[Evaluation of the accuracy of volume navigation of sonography and computed tomography using a phantom]. / Genauigkeitsevaluierung der Volumennavigation von Sonografie und Computertomografie anhand eines Phantoms.

BACKGROUND AND OBJECTIVE: In case of superimpositions of gas in the gastrointestinal tract or the ribs, tissue changes well detectable on computed tomography (CT) cannot be identified sonographically in a number of cases. Combining ultrasonography and CT provides enhanced information compared to sole sonography and volume navigation may be used as an effective tool. Tissue samples easily and safely obtained under sonographic guidance are often necessary to confirm the diagnosis of a suspicious focus. In these cases, the spatial fusion of CT and sonography may also be employed for improved visualization of foci by eliminating superimposition of sonographic images which is a limitation of ultrasound. This study investigated the potential benefit and improved informative value of the fusion of CT and sonography in case of superimpositions and aimed at determining the registration method with the best accuracy. MATERIALS AND METHODS: Sixteen models (10 models with peas [low contrast], 6 models with wooden spheres [high contrast] as round structures) were created. These models were examined by computed tomography and fused using 3 volume navigation protocols. Subsequently, volume-guided sonography was performed. The deviation of the specimens was measured. RESULTS: In total, 1026 measurements of the pea models and 648 measurements of the wooden sphere models were carried out. A fusion accuracy of 100 % was observed in 9.9 % (102/1026) resp. 9.9 % (64/648) of the models. In 85.4 % (876/1026) resp. 94.1 % (610/648) the deviation was < 5 mm and in 98.1 % (1006/1026) resp. 99.4 % (644/648) it was < 10 mm. The registration protocol in which all reference points were used for spatial fusion proved to be the most accurate CONCLUSION: The registration protocols for volume-guided ultrasound have sufficient biopsy accuracy to merge identical sites and provide the basis for improved volume-navigated biopsy sampling.

[Complications of ultrasound-guided liver biopsies in dogs and cats]. / Komplikationen sonographisch gestützter Leberbiopsien bei Hund und Katze.

OBJECTIVE: Ultrasound-guided biopsies are obtained generally to reach a sound diagnosis in the case of sonographically detectable hepatic changes. The most common and well-known complication associated with ultrasound-guided biopsies is haemorrhage after sampling, which may lead to the patient's death. The aim of this study was to evaluate a possible association between alterations in the coagulation parameters and sonographically observable haemorrhage following liver biopsies. MATERIALS AND METHODS: Dogs and cats in which an ultrasound-guided biopsy of the liver had been performed were retrospectively enrolled in the study. Inclusion criteria were thoroughly documented sonographic findings and the results of the coagula tion parameter thromboplastin time or a combination of the activated partial thromboplastin time and prothrombin time. The incidence of post-interventional ascites and possible risk factors were evaluated. RESULTS: A total of 105 patients met the inclusion criteria and the data of 94 dogs (89.5 %) and 11 cats (10.5 %) were analysed. Post-interventional complications occurred in 26 of 105 patients (24.8 %), 21.9 % being minor and 2.9 % being major. Free abdominal fluid after intervention was sonographically detected in 22 of 94 dogs (23.4 %) and four of 11 cats (36.4 %). Three of 10 dogs (2.9 %) with a clinically significant prolongated coagulation time of > 25 % had ascites after biopsy. Only a small amount of fluid was detected in two of these three dogs, while a moderate amount of ascites was observed in the third dog. One of two cats with a prolonged coagulation time of > 25 % developed a moderate amount of ascites after the puncture. No statistically significant association was found between the occurrence of post-interventional ascites and a prolongation of the coagulation time. CONCLUSION: According to the study results, there is no obvi ous correlation between alterations in coagulation and haemorrhage after an ultrasound-guided liver biopsy.

Abdominal pain symptoms are associated with anxiety and depression in young children.

