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Biomedical subjects

C Springer

Publications and source records attributed to C Springer.

At least 19 recordsLinked to original sources
PubMed2000

Exercise, methacholine, and adenosine 5'-monophosphate challenges in children with asthma: relation to severity of the disease.

Bronchial hyperreactivity is a characteristic feature of asthma and can be evaluated by different challenges. The aim of this study was to compare exercise, methacholine (MCH), and adenosine 5'-monophosphate (AMP) challenges in 135 children and young adults (mean age +/- SD, 12.4+/-3.9 years) with asthma, and to examine the utility of the different challenges in predicting those children with asthma likely to require prophylactic antiinflammatory treatment. The sensitivity of MCH challenge in detecting bronchial hyperreactivity (at or below 8 mg/mL) was 98%, that of AMP challenge (at or below 200 mg/mL) 95.5%, and that of exercise (more than 8.2% fall in FEV(1)) was 65%. There was a significant difference between mild asthmatic children (85 patients, intermittent asthma, step 1 of NIH guidelines) and moderate asthmatics (50 patients, steps 2 and 3 of guidelines) in relation to the logarithmic mean provocation concentration to elicit a 20% fall in FEV(1) (PC(20)) to MCH (0.49 mg/mL vs. 0.15 mg/mL, P<0.00001), that to AMP (7.67 mg/mL vs. 3.60 mg/mL, P = 0.001), and in relation to the mean percent fall in FEV(1) after exercise (13.9% vs. 22.0%, P = 0.001). Sensitivity and specificity curves between the two severity groups of asthma were constructed, and the intersection point of the two curves for each type of challenge was determined. When mild asthmatics were compared to moderate asthmatics, the intersection points for MCH, AMP, and exercise were 66%, 63%, and 61%, respectively. Logistic regression analysis and receiver operating characteristic (ROC) curves of the three challenges for the two severity groups of asthma showed that methacholine was a better discriminating challenge between the severity groups than the other two challenges. We conclude that the sensitivities of AMP and MCH challenges in the detection of bronchial hyperreactivity in children and young adults with asthma are very similar and higher than that of exercise. There is a significant difference between mild and moderate asthmatics within the three bronchial challenges, with MCH discriminating better than AMP or exercise between groups.

Adenosine Monophosphate↗
PubMed2000

Gender differences in young adolescents' exposure to violence and rates of PTSD symptomatology.

Gender differences in exposure to violence and levels of PTSD symptomatology were examined in a school-based sample of 621 young adolescents. Also investigated as predictors of PTSD symptoms were cognitive coping strategies, perceived social support, and the affective experience of fear. Results support the importance of evaluating gender differences, differentiating between violence by type and location, and considering both cognitive and affective factors as predictors of PTSD symptomatology.

Adaptation, Psychological↗
PubMed2000

Efficacy and safety of methacholine bronchial challenge performed by auscultation in young asthmatic children.

The measurement of bronchial reactivity is an important aid in the diagnosis of asthma, but the technique using spirometry is not feasible in young children. The aim of the present study was to determine the efficacy and safety of a modification of the chest auscultation method in the assessment of bronchial reactivity to inhaled methacholine in young asthmatic children. One hundred forty-six young children with asthma (mean age, 4.3 yr) underwent bronchial challenges with nebulized methacholine using the auscultation method (PCW). The end point was defined as the appearance of wheezing, oxygen desaturation, or tachypnea. For comparison, 30 children and young adults with asthma underwent bronchial provocation with methacholine using spirometry (PC(20)). A positive response using the auscultation method was observed in 95.9% of the younger children, and wheezes alone or in combination with other signs appeared in 80.8% of them. The mean desaturation at the end point was 4.6% (PCW) and 5.0% (PC(20)), with a similar pattern in the two groups. Cough was not helpful in determining the end point. We conclude that the modified auscultation method is effective and safe, with wheeze appearing at the end point in the large majority of the children.

Adolescent↗
PubMed1999

Cut-off points defining normal and asthmatic bronchial reactivity to exercise and inhalation challenges in children and young adults.

