Fungi infection in honeybee hives in regions affected by Brazilian sac brood / Contaminação fúngica em colmeias de abelhas de regiões afetadas pela cria ensacada brasileira

The Brazilian Sac Brood is a disease that affects apiaries of Africanized bee hives in Brazil, thereby making them susceptible to high losses. This study investigated the pathogenicity of Africanized bee hives by the entomopathogenic fungi in a Brazilian Sac Brood endemic region. The degree of fungal contamination, presence of mycotoxins in beehive elements, and vulnerability of healthy beehives in environments subjected and not subjected to the disease were investigated. From the contaminating fungal load, species that are mycotoxin producers and pathogenic causing mortality in the bees have been isolated. The analysis of bee pollen and bee bread samples did not show the presence of the toxic pollen of Stryphnodendron (Fabaceae), which has been indicated as the causative agent of mortality in pre-pupal stage larvae. However, bee bread showed the highest correlation between substrate and fungal contamination...

A cria ensacada brasileira é uma doença que afeta apiários de colmeias de abelhas africanizadas no Brasil, tornando-os suscetíveis a perdas elevadas. Este estudo investigou a patogenicidade de fungos entomopatogênicos em colmeias de abelhas africanizadas de uma região endêmica de cria ensacada brasileira. O grau de contaminação fúngica, a presença de micotoxinas em elementos colmeia e a vulnerabilidade das colmeias saudáveis em ambientes sujeitos e não sujeitos à doença foram investigados. A partir da carga fúngica contaminante, espécies produtoras de micotoxinas e patogênicas, que provocam a mortalidade de abelhas, foram isoladas. A análise do pólen e do pão de abelha não demonstrou a presença do pólen tóxico de Stryphnodendron (Fabaceae), que tem sido apontado como agente causador da mortalidade de larvas em fase de pré-pupa. No entanto, o pão de abelha foi o substrato mais correlacionado com a contaminação fúngica...

High proportion of large genomic deletions and a genotype phenotype update in 80 unrelated families with juvenile polyposis syndrome.

BACKGROUND: In patients with juvenile polyposis syndrome (JPS) the frequency of large genomic deletions in the SMAD4 and BMPR1A genes was unknown. METHODS: Mutation and phenotype analysis was used in 80 unrelated patients of whom 65 met the clinical criteria for JPS (typical JPS) and 15 were suspected to have JPS. RESULTS: By direct sequencing of the two genes, point mutations were identified in 30 patients (46% of typical JPS). Using MLPA, large genomic deletions were found in 14% of all patients with typical JPS (six deletions in SMAD4 and three deletions in BMPR1A). Mutation analysis of the PTEN gene in the remaining 41 mutation negative cases uncovered a point mutation in two patients (5%). SMAD4 mutation carriers had a significantly higher frequency of gastric polyposis (73%) than did patients with BMPR1A mutations (8%) (p<0.001); all seven cases of gastric cancer occurred in families with SMAD4 mutations. SMAD4 mutation carriers with gastric polyps were significantly older at gastroscopy than those without (p<0.001). In 22% of the 23 unrelated SMAD4 mutation carriers, hereditary hemorrhagic telangiectasia (HHT) was also diagnosed clinically. The documented histologic findings encompassed a wide distribution of different polyp types, comparable with that described in hereditary mixed polyposis syndromes (HMPS). CONCLUSIONS: Screening for large deletions raised the mutation detection rate to 60% in the 65 patients with typical JPS. A strong genotype-phenotype correlation for gastric polyposis, gastric cancer, and HHT was identified, which should have implications for counselling and surveillance. Histopathological results in hamartomatous polyposis syndromes must be critically interpreted.

[Congenital, solitary hepatic cyst: Observation of the development from birth upon the intervention in the 5th year of life]. / Kongenitale solitäre Leberzyste - Eine Verlaufsbeobachtung von der Geburt bis zur Intervention im 5. Lebensjahr.

BACKGROUND: Sonographic screening helps to discover pathological findings in asymptomatic patients. In these cases the decision about diagnostic and therapeutic consequences is difficult. CASE REPORT: We describe a girl with a congenital small solitary hepatic cyst with rapidly increasing size after the second year, which was interventionally sclerosed at the age of five years. CONCLUSION: Even in cases of small cysts long term follow up investigations are necessary, because the growth rate of the cyst can change.

Analysis of the RET, GDNF, EDN3, and EDNRB genes in patients with intestinal neuronal dysplasia and Hirschsprung disease.

