The effect of early measles vaccination at 4.5 months of age on growth at 9 and 24 months of age in a randomized trial in Guinea-Bissau.

BACKGROUND: Providing an early, additional measles vaccine (MV) at 4.5 months of age has been shown to reduce child mortality in low-income countries. We studied the effects on growth at 9 and 24 months of age. METHODS: A randomized controlled trial was conducted in Guinea-Bissau from 2003-2007 including 6,648 children. Children were randomized 1:1:1 to receive Edmonston-Zagreb measles vaccine at 4.5 and 9 months of age (group A), no vaccine at 4.5 months and Edmonston-Zagreb measles vaccine at 9 months (group B), or no vaccine at 4.5 months and Schwarz measles vaccine at 9 months (group C) Data on anthropometrics were obtained at enrolment at 4.5 months of age and again at 9 and 24 months of age. Analyses were stratified by sex, season of enrolment, and neonatal vitamin A supplementation (NVAS) status, as all these factors have been shown to modify the effect of early MV on mortality. RESULTS: Overall there was no effect of early MV on anthropometry at 9 months. At 24 months children who had received early MV had a significantly larger mid-upper-arm-circumference (MUAC/in cm) (Difference = 0.08; 95% CI (0.02;0.14)) compared with children in the control group; this effect was most pronounced among girls (0.12 (0.03;0.20)). The effect of early MV on MUAC remained significant in the dry season and in girls who received placebo rather than NVAS. CONCLUSION: Early MV was associated with a larger MUAC particularly in girls. These results indicate that a two-dose measles vaccination schedule might not only reduce child mortality but also improve growth. TRIAL REGISTRATION: ClinicalTrials.gov NCT00168558 . Registered September 9, 2005, retrospectively registered.

Lipid-based nutrient supplements do not affect efavirenz but lower plasma nevirapine concentrations in Ethiopian adult HIV patients.

OBJECTIVES: Lipid-based nutrient supplements (LNSs) are increasingly used in HIV programmes in resource-limited settings. However, the possible effects of LNSs on the plasma concentrations of antiretroviral drugs have not been assessed. Here, we aimed to assess the effects of LNSs on plasma efavirenz and nevirapine trough concentrations in Ethiopian adult HIV-infected patients. METHODS: The effects of LNSs were studied in adults initiating antiretroviral therapy (ART) in a randomized trial. Patients with body mass index (BMI) > 17 kg/m(2) (n = 282) received daily supplementation of an LNS containing whey (LNS/w), an LNS containing soy (LNS/s) or no LNS. Trough plasma concentrations of efavirenz and nevirapine were measured at 1 and 2 months. Genotyping for 516 G>T and 983 T>C polymorphisms of the cytochrome P450 (CYP) 2B6 locus was performed. Multilevel linear mixed-effects models were used to assess the associations between LNS and plasma efavirenz and nevirapine concentrations. RESULTS: In patients with BMI > 17 kg/m(2), nevirapine concentrations were lower in the LNS/w and LNS/s groups by a median of -2.3 µg/mL [interquartile range (IQR) -3.9; -0.9 µg/mL; P = 0.002] and -2.1 µg/mL (IQR -3.9; -0.9 µg/mL; P = 0.01), respectively, compared with the group not receiving supplements. There were no differences between groups with respect to efavirenz plasma concentrations. The CYP2B6 516 G>T polymorphism was associated with a 5 µg/mL higher plasma efavirenz concentration compared with the wild type (P < 0.0001), while it was not associated with plasma nevirapine concentrations. CONCLUSIONS: Intake of an LNS was associated with lower plasma nevirapine trough concentrations, indicating possible drug-LNS interactions. The clinical relevance of such reductions in nevirapine exposure is not clear. Plasma efavirenz concentration was not affected by the LNS.

Impact of genetic variants of RFC1, DHFR and MTHFR in osteosarcoma patients treated with high-dose methotrexate.

