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Biomedical subjects

J Oswald

Publications and source records attributed to J Oswald.

At least 19 recordsLinked to original sources

[Contrast-medium enhanced reflux ultrasound in children. A comparison with radiologic imaging up to now].

Voiding cystourethrography (VCUG) has long been the method of choice for the diagnosis of vesicoureteral reflux (VUR). Especially in the course of conservative treatment, the radiation dose involved might become quite high over the years. Since the development of such ultrasound echo-enhancing agents as Levovist (Schering, Germany), we now have the ability to assess the diagnostic efficacy of this agent in the evaluation of VUR with a view to replacing VCUG with the radiation-free ultrasound methodology. A total of 104 children with a mean age of 5.4 years were examined using echo-enhancing ultrasound after informed consent had been obtained from their parents. For control purposes, all children were examined by standard VCUG as well. The diagnosis of VUR was judged to be positive when microbubbles appeared in the ureter or renal pelvis. Correlations were sought between the sonographic findings and those obtained by standard VCUG. In 76 (37%) of the 208 ureter-kidney units investigated, VUR was detected by both technologies. VUR was diagnosed by ultrasonography only in 5 units and by VCUG only only in 3 units. All reflux grades (I-V) were identified. The specificity and sensitivity of the contrast reflux ultrasound were significantly high. The long contrast time of up to 30 min combined with the high contrast effect resulted in convincing images with high levels of diagnostic confidence. Our results clearly demonstrate that the safety and accuracy of the diagnosis of VUR by means of contrast-enhanced ultrasound is statistically comparable to those of standard radiologic VCUG. Therefore, this methodology is an exceptional approach to reducing the number of children being exposed to ionising radiation especially during conservative follow-up of children with reflux.

Adolescent↗

Prospective comparison and 1-year follow-up of a single endoscopic subureteral polydimethylsiloxane versus dextranomer/hyaluronic acid copolymer injection for treatment of vesicoureteral reflux in children.

OBJECTIVES: To compare, in a prospective study, the efficacy of a single injection of polydimethylsiloxane (Macroplastique) or dextranomer/hyaluronic acid copolymer (Deflux), a new biodegradable substance, and to assess the short-term and 1-year clinical effects concerning reflux resolution and the safety of these two bulking agents. Subureteral injection of bulking agents has recently demonstrated good success rates for endoscopic treatment of vesicoureteral reflux. Macroplastique has been one of the most popular bulking agents during the past years. Nevertheless, considering the synthetic property, new biodegradable substances have become more relevant. METHODS: From January 2000 to June 2001, 16 boys and 56 girls (total of 114 ureters) with a mean age of 34.5 months were treated endoscopically for vesicoureteral reflux. A single subureteral Macroplastique or Deflux injection was performed in 34 children (58 ureters) and 38 children (56 ureters), respectively. Both groups were comparable in terms of baseline parameters. Vesicoureteral reflux was grade II in 52, grade III in 57, and grade IV in 5 ureterorenal units. The procedure was performed on an outpatient basis, with the children under general anesthesia. In addition to the routine parameters, the follow-up evaluation consisted of renal ultrasonography and voiding cystourethrography at 3 and 12 months postoperatively. RESULTS: Endoscopic treatment was performed without any complications in all cases. At the 3-month follow-up visit, reflux was corrected in 50 (86.2%) of 58 refluxing ureters in the Macroplastique group and in 40 (71.4%) of 56 refluxing ureters in the Deflux group. At 1 year of follow-up, reflux correction was maintained in 80.9% of ureters in the Macroplastique group and in 67.6% of ureters in the Deflux group. No postoperative complications were observed in either group. CONCLUSIONS: A single subureteral injection of either polydimethylsiloxane (Macroplastique) or dextranomer/hyaluronic acid copolymer (Deflux) is an effective treatment modality for children with vesicoureteral reflux. The procedure was well tolerated, safe, and associated with low morbidity. Deflux, a new biocompatible, biodegradable substance, seems to be an alternative modality to other bulking agents for treating vesicoureteral reflux in children, with acceptable short-term and 1-year results.

