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Biomedical subjects

J T Cunningham

Publications and source records attributed to J T Cunningham.

At least 55 records · Page 3Linked to original sources
PubMed1995

Management of biliary strictures due to laparoscopic cholecystectomy.

Injury to the extrahepatic bile ducts during laparoscopic cholecystectomy (LC) is a cause of serious long-term patient morbidity. In order to identify management strategies and outcome, we undertook a retrospective review and analysis of patients referred to the Department of Surgery and the Division of Gastroenterology for management of bile duct strictures due to injury at LC. Eighteen patients (15 women, 3 men) with a mean age of 41 years were identified over a 4-year period. Six patients had injuries identified at LC. Ten patients had previously undergone an attempt at operative repair (8 end-to-end anastomoses, 1 choledochoduodenostomy, 1 cystic duct jejunostomy). There were 5 Bismuth Grade I strictures, 6 Grade II, 2 Grade III and 5 Grade IV. Ten patients were managed nonoperatively with stents placed by radiologic or endoscopic techniques. Four patients were managed with operation alone (2 choledochojejunostomy, 1 hepaticojejunostomy, and 1 external T-tube drainage) and 4 patients with a combined endoscopic and operative approach (all 4 with hepaticojejunostomy after initial endoscopic retrograde cholangiopancreatography or percutaneous transhepatic cholangiography management). Bile duct strictures due to LC are frequently located in the proximal bile ducts (Bismuth II-IV) and are technically difficult to repair. In the majority of cases, injuries are unrecognized at LC. Both immediate and delayed repair attempts prior to referral were frequently unsuccessful. Many bile duct strictures can be managed successfully in the early postoperative period with endoscopic and radiologic stenting techniques. Strictures which cannot be managed nonoperatively are repaired with Roux-en-Y hepaticojejunostomy.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1995

Mechanosensitive currents in putative aortic baroreceptor neurons in vitro.

1. Whole cell patch-clamp experiments were conducted to determine whether rat aortic baroreceptor neurons contain mechano-sensitive conductances. 2. Putative aortic baroreceptor neurons in the nodose ganglia were identified by injecting DiI onto the adventitia of the aortic arch. Nodose ganglia neurons were dissociated after > or = 1 wk. A fluorescein-conjugated tetanus toxin fragment was used to confirm that the cells labeled with DiI in culture were neurons. 3. Hypoosmotic stretch significantly increased the conductance of DiI-labeled neurons (n = 19). The reversal potential of the response was -11 +/- 1 (SE) mV. 4. In experiments on unlabeled neurons, only 7 of 13 cells showed increases in conductance. BC3H1 cells, a mouse tumor cell line, showed no changes in conductance. 5. Gadolinium (20 microM), a putative blocker of mechanosensitive channels, prevented the increase in conductance produced by hypoosmolality in seven of seven labeled cells. Equimolar concentrations of lanthanum (n = 6) and omega-conotoxin GVIA (1 microM, n = 4), which block voltage-gated calcium channels, failed to significantly affect the inward current.

Animals↗
PubMed1995

Structural versus functional modulation of the arterial baroreflex.

Structural changes in large arteries are often considered the predominant mechanism responsible for decreased baroreflex sensitivity and baroreceptor resetting in hypertension, atherosclerosis, and aging. Recent work has demonstrated that "functional" mechanisms, both at the level of the peripheral sensory endings and within the central nervous system, contribute significantly to altered baroreflex responses. We have conducted both reductive studies of mechanoelectrical transduction in cultured baroreceptor neurons and integrative studies with in vivo recordings of the activity of baroreceptor afferent fibers and efferent sympathetic nerves. Results suggest that the primary mechanism of mechanical activation of baroreceptor neurons involves opening of stretch-activated ion channels susceptible to blockade by gadolinium. Baroreceptor nerve activity is modulated by the activity of potassium channels and the sodium-potassium pump and by paracrine factors, including prostacyclin, oxygen free radicals, and factors released from aggregating platelets. Endothelial dysfunction and altered release of these paracrine factors contribute significantly to the decreased baroreceptor sensitivity in hypertension and atherosclerosis. The central mediation of the baroreflex depends on the pulse phasic pattern of afferent baroreceptor discharge. Baroreflex-mediated inhibition of sympathetic nerve activity is well maintained during pulse phasic afferent activity. Continuous, nonphasic baroreceptor discharge or a rapid (> 1.5 Hz) pulse phasic discharge results in disinhibition of sympathetic activity. This disinhibition during continuous baroreceptor input is exaggerated with aging. Thus, a defect in central mediation of the baroreflex may be a major cause of the impaired baroreflex and sympathoexcitation in the elderly. In summary, functional neural mechanisms, in addition to structural vascular changes, contribute importantly to altered baroreflex responses in normal and pathophysiological states.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1995

Endoscopic retrograde cholangiopancreatography in pregnancy.

