Antenatal ultrasound and postnatal autopsy findings in terminations after 12 weeks' gestation due to fetal abnormality: population-based study in Western Norway, 1988-2002.

BACKGROUND: Ultrasound screening has been part of antenatal care for several decades, and warrants high expertise to meet the criteria for a worthwhile screening program. In particular, the rate of false positives should be low. PURPOSE: To examine time trends of pregnancy terminations for fetal abnormality after 12 weeks' gestation, and to assess the agreement between antenatal ultrasound and post-termination autopsy findings for the main pathologies leading to termination. MATERIAL AND METHODS: During the period 1988 to 2002, 198 pregnancies were terminated for fetal abnormality after 12 weeks' gestation. We reviewed the case notes for those 151 who were autopsied (male/female/undetermined ;= ;91/56/4). Annual rates of live births and stillbirths were retrieved from the Medical Birth Registry of Norway. RESULTS: Antenatal ultrasound provided a correct diagnosis of the major abnormality in 149/151 cases (99%), based on post-termination autopsy findings. The annual rate of terminations after 12 weeks' gestation varied between 0.6 and 3.4 (mean 1.8) per 1000 live births, with a trend toward higher rates over the study period (P=0.001, chi-square test for linear-by-linear association). CONCLUSION: The specificity of antenatal ultrasound for major abnormalities was high, as compared to postnatal autopsy findings. The mean annual rates of termination after 12 weeks' gestation tended to increase over the 14-year study period.

Preventing injuries in female youth football--a cluster-randomized controlled trial.

A set of exercises--the "11"--have been selected to prevent football injuries. The purpose of this cluster-randomized controlled trial was to investigate the effect of the "11" on injury risk in female youth football. Teams were randomized to an intervention (n=59 teams, 1091 players) or a control group (n=54 teams, 1001 players). The intervention group was taught the "11," exercises for core stability, lower extremity strength, neuromuscular control and agility, to be used as a 15-min warm-up program for football training over an 8-month season. A total of 396 players (20%) sustained 483 injuries. No difference was observed in the overall injury rate between the intervention (3.6 injuries/1000 h, confidence interval (CI) 3.2-4.1) and control group (3.7, CI 3.2-4.1; RR=1.0, CI 0.8-1.2; P=0.94) nor in the incidence for any type of injury. During the first 4 months of the season, the training program was used during 60% of the football training sessions, but only 14 out of 58 intervention teams completed more than 20 prevention training sessions. In conclusion, we observed no effect of the injury prevention program on the injury rate, most likely because the compliance with the program was low.

Expression of a novel factor, com1, is regulated by 1,25-dihydroxyvitamin D3 in breast cancer cells.

Tumor cells and their surrounding microenvironment produce a variety of factors that promote tumor growth and metastasis. We recently identified a nuclear factor, termed com1, that is up-regulated in human breast carcinoma cells on formation of experimental metastatic tumors and is assumed to act as a growth-promoting factor in breast cancer. 1,25-Dihydroxyvitamin D3 [1,25(OH)2D3] is a potent inhibitor of growth in breast cancer both in vitro and in vivo. We compared the growth-regulatory mechanisms of nontumorigenic and estrogen-dependent MCF-7 cells with those of the tumorigenic and tamoxifen-resistant subline MCF7/ LCC2 in the presence of 1,25(OH)2D3. Proliferation of MCF7/LCC2 cells, which revealed constitutive com1 expression, was inhibited by 1,25(OH)2D3 (10(-7) M). This was strongly associated with cell cycle arrest in G1 phase, consistent with accumulation of the hypophosphorylated form of the retinoblastoma protein as well as the induction of the cyclin-dependent kinase inhibitor p21. These cell cycle events were preceded by a transient up-regulation (5-8-fold) of com1 mRNA. Furthermore, clonal growth of the MCF7/LCC2 cells was also inhibited by 1,25(OH)2D3 (10(-7) M), and when the com1-negative MCF-7 cells were stably transfected with com1, the resulting MCF7/com1 cells showed a significant decrease in colony formation. These results seem to indicate that rather than promoting growth, com1 may participate in the regulatory pathway involved in cellular growth inhibition when recruited by inhibitory signals.

