Biomedical subjects

B Beilin

Publications and source records attributed to B Beilin.

At least 19 recordsLinked to original sources

PubMed2006

Postoperative pain, morphine consumption, and genetic polymorphism of IL-1beta and IL-1 receptor antagonist.

Interleukin-1 beta (IL-1beta) and its endogenous IL-1 receptor antagonist (IL-1Ra) play an important role in inflammatory response and in pain modulation. It has recently been shown that polymorphism of the IL-1beta and IL-1Ra genes may account for variation in the production of these cytokines. The present study examined the hypothesis that polymorphism of IL-1beta and IL-1Ra genes is involved in pain sensitivity and morphine consumption in the immediate postoperative period. Genetic polymorphism was determined in 76 women undergoing transabdominal hysterectomy. The genotype of IL-1Ra was determined using PCR amplification of the variable number of tandem repeats (VNTR) of 86 base pair (bp) in intron 2, while for IL-1beta the cytosine to thymine transition at codon -511 of the promoter was determined by PCR. Morphine consumption and pain scores were evaluated in the first postoperative 24 h. The study group was divided based on morphine consumption to three sub-groups: low morphine consumers (LMC) (<28 mg/24 h), medium morphine consumers (MMC) (28-38 mg/24 h), and high morphine consumers (HMC) (>38 mg/24 h). Patients consuming the least amount of morphine postoperatively showed significant lower pain scores. IL-1Ra genetic polymorphism of the MMC group was significantly different compared to the other two groups. No difference in IL-1beta gene polymorphism was found among the three sub-groups. Since IL-1Ra polymorphism is known to affect the levels of both IL-1Ra and IL-1, cytokines associated with modulation of pain sensitivity and morphine analgesia, it is suggested that IL-1Ra genetic polymorphism may contribute to the variation in postoperative morphine consumption.

Adult↗

PubMed2006

Anesthesiologists at work: an increase in pro-inflammatory and Th2 cytokine production, and alterations in proliferative immune responses.

BACKGROUND: Anesthesiologists are a population at high risk of alcohol and drug abuse, depression, suicide, and psychiatric hospitalization. The impact of their working milieu on specific immune indices has scarcely been studied, and it is assumed that immune perturbations may contribute to some of the above risks. This study took advantage of an unplanned, 3-month long strike of anesthesiologists, and explored its relations to specific immune measures. METHODS: We assessed induced cytokine production and lymphocytes proliferative responses in blood samples taken from 10 anesthesiologists just before the strike and at its end, after a long period of markedly reduced workload. RESULTS: The results indicated that the proliferative responses to phytohemagglutinin (PHA) and concanavalin A (Con A) were significantly lower at the end of the strike. At this time point, we observed a significant decrease in the production of interleukin-6 (IL-6), IL-10 and IL1ra levels, and a significant increase in IL-2 production. A strong trend towards a decline in tumor necrosis factor-alpha (TNF-alpha) levels was evident, while levels of IL-1beta were unchanged. CONCLUSION: These findings suggest that the working conditions of anesthesiologists are associated with specific immune alterations, including a shift towards a Th2 cytokines' dominance, and an elevated pro-inflammatory cytokine response. A reduced Th1 profile has been related to increased susceptibility to infections, and high pro-inflammatory cytokine levels were recently proposed as etiological factors in cardiovascular diseases and in depression.

Adult↗

PubMed2005

Combining physostigmine with meperidine for sedation and analgesia during colonoscopy.

