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Biomedical subjects

J Cassuto

Publications and source records attributed to J Cassuto.

At least 37 records · Page 2Linked to original sources
PubMed1997

A randomized, blind comparison of remifentanil and alfentanil during anesthesia for outpatient surgery.

UNLABELLED: We compared remifentanil, an esterase-metabolized opioid, with alfentanil as part of balanced anesthesia with at least 0.8% isoflurane during outpatient surgery in a randomized, double-blind trial. One hundred two patients received remifentanil, and 99 patients received alfentanil. Patients who received remifentanil experienced significantly fewer stress responses to surgical stimuli (52.9% and 65.7%, P < 0.05); significantly fewer remifentanil patients responded to skin closure (11% and 22%, P < 0.05) than patients who received alfentanil. Significantly more patients in the alfentanil group required extra analgesia compared with the remifentanil group (P < 0.05). Time to respond to verbal command was shorter for alfentanil than remifentanil (median 7 min vs 9 min), and times to spontaneous respiration (median 5 min vs 8 min), adequate respiratory rate (median 6 min vs 9 min), and tracheal extubation (median 6 min vs 9 min) were significantly shorter for alfentanil in comparison with remifentanil (P < 0.05). Remifentanil patients, however, showed significantly better recovery of psychomotor and psychometric function between 30 and 90 min after surgery (P < 0.05). The incidences of hypotension intraoperatively and shivering postoperatively were significantly higher with remifentanil. No unexpected or serious adverse events were recorded with remifentanil; however, one patient who received alfentanil experienced severe recurrent respiratory depression after surgery. The metabolic profile of remifentanil allowed better intraoperative analgesia without compromising recovery. IMPLICATIONS: The pharmacological profile of remifentanil, a new opioid for use in anesthesia, suggests that rapid recovery will occur after its use. This study of 200 outpatients shows that the differences suggested from kinetic studies are not always borne out in clinical practice, although later recovery variables did, in fact, favor remifentanil.

Adolescent↗
PubMed1996

Effects of D-myo-Inositol-1,2,6-triphosphate on eicosanoid formation in burned skin.

D-myo-Inositol-1,2,6-triphosphate (IP3) has been shown to reduce edema and progressive ischemia following experimental skin burns. The mechanism(s) are not identified but could be related to antiinflammatory effects of the agent. In the present ex vivo study we compared the effects of IP3 with those of saline and indomethacin on eicosanoid formation by normal and burned rat skin. In burned skin IP 3 treatment reduced the release of thromboxane B2 (TXB2) (P < 0.01) and leukotriene B4 (LTB 4) (P < 0.05) but there was only a weak trend for less prostaglandin E (PGE) compared to burned control animals receiving saline. Indomethacin reduced the release of TXB2 (P < 0.01), and PGE (P < 0.001), but not LTB 4 from burned skin compared to skin from saline-treated burned animals. In non-burned skin IP 3 increased the release of PGE (P < 0.01) and LTB 4 (P < 0.01), but did not significantly influence TXB2 accumulation in the incubation fluid compared to the saline-treated group. Indomethacin reduced the release of TXB2 (P < 0.001) and PGE (P < 0.001), but increased LTB 4 (P < 0.001) in normal skin compared to the saline-treated group. In conclusion, IP 3 inhibited the release of TXB2 and LTB 4 from burned skin ex vivo, but increased PGE and LTB 4 release from normal skin. These results suggest that the mode of action of IP 3 differs from that of nonsteroidal antiinflammatory drugs. The effects of IP 3 on the arachidonic acid cascade also seem to differ in burned versus normal skin.

Animals↗
PubMed1996

Digital image analysis (DIA) of colour changes in human skin exposed to standardized thermal injury and comparison with laser Doppler measurements.

Clinical macrophotography followed by digitization and computer-assisted image analysis was performed on volunteers exposed to a mild experimental thermal injury. The aim was to elaborate a non-invasive technique allowing repetitive and quantitative monitoring of induced erythema and to evaluate a possible relationship with laser Doppler measurement of skin perfusion. A standardized 1 x 1 cm large thermal trauma was induced in the skin of the ventral forearm of 12 volunteers. Photographic recordings and skin blood flow measurements were made preburn and at 30-min, 1-h, 2-h, 4-h and 12-h postburn. Image analysis was performed with two colour systems, normalized rgb-values (rgb) and Hue-Saturation-Intensity (HSI). Erythema measured by rgb and HSI was most pronounced during the first hour postburn, after which it gradually decreased in order to increase again at 12 h postburn. Skin perfusion peaked at 30 min postburn and then continuously decreased during the course of the experiments. Degree of erythema could be quantified using both colour systems and a linear relationship was obtained between the observed colour changes of both systems and changes in skin perfusion. Results may also indicate that erythema can be present without a concomitant increase in skin perfusion, probably representing postburn venous stasis. The present study showed that digital image analysis is a non-invasive technique allowing repetitive and quantitative analysis of skin erythema which can be used to monitor pathophysiological changes in the body as well as the result of their treatment.

