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Biomedical subjects

D R Ferguson

Publications and source records attributed to D R Ferguson.

At least 37 records · Page 2Linked to original sources
PubMed1990

Effect of capsaicin on the rabbit urinary bladder. What is the function of sensory nerves that contain substance P?

The sensory innervation of the rabbit urinary bladder was studied using local application of the specific sensory neurotoxin capsaicin (8-methyl-N-vanillyl-6-nonenamide). This agent has its major effect by damaging small diameter unmyelinated sensory nerves. The drug produced a 51% reduction in the bladder content of the neuropeptide substance P. It therefore appears that a substantial proportion of the bladder's content of the peptide is to be found in capsaicin-sensitive sensory nerves. Cystometrograms carried out before and after treatment with capsaicin were similar; this suggests that capsaicin-sensitive sensory nerves may not be of importance in the afferent limb of the micturition reflex. In vitro muscle strip studies demonstrated a small reduction in the sensitivity of the detrusor muscle to electrical stimulation of its intramural nerves. It is possible that in vitro intramural nerve stimulation leads to release of neurotransmitters from sensory as well as motor nerves. It is proposed that small diameter sensory nerves in the bladder wall may have a role in the transmission of the sensation of pain and in the triggering of inflammatory reactions rather than forming the afferent limb of the micturition reflex.

Animals↗
PubMed1990

Effect of bladder outflow obstruction on the innervation of the rabbit urinary bladder.

The effects of bladder outflow obstruction on the innervation of the bladder were studied using a rabbit animal model. Partial occlusion of the bladder neck was obtained by the placement of a silk ligature at that level; control animals underwent a sham procedure. After a 3-month period, the presence of outflow tract obstruction was confirmed using urodynamic studies. The animals were then killed and pharmacological assessments of the bladder innervation undertaken. Detrusor muscle strip studies provided evidence of damage to the cholinergic innervation of the detrusor. Also, muscle strips from obstructed animals showed reduced inhibitory responses to beta-adrenergic stimulation with isoprenaline. In addition to these muscle strip studies, the bladder content of the neuropeptide substance P was assayed, but no significant change was observed in response to obstruction. This finding suggests that substance P-containing sensory nerves may be spared from the denervating effect of bladder outflow obstruction.

Animals↗
PubMed1989

The effect of enalapril on the renal response to tilting in humans.

1. Seventeen normal subjects were tilted on a tilt table and changes in blood pressure, heart rate and renal function were monitored in the absence of drug treatment; the same measurements were repeated during treatment with enalapril in eight of these subjects. 2. In the absence of drug, tilting of the whole body to the 45 degree head up position caused an antidiuresis, antinatriuresis and antikaliuresis; the antinatriuresis resulted from a transient fall in glomerular filtration and from a sustained increase in the tubular reabsorption of sodium, as reflected by a prolonged fall in fractional sodium excretion. 3. Enalapril caused a reduction in blood pressure in the upright position; there was no effect on heart rate. The antinatriuresis of tilt was significantly blunted by enalapril. This resulted from blunting of the transient fall in creatinine clearance and of the increase in tubular sodium reabsorption. Urinary potassium excretion during tilting was not altered by enalapril. 4. These findings are consistent with a direct intrarenal action of angiotensin II, mediating some of the alterations in renal function apparent on assumption of the upright position.

Adult↗
PubMed1989

Neurotransmission in pig renal artery: the actions of angiotensin II and dopamine.

1. Electrical stimulation of pig renal arteries causes contractions which are potentiated in the presence of angiotensin II (5 x 10(-8) M). 2. The potentiation is followed by a long-lasting inhibitory phase which is mimicked by dopamine and 2-amino-6,7,dihydroxy-1,2,3,4,-tetrahydronaphthalene (ADTN), but blocked by sulpiride (5 x 10(-8) M). 3. Release of noradrenaline from renal artery rings by 25 mM K+ was measured by h.p.l.c. and found to be increased by 5 x 10(-8) M angiotensin II. As this was done in the presence of 1 x 10(-6) M desmethylimipramine it was concluded that the increase was due to increase neuronal release of noradrenaline, not inhibition of neuronal uptake. 4. The experiments indicate that dopamine is present in the artery wall and produces its effects through DA2-receptors.

Angiotensin II↗
PubMed1989

Absence of effect of angiotensin II on adenylate cyclase in rat proximal renal tubular basolateral membranes.

3H-Angiotensin II binding was studied in rat renal proximal tubular basolateral membranes. The characteristics of binding were found to be consistent with a receptor for angiotensin II at this site. Effects of angiotensin II on cAMP production were studied in the basolateral membranes. Angiotensin II had no effect on the time course of basal or parathyroid hormone stimulated cAMP production in basolateral membranes. Angiotensin II did not exhibit a concentration-dependent effect on cAMP production in basolateral membranes, either alone or in the presence of parathyroid hormone. The concentration-response curves of cAMP production in response to parathyroid hormone in basolateral membranes were similar in the presence or in the absence of angiotensin II. We conclude that adenylate cyclase production is not linked to the receptor for angiotensin II in rat renal proximal tubular basolateral membranes.

