Magnesium sulphate in the treatment of ventricular fibrillation in amitriptyline poisoning.
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Adult↗
Biomedical subjects
K Knudsen
Publications and source records attributed to K Knudsen.
Epinephrine and sodium bicarbonate independently and additively increase survival in experimental amitriptyline poisoning.
OBJECTIVES: Cardiac depression is the main adverse effect of severe tricyclic antidepressant poisoning. The aim of this study was to investigate whether treatment with epinephrine or norepinephrine increases survival as compared with standard treatment with sodium bicarbonate in experimental amitriptyline poisoning. DESIGN: Nonrandomized, controlled intervention trial. SETTING: University laboratory. SUBJECTS: Male, anesthetized, paralyzed, and mechanically ventilated Sprague-Dawley rats (n = 91). INTERVENTIONS: Rats subjected to a 60-min infusion of amitriptyline (2 mg/kg/min) were treated with a continuous infusion of either epinephrine, norepinephrine, sodium bicarbonate, epinephrine plus sodium bicarbonate, norepinephrine plus sodium bicarbonate, or placebo. MEASUREMENTS AND MAIN RESULTS: Inotropic drug treatment was associated with an increased survival rate as compared with treatment with sodium bicarbonate and treatment with placebo. Epinephrine treatment was superior to norepinephrine. Additional treatment with sodium bicarbonate increased survival rate for each inotropic drug. Sodium bicarbonate and inotropic drug treatment independently increased the survival rate (p < .001 for both effects). No interaction between these two treatment effects was observed. CONCLUSIONS: Both epinephrine and norepinephrine increased the survival rate in tricyclic antidepressant poisoning in rats. Sodium bicarbonate increased the survival rate independent of inotropic drug treatment. Furthermore, epinephrine was superior to norepinephrine when used both with and without sodium bicarbonate, and the most effective treatment was epinephrine plus sodium bicarbonate.
Amitriptyline↗
Effects of sigmaS and the transcriptional activator AppY on induction of the Escherichia coli hya and cbdAB-appA operons in response to carbon and phosphate starvation.
The transcriptional regulation of two energy metabolism operons, hya and cbdAB-appA, has been investigated during carbon and phosphate starvation. The hya operon encodes hydrogenase 1, and the cbdAB-appA operon encodes cytochrome bd-II oxidase and acid phosphatase, pH 2.5. Both operons are targets for the transcriptional activator AppY. In exponential growth, expression of the hya and cbd operons was reduced in an rpoS mutant lacking the RNA polymerase sigmaS factor, and the induction of the two operons by entry into stationary phase in rich medium was strongly dependent on sigmaS. Both operons were induced by carbon starvation, but only induction of the hya operon was dependent on sigmaS, whereas that of the cbd promoter was dependent on AppY. The appY gene also showed sigmaS-dependent induction by carbon starvation. The cbd and hya operons were also found to exhibit a sigmaS-dependent transient twofold induction by osmotic upshift. Like the cbd operon, the hya operon was highly induced by phosphate starvation. For both operons the induction was strongly dependent on AppY. The induction ratio of the two operons was the same in rpoS+ and rpoS mutant strains, indicating that the phosphate starvation-induced increase in sigmaS concentration is not involved in the phosphate regulation of these operons.
Anaerobiosis↗
Serial CD4 and CD8 T-lymphocyte counts and associated mortality in an HIV-2-infected population in Guinea-Bissau.
In an urban community in Guinea-Bissau, we followed a cohort of human immunodeficiency virus type 2 (HIV-2) seropositive individuals (N = 47) and seronegative controls (N = 82). T-lymphocyte subset determinations were done in 1988, 1990, and 1992. Serial determinations of CD4 percentages, CD8 percentages, and CD4/CD8 ratios for the same individual were stable for 31 seropositive and 51 seronegative individuals with repeated measurements. We found no significant differences in the changes during a 2- or 4-year period in CD4 percentages, CD8 percentages, absolute CD8 T-lymphocyte counts, CD4/CD8 ratio, white blood cell counts, lymphocyte percentages, and absolute lymphocyte counts for HIV-2-seropositive compared with HIV-2-seronegative individuals. Only absolute CD4 T-lymphocyte counts changed more for the HIV-2-seropositive than for HIV-2-seronegative individuals (p = 0.037). HIV-2-infected individuals who lived with an HIV-2-infected spouse had a lower CD4/CD8 ratio and had higher mortality than HIV-2 infected individuals who lived with an uninfected spouse. However, there were no significant differences in immunological and hematological values for the 8 HIV-2 seropositive individuals who died and the 39 who survived in the 8-year follow-up period. In conclusion, progression of immunosuppression in HIV-2 infection seems to be slower than in HIV-1 infection and may not be inevitable in all individuals.
