PubMed Health⌕ Search

Biomedical subjects

J T Cunningham

Publications and source records attributed to J T Cunningham.

At least 19 recordsLinked to original sources
PubMed2003

Proposed role of the paraventricular nucleus in cardiovascular deconditioning.

AIM: Cardiovascular deconditioning occurs in individuals exposed to prolonged spaceflight or bedrest and is associated with the development of orthostatic intolerance. Although the precise mechanisms remain to be fully elucidated, astronauts returning from space or bedrest patients returning to normal upright posture present with decreases in plasma volume and alterations in autonomic function. The hindlimb unloaded (HU) rat has been a useful model to study the effects of cardiovascular deconditioning as it mimics many of the changes that occur after spaceflight and bedrest. RESULTS: Experiments performed in HU rats suggest that cardiovascular deconditioning attenuates baroreflex mediated sympathoexcitation and enhances cardiopulmonary receptor mediated sympathoinhibition. These alterations appear to be due to changes in the central nervous system and may contribute to the pre disposition towards orthostatic intolerance associated with cardiovascular deconditioning. The paraventricular nucleus (PVN) of the hypothalamus is important in basal and reflex control of sympathetic outflow. Recent evidence suggests that nitric oxide (NO) is an important inhibitory neurotransmitter in the PVN and that alterations in nitroxidergic transmission in the PVN may be involved in elevated sympathetic tone in certain disease states. CONCLUSION: Based on evidence from other laboratories and published and preliminary data from our own laboratories, this review proposes a role for the PVN in cardiovascular deconditioning. In particular, we discuss the hypothesis that increased NO in the PVN contributes to the altered cardiovascular reflexes observed following deconditioning and how these reflexes may be related to the orthostatic intolerance observed after prolonged spaceflight or bedrest.

Animals↗
PubMed2003

Lesions of the diagonal band of broca enhance drinking in the rat.

This study examined the role of the diagonal band of Broca (DBB) in drinking behaviour and vasopressin release. Adult male rats were anaesthetized (pentobarbital 50 mg/kg) and received DBB injections of either ibotenic acid (0.5 microl of 5 micro g/ microl) or vehicle (0.5 microl of phosphate-buffered saline). Although baseline drinking and urine output were not affected, drinking to 30% polyethylene glycol (MW 8000; 1 ml/100 g s.c.) and angiotensin II (0, 1.5 and 3.0 mg/kg s.c.) were significantly increased in ibotenic acid in phosphate-buffered saline (DBBX) rats. Drinking to hypertonic saline (0.9, 4 and 6%; 1 ml/100 g), and water deprivation were not significantly affected. DBBX rats had significantly lower basal heart rates than controls but the cardiovascular responses to infusions of angiotensin II (100 ng/kg/min i.v. for 45 min) were not affected. DBBX rats had significantly higher basal vasopressin, but angiotensin-stimulated vasopressin release was not significantly different. Although the DBB is not involved in basal water intake, it is involved in dipsogenic responses to hypovolemic stimuli and possibly basal autonomic function and basal vasopressin release.

Angiotensin II↗
PubMed2002

Fos immunoreactivity in the diagonal band and the perinuclear zone of the supraoptic nucleus after hypertension and hypervolaemia in unanaesthetized rats.

We used Fos immunocytochemistry to study the effects of hypertension and hypervolaemia on neurones in the diagonal band of Broca and the perinuclear zone of the supraoptic nucleus, two nuclei that are both involved in the baroreceptor regulation of vasopressin neurones in the supraoptic nucleus. In addition, we used sino-aortic denervation to examine the role of arterial baroreceptors in the response to these haemodynamic changes. Sham-operated and sino-aortic denervated rats were infused with phenylephrine sufficient to increase blood pressure for 2 h. Control rats were infused with the same volume of isontonic saline. Only Sham sino-aortic denervated rats showed reflex bradycardia in response to the increased blood pressure. Volume expansion was produced by infusing the rats with isotonic saline equal to 10% of their body weight for 10 min, which significantly increased central venous pressure. In the diagonal band of Broca and the perinuclear zone, the number of Fos-positive neurones was significantly increased after phenylephrine infusion. Sino-aortic denervation blocked the significant increase in both regions. After volume expansion, a significant increase in Fos staining was observed only in the perinuclear zone of the supraoptic nucleus. This increase was not blocked by sino-aortic denervation. Our results indicate that both the diagonal band of Broca and the perinuclear zone of the supraoptic nucleus are activated by stimulating arterial baroreceptors; however, the perinuclear zone of the supraoptic nucleus is stimulated during volume expansion. Furthermore, the activation of perinuclear zone of the supraoptic nucleus after volume expansion is not dependent on intact arterial baroreceptors.