BACKGROUND: Hirschsprung disease (HSCR) is a frequent congenital disorder with an incidence of 1 in 5000 live births, characterised by the absence of parasympathetic intramural ganglion cells in the hindgut resulting in intestinal obstruction in neonates and severe constipation in infants and adults. Intestinal neuronal dysplasia (IND) shares clinical features with HSCR but the submucosal parasympathetic plexus is affected. IND has been proposed as one of the most frequent causes of chronic constipation and is often associated with HSCR. METHODS: We examined 29 patients diagnosed with sporadic HSCR, 20 patients with IND, and 12 patients with mixed HSCR/IND for mutations in the coding regions of the RET, GDNF, EDNRB, and EDN3 genes. The entire coding regions were analysed by single strand conformational polymorphism and DNA sequencing. RESULTS: Only three RET mutations were detected in patients with HSCR. In patients with IND or a mixed HSCR/IND phenotype, no mutations in these genes were observed. While HSCR and HSCR/IND showed over representation of a specific RET polymorphism in exon 2, IND exhibited a significantly lower frequency comparable with that of controls. CONCLUSIONS: The mutation frequency found in our sporadic HSCR patients (10%) and the allelic distribution of RET polymorphisms are comparable with earlier published data. A significantly different allelic distribution in an established HSCR associated polymorphism argues against common genetic pathways for HSCR and IND.

[Peutz-Jeghers syndrome--new possibilities of noninvasive diagnosis]. / Peutz-Jeghers-Syndrom--Neue Möglichkeiten der nichtinvasiven Diagnostik.

The ultrasonographic findings on Peutz-Jeghers syndrome are demonstrated on two cases. As a non-invasive method the digitalized computered sonography may give the opportunity to detect even small polyps. The sensitivity of this method is comparable with the MRI and gives new perspectives in the follow up of Peutz-Jeghers syndrome.

Frequent 4-bp deletion in exon 9 of the SMAD4/MADH4 gene in familial juvenile polyposis patients.

Familial juvenile polyposis (FJP) is a hamartomatous polyposis syndrome characterized by the appearance of juvenile polyps in the gastrointestinal tract. Patients with this syndrome are at an increased risk for cancer of the colon, stomach, and pancreas. Recently, germline mutations in the SMAD4/DPC4 gene (official symbol MADH4) have been found in the majority of patients suffering from FJP. We have examined 11 unrelated patients with FJP for MADH4 germline mutations by direct sequencing of genomic DNA encompassing all 11 exons of the gene. Besides a novel mutation (959-960delAC at codon 277, exon 6) in one patient, we observed a 4-bp deletion (1372-1375delACAG) in exon 9 in two unrelated patients. Examination with microsatellite markers flanking MADH4 supports an independent origin of the mutation in these two families. The same 4-bp deletion in exon 9 has previously been described in three out of nine patients examined for MADH4 mutations. Our results combined with these previous data demonstrate that a unique 4-bp deletion in exon 9 of MADH4 accounts for about 25% of all FJP cases and that other MADH4 mutations occur in an additional 15% of patients. Genes Chromosomes Cancer 25:403-406, 1999.

MR cholangiography in children with autosomal recessive polycystic kidney disease.

BACKGROUND: Magnetic resonance cholangiography (MRC) is a relatively new, non-invasive imaging technique of the biliary tree that has shown good correlation with endoscopic retrograde cholangiopancreatography. The liver manifestation of autosomal recessive polycystic kidney disease (ARPKD) is congenital hepatic fibrosis (CHF). CHF may be accompanied by Caroli's disease, which is characterised by a non-obstructive dilation of the intrahepatic bile ducts. OBJECTIVE: A prospective study was conducted to determine the presence and extent of Caroli's disease in children with ARPKD. MATERIALS AND METHODS: Seven children with ARPKD aged from 3.0 to 10. 1 years were examined. CHF was confirmed in all biopsied cases (5 of 7). All children had been followed by repeated abdominal US examinations for many years. The MR examination included a morphological imaging study using a T2-weighted turbo spin-echo sequence and a heavily T2-weighted inversion-recovery turbo spin-echo sequence with three-dimensional maximum intensity projection (MIP) reconstructions for MRC. RESULTS: The diagnosis of Caroli's disease could be made in one case by US; in two other children Caroli's disease was suspected, but the differentiation from hepatic cysts was not possible. By MRC, Caroli's disease could be diagnosed in three of seven children. Furthermore, MRC with MIP reconstructions demonstrated the extent of the disease by showing the entire biliary tree from different angles. CONCLUSIONS: MRC is a valuable method to establish the diagnosis and demonstrate the extent of Caroli's disease.