Adult↗
Five year follow-up of morbidity and mortality among recipients of high-titre measles vaccines in Senegal.
At 3-5 years of age, female recipients of Edmonston-Zagreb high-titre (EZ-HT) and Schwarz high-titre (SW-HT) measles vaccine had lower survival rates than female recipients of Schwarz standard measles vaccine (SW-STD) in Guinea-Bissau, Senegal and Haiti. In Senegal, the children who received high-titre vaccines have now been followed to the age of 5-7 years to determine whether the difference in mortality persisted, and whether differences in vaccine efficacy were apparent. At this age there was no difference in mortality between female recipients of high-titre and standard titre measles vaccines. There was no indication that high-titre EZ-HT vaccine at 5 months (EZ-HT,5m) provided suboptimal protection, as vaccine efficacy after exposure was 97% and 95%, respectively, for EZ-HT,5m and SW-STD,10m vaccines, whereas SW-HT,5m vaccine had an efficacy of 81%. The difference in mortality between recipients of high-titre vaccines and SW-STD observed in several studies during the first few years after vaccination may be explained by non-specific beneficial effects of the standard measles vaccine rather than a harmful effect of the high-titre vaccines.
Female↗
Nutritional status and delayed mortality following early exposure to measles.
Community studies in Guinea-Bissau have found that exposure to measles prior to 6 months of age is associated with delayed mortality later in childhood. In an attempt to understand the underlying mechanism, we examined the role of pre-exposure nutritional status and the impact of exposure to measles on growth and subsequent mortality in these outbreaks. Though exposed children were lighter than controls, there was no association between pre-exposure weight-for-age and subsequent mortality adjusting for age. Although exposure was strongly associated with excess mortality, it did not have a negative impact on growth. Adjustment for state of nutrition did not alter the mortality ratio (MR) between 6 and 59 months of age for exposed children and controls; exposed children examined anthropometrically between 6-17 months had a MR of 3.70 compared with controls. This trend was the same for anthropometric measurements obtained at 18-59 months of age. Among the controls, there was a significant association between weight-for-age and subsequent mortality to the age of 5 years. However, for exposed children there was no association; the relation between weight-for-age and subsequent mortality was significantly different for exposed children compared with controls (tests for interaction between exposure and anthropometric measurements at 6-17 months: P = 0.05). Growth faltering as a consequence of early exposure to measles does not explain the marked excess mortality among these children. Further studies of the process underlying delayed mortality after early exposure to measles are warranted.
Anthropometry↗
No persistent T lymphocyte immunosuppression or increased mortality after measles infection: a community study from Guinea-Bissau.
BACKGROUND: Because measles immunization is reducing overall childhood mortality in addition to mortality from acute measles infection, it has been suggested that postmeasles cases have excess mortality, possibly related to persistent immunosuppression after measles infection. After an epidemic in 1988 in Guinea-Bissau, we therefore examined T lymphocyte subsets and long term survival among measles cases and controls. METHODS: We examined 69 children < 3 years of age with a median delay of 2 months after measles infection and 71 controls who did not contract measles. The immunoalkaline method was used to determine T lymphocyte subsets. The children were followed for 5 years. RESULTS: Compared with controls, there were no significant differences in white blood cell count, absolute lymphocyte count, CD4 percentage, CD8 percentage, total CD4 count and total CD8 count, although measles cases examined > 2 months after infection had slightly higher CD4 counts than controls (P = 0.06). Adjusted for age, sex and immunization status, postmeasles cases had a mortality rate ratio of 0.50 (95% confidence interval, 0.22 to 1.16) (P = 0.11) compared with controls. CONCLUSIONS: There is no indication of persistent suppression of T cell subsets after measles infection, and postmeasles cases did not have higher mortality than uninfected community controls.
Child, Preschool↗
Non-specific beneficial effect of measles immunisation: analysis of mortality studies from developing countries.