AIM: Abdominal pain symptoms and incontinence are common in childhood. The aim of this study was to analyse abdominal pain symptoms and their associations with incontinence and symptoms of anxiety and depression in young children. METHODS: We examined 1130 children during the school entry check-up (mean age 6.2 years) and 951 participated in the study. Parents completed a questionnaire contained 11 items regarding Rome-III functional gastrointestinal disorders (FGIDs) and incontinence and 14 items from the anxious/depressed scale of the Child Behavior Checklist (CBCL). RESULTS: Of the 951 children (55.6% boys) we recruited, 30.1% had experienced abdominal pain symptoms in the past two months and 14% had complained of them at least once a week. In addition, 2.6% had irritable bowel syndrome, 11.3% had childhood functional abdominal pain, 2.4% were affected by faecal incontinence, 2.1% were affected by daytime urinary incontinence, and 5.5% were affected by nocturnal enuresis. One in ten (10.6%) had symptoms of anxiety and depression, and these were significantly higher in the children with FGIDs, particularly if they were also incontinent. CONCLUSION: Nearly a third of the children (30.1%) had abdominal pain symptoms, and FGIDs were associated with significantly higher symptoms of anxiety and depression, especially if children were also incontinent.

Incontinence and parent-reported oppositional defiant disorder symptoms in young children--a population-based study.

BACKGROUND: Oppositional defiant disorder (ODD) and incontinence are common disorders of childhood. We have examined associations between ODD symptoms and incontinence in a representative sample of young children. METHODS: A questionnaire with seven questions referring to incontinence, eight DSM-IV items of ODD, 15 items of the Home Situations Questionnaire and six items regarding eating, drinking or toileting refusal was administered to the parents of 718 children at school-entry from a defined geographical area at school-entry. RESULTS: Of the 718 6-year-old children included in the analysis, 8.2% had nocturnal enuresis (NE), 1.5% had daytime urinary incontinence (DUI) and 1.1% had faecal incontinence (FI). Significantly more boys than girls had NE (12 vs. 4.3%). Overall, 6.7% of children had ODD symptoms. Rates of ODD symptoms were significantly higher in incontinent children (19.5%) than in continent children (5.2%), with the highest rate of ODD symptoms in children with DUI (36.4%). Children with incontinence (mean 6.1 episodes) or ODD symptoms (mean 8.4 episodes) showed non-compliant behaviours in more problem situations than continent children (mean 4.5 episodes) or children without ODD symptoms (mean 4.5 episodes). CONCLUSIONS: Incontinence and ODD are common comorbid disorders at school-entry age. Boys are more affected by both disorders. Children with DUI have the highest rate of ODD symptoms. As ODD symptoms affect many daily family situations, ODD needs to be diagnosed and treated in children with incontinence, as it can negatively affect compliance.

Eating problems in young children -- a population-based study.

AIM: To analyse the prevalence of atypical eating problems and their associations with anxious or oppositional behaviours in young children. METHODS: One thousand and ninety children examined in the school enrolment test in a defined geographical region were included (544 boys). The parents completed a 25-item questionnaire regarding their child's eating behaviour and anxious or oppositional behaviours. RESULTS: Half of the parents reported that their child avoids certain foods (53%). Twenty-three percent showed selective eating, 26% showed an aversion against new foods. Children with underweight avoided more types of food and ate smaller amounts than children with normal or overweight. Three groups could be differentiated. Sixty-one percent of the children were 'normal eaters' with avoidance of certain foods, normal weight status and low anxious or oppositional behaviour. Thirty-four percent showed selective and/or restrictive eating, and 5% worried about their weight. Children with selective eating and with weight concerns were more often affected by anxious and oppositional behaviours. CONCLUSION: Atypical eating problems are common in young children. Without accompanying weight loss, behavioural or emotional problems, selective eating should be seen as a normal feature in young eating behaviour. Parents of young children with selective, restrictive eating or with weight worrying and psychological problems should be offered advice/treatment.

Methylation status in females with rett syndrome.

The authors studied methionine and creatine metabolism in females with Rett syndrome. Plasma metabolites (including methionine, homocysteine, guanidinoacetate) and urine creatine/creatinine ratios in 29 females with Rett syndrome were within the age-appropriate range. Although the authors have not been able to identify any abnormalities, it can be speculated that patients with Rett syndrome may benefit from dietary intervention to increase the supply of labile methyl groups to affected tissues.