An analysis was undertaken to determine the optimal cut-off separating an asthmatic from a normal response to a bronchial provocation challenge by exercise and the inhalation of methacholine or histamine in children and young adults. Data were extracted, after appropriate correction, from published studies available in Medline of large random populations that complied with preset criteria of suitability for analysis, and the distribution of bronchial reactivity in the healthy population for exercise and inhalation challenges were derived. Studies on the response to exercise and methacholine inhalation in 232 young asthmatics of varying severity were carried out by the authors and the distribution of bronchial reactivity of a young asthmatic population obtained. Comparisons of the sensitivity and specificity of the challenges were aided by the construction of receiver operating characteristic curves. The optimal cut-off point of the fall in forced expiratory volume in one second (FEV1) after exercise was 13%, with a sensitivity (power) of 63% and specificity of 94%. For inhalation challenges, the optimal cut-off point for the dose of methacholine or histamine causing a 20% fall in FEV1 was 6.6 micromol, with a sensitivity of 92% and a specificity of 89%. The cut-off values were not materially affected by the severity of the asthma and provide objective data with which to evaluate the results of bronchial provocation challenges in children and young adults.

Administration, Inhalation↗
PubMed1999

Clinical and genetic risk factors for cystic fibrosis-related liver disease.

OBJECTIVE: The aim of this study was to define the role of possible risk factors for the development of cystic fibrosis (CF)-related liver disease and to analyze the association between liver disease and the different genotypes present in the Israeli CF patient population. PATIENTS AND METHODS: All patients followed at the seven CF centers in Israel were included in this study. Liver disease was determined by persistently elevated serum liver enzymes and/or bilirubin, and/or significant ultrasonographic changes suggestive of chronic liver disease. The following clinical parameters were evaluated: ethnic origin, age at assessment of liver function, sex, history of meconium ileus, pancreatic function, history of distal intestinal obstruction syndrome, pulmonary function, and cystic fibrosis transmembrane conductance regulator mutation analysis. RESULTS: Of the 288 patients screened, 80 (28%) had liver disease. Of the 256 patients with pancreatic insufficiency, 80 (31%) had liver disease compared with none of the 32 patients with pancreatic sufficiency. Genotype-phenotype correlation was performed on 207 patients carrying identified mutations that were previously classified according to phenotype severity. Liver disease was found in 56 (32%) of 173 patients carrying mutations associated with a severe phenotype and in 6 (38%) of 16 patients carrying at least one mutation associated with a variable genotype (G85E and/or 5T allele). None of the 18 patients carrying the 3849+10kb C->T mutation had liver disease. Prevalence of liver disease increased with age. No correlation was found between liver disease and severity of lung disease, nutritional status, history of meconium ileus, or distal intestinal obstruction syndrome. CONCLUSION: CF patients who have pancreatic insufficiency and carry mutations associated with a severe or a variable genotype are at increased risk to develop liver disease.

Adolescent↗
PubMed1998

Helix-helix packing angle preferences for finite helix axes.

Recently, James Bowie addressed the question of how to normalize correctly the distribution of observed helix-helix packing angles in proteins (Bowie, Nature Struct. Biol. 4:915-917, 1997). A hitherto unrealized yet significant bias toward crossed packing angles was revealed. However, the derived random reference distribution of packing angles requires that helices have to be assumed as infinite in length. Here, we complement Bowie's analysis by consideration of the more realistic case where helices are of finite length. As a result, the statistical bias toward near perpendicular packings appears to be even stronger.

Models, Molecular↗
PubMed1998

Lack of large, homozygous deletions of the nephronophthisis 1 region in Joubert syndrome type B. APN Study Group. Arbeitsgemeinschaft für Pädiatrische Nephrologie.

Joubert syndrome type B (JSB) is a developmental disorder of the nephronophthisis (NPH) complex with multiple organ involvement, including NPH, coloboma of the eye, aplasia of the cerebellar vermis, and the facultative symptoms of psychomotor retardation, polydactyly, and neonatal tachypnea. In isolated autosomal recessive NPH type 1 (NPH1), homozygous deletions have been described as causative in more than 80% of patients. Since different combinations of the extrarenal symptoms with NPH occur in JSB, a contiguous gene deletion syndrome in the NPH1 genetic region would seem a highly likely cause for JSB. We therefore examined 11 families with JSB for the presence of extended deletions at the NPH1 locus. Genomic DNA was examined using four consecutive polymerase chain reaction (PCR) markers that are deleted in NPH1 and three PCR makers flanking the NPH1 deletion. In all seven markers examined, there was no homozygous deletion detected in any of the 11 JSB families studied. Since these markers saturate the NPH1 deletion region at high density, this finding excludes the presence of large homozygous deletions of the NPH1 region in these JSB families, making it unlikely that deletions of the NPH1 region are a primary cause for JSB.

