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Biomedical subjects

K Knudsen

Publications and source records attributed to K Knudsen.

At least 55 records · Page 3Linked to original sources

[Higher mortality due to measles in Senegal for children with siblings of the opposite sex].

The impact on case fatality of contracting measles infection from a sibling of the opposite sex was examined using data collected over a 20 year period in 31 isolated villages in Eastern Senegal. The interval between outbreaks of measles in a village was usually greater than ten years. During outbreaks, 766 children lived in families with two maternal siblings under ten years of age; 107 (14.0%) died of measles. The risk of dying of measles decreased with age, increased with the age difference between siblings and decreased with the size of the village. Adjusting for these factors, children in families with a boy and girl were found to have higher mortality than children in families with two boys or two girls (odds ratio (OR) = 1.81 (1.17-2.82)). The increase in risk was the same for boys and girls in male-female families. Cross-sex transmission of measles may be an important determinant of severity of infection.

Child↗

Long-term survival after Edmonston-Zagreb measles vaccination in Guinea-Bissau: increased female mortality rate.

In an urban area of Guinea-Bissau, 384 children were enrolled in a randomized trial comparing morbidity and mortality rates after receiving high-titer Edmonston-Zagreb (EZ) measles vaccine administered from 4 months of age, with a control group receiving inactivated poliomyelitis vaccine at 4 months of age and the standard Schwarz vaccine from 9 months of age. Children were followed to the age of at least 3 years. The mortality ratio of the EZ vaccinees compared with control subjects was 1.79 (range, 1.06 to 3.02; p = 0.027) if children were excluded at the time of migration; if deaths after migration were included, the mortality ratio was 1.53 (range, 0.94 to 2.49; p = 0.087). Girls in the EZ group had significantly higher mortality rates than girls in the control group (mortality ratio = 1.95; range, 1.07 to 3.56; p = 0.027); there was no difference for the boys (mortality ratio = 0.98; range, 0.41 to 2.30). Adjustment for background factors in a Cox regression model did not modify these estimates. Furthermore, female recipients of EZ vaccine had more days with diarrhea (relative risk = 1.35; range, 1.17 to 1.56; p = 0.00003) and were more likely than control subjects to visit a health center in the month after vaccination (relative risk = 1.86; range, 1.05 to 3.31; p = 0.027); those who consulted were more likely to die subsequently (mortality ratio = 2.31; range, 0.99 to 5.41; p = 0.054). These observations were unplanned and require confirmation in larger studies.

Cause of Death↗

Excess mortality after early exposure to measles.

The impact of exposure to measles before 6 months of age has been investigated by comparing survival to 5 years of age for exposed children and controls in an urban (Bandim) and a rural (Quinhamel) area of Guinea-Bissau. In Bandim, cumulative mortality from time of exposure to age 5 years was 34.4% among exposed children and 9.3% among controls. In a matched pair analysis, exposed children had a mortality ratio (MR) of 3.80 (95% confidence interval [CI]: 1.42-10.18) compared with controls. In an unpaired analysis using Cox' regression model to standardize for background variables (sex, measles infection, age at exposure, exposure from own household, measles vaccination), there was little change in the MR (3.84, CI: 1.55-9.48). Even after 2 years of age, the exposed children tended to have higher mortality (MR = 7.96, CI: 0.98-64.74). In the rural area, the MR between exposed children and controls was 11.39 (CI: 1.42-91.51). Limited serological data suggest that at least some of the exposed had subclinical measles. In the urban area, where two studies of early exposure have been carried out, excess mortality among exposed children corresponds to 40% and 52%, respectively, of the acute measles mortality. Since these deaths would not be associated with measles in a study of protection against death after vaccination, measles immunization may have a much greater effect on childhood mortality than has previously been assumed.

Age Factors↗

Effects of epinephrine and norepinephrine on hemodynamic parameters and arrhythmias during a continuous infusion of amitriptyline in rats.

