Fractures of long bones occurring in neonatal intensive therapy units.
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Biomedical subjects
Publications and source records attributed to J Gibbs.
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The hypothesis that endogenous cholecystokinin (CCK) released from the small intestine during feeding causes satiety was tested in rat pups, 9 to 12 days old. Intragastric administration of soybean trypsin inhibitor, a procedure that releases CCK from the small intestine, decreased the subsequent intake of a test meal. This effect was reversed by prior treatment with MK-329, a selective antagonist of CCK at alimentary-type CCK (CCK-A) receptors. Thus, endogenous, small intestinal CCK can cause satiety in the neonatal rat and this effect involves CCK-A receptors.
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Intraperitoneal injection of 50 micrograms.kg-1 of the selective dopamine D-1 receptor antagonist, SCH 23390, significantly decreased sham feeding of 6% and 10% sucrose solutions, but not sham feeding of 100% corn oil. Intraperitoneal injection of raclopride, a D-2 antagonist, elicited a significant dose-dependent (200-400 micrograms.kg-1) decrease in sham intake of both sucrose concentrations and corn oil at doses that did not increase the latency to sham feed or produce overt motor impairment. The rank order of inhibitory potency for both SCH 23390 and raclopride was 6% sucrose greater than 10% sucrose greater than 100% corn oil. In a second experiment, we found that in 2-bottle preference tests, the rank order of preference for these three liquids was 100% corn oil greater than 10% sucrose greater than 6% sucrose. Assuming that preference measured the relative reward value of the liquids, the potencies of the two antagonists were inversely related to the reward value of the liquid that was sham fed. This result supports but does not prove the dopamine hypothesis of the positive reinforcing effect of orosensory stimulation by nutrients. In addition, the differential selectivity of the two antagonists for different classes of nutrients suggests that normal sensory and/or hedonic processing of sham-fed sucrose depends on stimulation of both D-1 and D-2 receptors, but the normal sensory and/or hedonic processing of sham-fed corn oil depends primarily, perhaps exclusively, on stimulation of D-2 receptors.
An infant presented with a non-metastatic renal spindle cell sarcoma and hypercalcaemia, which resolved after treatment with indomethacin. There was in vivo and in vitro evidence that hypercalcaemia was mediated by circulatory prostaglandins.
Percutaneous transluminal balloon angioplasty was attempted in seven patients with internal carotid artery stenosis, including one patient who had two procedures. All had recurrent, carotid territory, neurological symptoms considered haemodynamic in origin. Six had occlusion of the contralateral internal carotid artery. Cerebral blood flow studies confirmed diminished cerebrovascular reserve in six patients studied. In five patients (six procedures) angioplasty of the stenosed internal carotid artery was carried out successfully. With two patients technical difficulty in crossing the stenosis prevented angioplasty and in one patient with bilateral stenosis the procedure was not attempted on the second side because of the severity of the stenosis. In two patients transient aphasia developed during cannulation of the carotid artery and in another a transient monoparesis developed during the procedure. Both these haemodynamic complications recovered within ten minutes. No other complications occurred. Our experience suggests that balloon angioplasty is technically feasible in the management of stenotic carotid disease associated with haemodynamic stroke. It is a technically simple procedure requiring only a brief admission to hospital. However, its general application to patients with thromboembolic carotid-territory stroke will depend on the risk/benefit ratio compared to carotid endarterectomy or to conventional medical treatment.
The satiating effect of duodenally administered fats was investigated with intraduodenal infusions of Intralipid in sham-feeding rats. Intralipid rapidly inhibited sham feeding and elicited the behavioral sequence of satiety. The satiating potency of Intralipid infusions in concentrations of 0.125-1 kcal/ml was a function of the concentration infused. The time course for Intralipid-induced satiety showed that fats inhibited feeding and led to the behavioral sequence of satiety within 15 min after the infusions began. This time course is evidence for a preabsorptive site of action to the small intestine. To test this hypothesis we added the local anesthetic tetracaine to Intralipid infusions. Tetracaine significantly reduced the satiating potency of Intralipid infusion. This result supports the hypothesis of a preabsorptive site of action. We also tested the specificity of intraduodenal Intralipid for feeding by administering Intralipid to rats that were sham drinking. The effect of Intralipid was relatively specific because the threshold concentration of Intralipid necessary to inhibit sham drinking was higher than the threshold for sham feeding. In addition, at superthreshold concentrations, Intralipid inhibited sham drinking less than sham feeding and elicited different behaviors than were observed during sham feeding.
