Biomedical subjects

Ronald Fogel

Publications and source records attributed to Ronald Fogel.

11 recordsLinked to original sources

PubMed2004

Treatment Options for Primary Constipation.

Patients suffering from primary constipation often show symptom improvement with increased intake of fiber. Bulk laxatives are a core component of treatment if dietary fiber is unsuccessful in alleviating symptoms. Although there are a number of commercial laxative preparations available, only polyethylene glycol (PEG), an osmotic laxative, should be used on a daily basis. For the elderly, saline laxatives may be used on a regular basis, provided there are no cardiac or renal comorbid contraindications. Tegaserod, a 5-HT(4) partial receptor agonist, is approved for the treatment of constipation in female patients. The appropriate role of biofeedback remains to be determined. Surgery should be reserved for patients with slow transit constipation refractory to medical therapy. Patients being considered for surgery should be evaluated at institutions with substantial expertise in the investigation and management of this population.

Journal Article↗

PubMed2003

Galanin inhibits gut-related vagal neurons in rats.

Galanin plays an important role in the regulation of food intake, energy balance, and body weight. Many galanin-positive fibers as well as galanin-positive neurons were seen in the dorsal vagal complex, suggesting that galanin produces its effects by actions involving vagal neurons. In the present experiment, we used tract-tracing and neurophysiological techniques to evaluate the origin of the galaninergic fibers and the effect of galanin on neurons in the dorsal vagal complex. Our results reveal that the nucleus of the solitary tract is the major source of the galanin terminals in the dorsal vagal complex. In vivo experiments demonstrated that galanin inhibited the majority of gut-related neurons in the dorsal motor nucleus of the vagus. In vitro experiments demonstrated that galanin inhibited the majority of stomach-projecting neurons in the dorsal motor nucleus of the vagus by suppressing spontaneous activity and/or producing a fully reversible dose-dependent membrane hyperpolarization and outward current. The galanin-induced hyperpolarization and outward current persisted after synaptic input was blocked, suggesting that galanin acts directly on receptors of neurons in the dorsal motor nucleus of the vagus. The reversal potential induced by galanin was close to the potassium ion potentials of the Nernst equation and was prevented by the potassium channel blocker tetraethylammonium, indicating that the inhibitory effect of galanin was mediated by a potassium channel. These results indicate that the dorsal motor nucleus of the vagus is inhibited by galanin derived predominantly from neurons in the nucleus of the solitary tract projecting to the dorsal motor nucleus of the vagus nerve. Galanin is one of the neurotransmitters involved in the vago-vagal reflex.

Animals↗

PubMed2003

The central nucleus of the amygdala modulates gut-related neurons in the dorsal vagal complex in rats.

Using retrograde tract-tracing and electrophysiological methods, we characterized the anatomical and functional relationship between the central nucleus of the amygdala and the dorsal vagal complex. Retrograde tract-tracing techniques revealed that the central nucleus of the amygdala projects to the dorsal vagal complex with a topographic distribution. Following injection of retrograde tracer into the vagal complex, retrogradely labelled neurons in the central nucleus of the amygdala were clustered in the central portion at the rostral level and in the medial part at the middle level of the nucleus. Few labelled neurons were seen at the caudal level. Electrical stimulation of the central nucleus of the amygdala altered the basal firing rates of 65 % of gut-related neurons in the nucleus of the solitary tract and in the dorsal motor nucleus of the vagus. Eighty-one percent of the neurons in the nucleus of the solitary tract and 47 % of the neurons in the dorsal motor nucleus were inhibited. Electrical stimulation of the central nucleus of the amygdala also modulated the response of neurons in the dorsal vagal complex to gastrointestinal stimuli. The predominant effect on the neurons of the nucleus of the solitary tract was inhibition. These results suggest that the central nucleus of the amygdala influences gut-related neurons in the dorsal vagal complex and provides a neuronal circuitry that explains the regulation of gastrointestinal activity by the amygdala.

Amygdala↗

PubMed2003

Lateral hypothalamus modulates gut-sensitive neurons in the dorsal vagal complex.