Epinephrine and norepinephrine were evaluated in treatment of hemodynamic compromise in amitriptyline intoxication. One hundred and one male Wistar rats were monitored hemodynamically during amitriptyline intoxication and given one of three infusion rates (0.1, 0.5 or 5.0 mg/kg/min) of either epinephrine or norepinephrine. Sixteen rats served as controls and received only glucose after intoxication. Amitriptyline intoxication lowered mean arterial pressure, heart rate, left ventricular max dP/dt, and increased left ventricular end-diastolic pressure. All doses of norepinephrine and the two higher doses of epinephrine increased mean arterial blood pressure and left ventricular max dP/dt. Heart rate increased with both drugs, more with epinephrine, but not beyond pre-intoxicated levels at any dose. Left ventricular end-diastolic pressure was unaltered by both drugs. Malignant arrhythmias appeared in 7% of all animals, whereas a progressive decline of cardiac contractility caused cardiac arrest in 36% of all animals. This suggests that myocardial depression is the aspect most likely to cause death. At intermediate doses epinephrine resulted in significantly fewer arrhythmias and lower mortality compared to norepinephrine. We conclude that epinephrine and norepinephrine each appeared effective in reversing amitriptyline-induced hemodynamic alterations. Epinephrine had fewer arrhythmogenic properties than norepinephrine and may be preferable to norepinephrine.

Amitriptyline↗

Increased risk of death from measles in children with a sibling of opposite sex in Senegal.

OBJECTIVE: To examine whether contracting measles from a sibling of the opposite sex affects mortality. DESIGN: Prospective registration during 15-20 years of all births and deaths, including 243 measles related deaths. Measles infection was not registered; however, as in fatal cases measles was probably contracted from a maternal sibling the risk of dying during measles outbreaks was examined in families with two boys, two girls, or a boy and a girl. SETTING: 31 small villages in two rural areas of eastern Senegal. SUBJECTS: 766 children living in families with two children aged under 10 years during outbreaks of measles, 107 (14%) of whom died of measles. MAIN OUTCOME MEASURE: Deaths from measles, size of village, age and sex of maternal siblings. RESULTS: The interval between outbreaks in the same village was greater than 10 years. The risk of dying of measles was significantly related to age, increasing with the age difference between siblings and decreasing with the size of village. In a multiple logistic regression analysis adjusting for these background factors, children in families with a boy and a girl had a significantly higher mortality than children in families with two boys or two girls (odds ratio = 1.81, 95% confidence interval 1.17 to 2.82). The increase in risk was the same for boys and girls in families with two children one of whom was a boy and one a girl. CONCLUSION: Cross sexual transmission may be an important determinant of severity of measles infection.

Age Factors↗

Severe amitriptyline overdose: relationship between toxicokinetics and toxicodynamics.

The clinical features and toxicokinetics of amitriptyline were studied in nine patients with severe amitriptyline poisoning. Amitriptyline and amitriptyline metabolites were studied in plasma, red blood cells, and cerebral spinal fluid. Eight patients were intubated and six required assisted ventilation. Two patients had ventricular arrhythmias, three patients convulsions and two were hypotensive. All complications developed within four hours of admission. Early in the course of the intoxication the QRS duration correlated with plasma, unbound and red blood cell nortriptyline concentration. The QRS duration also correlated with unbound but not the plasma amitriptyline concentration. The level of consciousness correlated with the plasma and unbound amitriptyline both in alpha and beta phase and with red blood cell amitriptyline in alpha phase. There was no correlation between nortriptyline concentration and level of consciousness. No correlation between coma grade or QRS duration and cerebral spinal fluid concentration of amitriptyline was found. There was no correlation between any hydroxymetabolite in blood or cerebral spinal fluid and QRS duration or coma grade. The beta half-life for amitriptyline was shorter for two patients with high concentrations of hydroxymetabolites. Although intubated, neither patient required assisted ventilation or developed complications. Because of the wide range of concentrations of amitriptyline and amitriptyline metabolites observed between individuals, it is not possible to predict outcome based on a single tricyclic antidepressant concentration.

Amitriptyline↗

Amitriptyline and amitriptyline metabolites in blood and cerebrospinal fluid following human overdose.

The toxicokinetics of amitriptyline were studied in nine patients admitted to hospital in Matthew-Lawson Coma Scale grade III-IV after an estimated ingestion of 1-5 g amitriptyline. Gastric lavage was performed and 50 g activated charcoal were given orally. Venous blood samples were taken on admission and at 1, 2, 4, 8, and 24 h, and in some patients at 36 and 48 h after admission. Arterial blood samples were taken at 1, 4, 8, and 24 h after admission. Lumbar punctures were performed 1 h after admission in 8 patients and again 4 h later in 5 patients. A urine sample was screened for other drugs. The bound and unbound fraction of amitriptyline and its metabolites nortriptyline, E and Z forms of 10-OH-amitriptyline and nortriptyline were analyzed in plasma, whole blood, red blood cells, and cerebrospinal fluid using an HPLC technique. The T1/2 alpha and T1/2 beta for amitriptyline were 1.5 - 3.1 and 15 - 43 h respectively. The rate of elimination of amitriptyline was not dose-dependent. The arteriovenous differences in the total amitriptyline+nortriptyline concentration were maximal in patients admitted soon after intake of drugs. Amitriptyline concentrations in cerebrospinal fluid were quantitatively similar to the unbound amitriptyline concentration in blood. The highest cerebrospinal fluid amitriptyline concentration was 506 nmol/L. There were large individual differences in plasma, blood and cerebrospinal fluid concentrations between different individuals. Repeated quantitative analysis of amitriptyline and its metabolites is unlikely to contribute to the clinical management of most patients with amitriptyline overdose.