We studied the effect of fourth intracerebroventricular administration of neuropeptide Y (NPY) and peptide YY (PYY) on ingestive and other behaviors in awake nondeprived rats. Injection of NPY or PYY into the fourth ventricle produced a significant dose-related increase in food intake and reduction in the latency to eat. PYY was more potent than NPY in increasing food intake and decreasing latency to eat, suggesting that PYY-preferring receptors sensitive to the orexigenic effects of NPY and PYY exist in the hindbrain. In addition, both peptides increased water intake when food was present but not when food was absent, suggesting that a neural substrate supporting a direct action of NPY and PYY on water intake is not present in the hindbrain. In time sampling of behaviors occurring during a 90-min feeding test, we found that both peptides increased the time spent eating and reduced grooming. In addition PYY, but not NPY, reduced apparent sleep and increased exploratory activity. This suggests that PYY, but not NPY, influences a hindbrain neural substrate involved in sleep and activity.
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Our recently proposed ischymetric hypothesis of the control of feeding and sleep predicts that both of these phenomena must be closely related. Whether food was available or not, peripherally administered bombesin produced an enhancement of total sleep by specifically increasing the duration of slow wave sleep but not the duration of paradoxical sleep. In all experimental situations, paradoxical sleep latency was increased. The data suggest an active role for endogenous bombesin-like peptides in the regulation of satiety and sleep.
Historically, nutrients and related metabolic signals were considered to control the onset and offset of meals. Recent research has focused upon the roles of peptides found in the gastrointestinal tract and brain as alternate controllers of these processes. During a meal, the gut secretes a variety of peptides as part of the digestive process. Some of these substances, acting as hormonal or as local signals, may also provide information which is relayed to the central nervous system, causing eating to stop and producing the sense of satiety. When administered to animals or people before a meal, exogenous cholecystokinin (CCK), the most studied of the putative satiety peptides, reduces food intake in a dose-dependent manner. Recent findings support the concept that endogenous CCK acts during meals to limit meal size, and evidence is reviewed suggesting a possible pathophysiological role for CCK in bulimia. Adiposity is also regulated via peptide hormones, especially insulin. Insulin is secreted in direct proportion to adiposity, and blood-borne insulin gains access to brain areas important in the regulation of feeding. The administration of insulin into the brain causes reduced eating and weight loss.
Tuberous sclerosis (TS) results from an autosomal dominant gene which exhibits variable expression and reduced penetrance. Although there are well established diagnostic criteria for TS, examination of first degree relatives can cause diagnostic criteria for TS, examination of first degree relatives can cause diagnostic problems with consequent difficulties in genetic counselling. Using an extensive, non-invasive protocol consisting of skin examination with Wood's lamp, cranial CT scan, specialist ophthalmological and dental examination, skeletal survey, and echocardiography, we have examined 56 first degree relatives of persons with TS. These consisted of 40 parents and seven sibs from 25 sporadically affected families and nine persons from seven multigeneration families. In seven of the apparently sporadically affected families, three mothers had echocardiographical findings consistent with one or more rhabdomyoma. In another, the mother's renal ultrasound showed evidence of single cysts in both kidneys. In a fifth family, the father had suggestive but not diagnostic features of TS on the cranial CT scan and skeletal survey. In the sixth family, the mother was found to have atypical calcification on CT scan. In a seventh instance a sib from a two generation family had echocardiographical evidence of a rhabdomyoma. Even though the proband in three of the sporadically affected families presented with fits, developmental delay, and depigmented patches, and therefore did not strictly fulfil the diagnostic criteria for TS, two mothers were found to have evidence of rhabdomyomata on echocardiography and the brother of the third had typical depigmented patches. Although the presently accepted diagnostic criteria for TS may not allow one to make a definitive diagnosis of TS in these relatives, we recommend that an extensive screening protocol be used to examine first degree relatives and that caution be used in counselling apparently unaffected members of families at risk for TS.
