Diagnosis of left ventricular pseudoaneurysm by pulsed Doppler echocardiography.
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In 72 patients with previous myocardial infarction (MI), mitral regurgitation (MR) was assessed by pulsed-wave Doppler echocardiography and compared with physical and 2-dimensional echocardiographic findings. MR was found by Doppler in 29 of 42 patients (62%) with anterior MI, 11 of 30 (37%) with inferior MI (p less than 0.01) and in none of 20 normal control subjects. MR was more frequent in patients who underwent Doppler study 3 months after MI than in those who underwent Doppler at discharge (anterior MI = 83% vs 50%, p less than 0.01; inferior MI = 47% vs 27%, p = not significant). Of 15 patients who underwent Doppler studies both times, 3 (all with anterior MI) had MR only on the second study. Of the patients with Doppler MR, 12 of 27 (44%) with a left ventricular (LV) ejection fraction (EF) greater than 30% and 1 of 13 (8%) with an EF of 30% or less (p less than 0.01) had an MR systolic murmur. Mitral prolapse or eversion and papillary muscle fibrosis were infrequent in MI patients, whether or not Doppler MR was present. The degree of Doppler MR correlated with EF (r = -0.61), LV systolic volume (r = 0.47), and systolic and diastolic mitral anulus circumference (r = 0.52 and 0.51, respectively). Doppler MR was present in 24 of 28 patients (86%) with an EF of 40% or less and in 16 of 44 (36%) with EF more than 40% (p less than 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)
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OBJECTIVE: Bone loss occurs in young women who experience amenorrhea or ovulatory disturbances. The purpose of this study was to determine whether bone loss could be prevented by simulating a more normal hormonal pattern, using treatment with cyclic medroxyprogesterone, with or without calcium supplementation, in physically active women with disturbed menstruation. DESIGN: This study was a 1-year randomized, double-blind, placebo-controlled trial. Women who were stratified by menstrual cycle disturbance were randomized into four groups. The outcome variable was the change in spinal bone density measured by dual energy techniques. SETTING: A large metropolitan area. PARTICIPANTS: Sixty-one healthy, normal-weight physically active premenopausal women aged 21 to 45 years who experienced amenorrhea, oligomenorrhea, anovulation, or short luteal phase cycles completed the study. INTERVENTION: Therapies were cyclic medroxyprogesterone (10 mg/day for 10 days per month) and calcium carbonate (1,000 mg/day of calcium) in four groups: (A) (n = 16) cyclic medroxyprogesterone plus calcium carbonate; (B) (n = 16) cyclic medroxyprogesterone with calcium placebo; (C) (n = 15) placebo medroxyprogesterone with active calcium; or (D) (n = 14) both medroxyprogesterone and calcium placebos. RESULTS: The initial bone density (mean = 1.12 g/cm2) did not differ by group (P = 0.85). The 1-year bone density change was strongly related to treatment with medroxyprogesterone (P = 0.0001) and weakly to calcium (P = 0.072) treatment. Bone density increased significantly (+1.7% +/- 0.5%, +/- SEM, P = 0.004) in the medroxyprogesterone-treated groups (A and B), did not change in the calcium-treated group (C) (-0.7% +/- 0.6%, P = 0.28), and decreased on both placebos (D) (-2.0% +/- 0.6%, P = 0.005). CONCLUSIONS: Cyclic medroxyprogesterone increased spinal bone density in physically active women experiencing amenorrhea or ovulatory disturbances. POTENTIAL CLINICAL SIGNIFICANCE: Amenorrhea, oligomenorrhea, anovulation, and short luteal phase cycles are common in premenopausal women and associated with spinal bone loss occurring at a stage of life when bone density would normally be stable or increasing. This controlled trial shows a significant gain in bone in women in the cyclic medroxyprogesterone intervention group, whereas those subjects in the placebo group lost bone. Calcium supplementation appeared to be helpful but did not reach statistical significance. The implications of these findings for the prevention of osteoporosis warrant further investigation.
The abilities of the pancreatic cholecystokinin (CCK) receptor antagonists dibutyryl cyclic GMP, proglumide, benzotript, CBZ-tryptophan, CBZ-cysteine and CCK-27-32-amide to inhibit CCK binding to its receptor in the pancreas and brain of mice and guinea pigs was examined. In both species, the same relative potencies of the antagonists in brain and pancreas was seen except that dibutyryl cyclic GMP was considerably more potent on pancreas than on cerebral cortex CCK receptors. CCK-27-32-amide was the most potent inhibitor for both brain and pancreas but was more potent in the guinea pig than in the mouse. Proglumide, a relatively weak antagonist, was a more potent inhibitor of the guinea pig than of the mouse pancreas receptor. Thus, these data suggest that there are both tissue-specific and species-specific differences in CCK antagonist interactions with the CCK receptor.
