Decreased rotational flow and circumferential wall shear stress as early markers of descending aorta dilation in Marfan syndrome: a 4D flow CMR study.

BACKGROUND: Diseases of the descending aorta have emerged as a clinical issue in Marfan syndrome following improvements in proximal aorta surgical treatment and the consequent increase in life expectancy. Although a role for hemodynamic alterations in the etiology of descending aorta disease in Marfan patients has been suggested, whether flow characteristics may be useful as early markers remains to be determined. METHODS: Seventy-five Marfan patients and 48 healthy subjects were prospectively enrolled. In- and through-plane vortexes were computed by 4D flow cardiovascular magnetic resonance (CMR) in the thoracic aorta through the quantification of in-plane rotational flow and systolic flow reversal ratio, respectively. Regional pulse wave velocity and axial and circumferential wall shear stress maps were also computed. RESULTS: In-plane rotational flow and circumferential wall shear stress were reduced in Marfan patients in the distal ascending aorta and in proximal descending aorta, even in the 20 patients free of aortic dilation. Multivariate analysis showed reduced in-plane rotational flow to be independently related to descending aorta pulse wave velocity. Conversely, systolic flow reversal ratio and axial wall shear stress were altered in unselected Marfan patients but not in the subgroup without dilation. In multivariate regression analysis proximal descending aorta axial (p = 0.014) and circumferential (p = 0.034) wall shear stress were independently related to local diameter. CONCLUSIONS: Reduced rotational flow is present in the aorta of Marfan patients even in the absence of dilation, is related to aortic stiffness and drives abnormal circumferential wall shear stress. Axial and circumferential wall shear stress are independently related to proximal descending aorta dilation beyond clinical factors. In-plane rotational flow and circumferential wall shear stress may be considered as an early marker of descending aorta dilation in Marfan patients.

Short communication: Passive shedding of Mycobacterium avium ssp. paratuberculosis in commercial dairy goats in Brazil.

Goat farming is a low-cost alternative to dairy production in developing countries. In Brazil, goat production has increased in recent years due in part to the implementation of programs encouraging this activity. Mycobacterium avium ssp. paratuberculosis (MAP) is the causative agent of paratuberculosis, a disease that causes chronic granulomatous enteritis in ruminants, but MAP transmission dynamics are still poorly understood in goats. In a previously published study of our research group, 10 dairy goat farms (467 animals) from Minas Gerais state were analyzed for MAP detection; 2 fecal cultures and 11 milk samples tested positive for MAP by conventional PCR and were confirmed by sequencing. Because no clinical signs were observed over 1 yr of monitoring, we hypothesized that these MAP-positive goats could be passive shedders. Thus, in the present study, 4 positive goats (4/13) from the previous study were purchased and feces and milk samples were collected for evaluation (twice, with an interval of 3 mo between tests) by culture of MAP, IS900 PCR, or both. All analyses were negative for MAP. At the last time point, blood samples were collected for ELISA, the animals were killed, and tissues collected for tissue culture and histopathology. At necropsy, no macroscopic lesions related to paratuberculosis were observed. Similarly, no histological changes were observed and MAP in samples stained by Ziehl-Neelsen was not detected. These animals were characterized as potential passive shedders with upward contamination of the teat canal by MAP. This is the first report of the passive shedding phenomenon in goats in Brazil and it highlights the importance of identifying these animals for control programs and to ensure the quality of dairy products.

Comprehensive analysis of RET gene should be performed in patients with multiple endocrine neoplasia type 2 (MEN 2) syndrome and no apparent genotype-phenotype correlation: an appraisal of p.Y791F and p.C634Y RET mutations in five unrelated Brazilian families.

