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Biomedical subjects

R B Scott

Publications and source records attributed to R B Scott.

At least 55 records · Page 3Linked to original sources

Hyperplasia of the muscularis propria in response to massive intestinal resection in rat.

Adaptation of the muscularis propria to intestinal resection is not well studied. Growing, 150- to 200-g Sprague-Dawley rats were divided into a resected group (R), which had 75% of the jejunoileum removed; a sham-resected group (SR); and a group of untreated controls (C). Food intake and weight gain were documented. Animals were killed on days 0, 10, 20, 30, or 40 (n = 14 animals for each day in each group). Small-intestinal length and jejunal circumference, wet weight/cm, thickness of the muscle layers, muscle morphometry, mg protein, and micrograms DNA per cm of the muscularis propria were measured. R rats had an initially greater food intake than SR or C animals, but the rate of weight gain was not different between groups. There was no significant increase in length of the residual intestine in R animals during the postoperative adaptive period, but circumference was significantly increased in R compared with SR or C animals. Wet weight/cm, mg protein, and micrograms DNA per cm of the muscularis propria were significantly greater in R compared with SR or C animals, but there was no change in thickness of the smooth-muscle layers in R versus SR or C rats. The number of cross-sectioned circular smooth-muscle cells/mm2 and the ratio of mg protein/micrograms DNA/cm length of muscularis propria were not different in R compared with SR or C animals. Intestinal resection resulted in a significant increase in circumference but not length of the residual intestine. A significant increase in the mass/cm, with no change in the number of cross-sectioned circular smooth-muscle cells/mm2 or in mg protein/micrograms DNA/cm of the muscularis propria, indicates that the adaptive response of muscularis propria is characterized by hyperplasia. This response potentially confers benefit to the organ and animal as a whole as a mechanism that permits structural and functional adaptation of the muscularis propria to resection.

Animals↗

Massive intestinal resection depresses circular smooth muscle contractility in the rat.

To determine whether functional changes in in vitro contractility and in vivo gastrointestinal transit accompany the adaptive structural changes seen in jejunal circular muscle after massive intestinal resection, rats were subjected to either surgical resection of 75% of the mid-jejunoileum or a sham operation. Basal stress in response to stretch was similar for both groups on postoperative days 10, 20, 30, and 40. By day 10 after surgery, tissues from resected rats exhibited a significant reduction in bethanechol-stimulated tonic stress and in frequency of phasic contractions. The amplitude of spontaneous phasic activity was significantly increased; however, following cholinergic stimulation, the magnitude of the increase in the amplitude of phasic activity was significantly reduced. Experiments with tetrodotoxin (10(-6) M) indicated a myogenic origin to the reduction in bethanechol-stimulated tonic stress and the reduced frequency and altered amplitude of phasic contractile activity in resected animals. The tonic stress developed in response to depolarization with KCl did not differ significantly between sham-operated and resected rats. Transit studies showed no change in the rate of gastric emptying after resection but did reveal a significant reduction in the velocity of intestinal transit. Thus, following massive intestinal resection the bethanechol-stimulated tonic stress response and phasic contractile activity of circular smooth muscle are significantly reduced, concomitant with altered intestinal transit. The reduction in contractility in the resected animals may be due to an alteration at the level of the smooth muscle receptor and (or) its signal transduction pathway.

Animals↗

Intestinal anaphylaxis: mediation of the response of colonic longitudinal muscle in rat.

