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Biomedical subjects

R A Baker

Publications and source records attributed to R A Baker.

At least 19 recordsLinked to original sources
PubMed1992

Erythromycin and motilin stimulate sphincter of Oddi motility and inhibit trans-sphincteric flow in the Australian possum.

The actions of erythromycin lactobionate and porcine motilin on trans-sphincteric flow and simultaneous sphincter of Oddi motility were studied in 15 anaesthetized Australian Brush-tailed possums (Trichosurus vulpecula). Erythromycin (25-200 micrograms/kg) and motilin (25-200 ng/kg) were administered as graded doses by close intraarterial injection. Trans-sphincteric flow was measured as inflow and outflow. Both motilin and erythromycin decreased trans-sphincteric inflow (both P < 0.0001) and outflow (P < 0.0001 and P = 0.0017 respectively) in a dose-dependent manner. The highest dose of each agent abolished trans-sphincteric flow. These agents increased sphincter of Oddi phasic contraction frequency and basal pressure up to 2 and 3 fold respectively (P < 0.05). The amplitude of the sphincter of Oddi phasic contractions were not influenced in any consistent fashion by either agent. The durations of the responses (trans-sphincteric inflow) elicited by erythromycin and motilin were dose dependent (P = 0.0225 and P = 0.0001 respectively). The actions of erythromycin (200 micrograms/kg) or motilin (100 ng/kg) on trans-sphincteric flow and sphincter of Oddi motility were not influenced by neural blockade with tetrodotoxin. These findings support the hypothesis that erythromycin acts as a motilin agonist and both substances increase the resistance to flow through the sphincter of Oddi by raising the basal pressure and frequency of contractions.

Animals↗
PubMed1992

Motilin and erythromycin enhance the in vitro contractile activity of the sphincter of Oddi of the Australian brush-tailed possum.

Erythromycin has been shown to interact with gastrointestinal smooth muscle in a similar manner to motilin, and has been postulated as a motilin receptor agonist. We report that in isolated preparations from the biliary tract of thirty one Australian Brush-tailed Possums (Trichosurus vulpecula) erythromycin acts in a similar manner to motilin. In all muscle strips from the sphincter of Oddi, prepared in both the circular and longitudinal orientation, both synthetic porcine motilin (10(-10) M-10(-6) M) and erythromycin (lactobionate) (10(-8) M-10(-4) M) stimulated contractile activity in a concentration dependent manner, via a direct effect on the smooth muscle (the response was unaffected by tetrodotoxin, omega conotoxin GVIA or atropine). In strips prepared from the gallbladder neither agonist affected the contractile activity in 7 of 8 animals. Motilin was approximately 1000 fold more potent in stimulating contractile activity than erythromycin in both sphincter of Oddi circular strips [pD2 for peak response to motilin 8.67 (mean) +/- 0.06 (SEM) compared with erythromycin 5.67 +/- 0.09] and sphincter of Oddi longitudinal strips [pD2 for peak response to motilin 8.64 (mean) +/- 0.28 (SEM) compared with erythromycin 5.45 +/- 0.23]. The concentration response curves for motilin and erythromycin were similar and both agonists required the presence of extracellular calcium to elicit responses (responses were diminished by verapamil and abolished in calcium free Krebs solution). Our results support the hypothesis that erythromycin mimics the action of motilin in stimulating the sphincter of Oddi in vitro.

Animals↗
PubMed1992

Sphincter of Oddi regulates flow by acting as a variable resistor to flow.

Two models of transsphincteric flow and a model evaluating pumping activity were established in the anesthetized Australian brush-tailed possum to determine whether the sphincter of Oddi (SO) acts as a resistor or as a pump. A simple model of transsphincteric flow (inflow only) demonstrated that at physiological common bile duct (CBD) pressure, 9.5 +/- 0.3 cmH2O (n = 7), transsphincteric flow occurred between SO pressure waves (n = 10). A second more complex transsphincteric flow model was established that permitted simultaneous measurements of inflow, outflow, CBD pressure, SO basal pressure, SO contraction frequency, and amplitude. At physiological CBD pressure, inflow always equaled outflow (157.0 +/- 11.2 and 156.4 +/- 11.4 microliters/min, respectively; n = 7). The SO displayed regular contractions superimposed on a basal pressure of 1.1 +/- 0.4 mmHg. Contraction amplitude was 12.6 +/- 3.0 mmHg and the frequency was 3.6 +/- 0.4 contractions/min (n = 7). Pressure waves recorded in the CBD corresponded to the SO contractions and reflected SO activity. Transsphincteric flow occurred between SO contractions and was obstructed by these contractions. Stimulation of SO activity (basal pressure and contraction frequency) with intra-arterial injections of motilin (200 ng/kg) or erythromycin (200 micrograms/kg) abolished transsphincteric flow. Reduction in SO contraction frequency to 72.7 +/- 7.2% (P < 0.01, paired t test) after administration of Cisapride (2 mg/kg iv) increased transsphincteric flow to 147.6 +/- 12.3% (n = 7, P < 0.05, paired t test). In six possums, possible SO pumping action was evaluated. A manometer was connected to the CBD, and a second manometer was connected to the duodenum surrounding the papilla.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1991