BACKGROUND: We previously identified a four-generation family with medullary thyroid cancer (MTC) and a germline p.Y791F RET mutation whose cancer lacked a strong genotype-phenotype correlation. The entire gene coding region of the RET gene should be sequenced when genotype-phenotype discrepancies are observed in patients with multiple endocrine neoplasia type 2 (MEN 2), even if a RET hotspot mutation has been identified. METHODS: A new genetic test was performed in the index case of this family with the p.Y791F RET germline mutation. The entire coding region of the RET gene was investigated by direct sequencing of PCR products. Once a mutation was identified, the target exon was sequenced in all at-risk relatives. RESULTS: An additional p.C634Y germline mutation in the RET gene was identified in the reported family. The double mutation occurred in cis and segregated with the phenotype. Through the Brazilian Genetic Screening Program developed at our institution, we additionally report the combination of these two mutations (p.C634Y/p.Y791F) in the RET gene in four other unrelated families. The overall penetrance of MTC and pheochromocytoma in patients with the p.C634Y/p.Y791F mutations was 79% and 13%, respectively. CONCLUSION: Our data emphasises that a comprehensive analysis of the RET gene may reveal multiple germline mutations in MEN 2 patients who exhibit an atypical clinical course of the disease.

Heart failure: molecular, genetic and epigenetic features of the disease.

Factors that compete to establish heart failure (HF) are not completely known. In the last years the several technological improvements allowed us to deeply study the molecular and genetic aspects of this complex syndrome. This new approach to HF based on molecular biology new discoveries shows us more clearly the pathophysiological bases of this disease, and a future scenery where the genetics may be useful in the clinical practice, as screening of high risk populations, as well as in the diagnosis and therapy of underlying myocardial diseases. The purpose of this review was to analyse the molecular, genetic and epigenetic factors of HF. We described the molecular anatomy of the sarcomere and the pathogenesis of the heart muscle diseases, abandoning the previous monogenic theory for the concept of a polygenic disease. Different actors play a role to cause the illness by themselves, modifying the expression of the disease and, eventually, the prognosis of the patient.

Magnetic resonance hysterosalpingography in the evaluation of tubal patency in infertile women: an observational study.

The purpose of this study was to evaluate the ability of magnetic resonance hysterosalpingography (MR-HSG) to demonstrate fallopian tube patency in infertile women and to improve the MR-HSG technique. Sixteen consecutive infertile women were recruited for this trial. All subjects underwent clinically indicated MR-HSG: 10-15 ml of 1:10 solution of gadolinium and normal sterile saline (0.9%) was gently hand-injected intracervically through a 7 French balloon catheter while seven consecutive flash-3D dynamic (FL 3D DY) T1-weighted MR sequences were acquired. Two readers independently assessed image quality as well as anatomic and pathologic correlations. Patient comfort was evaluated using a specific score questionnaire. MR-HSG was successfully completed in all patients. In 14/16 (87.4%) patients, MR-HSG showed bilateral tubal patency with symmetric contrast agent diffusion and a regular tubo-ovarian relationship. One patient (6.3%) with monolateral hydrosalpinx presented no contrast agent diffusion in the affected side (monolateral tubal occlusion); in another patient (6.3%) the fallopian tube was displaced upward causing loss of the tubo-ovarian anatomical relationship resulting in asymmetric and inadequate contrast agent diffusion. Eight women (50%) were found to have abnormalities on MR imaging; these abnormalities included multi follicular ovaries (5 cases 31.1%), endometrioma (1 case, 6.3%), leiomyoma (1 case/6.3%) and endometrial polyp (1 case/6.3%). The average time required for the study was 25-30 minutes. Analysis of the questionnaires administered to the patients showed that 15/16 patients (93.7%) were fully satisfied with the procedure. All examinations were judged to be of high diagnostic quality and the two readers made similar diagnoses. In conclusion, MR-HSG is a feasible, useful and well tolerated tool for the assessment of the uterus, fallopian tubes, ovaries and extra-uterine structures. MR-HSG is a new promising imaging approach to female infertility.

Benefits of kinesiotherapy and aquatic rehabilitation on sickle cell anemia. A case report.

