Testing for Chlamydia trachomatis in urine.
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Antigens, Bacterial↗
Biomedical subjects
B Weber
Publications and source records attributed to B Weber.
Infection with hepatitis G virus in immunoglobulin recipients.
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Antibodies, Anti-Idiotypic↗
Diabetic angiopathy in children.
Among the secondary complications of diabetes, early stages of retinopathy and nephropathy are of foremost importance in paediatrics. Regular examinations of retinal status and of urinary albumin excretion therefore become necessary with the onset of puberty or after 5 years of diabetes duration. With fluorescein angiography, the first retinal changes can be expected after a median diabetes duration of 9 years, while the median time to clinically relevant background retinopathy is 14 years. This diagnosis is delayed by 4 and 6 years, respectively, if retinopathy is staged exclusively by ophthalmoscopy. Approximately 10 to 20% of children may develop microalbuminuria, starting in early puberty. Several risk factors for the development of diabetic angiopathy have been identified. The degree of glycaemic control, both before and after puberty, appears to be of outstanding importance, but the contribution of other factors may be of varying relevance in the individual patient. These include arterial blood pressure, lipid abnormalities, sex steroids, smoking and genetic factors. Apart from the best possible metabolic regulation, early treatment with antihypertensive drugs has been shown to be beneficial in hypertensive adolescents but may also be renoprotective in normotensive adolescents with permanent microalbuminuria. However, the relatively high prevalence of intermittent and transient microalbuminuria in paediatric patients (2 and 3% respectively), with unknown prognostic relevance, complicate the decision to start such treatment for a lifetime. Nevertheless, the early detection of risk factors and the implementation of appropriate intervention strategies are necessary to improve the long-term prognosis for children with diabetes.
Adolescent↗
Identification of 16 sulfamidase gene mutations including the common R74C in patients with mucopolysaccharidosis type IIIA (Sanfilippo A).
Mucopolysaccharidosis type IIIA (MPS IIIA or Sanfilippo A disease) is a storage disorder caused by deficiency of the lysosomal enzyme sulfamidase. Mutation screening, using SSCP/heteroduplex analyses on cDNA and genomic DNA fragments, was performed in a group of 42 European patients. Sixteen of the 17 different gene mutations characterized have not been previously described. The spectrum of gene lesions consists of two 1-bp deletions (1091delC, 1093delG), an 18-bp duplication (421ins18), a splice site mutation (IVS2-2A-->G), and 13 different missense point mutations. As in other lysosomal storage disorders, the phenotypic heterogeneity is associated with a considerable genetic heterogeneity. The missense mutation R74C, which alters an evolutionary conserved amino acid in the active site of the enzyme, was found on 56% of alleles of 16 Polish patients, whereas it was less frequent among German patients (21% of disease alleles). R245H, a previously reported common mutation, represents 35% of disease alleles in German patients, but only 3% in Polish patients. As the combined frequency of the common mutations (R74C and R245H) in German and Polish populations exceeds 55%, screening for these two mutations will assist molecular genetic diagnosis of MPS IIIA and allow heterozygote testing in these populations.
Binding Sites↗
Human hippocampus establishes associations in memory.
Studies of amnesia have demonstrated that the hippocampus is necessary for long-term memory, but its precise role in memory is unknown. We designed a positron emission tomography experiment with tailored encoding and retrieval tasks that permitted the isolation of different mnemonic functions theorized to be mediated by the hippocampus. These functions included encoding single items, establishing interitem associations, novelty detection, and retrieving recently formed associations. Of these, we found hippocampal and parahippocampal activation only during associative learning. Our results indicate that the hippocampal formation may be particularly involved in the establishment of associations among components of an episode in memory.
Association↗
The "knot before loop" technique for the endoscopic ligation and suture-instrument set. Knot formation and application.