BACKGROUND AND STUDY AIM: Opiate or benzodiazepine drugs are often used during colonoscopy, but they are associated with respiratory depression and prolonged recovery. Physostigmine, a tertiary anticholinesterase agent, is known to enhance analgesia and to reverse the central nervous system depressant effects of these drugs. This study compared the effect of giving meperidine alone with the effect of giving meperidine in combination with physostigmine in patients who were undergoing complete colonoscopy. PATIENTS AND METHODS: A total of 44 outpatients undergoing elective colonoscopy were randomly assigned to receive analgesia with either meperidine 0.5 mg/kg intravenously (group 1, n=24) or physostigmine 10 micrograms/kg intravenously, followed 5 minutes later by meperidine 0.5 mg/kg intravenously (group 2; n=20). The patients were assessed with regard to oxygen saturation, hemodynamic changes, pain perception and sedation scores, readiness to go home, and adverse effects. RESULTS: The group 1 patients' oxygen saturations consistently fell, both during the procedure and in the recovery period; in group 2, oxygen saturations remained stable throughout the procedure and recovery period (95.88%+/-0.99 vs. 98.15+/-0.99, P<0.001). Patients in group 2 reported lower pain perception scores during the procedure (measured using a visual analog scale) than patients in group 1 (1.46+/-0.31 vs. 1.75+/-0.41; F1,42=6.484, P<0.015) and were less sedated during recovery (F1,41=6.56, P<0.015). No significant differences were found between the two groups with regard to heart rate or arterial blood pressure. All patients in group 2 were ready to go home after 25 minutes in the recovery area; three patients in group 1 were not ready to leave at 25 minutes and left the facility after 60 minutes. Four patients suffered from minor side effects of physostigmine (sweating and nausea). CONCLUSIONS: Combining physostigmine with meperidine as preparatory treatment for patients undergoing colonoscopy prevents respiratory depression, improves analgesia, and shortens recovery time, with only mild side effects.

Adult↗

PubMed2005

Comparison of the Flexiblade levering laryngoscope with the English Macintosh laryngoscope in patients with a poor laryngoscopic view.

The effectiveness of two laryngoscopes, the English Macintosh and the Flexiblade (a levering laryngoscope), were compared in a clinical setting. An investigation was carried out in 100 patients admitted for surgery under general anaesthesia, to compare intubation with the Flexiblade or the Macintosh laryngoscope. The patients had two anatomical characteristics that may predict difficult intubation - Mallampati score II and III, and a thyromental distance </= 6.5 cm. Patients were randomly allocated to receive intubation with one of the laryngoscopes. The laryngeal view obtained during laryngoscopy, the intubation time, and the need for optimization manoeuvres and assistance required were compared in the two groups. The correlation between intubation time and anatomical characteristics was determined. Only 49 patients had a poor laryngeal view during initial laryngoscopy and required additional facilitating manoeuvres. In these patients, successful intubation time (in seconds) using the Flexiblade was significantly shorter than using the Macintosh laryngoscope (median 14.3 s, IQR 12.0-18.4 s [corrected] vs. median 20.8 s, IQR 14.9-25.5 s (U = 165, [corrected] p , 0.01). Assistance and additional manoeuvres were required significantly less frequently in the Flexiblade group (21%) compared to Macintosh group (67%) (p < 0.01). No correlation was found between intubation time, Mallampati scores, thyromental distance, or body weight. We concluded that in patients with an initial poor laryngoscopic view, the Flexiblade may enable faster and easier tracheal intubation.

Adult↗

PubMed2005

Continuous physostigmine combined with morphine-based patient-controlled analgesia in the postoperative period.

