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Biomedical subjects

J Cassuto

Publications and source records attributed to J Cassuto.

At least 19 recordsLinked to original sources

Gastric reflex relaxation by colonic distension.

Previous studies in human volunteers have demonstrated an inhibition of gastric motility following painless rectal distension. In the present study we investigated, in anaesthetized rats, the effects of colonic distension on gastric tone and looked at certain aspects of the underlying nervous mechanisms. Changes in gastric volume were monitored continuously by a volumetric method. Colonic distension induced an immediate and pronounced gastric relaxation which lasted throughout the period of distension. The inhibition of gastric tone following colonic distension was abolished by hexamethonium or by bilateral cervical vagotomy. The selective adrenergic alpha 1 blocker, prazosin, the alpha 2 blocker, yohimbine, and the non-selective beta-blocker, propranolol, had no significant effect on gastric relaxation following colonic distension. Likewise, naloxone, an opioid receptor antagonist, did not significantly influence gastric reflex inhibition. It is concluded that colonic distension induced a non-adrenergic inhibition of gastric tone mediated through the vagal nerves. Ganglionic receptors are also suggested to form part of the inhibitory pathway.

Anesthesia

Influence of lidocaine on leukocyte function in the surgical wound.

The inflammatory response of the wound is mediated to a large extent by leukocytes, which play an important role in the wound healing process. Local anesthetics, which are routinely administered before minor skin surgery and for postoperative pain relief, have been shown to have diverse effects on wound healing. Local anesthetics have also been reported to induce potent inhibition of leukocytes in vitro, although their effects on leukocyte activity in the surgical wound have not been elucidated. The present study investigated the in vivo effects of lidocaine on leukocyte function in the surgical wound of rats by sampling leukocytes from hollow titanium implants. The surgical wound was treated with lidocaine or placebo after implantation of the titanium chamber and before skin closure. Leukocyte metabolic activity was measured by chemiluminescence. Cell count was analyzed in a Bürker chamber. Results showed progressive increase in leukocyte counts in the wounds of control animals and significantly lower cell counts in the wounds of lidocaine-treated animals 48 h (P less than 0.05) and 72 h (P less than 0.05) after surgery. A pronounced inhibition of the metabolic response to serum-opsonized zymosan was seen after 8 h in the lidocaine-treated animals versus controls (P less than 0.05). After 24 h, leukocyte metabolic activity decreased dramatically in the control group and remained at a low level until 72 h after surgery. In the lidocaine-treated group, the leukocyte response to zymosan remained constantly low throughout the study. The effects of lidocaine were not a result of impaired leukocyte viability.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals

Actions of serotonin antagonists on cholera-toxin-induced intestinal fluid secretion.

The effects of several 5-hydroxytryptamine (5-HT) receptor antagonists were tested in rats in vivo on the intestinal fluid secretion evoked by cholera toxin. Five receptor antagonists were used, namely 2-bromolysergic acid diethylamine (2-bromo-LSD), granisetron, ketanserin, methysergide and ondansetron. The drugs were used in doses that inhibited the arterial hypertension and/or bradycardia evoked by 5-HT given i.v. Granisetron and ondansetron markedly diminished cholera-toxin-evoked secretion, whereas ketanserin was without any effect. Methysergide also diminished cholera-toxin-induced fluid secretion particularly when the drug was given as an i.v. infusion. The results are considered in relation to the pathophysiology of cholera secretion and to the current views of receptor subtypes for 5-HT. It is proposed that the receptor involved is a 5-HT3 receptor, possibly also a receptor of the 5-HT1 type. Results from experiments in which 5-HT (20 mM) was placed in the intestinal lumen to evoke an intestinal secretion suggest that the 5-HT3 receptor is located in the villus tissue. It was also demonstrated that zimeldine, an inhibitor of presynaptic 5-HT reuptake, diminished choleraic secretion, an effect that may be ascribed to a 5-HT tachyphylaxis caused by an accumulation of 5-HT in a synaptic cleft.