Animals↗
PubMed2002

Evaluation of unexplained acute and acute recurrent pancreatitis using endoscopic retrograde cholangiopancreatography, sphincter of Oddi manometry and endoscopic ultrasound.

BACKGROUND AND STUDY AIMS: Unexplained pancreatitis represents a diagnostic challenge. The aim of this study was to determine the diagnostic utility of endoscopic retrograde cholangiopancreatography (ERCP) with sphincter of Oddi manometry (SOM), bile analysis, and endoscopic ultrasound (EUS) in evaluating such patients. PATIENTS AND METHODS: Of 162 patients referred for evaluation of pancreatitis, 72 with a known cause were excluded. The remainder ( n=90) was classified as having prior acute ( n=24) or recurrent acute pancreatitis ( n=66). Bile sampling and SOM were performed at the time of ERCP. EUS was used to assess for tumors and for chronic pancreatitis. Clinical outcomes were evaluated by questionnaire. RESULTS: ERCP was successful in 88/89 patients (99 %). Manometry was successful in 63/67 patients (94 %), and 56 patients underwent EUS. Findings were categorized into five distinct etiologies: sphincter of Oddi dysfunction (SOD) ( n=28; 31 %), pancreas divisum ( n=18; 20 %), biliary ( n=18; 20 %), idiopathic ( n=18; 20 %) and tumor-related ( n=8; 9 %). Features of moderate or severe chronic pancreatitis by EUS and ERCP criteria were found in 18 patients (21 %); an additional nine patients had chronic pancreatitis by EUS criteria alone. EUS identified all the tumors. The condition was improved in 96 % of all patients undergoing endoscopic therapy. CONCLUSION: An etiology was identified in the majority of patients with unexplained pancreatitis. SOD represented the most common finding. Moderate to severe chronic pancreatitis was found in over one-fifth of these patients. Bile analysis, SOM, and EUS are useful tools in the evaluation of unexplained acute pancreatitis.

Acute Disease↗
PubMed2001

Cardiovascular regulation of vasopressin neurons in the supraoptic nucleus.

This paper reviews the regulation of hypothalamic vasopressin and oxytocin neurosecretory cells in the neural response to plasma volume expansion. Many questions remain unanswered regarding how an increase in volume affects neurohypophysial hormone secretion, what receptors are important in mediating this response, and which neural pathways are responsible for conveying the signal from those receptors to the hypothalamus. Plasma volume expansion activates regions of the central nervous system associated with inhibition of vasopressin release, oxytocin secretion, and inhibition of sympathetic nerve activity. Cardiac receptors, not arterial baroreceptors, are primarily responsible for activation of the regions associated with regulation of vasopressin secretion and sympathetic outflow. Other stimuli that as yet are undefined account for activation of oxytocin-secreting neurons. Electrophysiology experiments have measured the inhibition of vasopressin-secreting magnocellular neurons in the supraoptic nucleus by select stimulation of cardiac receptors in the caval-atrial junction. Further experiments suggest that the perinuclear zone, a population of neurons surrounding the supraoptic nucleus, is a necessary part of the pathway by which caval-atrial stretch decreases the excitability of vasopressin neurons. The perinuclear zone is also a necessary synapse for arterial baroreceptor-mediated inhibition of vasopressin neurons. This suggests that the neural pathways that inhibit vasopressin release in response to an increase in blood pressure and an increase in blood volume may overlap at the perinuclear zone of the supraoptic nucleus. Finally, the integration of various neural pathways activated by multiple receptors to ultimately determine the activity of magnocellular neurons and vasopressin secretion is discussed.