BACKGROUND: Recently, new drugs and techniques for the treatment of postoperative pain were introduced, with the goal of enhancing opiates' analgesia while minimizing their side-effects. Cholinergic agents play an antinociceptive role, but their clinical use is quite limited, due to side-effects. Physostigmine is a cholinesterase inhibitor, which crosses the blood-brain barrier and elevates brain acetylcholine level. Physostigmine can produce analgesia by itself, and enhance opiate analgesia; but these effects are of short duration following bolus administration. METHODS: We compared pain intensity and morphine consumption in two postoperative treatment groups: One group received continuous physostigmine infusion combined with morphine-based patient-controlled analgesia (PCA), and the other received PCA alone. Cholinergic anti-inflammatory pathways have recently been described. We therefore also compared changes in proinflammatory cytokine production in the two pain management groups. RESULTS: Continuous infusion of physostigmine combined with morphine-based PCA in the postoperative period significantly reduced opiate consumption, and enhanced the analgesic response. Patients in the physostigmine group also exhibited reduced ex-vivo production of the proinflammatory cytokine, IL-1beta. At the same time, physostigmine increased nausea and vomiting, mostly in the first 2 h of the postoperative period. CONCLUSIONS: Physostigmine combined with morphine in the postoperative period reduced morphine consumption, enhanced analgesia, and attenuated production of the proinflammatory cytokine, IL-1beta. This latter finding may account for the decreased pain observed in this group; this cytokine is known to mediate basal pain sensitivity and induce hyperalgesia in inflammatory conditions. Taking into account the other potential beneficial effects of physostigmine, we suggest that a continuous infusion of physostigmine should be considered as a useful component in multimodal postoperative analgesia.

Adult↗

PubMed2002

Immune response in asymptomatic smokers.

BACKGROUND: It has been demonstrated that cigarette smoking affects the immune system. Impairment of alveolar mononuclear cell function, described previously, may contribute to the higher rate of postoperative respiratory infections. However, increased susceptibility of smokers to infections of other origin (e.g. wound-related) implies that tobacco effect is not restricted to the respiratory immune competent cells. The present study was designed to investigate the systemic effect of tobacco smoking as it exerted on blood-derived immune cells. We measured systemic cytotoxic activity of natural killer cells, production of pro- and anti-inflammatory cytokines by blood mononuclear cells and their proliferation in response to mitogens. To minimize the immunosuppressive effect of other smoke-related factors, the smokers with chronic obstructive pulmonary disease (COPD) were excluded from this study. METHODS: Peripheral blood mononuclear cells (PBMC) from 24 chronic asymptomatic smokers, and 28 controls, age and gender matched, were isolated and incubated in vitro with lipopolysaccharide (LPS) or phytohemagglutinin (PHA) to induce secretion of IL-1beta, IL-1ra, IL-6, IL-10, TNFalpha and IL-2, respectively, from mononuclear cells. The level of the cytokines in the supernatants was measured using ELISA kits. The proliferative response to the mitogens PHA and concanavalin A (ConA) was evaluated by 3H-thymidine incorporation and NK cell cytotoxicity by 51Cr release assay. RESULTS: Mononuclear cells from smokers showed increased production of the pro-inflammatory cytokines IL-1beta, IL-6 and TNFalpha and enhanced proliferative response to mitogens as compared to non-smoking population. The secretion of IL-2 and the anti-inflammatory cytokines IL-1ra and IL-10 was similar in both groups. NK cell cytotoxic activity was suppressed in the smokers. CONCLUSION: Cigarette smokers without chronic obstructive pulmonary disease (COPD) exhibit impaired NK cytotoxic activity in peripheral blood and unbalanced systemic production of pro- and anti-inflammatory cytokines. These changes may serve as predisposing factors for respiratory and systemic infections in the postoperative period and should alert an anesthetist during perioperative management.

Cytokines↗

PubMed2002

Design evaluation of commonly used rigid and levering laryngoscope blades.

BACKGROUND: The shape of a laryngoscope blade affects the exposition of the larynx. This study evaluates and compares some rigid and levering blade designs based on previous investigative X-ray laryngoscopic studies. METHODS: Five rigid laryngoscope blades (Miller #3, Standard Macintosh #3, Classical Macintosh #4 and English-Macintosh #3 and #4) and two levering laryngoscope blades (McCoy in neutral and maximally elevated positions and Flexiblade in three basic positions: straight, neutral, and maximally curved) were evaluated. This study assesses two parameters derived from the depth of insertion: the eye line deviation from the ideal straight view line to the vocal cords, and the space occupied by the blade behind the mandible, which affects the contact of the blade tip with the base of the tongue. RESULTS: The best results on larynx exposition were produced by the English-Macintosh #4 at all insertion depths between 5 and 14 cm. It surpassed the Classical Macintosh #4 and both the English and Standard Macintosh #3. Although the Miller and the Flexiblade in a straight position afford a nearly ideal view line, both blades reduce the space reserved for the tongue behind the mandible. The McCoy with its tip maximally elevated provides limited view, while activation of the Flexiblade provides various ranges of larynx exposition. CONCLUSION: The difference in shape and design of Macintosh blades affects their performance. The distal portion of a large-sized curved blade is more effective than the full length of a shorter blade. The #4 English Macintosh is a better choice for routine clinical use. The Flexiblade performs as a multiblade device and can therefore be used for both routine and difficult intubations.