Adenylyl Cyclase Inhibitors↗
PubMed1989

[3H]angiotensin II binding to basolateral membranes from rat proximal renal tubule: effect of sodium intake and captopril.

Basolateral membranes were prepared from rat renal cortex by density gradient centrifugation. Their purity was confirmed by electron microscopy and by marker enzyme enrichment. The basolateral membrane preparation was shown to be derived predominantly from the proximal renal tubule by measurement of hormone-stimulated adenylate cyclase; marked stimulation of adenylate cyclase was found with parathyroid hormone, but not with isoprenaline, antidiuretic hormone or calcitonin. A single class of specific high-affinity [3H]angiotensin II-binding site was identified in the basolateral membrane preparation which, after correction of results for tracer degradation, showed equilibrium dissociation constant of 0.23 nmol/l and binding site concentration of 485.8 fmol/mg protein. Binding sites for [3H]angiotensin II were measured in basolateral membranes prepared from rats fed diets with a low, normal or high sodium content. A trend of increased binding site density with reduced sodium intake was found which did not reach statistical significance. No effect on affinity was demonstrated. Treatment of rats on a low-sodium diet with captopril (500 mg/l drinking water) caused a significant reduction in binding site density; no effect on affinity was demonstrated. These findings suggest that the density of angiotensin II receptors at this site is altered by the activity of the renin-angiotensin system.

Adenylyl Cyclases↗
PubMed1988

The use of endoscopic detrusor muscle biopsies for in vitro muscle strip studies.

A technique is described for performing in vitro muscle strip studies using samples of detrusor muscle taken by means of endoscopic biopsy forceps. This study of pig bladder muscle showed that the nerve mediated and drug induced responses of the muscle showed that the nerve mediated and drug induced responses of the muscle biopsies were similar to those produced by traditionally dissected muscle strips. The importance of continued access to human material for pharmacological studies is discussed.

Acetylcholine↗
PubMed1987

Endoscopic management of upper gastrointestinal polyps and periampullary lesions in familial adenomatous polyposis and Gardner's syndrome.

Upper gastrointestinal polyps and carcinoma, especially of the periampullary area, may occur in patients with familial adenomatous polyposis. Upper gastrointestinal polyps were present in about 43% of patients in the polyposis registry of the Cleveland Clinic who underwent screening esophagogastroduodenoscopy. Approximately one-third of these polyps were neoplastic. Three distribution patterns were recognized: 1. fundic, 2. duodenal, and 3. fundic plus duodenal. Despite the occurrence of a few gastric cancers in patients with familial adenomatous polyposis, the risk of carcinoma of the major duodenal papilla and periampullary area is more significant. It is necessary to examine the duodenal papilla with a side-viewing instrument and to obtain biopsy specimens from this structure in these patients. The major duodenal papilla was abnormal in about one-half of our patients in whom this structure was specifically examined with a side-viewing endoscope. The preliminary results of a trial of endoscopic treatment of upper gastrointestinal polyps and lesions of the major duodenal papilla in patients with familial adenomatous polyposis are described.

Adenomatous Polyposis Coli↗
PubMed1987

Bladder instability and denervation in patients with bladder outflow obstruction.

In vitro pharmacological studies were performed on endoscopic detrusor biopsies from patients with bladder outflow obstruction. Urodynamic studies had been undertaken to detect the presence of bladder instability. Muscle strips from patients with instability demonstrated supersensitivity to acetylcholine and reduction in nerve mediated responses, as compared with strips from stable bladders. These changes are interpreted as suggesting the presence of cholinergic denervation in obstructed patients with bladder instability.

Acetylcholine↗
PubMed1986

Mesenteric venous thrombosis as a possible complication of endoscopic sclerotherapy: a report of two cases.

Two cases of mesenteric venous thrombosis with bowel infarction occurring after endoscopic sclerotherapy are reported. In neither patient was the diagnosis suspected or recognized until the terminal phase of the illness. Clinicians should be aware of this possible association and complication of endoscopic injection sclerotherapy, as early diagnosis is critical for patient survival.

Adult↗
PubMed1985

Responses of the pig isolated renal artery to transmural electrical stimulation and drugs.