The lateral hypothalamus (LH) regulates metabolic, behavioral and autonomic functions. The influence of the LH on gastrointestinal function and feeding behavior may be mediated by the dorsal vagal complex (DVC). In the present experiment, we used tract tracing and neurophysiologic techniques to evaluate the interrelationship between the LH and DVC. Using the tracer DiI, we demonstrated that the LH projects to both the nucleus of the solitary tract (NST) and the dorsal motor nucleus of the vagus (DMNV). We determined the effects of electrical stimulation of the LH and/or distention of the gastrointestinal tract on the firing rates of 107 DMNV neurons and 68 NST neurons. As previously reported, the majority of the DMNV neurons were inhibited and the majority of the NST neurons were excited by gastrointestinal distention. Electrical stimulation of the LH significantly changed the spontaneous activities of 71% of the DMNV neurons (46 excited and 30 inhibited). Of the 68 NST neurons characterized, 25 neurons were inhibited and 8 were excited by LH stimulation. In a separate experiment, we characterized the effects of both electrical and chemical stimulation of the LH on 36 DMNV and 14 NST neurons. Glutamate (0.8 nM) induced similar responses in the DVC neurons as electrical stimulation of the LH. The results indicate that the LH influences the electrical activity of DVC neurons. This effect may be the mechanism by which the LH modulates gastrointestinal function and feeding behavior.

Action Potentials↗

PubMed2003

Involvement of glutamate in gastrointestinal vago-vagal reflexes initiated by gastrointestinal distention in the rat.

Vago-vagal reflexes play an integral role in the regulation of gastrointestinal function. Although there have been a number of reports describing the effects of various stimuli on the firing rates of vagal afferent fibers and vagal motor neurons, little is known regarding the neurotransmitters that mediate the vago-vagal reflexes. In the present work, we investigated the role of glutamate in the vago-vagal reflex induced by gastrointestinal distention. Using single-cell recording techniques, we determined the effects of gastric and duodenal distention on the firing rates of gut-related neurons in the dorsal vagal complex, in the absence and presence of glutamate antagonists. Kynurenic acid, a competitive glutamate receptor antagonist, injected into the dorsal vagal complex, blocked the neuronal response of neurons in the dorsal motor nucleus of the vagus and the nucleus of the solitary tract to gastrointestinal distention. Injection of glutamate into the nucleus of the solitary tract produced inhibition of dorsal motor nucleus of the vagus neurons that were also inhibited by gastric and/or duodenal distention. Thus, the distention-induced inhibition of dorsal motor nucleus of the vagus neurons may be mediated by glutamate-induced excitation of gut-related nucleus of the solitary tract neurons. To investigate the role of the various glutamate receptor subtypes in the distention-induced events, we studied the effects of 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX), a selective non-NMDA receptor antagonist, and DL-2-amino-5-phosphonopentanoic acid (DL-AP5), a selective NMDA receptor antagonist. CNQX injected into the dorsal vagal complex either blocked or attenuated the inhibitory response of the neurons in the dorsal motor nucleus of the vagus and nucleus of the solitary tract neurons to gastric and duodenal distention. In contrast, DL-AP5 had less effect, especially in the vago-vagal reflex elicited by gastric distention. The results suggest (1) distention activates vagal afferents in the gastrointestinal tract; (2) the central branches of the vagal afferents from the gut terminate in the nucleus of the solitary tract and release glutamate that mainly act on non-NMDA receptors; (3) glutamate activates the inhibitory neurons in the nucleus of the solitary tract that project to the dorsal motor nucleus of the vagus; and (4) the inhibitory neurotransmitter suppresses the activity of the dorsal motor nucleus of the vagus neurons. For the excitatory neuronal responses of the dorsal motor nucleus of the vagus neurons to gastrointestinal distention, the possible circuit is that the vagal afferents containing glutamate directly activate the receptors on the dendrites of the dorsal motor nucleus of the vagus.

2-Amino-5-phosphonovalerate↗

PubMed2002

Bleeding Angiodysplasia of the Colon.