Colonic smooth muscle function may be altered in food protein hypersensitivity reactions and could contribute to the clinical manifestation of diarrhea. To characterize such functional changes and elucidate the mediators and mechanisms involved. Hooded-Lister rats were sensitized by intraperitoneal injection of egg albumin (10 micrograms), and controls were sham sensitized with saline. Fourteen days later the contractility of longitudinally oriented distal colonic segments (mucosa intact) were studied in standard tissue baths in response to antigen (Ag) or other agents. After Ag exposure, a contractile response was documented in animals that were sensitized [specific immunoglobulin E (IgE) antibody levels > or = 1:64] and was specific for the sensitizing Ag. Mast cell involvement was suggested by a significant reduction in the number of granulated mucosal mast cells in sensitized tissues after Ag challenge and in the magnitude of the Ag-induced contractile response in the presence of mast cell stabilizers. The antigen-induced response was significantly and independently inhibited by both cyclooxygenase and lipoxygenase enzyme inhibitors and by leukotriene D4 and platelet activating factor receptor antagonists. The Ag-induced response was resistant to histamine and the 5-hydroxytryptamine antagonists, atropine and tetrodotoxin. These results suggest that the food protein-induced contraction of colonic longitudinal smooth muscle in the sensitized rat is due to IgE-mediated mast cell activation with the subsequent production and release of membrane-derived mediators that, in vitro, act directly on the smooth muscle.

Albumins↗

The acute chest syndrome in sickle cell disease: incidence and risk factors. The Cooperative Study of Sickle Cell Disease.

The acute chest syndrome (ACS), a pneumonia-like illness in sickle cell patients, is one of the most frequent causes of their morbidity and hospitalizations. Repeated ACS events may predict the development of chronic lung disease. ACS is reported as a frequent cause of death in these patients. We examine here the incidence and risk factors of ACS in 3,751 patients with sickle cell disease who were observed prospectively for at least 2 years (19,867 patient-years [pt-yrs]) as part of a multicenter national study group. The ACS, defined by a new pulmonary infiltrate on x-ray, occurred at least once in 1,085 patients (2,100 events). ACS incidence was higher in patients with homozygous sickle cell disease (SS; 12.8/100 pt-yrs) and in patients with sickle cell-beta(0) -thalassemic (9.4/100 pt-yrs), and lower in patients with hemoglobin (Hb) SC disease (5.2/100 pt-yrs) and patients with sickle cell-beta(+) thalassemia (3.9/100 pt-yrs). alpha-Thalassemia did not affect the rate of ACS incidence in SS patients. Within each Hb type the incidence was strongly but inversely related to age, being highest in children 2 to 4 years of age (25.3/100 pt-yrs in SS) and decreasing gradually to its lowest value in adults (8.8/100 pt-yrs in SS). In SS children (< 10 years of age), we documented an age-related within-person reduction in ACS attack rates. Adults with a higher ACS rate had a higher rate of mortality (from all causes) than those with low ACS rates. This increased rate of mortality might also have contributed to the decline in ACS rate with age. In multivariate analysis, other factors affecting incidence in SS patients were degree of anemia (lower ACS rates in patients with lower steady-state Hb levels) and fetal Hb (lower rates in patients with high fetal Hb). There was also a positive association between ACS rate and steady-state leukocyte count. The relationship of ACS rate to higher steady-state Hb levels in SS patients is unexplained but might be caused by increased blood viscosity.

Acute Disease↗

Rat gastric motor response to food protein-induced anaphylaxis.

BACKGROUND/AIMS: Antigen challenge of sensitized rats leads to delayed gastric emptying, but the mechanism (gastroparesis or prolonged trituration) and mediators are unknown. METHODS: Hooded Lister rats were sensitized by intraperitoneal injection of egg albumin as antigen, and control rats were sham-sensitized. On day 14, antral manometric and antroduodenal myoelectric activities in sensitized and sham-sensitized rats were recorded in response to antigen challenge, and the contractility of gastric antral circular muscle strips (mucosa intact) in standard tissue baths was measured in response to antigen or other agents. RESULTS: In vivo, the intragastric antigen challenge of sensitized (but not sham-sensitized) rats provoked diarrhea, reduction in the antral motility index, and disruption of the duodenal migrating motor complex. In vitro, antigen induced a tonic contraction of antral circular muscle segments from sensitized animals. Doxantrazole, but not disodium cromoglycate, inhibited antigen-induced contraction. Whereas histamine, 5-hydroxytryptamine, prostaglandins, leukotrienes, and platelet-activating factor contracted gastric muscle strips, neither specific antagonists, prostaglandin synthase, or 5-lipoxygenase inhibitors inhibited antigen-induced contraction. Tetrodotoxin increased antigen-induced contraction; however, the antigen-induced contraction was unaffected by atropine, guanethidine, or NG-nitro-L-arginine methyl ester. CONCLUSIONS: Food protein-induced, immunoglobulin E-mediated delayed gastric emptying in sensitized rats is associated with a transient reduction in gastric antral contractions. Antigen-induced contraction appears to be under nonadrenergic, noncholinergic, nonnitroxinergic inhibitory neural control.