Equipment Design↗

PubMed2000

Hypothermia affects the phagocytic activity of rat peritoneal macrophages.

To examine the effect of hypothermia on the phagocytic capacity of rat peritoneal macrophages for latex particles, male Wistar rats were exposed to 4 degrees C for 8 and 72 h. While the shorter exposure to cold did not affect body temperature and macrophage function, animals exposed to 4 degrees C for 72 h showed a mean decrease of their body temperature by 1.5 degrees C. The superoxide anion production was significantly increased whereas the number of phagocytic cells decreased. In addition, the mean number of latex particles engulfed by each individual cell was lower than that of controls. Peripheral blood mononuclear cells (PBMC) of these animals showed lower mitogen response to phytohaemagglutinin (PHA), while that for concanavalin A (Con-A) remained unchanged. Peritoneal macrophages exposed in vitro to 24 degrees C for 60 min showed a decreased phagocytic capacity in comparison with macrophages kept at 37 degrees C, an observation suggesting the development of an indigenous cell defect for phagocytosis at lower temperatures. On the other hand, the effect of additional humoral factor(s) on macrophage activity, such as an increase in serum level of catecholamines and corticosterone, cannot be excluded. The results of the study may contribute to understanding the predisposition to infections during exposure to cold.

Animals↗

PubMed1999

Decreased phagocytic capacity of rat peritoneal macrophages following photon abdominal irradiation.

Photon irradiation of the abdomen may be accompanied by complications due to a decrease in the immune defense of the recipient. Since peritoneal macrophages are an important component of the immune system, we examined the phagocytic activity and oxygen superoxide anion generation by peritoneal macrophages from rats 2 and 4 weeks after abdominal irradiation with 6 MV photons applying a single dose of 2 Gy. Two and 4 weeks after irradiation, peritoneal macrophages were harvested and their capacity to engulf latex particles and to produce oxygen superoxide anions was determined. Non-irradiated rats, treated identically otherwise, served as controls. Two weeks after irradiation the phagocytic capacity and oxygen superoxide anion generation decreased by 61 and 70%, respectively, compared with controls. This tendency persisted after 4 weeks post irradiation, the decrease in both functions being 50 and 74%, respectively. It is suggested that the altered function of peritoneal macrophages following irradiation may further compromise the immune defense in patients receiving abdominal radiotherapy.

Abdomen↗

PubMed1999

Hypothermia in barbiturate-anesthetized rats suppresses natural killer cell activity and compromises resistance to tumor metastasis: a role for adrenergic mechanisms.