Angiodysplasia should be considered in the differential diagnosis of hematochezia, gastrointestinal bleeding of obscure origin, and chronic iron deficiency anemia. Although the current medical literature lacks well-designed studies of the various therapeutic modalities, several conclusions appear warranted. Diagnosis of the bleeding site during colonoscopy and the use of endoscopic hemostasis techniques (electrocautery or laser) controls bleeding and may prevent rebleeding. When rebleeding occurs, it may be from the previously treated site or a different location. Estrogen-progestin therapy has not been shown effective in controlled trials but is used when other options fail. Surgery should be considered only when endoscopic therapy fails and the site of bleeding is localized. With all therapies, patients should be cautioned regarding the risk of recurrent bleeding.

Journal Article↗

PubMed2002

GRP mediates an inhibitory response of gut-related vagal motor neurons to PVN stimulation.

We previously characterized neurons in the dorsal motor nucleus of the vagus (DMNV) that were modulated by electrical stimulation of the PVN and by gastrointestinal distention. Bombesin has been identified in a subset of PVN neurons projecting to the DMNV. It is currently unknown whether this neurotransmitter is involved in descending communication from PVN to DMNV neurons. In this study we determined whether the specific bombesin antagonist, N-acetyl-GRP(20-26), influenced (1) the basal firing rate of DMNV neurons and (2) the response to electrical current stimulation of the PVN. Our results indicate that N-acetyl-GRP(20-26), significantly attenuated the inhibitory response of DMNV neurons to PVN stimulation. These results provide a possible mechanism by which bombesin regulates gastrointestinal function, body temperature homeostasis, and feeding behaviors.

Animals↗

PubMed2002

Vagal motor neurons in rats respond to noxious and physiological gastrointestinal distention differentially.

Low-pressure gastrointestinal distention modulates gastrointestinal function by a vago-vagal reflex. Noxious visceral distention, as seen in an obstruction of the gastrointestinal tract, causes abdominal pain, vomiting and affective changes. Using single neuron recording and intracellular injection techniques, we characterized the neuronal responses of neurons in the dorsal motor nucleus of the vagus (DMNV) to low- and high-pressure distensions of stomach and duodenum. Low-pressure gastric distention inhibited the mean activity of the DMNV neurons whereas high-pressure gastric distention excited many neurons. Of 47 DMNV neurons, low-pressure gastric distention inhibited 39, excited four, and did not affect four neurons. High-pressure gastric distention inhibited 26, excited 20, and left one unaffected. Thirteen of the 39 DMNV neurons inhibited by low-pressure distention of the stomach reversed their response to excitation during high-pressure gastric distention. Among 47 DMNV neurons, low-pressure duodenal distention inhibited 30, excited 10, and did not affect the remaining seven neurons. High-pressure distention of the duodenum inhibited 25 and excited 22 neurons. Eight DMNV neurons inhibited by low-pressure duodenal distention were excited in early response to high-pressure distention of the duodenum. High-pressure duodenal distention caused an early excitation and late inhibition in the mean activity of the DMNV neurons while low-pressure duodenal distention only produced late inhibition. These results suggest that different reflexes are present between physiological distention and noxious stimulation of gastrointestinal tract.

Action Potentials↗

PubMed2002

The economic impact of irritable bowel syndrome in a managed care setting.

GOALS: To compare the healthcare resource consumption of patients who have irritable bowel syndrome (IBS) with an age-, gender-, and comorbidity-matched cohort of patients without IBS from a managed care perspective. STUDY: Retrospective cohort analysis. Data were obtained electronically through the Henry Ford Health System corporate data warehouse. Patients with IBS were eligible if they had at least one primary diagnosis of irritable colon (ICD-9-CM 564.1). The control cohort was identified from an age, gender, and comorbidity population-matched (5:1) sample. The index date for the IBS and control cohorts was defined as the first initial diagnosis and first clinical encounter in 1998, respectively. The charges per patient by resource use type were collected for the 12 months before and after the index date. RESULTS: A total of 501 patients with IBS and 2505 controls fulfilled the inclusion and exclusion criteria (70% female, 58% between 40 and 65 years). The IBS cohort, before the IBS diagnosis, had significantly higher total charges (p < 0.001), drug charges (p < 0.001), and outpatient charges (p < 0.001) than the control cohort. During the postindex (postdiagnosis period), the patients with IBS had higher total charges (p < 0.006), outpatient charges (p < 0.022), and drug charges (p < 0.001) than the control population. The control cohort had higher procedure charges (p < 0.001) during both periods. CONCLUSIONS: Patients with an IBS diagnosis represent a substantial cost to managed care before and after the diagnosis of IBS. Costs associated with these patients result mainly from non-IBS conditions. Further research is warranted to identify these patients earlier, and to prevent the economic burden associated with them.