OBJECTIVE: To examine whether the reduction in mortality after standard titre measles immunisation in developing countries can be explained simply by the prevention of acute measles and its long term consequences. DESIGN: An analysis of all studies comparing mortality of unimmunised children and children immunised with standard titre measles vaccine in developing countries. STUDIES: 10 cohort and two case-control studies from Bangladesh, Benin, Burundi, Guinea-Bissau, Haiti, Senegal, and Zaire. MAIN OUTCOME MEASURES: Protective efficacy of standard titre measles immunisation against all cause mortality. Extent to which difference in mortality between immunised and unimmunised children could be explained by prevention of measles disease. RESULTS: Protective efficacy against death after measles immunisation ranged from 30% to 86%. Efficacy was highest in the studies with short follow up and when children were immunised in infancy (range 44-100%). Vaccine efficacy against death was much greater than the proportion of deaths attributed to acute measles disease. In four studies from Guinea-Bissau, Senegal, and Burundi vaccine efficacy against death remained almost unchanged when cases of measles were excluded from the analysis. Diphtheria-tetanus-pertussis and polio vaccinations were not associated with reduction in mortality. CONCLUSION: These observations suggest that standard titre measles vaccine may confer a beneficial effect which is unrelated to the specific protection against measles disease.
Bangladesh↗
Firefly luciferase assay of adenosine triphosphate as a tool of quantitation of the viability of BCG vaccines.
The purpose of the present study was to compare conventional colony forming unit (CFU) enumeration with a bioluminescent measurement in order to quantitate living bacteria in BCG vaccine. Forty batches of BCG vaccine quantitated with respect to weight (10 each of concentration 120 mg/vial, 30 mg/vial, 1.5 mg/vial and 0.75 mg/vial, respectively) were tested. Adenosine triphosphate (ATP) was extracted using the boiling Tris-EDTA extraction method preceded by treatment with the ATP-hydrolysing enzyme apyrase, and the liberated ATP was assayed using a LKB 1251 luminometer. The sensitivity of the assay was 10(-11) M ATP which corresponded to 5 x 10(5) CFU/ml. A proportional relation between CFU and ATP content per vial was found up to 30 mg/vial, but for 120 mg/vial the CFU method seemed unreliable in contrast to the bioluminescence method. The measurements error for the logarithm (base 10) of ATP was 0.051 and this method was therefore more exact than the CFU method (0.097). Because the bioluminescence method is sensitive, reliable, time-saving and less expensive it seems preferable to CFU enumeration in the quality control of BCG vaccines.
Adenosine Triphosphate↗
Antiarrhythmic effects of magnesium sulphate. Report of three cases.
A wide variety of antiarrhythmic agents is used in treatment of both supraventricular and ventricular arrhythmias. Magnesium sulphate has previously been used mainly in the treatment of torsade de pointe arrhythmias but several reports show that this agent may be used in the treatment of arrhythmias of different aetiology. We describe 3 patients who exhibited arrhythmias affecting haemodynamic performance. Case #1 had a subarachnoid haemorrhage and developed a supraventricular tachycardia. In case #2, ventricular tachycardia appeared during the postoperative course after abdominal surgery. Case #3 experienced critical heart failure due to dilated cardiomyopathy and had an irregular heart rhythm with multiple ectopic beats. In all three cases the administration of intravenous magnesium sulphate was successful in treating the arrhythmias. Magnesium sulphate is an antiarrhythmic agent that is effective mainly in treatment of ventricular arrhythmias. The drug can also be employed as second-line treatment of supraventricular arrhythmias.
Anti-Arrhythmia Agents↗
High-titre measles vaccines for boys.
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Child↗
Long-term survival in trial of medium-titre Edmonston-Zagreb measles vaccine in Guinea-Bissau: five-year follow-up.
A trial of protective efficacy which compared medium-titre Edmonston-Zagreb (EZ) measles vaccine (10(4.6) p.f.u.) from the age of 4 months with the standard Schwarz (SW) measles vaccine given from the age of 9 months was started in an urban community in Guinea-Bissau in 1985. Because trials of high-titre measles vaccine have found increased mortality among female recipients, we examined whether EZ medium-titre vaccine was associated with any long-term impact on mortality, suppression of T-cells, or growth. The mortality rate ratio over 5 years of follow-up was 1.12 for EZ children compared with children in the standard group (P = 0.63). Seventy-five percent of the children still residing in the area at 5 years of age took part in an immunological and anthropometric examination. There was no difference in T-cell subsets between the two groups. There was no difference in mid-upper-arm circumference, but EZ children were significantly shorter than the children in the standard group. In conclusion, medium-titre EZ was not associated with reduced survival or persistent immunosuppression.
