Predictive value of uterine contractility and the serum levels of progesterone and oestrogens with regard to preterm labour

A longitudinal investigation regarding the serum concentrations of oestradiol, oestriol and progesterone in relation to uterine activity has been performed in 80 healthy primigravid women during the course of pregnancy up to the 37th week of pregnancy. The frequency of uterine contractions was quantitatively objectivated by means of external toco-dynamometry; simultaneously the uterine activity has been recorded by the pregnant women qualitatively. It appears that there is a gradual increase of all the three mentioned hormones during the course of pregnancy. However, there is a large interindividual spread. There exists no relation between the hormonal serum levels and uterine activity (quantitatively as well as qualitatively recorded). Between these two latter there is a poor relation. It is impossible to predict the occurrence of preterm birth based on hormonal serum changes. This holds for the progesterone-oestradiol ratio.     

Psychometric properties of the Subjective Well-Being Under Neuroleptics scale and the Subjective Deficit Syndrome Scale

RATIONALE: Subjective experience of antipsychotic drugs is relevant for medication compliance and quality of life. There is, however, sparse knowledge about the assessment of subjective experience.OBJECTIVES: To examine the internal consistency, test-retest reliability, sensitivity to medication change and concurrent validity of two test instruments: the Subjective Well-Being Under Neuroleptics (SWN) and the Subjective Deficit Syndrome Scale (SDSS). METHODS: Both instruments were used at admission and after 6 weeks of medication stabilization in 105 consecutively admitted patients diagnosed with DSM-IV (Diagnostic and Statistical Manual of Mental Disorders, 4th edn) diagnoses of recent-onset schizophrenia, schizophreniform disorder or schizoaffective disorder. RESULTS: Almost all patients were capable of reproducing their subjective experience in a consistent way both before and after medication stabilization. The internal consistency of both instruments was high. The test-retest reliability was high if medication was not changed, especially for the SWN. The SWN was sensitive for changes in medication and dosage. The short form of the SWN (SWN-20 items) had comparable psychometric qualities to the original instrument (SWN-38 items). The concurrent validity of the SWN and the SDSS was good, indicating that both tests measure the same concept. CONCLUSIONS: The assessment of subjective experience with the SWN (both versions) may be used in evaluating differential effects of anti-psychotics and dose on subjective well-being.     

Pharmacokinetics and pharmacodynamics of midazolam administered as a concentrated intranasal spray. A study in healthy volunteers

AIMS: To investigate the pharmacokinetic and pharmacodynamic profile of midazolam administered as a concentrated intranasal spray, compared with intravenous midazolam, in healthy adult subjects. METHODS: Subjects were administered single doses of 5 mg midazolam intranasally and intravenously in a cross-over design with washout period of 1 week. The total plasma concentrations of midazolam and the metabolite 1-hydroxymidazolam after both intranasal and intravenous administration were described with a single pharmacokinetic model. beta-band EEG activity was recorded and related to midazolam plasma concentrations using an exponential pharmacokinetic/pharmacodynamic model. RESULTS: Administration of the intranasal spray led to some degree of temporary irritation in all six subjects, who nevertheless found intranasal administration acceptable and not painful. The mean (+/-s.d.) peak plasma concentration of midazolam of 71 (+/-25 ng ml-1) was reached after 14 (+/-5 min). Mean bioavailability following intranasal administration was 0.83+/-0.19. After intravenous and intranasal administration, the pharmacokinetic estimates of midazolam were: mean volume of distribution at steady state 1.11+/-0.25 l kg-1, mean systemic clearance 16.1+/-4.1 ml min-1 kg-1 and harmonic mean initial and terminal half lives 8.4+/-2.4 and 79+/-30 min, respectively. Formation of the 1-hydroxymetabolite after intranasal administration did not exceed that after intravenous administration. CONCLUSIONS: In this study in healthy volunteers a concentrated midazolam nasal spray was easily administered and well tolerated. No serious complications of the mode of administration or the drug itself were reported. Rapid uptake and high bioavailability were demonstrated. The potential of midazolam given via a nasal spray in the acute treatment of status epilepticus and other seizure disruptions should be evaluated.     

Measuring quality of life in children with inflammatory bowel disease: The Impact-II (NL)

Inflammatory bowel disease (IBD) is a chronic debilitating disorder. Measures of quality of life are only available for adult patient populations. We developed a new disease-specific health-related quality of life instrument in Dutch for pediatric patients with IBD, called Impact-II (NL). We translated and strongly modified the original (Canadian) Impact questionnaire. It comprises 35 items in six domains. Eighty-three children (66%rpar; completed the questionnaire, 39 children were assessed twice. Disease symptoms were recorded and disease course severity assessed through chart review. Summated disease activity scores and disease course severity scores were dichotomized into two categories. Reliability coefficients were good for five out of six domains (Cronbach's ranged from 0.57 to 0.86) and measures of test–retest stability in clinically stable patients were good for all domains (intra-class correlation coefficients ranged from 0.67 to 0.91). The instrument showed good discriminant validity between symptom groups and disease course severity on all domains. Convergent validity with a validated generic instrument [TNO-AZL Children's Quality of life questionnaire (Tacqol)] showed satisfactory coefficients. In conclusion, the developed questionnaire shows good psychometric properties. Test–retest stability and responsiveness to change should be further assessed in larger patient samples. Cross-cultural translation and validation procedures into other languages are being conducted to enable international use of Impact-II.     