The existence of a relationship between cholecystokinin (CCK)-induced satiety and the serotoninergic system was evaluated. The food intake of 3-h-fasted male rats was studied after treatment with the COOH-terminal octapeptide of CCK (CCK-8) alone or in combination with one of two blockers of serotonin (5-HT) receptors, metergoline (MET; 1.0 or 0.06 mg/kg), active in both the periphery and brain, or xylamidine tosylate (XYL; 1.5 mg/kg), active only in the periphery. CCK-8 reduced food intake in the 30 min after food presentation by 37% at 2 micrograms/kg, 68% at 4 micrograms/kg, and 80% at 8 micrograms/kg compared with controls. Both doses of MET attenuated CCK-8-induced satiety, increasing food intake of rats treated with all doses of CCK-8 to control values. Food intake was significantly increased over base line by the 1.0-mg/kg dose of MET alone but unaffected by the 0.06-mg/kg dose of MET alone. XYL had no effect either given alone or in combination with CCK-8. These results indicate that the inhibitory action of CCK-8 on food intake is dependent on intact functioning of the serotoninergic system, probably at central sites.
To investigate the hypothesized inhibitory effect of cholecystokinin (CCK) released from the small intestine on food intake and gastric emptying, we infused soybean trypsin inhibitor (STI) into the stomach or duodenum of male rats deprived of food for 17 h. Intraduodenal infusions of STI (100-200 mg) before real or sham feeding, or during sham feeding, had no effect on food intake. Intragastric infusions of STI (100-200 mg) also had no effect on gastric emptying. Identical infusions of STI, however, increased bioassayable plasma CCK six to ninefold. The failure of endogenous, small intestinal CCK released by STI to decrease food intake or to decrease gastric emptying is evidence against the hypothesis that the inhibitions of food intake and of gastric emptying are physiological functions of small intestinal CCK in food-deprived rats. In contrast to the negative results with STI, administration of exogenous CCK-8 (2-4 micrograms/kg ip) significantly inhibited food intake and gastric emptying despite producing smaller increases of plasma CCK than STI produced. The reason for the differential effects of exogenous and endogenous CCK is not clear and requires further investigation.
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Specific binding sites for cholecystokinin (CCK) in the gastrointestinal tract of the adult rat are limited to the gastroduodenal region and are concentrated in the circular muscle of the pyloric sphincter. To determine the relationship of these pyloric muscle binding sites to the inhibition by CCK of food intake and of gastric emptying, these inhibitory effects of CCK were investigated in rats that had the pyloric sphincter surgically removed or that had the pyloric sphincter contractile mechanism damaged by a pyloroplasty procedure. CCK-8 decreased food intake and gastric emptying significantly in rats after pylorectomy or pyloroplasty. This demonstrates that an intact pyloric sphincter is not necessary for these inhibitory effects in rats. Because we found autoradiographic evidence for CCK receptors near the gastroduodenal anastomosis, however, the results suggest either that these receptors mediated the inhibition of food intake and emptying by CCK-8 or that these effects depend on CCK receptors in other locations.
The systemic administration of exogenous cholecystokinin (CCK), (a peptide released into the circulation when nutrients arrive in small intestine) provokes inhibition of food intake in numerous animal species and a sensation of satiation in humans. The mechanism involved requires participation of vagal afferent neurons to transmit information, possibly on gastric distension, to brain stem. Two crucial questions remain unanswered: does peripheral endogenous cholecystokinin transport information necessary for satiation at end of normal meals and if so, how and when is this message coded and deciphered; other studies have demonstrated that very small doses of exogenous cholecystokinin (too low to induce satiation if administrated peripherally) will induce satiety if injected into cerebral ventricles or directly into cerebral parenchyma. This suggest but does not prove that cerebral endogenous CCK also plays a role in satiety. It is not known how the satiating action of centrally-administered CCK is related to that of peripherally-administered CCK. Current studies aim at establishing a coherent schema of neuro-endocrine mechanisms implicated (from the gastrointestinal wall via the brain to a motivated behaviour) in the fact that food taken during a meal induces the end of the latter.
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