Animals↗
PubMed2001

Endoscopic treatment of post-liver transplantation biliary leaks with stent placement across the leak site.

BACKGROUND: Biliary tract leaks occur in over 10% of patients undergoing liver transplantation and are the most common cause of biliary tract-related death in these patients. A number of treatment options are available, but a standard approach has not been established. METHODS: Twenty-six patients were retrospectively studied who had post-transplantation leaks develop with special reference to those who underwent endoscopic placement of a "leak-bridging" stent. RESULTS: Endoscopic retrograde cholangiography was performed in all cases with no procedure-related complications. Twenty-four patients had a leak-bridging stent, 1 a transpapillary stent, and 1 a nasobiliary drain. Leak resolution occurred in 23 cases (88%) after initial stent placement. The median time to stent removal was 8 weeks. Three patients did not respond to initial treatment; 2 were successfully treated with another stent and a single patient required surgical repair. Four deaths occurred during follow-up, all unrelated to the biliary leak. CONCLUSIONS: Placement of a leak-bridging stent is a safe and effective initial treatment for post-liver transplantation biliary leaks.

Bile↗
PubMed2001

The decision-making value of magnetic resonance cholangiopancreatography in patients seen in a referral center for suspected biliary and pancreatic disease.

OBJECTIVE: To assess the ability of MRCP to alter the differential diagnosis and to prevent diagnostic and/or therapeutic ERCP. The diagnostic accuracy of magnetic resonance cholangiopancreatography (MRCP) for biliary and pancreatic disease is well documented. Some believe MRCP may prevent diagnostic ERCP or add useful information, however there are no reports of its impact on clinical management. METHODS: Consecutive patients referred for ERCP underwent clinic evaluation, then MRCP, and then ERCP. In Phase 1, the number of differential diagnoses and the perceived need for diagnostic ERCP were evaluated after each step by the endoscopist who performed the ERCP. In Phase 2, the process was repeated after presenting clinical information and MRCP results to different individual physicians: another endoscopist, a hepatologist, a radiologist, and a surgeon (all were blinded to ERCP results). RESULTS: Forty patients were enrolled. Clinical contexts were jaundice (19.7%), abnormal liver enzymes (42.6%), abdominal pain (11.5%), recurrent acute pancreatitis (11.5%), and suspected complications of chronic pancreatitis (14.7%). In Phase 1, adding MRCP information to diagnostic ERCP information did not change the mean number of differential diagnoses significantly and prevented no therapeutic ERCP. In Phase 2, adding MRCP to clinical information only (without ERCP) reduced the differential diagnosis significantly for the radiologist and the surgeon only and would have prevented < or =3% of diagnostic and therapeutic ERCP for all physicians. CONCLUSION: The value of MRCP information may be limited if patient selection is inappropriate and may differ in physicians depending on their speciality.

Biliary Tract Diseases↗
PubMed2001

Integration of neuroscience and endocrinology in hybrid PBL curriculum.

At the University of Missouri-Columbia, the medical school employs a problem-based learning curriculum that began in 1993. Since the curriculum was changed, student performance on step 1 of the United States Medical Licensing Examination has significantly increased from slightly below the national average to almost one-half a standard deviation above the national mean. In the first and second years, classes for students are organized in classes or blocks that are 8 wk long, followed by 1 wk for evaluation. Initially, basic science endocrinology was taught in the fourth block of the first year with immunology and molecular biology. Student and faculty evaluations of the curriculum indicated that endocrinology did not integrate well with the rest of the material taught in that block. To address these issues, basic science endocrinology was moved into another block with neurosciences. We integrate endocrinology with neurosciences by using the hypothalamus and its role in neuroendocrinology as a springboard for endocrinology. This is accomplished by using clinical cases with clear neuroscience and endocrinology aspects such as Cushing's disease and multiple endocrine neoplastic syndrome type 1.

Curriculum↗
PubMed2001

Lesion of the perinuclear zone attenuates cardiac sensitivity of vasopressinergic supraoptic neurons.