BACKGROUND: Pancreaticobiliary disease in pregnancy is relatively uncommon. The frequency of choledocholithiasis in pregnancy requiring intervention has been reported to be as low as one in 1200 deliveries. Traditionally, intervention in these patients has been surgical. Although surgery has an overall low morbidity and mortality for the expectant mother, it carries with it a 4- to 6-wk recovery period and a possibly increased risk of fetal wastage. Published information regarding the role and safety of ERCP in pregnancy is limited. This series of 23 pregnant patients undergoing ERCP was collected from six different medical centers. METHODS: Twenty-three pregnant patients with symptomatic pancreaticobiliary disease underwent a total of 29 ERCPs (three patients had diagnostic ERCP, and 20 had therapeutic ERCP). Fifteen, eight, and six procedures were performed in the first, second, and third trimesters, respectively. The only ERCP complication was pancreatitis in one patient. There was one spontaneous abortion (3 months after ERCP) and one neonatal death; however, casual relationship to ERCP was not apparent. CONCLUSION: Diagnostic and therapeutic ERCP appears reasonably safe and effective in pregnancy. Cautious and selective use of this procedure offers a viable alternative to surgery or observation in patients with emergent pancreaticobiliary problems.

Adult↗
PubMed1994

Perinuclear zone and diagonal band lesions enhance angiotensin responses of rat supraoptic neurons.

Sinoaortic denervation in the rat is associated with an increased sensitivity of vasopressin neurons in the supraoptic nucleus (SON) to peripheral angiotensin II (ANG II). Lesion studies have indicated that the diagonal band of Broca (DBB) and the perinuclear zone of the SON in the lateral hypothalamus (PNZ) are essential components in the central pathway for the baroreceptor inhibition of vasopressin SON neurons. The present study examined the effect of ibotenate lesions in either the DBB or the lateral hypothalamus, which includes the PNZ, on the responses of SON neurons to peripherally administered ANG II (500 pmol/kg ia). Extracellular recordings obtained from vasopressin SON neurons in pentobarbital-anesthetized rats indicate that DBB and PNZ lesions not only interrupted the baroreceptor-mediated inhibition of SON neurons but also significantly increased the excitatory effects of ANG II on putative vasopressin SON neurons. These results suggest that ibotenate lesions of the DBB and the lateral hypothalamus that include the PNZ affect the ANG II-induced activation of putative vasopressin SON neurons in a manner consistent with results obtained from baroreceptor-denervated rats.

Angiotensin II↗
PubMed1993

Norepinephrine injections in diagonal band of Broca selectively reduced the activity of vasopressin supraoptic neurons in the rat.

In the rat, transient drug-induced elevations of arterial blood pressure, which are sufficient to activate peripheral baroreceptors, produce a brief and selective cessation in the spontaneous activity of vasopressin-secreting cells in the hypothalamic supraoptic nucleus. This response appears to require the noradrenergic innervation of the diagonal band of Broca. The present study evaluated whether injections of norepinephrine into the diagonal band of Broca affect the spontaneous activity of supraoptic vasopressin-secreting neurons. Extracellular recordings were obtained from antidromically identified supraoptic neurons in pentobarbital anesthetized rats using a transpharyngeal approach. Injections of 200 nl of 10 microM norepinephrine into the diagonal band of Broca region arrested the spontaneous activity of 80% (12/15) of vasopressin-secreting neurons but only 7% (1/14) of oxytocin secreting-neurons demonstrated a comparable decrease in excitability. Vehicle injections did not influence the activity of any of the neurons tested. These results are consistent with the hypothesis that the baroreceptor-sensitivity of vasopressin neurons is mediated by a noradrenergic mechanism in the diagonal band of Broca.

Action Potentials↗
PubMed1993

Use of endoscopic ultrasonography for evaluation of painless jaundice.

Precise preoperative evaluation and staging of cases of painless jaundice is extremely important. Many of the patients are older and may have multiple medical problems that increase their operative risk. Assessment of the distal common bile duct, ampulla of Vater, and head of the pancreas is particularly difficult. Various imaging modalities are available but are not sensitive enough to detect small lesions or local invasion. Endoscopic ultrasonography is a new technique that places the transducer closer to the organ being evaluated, adding a new dimension to defining tumor invasion and extension.

Adenocarcinoma↗
PubMed1993

Lateral hypothalamic lesions alter baroreceptor-evoked inhibition of rat supraoptic vasopressin neurones.

