Comparison of the neuromuscular blocking effect of cisatracurium and atracurium on the larynx and the adductor pollicis.

BACKGROUND: Cisatracurium unlike atracurium is devoid of histamine-induced cardiovascular effects and this alone would be the greatest advantage in replacing atracurium for the facilitation of tracheal intubation. On the other hand, 2 ED(95) doses of cisatracurium (100 micro g/kg) do not yield satisfactory intubating conditions such as those seen with equipotent doses of atracurium and therefore the recommended intubating dose of cisatracurium is 3 ED(95). To understand this discrepancy better, we evaluated the potency and onset of atracurium and cisatracurium directly at the larynx adductors in humans. METHODS: The study was conducted in 54 patients (ASA class I or II) undergoing peripheral surgery requiring general anesthesia. Cisatracurium 25-150 micro g/kg or atracurium 120-500 micro g/kg intravenous (i.v.) boluses doses were administered during anesthesia with propofol, nitrous oxide, oxygen and fentanyl. Neuromuscular block was measured by electromyography (single twitch stimulation every 10 s) at the larynx and the adductor pollicis. The dose-response effect measured at both muscles included maximum neuromuscular blockade achieved (Emax), the time to maximum depression of twitch height (onset) and time to spontaneous recovery of the twitch height to 25%, 75% and 90% (T25, T75, T90) of control value. RESULT: The onset at the larynx was of 196 +/- 28 s after the 100 micro g/kg cisatracurium dose compared with 140 +/- 14 s after the 500 micro g/kg atracurium dose (P < 0.05). Emax at the larynx was 92 +/- 1% and 98 +/- 1% after 100 micro g/kg cisatracurium and 500 micro g/kg atracurium, respectively (P < 0.05). The time to onset of maximum suppression Emax = 100 +/- 0% after a 150 micro g/kg cisatracurium dose was 148 +/- 29 s. At the larynx, the ED(50) was 25 micro g/kg for cisatracurium and 180 micro g/kg for atracurium and the ED(95) was 87 micro g/kg for cisatracurium compared with 400 micro g/kg for atracurium. CONCLUSION: The slow onset time at the laryngeal muscles after cisatracurium can be explained by the higher potency as compared with atracurium.

Renal effects of low-dose dopamine during vasopressor therapy for posttraumatic intracranial hypertension.

OBJECTIVE: To investigate the effects of low-dose dopamine (Dop) on renal hemodynamics and function in patients with brain trauma receiving norepinephrine (NE). DESIGN: Prospective clinical study. SETTING: Surgical intensive care unit of a university hospital. PATIENTS: 20 stable, non-septic, mechanically ventilated, sedated patients with brain trauma and normal renal function treated with intravenous NE (0.11-0.65 microg/kg per min) to maintain an adequate cerebral perfusion pressure (> 60 mmHg). INTERVENTIONS: Two successive 1-h study periods with NE alone then NE + Dop (2 microg/kg per min). During each period, creatinine (Cl(CREAT)), sodium (Cl(Na)), potassium (Cl(K)), osmolar (Cl(OSM)) and free water (Cl(H2O)), clearances were measured in all the patients. Effective renal blood flow (ERBF, para-aminohippurate clearance) and glomerular filtration rate (GFR, inulin clearance) were measured in 7 of the 20 patients. RESULTS: Dop during NE infusion induced increases in urine flow and natriuresis which were not correlated with possible changes in arterial pressure. Cl(CREAT), GFR and their difference remained unchanged, whereas ERBF tended to increase. Fractional sodium excretion [100 x (Cl(Na)/Cl(CREAT)] and C1(K) increased during Dop infusion. CONCLUSION: The mechanism of Dop-induced natriuresis during NE infusion in brain trauma patients seems mainly related to a direct tubular effect of the drug.

Respiratory effects of desflurane anesthesia on spontaneous ventilation in infants and children.

UNLABELLED: Volatile anesthetics depress spontaneous ventilation in a dose-dependent manner with variations in effects among different drugs. The goal of this prospective study was to assess respiratory changes during spontaneous ventilation using desflurane/O2/N2O anesthesia in two groups of children. Both groups were undergoing minor surgery and consisted of children < 2 yr old (Group I) and children > 2 yr old (Group II). They were examined at 0.5, 1, and 1.5 minimum alveolar anesthetic concentration desflurane anesthesia. Induction of anesthesia was performed via a face mask and a mixture of O2/N2O (40:60) with halothane. At lease 20 min after stopping halothane, the respiratory variables were recorded on desflurane anesthesia. Tidal volume and minute ventilation decreased significantly (P <0.05) as desflurane increased from 0.5 to 1.5 MAC in both groups. At 1.5 MAC, the respiratory rate was greater in Group II than in Group I (P <0.05). In both groups, the increase in end-tidal CO2 was significant at 1.5 MAC versus 1 and 0.5 MAC (P <0.05). Apnea, i.e., no respiratory movement for 20 s, occurred at 1.5 MAC in one patient in each group. The respiratory duty cycle did not change in any of the groups. Both indices of paradoxical respiration--amplitude index and delay index--did not change. IMPLICATIONS: Desflurane induces respiratory depression at concentrations higher than 1 minimum alveolar anesthetic concentration mainly due to a decrease in tidal volume. Therefore, desflurane at high concentrations should be used cautiously in infants and children with spontaneous ventilation.