Albumins↗

Alzheimer's disease and Down syndrome: leukocyte membrane fluidity alterations.

Down Syndrome (DS) patients over the age of 40 have brain lesions identical to those of patients with Alzheimer's Disease (AD). We have earlier shown that with some membrane probes, the plasma membranes of circulating leukocytes had increased fluidity in AD compared to the normally more rigid membranes in similarly aged subjects. We next questioned whether the occurrence of AD-like pathological lesions in older DS subjects would be associated with a similar increase in membrane fluidity. Fluidity was assessed by measurements of steady-state fluorescence anisotropy using TMA-DPH, which anchors at the plasma membrane surface, and a series of 9-anthroyloxy fatty acids substituted with the fluorescent moiety at different positions on the fatty acid, which permit measurement of fluidity at different depths of the plasma membrane. This was done simultaneously in neutrophils, lymphocytes, and monocytes utilizing flow cytometry. In older DS subjects (average age 52.6), plasma membrane fluidity was indeed increased, a finding similar to that with AD leukocytes. Membrane fluidity of leukocytes of young DS subjects (average age 23.6 years) was less than that seen in older subjects. Membrane changes may result from lipophilic substances released from the central nervous system, or may reflect intrinsic differences in membrane structure unique in DS.

Adolescent↗

Allergic colitis in infancy: clinical and pathologic aspects.

This study prospectively evaluated 35 consecutive infants who presented with fresh blood mixed with stools. The mean age at onset of bleeding was approximately 4 weeks. All infants were otherwise asymptomatic and exhibited normal growth and physical examinations. None had evidence of a bleeding diathesis, viral or bacterial enteritis, or necrotizing enterocolitis. Consent for limited colonoscopy and biopsy was obtained for 34 infants. Twenty-five had macroscopic colitis and 10 infants had marked nodular lymphoid hyperplasia. Thirty-one infants had histopathological evidence of colitis characterized by a marked eosinophilic infiltrate. Compared with 19 controls (age, 4.1 +/- 3.6 months) the mean number of eosinophils per high-power field was greater in the patients with colitis. Patients with colitis also had an elevated mean absolute peripheral eosinophil count and a low mean serum albumin compared to control values. The 31 infants with colitis were receiving solely breast milk (10), cow's milk formula (9), soya formula (9), breast milk with cow's milk formula (2), or nutramigen (1) at the time of presentation. Nineteen infants had rapid resolution of frank bleeding and gradual correction of serum albumin with dietary change. While limited colonoscopy and biopsy were useful in establishing a definitive diagnosis, a low serum albumin and high peripheral eosinophil count suggested the diagnosis. Colitis characterized histologically by > 20 eosinophils per high-power field is a common cause of rectal bleeding in otherwise healthy young infants. Resolution of bleeding and increase in serum albumin after dietary change suggest that this is an allergic colitis: however, the pathogenesis of this disorder needs further clarification.

Animals↗

Recurrent abdominal pain during childhood.

Recurrent abdominal pain is a common presenting complaint among children. A thorough history and physical examination and limited laboratory investigation should enable a physician to make a positive diagnosis of "functional" recurrent abdominal pain in 90% to 95% of cases; an organic cause is identified in only 5% to 10%. The care and thoroughness of the history and physical examination establish the physician's credibility; explaining the clinical basis for the diagnosis and educating the child and parents on what is known about the condition reassures the parents.

Abdominal Pain↗

Mediation of anaphylaxis-induced jejunal circular smooth muscle contraction in rats.