Osteosarcoma patients are commonly treated with high doses of methotrexate (MTX). MTX is an analog of folate, which is essential for DNA synthesis. Genetic polymorphism at single nucleotide can be indicative to the prognostic outcome in patients. Germ-line variants in candidate genes, coding for enzymes active in the metabolism of MTX, were studied in 62 osteosarcoma patients. Patients harboring the GG genotype in reduced folate carrier 1 (RFC1) rs1051266 had significantly better survival in comparison with patients having the AA genotype (P=0.046). These patients also had a lower frequency of metastasis (15%, P=0.029). Also patients homozygous for the G allele of rs1053129 in the dihydrofolate reductase (DHFR) gene were more likely to have a metastasis (45%, P= 0.005), and the methylenetetetrahydrofolate reductase (MTHFR) 677C allele was associated with higher degree of liver toxicity (88%, P=0.007). The study suggests that germ-line variants in the MTX metabolic pathway are associated with survival and side effects in patients treated with MTX.

Cortical glutamate levels decrease in a non-human primate model of dopamine deficiency.

While Parkinson's disease is the result of dopaminergic dysfunction of the nigrostriatal system, the clinical manifestations of Parkinson's disease are brought about by alterations in multiple neural components, including cortical areas. We examined how 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) administration affected extracellular cortical glutamate levels by comparing glutamate levels in normal and MPTP-lesioned nonhuman primates (Macaca mulatta). Extracellular glutamate levels were measured using glutamate microelectrode biosensors. Unilateral MPTP-administration rendered the animals with hemiparkinsonian symptoms, including dopaminergic deficiencies in the substantia nigra and the premotor and motor cortices, and with statistically significant decreases in basal glutamate levels in the primary motor cortex on the side ipsilateral to the MPTP-lesion. These results suggest that the functional changes of the glutamatergic system, especially in the motor cortex, in models of Parkinson's disease could provide important insights into the mechanisms of this disease.

Intrafollicular endocrine milieu after addition of hCG to recombinant FSH during controlled ovarian stimulation for in vitro fertilization.

CONTEXT: The role of human chorionic gonadotropin (hCG) supplementation on the intrafollicular steroid milieu has been studied. OBJECTIVE: The objective of the study was to assess the impact on steroid levels in follicular fluids (FFs) after different doses of hCG supplementation to recombinant FSH for controlled ovarian stimulation. SETTING: This was a prospective randomized dose-response study conducted at Copenhagen University Hospital, Rigshospitalet, Denmark. PATIENTS: From 62 in vitro fertilization patients, 334 FFs were selected for analyses. INTERVENTIONS: Patients were treated using a GnRH agonist protocol with recombinant FSH 150 IU/d and randomized from stimulation day 1 to supplementation with hCG: D0, 0 IU/d; D50, 50 IU/d; D100, 100 IU/d; and D150, 150 IU/d. MAIN OUTCOME MEASURE: Intrafollicular hormone concentrations in relation to treatment groups, follicular sizes, and embryo quality were measured. RESULTS: In large follicles, hCG supplementation induced a nearly 3-fold increase of estradiol (nanomoles per liter) [D0: 1496; D50: 3138; D100: 4338; D150: 4009 (P < .001)], a significant 3-fold increase of androstenedione, and a 5-fold increase of T (nanomoles per liter) [D0: 15; D50: 38; D100: 72; D150: 56 (P < .001)]. The estradiol to T ratio decreased significantly, with the lowest ratio in D100 and the highest in D0. Large follicles giving rise to good-quality embryos had significantly higher estradiol and progesterone levels and estradiol to T, estradiol to androstenedione, and progesterone to estradiol ratios, compared with small follicles, leading to poor-quality embryos. CONCLUSIONS: Increasing doses of hCG supplementation markedly stimulated the intrafollicular concentration of both estradiol and androgens, with a shift toward a more androgenic milieu. In large follicles with oocytes giving rise to good-quality embryos, the FFs were significantly more estrogenic than in small follicles with oocytes developing into poor quality embryos.