Adult↗
PubMed1996

Increased dermal perfusion after skin burn injury by D-myo-inositol-1,2,6-trisphosphate.

Full-thickness burn injury results in a continuous deterioration of blood flow due to vascular sludging, thrombosis formation and oedema leading to irreversible ischaemia and tissue necrosis. D-myo-inositol-1,2,6-trisphosphate (IP3) has previously been shown to reduce burn-induced oedema formation and inflammation involved in the pathophysiology of progressive ischaemia. A full-thickness burn injury (1 cm2) was induced in the abdominal skin of anaesthetized rats using an electrically heated thermoprobe. Blood flow in the experimental area was measured by laser Doppler flowmetry during 6.5 h postburn. The experiments included five groups. Three burned groups were treated intravenously with IP3 and received respectively: a bolus dose of 4 mg/kg followed by a continuous intravenous infusion of 20 mg/kg/h, 8 mg/kg + 40 mg/kg/h or 16 mg/kg + 60 mg/kg/h. One burned and one unburned control group received a corresponding bolus dose and infusion of saline. Results showed a significant inhibition of dermal ischaemia in the burned groups receiving IP3 at all dose intervals as compared to saline-treated burned rats (all P < 0.001). We conclude that IP3 improved local dermal perfusion in burned skin. Probable mechanisms of action could be the vasodilatory and anti-inflammatory properties of the agent.

Animals↗
PubMed1996

Small-bowel obstruction and the effects of lidocaine, atropine and hexamethonium on inflammation and fluid losses.

BACKGROUND: The profuse fluid losses and morbidity of patients suffering from obstructive ileus are closely related to inflammatory changes in the obstructed bowel wall. Previous experimental studies have shown that use of steroids and NSAIDs can reduce fluid losses in obstructive ileus. In the present study, we investigated the effects of lidocaine on fluid losses since local anesthetics have been shown to possess wide and potent anti-inflammatory properties. Hexamethonium and atropine were used to study the importance of the autonomic nervous system in bowel obstruction. METHOD: Experiments were performed in rats in vivo. After 18 h of total obstruction of the jejunum by thread ligation, a segment of the obstructed jejunum was placed in a chamber with intact nervous and vascular supply and net fluid transport was continuously registered by a gravimetric technique. Extravasation of Evans blue albumin as marker of inflammation was quantified by spectrophotometry. RESULTS: Hexamethonium (10 mg.kg-1 i.v.) significantly inhibited net fluid secretion (P < .05), while atropine (0.25 mg.kg-1 i.v.) had no significant effect. Net fluid secretion was reversed into absorption following an intravenous bolus dose of lidocaine (2 mg.kg-1) (P < 0.01) and topical administration of lidocaine (20 mg) on the serosa of the obstructed gut (P < 0.01). Single topical administration of lidocaine (20 mg) immediately before ligation significantly reduced net fluid secretion (P < 0.05) and inflammation (P < 0.05) in the obstructed bowel 20 h post-ligation compared to obstructed controls. CONCLUSION: Lidocaine significantly inhibited or prevented fluid losses when administered intravenously or topically to the obstructed gut. Mechanisms of action could be inhibition of nerve reflexes involved in fluid secretion and by inhibition of inflammation in the bowel wall. The inhibition of fluid losses by hexamethonium further supports the importance of the autonomic nervous system in the pathophysiology of bowel obstruction.

Administration, Topical↗
PubMed1996

Postoperative pain relief by topical lidocaine in the surgical wound of hysterectomized patients.