Pig isolated renal arteries contract in response to addition of noradrenaline, 5-hydroxytryptamine, histamine, angiotensin II, vasopressin and carbachol, whereas cholecystokinin, adenosine, and inosine produce relaxation. Transmural stimulation of the tissue causes contraction of circular muscle in the arterial wall which produces apparent elongation of the vessel. The effects of transmural stimulation are partially blocked by prazosin and potentiated by propranolol, indicating that noradrenaline acts through both alpha- and beta-adrenoceptors. Guanethidine (10(-5) M) reduces the size of responses to transmural stimulation in the presence of both prazosin (10(-6) M) and propranolol (10(-7) M). Both saralasin (10(-7) M), and desensitization of angiotensin II receptors by prolonged contact with the peptide, produced a reduction in response to transmural stimulation, indicating that angiotensin II may be involved in neurotransmission. This effect was blocked by tetrodotoxin. Transmural stimulation produces relaxation of renal arteries in the presence of maximal doses of saralasin, prazosin, and propranolol, suggesting that a third unidentified substance is also released from autonomic nerves.

Angiotensin II↗
PubMed1984

Gastrointestinal neurofibromatosis.

Progressive anemia, melena, and sudden massive upper gastrointestinal bleeding in a man with cutaneous neurofibromatosis (von Recklinghausen's disease) since childhood prompted endoscopic demonstration of multiple gastric neurofibromas. One source of gastric bleeding removed by endoscopic electrosurgery proved to be a malignant schwannoma (spindle cell sarcoma). A pulmonary schwannoma, multifocal intracerebral spindle cell sarcomas, an extra-adrenal pheochromocytoma, and ocular neurofibromas were other features of this neuroectodermal dysplasia. Neurogenic tumors of the gastrointestinal tract are rare, commonly present with dyspepsia, abdominal pain, anemia, or hemorrhage, and should be suspect in the clinical setting of cutaneous neurofibromatosis. In the patient with systemic neurofibromatosis, endoscopic removal represents a safe method of diagnosis and treatment of bleeding neoplasms in the stomach or duodenum.

Adrenal Gland Neoplasms↗
PubMed1984

Duodenal Crohn's disease complicated by common bile duct obstruction: report of a case and review of the literature.

A 28-year-old woman with Crohn's disease involving the duodenum and terminal ileum presented with biochemical evidence of incomplete, extrahepatic biliary obstruction. Percutaneous transhepatic cholangiography showed partial obstruction of the intramural duodenal portion of the common bile duct. Cholangiography was complicated by cholangitis. Surgical decompression of the biliary system and bypass of the affected duodenal segment were performed after intraoperative confirmation of Crohn's disease involving the ileum, duodenum, and ampulla of Vater. The patient made a complete recovery and all previously abnormal cholestatic liver function test results returned to normal.

Adult↗
PubMed1984

Percutaneous endoscopic gastrostomy: a preferred method of feeding tube gastrostomy.

Percutaneous endoscopic gastrostomy was attempted in 16 patients using local anesthesia and intravenous meperidine and diazepam sedation. The procedure was shown to be safe, easy to perform, and avoided the need for laparotomy. We suggest percutaneous endoscopic gastrostomy be the preferred route of alimentation in those patients requiring feeding gastrostomy.

Enteral Nutrition↗
PubMed1983

Drug and treatment efficacy of chenodeoxycholic acid in 97 patients with cholelithiasis and increased surgical risk.

Patients with symptomatic cholelithiasis who represent higher than normal surgical risks may be the most suitable candidates for medical dissolution of gallstones. Chenodeoxycholic acid was given to 97 patients in a dosage of 15 mg/kg of body weight per day for a period of two years. Complete gallstone dissolution occurred in 27 of 97 patients (28%). If dropouts are excluded then the success rate is 27 of 64 patients (42%). Diarrhea was a common but manageable side effect for most. Thirty-two percent of patients developed chemical liver test abnormality; however, in only 13% was the degree of abnormality sufficient to require temporary (3%) or permanent (10%) cessation of therapy. Although better chemotherapeutic agents are needed, chenodeoxycholic acid is a reasonable choice for patients with non-calcified cholelithiasis in a functioning gallbladder if the patient is a heightened surgical risk. Because of the prolonged treatment period and the possibility of hepatotoxicity this treatment program requires a substantial commitment on the part of both the patient and the physician.

Chenodeoxycholic Acid↗
PubMed1981

Pruritus in cholestasis: no direct causative role for bile acid retention.

Discrepancies have existed regarding the correlation between raised bile acid levels in cholestasis and the presence of pruritus. Nevertheless, the prevalent view is that bile acids have a direct etiologic role. To resolve the issue, we quantified separately all naturally-occurring bile acid species detectable in serum and skin, and on the skin surface of 13 patients with pruritus associated with cholestasis, 10 patients with cholestasis who did not have pruritus, three patients with uremia and generalized pruritus and in 10 controls. We were unable to find any correlations between the presence of pruritus and bile acid levels from the various sources. We did find great overlap in these same values with data from the group with cholestasis but without pruritus. As expected, the symptomatic (uremic) and asymptomatic control groups showed comparable levels. The results of the present study together with those of a similar recent study provide strong evidence against the hypothesis of a direct causative role for retained bile acids in pruritus associated with cholestasis.

Adult↗