Biocompatible Materials↗

Blood viscosity and platelet function in patients with obstructive sleep apnea syndrome treated with nasal continuous positive airway pressure.

Patients with obstructive sleep apnea syndrome (OSA) have a high incidence of cardiovascular events. We measured whole blood viscosity at high (94.5 s(-1)) and low (0.1 s(-1)) shear rate, hematocrit, fibrinogen, and platelet hemostatic function (PTA-100) at 7-8 p.m. and 7-8 a.m. in 8 controls and 13 patients, once with the established nasal continuous positive airway pressure (NCPAP) treatment and once without. OSA patients had a higher plasma viscosity (1.37+/-0.11 vs. 1.19+/-0.11 mPa.s in the evening, p<0.05) and fibrinogen (2.61+/-0.49 vs. 2.11+/-0.29 g/l, p<0.05) than controls, without diurnal difference, and similar values with or without NCPAP. Whole blood viscosity and hematocrit were similar in controls and patients before and after a night with or without NCPAP. Platelet activity was significantly higher in the morning than in the evening in controls and patients with or without NCPAP. We conclude that blood viscosity and platelet activity are similar in controls and patients with OSA on a long-term treatment with NCPAP, which is not worsened by a single night without NCPAP. The increase of plasma viscosity and fibrinogen in OSA patients as well as the general increase of platelet aggregation in the morning may contribute to the increased incidence of cardiovascular events.

Aged↗

Routine breast screening for women aged 65-69: results from evaluation of the demonstration sites.

Routine programme data and specially designed surveys from 3 demonstration sites were analysed to determine the implications of extending the NHS Breast Screening Programme (NHSBSP), to include routine invitations for women up to 69 years. All women aged 65-69 and registered with GPs in these areas received routine invitations for breast screening along with those aged 50-64. Overall uptake was 71% in women aged 65-69 compared with 78% in younger women, but was > or = 90% in both groups who had previously attended within 5 years. Recall rates were lower for older women, but with a higher positive predictive value for cancer. The percentages of invasive cancer in different prognostic categories were similar in the 2 age groups. Older women took no longer to screen than younger women. The costs per woman invited or per woman screened were also similar to those for women aged 50-64, whilst the cost per cancer detected was some 34% lower in older women. Breast screening is as cost effective for women aged 65-69 as for those aged 50-64, with a higher cancer detection rate balancing shorter life expectancy. The proposed extension to the national programme will have considerable workforce implications for the NHSBSP and require additional resources.

Aged↗

[Pseudotumor cerebri in minocyline treatment].

Pseudotumor cerebri or benign intracranial hypertension is a syndrome of raised intracranial pressure without obvious explanation. Most patients are obese women at childbearing age. Symptoms and signs usually include headache, nausea, vomiting, edema of the papilla, visual obscurations and rarely palsy of the nervus abducens. The prognosis is generally good, but progressive visual loss and eventual blindness are major risks. We report the case of a 21-year-old non-obese young woman who developed pseudotumor cerebri while taking minocycline for acne therapy. Identical symptoms occurred upon inadvert rechallenge with minocycline for the second time.

Acne Vulgaris↗

The use of isosulphan blue to identify lymphatic vessels in high retroperitoneal ligation of adolescent varicocele--avoiding postoperative hydrocele.

OBJECTIVE: To assess whether identifying and preserving the lymphatic vessels, using vital dyes, avoids postoperative hydrocele in adolescents with varicocele undergoing high retroperitoneal ligation (Palomo procedure). PATIENTS AND METHODS: The results were assessed from 28 consecutive adolescent patients undergoing varicocelectomy, treated between 1998 and 1999 by the Palomo procedure. The lymphatic vessels were identified and preserved using vital dyes, to avoid postoperative hydrocele formation. RESULTS: In 24 of the 28 patients (86%) the identification and preservation of lymphatic vessels was feasible. Over a mean (range) follow-up of 14 (4-24) months there were no postoperative hydroceles and no clinical recurrences. CONCLUSION: Identifying and preserving the lymphatic drainage of the testis and tunica vaginalis using vital dyes prevents the development of postoperative hydrocele in adolescents undergoing the Palomo procedure.