A physiological threshold for protection against menadione toxicity by human NAD(P)H:quinone oxidoreductase (NQO1) in Chinese hamster ovary (CHO) cells

NAD(P)H:quinone oxidoreductase 1 (NQO1) has often been suggested to be involved in cancer prevention by means of detoxification of electrophilic quinones. In the present study, a series of Chinese hamster ovary (CHO) cell lines expressing various elevated levels of human NQO1 were generated by stable transfection. The level of NQO1 over-expression ranged from 14 to 29 times the NQO1 activity in the wild-type CHO cells. This panel of cell lines, allowed investigation of the protective role of NQO1 in quinone cytotoxicity. It could be demonstrated that menadione toxicity was significantly reduced in all NQO1-transfected CHO clones compared to the wild-type cells, but the clones did not show differences in their level of protection against menadione. This observation pointed at a critical threshold concentration of NQO1 above which a further increase does not provide further protection against quinone cytotoxicity. Additional studies in which the NQO1 activity was inhibited by dicoumarol showed that only dicoumarol concentrations of about five times the EC(50) for NQO1 inhibition were able to reduce NQO1 levels below the apparent threshold, making the cells more sensitive. The level of this threshold was estimated to be in the range of base line NQO1 activities observed in several tissues and species. Thus, the results of the present study indicate that beneficial effects of NQO1 induction by, for example, cruciferous vegetables might be absent or present depending on the NQO1 activity threshold for optimal protection and the basal level of NQO1 expression in the tissue and species of interest.     

The reliability of assessment of vibration sense

OBJECTIVES: To assess the reliability of quantitative assessment of vibration sense with a Vibrameter type III. MATERIAL AND METHODS: We examined 111 healthy subjects (21-69 years). For intraobserver reliability, short-term (15 min between measurements) (n=11) and 24-h (n=28) reliability was tested. For interobserver reliability, a second tester performed the second measurement 15 min after the initial test (n=39). We also assessed the independent impact of effects of age, gender and height on vibration thresholds. RESULTS: In our study the intraobserver reliability is good [intraclass correlation coefficients (ICC) ranging from 0.55 to 0.99], whereas the interobserver reliability is moderate (ICC ranging from 0.32 to 0.88). Multiple linear regression analysis showed that age and--to a lesser extent--height was independently associated with the threshold values of the feet, but not with the thresholds of the hands. CONCLUSION: The use of a Vibrameter for measuring vibration thresholds in clinical practice and in multicentre studies is restricted because of the moderate interobserver reliability.     

Incipient CADASIL

BACKGROUND: Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is caused by mutations in the NOTCH3 gene. Knowledge of disease expression in young adult NOTCH3 mutation carriers (MCs) is limited. OBJECTIVE: To characterize clinical, neuropsychological, and radiological status in NOTCH3 MCs younger than 35 years. DESIGN: Clinical characterization and blinded survey comparing MCs with non-MCs. SETTING: Referral center. PARTICIPANTS: Individuals younger than 35 years who were at a 50% risk of a NOTCH3 mutation, from our CADASIL database. Thirteen individuals, from 8 families, met the criteria. METHODS: Comprehensive clinical, genetic, neuropsychological, and radiological investigations. Magnetic resonance images were scored according to a standardized white matter hyperintensities rating scale. RESULTS: Six individuals, from 5 families, were MCs. Clinical symptoms consisted of migraine (with aura), stroke, and stroke-like episodes. We did not find evidence for psychiatric disturbances, functional disability, or cognitive dysfunction, compared with non-MCs. Radiologically, a characteristic magnetic resonance imaging lesion pattern emerged for all MCs. This comprised white matter hyperintensities in the anterior temporal lobes, the frontal lobes, and the periventricular frontal caps. CONCLUSIONS: Migraine (with aura) and stroke can present in NOTCH3 MCs younger than 35 years; however, more importantly, physical function and cognition are intact. Possible subtle cognitive dysfunction needs to be assessed in a larger study. White matter hyperintensities on magnetic resonance imaging are characteristic, and are consistently visualized from the age of 21 years and onward. Awareness of the clinical and radiological features of CADASIL in those younger than 35 years should increase early diagnosis and allow for customized counseling of young adults from families with CADASIL.