Epidural anaesthesia for caesarean delivery in triple and quadruple pregnancies.

BACKGROUND: Mechanical and/or hormonal factors may increase the spread of epidural anaesthesia in pregnancy, and hormonal changes are more pronounced in high-order pregnancies. However, no previous study has evaluated the dose requirements and haemodynamic effects of epidural anaesthesia for caesarean delivery in this latter situation. METHODS: The anaesthetic requirements to obtain a T4 upper sensory level were retrospectively compared in triple (n = 19) or quadruple (n = 2) pregnancies to 31 singleton pregnancies who received epidural anaesthesia for elective caesarean delivery using 2% lidocaine with 1/200,000 adrenaline. RESULTS: In high-order pregnancies, the gestational age at delivery was lower than in singleton pregnancies (34.9 +/- 1.9 weeks vs 38.2 +/- 1.1 weeks; P = 0.0001) whereas maternal body weight (76.5 +/- 8.7 kg vs 73.4 +/- 14.8 kg; NS) and lidocaine requirements (428 +/- 95 mg vs 426 +/- 98 mg; NS) were similar. Moreover, although the overall incidence of hypotension was not different (multiple pregnancy; 65% vs 58% in singletons), ephedrine (5.4 +/- 5.3 mg vs 10.7 +/- 13.8 mg; P < 0.05) and additional fluid requirements during onset of the block (4.3 +/- 1.7 mL/kg vs 5.3 +/- 2.6 mL/kg; P = 0.03) were less than in singletons. CONCLUSION: We found surprisingly similar anaesthetic requirements for epidural anaesthesia in high-order and singleton pregnancies. Mechanical factors may have played an important role. Moreover, the need for ephedrine and fluids was less in high-order pregnancies. This could be related to more pronounced physiological changes or to different physician attitudes.

Prophylactic treatment of BALB/c mice with cyclosporine A and its analog B-5-49 enhances resistance to Leishmania major.

The effect of cyclosporine A (Cs A) and its analog B-5-49 on Leishmania major in vitro and in vivo in the highly susceptible BALB/c mouse strain has been investigated. In vitro, both of these drugs showed significant toxicity toward L. major, but only at relatively high levels (greater than 25 micrograms/ml). However, at 5 and 10 micrograms/ml, levels which correspond more closely to physiologically achievable concentrations, no growth-inhibitory effect in vitro was observed. On administration of the drugs to animals with established lesions, no beneficial effect was observed and, in fact, some exacerbation of lesion development and disease progression was noted. Surprisingly, a majority of the mice treated prophylactically with Cs A for a period of 7 consecutive days beginning 1 day before infection with L. major did not develop ulcerated cutaneous lesions, although some footpad swelling was observed 10 days to 2 wk after infection. These resistant animals displayed a sustained DTH after infection, and were resistant to further challenge with virulent L. major. Prophylactic treatment with the B-5-49 analog of Cs A was also effective in enhancing resistance to L. major infection in BALB/c mice, although to a somewhat lesser degree. Because the cyclosporines tested do not appear to be directly toxic nor inhibitory in vivo for established L. major infections, it appears that these drugs may be effective in modulating the induction stage of the immune response toward the parasites in the BALB/c mouse in such a way as to allow a protective immunity to develop.

"Nonspecific" immunoenhancing T cells in tumor-bearing mice include anti-idiotypic subsets.