BACKGROUND: In minimally invasive surgery intracorporal knot-tying is complicated by a limited field of vision and depth perception. METHODS: The "knot before loop" technique aims to reduce intraabdominal movements in number and space needed. A grasping instrument 3 mm in diameter guides a slipfit hollow knot pusher with a notch to hold the thread, when extracorporally forming the knot on the instrument tip and an axial slot. The loop is finished under endoscopic vision, yet a second loop is created along the thread. The knot is tightened and secured by closing the second loop without troublesome instrument change. RESULTS: The strength of the knot was tested and the feasibility of the instrument set was proven in pigs and 25 cholecystectomies and hernia repairs in humans. CONCLUSIONS: Endoscopic application of a secured slip knot is simplified by the "knot before loop" technique. The independent formation of the knot by the assisting personnel allows quick application, equivalent to the use of clips and staples. The benefit in cost saving is high.
Feasibility Studies↗
The effect of intermittent-release intraperitoneal chemotherapy on wound healing.
OBJECTIVE: Our purpose was to study the effect on wound healing when intraperitoneal chemotherapy was instilled on a daily basis. STUDY DESIGN: Intraperitoneal carboplatin, Taxol, or saline solution was instilled daily into 70 rats after they underwent laparotomy. The animals were killed and analyzed for adhesions. An area measuring 5 x 5 cm including the incision was also harvested for biomechanical testing. The wound thickness was measured, and the Shore Western Materials Testing System (Monrovia, Calif.) was used to test the force required to break the wound, the stress, and the stiffness. RESULTS: Groups of 10 rats received saline solution control, carboplatin 6 mg/kg, 7 mg/kg, 8 mg/kg, or Taxol 2.5 mg/kg, 3.0 mg/kg, or 3.5 mg/kg. The total dose was divided into seven equal amounts, administered daily. No significant adhesions developed in any of the animals. The carboplatin group experienced no significant decrease in wound thickness whereas the higher-dose Taxol group had a significant decrease in thickness from 1.06 mm to 0.72 mm (p = 0.02). The wound-breaking strength (force) also decreased for the highest-dose Taxol group from 710 gm to 411 gm (p = 0.02). The wound stiffness was also decreased from 69 gm/mm to 46 gm/mm (p = 0.01). The other measured parameters for both the Taxol and carboplatin groups were not significantly decreased when compared with those of controls. CONCLUSION: The immediate instillation of divided daily carboplatin did not influence wound strength whereas the use of Taxol on a similar schedule significantly decreased wound strength.
Animals↗
High-pass-filtered magnetocardiogram and cardiomyopathy in patients with type 1 diabetes mellitus.
Prolonged and/or fractionated depolarization due to tissue degeneration of the ventricular myocardium is a feature of cardiomyopathy. Signal averaged electrocardiography uses high-pass filters of the Butterworth type to quantify, noninvasively, fractionated high-frequency components at the end of the QRS complex. In this study a finite impulse response high-pass filter of the 90th order (cutoff at 37 Hz) was applied to magnetocardiograms (MCGs) and high-resolution electrocardiograms (ECGs) order to quantify high-frequency components throughout the myocardial depolarization. Additionally, late-potential analysis on the signal-averaged ECG was performed. A prospective investigation was made of 23 cardiologically asymptomatic patients, 11 females and 12 males, with type I diabetes mellitus. Their mean age was 21.7 years (range, 13-34 years). The mean duration of diabetes was 14 years (range, 1-27 years). Data were compared with those of 22 control subjects (12 females, 10 males) of mean age, 23.2 years (range, 11-35 years). The ECGs and MCGs were simultaneously recorded and signal-averaged, digitally filtered, and quantified by a score obtained by multiplying the amplitude variation of the signal by the number of maximal/minimal in the QRS complex. Echocardiograms were used to calculate the left ventricular mass and to document the presence of cardiomyopathy. Scores were higher in the MCGs of with type I diabetes mellitus than in the control subjects (P < .001). High scores correlated with an increased left ventricular muscular mass index (P < .05) and duration of the diabetes (P < .05). The high-resolution ECG, processed analogously, showed similar results in relation to left ventricular mass (P = .06) and duration of diabetes (P = .07), respectively (nonsignificant). No late potentials were found. These findings suggest that using a linear-phase high-pass finite impulse response filter may be useful for the noninvasive identification of patients with cardiomyopathy who exhibit possible disturbances of intraventricular depolarization. Our findings also suggest that analysis using the total QRS complex, rather than the final part of the QRS complex only, may improve identification of patients at risk.