Innervation of the sphincter of Oddi: physiology and considerations of pharmacological intervention in biliary dyskinesia.

The sphincter of Oddi is a small sphincter which is strategically placed at the junction of the bile duct and pancreatic duct with the duodenum. It regulates the flow of bile and pancreatic juice into the duodenum and prevents reflux of duodenal contents into the ducts. The structure of the sphincter of Oddi differs from species to species and consequently its physiological action varies in different species. Anatomical and immunohistochemical investigations have demonstrated that the sphincter of Oddi is richly innervated by cholinergic, adrenergic and peptidergic neurons. In addition, neural connections exist between the sphincter, gallbladder and proximal gastrointestinal tract. These nerves in addition to hormones are important in the control of sphincter of Oddi motility and function. The normal human sphincter of Oddi is characterized by prominent phasic contractions which are superimposed on a modest basal pressure. These contractions are present throughout the interdigestive period. The contractions and basal pressure are inhibited by ingestion of a meal or infusion of cholecystokinin octapeptide, thus enhancing the flow of bile and pancreatic juice into the duodenum. Sphincter of Oddi dysfunction has been described in patients who present with recurrent biliary type pain and no evidence of a structural cause for the pain. Motility disorders characterized as an elevated basal pressure, rapid contraction frequency, paradoxical response to cholecystokinin octapeptide or excess of retrograde contractions have been identified. A number of pharmacologically active substances have been used in an attempt to treat these patients. Such pharmaceuticals include nitrites, Ca2+ channel blockers and smooth muscle relaxants. Their effect is transient and side effects relating to cardiovascular actions preclude their longterm use. Division of the sphincter either endoscopically or by open operation has been demonstrated by prospective clinical trials to be the most efficacious treatment for patients with a stenosed sphincter manometrically demonstrated by a high basal pressure. Improved understanding of the controlling mechanisms of sphincter of Oddi motility and the pathophysiology of sphincter of Oddi dysfunction should assist in the development of effective pharmacotherapy for these disorders.

Animals↗
PubMed1991

Effect of ethanol on maternal and offspring characteristics: comparison of three liquid diet formulations fed during gestation.

Maternal blood alcohol levels, weight gain during pregnancy, parturition time, perinatal mortality, and postnatal growth of offspring were compared in groups of pregnant rats fed one of three ethanol-containing liquid diets (Kahn's formula = BSA diet, Revised Wiener's = RA6 diet, and Lieber-DeCarli's high protein 82C diet = LDA diet). The three ethanol diets all contained the same amount of ethanol-derived energy (36% of total energy), but differed in the amount of energy contributed by protein (17, 30, and 25%), fat (36, 24, and 13%), and carbohydrate (12, 10, and 27%), respectively. The experimental design also included dams that were pair-fed isocaloric ethanol-free versions of the three ethanol diets (designated BSP, RP6, and LDA, respectively) and a group of dams fed a pelleted casein-based solid diet (PC diet). All experimental diets were fed ad libitum from gestational day 7 to delivery. The effect of ethanol exposure in utero was most severe in mothers and offspring fed the BSA diet. The feed efficiency ratio (maternal weight gain/total dietary energy consumed) of this low-protein ethanol diet was less than that of RA6 or LDA diets. The feed efficiency ratio calculated for RA6 and LDA diets was not different from that of PC diet. Compared with rats fed RA6 and LDA diets, the rats that were fed BSA diet exhibited deficient maternal weight gain, greater parturition delay, impaired fetal growth, and increased perinatal mortality among the offspring. BSA dams had the highest blood ethanol levels of all groups fed ethanol diets, and exhibited the least difference in blood ethanol concentrations between the day (2 PM) and night (9 PM) periods of the diurnal cycle.(ABSTRACT TRUNCATED AT 250 WORDS)

Alcoholism↗
PubMed1990

Neurotransmitter-specific uptake and retrograde transport of [3H]glycine from the inferior colliculus by ipsilateral projections of the superior olivary complex and nuclei of the lateral lemniscus.