Research approaches to describe the mechanisms of injuries in sport: limitations and possibilities.

A number of different methodological approaches have been used to describe the inciting event for sports injuries. These include interviews of injured athletes, analysis of video recordings of actual injuries, clinical studies (clinical findings of joint damage are studied to understand the injury mechanism, mainly through plain radiography, magnetic resonance imaging, arthroscopy, and computed tomography scans), in vivo studies (ligament strain or forces are measured to understand ligament loading patterns), cadaver studies, mathematical modelling and simulation of injury situations, and measurement/estimation from "close to injury" situations. In rare cases, injuries have even occurred during biomechanical experiments. This review describes each research approach and assesses its strengths and weaknesses in contributing to the understanding and prevention of sports injuries.

The reliability and functional validity of visual and semiautomatic sleep/wake scoring in the Møll-Wistar rat.

The present paper has three major objectives: first, to document the reliability of a published criteria set for sleep/wake scoring in the rat; second, to develop a computer algorithm implementation of the criteria set; and third, to document the reliability and functional validity of the computer algorithm for sleep/wake scoring. The reliability of the visual criteria was assessed by letting two raters separately score 8 hours of polygraph records from the light period from five rats (14,040 10-second scoring epochs). Scored stages were waking, slow-wave sleep-1, slow-wave sleep-2, transition type sleep and rapid eye movement (REM) sleep. The visual criteria had good interrater reliability [Cohen's kappa (kappa) = 0.68], with 92.6% agreement on the waking/nonrapid eye movement (NREM) sleep/REM sleep distinction (kappa = 0.89). This indicated that the criteria allow separate raters to independently classify sleep/wake stages with very good agreement. An independent group of 10 rats was used for development of an algorithm for semiautomatic computer scoring. A close implementation of the visual criteria was chosen. The algorithm was based on power spectral densities from two electroencephalogram (EEG) leads and on electromyogram (EMG) activity. Five 2-second fast Fourier transform (FFT) epochs from each EEG/EMG lead per 10-second sleep/wake scoring epoch were used to take the spatial and temporal context into account. The same group of five rats used in visual scoring was used to appraise reliability of computerized scoring. The computer score was compared with the visual score for each rater. There was a lower agreement (kappa = 0.57 and 0.62 for the two raters) than in interrater visual scoring [percent agreement 87.7 and 89.1% (kappa = 0.82 and 0.84) in the waking/NREM sleep/REM sleep distinction]. Subsequently, the computer scores of the raters were compared. The interrater reliability was better than the interrater reliability for visual scoring (kappa = 0.75), with 92.4% agreement for the waking/NREM sleep/REM sleep distinction (kappa = 0.89). The computer scoring algorithm was applied to data from a third independent group of rats (n = 6) from an acoustical stimulus arousal threshold experiment, to assess the functional validity of the scoring directly with respect to arousal threshold. The computer algorithm scoring performed as well as the original visual sleep/wake stage scoring. This indicated that the lower intrarater reliability did not have a significant negative influence on the functional validity of the sleep/wake score.

Diurnal differences in L-tryptophan sleep and temperature effects in the rat.

Sleep/waking and EEG power spectra were investigated for 6 h periods in rats following administration of the essential amino acid L-tryptophan (40 mg/kg), the selective serotonin uptake inhibitor zimeldine (20 mg/kg), and following a combination of L-tryptophan and zimeldine. In contrast to earlier studies, L-tryptophan decreased waking and increased total slow wave sleep when administered late in the light phase (8 1/2 h after light onset). No sleep effects were seen after early light phase injections (2 h after lights on). In agreement with earlier studies, zimeldine initially increased wakefulness, followed by an increase in slow wave sleep-2. REM sleep was abolished after zimeldine treatment. Zimeldine increased EEG delta activity and decreased EEG activity above 7 Hz. L-Tryptophan potentiated the zimeldine induced increase in waking only when given early in the light phase. In a separate experiment, body temperature was monitored after L-tryptophan injections in both early and late light phase. A thermogenic effect of L-tryptophan was seen in the early light phase, while the opposite was seen in the late light phase. The data indicate diurnal differences in sleep/waking and temperature effects of a physiological dose of L-tryptophan.