Endocrine effects of hCG supplementation to recombinant FSH throughout controlled ovarian stimulation for IVF: a dose-response study.

OBJECTIVE: To analyse the endocrine response in relation to the Δ-4 and Δ-5 pathways of ovarian steroidogenesis after different doses of human chorionic gonadotrophin (hCG) supplementation to recombinant FSH from Day 1 of controlled ovarian stimulation for IVF. DESIGN: A randomized dose-response pilot study. PATIENTS: A total of 62 IVF patients aged 25-37 years with regular cycles and FSH <12 IU/l were treated with a fixed dose of rFSH 150 IU/day and randomized to four hCG dose groups: Dose 0: 0 IU/day, Dose 50: 50 IU/day, Dose 100: 100 IU/day and Dose 150: 150 IU/day. RESULTS: A significant hCG dose-dependent incremental increase was found for progesterone (49-160%), 17-OH-progesterone (223-614%), androstenedione (91-340%) and testosterone (95-338%) from Dose 0 to Dose 150, respectively. Dehydroepiandrosterone (DHEA) showed minor changes during stimulation and no differences between the groups. The highest oestradiol concentrations were observed in Dose 100 and Dose 150. Sex hormone-binding globulin (SHBG) increased similarly in all groups at the end of stimulation. No difference was observed for anti-müllerian hormone (AMH) concentration between the groups, but a 50% decline from the start to the end of the stimulation was found. CONCLUSION: Supplementation with hCG resulted in a clear dose-related response for androgens, progesterone and 17-OH-progesterone. Oestradiol concentration reached maximum levels with an hCG dose of 100 IU/day, suggesting saturation of aromatase function. No difference between the groups was observed for DHEA, supporting that the stimulatory effects of hCG doses on androgens and oestrogen production were mainly induced via the Δ-5 pathway. SHBG, being a biomarker of oestrogen/androgen balance, was not changed by increasing hCG.

A randomized controlled dose-response pilot study of addition of hCG to recombinant FSH during controlled ovarian stimulation for in vitro fertilization.