Discrete stretch of the caval-atrial junction decreases the activity of vasopressin-secreting neurons in the supraoptic nucleus (SON). The perinuclear zone (PNZ) of the SON is necessary for inhibition of vasopressin neurons following an increase in blood pressure. To determine whether the PNZ is necessary for cardiopulmonary regulation of vasopressin neurons, male rats received three unilateral injections of the excitotoxin ibotenic acid (n = 9) or phosphate-buffered saline vehicle (n = 10) into the PNZ. Extracellular activity of antidromically identified phasic vasopressin neurons in the ipsilateral SON was recorded. Of the 26 neurons recorded from vehicle-injected rats 26 were inhibited by an increase in blood pressure and 22 of those neurons were sensitive to caval-atrial distension. Of the neurons recorded from PNZ-lesion rats, only 12 of 29 were inhibited by an increase in blood pressure (P < 0.05), and only 11 neurons were sensitive to caval-atrial stretch (P < 0.05). Functional lesion of the PNZ significantly attenuates both arterial and cardiopulmonary baroreceptor-mediated inhibition of supraoptic vasopressin neurons, suggesting that the PNZ is a necessary component of both pathways.

Animals↗
PubMed2000

Therapeutic ERCP in the management of pancreatitis in children.

BACKGROUND: The use of diagnostic and therapeutic endoscopic retrograde cholangiopancreatography (ERCP) is increasing in the management of pancreatobiliary diseases in children. METHODS: Over a 32-month period, we performed 34 ERCP procedures for the treatment of pancreatitis in 22 children at two university hospitals. Demographics and clinical data and ERCP findings were documented. Clinical status was assessed 6 months before the first ERCP and 6 months after the last ERCP, according to general condition, severity and frequency of pain, and health care encounters (emergency department visits, clinic visits, and hospital admissions related to the pancreatitis). RESULTS: Mean age of the patients was 10.7 years (range 1.5 to 17 years). Abdominal pain was the main presenting symptoms with hyperamylasemia and hyperlipasemia. Clinical diagnoses included acute pancreatitis (6), recurrent pancreatitis (5), and chronic pancreatitis (11). The mean follow-up was 16.4 months. Nine patients had sphincter manometry, with abnormal results leading to biliary sphincterotomy in 4. Fifteen patients underwent a total of 23 therapeutic ERCP procedures unrelated to sphincter dysfunction. There were 2 complications of 34 procedures (6%), both being mild pancreatitis after sphincter manometry. There were no deaths. There was a significant reduction in frequency (p < 0.01) and severity of pain (p < 0.01) after intervention. Patients without pancreatographic changes of chronic pancreatitis had the most marked clinical improvement (p < 0.05). In those with ductal changes of chronic pancreatitis, clinical improvement was not predicted by the extent of ductal changes. There was a significant decrease in health care encounters (p < 0.05) and improvement in general condition (p < 0.01) after endoscopic therapy, especially in those with a normal pancreatogram. CONCLUSIONS: Therapeutic ERCP is safe in pediatric patients with pancreatitis. Significant clinical improvement is achieved in patients with biliary or pancreatic stone disease. Prospective studies with long-term follow-up are needed to determine the impact of endoscopic therapy in patients with chronic pancreatitis and sphincter of Oddi dysfunction.

Acute Disease↗
PubMed2000

Effects of right atrial distension on the activity of magnocellular neurons in the supraoptic nucleus.

A small balloon placed at the junction of the superior vena cava and right atrium was used to stimulate cardiac volume receptors in pentobarbital sodium-anesthetized male rats. Extracellular recordings were obtained from antidromically identified vasopressinergic and oxytocinergic neurosecretory cells of the supraoptic nucleus. Cells were considered sensitive to the stimulus if balloon inflation resulted in a 30% change in firing frequency. Balloon inflation that did not stretch the caval-atrial junction had no significant effect on vasopressin neurons (n = 51, P > 0.05). Stretch of the caval-atrial junction decreased the firing activity in 64 of 83 putative vasopressin neurons (P < 0.01 compared with control). Stretch of the caval-atrial junction influenced the firing activity of only 3 of 26 antidromically activated oxytocinergic neurons, an effect not statistically different from control (P > 0. 05). When bilateral vagotomy was performed while recording from vasopressin neurons (n = 5), sensitivity to stretch of the caval-atrial junction was eliminated. Cardiac receptors located at the junction of the superior vena cava and right atrium may be important in regulating the activity of vasopressinergic but not oxytocinergic neurons of the supraoptic nucleus.