Complicated deliveries, critical care and quality in emergency obstetric care in Northern Tanzania.

Our objective was to determine the availability and quality of obstetric care to improve resource allocation in northern Tanzania. We surveyed all facilities providing delivery services (n=129) in six districts in northern Tanzania using the UN Guidelines for monitoring emergency obstetric care (EmOC). The three last questions in this audit outline are examined: Are the right women (those with obstetric complications) using emergency obstetric care facilities (Met Need)? Are sufficient quantities of critical services being provided (cesarean section rate (CSR))? Is the quality of the services adequate (case fatality rate (CFR))? Complications are calculated using Plan 3 of the UN Guidelines to assess the value of routine data for EmOC indicator monitoring. Nearly 60% of the expected complicated deliveries in the study population were conducted at EmOC qualified health facilities. 81.2% of the expected complicated deliveries are conducted in any facility (including facilities not qualifying as EmOC facilities). There is an inadequate level of critical services provided (CSR 4.6). Voluntary agencies provide most of these services in rural settings. All indicators show large variations with the setting (urban/rural location, level and ownership of facilities). Finally, there is large variation in the CFR with only one facility meeting the minimum accepted level. Utilization and quality of critical obstetric services at lower levels and in rural districts must be improved. The potential for improving the resource allocation within lower levels of the health care system is discussed. Given the small number of qualified facilities yet relatively high Met Need, we argue that it is neither the mothers' ignorance nor their lack of ability to get to a facility that is the main barrier to receiving quality care when needed, but rather the lack of quality care at the facility. Little can be concluded using the CFR to describe the quality of services provided.

Bone morphogenetic protein-9 suppresses growth of myeloma cells by signaling through ALK2 but is inhibited by endoglin.

Multiple myeloma is a malignancy of plasma cells predominantly located in the bone marrow. A number of bone morphogenetic proteins (BMPs) induce apoptosis in myeloma cells in vitro, and with this study we add BMP-9 to the list. BMP-9 has been found in human serum at concentrations that inhibit cancer cell growth in vitro. We here show that the level of BMP-9 in serum was elevated in myeloma patients (median 176 pg/ml, range 8-809) compared with healthy controls (median 110 pg/ml, range 8-359). BMP-9 was also present in the bone marrow and was able to induce apoptosis in 4 out of 11 primary myeloma cell samples by signaling through ALK2. BMP-9-induced apoptosis in myeloma cells was associated with c-MYC downregulation. The effects of BMP-9 were counteracted by membrane-bound (CD105) or soluble endoglin present in the bone marrow microenvironment, suggesting a mechanism for how myeloma cells can evade the tumor suppressing activity of BMP-9 in multiple myeloma.

Radiography following perinatal death: a review.

Radiography of the perinatally dead infant provides detailed information about the skeleton and is valuable as an adjunct to autopsy. This article reviews the potential benefits and discusses the pitfalls in assessment of growth stage. Reference charts for individual bone lengths and secondary ossification centers are presented.

Apparent diffusion coefficient maps of pediatric mass lesions with free-breathing diffusion-weighted magnetic resonance: feasibility study.