BACKGROUND: To improve postoperative analgesia, local anesthetics have been administered perioperatively as infiltration or as aerosol in the surgical area. A previous study showed good analgesic effects by topical lidocaine in the wound in minor extraabdominal surgery (herniorraphy), while the same treatment in minor lower laparothomies did not improve postoperative analgesia. The present study investigated the effect of topical wound anesthesia using lidocaine aerosol on postoperative pain following major lower abdominal surgery. METHODS: Postoperative pain and analgesic requirements were studied in a double-blind randomized trial including 30 hysterectomized patients. Patients were randomized to receive single wound treatment either with lidocaine aerosol 500 mg (100 mg/ml; Xylocain aerosol, ASTRA, Sweden) (n = 15) or placebo aerosol (n = 15). Postoperative pain was evaluated by visual analogue scale (VAS). Requirements of opiate analgesics (buprenorphine) after surgery were monitored. RESULTS: Lidocaine aerosol induced a significantly (P < 0.001) better analgesia at rest (VAS) and a significant (P < 0.001) reduction in postoperative requirements of buprenorphine during the first 24 hours after surgery compared to placebo aerosol. Differences between the groups in pain scores (VAS) and buprenorphine requirements during the second postoperative day were not significant. Mean pain scores upon mobilization 24 h after surgery were significantly lower in the group receiving lidocaine aerosol (P < 0.05). The plasma lidocaine concentration 4 h after the administration of lidocaine was well below toxic level and plasma lidocaine was detectable 48 h postoperatively. No drug-related side effects were reported. CONCLUSION: A single dose of lidocaine aerosol topically administered in the surgical wound of hysterectomy patients improved analgesia during the first postoperative day with minimal risk of side effects.

Adult↗
PubMed1996

The effect of alpha-trinositol on cholera toxin-induced hypersecretion and morphological changes in pig jejunum.

alpha-Trinositol (D-myo-inositol 1,2,6-trisphosphate, PP56) is a novel antiinflammatory drug. This study elucidates the effect of intravenous alpha-trinositol on basal and acute fluid transport and morphological changes following cholera toxin administration in pig jejunum in vivo. Using isolated jejunal tied-off loops, the fluid hypersecretory (accumulation) effect of different doses of cholera toxin was studied in pigs treated intravenously with saline added different doses (0, 4, 8, 16 and 32 mg x kg-1 x hr-1) of alpha-trinositol. Levels of alpha-trinositol, as well as stereomicroscopical, light microscopical and scanning electron microscopical morphological studies were performed. Cholera toxin evoked a dose-dependent fluid hypersecretion. Treatment with alpha-trinositol caused a dose-dependent inhibition of the cholera toxin-induced fluid hypersecretion and did not affect basal fluid absorption. The 16 mg x kg-1 x hr-1 alpha-trinositol dose gave a maximal inhibition of 36%. Morphological studies showed only minor changes following 6 hr of exposure to 20 micrograms x loop-1 cholera toxin. These changes consisted of dilation of the villus capillaries, an increase of apical membrane blebbing and a reduction of the intercellular space. Treatment with 16 mg x kg-1 x hr-1 alpha-trinositol alone did not induce any morphological changes, and did not alter the morphological changes induced by cholera toxin, which caused fluid hypersecretion and only minor acute morphological changes. In conclusion, alpha-trinositol treatment reduced cholera toxin-induced fluid hypersecretion without altering basal fluid absorption, basal morphology, or cholera toxin-induced morphological changes in pig jejunum in vivo.

Animals↗
PubMed1995

Importance of vasoactive intestinal peptide and somatostatin for fluid losses in small-bowel obstruction.

BACKGROUND: Previous observations have shown vasoactive intestinal peptide (VIP) to be an important secretagogue in the gut, whereas somatostatin has been reported to inhibit VIP release and fluid secretion. METHODS: The possible role of VIP as mediator of the inflammation and fluid losses in obstructive ileus was investigated in vivo and in a chronic rat model with thread ligation of the jejunum. Extravasated Evans blue (Eb)-stained albumin was quantified by spectrophotometry. Net fluid secretion was measured by a gravimetric technique. VIP antiserum was used to inhibit the effects of endogenous VIP. A somatostatin analogue, octreotide, was used to inhibit the release of VIP. RESULTS: Results showed a pronounced plasma Eb-albumin extravasation in the wall of the obstructed gut, which was significantly inhibited by VIP antiserum (p < 0.05) or octreotide (p < 0.01). Obstruction of the jejunum resulted in net fluid secretion that was significantly reduced by administration of octreotide (p < 0.01) or VIP antiserum (p < 0.05). Net fluid secretion in control animals remained constant. CONCLUSIONS: These findings suggest that VIP is an important mediator of the pathophysiology in mechanical intestinal obstruction and that somatostatin may be involved in the endogenous control of fluid losses.

Animals↗
PubMed1995

Influence of adrenoceptor agonists and antagonists on fluid secretion in small bowel obstruction.