STUDY QUESTION: Is it possible to define an optimal dose of hCG in combination with rFSH from the first day of stimulation in the GnRH agonist protocol applied to IVF? SUMMARY ANSWER: Supplementation with hCG from the first day of stimulation may increase the number of top-quality embryos per patient. Daily doses of hCG up to 150 IU are compatible with good live birth rates. A ceiling level of estradiol (E(2)) was reached with hCG doses above 100 IU/day. A positive dose-response was seen for pre-ovulatory progesterone, but concentrations remained below values for which an impairment of endometrial receptivity has been previously reported. We suggest a large clinical trial to be proceeded with a group given 100 IU hCG daily versus a control group. WHAT IS KNOWN AND WHAT THIS PAPER ADDS: Prospective multicentre studies have indicated increased live birth rates and increased number of top-quality embryos when low doses of hCG were associated with FSH. We analysed the clinical, embryological and endocrine aspects of adding increasing doses of hCG to rFSH from the first day of stimulation for IVF. DESIGN: A prospective randomized, controlled, open-label dose-response pilot study was conducted between February 2009 and June 2010 at Copenhagen University Hospital, Rigshospitalet, Denmark. Adequate allocation concealment was assured from sequentially numbered, opaque, sealed envelopes prepared from a computer-generated list. Scoring of the embryos was done in an assessor-blinded way. PARTICIPANTS AND SETTING: Endocrinologically normal IVF patients aged 25-37 years, BMI 18-30 kg/m(2), regular cycles and FSH <12 IU/l, were treated with a fixed dose of rFSH 150 IU/day and randomized to daily hCG dose of 0, 50, 100 or 150 IU from Day 1 of stimulation. Primary end-point was the total number of top-quality embryos on Day 3. DATA ANALYSIS METHOD: Data were analysed by analysis of variance, Kruskal-Wallis test, chi-squared test or Poisson distribution count. MAIN FINDINGS: A total of 62 patients were randomized into four hCG dose groups: Dose 0 (D0; n= 16), Dose 50 (D50; n= 15), Dose 100 (D100; n= 16) and Dose 150 (D150; n= 15). Two patients in D150 were withdrawn after randomization because of major (10- to 30-fold) hCG dosing errors, leaving 13 patients in this group. Thus, the results are based on the per protocol population. The mean numbers of top-quality embryos per patient were D0: 0.8 ± 1.2, D50: 0.5 ± 0.7, D100: 1.2 ± 1.7 and D150: 1.5 ± 1.7 (P= 0.04). All pregnancies were singleton gestations, and the live birth rates per started cycle were D0: 25%, D50: 27%, D100: 25% and D150: 31% (P= 0.98). Steady state level of serum (s)-hCG was reached on Day 6 of stimulation. S-hCG levels (IU/l) on the day of hCG administration were D0: <0.1, D50: 3.1 (2.6-3.6), D100: 5.5 (4.1-7.4) and D150: 11.0 (8.9-13.6) (P< 0.01). The patients receiving hCG supplementation were stratified by 33 and 66% percentiles into three groups according to the concentration of s-hCG on Day 6 of stimulation: 0.5-3.5 IU/l (n= 16), 3.5-8.0 IU/l (n= 14) and 8.0-21.1 IU/l (n= 14). The mean numbers of top-quality embryos in the three groups were 0.5 ± 0.9, 1.1 ± 1.8 and 1.5 ± 1.5, respectively (P= 0.03). The progesterone increments from stimulation Day 1 to the day of hCG triggering were D0 = 49%, D50 = 79%, D100 = 110% and D150 = 160% (P= 0.02). S-androstenedione level was highest in D150 (P< 0.01). S-E(2) was 2-fold higher in the D100 and D 150 compared with D0 (P= 0.09). BIAS, LIMITATION, GENERALISABILITY: Our study has a limited sample size. Supplementation with daily hCG dose up to 150 IU throughout stimulation has never been used before. Hence, this had to be tested in a small study before conducting a larger trial. STUDY FUNDING/COMPETING INTERESTS: Ferring Pharmaceuticals, Research and Development, provided funds for the endocrine measurements. CLINICALTRIAL.GOV REGISTRATION: NCT00844311.

Dietary long-chain n-3 PUFA, gut microbiota and fat mass in early postnatal piglet development--exploring a potential interplay.

Dietary n-3PUFA and gut bacteria, particularly Bacteroidetes, have been suggested to be related to adiposity. We investigated if n-3PUFA affected fat storage and cecal bacteria in piglets. Twenty-four 4-day-old piglets were allocated to formula rich in n-3PUFA (∼3E%) from fish oil (FO) or n-6PUFA from sunflower oil (SO) for 14 days. We assessed body weight, fat accumulation by dual-energy X-ray absorptiometry and microbial molecular fingerprints. Dietary PUFA-composition was reflected in higher erythrocyte n-3PUFA in the FO- than the SO-group (P<0.001). Principal component analysis revealed group differences in the overall microbiotic composition, which involved a larger Bacteroides community in the SO-group (P=0.02). There was no significant difference in body fat percentage and no relationship between fat accumulation and gut Bacteroides. Hence, this study does not support an impact of n-3PUFA or microbiota on fat accumulation during the postnatal maturation period. The impact of dietary PUFA on the gut Bacteroides warrants further investigation.

Effects of dose-intensive chemotherapy and radiotherapy on serum n-terminal proatrial natriuretic peptide in high-risk breast cancer patients.