BACKGROUND: Clinical studies have implicated surgery in promoting infections and compromising immune functions, including natural killer cell activity. Animal studies indicate that surgery-induced suppression of natural killer cell activity also promotes tumor metastasis. Hypothermia, a common surgical complication, has been suggested to underlie some of the deleterious consequences of surgery. This study evaluated the effect of hypothermia on the activity and number of blood natural killer cells and on host susceptibility to metastasis. The involvement of adrenergic mechanisms was also considered. METHODS: Fischer-344 rats remained awake in their cages (control group) or were anesthetized with 70 mg/kg thiopental and maintained for 2.5 h at core body temperatures of 30-32 degrees C (hypothermia group) or 38 degrees C (normothermia group). Thereafter, at several time points, blood was drawn so natural killer cell activity could be assessed, or rats were injected with syngeneic MADB106 tumor cells that metastasize only to the lungs. Lungs were removed 9 h later for assessment of lung tumor retention, or 4 weeks later for counting of metastases. RESULTS: Normothermic anesthesia reduced natural killer cell activity (lytic units at 30% specific killing, mean +/- SEM) to 39+/-6.2% of control levels and hypothermia further reduced it to 15+/-6.6%. These changes were not accompanied by alterations in the numbers of circulating natural killer cells. Hypothermia increased tumor retention to 250% of control levels, and the number of metastases increased from 1.1+/-0.4 to 4.7+/-1.2. Normothermia had no significant effects on this index. Nadolol (0.4 mg/kg), a beta-adrenergic antagonist, significantly attenuated the effect of hypothermia on tumor retention. CONCLUSIONS: Hypothermia under thiopental anesthesia suppresses natural killer cell activity and compromises host resistance to metastatic formation, possibly via adrenergic mechanisms. Such suppression may place patients with metastasizing tumors or dormant viral infections at greater risk for complications after intraoperative hypothermia.

Adrenergic beta-Antagonists↗

PubMed1998

Effect of sodium thiopentone anesthesia on the phagocytic activity of rat peritoneal macrophages.

To elucidate the effect of sodium thiopentone anesthesia on the function of phagocytic cells, albino rats were anesthetized with 60 mg/kg. of sodium thiopentone. After 90 min., peritoneal macrophages were harvested and their capacity for superoxide anion generation was detected. Following anesthesia for 90 min. latex particles were injected intraperitoneally, and after additional 30 min. the macrophages were derived, embedded in agar and the number of cells engaged in phagocytosis, as well as the number of latex particles engulfed by each individual cell were counted in semi-thick sections. Macrophages of anesthetized animals showed a statistically significant decrease of both superoxide anion generation and mean number of phagocytic cells, and engulfed fewer particles than those of the controls. Similar results were obtained following incubation of the cells with sodium thiopentone in vitro. The serum corticosterone level in anesthetized rats was significantly higher than that of the control animals. The results indicate that impaired phagocytosis following anesthesia induced by sodium thiopentone, in addition to alterations of the immune system caused by surgical trauma, may be one of the reasons for increased susceptibility to infections of surgical patients during the postoperative period.

Anesthesia↗

PubMed1998

Effects of mild perioperative hypothermia on cellular immune responses.

BACKGROUND: Unintentional perioperative hypothermia is a common complication of anesthesia and surgery associated with adverse effects on several systems, including impaired wound healing and more frequent wound infections. Mild hypothermia affects various immune functions. In the current study, the authors sought to determine whether immune alterations in the perioperative period might be induced, at least in part, by impaired thermoregulation during this period. METHODS: Sixty patients undergoing abdominal surgery were randomly assigned to two thermal care groups: routine care or forced-air warming. The patients' anesthetic care was standardized. Venous blood samples were collected 90 min before induction of anesthesia and immediately, 24 h, and 48 h after surgery. White cells were separated and frozen. Peripheral blood mononuclear cells were used to test cytokine production (interleukins [IL] -1beta, -2, and -6; tumor necrosis factor-alpha [TNF-alpha]), mitogens-induced proliferation, and natural killer NK cell cytotoxicity. Plasma cortisol levels were also determined. RESULTS: Patients in the normothermia group maintained normal body core temperature, whereas temperature decreased by approximately 1 degree C in the hypothermia group. Mitogenic responses were suppressed in cells from patients in the hypothermia but not in the normothermia group 24 and 48 h after surgery. Proinflammatory cytokine (IL-1beta, IL-6, TNF-alpha) production increased in both groups, although the production of IL-1beta was significantly higher in the normothermia group 24 h after surgery. Production of IL-2 was suppressed in the hypothermia but not in the normothermia group at 24 h. CONCLUSIONS: Mild perioperative hypothermia suppressed mitogen-induced activation of lymphocytes and reduced the production of certain cytokines, IL-1beta and IL-2, and in this way may contribute to the immune alterations observed in the perioperative period.