Adolescent↗
With aging in humans the activity of the hypothalamus-pituitary-adrenal system increases and its diurnal amplitude flattens.
There is compelling evidence for feedback disturbances in the hypothalamus-pituitary-adrenal system associated with human aging as assessed by challenge tests. However, reports about age-related changes in human basal activity are ambiguous and to date little is known about changes in the pulsatile features of the HPA system. To investigate these changes we studied twenty-two healthy male and eleven healthy female subjects ranging from 23 to 85 and 24 to 81 years respectively. 24-hour blood sampling with 30 minute sampling intervals was performed. From 18.00 to 24.00 hours blood was sampled every 10 minutes for analysis of pulsatile features of HPA activity. Statistical analysis revealed that age in particular had major effects upon basal HPA-system activity: there was a significant age-associated increase in minimal (p < 0.0001) and mean (p < 0.02) cortisol plasma concentrations, but no alteration in pulsatile features. We found no age-cortisol correlation during daytime, but were able to demonstrate a strong impact of age upon cortisol plasma levels from 20.00 to 1.30 hours. The diurnal amplitude of cortisol (p < 0.005) and ACTH (p < 0.006), relative to the 24-hour mean of the hormones, showed an age-associated decline. Additionally, the evening cortisol quiescent period (p < 0.01) was shortened in the elderly, suggesting increasingly impaired circadian function in aging. Our results suggest an increased basal activity and a flattened diurnal amplitude of the HPA system in the elderly.
Adult↗
Detection of human immunodeficiency virus type 1 and type 2 antibodies by a new automated microparticle immunoassay AxSYM HIV-1/HIV-2.
A new automated microparticle enzyme immunoassay (MEIA) for the AxSYM instrument developed recently by Abbott Laboratories was compared with two established assays, i.e. HIV-1/HIV-2 3rd Gen. Plus EIA (Abbott, Delkenheim, FRG) and Wellcozyme HIV 1 + 2 (Murex Diagnostics, Dartford, England) devised for the detection of human immunodeficiency virus type 1 (HIV-1) and HIV-2 antibodies. A total of 7293 serum samples were tested by the AxSYM HIV-1/HIV-2. The test panel included seroconversions (n = 22), samples from HIV-1 and HIV-2 positive individuals, hospitalized patients, blood donors, high risk individuals. To challenge further the specificity of the assays, large numbers of EIA repeatedly reactive but Western blot negative samples, potentially cross-reactive sera, Western blot indeterminate specimens and samples from pregnant women were tested. In four seroconversion panels, HIV-1 infection was detected one bleed earlier with the AxSYM HIV-1/HIV-2 than with the Abbott HIV-1/HIV-2 3rd Gen. Plus EIA. Although the AxSYM HIV-1/HIV-2 was tested with a higher number of challenging sera than the alternative assays, the specificity was very high (99.4%). The highest number of false positive results was obtained with serum samples that were repeatedly reactive in EIAs different from those compared in the present study. The automated AxSYM system permits the testing of a large sample number in a rapid turn-around time and by random access urgent tests can be carried out even when an assay is in progress.
Automation↗
Insulin-like growth factor-I (IGF-I) plasma concentrations are increased in depressed patients.