Adolescent↗

Bisulfite-based methylation analysis of imprinted genes.

Genomic imprinting is an epigenetically controlled form of gene regulation leading to the preferential expression of one parental gene copy. To date, approximately 40 imprinted genes have been described that are exclusively or predominantly expressed from either the paternal or the maternal allele (www.mgu.har.mrc.ac.uk/imprinting/implink.html). Changes in the imprinted expression of such genes result in developmental abnormalities; in the human they are associated with several diseases and various types of cancer (1-3).

Animals↗

Teens and tobacco in Minnesota. New findings from the Minnesota youth tobacco survey.

The Minnesota Youth Tobacco Survey (MYTS) was administered to 12,376 public school students in grades 6 through 12 to obtain baseline data at the start of the state's latest efforts to reduce tobacco use among youth. The sample is representative of public school students in the state. More than one-third of high school students (38.7%) and 12.6% of middle school students are current tobacco users, defined as use of tobacco on one or more days in the previous 30 days. Current use of cigarettes is 32.4% in high school and 9.1% in middle school. More than 90% of students, including most smokers, agree that tobacco use is addictive and harmful. More than three-fourths (78.4%) of current smokers report that two or more of their four closest friends are smokers. Students who live with a smoker are more likely to become current smokers than students who do not live with anyone who smokes (42.5% to 25.1% in high school). Most current smokers (61.0%) tried to quit smoking at least once in the past 12 months. Eighty-eight percent (88.4%) of current smokers in high school smoke one of the top three advertised brands: Marlboro, Camel, or Newport. Results of the MYTS illustrate some of the challenges facing the state's tobacco reduction efforts and some of the factors that must be considered as Minnesota tries to design and implement effective programs.

Adolescent↗

Measuring clinical performance: comparison and validity of telephone survey and administrative data.

OBJECTIVE: To compare and validate self-reported telephone survey and administrative data for two Health Plan Employer Data and Information Set (HEDIS) performance measures: mammography and diabetic retinal exams. DATA SOURCES/STUDY SETTING: A telephone survey was administered to approximately 700 women and 600 persons with diabetes randomly chosen from each of two health maintenance organizations (HMOs). STUDY DESIGN: Agreement of survey and administrative data was assessed by using kappa coefficients. Validity measures were assessed by comparing survey and administrative data results to a standard: when the two sources agreed, that was accepted as the standard; when they differed, confirmatory information was sought from medical records to establish the standard. When confirmatory information was not available ranges of estimates consistent with the data were constructed by first assuming that all persons for whom no information was available had received the service and alternately that they had not received the service. PRINCIPAL FINDINGS: The kappas for mammography were .65 at both HMOs; for retinal exam they were .38 and .40. Sensitivity for both data sources was consistently high. However, specificity was lower for survey (range .44 to .66) than administrative data (.99 to 1.00). The positive predictive value was high for mammography using either data source but differed for retinal exam (survey .69 to .78; administrative data .99 to 1.00). CONCLUSIONS: Administrative and survey data performed consistently in both HMOs. Although administrative data appeared to have greater specificity than survey data the validity and utility of different data sources for performance measurement have only begun to be explored.

Adult↗

Active demethylation of the paternal genome in the mouse zygote.

DNA methylation is essential for the control of a number of biological mechanisms in mammals [1]. Mammalian development is accompanied by two major waves of genome-wide demethylation and remethylation: one during germ-cell development and the other after fertilisation [2] [3] [4] [5] [6] [7]. Most previous studies have suggested that the genome-wide demethylation observed after fertilisation occurs passively, that is, by the lack of maintenance methylation following DNA replication and cell division [6] [7], although one other study has reported that replication-independent demethylation may also occur during early embryogenesis [8]. Here, we report that genes that are highly methylated in sperm are rapidly demethylated in the zygote only hours after fertilisation, before the first round of DNA replication commences. By contrast, the oocyte-derived maternal alleles are unaffected by this reprogramming. They either remain methylated after fertilisation or become further methylated de novo. These results provide the first direct evidence for active demethylation of single-copy genes in the mammalian zygote and, moreover, reveal a striking asymmetry in epigenetic methylation reprogramming. Whereas paternally (sperm)-derived sequences are exposed to putative active demethylases in the oocyte cytoplasm, maternally (oocyte)-derived sequences are protected from this reaction. These results, whose generality is supported by findings of Mayer et al. [9], have important implications for the establishment of biparental genetic totipotency after fertilisation, the establishment and maintenance of genomic imprinting, and the reprogramming of somatic cells during cloning.