PURPOSE: To assess the technical feasibility of apparent diffusion coefficient (ADC) mapping based on free-breathing diffusion-weighted magnetic resonance (DW-MR) outside the CNS in children. MATERIAL AND METHODS: Twelve children with mass lesions of varied histopathology were scanned with short-tau inversion recovery (STIR), contrast-enhanced T1-weighted (CE-T1W), and diffusion-weighted (b=0, 500 and 1000 s/mm2) sequences. ADC maps were calculated. Lesion-to-background signal intensity ratios were measured and compared between STIR/CE-T1W/ADC overall (Friedman test) and between viable embryonal tumors and other lesions (Kruskal-Wallis test). RESULTS: ADC maps clearly depicted all lesions. Lesion-to-background signal intensity ratios of STIR (median 3.7), CE-T1W (median 1.4), and ADC (median 1.6) showed no overall difference (chi-square=3.846; P=0.146), and there was no difference between viable embryonal tumors and other lesions within STIR/CE-T1W/ADC (chi-square 1.118/0.669/<0.001; P=0.290/0.414/1.000, respectively). CONCLUSION: ADC mapping is feasible in free-breathing imaging of pediatric mass lesions outside the CNS using standard clinical equipment.

Injury pattern in youth team handball: a comparison of two prospective registration methods.

The purpose of this study was to examine the injury incidence and pattern of injuries in youth female and male team handball players using two different prospective registration methods; match reports (90 teams, 1080 players) and coach reports (34 teams, 428 players). A total of 118 injuries were recorded by the coach report, of which 93 (79%) were acute injuries (incidence training: 0.9+/-0.16 injuries/1000 player hours; matches: 9.9+/-1.26; rate ratio vs training: 10.8 [95% confidence interval (CI) 7.0-16.6]; P<0.0001) and 25 (21%) were overuse injuries. Knee (26%) and ankle (24%) injuries accounted for half of the acute injuries (training: 0.5+/-0.12 injuries/1000/h; matches: 4.4+/-0.84; rate ratio vs training: 8.0 (95% CI 4.5-14.5); P<0.0001). No gender difference was found in the injury rate (rate ratio female vs male: 1.3 (95% CI 0.8-2.1); P=0.40). Most of the injuries occurred in the attacking phase by back or wing players doing a plant-and-cut, landing or turning movement, and more than half in contact situations with the opponent. Similar results were observed for acute match injuries in the match report. These results indicate that the rate of injuries in youth team handball is as high as at the senior level, and prevention should focus on knee and ankle injuries. The coach report seems to be the best method to register injuries in youth team handball to provide a full spectrum of injuries according to their type, incidence and severity.

Surveillance for Wilms tumour in at-risk children: pragmatic recommendations for best practice.

BACKGROUND: Most Wilms tumours occur in otherwise healthy children, but a small proportion occur in children with genetic syndromes associated with increased risks of Wilms tumour. Surveillance for Wilms tumour has become widespread, despite a lack of clarity about which children are at increased risk of these tumours and limited evidence of the efficacy of screening or guidance as to how screening should be implemented. METHODS: The available literature was reviewed. RESULTS: The potential risks and benefits of Wilms tumour surveillance are finely balanced and there is no clear evidence that screening reduces mortality or morbidity. Prospective evidence-based data on the efficacy of Wilms tumour screening would be difficult and costly to generate and are unlikely to become available in the foreseeable future. CONCLUSIONS: The following pragmatic recommendations have been formulated for Wilms tumour surveillance in children at risk, based on our review: (1) Surveillance should be offered to children at >5% risk of Wilms tumour. (2) Surveillance should only be offered after review by a clinical geneticist. (3) Surveillance should be carried out by renal ultrasonography every 3-4 months. (4) Surveillance should continue until 5 years of age in all conditions except Beckwith-Wiedemann syndrome, Simpson-Golabi-Behmel syndrome and some familial Wilms tumour pedigrees where it should continue until 7 years. (5) Surveillance can be undertaken at a local centre, but should be carried out by someone with experience in paediatric ultrasonography. (6) Screen-detected lesions should be managed at a specialist centre.

Garlic arrests MDA-MB-435 cancer cells in mitosis, phosphorylates the proapoptotic BH3-only protein BimEL and induces apoptosis.