Adult↗

Interquarter comparison of markers of subclinical mastitis: somatic cell count, electrical conductivity, N-acetyl-beta-glucosaminidase and antitrypsin.

We have evaluated the usefulness in mastitis diagnostics of new diagnostic measures using the continuous nature of the variation in quarter milk samples of four inflammatory markers: somatic cell count, N-acetyl-beta-glucosaminidase (EC 3.2.1.30), electrical conductivity and antitrypsin. A two-way analysis of variance was performed for each of the inflammatory markers on results from 273 cows sampled six times at 14 d intervals. Adjustment for the individual cow's mean removed approximately half the total variation for all four markers, indicating that comparisons in marker levels between quarters without taking the cows' overall level into account, as is done in diagnostic keys based on fixed threshold, is a rash procedure. After adjusting for the individual cow means, the total variation of the marker observations was partitioned in three sources of variation: between the four quarter levels, between different sampling days, and the experimental error, i.e. the variation within each quarter over the study period. As expected, the variation between quarters accounted for the largest percentage of the variation (44-65%). In contrast the variation between days was only 16-34% and of the same magnitude as the experimental error. These figures can profitably be taken into account when designing experiments in future mastitis research studies. They imply that mastitis diagnostics based on quarter milk samples collected over time will be influenced only slightly by random biological variation and that the same relative differences that exist in marker levels between the four quarters of a cow as a rule will be disclosed irrespective of sampling day. Thus, the udder health state is relatively stable when determined by these inflammatory markers. In addition to simple correlations between markers measured on the same day, correlations of the logarithm of the interquarter ratios and of the experimental errors were computed. Stronger associations between the markers emerged and these correlations reflect more precisely than simple correlations the real diagnostic relations of the markers.

Acetylglucosaminidase↗

[Blood pressure elevation among industrial workers exposed to stress].

A standardized, annual medical examination of a group of heat workers exposed to, and another group not exposed to heat in a Norwegian ferro-alloy plant over a period of six years showed no statistically significant difference in blood pressure between the two groups. However, following three years of stable blood pressure and heart rates, both parameters increased markedly in both groups. The occurrence of this sudden increase in blood pressure coincided with the plant being threatened with the possibility of closure due to inability to operate at a profit. This threat persisted for more than two years, but even afterwards, when it was quite clear that jobs at the plant were no longer threatened, the blood pressure remained markedly elevated. These findings emphasize the importance of being aware of the possible relationship between prolonged mental stress and hypertension.

Adult↗

The diagnosis of subclinical mastitis by redefinition of the interquarter ratio and definition of the interquarter variation using analysis of variance methods.

A definition is proposed for the interquarter ratio of markers of inflammation in the bovine mammary gland which in contrast to present measurement procedures has well-defined distributional properties and thus facilitates statistical analysis. Our proposal of an interquarter ratio is equally applicable to evaluation of both single and multi-sample experiments. Finally, we define a new index for diagnosis of subclinical mastitis at the cow level, the interquarter variation, which assesses the degree of dispersion of the four quarter levels for values of any continuous inflammatory marker.

Analysis of Variance↗

Measles incidence, vaccine efficacy, and mortality in two urban African areas with high vaccination coverage.

Measles incidence, vaccine efficacy, and mortality were examined prospectively in two districts in Bissau where vaccine coverage for children aged 12-23 months was 81% (Bandim 1) and 61% (Bandim 2). There was little difference in cumulative measles incidence before 9 months of age (6.1% and 7.6%, respectively). Between 9 months and 2 years of age, however, 6.1% contracted measles in Bandim 1 and 13.7% in Bandim 2. Even adjusting for vaccination status, incidence was significantly higher in Bandim 2 (relative risk 1.6, P = .04). Even though 95% of the children had measles antibodies after vaccination, vaccine efficacy was not more than 68% (95% confidence interval [CI] 39%-84%) and was unrelated to age at vaccination. Unvaccinated children had a mortality hazard ratio of 3.0 compared with vaccinated children (P = .002), indicating a protective efficacy against death of 66% (CI 32%-83%) of measles vaccination. These data suggest that it will be necessary to vaccinate before age 9 months to control measles in hyperendemic urban African areas.