Age Factors↗
Effects of magnesium sulfate and lidocaine in the treatment of ventricular arrhythmias in experimental amitriptyline poisoning in the rat.
OBJECTIVES: Amitriptyline poisoning is associated with ventricular arrhythmias. Standard treatment is sodium bicarbonate but further intervention may be necessary. The present study compared the actions of lidocaine and magnesium sulfate on ventricular tachycardia induced by amitriptyline. DESIGN: Nonrandomized, controlled, intervention trial. SETTING: University laboratory. SUBJECTS: Thirty male Wistar rats anesthetized with pentobarbital and mechanically ventilated. INTERVENTIONS: After pretreatment with norepinephrine, the animals were subjected to a continuous infusion of amitriptyline. After the appearance of ventricular tachycardia, they were treated with magnesium sulfate (45 mg/kg + 15 mg/kg/min) or lidocaine (1 mg/kg + 0.5 mg/kg/min) or glucose infusion as a control. MEASUREMENTS AND MAIN RESULTS: In the group treated with magnesium sulfate, electrocardiogram tracings demonstrated that nine of ten animals converted from ventricular tachycardia to sinus rhythm compared with one of ten in both the lidocaine- and glucose-treated groups (p < .001). The animals treated with magnesium sulfate also had a significantly longer total time in sinus rhythm (10.0 +/- 1.6 mins) than those rats treated with lidocaine (1.7 +/- 1.5 mins) or glucose (1.5 +/- 1.5 mins). Magnesium sulfate significantly decreased blood pressure and heart rate, but no severe hemodynamic side effects were observed. CONCLUSIONS: Magnesium sulfate is effective in converting ventricular tachycardia in hyperadrenergic amitriptyline poisoning. In contrast, lidocaine had no effect on arrhythmias.
Amitriptyline↗
Long term impact of high titer Edmonston-Zagreb measles vaccine on T lymphocyte subsets.
Several trials of high titer measles vaccine (> 10(4.7) plaque-forming unit) have found female recipients of Edmonston-Zagreb (EZ) vaccine to have lower survival than female recipients of standard measles vaccine. Two trials with medium and high titer EZ vaccine from the age of 4 months were conducted in Guinea-Bissau. To test for possible long term impact on the immune system, an investigation of T cell subsets was conducted among all children still residing in the community at 3 to 5 years of age. No differences were found between recipients of medium titer vaccine and controls. In the second trial, however, recipients of high titer had lower CD4:CD8 ratios than controls and had significantly higher CD8 percentages and lower CD4:CD8 ratios than recipients of medium titer EZ. When analyzed by sex, differences were found only among the girls. However, these differences were small and seemed unlikely to explain the reduced survival which has been associated with high titer EZ measles vaccination. In the 2 years after the investigation of T cell subsets, there was no increased mortality for recipients of EZ vaccine. Hence it is unlikely that high titer vaccine has an persistent adverse effect on survival after 3 years of age.
CD4-CD8 Ratio↗
8-methoxypsoralen increases daytime plasma melatonin levels in humans through inhibition of metabolism.
It is well established that in healthy humans oral intake of 5- or 8-methoxypsoralen (5- and 8-MOP) is followed by a significant increase in plasma melatonin concentrations. The effect of psoralen on rat melatonin has been studied in vitro and in vivo and a stimulation of release or secretion from the pineal gland has been suggested. In this study we examined the time-related changes in plasma concentrations of 8-MOP, melatonin and 6-sulfatoxymelatonin in 15 patients admitted for routine psoralen plus UVA therapy. On the first day of treatment blood samples were collected before, and 30, 60, 66 and 90 min after intake of 8-MOP (0.6 mg/kg). Although the rate of 8-MOP absorption varied greatly, a significant increase (P = 0.0002) in melatonin levels was found 60 min after 8-MOP intake. During UVA exposure a strongly correlated decrease in mean melatonin and mean 8-MOP concentrations was found, indicating an effect of UVA radiation, either direct or 8-MOP mediated, on circulating melatonin levels. Plasma 6-sulfatoxymelatonin concentrations decreased significantly between all time points, suggesting inhibition of melatonin metabolism.