Neurotransmitter-specific uptake and retrograde axonal transport of [3H]glycine were used to identify glycinergic projections to the inferior colliculus in chinchillas and guinea pigs. Six h after injection of [3H]glycine in the inferior colliculus, autoradiographically labeled cells were found ipsilaterally in the ventral nucleus of the lateral lemniscus, the lateral superior olive and the dorsomedial periolivary nucleus. These 3 regions accounted for 95% of the labeled projection neurons, with the remainder scattered elsewhere in the ipsilateral superior olivary complex. No labeled cells were found contralaterally even after survival times as long as 24 h. Retrograde transport of HRP from the inferior colliculus in these same cases confirmed the presence of additional projections that did not accumulate [3H]glycine. These included ipsilateral projections from the medial superior olive and cochlear nucleus and contralateral projections from the inferior colliculus, dorsal nucleus of the lateral lemniscus, lateral superior olive, periolivary nuclei and cochlear nucleus. The results implicate uncrossed projections from the ventral nucleus of the lateral lemniscus, lateral superior olive, and dorsomedial periolivary nucleus as the principal sources of inhibitory glycinergic inputs to the inferior colliculus.

Animals↗
PubMed1990

Differing effects of pethidine and morphine on human sphincter of Oddi motility.

The aim of this study was to evaluate the effects of morphine and pethidine on human sphincter of Oddi motility. The action of these opioids on the sphincter of Oddi was evaluated by means of intraoperative manometry in 36 patients undergoing elective cholecystectomy. Both opioids were given in intravenous cumulative equipotent doses up to a maximum of 10 micrograms/kg morphine or 100 micrograms/kg pethidine. At these doses, morphine increased the mean(s.d.) frequency of contractions from 2.4(1.0) to 7.9(1.6) (P less than 0.001); this effect was reduced by naloxone (0.04 mg bolus, P less than 0.05). Pethidine inhibited the frequency of contractions from 1.5(0.8) to 0.8(0.5) (P less than 0.05); this response was blocked by atropine (0.6 mg bolus, P less than 0.01). Pretreatment with atropine or naloxone reduced the frequency of contractions significantly (P less than 0.05). The results illustrate different responses to pethidine and morphine of the sphincter of Oddi, and provide a pharmacological explanation for the suitability of pethidine over morphine as the analgesic of choice in patients experiencing biliary pain.

Adult↗
PubMed1990

Cisapride inhibits motility of the sphincter of Oddi in the Australian possum.

Cisapride has been shown in a number of recent studies to have prokinetic effects on the gastrointestinal tract. Studies of its action on the biliary tract have been limited. In this study we determined the effect of cisapride on sphincter of Oddi motility of the Australian brush tailed possum in vivo, and evaluated possible mechanisms for its effect. Cisapride produced a dose-dependent inhibition of sphincter of Oddi phasic contractions. The inhibitory effect was not blocked by atropine, phentolamine, propranolol, methysergide, or hexamethonium administration, or after cervical truncal vagotomy. Tetrodotoxin, however, abolished the sphincter response to cisapride. We conclude that cisapride has an inhibitory effect on the possum sphincter of Oddi. This inhibitory effect is mediated via nonadrenergic, noncholinergic inhibitory neurons and is similar to the inhibitory effect of cholecystokinin on the sphincter of Oddi.

Ampulla of Vater↗
PubMed1990

Antimicrobial activity of naphthoquinones from fusaria.

Twenty-two naphthoquinone compounds isolated or derived synthetically from culture extracts of Fusarium solani and F. oxysporum were examined for antimicrobial activity. Fifteen exhibited antibiotic activity against Staphylococcus aureus, and 12 were active against Streptococcus pyogenes, but none were active at the highest rate of 128 micrograms/ml against Escherichia coli, Klebsiella pneumoniae, Salmonella typhi, Proteus vulgaris, Serratia marcescens, or Pseudomonas aeruginosa. Of 8 plant pathogenic bacteria tested against 11 naphthoquinones, Corynebacterium poinsettiae was inhibited by 6 compounds, and Pseudomonas viridiflava was weakly inhibited by one. Only one of a group of 6 fluorescent soil pseudomonads was inhibited by one naphthoquinone. Antifungal activity of 10 compounds against 8 fungal plant pathogens was limited to inhibition of Phytophthora parasitica by one naphthopyran.