By using N-terminal proatrial natriuretic peptide (proANP) in serum as a marker of cardiac function, we compared the cardiac side effects of two intensive adjuvant treatment regimens for breast cancer. Patients received either 9 cycles of FEC (5-fluorouracil, epirubicin and cyclophosphamide) where the doses of epirubicin and cyclophosphamide were escalated according to the leucocyte nadir (n = 49, FEC-group) or three cycles of FEC followed by high-dose chemotherapy with alkylating agents (n = 56, CTCb-group) given with the support of peripheral blood stem cells support. Both groups received adjuvant radiotherapy. Serial measurements of proANP were performed up to three years after treatment. Mean proANP values in the FEC-group was on average 19% higher than in the CTCb-group (p = 0.002). The proANP levels showed a significant association with the cumulative dose of epirubicin (p < 0.001) but not with cyclophosphamide (p = 0.151) and 5-FU (p = 0.160). The pharmacokinetics of epirubicin was studied at the first and third chemotherapy course. The proANP levels after treatment were significantly related to the AUC (p = 0.034) and Cmax(p = 0.037) of epirubicin. Left-sided chest irradiation was associated with on average 12% higher proANP values than right-sided (p = 0.031). We conclude that dose-escalated FEC causes a stronger increase in proANP than 3 FEC followed by high-dose CTCb-treatment. Increase of proANP levels might represent an early sign of cardiotoxicity secondary to chemotherapy and radiation treatment. Long-time follow-up is necessary to determine the clinical significance of these findings.

Purification and characterisation of a new hypothalamic satiety peptide, cocaine and amphetamine regulated transcript (CART), produced in yeast.

Cocaine and amphetamine regulated transcript (CART) is a newly discovered hypothalamic peptide with a potent appetite suppressing activity following intracerebroventricular administration. When the mature rat CART sequence encoding CART(1-102) was inserted in the yeast expression plasmid three CART peptides could be purified from the fermentation broth reflecting processing at dibasic sequences. None of these corresponded to the naturally occurring CART(55-102). In order to obtain CART(55-102) the precursor Glu-Glu-Ile-Asp-CART(55-102) has been produced and CART(55-102) was generated by digestion of the precursor with dipeptidylaminopeptidase-1. All four generated CART peptides have been characterised by N-terminal amino acid sequencing and mass spectrometry. The CART peptides contain six cysteine residues and using the yeast expressed CART(62-102) the disulphide bond configuration was found to be I-III, II-V and IV-VI. When the four CART peptides were intracerebroventricularly injected in fasted mice (0.1 to 2.0 microg) they all produced a dose dependent inhibition of food intake.

Comparison of information on occupation and lifestyle habits obtained from European man-made vitreous fibre production workers and their relatives.

BACKGROUND: Studies of the aetiology of fatal diseases often rely on data obtained from relatives, which can cause loss of precision and introduce bias. We assessed the quality of such information on demographics, occupation, smoking and alcohol habits. METHODS: We compared contemporary interviews, based on a structured questionnaire, with male workers from the man-made vitreous fibre production industry in four European countries and their relatives. The participation rate was 63% (74 pairs of workers and relatives). RESULTS: Only minor differences in the ability to answer the questions appeared among workers and relatives, except for specific occupational questions. There was moderate to excellent agreement for demographics, residential and work history (kappa or intraclass correlation range: 0.44-0.98). For smoking habits, beer and wine consumption the agreement was good to excellent (range: 0.59-0.99). In particular, number of different residential areas, jobs, industries, and duration of wine drinking were significantly underreported by the relatives. No general determinant for reduced agreement appeared. CONCLUSIONS: In general, the quality of information obtained from relatives appeared good. However, information on specific occupational exposures may be improved by supplementing the information from relatives with details obtained from colleagues, occupational hygiene experts or occupation-exposure matrices.

[Micro-insemination with intracytoplasmic sperm injection]. / Mikroinsemination med intracytoplasmatisk saedcelleinjektion.