Splenocytes from DBA/2 mice inoculated 3 wk earlier with syngeneic P815 mastocytoma tumor cells produce increased numbers of antibody plaque-forming cells (PFC) when stimulated with either sheep red blood cells (SRBC) or phosphorylcholine (PC) on Streptococcus pneumoniae R36a in vitro. The nature of this nonspecific hyperreactivity was investigated in mixed cultures of purified splenic T and B cells. The addition of T cells from P815 tumor-bearing mice (TP815) into the cultures of normal B cells produced a significant enhancement of the PFC response to both SRBC and PC, when compared with the effect of normal T cells added to control cultures. The idiotypic profile of the enhanced anti-PC response was studied by a PFC-inhibition assay with monoclonal antibodies against two distinct idiotopic determinants (Id) of the T15 family. Normal B cells produced greater than 90% of T15 Id-positive (Id+) PFC. Addition of normal T cells diminished the proportion of T15 Id+ PFC to approximately 60%, whereas the rest of PFC were Id-. Addition of the immunoenhancing TP815 cells into the normal B cells cultures elevated the number of both T15 Id+ and Id- PFC responses, proportionally. However, when TP815 cells were first incubated on T15 protein-coated dishes and the non-adherent fraction was added to B cell cultures, the anti-PC PFC response remained enhanced but consisted of predominently T15 Id- PFC. These observations suggest that the early stage of P815 tumor growth activates various populations of specific helper/amplifier T cells including subsets with anti-idiotypic activity and that the generalized increase of antibody response to various antigens in tumor-bearing mice may be regarded as a polyclonal activation of specific T cells.

Augmentation of B-cell responsiveness by a tumor-activated T-cell factor.

The growth of the P815 mastocytoma in syngeneic DBA/2 mice led to an activation of Ly1+2- T cells. These T cells produced a soluble factor or factors in culture which, when added to normal spleen cells or B cells in the presence of syngeneic Ly1 cells, caused a genetically unrestricted augmentation of the plaque-forming response toward sheep red blood cells (SRBC). The culture supernatant of the activated T cells did not support the proliferation of an interleukin-2 (IL-2)-dependent cell, nor exhibit properties of late-acting TRF. Active supernatants appeared to affect directly B cells during the first 48 hr of culture with SRBC in such a way as to make them more responsive to antigen-specific Ly1-cell help.

Activation of T cells in tumor-bearing mice.

Subcutaneous transplantation of the syngeneic P815 mastocytoma in DBA/2J mice induced an activation of splenic T cells which resulted in a hyperresponsiveness of the tumor-bearing animal to the unrelated antigens pneumococcal polysaccharide (Pn) and sheep red blood cells (SRBC). These tumor-activated T cells appeared to increase the plaque-forming cell (PFC) potential of suboptimal numbers of spleen cells, caused normal spleen cells to express increased numbers of PFC, and produced lymphokine(s) which also increased PFC responses of normal splenocytes. The tumor-activated T cells responsible for stimulating normal splenocytes in an in vitro antibody response were shown to be Ly+2- cells. The activity of the tumor-activated T-cell supernatants was not genetically restricted and required additional Ly1 T cells in order to induce rigorously clean B cells to produce antibody. The T cells capable of stimulating non-specific antibody responses were also capable of slowing tumor growth when injected with tumor cells in normal recipient mice. These results suggest that T cells activated by tumor antigens release immunostimulatory lymphokines and, at the same time, are capable of leading to inhibition of tumor growth.

Immunological findings in kala-azar, Iran.

Quantitation of immunoglobulins in patients with systemic leishmaniasis show a rise in IgM and IgG. Complement C3 levels in severely ill patients were very low, whereas generally within normal range in patients with uncomplicated recoveries. The cell mediated immune response of those kala-azar patients examined appeared to be depressed as measured by PHA skin tests. This depression was rapidly reversed following chemotherapy with Glucantim.

Evidence for the presence of circulating immune complexes in serum and C3b and C3d on red cells of kala-azar patients.

The presence of immune complexes in serum, and the existence of immunoglobulin and complement on the surface of red blood cells of kala-azar patients was studied. IgG, C3b and C3d were detected on the surface of red cells of some of the patients by a direct anti-globulin test. PEG precipitation and platelet aggregation techniques demonstrated the existence of immune complexes in the sera of all nine patients examined. Both Leishmania antigen and anti-Leishmania antibody were detected in the PEG-precipitated immune complexes.

Immunity to Toxoplasma and Listeria induced by homologous and heterologous organisms.

Cross protection of animals against various organisms have been shown for many years. This type of resistance to phylogenetically unrelated organisms might be attributed to certain immunological phenomena such as non-specific macrophage activation. In this report the cross-protective effect of some organisms against Toxoplasma gondii RH strain and Listeria monocytogenes is described. Groups of mice were immunized with BCG, Toxoplasma lysate antigen, viable cysts of T. gondii Tehran strain and heat killed L. monocytogenes. Seventeen days after initial immunization, the animals were tested for delayed hypersensitivity by a skin test. The hypersensitive animals in each group were challenged with either lethal doses of T. gondii RH strain or 5 x 10(5) viable L. monocytogenes. Among the animals challenged with T. gondii, it was observed that complete protection was achieved only in those mice immunized with viable cysts of T. gondii Tehran strain. Although all other immunized mice eventually died after infection, they did show some degree of resistance as their deaths were delayed considerably as compared to non-immunized animals. In animals which were infected with 5 x 10(5) L. monocytogenes, complete resistance was observed only in BCG immunized mice. The other antigens including L. monocytogenes induced partial resistance as evidenced by their survival times and the multiplication of the bacteria in various internal organs.