Adult↗
Sex-specific differences in mortality after high-titre measles immunization in rural Senegal.
Administration of high-titre measles vaccine (Edmonston-Zagreb (EZ) at > 10(5) plaque-forming units (PFU) per dose) before the age of 9 months has been recommended in areas with high measles mortality before the routine age of immunization after 9 months. The study compares the long-term survival after high-titre measles immunization at 5 months of age with that following routine immunization with standard-titre vaccine at 10 months of age. At 5 months of age the high-titre group received Edmonston-Zagreb (EZ-HT, 5 months) or Schwarz (SW-HT, 5 months) at titres > 10(5) PFU per dose, while the standard-titre group received placebo at 5 months of age and < 10(4) PFU per dose of Schwarz vaccine at 10 months (SW-std, 10 months). All the children were followed up to at least 36 months of age. The mortality ratio (MR) for infants in the EZ-HT, 5 months and SW-HT, 5 months groups was 1.32 (P = 0.089) and 1.45 (P = 0.092), respectively, which did not differ significantly from that of recipients of the SW-std, 10 months. The higher MR among recipients of the high-titre vaccines was due to the significantly lower survival among females compared with the females who received SW-std vaccine (EZ-HT, 5 months MR = 1.76, P = 0.013; SW-HT, 5 months MR = 2.14, P = 0.017). For children aged 5-10 months the high-titre measles vaccine did not increase mortality relative to unvaccinated children who had received placebo.
Bias↗
Effects of epinephrine, norepinephrine, magnesium sulfate, and milrinone on survival and the occurrence of arrhythmias in amitriptyline poisoning in the rat.
OBJECTIVES: Cardiac depression is the main adverse effect of severe tricyclic antidepressant poisoning. The aim of this study was to compare the effects of several inotropic drugs on survival and the occurrence of arrhythmias in the treatment of amitriptyline poisoning. DESIGN: Nonrandomized, controlled intervention trial. SETTING: University laboratory. SUBJECTS: Eighty-six male Wistar rats anesthetized with pentobarbital and mechanically ventilated. INTERVENTIONS: Rats subjected to a 60-min continuous infusion of amitriptyline (1.25 mg/kg/min) were treated with a continuous infusion of either epinephrine, norepinephrine, milrinone, magnesium, epinephrine + magnesium, or norepinephrine + magnesium. MEASUREMENTS AND MAIN RESULTS: Without treatment, all animals exhibited arrhythmias on the electrocardiogram within 20 mins. All treatment drugs delayed the onset of arrhythmias, but significant differences were only observed after administration of epinephrine, epinephrine + magnesium sulfate, and norepinephrine + magnesium sulfate. All the inotropic drugs markedly increased survival. Sodium concentrations were unaffected by all treatments. In control animals, potassium concentrations increased during amitriptyline infusion. Norepinephrine treatment had no effect on potassium concentrations, whereas all other treatments resulted in decreased potassium concentrations. CONCLUSIONS: All inotropic drugs used in the study increased survival in tricyclic antidepressant poisoning in rats without increasing the risk of arrhythmias. Furthermore, epinephrine and norepinephrine + magnesium sulfate were effective in preventing arrhythmias, possibly due to improved hemodynamic performance or potassium homeostasis.
Amitriptyline↗
Divergent mortality for male and female recipients of low-titer and high-titer measles vaccines in rural Senegal.
The female/male mortality ratio among unimmunized children and children vaccinated with standard or high-titer measles vaccines was examined for all children born in the period 1985-1991 in a rural area of Senegal. The female/male mortality ratio from 9 months to 5 years of age for unvaccinated children was 0.94 (95% confidence interval (CI) 0.75-1.19), significantly different from the ratio of 0.64 (95% CI 0.48-0.85) for recipients of the Schwarz standard measles vaccine (p = 0.040). In the 4-year period, where high-titer measles vaccines were used in the study area, the female/male mortality ratio was 1.33 (95% CI 1.00-1.78) for recipients of high-titer Edmonston-Zagreb or Schwarz vaccines compared with 0.67 (95% CI 0.42-1.07) for recipients of the Schwarz standard vaccine (p = 0.013). Hence, the Schwarz standard and high-titer measles vaccines have divergent sex-specific effects on mortality throughout childhood. Further studies of the underlying mechanisms are needed.
Cause of Death↗