Cerebellar Diseases↗
PubMed1998

Gene-directed enzyme prodrug therapy: quantitative bystander cytotoxicity and DNA damage induced by CB1954 in cells expressing bacterial nitroreductase.

Clones of human colon carcinoma (WiDr), ovarian carcinoma (SK-OV-3), and Chinese hamster V79 cells expressing the nitroreductase enzyme (NR) from E. coli B were 52-, 225- and 177-fold respectively more sensitive to a 24-h incubation with the prodrug 5-(aziridin-1-yl)-2,4-dinitrobenzamide (CB1954) than the parent lines. The IC50s of non-NR-expressing bystander cells were measured in the presence of differing proportions of NR-expressing cells. The shift in IC50 was used to calculate a value for the bystander effect, termed the transmission efficiency (TE), which is the decrease in IC50 due to bystander effect as a percentage of the maximum decrease possible. The percentage of NR-expressing cells for which the TE was 50%, (the TE50) is a single datum of bystander efficacy. WiDr and V79 cell lines, had a similar TE50 of approximately 2%. SK-OV-3 gave a lower value of 0.3%. These TE50 correlate with concentrations of cytosolic NR activity, which is distinguished from endogenous DT diaphorase activity by kinetic differences. A novel method is described which enables both DNA crosslinks and drug-induced single-strand breaks to be simultaneously quantified in a sedimentation assay. Using this technique, bystander DNA damage was demonstrated in V79 cells, of approximately 50% of that in activator cells.

Aziridines↗
PubMed1998

Rehabilitation of hypoxemic patients with COPD at low altitude at the Dead Sea, the lowest place on earth.

BACKGROUND: In patients with COPD, oxygen therapy has been shown to improve exercise capacity and survival. Increase in barometric pressure at low altitude can serve as a simple way to improve arterial oxygenation in hypoxemic patients. We have tried to evaluate the effect of staying at low altitude on arterial oxygenation and exercise performance in patients with COPD. PATIENTS AND METHOD: Eleven patients with COPD (9 male, 2 female) aged 38 to 79 years (mean FEV1, 0.96 L; 36% predicted) with hypoxemia (mean PaO2, 54.2+/-8.9 mm Hg) at Jerusalem (altitude 800 m above sea level) were taken down to the Dead Sea area (altitude 402 m below sea level) for 3 weeks. At both locations we tested arterial blood gases, spirometry, progressive exercise, 6-minute walking distance, and sleep oximetry. The study was repeated 2 weeks after returning to Jerusalem. RESULTS: Spirometry results were unchanged. Mean arterial PaO2 rose from 54.2+/-8.9 mm Hg to 69.5+/-11 at the first week and to 66.6+/-11 at the third week of stay (p<0.001). PaCO2 rose from 43.5+/-9.8 mm Hg to 47.7+/-9 and 49.5+/-8.4 (p<0.006). Six-minute walking distance rose from 337+/-107 m to 449+/-73 and 507+/-91 in the third week (p<0.005). Maximum oxygen consumption (VO2max) rose from 901+/-257 mL/min to 1,099+/-255 and 1,063+/-250 mL/min (p=0.01). Sleep oximetry showed an increase in mean sleep arterial oxygen saturation from 86.0+/-4.3% to 89.9+/-4.2% and 88.3+/-3.0 at 1 and 3 weeks, respectively (p<0.05). Following the return to Jerusalem, arterial gases returned to their baseline levels (PaO2, 52.9+/-9.4 mm Hg) but 6-min walking distance remained significantly high, 453+/-47 (p<0.02), and VO2max remained high as well (1,102+/-357 mL/min), although it did not reach statistical significance. CONCLUSIONS: Decline to low altitude or staving at high oxygen environment improves arterial oxygenation and exercise capacity in hypoxemic patients residing in moderate or high altitude. Low altitude (or pressurized wards) can improve pulmonary rehabilitation of hypoxemic patients with COPD.

Adult↗
PubMed1997

The adjacent yeast genes ARO4 and HIS7 carry no intergenic region.