1. Previous electrophysiological studies on rat hypothalamic supraoptic nucleus neurones have demonstrated that both the activation of peripheral baroreceptors (induced by a brief rise in arterial pressure consequent to an intravenous injection of an alpha-adrenergic agonist, metaraminol) and electrical stimulation in the diagonal band of Broca evokes a GABA-mediated postsynaptic inhibition which selectively involves the phasic-firing (putative vasopressin-secreting) neuronal population. Although baroreceptor-triggered inhibitions are abolished after diagonal band lesions, anatomical data support the hypothesis that the GABAergic neurones mediating both the baroreflex and electrically induced inhibitions are not located in the diagonal band, but rather in the lateral hypothalamus adjacent to the supraoptic nucleus. To determine the validity of this hypothesis, excitotoxic lesions were placed in the lateral hypothalamus and their effects on both baroreceptor- and diagonal band-evoked inhibitions were evaluated. 2. Male Long-Evans rats were initially anaesthetized with intraperitoneal pentobarbitone, stereotaxically injected with an excitotoxin (ibotenic acid) or vehicle into the lateral hypothalamus on the left side and allowed to recover. Three or more days later, animals were again anaesthetized with pentobarbitone and the ventral surface of their hypothalamus was exposed for electrophysiological recording of neurones in the left supraoptic nucleus. In all injected animals, extracellular recordings from antidromically identified, phasically firing supraoptic neurones were evaluated for their response to activation of peripheral baroreceptors and to electrical stimulation in the diagonal band. 3. Increases in arterial pressure sufficient to activate peripheral baroreceptors were achieved by intravenous bolus infusions of metaraminol (10 micrograms/10 microliters). In vehicle control animals (n = 6), the activity of 34/39 neurones was inhibited by baroreceptor activation. In lesion control animals (n = 13) similar inhibitions were observed from 60/65 neurones. In the lateral hypothalamic lesioned group (n = 7), the activity of only 12/34 neurones were inhibited by similar elevations in blood pressure. 4. Ibotenic acid lesions in the lateral hypothalamus also disrupted the responsiveness of supraoptic neurones to electrical stimulation in the diagonal band. Whereas diagonal band stimulation in vehicle control and lesion control rats reduced the excitability in 7/9 cells and 15/19 cells respectively, only 1/7 cells responded in the lesioned animals. 5. Lesions having a significant effect on the responsiveness of vasopressin-secreting neurones to baroreceptor activation extended laterally towards the nucleus of the lateral olfactory tract, dorsally into the striatum and medially to the fornix.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1992

The effects of ibotenate lesions of the median preoptic nucleus on experimentally-induced and circadian drinking behavior in rats.

Male Sprague-Dawley rats were injected with either ibotenic acid or vehicle in the region of the median preoptic nucleus (MnPO) during methoxyflurane anesthesia. Later, the rats were tested for drinking responses elicited by angiotensin II (1 and 2 mg/kg s.c.) and hypertonic saline (3 and 6% w/v s.c.). Tests were conducted at 3 different phases of a 12:12 light-dark (LD) cycle (in the middle of the light phase and in the early and midportion of the dark phase). The rats with ibotenate lesions of the MnPO drank significantly less than vehicle-injected and lesion control groups regardless of when the tests were conducted. Subsequent monitoring of the diurnal rhythm of drinking, employing electrical lickometers, detected no difference between the rhythms of 4 rats with ibotenate lesions of the MnPO who failed to drink to homeostatic challenges and 4 vehicle-injected control rats. The results indicate that ibotenic acid lesions of the MnPO block drinking behavior stimulated by angiotensin II and hypertonic saline without disrupting the entrainment or pattern of ad libitum drinking.

Angiotensin II↗
PubMed1992

Rat supraoptic neurons are resistant to glutamate neurotoxicity.

Magnocellular neurosecretory cells of the supraoptic nucleus (SON) are thought to be endogenously resistant to glutamate toxicity. In this study, we sought physiological and morphological evidence of this resistance in rats that received multiple peri-nuclear injections of ibotenate. In this preparation, ibotenate produced a large necrotic zone encompassing the SON but not within the nucleus itself. Extracellular recordings in vivo from 68 'spared' SON neurons from lesioned rats revealed normal patterns of electrical activity. Intracellular analysis in vitro from 13 'spared' SON neurons indicated that their intrinsic membrane properties, osmosensitivity and spontaneous synaptic activity did not differ significantly from that of controls. We conclude that SON neurons retain both a morphological and a physiological resistance to glutamate neurotoxicity.

Animals↗
PubMed1992

Catecholamine depletion of the diagonal band reduces baroreflex inhibition of supraoptic neurons.

In the rat, neurons in the diagonal band of Broca (DBB) participate in baroreceptor-induced depression of spontaneous activity of vasopressin neurons in the supraoptic nucleus (SON). The present study examined the role of the catecholaminergic innervation of the DBB in this response. Male rats were anesthetized with pentobarbital (50 mg/kg ip) and stereotaxically injected in the DBB with either vehicle (2 microliters), 6-hydroxydopamine (6-OHDA; 4 micrograms/2 microliters), or 6-OHDA preceded 20 min earlier by desimipramine (25 mg/kg ip), a norepinephrine uptake inhibitor. Two weeks later, the rats were reanesthetized and a transpharyngeal approach was used for extracellular recording from SON neurons. In vehicle-injected controls, baroreceptor stimulation produced by brief increases in blood pressure from metaraminol injections (10 micrograms/10 microliters iv) transiently arrested the spontaneous activity of 24 of 24 phasically active neurons tested. Sixty-three percent of the vasopressin neurons were not affected by comparable increases in blood pressure in 6-OHDA-treated rats, and the norepinephrine content of the DBB was significantly reduced. In experiments with desimipramine-pretreated rats, 92% of the vasopressin neurons were silenced by increases in blood pressure while the norepinephrine content of the DBB was not affected. Thus the noradrenergic innervation of DBB appears to participate in the baroreceptor sensitivity of SON vasopressinergic neurons.

Animals↗