There is some evidence that the somatotrophic system in depression, as assessed by basal growth hormone (GH) concentrations and by GH releasing hormone (GHRH) challenge, might be dysfunctional. However, the rather limited data have been inconclusive so far and plasma concentrations of both insulin-like growth factor-1 (IGF-I) and binding proteins (IGFBP 1 to IGFBP-6) have not been measured simultaneously in depressed patients. We studied 24 severely depressed patients and 33 healthy controls and estimated 24-hour mean plasma cortisol, six-hour evening mean plasma growth hormone (GH), morning plasma IGF-I, IGFBP 2 and 3 and GH-binding protein (GH-BP). Twenty-four-hour mean cortisol (306 +/- 69 vs. 196 +/- 30 nmol/l, p < .001) and IGF-I (157 +/- 40 vs. 120 +/- 33 micrograms/l, p < .01) plasma concentrations were found to be significantly increased in depressed patients, while there was no difference in GH or binding proteins between both groups. MANOVA analysis revealed age and diagnosis to have main effects upon plasma IGF-I. Especially young age and a diagnosis of major depression are associated with higher plasma IGF-I. After treatment only patients in remission had attenuated IGF-I plasma concentrations. We conclude that plasma IGF-I is increased in acutely depressed patients similar to other states of hypercortisolemia.
Adult↗
Efficacy of a new prostaglandin E1 regimen in outpatients with severe intermittent claudication: results of a multicenter placebo-controlled double-blind trial.
For the first time efficacy and safety of a new prostaglandin E1 (PGE1) regimen in the treatment of intermittent claudication were evaluated in a randomized, double-blind, placebo-controlled multicenter clinical trial. The study involved 213 outpatients with a maximum walking distance of 50 to 200 m measured on the treadmill (3 km/hr, 12% grade). After a 2-week run-in phase they received a 2-hour intravenous infusion of 60 micrograms PGE1 or placebo 5 days a week for 4 weeks. It was followed by a 4-week interval treatment with the same medication administered only twice a week. Patients were monitored for 3 months when they received no study medication. In the PGE1 group the intention-to-treat analysis (n = 208) revealed an increase in walking distance after 4 weeks of 75% (placebo, 43%). At the end of the interval treatment the walking distance had improved to 101% (placebo, 60%). The results remained virtually constant during follow-up (PGE1, 104%, placebo, 63%). Between-group comparisons showed significant differences in favor of PGE1 for all three time points of measurement (p < 0.05, p < 0.01, and p < 0.05). PGE1 was well tolerated; the rate of adverse reactions related to the treatment was 12.8% (placebo, 7.7%). In summary, these results show that the new PGE1 regimen is effective and safe in the treatment of outpatients with intermittent claudication.
Aged↗
Comparison between esophageal Wallstent and Ultraflex stents in the treatment of malignant stenoses of the esophagus and cardia.
BACKGROUND AND STUDY AIMS: Several published studies have examined various self-expanding metal esophageal stents for use in the palliative treatment of esophageal or cardiac neoplasia, but few have compared different self-expanding metal stents. The aim of this study was to evaluate non-covered Wallstent and Ultraflex prostheses in the treatment of malignancies in the esophagus and the cardiac region. MATERIALS AND METHODS: In a retrospective study, the effectiveness of non-covered Wallstents (46 patients) and Ultraflex stents (36 patients) was compared in the treatment of malignancies in the esophageal and cardiac regions. RESULTS: Reintervention procedures were necessary in 16 of the 46 Wallstent patients (six patients during an early phase) and in 22 of the 36 Ultraflex patients (13 during an early phase) (overall P = 0.022; early P = 0.018). The major complication in the Wallstent group was tumor ingrowth (12 of 35 complications), while in the Ultraflex group, it was incomplete deployment (18 of 49 complications). Incomplete stent deployment occurred more often in patients treated with Ultraflex (P = 0.01), and food impaction was more often observed in the Wallstent group (P = 0.001). In addition, in patients with Ultraflex stents, more complex reinterventions were necessary than those required with Wallstents (four vs. 13 complex reinterventions, P = 0.0046). Wallstents tended to improve dysphagia better than Ultraflex stents. CONCLUSION: Compared to Ultraflex stents, Wallstents have several significant short-term and long-term advantages in the palliative treatment of malignancy of the esophagus and cardia.