Antibody-Dependent Cell Cytotoxicity↗

PubMed1998

Labor affects cytokine production in newborns.

PROBLEM: To investigate whether the mode of delivery or the drugs given to the mother during labor may affect the newborns' immune system. METHOD OF STUDY: Three groups of term newborns were included: A, spontaneously delivered with i.v. analgesia (n = 37); B, spontaneously delivered with epidural analgesia (n = 26); and C, delivered by cesarean section under general anesthesia (n = 29). Natural killer (NK) cell cytotoxicity, mitogenic response, and the capacity of peripheral blood mononuclear cells (PBMCs) to produce interleukin (IL)-1 beta, IL-2, IL-3, IL-6, and tumor necrosis factor (TNF)-alpha were examined. RESULTS: NK cell cytotoxicity increased significantly in all three groups of newborns on the second day of life. Decreased IL-2 production was observed in newborns delivered by cesarean section. Spontaneous IL-1 beta secretion was higher in newborns to mothers treated with epidural analgesia. Spontaneous IL-6 secretion was elevated in infants to mothers undergoing general anesthesia and surgery or epidural analgesia. TNF-alpha production was increased in newborns delivered by cesarean section. CONCLUSION: The immune response of the newborn is affected by the mode of delivery and/or drugs given to the mother during labor.

Analgesia, Epidural↗

PubMed1997

Systemic physostigmine increases the antinociceptive effect of spinal morphine.

In this study we evaluated the antinociceptive effect of concurrent intrathecal (i.t.) and subcutaneous (s.c.) administration of morphine and physostigmine, respectively. The experiments were performed on male Wistar rats. Intrathecal administration of morphine was performed through a catheter implanted in the subarachnoid space. The 'tail-immersion' test was used to measure animals' responses to evoked nociceptive stimuli. Interaction of drugs was analyzed using a dose addition model. Both i.t. (1-5 microg) administration of morphine and s.c. (50-250 microg/kg) administration of physostigmine increased the latencies of nociceptive responses in a dose-dependent manner. Two micrograms of i.t. morphine and 100 microg/kg of s.c. physostigmine demonstrated 31.6 +/- 10.6 and 34.2 +/- 11.4 percentage of maximal possible effect (%MPE), respectively. Simultaneous administration of 1 microg of i.t. morphine and 50 microg/kg of s.c. physostigmine produced a %MPE equal to 84.8 +/- 16.9. Thus, combined administration of 1 microg i.t. morphine and 50 microg/kg s.c. physostigmine resulted in a strong, highly significant antinociceptive effect. This effect was much higher than the effect expected if both drugs acted in an additive manner. Supra-additive interaction observed in this study might be a result of simultaneous activation of different neurotransmitter systems involved in nociceptive processing at the spinal as well as at the supraspinal level of the CNS.

Analgesics, Opioid↗

PubMed1996

Effect of oral chemotherapy on the mitochondrial size of mouse intestinal cells.

Since orally given cytotoxic agents may cause intestinal disfunction, the effect of oral administration of three cytotoxics, i.e., methotrexate (MTX), cyclophosphamide (CPA), and ftoral, a derivative of 5-fluorouracil (5-FU), on the gastric, liver, and small-intestine cells of C57B1 mice was studied by transmission electron microscopy. Although no ultrastructural alterations could be detected in the cells of the first two organs, the epithelial cells of the small intestine showed a marked increase in size of their mitochondria. In the control animals the mitochondrial size was in the range of 0.04-1.8 micron (mean +/- SE 0.54 +/- 0.01 micron). In the treated animals the size of the mitochondria ranged between 0.15 and 4.33 micron (mean +/- SE 0.73 micron) for those treated with MTX, 0.24-2.88 micron (mean +/- SE 0.80 +/- 0.02 micron) for those given CPA, and 0.28-5.3 micron (mean +/- SE 1.18 +/- 0.48 micron) for those treated with 5-FU. These findings were significantly different from those obtained in controls (P < 0.0001). In addition, in animals treated with MTX the mitochondria of the jejunal cells were surrounded by channels of rough endoplasmic reticulum. The cytoplasm contained long, winding channels of smooth endoplasmic reticulum, vacuoles, and myelin figures. Fluid retention in the small intestine due to administration of cytotoxic drugs is suggested as a possible mechanism for distention of the mitochondria.