Since estradiol (E2) either increases or reduces the number of dopamine receptors in the corpus striatum of adult rats, depending on the dose and length of administration, the sensitivity of the two receptor subpopulations (D1 and D2) to E2 during ontogenesis was investigated. Rats of both sexes received either 10 micrograms/kg E2 for 3 days or 50 micrograms/kg for 6 days, and were sacrificed at the age of 15, 21, 40 and 120 days. D1 receptors (identified by [3H]SCH 23390 binding) displayed no changes in density and affinity in function of age, sex or E2 dose, whereas the D2 receptors (identified by [3H]spiperone binding) fell after the lower dose in all groups, and the higher dose resulted in supersensitivity in males of all ages, but only in the 15-day-old females. These findings show that the effect of E2 is bivalent on D2 density only. The effect of its brief administration at a low dose is not sex-dependent, whereas at higher doses administered for longer periods it appears to involve mechanisms linked to sexual differentiation after birth.
A [125I]cholecystokinin (CCK) analog and [125I]peptide YY (PYY) were used to localize and characterize CCK and neuropeptide Y (NPY) receptor binding sites in the rabbit vagal afferent (nodose) ganglion. High concentrations of CCK and NPY binding sites were observed in 10.6% and 9.2% of the nodose ganglion neurons, respectively. Pharmacological experiments using CCK or NPY analogs suggest that both subtypes of CCK (CCK-A and CCK-B) and NPY (Y1 and Y2) receptor binding sites are expressed by discrete populations of neurons in the nodose ganglion. These results suggest sites at which CCK or NPY, released in either the nucleus of the solitary tract or a peripheral tissue, may modulate the release of neurotransmitters from a select population of visceral primary afferent neurons. Possible functions mediated by these receptors include modulation of satiety, opiate analgesia, and the development of morphine tolerance.
Recent pharmacological and biochemical studies have suggested that there may be more than one molecular form of the neurokinin-1 receptor (NK-1), a long and short isoform differing in the length of their cytoplasmic carboxyl-terminal tails, but no definitive evidence of the existence of such NK-1 receptor isoforms in tissue has been presented. To examine whether these different isoforms are expressed in vivo we have compared the distribution of high affinity substance P (SP) binding sites (visualized by autoradiography with [125I]SP), with the distribution of the C-terminal epitope of the full length receptor (visualized with a specific antibody against the extreme C-terminal sequence). The former method labels both long and short forms of the NK-1 receptor, while the latter labels only the long form of the protein. In the rat there is a close correspondence of [125I]SP binding and NK-1 immunoreactivity in the striatum, suggesting that the long isoform predominates in this tissue. In the parotid and submaxillary gland, there are very high levels of [125I]SP binding but only low levels of NK-1 immunoreactivity, suggesting that expression of the short form predominates in these tissues. These results imply that different tissues express different ratios of the two isoforms of the NK-1 receptor. This differential expression provides the theoretical basis for tissue specific pharmacological targeting of NK-1 receptors.
The goal of these studies was to determine the tissue and cell types possessing specific binding sites for bombesin/gastrin-releasing peptide in the canine gastrointestinal tract. Monoiodinated, biologically active (Tyr-4)-bombesin 14 (100 pM) was applied to sections of canine gut and localized using quantitative autoradiography. The highest density of bombesin/gastrin-releasing peptide specific binding sites occurred over endocrine cells in the antral mucosa. Specific binding sites were also found on the circular muscle layer of the gastric fundus, gastric antrum, and ileum, on longitudinal muscle of the gastric fundus and antrum, and on neuronal elements in the myenteric plexus in the gastric fundus, antrum, and small intestine. No evidence for specific binding of 125I-(Tyr-4)-bombesin 14 was found in sections of canine esophagus, gastric cardia, gallbladder, pancreas, or colon. These results suggest sites of direct action of bombesin and endogenous gastrin-releasing peptide for gastrin release and gastrointestinal motility.
The goal of the present studies was to identify and characterize the site of secretin action in the liver. Sections of normal and bile duct-ligated rat livers were used for in vitro 125I-secretin receptor autoradiography. Saturable binding was observed in both normal and bile duct-ligated livers but was much greater in the bile duct-ligated preparations. Binding was limited to biliary epithelium and the increased secretin binding observed in the ligated livers correlated with the increase in ductular tissue. Saturable binding was inhibited in a dose-dependent fashion by increasing concentrations of nonradioactive secretin. Analysis of saturation binding showed that 125I-secretin binding was best fit by a one-site receptor model with a Kd of 5.3 +/- 1.1 nmol/L. Glucagon, vasoactive intestinal polypeptide, gastric inhibitory polypeptide, growth hormone-releasing hormone, and cholecystokinin did not inhibit saturable 125I-secretin binding at concentrations of 1 pmol/L to 1 mumol/L. The authors conclude that high-affinity, specific secretin binding sites are present in rat intrahepatic biliary epithelium. When bile ducts are stimulated to proliferate by bile duct ligation, secretin binding is also increased.