[3D-TSE MR cholangiopancreatography with breath triggering to clarify unclear hepatopathies in children]. / 3D-TSE MR-Cholangiopankreatikographie mit Atemtriggerung zur Abklärung von unklaren Hepatopathien bei Kindern.

PURPOSE: Evaluation of 3D-TSE MR-cholangiography with respiratory triggering in the work up of hepatopathies in infants and young children. PATIENTS AND METHOD: 16 infants (4-16 years) with increased transaminases, two with recurrent pancreatitis, were examined at 1.5 T (ACS-NT II, Philips Medical Systems) using a 3D-TSE MRCP with respiratory triggering in addition to a regular MRI of the liver. The MRCP was compared to ERCP. Two radiologists and one gastroenterologist evaluated the technical quality, visualization of the pancreaticobiliary system, and the diagnostic value of the examinations. RESULTS: Technically feasible were 14/16 MRCPs and 13/16 ERCPs. Two MRCP were not of diagnostic value due to motion artifacts and in three ERCP cannulation of the papilla was not possible. 14/16 ERCP required general anaesthesia, while MRCP needed i.v. sedation in two patients only. Extrahepatic ducts/cystic duct/pancreatic duct were visualized in 14/12/8 patients using MRCP, and in 13/10/3 patients using ERCP, both without adverse effects or complications. Intrahepatic ducts were better delineated with MRCP. In 10 patients with histologically proven periportal fibrosis (n = 7) and liver fibrosis (n = 1) or antineutrophil cytoplasmatic antibodies and associated inflammatory bowel disease, MRCP and ERCP revealed pathological results. CONCLUSION: MRCP using a 3D-TSE sequence with respiratory triggering is a good non-invasive technique for delineation of the biliary tract in infants and young children for the work up to hepatopathies.

Dual versus triple therapy of Helicobacter pylori infection: results of a multicentre trial.

OBJECTIVE: To compare dual therapy (omeprazole and amoxicillin) with triple therapy (omeprazole, amoxicillin, and clarithromycin) in the treatment of Helicobacter pylori infection. The efficacy of 1 mg/kg/day omeprazole was randomly compared with 2 mg/kg/day. STUDY DESIGN: 252 patients (median age, 11.0 years; range, 3-18) presenting with chronic abdominal pain underwent endoscopy and a 13C-urea breath test. Gastric biopsy specimens were taken for histological examination and for the rapid urease test. Patients were treated for two weeks: group A (n = 63) received amoxicillin (50 mg/kg; maximum, 2 g/day), group B (n = 73) received amoxicillin and clarithromycin (20 mg/kg; maximum, 1 g/day). Both groups were randomly treated with either 1 or 2 mg/kg omeprazole (maximum, 80 mg/day). Diagnostic procedures were repeated four weeks after the end of treatment. RESULTS: 11 patients were excluded; 136 patients were H pylori positive (56%), 105 of whom were re-examined after treatment. Helicobacter pylori was eradicated in 52% of group A and 83% of group B. The dose of omeprazole had no influence on the eradication rate. Specificity and sensitivity of the rapid urease test were 94% and 93%, respectively. Specificity and sensitivity of the 13C-urea breath test were 93% and 95%, respectively. CONCLUSIONS: Dual therapy can no longer be recommended. Triple therapy is more effective than dual therapy in the eradication of H pylori infection. The lower dose of 1 mg/kg omeprazole was as effective as 2 mg/kg.

Rectal biopsy for diagnosis of intestinal neuronal dysplasia in children: a prospective multicentre study on interobserver variation and clinical outcome.

BACKGROUND: Intestinal neuronal dysplasia (IND) of the colonic submucous plexus is considered to be a congenital malformation of the enteric nervous system causing symptoms resembling those of Hirschsprung's disease. In contrast with the established diagnosis of aganglionosis using enzyme histochemistry, controversy exists over the diagnostic criteria of IND on rectal biopsies previously defined by a consensus report and the causal relation between morphological findings and clinical symptoms. AIMS: The interobserver variability was prospectively investigated with respect to final diagnoses and several histological features in rectal biopsy specimens from children suspected of having colonic motility disturbances. METHODS: 377 biopsy specimens from 108 children aged 4 days to 15 years were independently coded without knowledge of clinical symptoms by three experienced pathologists for 20 histological features, and a final diagnosis was given for every case. Interobserver variation for the different items and the final diagnosis were analysed using Cohen's kappa statistic. Clinical data at biopsy and outcome after 12 months were related to morphological findings. RESULTS: The three pathologists agreed completely with respect to the diagnosis Hirschsprung's disease (kappa = 1), but in only 14% of the children without aganglionosis. In 15 (17%) of the 87 children without aganglionosis, at least one pathologist judged the case as normal, while another diagnosed IND. kappa values were close to the zero value expected by chance for the diagnoses normal and IND. Young age was related to the presence of several morphological features-for example, acetylcholine esterase staining and presence of giant ganglia. Children with chronic constipation diagnosed as having IND, given no other specific diagnosis by any of the pathologists, were significantly younger (median 8.8 months) and had a higher cure rate after one year (60%) than constipated patients considered by all observers to have no histological abnormalities (median 6.1 years, cure rate 23%). CONCLUSIONS: In contrast with Hirschsprung's disease, there is a high interobserver variation with regard to the different morphological features and final diagnosis of IND, based on the criteria and conditions of the previous consensus report. The high frequency of histological "abnormalities" in young infants suggests that some of the features may represent a normal variant of postnatal development rather than a pathological process. Investigations using more refined and morphometric methods in rectal specimens from infants and children without bowel disease are needed to define the normal range of morphological appearance at different ages. These preliminary data indicate that, with current knowledge, rectal biopsy for diagnostic purposes should only be performed in constipated children for diagnosis of Hirschsprung's disease.