Adolescent↗

PubMed2002

Glutamate mediates an excitatory influence of the paraventricular hypothalamic nucleus on the dorsal motor nucleus of the vagus.

Data have shown that the paraventricular nucleus of the hypothalamus (PVN) and the dorsal motor nucleus of the vagus (DMNV) play important roles in the regulation of gastrointestinal function and eating behavior. Anatomical studies have demonstrated direct projections from the PVN to the DMNV and physiological studies showed that the DMNV mediates many of the effects of PVN stimulation and electrical current stimulation of the PVN excites a subset of DMNV neurons. The aim of this study was to characterize the role of glutamate receptors in the excitatory influence of the PVN on gut-related DMNV neurons. Using single-cell recording techniques, we determined the effects of kynurenic acid, 6-cyano-7-nitroquinoxalene-2,3-dione (CNQX), and DL-2-amino-5-phosphonopentanoic acid (DL-AP5) on the increase in firing rate due to electrical current stimulation of the PVN. In initial experiments, we studied 24 DMNV neurons excited by electrical current stimulation of the PVN. Kynurenic acid, a broad-spectrum glutamate receptor antagonist, prevented the PVN effect in 22 neurons and significantly attenuated the effect in the other cells. Nine of these neurons demonstrated an inhibition in firing rate with PVN stimulation after pretreatment with kynurenic acid. In a separate group of 12 neurons, we determined the effects of CNQX (1.2 nmol) injected into the DMNV. This AMPA receptor antagonist completely blocked the excitatory response to PVN stimulation of six DMNV neurons and significantly attenuated the response of the other six DMNV neurons. The addition of 1.2 nmol DL-AP5, a N-methyl-D-aspartate (NMDA) receptor antagonist, further attenuated the response to PVN stimulation in four of the five DMNV neurons that were still excited after CNQX treatment. The fifth neuron demonstrated PVN- induced inhibition of firing rate after treatment with CNQX and DL-AP5. In a separate group of 11 DMNV neurons excited by electrical stimulation of the PVN, DL-AP5 partially attenuated the excitatory responses of only four DMNV neurons and did not block the excitation of any cells. The mean latency (14 neurons tested) from the PVN to the DMNV was 37.71 +/- 2.40 (SE) ms. Monosynaptic action potentials and excitatory postsynaptic potentials were demonstrated in three DMNV neurons by intracellular recording. Our results indicate that glutamate released from PVN neurons projecting to the DMNV excite the gut-related vagal motor neurons by acting predominantly on the AMPA receptor. The NMDA receptor plays only a minor role in the excitatory effect.

Animals↗

PubMed2001

Fecal Incontinence.

Fecal incontinence is a socially devastating clinical condition. Initial symptomatic treatment includes exclusion of foods that precipitate the problem, increased use of fiber, and drug therapy with loperamide. Persistence of incontinence after these lifestyle modifications requires the physician to evaluate the internal and external anal sphincters. Anal endosonography and manometry provide an evaluation of sphincter structure and function. If an isolated muscle defect is seen, sphincteroplasty can be tried. If this surgical procedure is not indicated, biofeedback may be an option. Biofeedback should be considered for patients with neurogenic fecal incontinence, a weak but structurally intact external sphincter, or a decreased ability to perceive rectal distention. Muscle transposition to create a neosphincter should be offered only by surgeons with extensive experience performing this surgery. Because of the cosmetic sequela of colostomy, this surgery is often considered as a last-step procedure, despite being safe and effective.

Journal Article↗