Animals

Pain-induced inhibition of gastric motility is mediated by adrenergic and vagal non-adrenergic reflexes in the rat.

Painful stimuli have been shown to inhibit gastric motility in animal experiments and delay gastric emptying in humans. The aim of the present study was to investigate in detail mechanisms involved in pain-induced gastric inhibition. Pain stimulation by exerting pressure on a testicle induced a prompt gastric relaxation which lasted throughout the period of stimulation. Pain-induced gastric relaxation was significantly reduced by the selective alpha-1 blocker, prazosin, and by the non-selective beta-blocker, propranolol. Similarly pain-induced inhibition of gastric tone was significantly reduced by bilateral cervical vagotomy. In contrast, gastric relaxation following pain stimulation was significantly potentiated by the selective adrenergic alpha-2 blocker, yohimbine. Combined administration of prazosin and propranolol followed by bilateral cervical vagotomy abolished gastric relaxation in response to pain stimulation. In conclusion, gastric relaxation in response to painful stimulation was found to be reflex-mediated via sympathetic neurons acting on alpha-1 and beta receptors and possibly also via vagal non-adrenergic fibres. Pain-induced inhibition of gastric tone was significantly increased by yohimbine. It is suggested that yohimbine by blocking presynaptic inhibitory receptors on adrenergic neurons facilitates the release of noradrenaline in response to pain stimulation.

Anesthesia

Patterns of propulsive motility in the human colon after abdominal operations.

Twenty patients about to undergo elective cholecystectomy who were not using laxatives or drugs known to affect gastrointestinal motility and who did not give a history of gastrointestinal disease were investigated in a prospective open study. Patients swallowed two capsules each containing four radio-opaque markers every 12 hours starting 48 hours before operation. The pattern of resolution of postoperative colonic paralysis was monitored by serial abdominal radiographs taken every 12 hours until motility had returned to the rectum/sigmoid colon. In all 17 patients who completed the study propulsive motility started significantly earlier in the right colon (mean 61 hours) than in any other part (p less than 0.01). The gradient of resolution of postoperative colonic paralysis was always from proximal to distal, adding to the accumulating body of experimental evidence that implicates the right colon to return to normal first.

Abdomen

Inhibition of burn pain by intravenous lignocaine infusion.

Patients with burns often suffer severe pain, especially during dressing of wounds, but there are no established alternatives to potent opiate analgesics, with their various side-effects. Intravenous lignocaine infusion strikingly reduced self-assessed pain scores in 7 patients during the first 3 days after second-degree burns, without need for supplementary opiate analgesia.

Burns

Effects of selective adrenergic agonists and antagonists on gastric tone in the rat.

The aim of the present in vivo study was to investigate in anaesthetized rats, the effects of selective adrenergic agonists and antagonists on basal gastric tone and phasic contractions by the use of a volumetric method. L-phenylephrine, an alpha-1 agonist, induced hypertension, bradycardia and a significant gastric relaxation. Clonidine, an alpha-2 agonist, caused hypotension, bradycardia and a significant gastric contraction and a reduction of the amplitude of phasic contractions. Salbutamol, a beta-2 agonist, induced a dose-dependent tachycardia and a significant inhibition of gastric tone whereas prenalterol, a beta-1 agonist, induced tachycardia without any significant influence on gastric basal tone. Yohimbine, an alpha-2 blocker, significantly decreased gastric basal tone and reversed the inhibition of phasic contractions induced by clonidine. Prazocine, a selective alpha-1 blocker, and propranolol, a non-selective beta-blocker, had no significant influence on gastric basal tone or phasic contractions. It is concluded that sympathetic inhibition of basal gastric tone in the rat is mediated by alpha-1 and beta-2 adrenergic receptors. Activation of alpha-2 adrenergic receptors significantly increased basal gastric tone and reduced the amplitude of phasic contractions. A blockade of alpha-2 receptors significantly decreased basal gastric tone and restored the amplitude of phasic contractions.