Primary pigmented nodular adrenocortical disease (PPNAD) and pituitary adenoma in a boy with sporadic Carney complex due to a novel, de novo paternal PRKAR1A mutation (R96X).

We report the sporadic case of a 9 year-old boy with Carney syndrome, who presented with precocious puberty due to the endocrinological effects of primary pigmented nodular adrenocortical disease (PPNAD) and a synchronous pituitary adenoma. The adrenal tumor was removed surgically. Following unsuccessful treatment with bromocriptine the pituitary adenoma was also resected and a residual tumor irradiated. Thirty months after diagnosis the boy is free of symptoms. Mutation screening of the entire coding region of the PRKAR1A gene identified five single nucleotide exchanges, four of which were either heterozygous or homozygous polymorphic variants that were also present in his parents. However, the hitherto unreported disease-relevant mutation R96X in exon 3 had occurred de novo on the paternal allele.

Rapid genetic testing for Gaucher disease by reverse hybridization.

BACKGROUND: We evaluated a reverse hybridization method for the simultaneous detection of nine mutations that are associated with Gaucher disease. RESULTS AND CONCLUSION: Results were in agreement with those obtained by a polymerase chain reaction-restriction digestion method. The hybridization method produced results more quickly and with less operator input.

Plasminogen activator inhibitor 1 4G/5G polymorphism and coagulation factor XIII Val34Leu polymorphism: impaired fibrinolysis and early pregnancy loss.

BACKGROUND: A successful outcome of pregnancy depends on proper placental formation. In the very beginning of this process, trophoblast invasion and fibrin deposition into the wall of the decidual veins play an important part. Two polymorphisms, coagulation factor XIII (FXIII) Val34Leu and plasminogen activator inhibitor 1 (PAI-1) 4G/5G, interfere with fibrin cross-linking and regulation of fibrinolysis and may therefore contribute to early pregnancy loss. METHODS: We enrolled 49 unrelated Caucasian women with a history of two consecutive or three to six nonconsecutive early pregnancy losses and 48 unrelated parous healthy controls without a history of pregnancy loss and evaluated them for the following genetic variants: the factor V Leiden and prothrombin G20210A gene mutations, the methylenetetrahydrofolate reductase C677T and A1298C polymorphisms, and the PAI-1 4G/5G and FXIII Val34Leu polymorphisms. RESULTS: For the isolated occurrence of PAI-1 4G/5G or FXIII Val34Leu, we found no statistically significant difference between cases and controls. For homozygosity of either or compound carrier status of both mutations, the overall relative risk for early pregnancy loss was significantly increased (odds ratio = 2.4; 95% confidence interval, 1.1-5.5; P = 0.032). We observed no statistically relevant association of any of the other tested mutations with early pregnancy loss. CONCLUSION: Homozygosity for PAI-1 4G or FXIII 34Leu polymorphisms as well as compound carrier status is associated with early pregnancy loss.

Analysis of HFE and TFR2 mutations in selected blood donors with biochemical parameters of iron overload.

BACKGROUND AND OBJECTIVES: Hereditary hemochromatosis is a recessive condition characterized by iron accumulation in several organs, followed by organ damage and failure. The disorder is prevalently due to C282Y and H63D mutations in the HFE gene, but additional HFE and TFR2 mutations have been reported. Early iron overload may be assessed by biochemical parameters such as increased transferrin saturation and serum ferritin. DESIGN AND METHODS: Taking advantage of the collection of 178 DNA samples selected for increased transferrin saturation (>50% in males and >45% in females) from a previous large scale screening of Italian blood donors, we simultaneously assessed the presence of 14 hemochromatosis-associated molecular defects (11 of HFE and 3 of TFR2) by a reverse hybridization-based strip assay. RESULTS: In the series studied the overall C282Y allele frequency was 9% and that of the H63D and S65C was 22.2% and 1.4%, respectively. One rare HFE allele (E168Q), but no TFR2 mutation was detected. When checked at a second examination, transferrin saturation was significantly higher in C282Y homozygotes, H63D/ C282Y compound heterozygotes and H63D homozygotes as compared to wild-type subjects (p<0.05). INTERPRETATION AND CONCLUSIONS: Our results confirm previous findings on C282Y and H63D mutations in Italy, show that the C282Y allele frequency is enriched in samples selected for altered iron parameters, and that a few rare genotypes are present in Northern Italy. None of the known TFR2 mutations was identified in this series confirming the preliminary indication of their rare occurrence. Subjects with hemochromatosis-associated genotypes show a persistently higher mean transferrin saturation than do those with wild type genotypes.