BACKGROUND/AIMS: Cholecystokinin (CCK) is a neuropeptide that exerts numerous effects in the gut. To determine the sites of action of CCK, the distribution and properties of CCK receptor subtypes were studied. METHODS: CCK receptors were localized by autoradiographic analysis of 125I-CCK binding to frozen sections of the canine upper gastrointestinal tract. RESULTS: In the cardiac and fundic stomach, CCK-B/gastrin receptors were found in the mucosa and in a subpopulation of neuronal elements in the circular muscle. The antrum expressed CCK-B/gastrin receptors in a few neurons in the circular muscle and in the entire myenteric plexus; no receptors were observed in the antral mucosa or esophagus. The duodenum showed a high concentration of CCK-B/gastrin receptors in the myenteric plexus. The cardiac and fundic basal mucosae expressed CCK-A receptors. Two nonpeptide CCK receptor antagonists were unable to differentiate between the receptor subtypes. CONCLUSIONS: The differential expression of CCK receptor subtypes in the gastric mucosa provides a morphological basis for the separate regulatory roles of CCK and gastrin in gastric function. CCK-B/gastrin receptor expression in a subset of neurons in gastric circular muscle suggests a novel site of action for CCK and/or gastrin.
BACKGROUND & AIMS: Although clinical and pathological differences exist between Crohn's disease (CD) and ulcerative colitis (UC), distinguishing features are often absent, making diagnosis and treatment problematic. This study evaluated the differences in the expression of substance P (SP) receptors in patients with CD or UC. METHODS: Tissue samples from patients with inflammatory bowel disease or control patients were obtained at surgery, processed for 125I-SP binding, and analyzed by quantitative autoradiography. RESULTS: Patients with CD showed a massive increase in SP receptors in lymphoid aggregates, small blood vessels, and enteric neurons of the small and large bowel relative to controls. Six of 16 CD specimens had no pathological evidence of CD yet continued to express high concentrations of SP receptors. Pathologically positive patients with UC showed high concentrations of SP receptors on colonic lymphoid aggregates and small blood vessels but not enteric neurons. No increased SP binding was evident in clinically and pathologically quiescent UC colons and normal UC ileostomy samples. CONCLUSIONS: The increased expression of SP receptors on the enteric neurons of patients with CD distinguishes CD from UC. The persistent increased SP binding in pathologically normal CD tissue may indicate a subclinical disease state. SP receptor expression may have important diagnostic, etiologic, and therapeutic usefulness in inflammatory bowel disease.
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Twenty-six species of invertebrates representing eight phyla were surveyed for the presence of cholecystokinin/gastrin-like (CCK/gastrin-like) peptides by radioimmunoassay of various tissue extracts. This is the first report of the presence of CCK/gastrin-like peptides in representatives of the phylum Ectoprocta, the arthropodan classes Crustacea and Merostomata, and in the nervous systems of the gastropod mollusc Aplysia californica and the oligochaete annelid Lumbricus terrestris. It has been proposed that CCK/gastrin evolved in the invertebrates as a neural peptide and was subsequently exploited by the vertebrates as a regulatory peptide in both the nervous system and the gastrointestinal endocrine system. The present results indicate that some gastropod molluscs, a merostomatan arthropod, and an annelid have detectable CCK/gastrin in both nervous and gut tissue. However, extractable CCK/gastrin was found only in gut tissue and not in the central nervous system of a crustacean arthropod. The tissue origin of the extracted CCK/gastrin in Bugula (phylum Ectoprocta) was not determined. Final resolution of the question of the nervous versus gut endocrine cellular origin of CCK/gastrin in invertebrates awaits further investigation. CCK/gastrin-like peptides are widely distributed among the invertebrates, which thus provide a rich source of comparative material for study of these regulatory substances.
The distribution of the intestinal hormone, cholecystokinin (CCK), was studied in the gastrointestinal tract of a holostean fish, the bowfin (Amia calva), and compared to a teleostean fish, the bluegill (Lepomis macrochirus), and an amphibian, the bullfrog (Rana catesbeiana), using an antiserum specific for the carboxyl terminal tetrapeptide of CCK in an unlabeled biotin-avidin immunoperoxidase procedure. In the bowfin CCK immunostained cells were detected only in the anterior and mid-intestine; the stomach and the rest of the gastrointestinal tract were negative. Immunoreactive cells were open in appearance and were scattered along the intestinal mucosal epithelium, with cells in mid-intestine relatively more abundant than in anterior intestine. These relative distributions were confirmed by radioimmunoassay of tissue extracts. Additional immunostained cells of uncertain function were detected in the lamina propria of the intestine. In bluegill gut immunoreactive cells were observed in the anterior and mid-intestine and in the pyloric caeca, where cells were clustered near the intestinal opening. Immunoreactive cells occurred relatively uniformly along the anterior and mid-intestine. Bullfrog CCK-containing cells were detected both in the antral stomach and in the duodenum. CCK in gut tissues likely originated in the intestine. The redistribution of CCK cells toward the anterior part of the intestine during evolution coincides with the development of a compact pancreas in higher classes of vertebrates. Such a redistribution constitutes an adaptive placement of endocrine cells for signaling during the intestinal phase of digestion.