OBJECTIVES: To investigate the importance of adrenoceptors on fluid losses in small bowel obstruction. DESIGN: Evaluation of the effects of adrenergic agonists and antagonists on in-vivo net fluid secretion in chronic small bowel obstruction in rats. METHODS: Net fluid transport in a jejunal segment was continuously registered in vivo after 18 h of mechanical obstruction of the small bowel in anaesthetized rats. The effect on net fluid transport of adrenoceptor agonists and antagonists and of isotonic saline was quantified. RESULTS: Clonidine, an alpha 2-agonist, had a significant (P < 0.05) anti-secretory effect, while yohimbine, an alpha 2-antagonist, significantly (P < 0.05) increased net fluid secretion. Phenylephrine, an alpha 1-agonist, and prazosin, an alpha 1-antagonist, lacked significant effects on net fluid transport. Similarly, prenalterol, a beta 1-agonist, and metoprolol, a beta 1-antagonist, had no significant effect on the net fluid transport. The beta 2-agonist salbutamol significantly (P < 0.001) decreased net fluid secretion, while the beta-antagonist propranolol significantly (P < 0.001) decreased net fluid secretion. CONCLUSION: Activation of alpha 2-adrenoceptors and blockade of beta 2-adrenoceptors significantly reduce net fluid secretion in small bowel obstruction. Results also demonstrate a continuous stimulatory effect on fluid secretion mediated by beta 2-receptors and a continuous inhibitory effect mediated by alpha 2-receptors.

Adrenergic Agonists↗
PubMed1994

Adrenergic, cholinergic and VIP-ergic influence on gastric phasic motility in the rat.

We investigated the effects of adrenergic, cholinergic and vasoactive intestinal polypeptide (VIP)-ergic agonists and antagonists on the amplitude of gastric phasic contractions in the anaesthetized rat using a volumetric model. The amplitude of the phasic contractions was reduced significantly by atropine, hexamethonium or bilateral cervical vagotomy indicating that cholinergic neural activity involving both muscarinic and nicotinic receptors and intact vagal nerve function are integral parts of the control of basal gastric phasic motility. In contrast, neither selective alpha 1-, alpha 2- or non-selective beta-blockers had any significant influence on the amplitude of the gastric contractions suggesting that adrenergic neurones are not tonically active in the maintenance of basal phasic motility in the stomach. The amplitude of the gastric phasic contractions was, however, significantly reduced by the alpha 1-agonist L-phenylephrine, the alpha 2-agonist clonidine and a close intraarterial injection of VIP (3 micrograms kg-1) but not be the selective beta 1-agonist, prenalterol, or the beta 2-agonist, salbutamol. These data suggest the presence of superimposed inhibitory control of phasic activity by VIP-ergic stimulation and by adrenergic neurones via alpha-receptor stimulation.

Adrenergic alpha-1 Receptor Antagonists↗
PubMed1994

Effect of lignocaine on eicosanoid synthesis by pieces of human gastric mucosa.

Lignocaine can affect prostaglandin synthesis in various tissues, and it has anti-inflammatory activity. No studies have been made previously on human isolated gut tissues. When concentrations of 5, 50 and 250 micrograms mL-1 lignocaine were incubated with human gastric mucosa/submucosa at 37 degrees C for 30 min, only the highest concentration reduced the levels of prostaglandin E, thromboxane B2 and 6-keto-PGF1 alpha in the incubates, and leukotriene C4/D4 was unaffected. Therapeutically relevant amounts of lignocaine given parenterally would therefore seem unlikely to alter gastric mucosal prostanoids, but high doses can be given orally because of extensive first-pass metabolism in the liver.

6-Ketoprostaglandin F1 alpha↗
PubMed1993

Involvement of vasoactive intestinal polypeptide in gastric reflex relaxation.

We have previously presented evidence for a non-adrenergic, vagally mediated colono-gastric inhibitory reflex induced by distension of the colon. We also found that pain stimulation by putting pressure on a testicle induced a pronounced gastric relaxation mediated by both adrenergic and vagal non-adrenergic fibres in anesthetized rats. Previous in vitro studies by other workers have strongly indicated that vasoactive intestinal polypeptide (VIP) is a neural mediator of gastric relaxation. The aim of the present in vivo study was to investigate, in anesthetized rats, whether VIP is involved in the gastric reflex relaxation induced by colonic distension and pain stimulation. A volumetric method was used to monitor changes in gastric volume. Gastric reflex relaxation following colonic distension was significantly and markedly inhibited by VIP antiserum as compared to the control relaxation before administration of the antiserum. Non-immunized control serum did not significantly influence gastric relaxation caused by colonic distension. Pain-induced gastric relaxation was moderately but significantly reduced after the administration of VIP antiserum but not after control serum. The selective beta 2-adrenoceptor agonist, salbutamol, induced a pronounced gastric relaxation of the same magnitude before and after the administration of VIP antiserum. VIP antiserum changed the pattern of gastric motility by inducing a specific type of gastric contraction appearing spontaneously or in response to colonic distension. A close intra-arterial injection of VIP induced gastric relaxation and inhibition of phasic gastric contractions. The present results in the rat suggest that VIP or a VIP-like peptide is involved in gastric reflex relaxation induced by colonic distension and pain stimulation.