The process of hemoglobin polymerization and the consequent sickling of red blood cells that occurs in patients with sickle cell disease shortens the half-life of red blood cells. It causes vaso-occlusive complications, as well as pain and pulmonary and cardiovascular dysfunction. We evaluated an aquatic rehabilitation program used for patients with sickle cell anemia and examined the possible benefits that exercise in warm water has for the circulatory system, for relieving pain, and for increasing lung capacity. The patient was a 32-year-old female. The parameters that we used in this study include respiratory muscle strength (which was calculated by measuring maximum inspiratory pressures and maximum expiratory pressures), the McGill and Wisconsin pain questionnaires (in order to evaluate the patients' characterizations and descriptions of their pain), and the SF-36 Health Survey. The treatment included warm water exercises, stretching, aerobic exercise, and relaxation, during two sessions of 45 min per week for 5 weeks. The patient experienced a significant decrease in pain, a significant increase in the strength of respiratory muscles, and improved quality of life. We conclude that aquatic rehabilitation can be used to improve the clinical condition of sickle cell anemia patients, and we encourage more research on this new treatment regime, in comparison with other types of therapies.

Orthodontic treatment need and timing: Assessment of evolutive malocclusion conditions and associated risk factors.

AIM: Orthodontic treatment need indexes are indispensable tools for collecting aepidemiological information, to define the need for clinical intervention on a graduated risk scale and to monitor the evolution of clinical conditions over time. The purpose of this research is to evaluate the prevalence of malocclusion and associated risk factors, and to compare the prevalence of malocclusion related to children's growth. Investigating the correlation between malocclusion and dental occlusion development is crucial to define orthodontic timing and the most suitable treatment modalities. MATERIALS AND METHODS: A cross-sectional, multi-center, observational study was carried out throughout Italy: 4,422 patients aged between 2 and 13 years were visited. The patients were divided into two age groups: one composed of patients aged 2 -7 years, and one of children between 8 and 13 years of age. The prevalence data were classified according to the items of the Baby ROMA (first group, deciduous/early mixed dentition) and ROMA Index (second group, late mixed/permanent dentition). Pearson's Chi-square test was applied for the calculation of statistical significance in the comparison of prevalence data between the two age groups (P <0.05). RESULTS: The need for orthodontic treatment among Italian children is high. In the sample aged between 2 and 7 years, the most frequent malocclusions are the moderate and severe open bite (23%), moderate and severe Class II (21.2%), deep bite (18.8%), cross bite (16.5%), Class III (7.7%), and crowding (5.1%). In the sample aged between 8 and 13 years the most frequent malocclusions are crowding (50.8 %), Class II (33.1%), deep bite (19.2%) crossbite (18.1%), Class III (9.1%), open bite (6.6%), facial or mandibular asymmetries (3.3%), and functional asymmetries (3.2%). It was found a statistically significant variation of the different malocclusion conditions according to age. CONCLUSION: The study confirms that some risk factors occur during growth, and worsen the malocclusion. Therefore, it is important to reduce this risk of worsening by counteracting those factors with an early orthodontic intervention. Some malocclusions are less affected by environmental risk factors. In these case it would be better defer treatment until adolescence.

The evolution and diversity of TNF block haplotypes in European, Asian and Australian Aboriginal populations.

The region spanning the tumour necrosis factor (TNF) cluster in the human major histocompatibility complex is implicated in susceptibility to immunopathological disease, but ethnic differences and linkage disequilibrium have hampered identification of critical polymorphisms. Here, we investigate Europeans, Asians (Bidayuh, Chinese, Indian, Jehai, Malay, Temuan) and Australian Aborigines to provide a framework for disease-association studies. DNA from 999 unrelated healthy donors was genotyped at 38 loci, primarily in coding and promoter regions over a 60-kb region spanning seven genes near TNF. The PHASE algorithm was used to statistically infer TNF block haplotypes and estimate their frequencies in each population. The TNF block is carried as 31 haplotypes in all populations combined, with <19 in any single population. Only six haplotypes have a unique tag single nucleotide polymorphism (SNP) valid for all populations, but seven haplotypes could be tagged with individual SNPs in selected populations. Four to eight TNF block haplotypes exist across all ethnicities, and hence must pre-date the divergence of these populations from a common ancestor >160,000 years ago. Some haplotypes are unique to isolated populations, but they do not contain unique SNP. Hence, they reflect restricted migration and/or extinction of some families rather than de novo mutation.