Actins↗

Comparison of the perimeatal-based flap (Mathieu) and the tubularized incised-plate urethroplasty (Snodgrass) in primary distal hypospadias.

OBJECTIVES: To determine whether the perimeatal-based flap technique or the tubularized incised-plate repair is the more appropriate treatment for distal hypospadias in terms of fistula rate, cosmesis of the meatus and operative duration. PATIENTS AND METHODS: Between July 1997 and August 1998, 60 children (none of whom had previously undergone a procedure for hypospadias) underwent primary distal hypospadias repair in a prospective randomized trial. Thirty patients were allocated to undergo a Mathieu repair (mean age 24.9 months, range 9-72) and 30 a Snodgrass procedure (mean age 23.1 months, range 7-19). The mean follow-up was 15.4 months. RESULTS: The mean duration of surgery was significantly lower for the Snodgrass procedure than for the Mathieu repair (75 vs 115 min, P < 0.05). Three children undergoing a Mathieu repair had complications (two a urethrocutaneous fistula and one a meatal stenosis), compared with only one in the Snodgrass group (glanular dehiscence). The resultant meatus was slit-like in all patients undergoing the Snodgrass repair whereas those with a Mathieu repair had a rounded and horizontal meatus. CONCLUSION: The overall complication rate was lower and the surgery significantly quicker with the Snodgrass urethroplasty, which also had a better cosmetic outcome. The Snodgrass technique is recommended as a primary treatment for distal hypospadias.

Fistula↗

Verification of bacterial killing effects of cage wash time and temperature combinations using standard penicylinder methods.

We conducted the present study to evaluate various time and hot-water temperature combinations necessary to kill three common bacterial species in standardized cultures on stainless steel penicylinders, in accordance with methods approved by the Association of Official Analytical Chemists. Exposure for no more than 2 sec to water at 82.2 degrees C killed all three bacterial species, as did exposure for 3 sec to water at 80 degrees C, 4 sec at 77.8 degrees C, and 5 sec at 75.6 degrees C. We conclude that temperatures in the range of 75.6 degrees C to 82.2 degrees C will effectively kill vegetative bacteria in a matter of seconds and that failure to kill these bacteria in cagewash operations, with belt travel times in minutes rather than seconds, is due to other factors that prevent the effective application of sufficiently hot water to the bacterial load.

Animals↗

H19 and Igf2 are expressed and differentially imprinted in neuroectoderm-derived cells in the mouse brain.

Igf2 and H19 are reciprocally imprinted genes that are closely linked and coexpressed in tissues of mesodermal and endodermal origin. Here we report that coexpression of these genes is also found in specific fetal tissues of neuroectodermal origin, that is in the ventral midline region of both the hindbrain and spinal cord. For cells of neuroectodermal origin, complete absence of Igf2 and H19 transcription was previously described. Analysis of allele-specific expression of both Igf2 and H19 in the ventral midline region of the hindbrain shows that H19 is expressed monoallelically, with the paternal allele being silent, whereas Igf2 is expressed biallelically. Furthermore, we observed a strong influence of the parental species background, in that the Mus musculus allele was always expressed at higher levels than the M. spretus allele. This was observed when the M. spretus allele was contributed by the mother or by the father. An analysis of Igf2 methylation by bisulphite genomic sequencing provided no clear answer as to whether Igf2 expression and methylation are linked in a tissue of neuroectodermal origin. Taken together, our results provide novel information on H19 and Igf2 expression and imprinting patterns in the fetal mouse brain. In addition, they indicate that some aspects of Igf2 regulation in cells of neuroectodermal origin do not follow the pattern that exists in mesoderm- and endoderm-derived tissues. Apart from the ventral midline region, H19 and Igf2 were found to be coexpressed in the ectodermally derived Rathke's pouch and in some circumventricular organs of the brain, such as the organum vasculosum of the lamina terminalis (OVLT) and the pineal gland.