Animals↗
PubMed1993

Inhibitory effects of amide local anaesthetics on stimulus-induced human leukocyte metabolic activation, LTB4 release and IL-1 secretion in vitro.

The anti-inflammatory effects of the amide local anaesthetics lidocaine and bupivacaine were evaluated in vitro by examination of the metabolic activation and secretory responses of human polymorphonuclear granulocytes (PMNGs) and mononuclear cells. Pretreatment with lidocaine or bupivacaine had a dose-dependent inhibitory effect on PMNG luminol-amplified chemiluminescence stimulated by bovine serum albumin (BSA)/anti-BSA immune complexes (IC) or by serum-opsonized zymosan (SOZ) particles. Both lidocaine and bupivacaine inhibited the release of the inflammatory mediators leukotriene B4 (LTB4) and interleukin-1 (IL-1) evaluated by radioimmunoassay (RIA). Pretreatment of suspended PMNGs and monocytes with the anaesthetics caused a marked inhibition of LTB4 release when the cells were stimulated with SOZ. In short-term (24 h) cultures of mononuclear cells the addition of lidocaine or bupivacaine reduced, in a dose-dependent manner, the level of IL-1 detected after stimulation with lipopolysaccharide (LPS). In all three assays (chemiluminescence, LTB4 and IL-1 RIA) bupivacaine was found to be more potent than lidocaine. The present results show that amide local anaesthetics have marked suppressive effects on the metabolic activation and secretory functions of leukocytes stimulated by different agonists. Although the detailed mechanisms for these effects are not known, they may explain part of the potent anti-inflammatory actions of local anaesthetics previously described in vivo.

Antigen-Antibody Complex↗
PubMed1993

Inflammation as a major cause of fluid losses in small-bowel obstruction.

The importance of inflammation for fluid losses in obstructive ileus was investigated in vivo in the rat. Inflammation was quantified by spectrophotometry of extravasated Evans blue (Eb)-albumin. Net fluid secretion in the obstructed jejunum was measured by a continuous gravimetric technique. The inflammation in the obstructed gut wall was significantly more pronounced than that in the gut distal to the obstruction and the sham-obstructed gut. The inflammation was significantly more pronounced in the serosa and external muscle layer than in the mucosa-submucosa. Acid-base balance in obstructed animals showed a significant metabolic alkalosis, whereas serum albumin and electrolytes were normal. Lumen fluid in obstructed animals showed low levels of albumin and total calcium as compared with serum, whereas fluid from the peritoneal cavity of obstructed rats showed high contents of albumin. Indomethacin and hydrocortisone given intravenously to obstructed animals significantly reduced the degree of extravasated Eb-albumin in the obstructed gut wall. Sham-operated animals showed net fluid absorption, whereas obstructed rats showed net fluid secretion. Secretion in obstructed animals was in all cases reversed into net fluid absorption after intravenous administration of indomethacin and hydrocortisone. These findings suggest that a pronounced inflammation occurs in the wall of the obstructed small intestine and that this inflammation plays an important role in the pathogenesis of the profuse fluid losses of obstructive ileus.

Analysis of Variance↗
PubMed1993

The use of modulated energy carried on a high frequency wave for the relief of intractable pain.

Ten volunteer patients with chronic neck/shoulder or back pain had been taking analgesics, and using conventional transcutaneous electrical nerve stimulation (TENS) with no significant pain relief. On entry to the trial, they were requested to stop taking their analgesics for two days prior to the study and for two days after starting to use the Liss Bipolar Body Stimulator for 20 min 3-5 times daily. Resumption of medication was then allowed. The stimulator (15,000 Hz carrier wave with a double modulation of 15 and 500 Hz) was connected to two adhesive electrodes placed so that the current field encompassed the trigger points, and used at a current that was just threshold for perception (1-4 mA). A visual analogue pain score was recorded before the study, and each evening of the month's study. The pain showed an overall highly significant rapid reduction of approximately 62% (p < 0.001), and all but two of the patients received substantial benefit throughout the study. We conclude that the Liss Bipolar Body Stimulator usually causes a substantial reduction of pain even in patients not helped by conventional TENS devices.

Back Pain↗
PubMed1992

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↗
PubMed1992

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↗