Peutz-Jeghers syndrome: four novel inactivating germline mutations in the STK11 gene. Mutations in brief no. 227. Online.

The diagnosis of Peutz-Jeghers syndrome is based on the occurrence of hamartomatous gastrointestinal polyps and perioral pigment spots. In view of the development of hamartomatous polyps in several syndromes and the variability of pigment spots in Peutz-Jeghers patients, identification of affected individuals is difficult. Recently, germline mutations in the STK11 gene have been reported as a molecular cause of Peutz-Jeghers syndrome. We present four novel inactivating mutations identified by direct sequencing of all 9 exons of the STK11 gene in 4 patients suggestive of Peutz-Jeghers syndrome: three frameshift mutations (125-137del; 474-480del; 516-517insT) and one nonsense mutation (Q220X). Our data obtained in these patients and in those reported previously emphasize the diagnostic value of histological discrimination between different types of hamartomatous polyps and of molecular analysis, particularly in cases with no family history of the disease.

Postoperative ramifications of total ear replantation.

Complete avulsion of the external ear, much less common than other minor ear trauma, presents a complex and difficult problem. The authors present a 35-year-old male cigarette smoker who suffered traumatic avulsion of the right ear, and describe the replantation procedure and the patient's postoperative course. Aesthetic positioning of the replanted ear, treating the external auditory meatus, protecting the ear against exposure to the sun, and counseling the patient about issues related to sensation are important factors in the care of patients who have undergone such a procedure.

[Quality assurance in therapy of mucoviscidosis: value of the Bonn patient information system]. / Qualitätssicherung in der Mukoviszidosetherapie: Stellenwert des Patienten-Informations-Systems Bonn.

BACKGROUND: Differences in the survival rates of patients in two large CF-clinics (Toronto, Boston) were explained by differences in dietary regimens: Toronto favoured a fat-enriched diet and had the better outcome. This example may explain how important high quality medical data are for improving treatment and prognosis of CF. AIM: A local patient-information-system is described to improve internal and external quality control. RESULTS: The system was developed over years in a fruitful collaboration between a realistic statistician and active CF doctors. It is easy to use and facilitates documentation, follow-up, researches and preparation of data for scientific presentation and clinical routine. Graphical outline may be used to motivate individual patients. Internal controlling for plausibility improves quality of data also serving the national system for quality control. CONCLUSIONS: We believe, our system is able to improve internal quality control and to serve the national system for quality control very efficiently without additional workload of the local CF-clinic.

Quality of life in patients with cystic fibrosis and their parents: what is important besides disease severity?

BACKGROUND: Cystic fibrosis is the most common inherited disease with a fatal outcome in industrialised nations. With the improvement in life expectancy, supporting patients and their families in adapting to life with this chronic progressive disease has become increasingly important. The aim of the present study was to investigate the relationship between health related quality of life (HRQOL) in this population, severity of disease, and cognitive/behavioural factors such as subjective health perception and ways of coping. METHODS: A sample of 89 adolescent and adult patients with cystic fibrosis and 125 parents of younger patients with cystic fibrosis completed questionnaires on health related quality of life and on ways of coping with the illness. Parents were asked to fill out the questionnaires regarding their own quality of life and coping. Multiple regression analyses were performed to examine the relationship between different predictor variables and quality of life. RESULTS: After accounting for the impact of disease severity and hours of treatment per day, the subjective health perception of patients significantly explained variance in their quality of life. Ways of coping were also significantly correlated with HRQOL. In parents the most important factor in explaining variance of HRQOL seems to be the coping style, whereas disease severity of the child and subjective health perception did not show any influence. CONCLUSIONS: The findings support the important role of cognitive and behavioural factors in specific subjective health perception and ways of coping in the adaptation to this severe chronic disease, both in patients themselves and in parents. The results call for a careful assessment of issues of coping and professional support for families of patients with cystic fibrosis in the early course of disease.