Adult↗
Molecular defects in Sanfilippo syndrome type A.
Sanfilippo A syndrome (mucopolysaccharidosis type IIIA, MPS-IIIA) is an autosomal recessive neurodegenerative disorder due to an enzymatic defect of the lysosomal enzyme sulphamidase (EC 3.10.1.1) required for the degradation of heparan sulphate. In this study, molecular defects in the sulphamidase gene of MPS-IIIA patients were investigated in a group of 10 patients of Australian and American origin. The entire coding region of the sulphamidase gene was RT-PCR amplified and one polymorphism (R456H), four novel mutations (S66W, R245H, E447K, 1307 del 9) and one previously described mutation (1284 del 11) were identified by direct PCR sequencing. R245H was present in six patients including one severely affected homozygote. In three of the other patients with R245H, second mutant alleles were identified as S66W, 1284 del 11 and E447K, respectively. S66W was also detected in another patient where the other mutant allele remains undefined. In addition, 1307 del 9 was also detected in a patient with the other mutant allele remaining undefined. Allele specific oligonucleotide hybridisation was used to determine the incidence of these in a population of 26 MPS-IIIA patients (Australian and American) and 60 normal controls (Australian). R245H represented 27% (14/52 alleles) in this total patient population, while the other three changes ranged from 1.9 to 9.6% (1-5 of 52 alleles). The sequence variant, R456H, was shown to be polymorphic as it was present in 55% of normal and 38% of patient alleles. The total combined incidence of these five is 46% of alleles. This is the first study of the molecular defects in MPS-IIIA patients and will greatly assist the development of molecular analysis for MPS-IIIA patients and studies concerned with genotype to phenotype relationships.
Age of Onset↗
Novel mutations in Sanfilippo A syndrome: implications for enzyme function.
Sanfilippo syndrome type A or mucopolysaccharidosis IIIA (MPS IIIA) is an autosomal recessive lysosomal storage disorder caused by the deficiency of sulfamidase. The resulting lysosomal storage of heparan sulfate may lead to severe neurodegeneration preceded by progressive dementia, often combined with aggressive and hyperactive behaviour. A total of 109 patients from four different geographic areas were screened for the common mutation R245H and two other previously identified mutations. SSCP analysis of exons was used to characterize the unknown alleles. We identified 16 novel sequence variants, 12 of them likely to be pathogenic. The majority of the pathogenic variants were single base pair changes leading to missense mutations. Several single base pair deletions/insertions and one nonsense mutation were also identified. Altogether, we were able to characterize 55% of the pathogenic alleles. Sequence homology between sulfamidase and N-acetylgalactosamine 4-sulfatase, the first sulfatase to have its tertiary structure defined, suggests that amino acid residues R74 and T79, which were found to be mutated, are likely to be involved in the formation of the active site of sulfamidase. R245H accounts for 31% of the Sanfilippo A alleles in Australasia, for 19.2% of the alleles in patients from the UK and has a high frequency of 57.8% in patients from The Netherlands. The identification of mutations common in certain geographic regions or ethnic groups will help in the diagnosis of MPS IIIA and allow carrier testing and improved genetic counselling.
DNA Primers↗
Pulse-dosing and conventional application of doxepin: effects on psychopathology and hypothalamus-pituitary-adrenal (HPA) system.