Animals↗
PubMed2000

Role of the locus ceruleus in baroreceptor regulation of supraoptic vasopressin neurons in the rat.

The goal of this study was to identify the source of baroreceptor-related noradrenergic innervation of the diagonal band of Broca (DBB). Male Sprague-Dawley rats underwent sinoaortic denervation (SAD, n = 13) or sham SAD surgery (n = 13). We examined Fos expression produced by baroreceptor activation and dopamine-beta-hydroxylase immunofluorescence in hindbrain regions that contain noradrenergic neurons. Baroreceptors were stimulated by increasing blood pressure >40 mmHg with phenylephrine (10 microgram. kg(-1). min(-1) iv) in sham SAD and SAD rats. Controls were infused with 0.9% saline. Only the locus ceruleus (LC) demonstrated a baroreceptor-dependent increase in Fos immunoreactivity in dopamine-beta-hydroxylase-positive neurons. In a second experiment, normal rats received rhodamine-labeled microsphere injections in the DBB (n = 12) before phenylephrine or vehicle infusion. In these experiments, only the LC consistently contained Fos-positive cells after phenylephrine infusion that were retrogradely labeled from the DBB. Finally, we lesioned the LC with ibotenic acid and obtained extracellular recordings from identified vasopressin neurons in the supraoptic nucleus. LC lesions significantly reduced the number of vasopressin neurons that were inhibited by acute baroreceptor stimulation. Together, these results suggest that noradrenergic neurons in the LC participate in the baroreflex activation of the DBB and may thus be important in the baroreflex inhibition of vasopressin-releasing neurons in the supraoptic nucleus.

Animals↗
PubMed2000

Baroreceptor sensitivity of rat supraoptic vasopressin neurons involves noncholinergic neurons in the DBB.

Previous studies suggest that cholinergic neurons in the diagonal band of Broca (DBB) participate in the baroreceptor-mediated inhibition of phasic vasopressin neurons in the supraoptic nucleus (SON). To test this hypothesis, extracellular recordings were obtained from putative vasopressin SON neurons of anesthetized rats injected with the cholinergic immunotoxin 192 IgG-saporin (0.8 microg/microl) in the DBB. Baroreceptor sensitivity of neurons was tested with brief phenylephrine-induced (10 microg/10 microl iv) increases in blood pressure of at least 40 mmHg. In rats injected with vehicle or unconjugated saporin, 19 of 21 and 18 of 20 phasic neurons, respectively, were inhibited by increased blood pressure. In rats injected with 192 IgG-saporin, which significantly reduced the number of choline acetyltransferase (ChAT)-positive DBB neurons, 33 of 36 phasic neurons were inhibited. Normal rats and rats with DBB saporin injections received rhodamine bead injections into the perinuclear zone (PNZ) to retrogradely label DBB neurons, and their brains were stained for ChAT. ChAT-positive DBB neurons were not retrogradely labeled from the PNZ. Together, these results indicate that the pathway relaying baroreceptor information to the SON involves noncholinergic DBB neurons.

Animals↗
PubMed1999

Comparative costs of metal versus plastic biliary stent strategies for malignant obstructive jaundice by decision analysis.