Administration, Oral↗

PubMed1996

Effects of anesthesia based on large versus small doses of fentanyl on natural killer cell cytotoxicity in the perioperative period.

Surgical stress and general anesthesia suppress immune functions, including natural killer cell cytotoxicity (NKCC). This suppression could be attributable, at least in part, to opiates. We have previously shown that large-dose fentanyl administration suppressed NKCC in rats. The present study sought to compare the effects of two anesthetic protocols, based on large- (LDFA) versus small (SDFA)-dose fentanyl anesthesia on NKCC in the perioperative period. Forty patients were included in this study; half were assigned to each protocol of anesthesia. In each anesthetic group, half the patients were undergoing surgery for malignant diseases, and half for benign conditions. Blood samples were collected during the perioperative period. NKCC was assessed using the chromium release assay. Initially, both types of anesthesia similarly suppressed NKCC, with a peak effect 24 h after surgery. The two types of anesthesia, however, differed in the rate of recovery of NKCC suppression. By the second postoperative day, NKCC returned to control values in the SDFA patients, whereas NKCC was still significantly suppressed after LDFA. These results indicate that LDFA causes prolonged suppression of NK cell function. Whether this suppression might have a long-term impact on the overall outcome, especially in cancer patients, remains to be determined.

Adult↗

PubMed1996

Effect of high doses of 2-CdA on Schwann cells of mouse peripheral nerve.

The present study was undertaken to examine the effect of 2-CdA (Leustatin) on the Schwann cells of myelinated and unmyelinated fibers of peripheral mouse nerve. Two groups of mice were injected intravenously for seven days with 2-CdA: one group received daily doses of 1 mg/kg and the other 0.5 mg/kg. Both doses exceeded those accepted in clinical practice. Mice injected with saline served as controls. The sciatic nerve was then dissected and examined with a transmission electron microscope. The Schwann cells of both the myelinated and unmyelinated nerve fibers of the animals receiving the higher doses of 2-CdA showed nuclear and nucleolus damage, loss of heterochromatin, vacuolization and disorganization of the myelin sheaths. The mesaxons and the axons were also damaged. The Schwann cells of the animals treated with the lower doses appeared undamaged. The results indicate that in contrast to other anticancer drugs known to produce peripheral neuropathy, 2-CdA may cause damage to the Schwann cells only at doses exceeding the therapeutic ones.

Animals↗

PubMed1992

Narcotic-induced suppression of natural killer cell activity in ventilated and nonventilated rats.

Surgical stress and general anesthesia can suppress immune function and thus may increase postsurgical infections and tumor metastasis. We previously reported that two narcotics commonly used in high-dose opiate anesthesia (fentanyl and sufentanil) suppress natural killer (NK) cell activity in rats. Such doses of narcotics also cause respiratory depression accompanied by hypoxia, hypercarbia, and acidosis, which might account for the observed narcotic-induced NK suppression. In the present study, we compared the effects of fentanyl on NK activity in ventilated and non-ventilated rats. Fentanyl significantly suppressed NK cell activity to the same magnitude in the two groups, although the groups significantly differed in CO2 and O2 levels. The fact that high-dose fentanyl-induced NK suppression can be demonstrated in ventilated rats accentuates the relevance of these findings to clinical studies showing NK suppression in the immediate postoperative period. Such immunosuppression could be a risk factor for patients undergoing surgery, especially in cancer-related operations.

Animals↗