Validation of cutaneous pressure threshold measurements for the evaluation of hand function.

The relationship of measures of pressure perception to hand function was evaluated by correlating the results of the Mayo Dexterity Test and a timed object recognition test with the one- and two-point static and moving touch thresholds for the index finger pulp of 44 hands. The Mayo Dexterity Test permits the use of vision, while the object recognition test does not. Quantitative sensory testing was done with the Pressure-specifying Sensory Device. Cutaneous pressure threshold measurements with this device had a statistically significant correlation with the small-object subset of the Mayo Dexterity Test (p < 0.006) and with the object recognition test (p < 0.001), demonstrating that the Pressure-specifying Sensory Device is a valid tool for evaluating the sensory aspect of hand function.

Computer-assisted quantitative sensorimotor testing in patients with carpal and cubital tunnel syndromes.

This study reports the use of computer-assisted sensorimotor testing in 75 patients with chronic peripheral nerve compression. Pinch and grip strength, and the cutaneous pressure threshold were measured. The reliability of this equipment for repeated measurements was excellent (r = 0.95). The pressure threshold at which a one-point static stimulus could be distinguished from a two-point static stimulus was found to be the first variable to become abnormal with computer-assisted sensorimotor testing. Criteria are suggested for screening with this equipment to detect carpal and/or cubital tunnel syndrome.

Novel and characteristic CFTR mutations in Saudi Arab children with severe cystic fibrosis.

More than 600 different CFTR (cystic fibrosis transmembrane conductance regulator) gene mutations have been identified so far that are considered to cause the fatal genetic disorder cystic fibrosis (CF). We have investigated 15 Arab children from 12 families, who were diagnosed as having CF, for mutations in the coding region and in the flanking intron sequences of the CFTR gene. Six different CFTR mutations were identified including two novel mutations, 1548delG in exon 10 and 406-2A-->G in intron 3. Prominent mutations were the splice mutation 3120 + 1G-->A (intron 16) followed by N1303K (exon 21) and 1548delG (exon 10). Most CF children were homozygotes who presented with a severe form of the disease including failure to thrive, recurrent chest infections, particularly with Pseudomonas aeruginosa, and frequent hospital admissions. Identification of the CFTR mutations facilitates molecular investigation of the disease and better understanding of its pathophysiology in Arab children, among whom CF is probably an underdiagnosed disease.

Rational design and synthesis of small molecule, non-oligosaccharide selectin inhibitors: (alpha-D-mannopyranosyloxy)biphenyl-substituted carboxylic acids.

The calcium dependent E-selectin/sialyl Lewisx (sLex) interaction plays a key role in inflammation where it mediates the rolling of leukocytes prior to firm adhesion and extravasation from the vasculature. A model of E-selectin/sLex binding, along with previously reported structure-activity relationships of sLex-related oligosaccharide, was used in the rational design of non-oligosaccharide inhibitors of this pivotal interaction. A palladium-mediated biaryl-coupling (Suzuki) reaction was used as the key step to prepare a number of substituted biphenyls which were assayed for their ability to inhibit the binding of E-, P-, and L-selectin-IgG fusion proteins to sLex expressed on the surface of HL60 cells. Some of the compounds developed had greater in vitro potency than the parent sLex tetrasaccharide and are currently being evaluated in in vivo models of inflammation to select a candidate for clinical development.

[Clostridium difficile in early childhood ulcerative pancolitis]. / Clostridium difficile bei frühkindlicher Pancolitis ulcerosa.

Ulcerative colitis is a rare disease in young infants. Less than one per cent of cases occur during the first two years of life. We describe a male child who developed frequent bloody diarrhea at the age of 20 months. More common causes like infections or gastrointestinal food allergy were excluded. Endoscopy and histopathological evaluations revealed ulcerative colitis of the entire colon. Treatment with sulfasalazine and prednisone resulted in a clinical remission after seven weeks. The follow-up of 15 months was complicated by Rotavirus infection. Two relapses were caused by Clostridium difficile infections. The latter were successfully treated with oral vancomycine, but in the last relapse an increased dosage of prednisone was required, too. In relapses of inflammatory bowel disease gastrointestinal infections, especially caused by Clostridium difficile should be considered and treated adequately.