Altered intestinal motility and diarrhea are features of food protein-induced intestinal anaphylaxis in the conscious rat. These experiments were performed to determine the mediator(s) responsible for jejunal circular smooth muscle contraction during this response. Hooded-Lister rats were sensitized by intraperitoneal injection of 10-micrograms egg albumin, and controls were sham-sensitized with saline. Fourteen days later the contractility of the circular muscle in jejunal segments (mucosa intact) was examined in standard tissue baths in response to antigen (Ag) or other agents. While control and sensitized tissues contracted in similar fashion in response to stretch, bethanechol, histamine, or 5-hydroxytryptamine (5HT), Ag contracted only the segments of sensitized animals. The contractile response was: (1) specific to the sensitizing Ag, as bovine serum albumin did not induce contraction and (2) could be passively transferred with serum containing specific immunoglobulin E antibody (IgE-Ab). Concanavalin A, which degranulates both mucosal and connective tissue-type mast cells, and compound 48/80, which degranulates only connective tissue-type mast cells produced contractile responses. Ag-induced contraction was significantly inhibited by the mucosal and connective tissue-type mast cell stabilizer doxantrazole, but not the connective tissue mast cell stabilizer disodium cromoglycate. Diphenhydramine and cimetidine together significantly inhibited histamine-induced contraction, but failed to effect the Ag-induced contraction in sensitized tissues. While the contractile response to 5HT was reduced in the presence of methysergide (5HT1-receptor antagonist), cinanserin (5HT2-receptor antagonist), and ICS 205-930 (5HT3-receptor antagonist), only cinanserin significantly inhibited the contractile response to Ag. Indomethacin significantly inhibited Ag-induced contraction. Ag-induced contraction was resistant to atropine and tetrodotoxin.(ABSTRACT TRUNCATED AT 250 WORDS)

Anaphylaxis↗

Poisoning in the elderly: characterization of exposures reported to a poison control center.

OBJECTIVE: To determine the incidence of poison center calls involving the elderly, characterize these poisonings, and compare them with poisonings that occur in people younger than 60 years of age. DESIGN: Concurrent, observational survey. SETTING: The Virginia Poison Center in Richmond, Virginia. PARTICIPANTS: All persons 60 years of age and older who were involved in a poison exposure reported to the Virginia Poison Center from October 1, 1991 through March 31, 1992. MEASUREMENTS: Incidence, type, route, location, management site, medical outcome of exposures and reasons for these exposures. RESULTS: Exposures in persons 60 years of age and older accounted for 2.3% of all poison center calls during the 6-month study period. These calls were most likely to involve women who unintentionally ingested extra doses of medications. The majority of these exposures occurred in the home and resulted in either no effect or minor effects. For those exposures that necessitated an emergency room visit, elderly persons were more likely to be admitted to the hospital than younger persons (P < 0.05). CONCLUSIONS: The majority of poisonings that occur in persons 60 years of age and older are unintentional and may be amenable to poison prevention education.

Age Factors↗

Neural modulation of canine duodenal bile acid delivery in the interdigestive and postprandial periods.

The neural modulation of gallbladder filling-emptying and duodenal delivery of canine hepatic biliary output was studied in conscious dogs using transient cold blockade or transection of the cervical vagosympathetic nerves previously isolated in skin loops on either side of the neck. Gallbladder filling-emptying was defined as the algebraic difference between a steady-state rate of hepatic secretion [established by a continuous intravenous infusion of [14C]taurocholic acid (TCA)] and the duodenal rate of delivery of [14C]TCA (measured by duodenal marker perfusion). Duodenal motility was recorded manometrically. Experiments in the fasted and fed state were performed under control conditions, during cold blockade, and after transection of the cervical vagosympathetic nerves. Under control conditions: 1) during fasting, the majority of hepatic [14C]TCA output was stored in the gallbladder during the first half of the migrating myoelectric complex (MMC). An increased rate of duodenal delivery and partial gallbladder emptying occurred before phase III of the MMC. 2) Feeding induced an immediate increase in duodenal bile acid delivery and gallbladder emptying. After cold blockade or transection: 1) partial gallbladder emptying before phase III of the MMC was abolished. 2) The immediate postprandial increase in duodenal bile acid delivery and gallbladder emptying was abolished even when the animal received a continuous duodenal infusion of the duodenal aspirate of another fed animal (to control for the effect of impaired gastric emptying after cold blockade). In addition, cold blockade significantly reduced the effect of an exogenous infusion of cholecystokinin octapeptide on gallbladder emptying. These results suggest that neurons in the canine cervical vagosympathetic nerves play a major role in the regulation of rhythmic partial emptying of the gallbladder in the interdigestive period, coordinate a cephalic phase of postprandial gallbladder emptying, and are important in mediating the effects of cholecystokinin on the gallbladder during the gastric and enteric phases of postprandial gallbladder emptying.

