting is a rare complication. To reduce this risk, some endoscopists routinely perform biliary sphincterotomy before stenting, but the value of this practice is not established. METHODS: The incidence of pancreatitis was reviewed in patients undergoing biliary stenting with and without a biliary sphincterotomy. RESULTS: Postprocedure pancreatitis occurred in 4 of 83 (4.8%) patients treated with transpapillary biliary stents. Patients with proximal biliary strictures were at significantly increased risk for postprocedure pancreatitis (4 of 24) versus those with distal or no strictures (0 of 59) (p = 0.006). The four patients with pancreatitis after stenting had not undergone sphincterotomy. Of those treated conservatively, two cases were graded severe (one fatal), and one was mild. The other patient was markedly symptomatic from pancreatitis, but improved dramatically after treatment with a needle-knife sphincterotomy done within 24 hours of the original ERCP. CONCLUSION: The risk of pancreatitis following transpapillary biliary stenting is increased in patients with proximal biliary strictures. Such lesions (malignant or benign) may serve as a fulcrum, leading to medial deflection of the stent and compression of the pancreatic orifice. The hypothesis that sphincterotomy may decrease the risk of biliary stent-induced obstructive pancreatitis should be tested in patients with proximal biliary strictures.

Adult↗

Sphincter of Oddi dysfunction is associated with chronic pancreatitis.

OBJECTIVES: Chronic pancreatitis can be caused by ductal obstruction resulting from cicatricial papillary stenosis, but sphincter of Oddi motility studies have been inconclusive in patients with established chronic pancreatitis. We sought to determine whether there is an association between papillary sphincter dysfunction and changes of early chronic pancreatitis. METHODS: Consecutive patients who underwent sphincter of Oddi manometry to investigate unexplained upper abdominal pain (n = 104) were assessed for evidence of chronic pancreatitis by pancreatic ductography, endoscopic ultrasound, and pancreatic fluid bicarbonate concentration. RESULTS: Sphincter of Oddi dysfunction patients were four times more likely (odds ratio = 4.6) to have evidence of chronic pancreatitis than were those without sphincter dysfunction (p = 0.01). Of 68 patients with sphincter of Oddi dysfunction, 20 (29%) had structural evidence of chronic pancreatitis. Twenty of 23 (87%) patients with chronic pancreatitis had sphincter of Oddi dysfunction. CONCLUSIONS: Sphincter of Oddi dysfunction is associated with changes of chronic pancreatitis in patients with unexplained pancreaticobiliary pain. Longitudinal follow-up is required to confirm these preliminary findings.

Adult↗

Integrative role of the lamina terminalis in the regulation of cardiovascular and body fluid homeostasis.

1. Cardiovascular and body fluid homeostasis depends upon the activation and co-ordination of reflexes and behavioural responses. In order to accomplish this, the brain receives and processes both neural and chemical input. Once in the brain, information from sources signalling the status of the cardiovascular system and body fluid balance travels, and is integrated, throughout a widely distributed neural network. Recent studies using neuroanatomical and functional techniques have identified several key areas within this neural network. One major processing node is comprised of structures located along the lamina terminalis. 2. Structures associated with the lamina terminalis include the median preoptic nucleus (MePO) and two sensory circumventricular organs (SCVO), the subfornical organ (SFO) and the organum vasculosum of the lamina terminalis (OVLT). Current evidence indicates that blood-borne signals, such as angiotensin II (AngII), reach SCVO (e.g. SFO) where they are transduced. This information is then carried via neural pathways to brain nuclei (e.g. MePO) where it is integrated with other inputs, such as those derived from systemic arterial blood pressure and volume receptors. 3. Because of their receptive and integrative functions, lamina terminalis structures are essential for the normal control of hormone release (e.g. vasopressin), sympathetic activation and behaviours (thirst and salt appetite), which collectively contribute to maintenance of cardiovascular and body fluid homeostasis.

Adrenergic Fibers↗