Hepatitis-associated antigen in patients with liver diseases and in rural population of Iran. Increased incidence in men.

Using the counter-immunoelectrophoresis technique, the presence of HBsAg was determined in sear of 227 cirrhotics, 132 patients with acute hepatitis, and 254 apparently normal villagers and 220 hospital personnel in Southern Iran. Findings show a very high frequency of antigenemia in cirrhotics as compared to the apparently normal population. Of interest was the male predominance of antigenemia both in cirrhotics (50% vs. 27%) and normals (2.1+ vs. 0.4%) but not in patients with acute hepatitis (42.6% vs. 32.8%). This data suggests the importance of HB antigenemia in the pathogenesis of postnecrotic cirrhosis in Iran, and the importance of male predisposition for the development of the carrier state in either healthy or cirrhotic individuals.

Enteric pathogens in infants and children in Shiraz, Iran: A study of their incidences and infectious drug resistance.

Gastroenteritis is a serious problem among young children in Shiraz Iran and often requires antibiotic therapy as it is commonly superimposed on other debilitating clinical conditions. Stool specimens from over four hundred cases of gastroenteritis among children up to six years of age were examined for the presence of bacterial pathogens and the pattern of drug sensitivity for each pathogenic genus was determined. The presence of infectious drug resistance factors among these isolates was also established.

Immunofluorescence and counter immunoelectrophoresis in the diagnosis of kala-azar.

Techniques of indirect immunofluorescence (IF) and counter current immunoelectrophoresis (CIEP) were employed and compared for the diagnosis of kala-azar among children in Fars Province of Iran. It is suggested that the diagnostic titre for kala-azar by immuno fluorescence is over 1 in 64. In fact a majority of the cases had a titre of more than 1 in 256. CIEP using soluble antigens prepared form the promastigote form of Leishmania donovani, was also applied to sera from patients with systemic leishmaniasis and other diseases. The CIEP test correlated well with the indirect immunofluorescent test. It is therefore suggested that CIEP, which is a rapid and less sophisticated test, can be applied for the diagnosis of kala-azar cases and epidemiological surveys.

Application of immunofluorescence to detection of antibody in Leishmania infections.

Indirect immunofluorescence was used for determination of antibody in human cases of cutaneous leishmaniasis, mice infected with Leishmania tropica and guinea pigs infected with L. enriettii. Results indicated that antibody in mice is detectable 23 days after infection with L. tropica. The antibody titre correlates well with the extent of infection. In guinea pigs infected with L. enriettii, antibody appears much faster and is detectable 12 days after infection. Here also the antibody titre increased during the course of infection until about 76 days at which time the leishmanial lesion was at its height. Guinea pigs having metastatic lesions consistently showed a high titre of antibody. In several cases of human cutaneous leishmaniasis antibody was detectable at the titre of not more than 1/128. In five cases of suspected systemic leishmaniasis antibody titre was much greater than in cutaneous leishmanial infection. Upon characterization of anti-leishmanial serum of guinea pig with DEAE-cellulose chromatography and analysis of the fractions by immunoelectrophoresis, it was found that the antibody activity detected by the indirect immunofluorescence resided in the gamma2 portion of guinea pig globulin.

Regulation of two aspartokinases in Bacillus subtilis.

When grown on minimal glucose medium, transformable Bacillus subtilis strains contained two distinct aspartokinases (ATP:l-aspartate 4-phosphotransferase, EC 2.7.2.4). One of these enzymes was inhibited by l-lysine (Lys), whereas the other was insensitive to inhibition but was activated by l-leucine. None of the other amino acids tested had any effect, and the addition of l-threonine did not enhance the inhibition by Lys, in contrast to the concerted inhibition observed for other bacilli. At the end of exponential growth, the Lys-sensitive aspartokinase activity decreased, whereas the Lys-insensitive activity remained relatively constant throughout the stationary phase. The two activities were separated by (NH(4))(2)SO(4) fractionation and Sephadex G-200 chromatography. Growth in the presence of Lys reduced the specific activity of aspartokinase by about 50% and eliminated the inhibition by Lys. In extracts of these cells, only Lys-insensitive activity was found upon (NH(4))(2)SO(4) fractionation and Sephadex G-200 chromatography. Lys apparently repressed the synthesis of the Lys-sensitive enzyme.