Components of garlic (Allium sativum) can cause disruption of microtubules, cell cycle arrest, and apoptosis in cancer cells. We show here that a water-soluble extract of garlic arrested MDA-MB-435 cancer cells in mitosis and caused apoptosis. The proapoptotic BH3-only, bcl-2 family protein BimEL, which in healthy cells can be tightly sequestered to the microtubule-associated dynein motor complex, was modified after garlic treatment. The main effect of garlic on BimEL was a considerable increase in a phosphorylated form of the protein. This phosphorylation(s), probably partly dependent on c-jun N-terminal kinase activity, promoted mitochondrial localisation of BimEL. Furthermore, inhibition of extracellular signal-regulated kinases 1/2 increased the amount of another form of BimEL present in the mitochondrial cellular fraction. Treatment of cells with the garlic compound diallyl disulphide had similar effects on BimEL. The results indicate that the apoptotic effect of garlic and a combination of garlic and the inhibitor of extracellular signal-regulated kinases 1/2 in MDA-MB-435 cells partly is due to modifications that are necessary for translocation of the proapoptotic protein BimEL to mitochondria where it executes its proapoptotic function.

Congenital absence of the nose: a case report and literature review.

A case of congenital absence of the nose is presented. The etiology of this rare condition is unknown. A review of the literature reveals that the previously applied terms, e.g. 'arhinia', are unclear. In the reviewed cases there seems to be a pattern of facial anomalies associated with nasal absence. In most cases, one could probably expect a lack of the olfactory bulbs and tracts. We suggest a new terminology and summarize the aims of the radiological evaluation of this condition.

Relationship between floor type and risk of ACL injury in team handball.

The purpose of this study was to compare the ACL injury rate between two different floor types - wooden floors (parquet, generally having lower friction) and artificial floors (generally having higher friction). ACL injuries have been recorded prospectively from the three top divisions for men and women in Norwegian team handball during seven seasons (1989-2000). A total of 174 ACL injuries have been recorded, and of these 53 occurred in regular league games. The floor types for all regular games from the same seasons have been determined retrospectively based on match schedules. The matches were divided into two groups: those played on wooden floors and those played on artificial floors. A total of nine injuries occurred among men (incidence: 0.24+/-0.09 injuries per 1000 player hours) and 44 among women (0.77+/-0.04 injuries 1000 h(-1); OR vs. men: 3.21 (1.56-6.58); P=0.001). Among men, four injuries occurred on wooden floors (0.32+/-0.13 injuries 1000 h(-1)) and five injuries occurred on artificial floors (0.20+/-0.12 injuries 1000 h(-1); OR vs. wooden floors: 0.63 (0.17-2.37); ns). Among women, eight injuries occurred on wooden floors (0.41+/-0.09 injuries 1000 h(-1); OR vs. men: 1.29 (0.39-4.28); ns) and 36 on artificial floors (0.96+/-0.04 injuries 1000 h(-1); OR vs. wooden floors: 2.35 (1.09-5.07); P=0.03; OR vs. men: 4.77 (1.87-12.18); P=0.001). These results indicate that the risk of ACL injury for women is higher on artificial floors than on wooden floors.

Inhibition by angiotensin II of some vasopressin effects on renal function in sheep.

The effects of intravenous infusions of arginine vasopressin (AVP) alone and with angiotensin II (AII) on renal function were studied in conscious Merino ewes. AVP at 11.5 pmol.min-1 caused an increase in water and electrolyte output which was associated with a rise in glomerular filtration rate (GFR), solute clearance, solute-free water reabsorption and tubular sodium reabsorption. Addition of AII of 100 ng.min-1 generally reversed all of these effects. The filtration fraction, which rose during AVP infusion, increased further when AII was added due to a greater fall in renal plasma flow than in GFR. The diuretic and electrolyte-excreting effects of infused AVP appeared to be brought about by an increase in GFR. It is suggested that this inappropriate effect of AVP, which is secreted in response to water deprivation, could be countered by the simultaneous production of AII.