TNF block haplotypes associated with conserved MHC haplotypes in European, Asian and Australian Aboriginal donors.

Associations between major histocompatibility complex (MHC) ancestral haplotypes (AHs) and immunopathological diseases are traditionally ascribed to human leukocyte antigen (HLA) class I or class II alleles. However, polymorphisms in TNF and nearby genes in the central MHC can influence risk. We have defined TNF block haplotypes in Asian, European and Australian Aboriginal donors and shown conservation of TNF block haplotypes in geographically distinct populations, consistent with a common evolutionary origin. Here we show that most TNF block haplotypes do not align with a single MHC AH and associations often vary with ethnicity. This suggests more recent recombination events between the TNF block and the HLA alleles.

Relationships between eye fluids and blood values after exercise in lidia cattle: mineral parameters.

Eye fluids (aqueous humour and vitreous humour) may be helpful in estimating ante-mortem blood levels, since some parameters measured in these fluids have proved to be stable or to change in a predictable way after death. This would help in diagnosing the cause of death in some diseases or to evaluate ante-mortem blood levels in certain animals not easy to handle or with difficult access. In order to establish reference values of some parameters in blood and eye fluids (aqueous humour and vitreous humour), as well as the possible correlation among these three different fluids, various minerals and electrolytes (Ca, P, Mg, K, Na, Fe, Cr, Co, Ni, Cu, Zn, Se and Mo) were measured in 15 four to five year-old Lidia bulls, all dying after a period of significant stress and major exertion. Plasmatic values of Mg and P were much greater than reported in the literature. In general, mineral plasmatic values were greater than those found in ocular fluids (aqueous and vitreous), while Na, K and Cr were similar in the three fluids. We have verified the existence of correlations in P, Co and Mo among the three fluids measured, and between Se of plasma and vitreous humour. But the most marked correlations were observed in Mo (plasma -aqueous humour, r = 0.893, plasma-vitreous humour, r = 0.945, HA -HV, r = 0.849), in P (plasma-vitreous humour, r = 0.726) and in Co (plasma-vitreous humour, r = 879).

[Vascular access for dialysis in elderly: AVF versus permanent CVC]. / L'accesso vascolare nell'anziano: confronto FAV versus CVCp.

The type of hemodialysis vascular access (fistula, graft, catheter) employed plays an important role in the results of dialysis treatment. Moreover, different complications can affect the vascular access and interfere with the morbidity and mortality of patients. The ideal vascular access is the Cimino Brescia fistula, followed by graft. Tunnelled central venous catheters should be considered as 'second choice' because they present a higher incidence of complications, mainly due to thrombosis and infections. Finally, in elderly patients the vascular bed is frequently damaged and this may make it difficult to create a Cimino (Brescia) fistula (AVF). The use of instrumental tests, as echo-color Doppler or angiography in order to evaluate the real status of vascular bed in elderly patients can offer a great opportunity in order to find the best position where it is possible to create a fistula or graft. We suggest that a native fistula can be easily created in elderly patients and the 'second choice' access should be limited to a small proportion of patients. Although patient selection is important, even patients of 80 years or older who are considered suitable for surgical placement of access should not be denied an AVF solely because of age. Nephrologists or vascular surgeons, who create vascular access, should develop a good patient and site selection to predict which vascular access will function successfully rather than risk complications of prolonged central catheters.

Water-use strategies in two co-occurring Mediterranean evergreen oaks: surviving the summer drought.