The region between the open reading frames of the adjacent yeast genes ARO4 and HIS7 consists of 417 base pairs (bp). Termination of ARO4 transcription and initiation of HIS7 transcription has to take place within this interval, because both genes are transcribed into the same direction. We show that the ARO4 terminator and the HIS7 promoter are spatially separated, nonoverlapping units. The ARO4 terminator includes 84 bp of the ARO4 3'-untranslated region with several redundant ARO4 3' end processing signals. Deletion of the ARO4 terminator does reduce but not completely shut down its expression. The adjacent region of 40 bp is neither required for correct ARO4 3' end formation nor for HIS7 initiation but contains the nucleotides corresponding to the wild type mRNA 3' ends. The following 280 bp are required for the HIS7 promoter. Replacement of the housekeeping ARO4 promoter by the stronger ACT1 promoter leads to reduced HIS7 expression due to transcriptional interference. This underlines the compactness of the yeast genome carrying virtually no intergenic regions between adjacent genes.

Base Sequence↗
PubMed1997

Yield from flexible bronchoscopy in children.

Flexible fiberoptic (FO) bronchoscopy can now be undertaken readily in children using topical anesthesia and light sedation and has largely supplanted rigid open tube (OT) bronchoscopy for diagnostic purposes. The present study examined the contribution of the FO bronchoscope to clinical management in children presenting with specific types of problems. We examined the first 200 consecutive flexible bronchoscopies performed in 1995 in children under 18 years of age (median age, 2.27 years). Indications for bronchoscopy were noisy breathing (26.5%), recurrent pneumonia (21.0%), suspected pneumonia in an immunocompromised patient (10.5%), atelectasis or bronchial toilet (12.5%), possible foreign body aspiration (13.0%), and miscellaneous other reasons (16.5%). Inspection of the airway was abnormal in 67.0% of all investigations and made a clinically meaningful contribution to management in 67.5%, especially in those with noisy breathing (98.1%), possible foreign body aspiration (100%), and atelectasis (76.0%). Bronchoalveolar lavage (BAL) cytology was abnormal in 80.4% of the 107 lavages, but contributed little to management except in those with recurrent pneumonia (73.8%). Bacteria were isolated in 26.6% of the 109 specimens cultured, but this finding rarely affected management. Fungi were isolated in 47.4% of the 19 lavages in the immunocomprised group. Together, inspection, BAL and microbiology contributed to management in a mean of 90.5% (range, 76.2-100%) of patients in the various groups. We concluded that a high yield of clinically meaningful information can be expected from FO bronchoscopy in children when coupled with BAL and microbiological studies of lavage fluid.

Bronchoalveolar Lavage Fluid↗
PubMed1997

Regulation of the yeast HIS7 gene by the global transcription factor Abf1p.

The HIS7 gene of Saccharomyces cerevisiae encodes a bifunctional glutamine amidotransferase: cyclase that catalyzes the formation of biosynthetic precursors for histidine and adenine. HIS7 is activated by Gcn4p upon amino acid starvation and by the Bas1/2p complex in response to adenine limitation. Mutation analysis of the HIS7 promoter in a deltagcn4 background revealed a polyd(A/T) stretch and a d(CT) repeat as essential elements for Gcn4p-independent basal HIS7 transcription. The protein binding this element was enriched and identified as the multifunctional DNA-binding protein Abf1p. Abf1p binds specifically to the d(CT) repeat sequence, which represents a novel Abf1p-binding motif, and protects 17 nucleotides from digestion by DNase I. In addition, Abf1p binding causes bending of the HIS7 promoter structure.

Aminohydrolases↗
PubMed1997

[Color Doppler ultrasound of uterine, fetoplacental and fetal blood vessels in the 2nd trimester in normal pregnancies].

We investigated 69 healthy women with normal pregnancy and delivery in order to establish normal values for the second trimester of gestation. In a cross-sectional study we measured the pulsatility index (PI), the maximal systolic velocity (V-MAX) and the mean velocity (V-MEAN) in the uterine arteries (UAA), the umbilical artery (UA), the fetal thoracic aorta (FTA) and the middle cerebral artery (MCA) from the 14th to the 24th week of gestation. A regression analysis shows a significant slope of the PI of UAA and UA (p < 0.01), whereas in contrast to the UA there is no significant difference of the median values of the UAA-PI from the 18th week of gestation. With progressive gestation V-MEAN of UAA increases more (p < 0.001) than V-MAX (p < 0.05) as a result of the increasing diastolic blood flow. In the UA there is also a significant rising trend of V-MAX and V-MEAN (p < 0.0001). No significant changes of the PI of FTA and MCA are seen, although there is a slight increasing trend. After the 20th week in the MCA a marked tendency to high PI-values is observed, whereas there is a change between different flowpatterns prior to the 20th week. V-MAX and V-MEAN of FTA increases significantly, but there is no change in the MCA. Our results for UAA and UA correspond to the known morphologic changes in the utero- and fetoplacental vessels in the second trimester and are comparable to other results. Particularly the physiology of the cerebral perfusion needs to be investigated more intensively. These normal values provide a good basis for early and complex assessment of a disturbed perfusion in the second trimester.