The effect of intravenous hypertonic saline infusion on renal function and vasopressin excretion in sheep.

Conscious Merino ewes were given an intravenous hypertonic sodium chloride load of 4 mmol.min-1 for 100 min. This resulted in increases in urine flow, sodium and potassium excretion and plasma sodium concentration and osmolality. Urinary vasopressin output and solute-free water reabsorption increased and plasma renin activity declined. Renal plasma flow and glomerular filtration rate (GFR) rose, as did the solute clearance. The change in urinary osmolality was related to the initial urine osmolality such that when the initial urine osmolality was high the urine became more dilute, and vice versa. Tubular sodium reabsorption increased but the fractional reabsorption rate fell. It is suggested that the increase in GFR was at least partly due to the increase in AVP and that the electrolyte loss can be accounted for by the increase in GFR without necessarily involving AVP or other hormonal effects at the tubular level.

The effects of two analogues of arginine-vasopressin (ornithine-vasopressin and desamino-D-arginine-vasopressin) on kidney function in sheep.

The effects of intravenous infusion of ornithine-vasopressin (OVP) and desamino-D-arginine-vasopressin (dDAVP) were studied in normal and hydrated Merino sheep. In normal sheep, OVP resulted in a diuresis, increased urinary sodium and potassium excretion, and a fall in the plasma potassium concentration. Renal plasma flow remained constant but glomerular filtration rate and filtration fraction rose markedly. dDAVP in normal sheep was antidiuretic, but its only significant effect was a small decrease in plasma osmolality. In the hydrated sheep OVP was antidiuretic and resulted in increased urinary excretion of sodium and potassium, and a fall in the plasma potassium level. Renal plasma flow fell, but glomerular filtration and filtration fraction tended to rise. dDAVP in the hydrated sheep was also antidiuretic but urinary sodium and potassium excretion was reduced. Renal plasma flow and glomerular filtration fell, with a small decrease in filtration fraction. These results suggest that the diuretic effect in normal sheep and the electrolyte-excreting effects in both normal and hydrated sheep of OVP are related to the increase in glomerular filtration, which in turn is dependent on the vasopressor activity of the hormone. The increase in glomerular filtration caused by OVP is due to an increase in the filtration fraction of an unchanged renal plasma flow, which could be brought about by an increase in renal efferent arteriolar tone. The effects of hydration of the sheep were the conventional increased urine flow, decreased urine osmolality and decreased solute-free water reabsorption. Sodium and potassium excretion rose slightly and plasma osmolality fell. Renal plasma flow and glomerular filtration both increased with little change in filtration fraction. These effects could be brought about by suppression of endogenous vasopressin and a decrease in both afferent and efferent renal arteriolar tone.

The composition and flow of parotid saliva during acute hyperkalaemia in sodium-deficient sheep.

Sheep were infused intravenously with 0-43 M-KCl at 2 ml/min for 2 hr while they were either sodium-replete or sodium-deficient after the unilateral loss of parotid saliva for 18 hr or 3 days. Salivary flow was depressed during potassium infusion and the flow rates observed at maximum hyperkalaemia were similar in all three states of sodium balance despite the large differences in flow rate before potassium infusion. The fall in salivary Na/K ratio during potassium administration was diphasic, the initial decline being slow and followed by a more rapid fall in the ratio. The duration of the initial period of slow decline in this ratio ranged from 75-105 min, 45-60 min, and about 15 min in the sodium-replete, mildly sodium-deficient and severely sodium-deficient states respectively. The decline in salivary flow during sodium depletion was associated with decreasing salivary bicarbonate concentration and increasing salivary phosphate and hydrogen ion concentrations with the concentration of chloride showing no consistent trend. During acute hyperkalaemia the chloride and phosphate concentrations were negatively correlated with salivary flow, the bicarbonate concentration was positively correlated with flow and the hydrogen ion concentration was unaltered. The sodium concentration of the saliva showed a statistically significant correlation with flow only when the sheep were severely sodium-deficient.