Adrenergic alpha-Agonists

Treatment of postoperative paralytic ileus with cisapride.

The effect of cisapride on postoperative colonic motility was studied in 40 patients undergoing cholecystectomy under randomized, double-blind conditions. The patients received 10 mg of cisapride or placebo by intravenous injection starting on the day of surgery and repeated every 12 h until the 3rd postoperative day. The return of propagative motility in the colon was visualized by means of radiopaque markers and serial abdominal radiographs. Cisapride induced a significantly earlier return of propulsive motility in the right colon, as indicated by the propagation of markers from the ascending colon to the transverse colon (p less than 0.05). Radiopaque markers reached the descending colon (p less than 0.05) and the rectosigmoid colon (p less than 0.05) significantly earlier in the cisapride group than in controls. The first passage of feces occurred significantly earlier in cisapride-treated patients than in controls (p less than 0.05). The first passage of gas after surgery did not differ significantly between the groups. Our results suggest that cisapride can be used to induce earlier return of propagative motility in the colon after major abdominal surgery.

Cholecystectomy

A radiologic method for the study of postoperative colonic motility in humans.

Propulsive colonic motility in the postoperative period was studied, in 49 patients undergoing cholecystectomy, by means of radiopaque markers, water-soluble contrast, and serial abdominal radiographs. The colon was divided into four segments, and the propagation of the markers and contrast to the segments was registered. Marker propagation correlated significantly with the propagation of the contrast to all segments of the colon (p less than 0.001). The first postoperative passage of gas did not correlate significantly with the propagation of the markers or the contrast to the various colonic segments. The first passage of faeces postoperatively did not correlate significantly with the return of propulsive motility in the right colon; however, there was a significant correlation with the propulsion of markers to the descending colon (p less than 0.05) and the rectosigmoid colon (p less than 0.05). The duration of postoperative paralytic ileus, as measured by the start of propagation of the markers from the caecum, correlated directly with the consumption of opiate analgesics in the postoperative period (p less than 0.01) but inversely with age (p less than 0.05). The duration of surgery did not correlate significantly with the duration of paralytic ileus in the colon. In conclusion, a limited number of radiopaque markers can be used to study the return of postoperative propulsive motility in the colon. The first postoperative passage of gas is not an indicator of the duration of postoperative paralytic ileus, whereas the first passage of faeces is primarily representative of the return of propagative motility in the left colon.

Adult

Lack of effect of metoclopramide on colonic motility after cholecystectomy.

The effect of metoclopramide on postoperative colonic ileus was evaluated in a randomised, double-blind study in 20 patients after cholecystectomy. The start of propulsive colonic motility and colonic transit time after operation were measured by radio-opaque markers and serial abdominal radiographs. Metoclopramide 20 mg given intravenously three times a day until the fourth postoperative day (n = 10) did not significantly reduce the duration of postoperative colonic paralysis compared with control patients (n = 10), nor were there any differences between the groups when the time of first postoperative passage of gas and faeces were compared. In conclusion, the use of metoclopramide in the postoperative period did not result in a quicker return of propulsive motility in the right or left colon as judged by the radio-opaque markers and serial abdominal radiographs.

Cholecystectomy

Amide local anesthetics reduce albumin extravasation in burn injuries.

Burn injury was induced in anesthetized rats by exposing the abdominal skin to a temperature of 55 degrees C by means of a hot aluminum rod. Temperature was registered on a Grass polygraph. Skin exposure was interrupted when hot rod temperature had decreased to 45 degrees C. A full-thickness burn trauma of the skin was induced as judged from histologic sections. The burned skin was dissected and extravasation of Evans blue (EB) bound plasma albumin was quantified by a spectrophotometric technique and visualized by fluorescence microscopy. In the first set of experiments, one group of rats (n = 15) was topically treated with a lidocaine-prilocaine cream 5% (25 mg of each in 1 g; EMLA) for 1.5 h starting 15 min after inducing the burn injury. In one control group (n = 14) the thermal injury was treated with placebo cream. A second control group (n = 15) was topically treated with placebo cream without being exposed to thermal trauma. Results showed a significant inhibition of EB-albumin extravasation in the skin of burned rats treated with lidocaine-prilocaine cream compared with placebo-treated burned skin (P less than 0.001). EB-albumin contents in the skin of burned rats treated with lidocaine-prilocaine cream did not differ significantly from unburned skin (P greater than 0.05). In the second set of experiments continuous iv lidocaine infusions at a rate of 5 (n = 10), 10 (n = 12), 20 (n = 10), or 30 (n = 10) micrograms.kg-1.min-1 was given.(ABSTRACT TRUNCATED AT 250 WORDS)