Animals↗

Long-term use and tapered dose reduction of intranasal desmopressin in the treatment of enuretic children.

OBJECTIVE: To determine the time taken to achieve complete dryness, the management of desmopressin dosage to reduce the relapse rate, the mean dosage in those responding and any side effects of long-term treatment. PATIENTS AND METHODS: Enuretic children (155, 68% boys and 32% girls, mean age 8 years, range 5-19) were treated with desmopressin and assessed. Treatment (intranasal spray) was started with 20 microg desmopressin and titrated to 40 microg (maximum 50 microg) after 2 days if the child did not become dry within 48 h. The maximum dosage was maintained for at least 4-6 weeks. After 4 weeks of complete dryness, the dosage was reduced by 10 microg initially, and after each additional 4 dry weeks, by a further 10 microg; medication was stopped only after 4 dry weeks at 10 microg. RESULTS: Of the children, 85% responded to intranasal desmopressin therapy; 71% achieved complete dryness with no relapses, remaining dry with no further treatment, 7% achieved dryness after relapses during or after therapy, 7% improved (no more than two wet nights per week) and 15% did not respond to therapy or improved only slightly (> 2 wet nights per week). The mean duration of therapy was 28 weeks, the mean dose of desmopressin was 30 microg and the median follow-up 18 months. There were no significant side-effects. CONCLUSION: This study indicates that rapid titration until dryness within 1-3 days, a long maintenance therapy of at least 4-6 weeks and a slow stepwise reduction of dose decreases the frequency of relapse and improves the outcome.

Administration, Inhalation↗

Loss of the maternal H19 gene induces changes in Igf2 methylation in both cis and trans.

Recent investigations have shown that the maintenance of genomic imprinting of the murine insulin-like growth factor 2 (Igf2) gene involves at least two factors: the DNA (cytosine-5-)-methyltransferase activity, which is required to preserve the paternal specific expression of Igf2, and the H19 gene (lying 90 kb downstream of Igf2 gene), which upon inactivation leads to relaxation of the Igf2 imprint. It is not yet clear how these two factors are related to each other in the process of maintenance of Igf2 imprinting and, in particular, whether the latter is acting through cis elements or whether the H19 RNA itself is involved. By using Southern blots and the bisulfite genomic-sequencing technique, we have investigated the allelic methylation patterns (epigenotypes) of the Igf2 gene in two strains of mouse with distinct deletions of the H19 gene. The results show that maternal transmission of H19 gene deletions leads the maternal allele of Igf2 to adopt the epigenotype of the paternal allele and indicate that this phenomenon is influenced directly or indirectly by the H19 gene expression. More importantly, the bisulfite genomic-sequencing allowed us to show that the methylation pattern of the paternal allele of the Igf2 gene is affected in trans by deletions of the active maternal allele of the H19 gene. Selection during development for the appropriate expression of Igf2, dosage-dependent factors that bind to the Igf2 gene, or methylation transfer between the parental alleles could be involved in this trans effect.

Alleles↗

A modified and improved method for bisulphite based cytosine methylation analysis.

Sequencing of bisulphite modified genomic DNA is the most powerful method to determine methylation patterns in chromosomal DNA. In many experimental systems, the amount of material available for analysis is very small which makes it necessary to perform experiments at extreme levels of sensitivity and reproducibility. In this communication, we present an improved modification of the bisulphite based sequencing method. Our strategy is to perform the bisulphite treatment and subsequent PCR steps on material embedded into agarose beads. This prevents loss of DNA during the experimental procedure and ensures an optimal bisulphite reactivity by maintaining the DNA in the single stranded form. The modification improves previously published protocols in that it facilitates the handling of probes and reproducibly reaches a very high level of sensitivity.

Cell Line↗