Prevalence of C282Y and E168X HFE mutations in an Italian population of Northern European ancestry.

BACKGROUND AND OBJECTIVES: In Italy, the prevalence of C282Y is lower than in Northern European countries. We hypothesized a higher prevalence of C282Y in Northern than in Southern Italian populations. We previously identified a nonsense mutation (E168X) in hemochromatosis probands originating from a region in the north-west of Italy. We aimed to define the prevalence of C282Y and E168X in that region and the origin of the E168X mutation by haplotype analysis. DESIGN AND METHODS: Six-hundred and six blood donors were investigated for C282Y, H63D, S65C and E168X mutations by polymerase chain reaction (PCR)-restriction assays. Three hundred were also tested for rare HFE and TFR2 mutations by reverse-hybridization test strips. D6S265, D6S105 and D6S1281 microsatellites were analyzed to define E168X 6p-associated haplotypes. RESULTS: One C282Y homozygote, thirteen C282Y/ H63D compound heterozygotes, four E168X heterozygotes and three E168X/H63D compound heterozygotes were found. The allele frequencies of C282Y, H63D, S65C, and E168X were 4.7%, 14.9%, 0.74% and 0.58%, respectively. INTERPRETATION AND CONCLUSIONS: The prevalence of C282Y in the region investigated was much higher than that previously reported in Italy. This finding is probably due to the heavy Celtic component of this north-western population and suggests that in populations of Northern Italian descent screening studies for hemochromatosis could be cost-effective. The prevalence of E168X in this region, although low, suggests that the mutation probably originated here many years ago and its frequency increased as a result of a local founder effect. Given its severity, we suggest that the E168X mutation should be searched for in all hemochromatosis patients of Northern ancestry with an incomplete HFE genotype.

Simultaneous detection of multiple familial hypercholesterolemia mutations facilitates an improved diagnostic service in South african patients at high risk of cardiovascular disease.

AIM: DNA testing can provide a definitive diagnosis of familial hypercholesterolemia (FH), even in the absence of the clinical characteristics of this inherited cardiovascular disease (CVD) subtype. Our aim was to design a rapid diagnostic assay capable of simultaneously analyzing seven point mutations in the low-density lipoprotein receptor (LDLR) gene, which occur at high frequency in South African FH patients. METHODS: The test is based on multiplex DNA amplification and hybridization to membrane strips presenting a parallel array of immobilized allele-specific oligonucleotide probes. RESULTS: A reverse-hybridization assay for genotyping LDLR point mutations D154N, D200G, D206E, C356Y, G361V, V408M, and P664L was set-up and validated using pretyped human DNA samples, as well as recombinant plasmid clones containing mutant alleles. The procedure is rapid (6 hours) and may be automated to a large extent. CONCLUSIONS: The new FH strip-assay forms an important part of the comprehensive cardiovascular genetic screen offered routinely to high-risk population groups in South Africa. A genetic approach based on FH testing in conjunction with other 'genetic' CVD risk factors is feasible and justified, since the spectrum of disease-related mutations have been defined to a large extent in the genetically distinct population groups of South Africa. Knowledge of a significantly increased CVD risk due to the presence of gene variations, which can be targeted for risk reduction by the avoidance of relevant environmental risk factors and the appropriate treatment, provides a powerful message to motivate people into implementing preventative measures based on their genetic profile.