Intracytoplasmic sperm injection (ICSI) is now established in the treatment of infertility. Fertilization is achieved by microinjection of a single spermatozoon into the ooplasma. Oligoasthenoteratozoospermia is the main indication, but ICSI is also used in cases of failed fertilization after standard IVF, retrograde ejaculation and male immunological infertility. In obstructive azoospermia ICSI is performed after aspiration of epididymal or testicular spermatozoa. In some anejaculatoric men spermatozon can be obtained following penile vibration or electro-stimulation, but they often have poor motility and ICSI may be used for fertilization. ICSI may also be used after thawing of semen cryopreserved prior to treatment of a malignant disease. Since 1991 the ICSI technique has been improved, and today the pregnancy rates are at least as good as after standard IVF. So far, studies of the foetuses and children born after ICSI show that the number of malformations and abnormal karyotypes is within the range of the normal population.

Physical examinations and laboratory tests in antenatal care visits in Denmark. Do reported practice and current official guidelines concord with results of literature reviews? A nationwide study of the public scheme of shared antenatal care in general practice, centres of midwifery and hospital outpatients' clinics.

OBJECTIVE: To analyse physical examinations and laboratory tests reported in antenatal care visits in relation to official guidelines and reviews of appropriateness. DESIGN: A nationwide cross sectional study based on questionnaires completed by general practitioners (GPs), midwives, and hospital doctors. Physical examinations and laboratory tests in connection with one specific visit were reported. SUBJECTS: The questionnaires were completed by 722 GPs (61% of eligible from a random sample), 584 midwives (86% of eligible), 250 hospital doctors who made health examinations in pregnancy, week 16-18 (63% of eligible), and 181 hospital doctors who saw women with at-risk pregnancies (55% of eligible). RESULTS: General practice: weight, blood pressure (BP) measurement, and test for proteinuria were reported in more than 90% of visits. Urine culture was reported in 46%, and cervical smear in 41% of first visits. Rubella antibody test at the first visit was only reported in 23% of nulliparae. Vaginal examination was reported in 95% of first visits. Fewer were reported in second (27%) and third (48%) routine visits during pregnancy. Midwives: checks of BP, oedema, and proteinuria were reported in more than 95% of visits irrespective of week of gestation. Vaginal examination was reported in about a third of checkups. Hospitals: vaginal examination was reported in 66% of checkups in at-risk pregnancies. CONCLUSIONS: A surplus of resources were spent on (repeat) examinations and tests with little or no documented benefit. Cervical cytology was grossly overused. Urine culture and rubella serology were not sufficiently applied.

Renal and hepatic toxicity after high-dose 7-hydroxymethotrexate in the rat.

To examine directly the hepatic and renal toxicity of 7-hydroxymethotrexate (7-OH-MTX) without interference of the parent compound methotrexate (MTX), we purified and gave 100 mg/kg 7-OH-MTX to rats, a dose resulting in serum levels of 7-OH-MTX comparable with those achieved in the clinic after the administration of high-dose MTX (HD-MTX). After only 5 h, the 7-OH-MTX-treated rats demonstrated 2.6-fold increases in serum creatinine values and 2-fold elevations in serum aspartate aminotransferase (ASAT) levels as compared with the controls. Morphologic evidence of toxicity, however, was apparent only in the kidneys. Intraluminal cellular debris containing membranous material and deteriorated organelles was seen, but no precipitate of the delivered drug. The peak serum concentration of 7-OH was up to 939 microM, and concentrations of 7-OH-MTX declined triphasically, showing a t1/2 alpha value of 2.45 min, a t1/2 beta value of 30.5 min, and a terminal half-life (t1/2 gamma) of 240 min. The total clearance value was 14.5 ml min-1 kg, and the postdistributional volume of distribution (V beta) was 5070 ml/kg. Our results may indicate a direct toxic effect of 7-OH-MTX on kidney and liver cells.

The JANUS serum bank.