Anti-Bacterial Agents↗
PubMed1990

Insulin-dependent diabetes mellitus associated with danazol.

Insulin-dependent diabetes mellitus developed in a young woman 8 weeks after the initiation of danazol for treatment of pelvic endometriosis. After discontinuation of danazol the diabetes completely resolved. We suspect a possible cause-and-effect relationship, which has not previously been reported in the literature.

Adult↗
PubMed1989

Human fasting and postprandial sphincter of Oddi motility.

Sphincter of Oddi motility was evaluated in post-cholecystectomy patients with indwelling T tubes during fasting and after feeding. A triple-lumen catheter was positioned to record from the sphincter of Oddi and duodenum. The sphincter of Oddi was characterized by phasic contractions independent of duodenal contractions. During fasting duodenal wave frequency exhibited four phases, whereas only two phases could be identified from the sphincter of Oddi. A prolonged phase A in the sphincter of Oddi corresponded to duodenal phases I, II and IV. A short phase B in the sphincter of Oddi just preceded the onset of duodenal phase III and was temporally related to it. Sphincter of Oddi basal pressure increased during duodenal phases III and IV. After ingestion of food, sphincter of Oddi basal pressure, wave amplitude and duration decreased, but the frequency remained unchanged. Conversely, duodenal frequency increased but there was no change in amplitude. Thus, the human sphincter of Oddi and duodenum exhibited independent motility demonstrating distinct phases during the interdigestive period. After food, sphincter of Oddi motility altered in a manner which would facilitate the passive flow of fluid into the duodenum.

Adult↗
PubMed1988

Acute fulminating fatal leukoencephalopathy as the only manifestation of human immunodeficiency virus infection.

A case of acute human immunodeficiency virus (HIV) infection manifested by a rapidly fulminating, necrotizing, demyelinating encephalopathy that led to brain death in 5 days is reported. Autopsy demonstrated predominant white matter lesions, acute neuronal damage, and scanty cellular response. Cultures of cerebrospinal fluid were positive for HIV, suggesting an acute infection.

Acquired Immunodeficiency Syndrome↗
PubMed1988

Myelopathy due to intracranial dural arteriovenous fistulas draining intrathecally into spinal medullary veins. Report of three cases.

Arteriovenous malformations (AVM's) of the spine commonly cause progressive myelopathy. Occasionally, myelography reveals serpentine filling defects characteristic of a spinal AVM, but an AVM or arteriovenous (AV) fistula cannot be demonstrated arteriographically, despite selective catheterization of all vessels known to have the potential of supplying the spinal cord and spinal dura. Often, and particularly in the setting of subacute or acute deterioration, this has been attributed to spontaneous thrombosis of the veins (the Foix-Alajouanine syndrome). Three patients are reported in whom intracranial dural AV fistulas, supplied by branches of the internal and external carotid arteries, drained into spinal veins and produced myelopathy. In one patient, motor and sensory deficits were limited to the lower extremities. In all three patients, disconnection of the fistula from its spinal venous drainage permitted arrest of a rapidly progressive myelopathy and partial recovery. These findings indicate that some patients who appear to have spinal cord AVM's but exhibit negative spinal arteriography are suffering from cranial dural AV fistulas and therefore need carotid as well as spinal arteriography. The considerable distance of these fistulas from the level of neurological expression supports venous hypertension as a pathophysiological mechanism of spinal cord injury. Interruption of a cranial dural fistula draining into spinal veins permits recovery of the myelopathy.

Adult↗
PubMed1986

Outpatient metrizamide myelography: prospective evaluation of safety and cost effectiveness.

A group of 228 consecutive patients undergoing metrizamide myelography was prospectively evaluated for postprocedure symptoms. The observed prevalence of these symptoms concurs with previously reported inpatient studies, with the most common sequelae being exacerbation or onset of spine or extremity pain, headache, nausea, and paresthesia. Limitation of administered dose of metrizamide in lumbar myelography may slightly reduce the occurrence of common symptoms, but withdrawal of contrast medium at the completion of examination had no impact on their occurrence. There was a higher occurrence of paresthesia in cervical myelography, but otherwise there was no significant difference in symptoms between cervical and lumbar studies. Outpatient metrizamide myelography can be performed with relative safety with the potential for significant cost savings.

Adolescent↗