In the Mediterranean evergreen oak woodlands of southern Portugal, the main tree species are Quercus ilex ssp. rotundifolia Lam. (holm oak) and Quercus suber L. (cork oak). We studied a savannah-type woodland where these species coexist, with the aim of better understanding the mechanisms of tree adaptation to seasonal drought. In both species, seasonal variations in transpiration and predawn leaf water potential showed a maximum in spring followed by a decline through the rainless summer and a recovery with autumn rainfall. Although the observed decrease in predawn leaf water potential in summer indicates soil water depletion, trees maintained transpiration rates above 0.7 mm day(-1) during the summer drought. By that time, more than 70% of the transpired water was being taken from groundwater sources. The daily fluctuations in soil water content suggest that some root uptake of groundwater was mediated through the upper soil layers by hydraulic lift. During the dry season, Q. ilex maintained higher predawn leaf water potentials, canopy conductances and transpiration rates than Q. suber. The higher water status of Q. ilex was likely associated with their deeper root systems compared with Q. suber. Whole-tree hydraulic conductance and minimum midday leaf water potential were lower in Q. ilex, indicating that Q. ilex was more tolerant to drought than Q. suber. Overall, Q. ilex seemed to have more effective drought avoidance and drought tolerance mechanisms than Q. suber.

Crystallization and preliminary structure determination of the membrane-bound complex cytochrome c nitrite reductase from Desulfovibrio vulgaris Hildenborough.

The cytochrome c nitrite reductase (cNiR) isolated from Desulfovibrio vulgaris Hildenborough is a membrane-bound complex formed of NrfA and NrfH subunits. The catalytic subunit NrfA is a soluble pentahaem cytochrome c that forms a physiological dimer of about 120 kDa. The electron-donor subunit NrfH is a membrane-anchored tetrahaem cytochrome c of about 18 kDa molecular weight and belongs to the NapC/NirT family of quinol dehydrogenases, for which no structures are known. Crystals of the native cNiR membrane complex, solubilized with dodecylmaltoside detergent (DDM), were obtained using PEG 4K as precipitant. Anomalous diffraction data were measured at the Swiss Light Source to 2.3 A resolution. Crystals belong to the orthorhombic space group P2(1)2(1)2(1), with unit-cell parameters a = 79.5, b = 256.7, c = 578.2 A. Molecular-replacement and MAD methods were combined to solve the structure. The data presented reveal that D. vulgaris cNiR contains one NrfH subunit per NrfA dimer.

tTGase/G alpha h protein expression inhibits adenylate cyclase activity in Balb-C 3T3 fibroblasts membranes.

Stably transfected Balb-C 3T3 fibroblasts (clone 5), overexpressing a catalytically active tissue transglutaminase, showed a basal adenylate cyclase activity lower than control cells (clone 1). Several modulators of the adenylate cyclase activity (forskolin, Mn2+ and pertussis toxin) showed the existence of a marked negative control on the adenylate cyclase activity present in clone 5 cells. Very interestingly, this same marked negative control was also found in a Balb-C 3T3 fibroblast clone stably transfected with a mutagenized human tissue transglutaminase (mut277 cys > ser) virtually devoid of transglutaminase catalytic activity (clone Ser). Conversely, a significant increase of the adenylate cyclase activity was observed in bovine aortic endothelial cells after the lowering of tissue transglutaminase expression levels by the transfection of an eukaryotic expression vector containing the gene for tissue transglutaminase in antisense orientation. All these findings suggest a possible role for type II tissue transglutaminase as a negative modulator of the adenylate cyclase activity in different cell types, beside its transglutaminase enzyme activity.

Principal component analysis of some oxidative stress parameters and their relationships in hemodialytic and transplanted patients.