The on-going JANUS project was initiated by the Norwegian Cancer Society in 1973. The serum bank comprises close to 0.5 million serum samples collected from 170,000 donors. From 2-16 consecutive samples are available from each donor. The sera are stored at -25 degrees C. At regular intervals the JANUS-collection is matched against the files of the Norwegian Cancer Registry. From 1973 to 1991 almost 5000 of the donors have developed some form of cancer. Frozen serum samples collected from a few months to 18 years prior to clinical recognition of their disease are consequently available for research purposes. The aim of the JANUS-project is to search in these premorbid sera for chemical, biochemical, immunological or other changes that might be indicative of cancer development at early stages. Gas chromatography-mass spectrometry and two-dimensional protein electrophoresis have been used to evaluate the stability of the frozen sera. Some recent findings are: CA125 is elevated several months prior to diagnosis of ovarian cancer; serum thyroglobulin may be a preclinical tumour marker in subgroups of thyroid cancer; low level of selenium in serum reflects increased risk of thyroid cancer; and raised antibodies in serum against Epstein-Barr virus is a risk factor for development of Hodgkin's disease. On-going research includes trace elements and cancer, and studies on lipid-profiles, diet and cancer. The serum bank may in principle be used for other purposes, e.g. in environmental studies. Analysis of sequential sera may determine chemical substances in the sera that might reflect differences in exposure to environmental pollutants in the period 1973-1991.

[Preventive health examinations of pregnant women in Denmark. Anamnestic practice and discussion of prenatal diagnosis in early pregnancy examinations in general practice, birth clinics and birthing centers]. / Forebyggende helbredsundersøgelser af gravide kvinder i Danmark. Anamnesepraksis og samtale om proenatal diagnostik ved tidlig undersøgelse i svangerskabet hos praktiserende loege, på fødestedet og hos jordemoder.

In Denmark, pregnant women are offered antenatal care in a nationwide programme. This programme is organized around health examinations in general practice, hospital outpatient departments and at midwives' centres. During winter 1986-1987, a nationwide investigation of antenatal care was carried out. A random sample of approximately 1/3 of the general practitioners, all of the midwives who had antenatal consultations and the medical staffs of 26 departments of obstetrics and gynaecology received a questionnaire about content of a definite antenatal examination. 62% of the general practitioners, 63% of the doctors at the place of delivery and 86% of the midwives replied. Among the pregnant women, 92% replied from general practice, 84% from hospital outpatient departments and 91% from midwives' centres. The interviews about date of delivery and genetic counselling at early visits in general practice, hospital outpatient departments and at midwives' centres were in agreement with the nationwide guidelines. Employment of routine ultrasound scanning was not associated with less detailed history taking by the doctors at hospital outpatient departments, where ultrasound scanning was employed only on special indications. It was concluded that there was a considerable overlap between the interview about the date of delivery and genetic counselling at early visits in general practice and in hospital outpatient departments and, to some extent, at the midwives' centres. The sharing of responsibility for care of pregnant women by three professional groups requires specification of the content of the consultation. Official guidelines should be more specific about this point.

Sensorimotor cortical lesion effects and treatment with nimodipine.

Rats with unilateral ablations of the sensorimotor cortex and others with control operations were tested for their ability to touch and remove adhesive tape applied to both forelimbs. Half of each group was administered a calcium channel antagonist (nimodipine) for two weeks following the lesions and the other half received vehicle. The rats with lesions showed a bias to remove the ipsilateral stimulus first and exhibited contralateral deficits relative to control animals. Nimodipine was shown to reduce the contralateral stimulus removal time when the animals began testing two weeks after surgery, but not when testing began 1 day after surgery and overlapped the period of drug administration. Lesion effects also appeared on tests for neurologic impairment and activity, but nimodipine did not reduce these deficits. These findings indicate that nimodipine has the potential to reduce some deficits after sensorimotor cortical lesions, but that the effects of this drug may be task specific.