Adult↗
PubMed1997

[Multivariate analysis of the significance of vaginal bacterial colonization in the occurrence of a preterm birth with various risk parameters].

Using a discriminance analysis we investigated the interactions between parameters of the vaginal flora and subclinical infection regarding preterm birth. The prospective study includes 222 single pregnancies, 114 of them with preterm labour or premature rupture of the membranes (PROM). The analysis includes information of a vaginal/ cervical smear (total number of pathogenic germs, species and groups of pathogenic germs), vaginal pH, maternal white blood cell count (WBC), C-reactive protein (CRP) and temperature. A normal vaginal flora was found in only 19%. Pregnancies with preterm labour have a higher quantity of pathogenic germs, whereas there is no difference of the germ group distribution. Moreover, pregnancies with preterm labour and 2 or 3 pathogenic germs have a higher rate of preterm birth. The discriminance analysis shows that only the affiliation the risk group with preterm labour and the parameters CRP and WBC have a significant selectivity for consequent preterm birth, but not the parameters containing information of the vaginal flora. The same is valid for the group with preterm labour, where only the parameters PROM and WBC are able to select significantly for preterm birth.

Adult↗
PubMed1997

[Infantile type Bland-White-Garland syndrome as a cause of death in Rh incompatibility].

The faulty origin of the left coronary artery from the pulmonary artery is with an incidence of 1:300,000 newborns a very rare heart defect. We report a case of a pregnancy with two intrauterine blood transfusions in the 30th and 32nd week of gestation because of Rh-incompatibility and fetal anaemia. Dopplersonographic and echocardiographic parameters were normal. In the 32nd week of gestation delivery was induced (birth weight 2240 g, cord pH value 7.35, Apgar-score 8/9/9). Under a therapy with respiration, blood exchange transfusion and cardiotonic drugs the newborn died in the second week. The autopsy showed a general immaturity, a haemosiderosis of spleen, liver and lungs, a marked cellular jaundice and signs of a multi-organ-failure. The sinus of the pulmonary valve was the origin of the left coronary artery. In case of a seriously impaired pumping action and after exclusion of other heart defects the Bland-White-Garland-Syndrome (BWGS) has to be considered. Although a prenatal diagnosis of BWGS is with high resolution-ultrasound possible, the early postnatal diagnosis seems to be more relevant.

Adult↗
PubMed1996

Amino acid and adenine cross-pathway regulation act through the same 5'-TGACTC-3' motif in the yeast HIS7 promoter.

The HIS7 gene of Saccharomyces cerevisiae encodes a bifunctional glutamine amidotransferase:cyclase catalyzing two reactions that lead to the formation of biosynthetic intermediates of the amino acid histidine and the purine adenine. The HIS7 gene is activated by GCN4p under environmental conditions of amino acid starvation through two synergistic upstream sites GCRE1 and GCRE2. The BAS1p-BAS2p complex activates the HIS7 gene in response to adenine limitation. For this activation the proximal GCN4p-binding site GCRE2 is required. GCN4p and BAS1p bind to GCRE2 in vitro. Under conditions of simultaneous amino acid starvation and adenine limitation the effects of GCN4p and BAS1/2p are additive and both factors are necessary for maximal HIS7 transcription. These results suggest that GCN4p and BAS1/2p are able to act simultaneously through the same DNA sequence in vivo and use this site independently from each other in a non-exclusive manner.

Acyltransferases↗
PubMed1996

[An unusual bronchial foreign body: a fragment of a tracheostomy tube].

A fragment of a fractured tracheostomy tube as a foreign body in the bronchus is very unusual. We report an 18-year old male with Hunter's syndrome who presented with fever and bronchorrhea. He had worn a tracheostomy tube for 2 years without its being removed for cleaning. Chest X-ray showed an opaque foreign body in the right main bronchus which was removed through a flexible bronchoscope and found to be a piece of the broken edge of the outer cannula of a tracheostomy tube. We suggest regular examination of tracheostomy tubes for signs of wear-and-tear and recommend their periodic renewal before they become worn out.

Adolescent↗