Animals↗

Common blood disorders: a primary care approach.

Many anemias and diseases of the blood-forming elements increase in incidence with advancing age. Iron deficiency remains the cause of most cases of anemia and may be related to inapparent blood loss. Other responsive anemias that can be managed by the primary care physician include vitamin B12 and folate deficiencies and drug- or autoimmune-related hemolytic anemia. Nonresponsive anemias, including hematologic malignancies, are quite common in older patients and require referral to a specialist. Platelet disorders are often produced by certain drugs and, like most refractory anemias, often require a bone marrow aspirate for diagnosis.

Aged↗

Yersinia enterocolitica enteritis affects rabbit intestinal longitudinal smooth muscle function.

To determine whether Yersinia enterocolitica (YE) enteritis has an effect on the biomechanical properties of intestinal smooth muscle, New Zealand White rabbits (600-900 g) were divided into an infected group (n = 9) and sham-infected animals fed ad libitum (n = 9), or pair fed with the infected group (n = 9). Animals were inoculated with 10(10) organisms of YE in 10 ml NaHCO3 (infected group) or 10 ml NaHCO3 (sham-infected control and pair-fed groups) at time 0. Daily food intake, weight gain, and YE excretion were noted. Six days later animals were killed and longitudinal smooth muscle strips prepared from proximal (P), medial (M), and distal (D) segments of intestine in each treatment group. Isometric tension was recorded in tissue baths perfused with oxygenated Krebs solution and 10(-6) M tetrodotoxin. Basal and active (the response to 10(-5) M carbachol) length-tension curves were generated. Then, with the muscle strips stretched to their optimum length for tension development, the dose response to carbachol and to graded depolarization with KCl was determined. Infected animals had a significantly reduced food intake and weight gain compared with controls. The development of basal tension with stretch was not significantly different in infected compared with control or pair-fed tissues from the same site.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Smoking is a factor in causing acute chest syndrome in sickle cell anemia.

A link between cigarette smoking and "acute chest syndrome" in sickle cell anemia is suggested. Acute chest syndrome in the patient with sickle cell anemia is characterized by fever, leukocytosis, cough, chest pain, and pulmonary infiltrates in the chest radiograph. This article describes the results of a study of 69 adolescent and young adult sickle cell anemia patients. Twenty-nine of these patients were smokers, three were former smokers, and 37 were nonsmokers. Patients completed respiratory questionnaires that focused on smoking habits and included a history of chest syndrome. Information obtained was confirmed by review of clinical records. The chi-square test demonstrated a strong relationship between cigarette smoking and chest syndrome in sickle cell anemia. All 29 smokers had a history of chest syndrome, but only 24 of 37 nonsmokers had such a history. Although the exact mechanism of the relationship between smoking and the development of acute chest syndrome remains speculative, cigarette smoking joins infection, hypoxia, acidosis, infarction, dehydration, and analgesics as a causative factor in adolescent and adult patients with sickle cell anemia. Behavioral modification of the smoking habit in patients with sickle cell anemia may decrease the frequency of acute chest syndrome and sequelae of sickle cell lung disease.

Acute Disease↗