Age Factors↗

Increased postperinatal child mortality among children of mothers exposed to measles during pregnancy.

Previous studies of an urban and a rural epidemic in Guinea-Bissau have shown perinatal mortality to be statistically significantly higher among children whose mothers have been exposed to measles during pregnancy. After the epidemic in 1970 in Bandim, a district in the capital of Guinea-Bissau, such children also had a postperinatal childhood mortality risk (7 days to 5 years of age) of 0.229, compared with 0.134 for other children in the community. None of the mothers had developed clinical measles. In a Cox regression analysis adjusting for known background factors, the mortality hazard ratio between the exposed and the controls was found to be 2.0 (95% confidence interval 1.1-3.8). After a small rural measles epidemic in Quinhamel in 1983, the mortality hazard ratio for children of mothers exposed during pregnancy compared with controls was 1.7 (95% confidence interval 0.6-4.6). Exposure to measles or some concomitantly transmitted pathogen during fetal life may contribute to the high childhood mortality found in many developing countries.

Child, Preschool↗

Immunodeficiency in HIV-2 infection: a community study from Guinea-Bissau.

In a community study in Guinea-Bissau, West Africa, 47 HIV-2-seropositive cases and 87 matched controls were evaluated immunologically using immuno-alkaline phosphatase linked to avidin-biotin complex for the assessment of CD4 and CD8 status. HIV-2-seropositive individuals had significantly lower total numbers of CD4 cells and CD4/CD8 ratios, 38% having a total number of CD4 cells less than or equal to 0.5 x 10(9)/l and 36% having a CD4/CD8 ratio less than or equal to 0.8. Total numbers of CD4 cells less than or equal to 0.5 x 10(9)/l or CD4/CD8 ratio less than or equal to 0.8 were found in 53% of the HIV-2 seropositives compared with 11% among controls [odds ratio (OR) = 7.3; 95% confidence interval (CI): 3.1-17.1]. Lymphadenopathy was significantly more frequent among HIV-2 seropositives than among controls (OR = 3.4; 95% Cl: 1.5-7.6). HIV-2 seropositives with lymphadenopathy had significantly fewer lymphocytes (P = 0.008) and lower total CD4 (P = 0.029) and total CD8 number (P = 0.011) than HIV-2 seropositives without lymphadenopathy. This study indicates that HIV-2 has a significant immunosuppressive effect.

Adult↗

Child mortality related to seroconversion or lack of seroconversion after measles vaccination.

When blood samples were analyzed for seroconversion after measles vaccination, it was discovered that the vaccine had been ineffective for a certain period. During the 2 years between vaccination and the time of seroanalysis, nonseroconverters had a significantly higher mortality than seroconverters (P less than 0.05). The incidence of measles among nonseroconverters was 30% during the period. Between 9 months and 3 years of age, cumulative mortality was 15.1% for nonseroconverters and 4.5% for seroconverters. The difference in mortality was larger when high risk groups (twins, motherless children) were excluded from the analysis (P less than 0.01). The difference in mortality was particularly marked among children vaccinated in the age group 9 to 11 months. This as well as other community studies suggest that measles vaccination reduces child mortality from the age of vaccination by at least 30%.

Antibody Formation↗

Trial of high-dose Edmonston-Zagreb measles vaccine in Guinea-Bissau: protective efficacy.

In a randomised study of 558 children in an urban African community, the protective effect of the Edmonston-Zagreb (EZ) measles vaccine given in a dose of 40,000 plaque forming units from the age of 4 months was compared with the effects of a standard dose (6000 tissue culture infectious units) of Schwarz measles vaccine given from the age of 9 months. During two years of follow-up, all 14 clinical cases of measles occurred in the Schwarz group; 10 of the children contracted measles before vaccination and 4 after measles vaccination. Thus the EZ vaccine provided significant protection against measles both before and after the usual age of vaccination. Among the children who were exposed to measles at home, those given EZ vaccine were better protected than either unvaccinated children or those given the Schwarz vaccine.

Age Factors↗