Anesthetics, Local

Treatment of postoperative paralytic ileus by intravenous lidocaine infusion.

The effects of continuous intravenous infusion of lidocaine on postoperative paralytic ileus in cholecystectomized patients was investigated in this double-blind study. An infusion of lidocaine (3 mg/min, n = 15) or an infusion of an equal volume of saline (n = 15) was started 30 min before induction of anesthesia and continued for 24 h after surgery. Postoperative colonic motility was evaluated by radiopaque markers and serial abdominal radiographs. A record was kept of the first passage of gas and feces. Results showed significantly earlier return of propulsive motility in the colon of lidocaine-treated patients. Radiopaque markers in the lidocaine group were propelled significantly earlier from the cecum/ascending colon to the transverse colon (P less than 0.05) and appeared significantly earlier in the descending colon (P less than 0.05) and the rectosigmoid colon (P less than 0.05) than in saline-treated patients. Despite the fact that the mean time for postoperative defecation occurred 17 h earlier in lidocaine-treated patients, differences between the groups were not statistically significant--a fact due, perhaps, to great individual variations in defecation habits. The time to first passage of gas, a variable representative of changes in anorectal or colonic tone rather than propagative motility, also did not differ significantly between the groups. No adverse reactions to lidocaine were reported. The results suggest that continuous intravenous infusion of lidocaine during the first postoperative day shortens the duration of paralytic ileus in the colon after abdominal surgery. Suppression of inhibitory gastrointestinal reflexes by reduction of postoperative peritoneal irritation is suggested as the mechanism of action.

Cholecystectomy

Intravesical lidocaine in severe interstitial cystitis. Case report.

We report on a patient with a 2-year history of severe interstitial cystitis with disabling symptoms of painful urgency and urinary incontinence. The condition is characterized by a severe inflammatory reaction in the cystic wall and varying degrees of success for most therapeutic measures employed. Repeated vesical instillations of lidocaine in the urinary bladder relieved the patient from her pain and induced a long-lasting and potent anti-inflammatory effect on the cystic wall. Plasma lidocaine concentrations were below toxic levels and no adverse reactions were reported.

Administration, Intravesical

Topical anesthesia with lidocaine aerosol in the control of postoperative pain.

Postoperative pain was assessed in patients undergoing inguinal hernia repair. Ten patients received lidocaine aerosol in the surgical wound before skin closure, ten patients received placebo aerosol devoid of lidocaine, and ten patients were untreated. The lidocaine-treated group had significantly lower pain scores and meperidine requirements during the first postoperative day compared to the control groups. During the second day after surgery, these variables did not differ between groups. Wound anesthesia, assessed by palpation of the wound 24 h after surgery by a blinded investigator, was significantly more pronounced in the group treated with lidocaine aerosol than in the control groups. Similarly, in patients undergoing bilateral herniorraphy, wound pain following palpation was significantly reduced on the lidocaine-treated side compared to the untreated side. Patients in the group receiving lidocaine aerosol indicated less pain in connection with mobilization than untreated patients, but not compared to patients treated with placebo aerosol. Plasma substance P (SP) and beta-endorphin (BE) measured in lidocaine-treated patients and in untreated patients before and after drug administration showed no significant differences regarding SP, while BE was significantly increased 1 h after surgery in the untreated group. Plasma lidocaine concentrations were well below toxic levels. Results show that lidocaine aerosol used as topical anesthetic in the surgical wound is simple to use, and results in a long-lasting reduction of pain after a single administration. Moreover, postoperative mobilization is facilitated, and the requirement for postoperative analgesics is reduced. Wound healing was normal, and no adverse reactions to lidocaine were reported.