It has been shown that a single pulse-dosing (PD) dose of clomipramine improves depressive symptoms. However, so far PD and conventional (CONV) application of antidepressants have never been directly compared for an extended period. We performed a double-blind study of PD and CONV application of doxepin (DOX) in depressed patients. After a 1-week placebo treatment, nine parents in the PD group received 250 mg of DOX every 6 days and placebo on the other days until day 39. Ten patients in the CONV group received increasing dosages of DOX until day 7 and 250 mg DOX on the other days for 39 days. Three dexamethasone (DEX)-suppression/corticotropin-releasing hormone (CRH)-stimulation tests were completed: (1)during the initial placebo period; (2)on day 9; and (3)on day 21. In the PD group, scores on the Hamilton Rating Scale for Depression (HAM-D) differed from baseline only after day 36 (17.1 +/- 7.0 vs. 22.7 +/- 2.8, p < 0.03). In the CONV group, however, HAM-D scores improved significantly after 2 days (22.8 +/- 7.2 vs. 26.5 +/- 5.7, p < 0.02) and continued to improve until day 39 (7.3 +/- 5.8). From day 25 to 39, there were significant differences between the HAM-D scores of the two groups. In the PD group, the decline of cortisol after DEX pretreatment was nonsignificant (NS) at both follow-up test occasions (35.9 +/- 40.7 vs. 24.0 +/- 20.7 vs. 23.6 +/- 26.6 micrograms/mL). In the CONV group, a significant decrease was observed at the second test (61.8 +/- 61.9 vs. 10.7 +/- 4.2 vs. 19.8 +/- 19 micrograms/mL, p < 0.05, respectively, NS). The area-under-the-curve cortisol response after CRH was attenuated in the PD group (5,667 +/- 2,910 vs. 1,883 +/- 2,178 vs. 2,239 +/- 2,583 [arbitrary unit], p < 0.01, respectively, p < 0.01) and in the CONV group (5,710 +/- 4,734 vs. 1,267 +/- 2,053 vs. 445 +/- 1,016 [arbitrary unit], NS, respectively, p < 0.02. We conclude that CONV application of DOX is clinically superior compared with PD and that both modes of application have attenuating effects on hypothalamus-pituitary-adrenal system activity.
Adult↗
Rapid diagnosis of enterovirus infection by a new one-step reverse transcription-PCR assay.
The AMPLICOR Enterovirus Test was evaluated with 103 cerebrospinal fluid (CSF) specimens. Twenty-seven CSF specimens were culture positive. With the AMPLICOR test, enterovirus RNA was detected in 34 specimens. Compared with culture, the AMPLICOR test gave a sensitivity of 96.3% and a specificity of 100%. The sensitivity of culture was 79.4% in comparison with the AMPLICOR test.
Enterovirus↗
Recent advances in antiretroviral therapy and HIV infection monitoring.
Potent new antiretroviral drugs combined with updated treatment strategies have now achieved efficient inhibition of HIV replication in most patients. The major targets for antiretroviral therapy are the reverse transcriptase and the protease of HIV. Up to date, 11 antiretroviral drugs have been licensed in the US. New nucleoside reverse transcriptase inhibitors (NRTI), i.e. abacavir, and adefovir dipivoxil proved to be effective in clinical trials. The antiretroviral activity and impact on clinical outcome of nonnucleoside reverse transcriptase inhibitors (NNRTI) are mostly short lived. Compared to NRTIs, protease inhibitors (PIs) have the highest antiretroviral activity. New PIs that conserve activity against mutant HIV strains or derivatives that have a simpler biosynthesis are being developed. A major drawback of highly active antiretroviral therapy is the selection of resistant mutants under suboptimal dosage, in advanced stages of disease or after pre-treatment with mono- or double-combination regimens. Monitoring of antiretroviral therapy is achieved by measurement of viral load using nucleic acid amplification techniques. The goal of antiretroviral therapy should be to reduce viral load below the detection limit of current assays in order to delay the emergence of resistant mutants and to maximally reduce disease progression. Recommendations for antiretroviral therapy and monitoring are evolving constantly due to the rapid progress in the development of active compounds and new insights into HIV pathogenesis. Resistance determination of HIV patient isolates seems to play a progressively increasing role in monitoring of antiretroviral treatment since treatment-naive patients may already harbour drug-resistant virus. Due to cross-resistance between different compounds, the choice of the treatment regimen should be guided by resistance patterns of HIV in order to warrant maximal and long-lasting efficiency.
Dideoxynucleosides↗