BACKGROUND: For palliation of patients with malignant obstructive jaundice, expansile metal stents provide longer patency than plastic stents but are more expensive. The optimal cost-effective strategy has not been established. Our aim was to compare the relative costs of 3 strategies: (1) plastic stent, with exchange on occlusion; (2) metal stent initially, with coaxial plastic stent insertion in the event of occlusion; or (3) plastic stent initially, with metal stent exchange in the event of occlusion. METHODS: A decision analysis model was created using DATA 2.6 software to assess the relative costs of the three strategies. Values for variables including the probabilities of reintervention and patient survival were obtained from published data. Costs were based on Medicare reimbursements of hospital charges, and the model was evaluated from the perspective of a third-party payer. One-way and two-way sensitivity analysis of the variables was performed over a wide range. RESULTS: The outcome is highly sensitive to the ratio of metal stent cost relative to endoscopic retrograde cholangiopancreatography cost (cost ratio M:ERCP) and to the length of survival of the patient. The most economical strategies were (2), (3) and (1) for M:ERCP cost ratios of <0.5, 0.5 to 0.7, and >0.7, respectively. CONCLUSIONS: The choice of stent should be guided by the relative local costs of ERCP and metal stents and by the prognosis of the patient. At current metal stent costs and Medicare reimbursement rates, initial placement of a plastic stent, followed by metal stent placement at first occlusion in longer survivors, is an economical option. If metal stent cost is less than half of ERCP cost, then initial insertion of a metal stent would be most economical. Use of plastic stents is preferable for patients surviving less than 4 months, whereas metal stents are more economical for patients with longer survival.

Biliary Tract Neoplasms↗
PubMed1999

Same-day discharge after endoscopic biliary sphincterotomy: observations from a prospective multicenter complication study. The Multicenter Endoscopic Sphincterotomy (MESH) Study Group.

BACKGROUND: Same-day discharge after endoscopic biliary sphincterotomy (ES) is a common clinical practice, but there have been few data to guide appropriate selection of patients. Using a prospective, multicenter database of complications, we examined outcomes after same-day discharge as it was practiced by a variety of endoscopists and evaluated the ability of a multivariate risk factor analysis to predict which patients would require readmission for complications. METHODS: A 150-variable database was prospectively collected at time of ES, before discharge and again at 30 days in consecutive patients undergoing ES at 17 centers. Complications were defined by consensus criteria and included all specific adverse events directly or indirectly related to ES requiring more than 1 night of hospitalization. RESULTS: Six hundred fourteen (26%) of 2347 patients undergoing ES were discharged on the same day as the procedure, ranging from none at 6 centers to about 50% at 2 centers. After initial observation and release, readmission to the hospital for complications occurred in 35 (5.7%) of 614 same-day discharge patients (20 pancreatitis and 15 other complications, 3 severe). Of the same-day discharge patients, readmission was required for 14 (12.2%) of 115 who had at least one independently significant multivariate risk factor for overall complications (suspected sphincter of Oddi dysfunction, cirrhosis, difficult bile duct cannulation, precut sphincterotomy, or combined percutaneous-endoscopic procedure) versus 21 (4.2%) of 499 without a risk factor (odds ratio 3.1: 95% confidence interval [1.6, 6.3], p < 0.001). Of complications presenting within 24 hours after ES, only 44% presented within the first 2 hours, but 79% presented within 6 hours. CONCLUSIONS: Same-day discharge is widely utilized and relatively safe but results in a significant number of readmissions for complications. For patients at higher risk of complications, as indicated by the presence of at least one of five independent predictors, observation for 6 hours or overnight may reduce the need for readmission.

Adult↗
PubMed1999

Fos expression in brain stem nuclei of pregnant rats after hydralazine-induced hypotension.

Fos and dopamine beta-hydroxylase immunoreactivity were evaluated in the brain stems of 21-day pregnant and virgin female rats injected with either hydralazine (HDZ; 10 mg/kg iv) or vehicle. HDZ produced significant hypotension in both groups, although baseline blood pressure was lower in pregnant rats (96 +/- 2.5 mmHg) than in virgin female rats (121 +/- 2.8 mmHg). There were no differences in Fos immunoreactivity in the brain stems of pregnant and virgin female rats after vehicle treatment. HDZ-induced hypotension significantly increased Fos expression in both groups; however, the magnitude of the increases differed in the caudal ventrolateral medulla (CVL), the area postrema (AP), and the rostral ventrolateral medulla (RVL). Fos expression after HDZ in pregnant rats was augmented in noncatecholaminergic neurons of the CVL but was attenuated in the AP and in noncatecholaminergic neurons in the RVL. These results are consistent with differences in the sympathetic response to hypotension between pregnant and virgin female rats and indicate that the central response to hypotension may be different in pregnant rats.

Animals↗