Adult

Inhibition of peritonitis by amide local anesthetics.

Peritonitis was induced in rats by exposing the peritoneal surface to 0.1 M hydrochloric acid (HCl). Peritonitis was quantified by extraction of Evans blue-bound albumin from the tissue exposed to HCl and analyzed by a spectrophotometric technique. In the first set of experiments, one group of rats had the peritoneal surface exposed to HCl following local pretreatment with isotonic saline; a second group of rats had the peritoneum exposed to HCl after topical pretreatment with an equal volume of lidocaine 1%, whereas in a third group the peritoneal surface was exposed only to saline without HCl. The experimental design in the second set of experiments was similar to that of the first set except that bupivacaine 0.5% was used instead of lidocaine in the second group. Results show a significant inhibition of peritonitis in the groups pretreated with lidocaine (P less than 0.01) and bupivacaine (P less than 0.05) compared with rats in the saline pretreated group. In the lidocaine-pretreated group Evans blue-albumin extravasation did not differ significantly from the rats not receiving HCl, whereas the bupivacaine-pretreated group showed a slightly but significantly (P less than 0.05) more pronounced peritonitis than control rats not exposed to HCl. In the third set of experiments the peritoneum was topically treated with either lidocaine 1%, bupivacaine 0.5%, or isotonic saline after first having exposed the peritoneal surface to HCl. A significant inhibition of albumin extravasation was seen following lidocaine (P less than 0.001) or bupivacaine (P less than 0.001) treatment compared with treatment with isotonic saline.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals

Influence of intraperitoneal anesthesia on pain and the sympathoadrenal response to abdominal surgery.

The effects of intraperitoneal administration of bupivacaine on pain and the sympathoadrenal response to surgery were studied in a double-blind randomized trial in 19 patients undergoing cholecystectomy. Bupivacaine (2 mg/kg) was dissolved in 300 ml isotonic saline and administered into the peritoneal cavity 10 min before the operation (n = 9). Saline was administered in a comparable group of patients (n = 10). There were no significant differences in pain scores between the groups during the first day after surgery (P greater than 0.05). Postoperative requirements of pethidine during the first 2 days after surgery did not differ significantly between the groups. Blood glucose levels were significantly lower in the bupivacaine-treated group 1 h (P less than 0.05) and 4 h (P less than 0.05) after skin incision. No significant differences were observed between the groups regarding plasma catecholamine and serum cortisol levels during and after surgery. Differences between the groups regarding urine output of catecholamines during the first and second postoperative days were not significant. Our results suggest that single administration of a local anesthetic intraperitoneally does not reduce pain or the sympathoadrenal response to upper abdominal surgery.

Adrenal Medulla

Opioids and opioid receptors in peripheral tissues.

Opioid peptides belonging to the enkephalin, beta-endorphin or dynorphin family, acting on specific opiate receptors may be found in peripheral tissues. Enkephalins have a widespread peripheral distribution, while beta-endorphin and dynorphin may be found locally in the enteric nervous system. The peptides of the various families are formed from specific precursor molecules. Apart from the enteric nervous system, opioids are also found in the adrenal medulla as well as in several autonomic ganglia. There is some evidence of three different classes of opioid receptors in peripheral tissues, i.e. mu-, delta- and kappa-receptors. These receptors are not only found on enteric nervous and mucosa cells but also on various cells in the immune system where opioid peptides seem to have important actions and appear to link the neuroendocrine and immune systems to control immunological functions. The physiological as well as the pathophysiological role of opioid peptides in the periphery is gradually being elucidated and, based on such knowledge, new therapeutic implications in gastrointestinal or immune diseases may be developed.

Animals