BACKGROUND: Oxidative stress profoundly influences the biochemistry of proteins and many other molecules in tissues of uremic patients. In three different groups of uremic patients, the concentrations of the free and bound pentosidine and low-molecular-weight-advanced glycoxydation end products (LMW-AGEs), carbonyls (LMW-C), advanced oxidation protein products (AOPP) and the total antioxidant power of serum were studied in order to determine the relationships between these factors in hemodialytic and transplanted patients. PATIENTS AND METHODS: The above-mentioned parameters were determined in 10 subjects who were currently in hemodialysis (HD) treatment, 10 kidney transplanted patients with chronic renal failure (Tx-CRF), 10 kidney transplanted patients with normal renal function (Tx-N) and 10 healthy subjects (Ctr). The data matrix (40x7) was analyzed using the principal component analysis (PCA). RESULTS: AGEs, carbonyls and AOPP were strongly correlated, while the total antioxidative serum capacity was not related to the other oxidative stress parameters. All the oxidative stress-related parameter values (AGEs, AOPP and LMW-C) in the Tx patients were similar to those of the control group, but were higher in the patients with chronic renal failure. CONCLUSIONS: The correlation between early and advanced oxidative stress markers indicates that reactive oxygen species are involved in a common step in the mechanism of protein modification in all the patient examined. The relationships between carbonyls and AGEs (free, bound pentosidine and LMW-AGEs) support the hypothesis of "carbonyl stress". The common mechanism of the formation of oxidation products in healthy and diseased subject suggests their role of detoxification within kidney function. The total antioxidant power of the serum is not related to the other parameters, which indicates a possible role of molecule interfering.

Evidence against depletion of the growth hormone (GH)-releasable pool in human primary hypothyroidism: studies with GH-releasing hormone, pyridostigmine, and arginine.

We investigated whether the impaired GH secretion of hypothyroid patients could be due to an increase in hypothalamic somatostatinergic tone. Twenty-four patients with primary hypothyroidism [20 females and 4 males; mean age (+/- SE), 47.5 +/- 2.7 yr] and 20 normal subjects (17 females and 3 males; age, 47.6 +/- 3.0 yr) were studied. In the first group of 12 hypothyroid patients, administration of pyridostigmine, a cholinergic agonist drug (120 mg, orally, at -60 min), notably increased GH responses to GH-releasing hormone (GHRH; 1 microgram/kg, iv, at 0 min; peak GH levels for pyridostigmine plus GHRH vs. placebo plus GHRH, 16.6 +/- 4.9 vs. 6.0 +/- 1.8 micrograms/L; P < 0.01). The GH responses to pyridostigmine plus GHRH, however, were considerably lower than those in 10 normal subjects (peak GH levels, 53.0 +/- 3.5 micrograms/L; P < 0.001). In the second group of 12 hypothyroid patients, arginine infusion (30 g, iv, from 0-30 min) markedly increased the GH responses induced by GHRH administration (1 microgram/kg, iv, at 0 min; peak GH levels for arginine plus GHRH vs. placebo plus GHRH, 30.6 +/- 4.7 vs. 5.3 +/- 1.0 micrograms/L; P < 0.001). However, GH release after GHRH plus arginine was greater in 10 normal subjects than in the hypothyroid patients (peak GH levels, 50.9 +/- 5.3 micrograms/L; P < 0.001). Pyridostigmine and arginine inhibit hypothalamic somatostatin tone. The stimulatory effect of both agents on GHRH-induced GH release indicates that reduced GH secretion in hypothyroidism can be reversed to a considerable extent by inhibiting hypothalamic somatostatinergic tone. The relatively greater potency of arginine compared to pyridostigmine suggests that hypothyroid patients may have an impairment of the cholinergic pathways. Furthermore, these data show that hypothyroid patients have a somatotrope secretory capacity much greater than previously thought.

Growth hormone (GH) responsiveness to combined administration of arginine and GH-releasing hormone does not vary with age in man.

At present, the mechanism(s) underlying the reduced spontaneous and stimulated GH secretion in aging is still unclear. To obtain new information on this mechanism(s), the GH responses to both single and combined administration of GH-releasing hormone (GHRH; 1 microgram/kg iv) and arginine (ARG; 30 g infused over 30 min), a well known GH secretagogue probably acting via inhibition of hypothalamic somatostatin release, were studied in seven elderly normal subjects and seven young healthy subjects. Basal GH levels were similar in both groups, while insulin-like growth factor-I levels were lower in elderly subjects (76.7 +/- 9.2 vs. 258.3 +/- 29.2 micrograms/L; P = 0.01). In aged subjects GHRH induced a GH increase (area under the curve, 314.9 +/- 91.9 micrograms/L.h) which was lower (P = 0.01) than that in young subjects (709.1 +/- 114.4 micrograms/L.h). On the other hand, the ARG-induced GH increase in the elderly was not significantly different from that in young subjects (372.8 +/- 81.8 vs. 470.6 +/- 126.5 micrograms/L.h). ARG potentiated GH responsiveness to GHRH in both elderly (1787.1 +/- 226.0 micrograms/L.h; P = 0.0001 vs. GHRH alone) and young subjects (2113.0 +/- 444.3 micrograms/L.h; P = 0.001 vs. GHRH alone). The potentiating effect of ARG on the GHRH-induced GH response was greater in elderly than in young subjects (1013.0 +/- 553.5% vs. 237.9 +/- 79.1%; P = 0.0001); thus, the GH increase induced by combined administration of ARG and GHRH overlapped in two groups. In conclusion, these results show that, differently from the GHRH-induced GH increase, the somatotroph response to combined administration of ARG and GHRH does not vary with age. Our finding suggests that an increased somatostatinergic activity may underlie the reduced GH secretion in normal aging.

ras oncogene-induced transformation of a rat seminal vesicle epithelial cell line produces a marked increase of adenylate cyclase and protein kinase C activities.

Cells transformed by Kirsten murine sarcoma virus (Ki-MSV) have basal adenylate cyclase activity (AC) higher than control cells and comparable level of forskolin-stimulated AC activity. Moreover, a higher protein kinase C (PKC) activity was found to be present in the transformed cells. The molecular mechanism underlying the increase of AC activity was investigated. Our findings strongly suggest that this biochemical event is due to a marked decrease of the alpha i negative control of the enzyme, even though the alpha i of transformed cells appears to possess fully functional domains interacting with both the effector enzyme and the agonist-activated receptor.

Introduction: the EUROCARE II Study.

This introduction provides a general overview of the aims, methods and procedures used in the EUROCARE II study and the types of analyses presented in each article of this Special Issue of the European Journal of Cancer. The main aims of the EUROCARE II project are the updating of the survival database of the European Cancer Registries, the study of recent trends in relative survival rates and the interpretation of the survival differences observed both in time and across populations. Once having completed the preliminary stage of data checking, a total of 3,473,659 individual records from patients of all cancer sites, diagnosed between 1978 and 1989 and provided by 45 cancer registries in 17 European countries were accepted to build up the EUROCARE database. The quality of these data, in terms of the accuracy of the diagnosis and the validity of vital status assessment, was checked by indirect indicators, based on cross-validation analysis of consistency of the relevant variables. Statistical analysis was based on age-specific relative survival rates, computed for each cancer sites as the ratio of observed survival to the expected survival of the general population of the same area, gender and age, according to the Hakulinen method. An estimate of the European survival was computed as a weighted mean of the corresponding survival of the different countries, using as weights the expected yearly number of incident cases in each country. For comparison purposes, age-standardised survival was also calculated for Europe and for each country involved in the study.

Anterior fontanelle pressure variations during sleep in healthy infants.

Our aim was to study the intracranial pressure (ICP) variations during sleep normal infants. Using a noninvasive method, ICP was measured continuously during polysomnography in 12 healthy infants aged from 1 to 11 months (median 3.5 months). We analyzed the variations of mean basal ICP, mean basal pulse pressure amplitude and maximal amplitude of both plateau and B-like waves between transient sleep, quiet sleep and rapid eye movement (REM) sleep. Mean ICP, mean pulse pressure amplitude and B-like wave amplitude increased significantly during transient sleep and REM sleep. Plateau waves occurred during transient sleep and especially REM sleep. By contrast, noninvasive ICP recordings were relatively flat during quiet sleep stages 2 and 3. ICP variations and pressure waves seem to be related to cerebrovascular changes associated with sleep. The physiological ICP variations during sleep must be known in order to allow correct interpretation of continuous ICP measurements in infants.