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Biomedical subjects

K Schmitt

Publications and source records attributed to K Schmitt.

At least 19 recordsLinked to original sources
PubMed1996

Construction of a radiation hybrid map of chromosome 9p.

A radiation hybrid panel has been constructed for chromosome 9 using the somatic cell hybrid GM10611 as the donor cell line fused to the hamster cell line A23. The hybrid GM10611 was characterized by fluorescence in situ hybridization and reverse painting onto spreads of normal human metaphase chromosomes; it contains human chromosome 9 as the only cytogenetically detectable human material. GM10611 was irradiated with 6000 rads of X rays prior to fusion, a total of 93 independent clones were selected, and frozen stocks and DNA were prepared from each clone. These clones were screened by PCR amplification with oligonucleotide primers for sequence-tagged sites specific for 50 single-copy loci mapping to the short arm of chromosome 9. The average retention frequency of these hybrids was approximately 23%. The markers were ordered into a framework map by analyzing coretention patterns, minimizing the number of obligatory chromosome breaks, and finally confirming the order by maximum likelihood methods. A framework map ordering 27 markers with odds greater than 1000:1 was constructed. A further 16 markers that could not be uniquely placed on the map with the required support were positioned within a range of adjacent intervals.

Animals↗
PubMed1996

Construction of a mouse whole-genome radiation hybrid panel and application to MMU11.

Whole-genome radiation hybrids have been used to construct human genome maps that integrate different types of markers. To investigate this methodology in mammalian species other than humans, a panel of 164 mouse x hamster whole-genome radiation hybrids was constructed. This set of hybrids was used to produce a high-resolution map of a region on MMU11 that included microsatellite markers and cDNA sequences. The mouse homologue of the human SRY-related gene SOX9 was mapped to an interval of approximately 1.1 cM flanked by the microsatellite markers D11Mit11 and D11Mit291. This interval includes the region containing the mouse Tail-short mutation, a possible homologue of the human syndrome campomelic dysplasia, which is caused by mutations in SOX9. Our results suggest that whole-genome radiation hybrid technology will be a useful adjunct to mapping the genomes of nonhuman mammalian species.

Animals↗
PubMed1996

All-trans retinoic acid and short-time, high-dose cytarabine in two children with acute promyelocytic leukemia.

We report on two girls, 3 and 13 years old, with acute promyelocytic leukemia (APL) who were successfully treated with all-trans retinoic acid (ATRA) 45 mg/m2/day. "Retinoic acid syndrome" was prevented with short-time treatment of high dose (4 x 1.5 g/m2) cytarabine. This regimen was well tolerated, although both children were critically ill. They achieved a complete remission confirmed by light microscopy, but reverse transcriptase polymerase chain reaction remained positive after ATRA, underlining the need of further chemotherapy.

Adolescent↗
PubMed1996

Regional assignment of human ESTs by whole-genome radiation hybrid mapping.

The UK HGMP Resource Centre's collection of human partial cDNA sequences (ESTs) have been examined for suitability for mapping by PCR on a panel of somatic cell hybrids. The chromosomal assignments of 92 ESTs were determined with a monochromosomal hybrid panel, and a subset of 45 were linked to genetic markers with a panel of whole-genome radiation hybrids (WG-RHs). These results demonstrate the potential of WG-RHs to construct a transcript map of the human genome.

Base Sequence↗
PubMed1996

Spontaneous closure of the human fetal ductus arteriosus--A cause of fetal congestive heart failure.

OBJECTIVE: Closure of the fetal ductus arteriosus, which is usually due to nonsteroidal antiinflammatory agents, may be detrimental. Therefore prenatal and postnatal clinical and echocardiographic findings in four human fetuses with spontaneous ductus arteriosus occlusion are reported. STUDY DESIGN: Echocardiographic and clinical data were retrospectively analyzed. RESULTS: Spontaneous closure of the ductus arterious was discovered in four fetuses (gestational age 34 to 38 weeks). No mother had received nonsteroidal antiinflammatory agents. Enlargement of the right heart and pulmonary arteries and tricuspid and pulmonary regurgitation were present in all cases. Two fetuses had right ventricular hypertension. Postnatally their right ventricular function recovered promptly. The others had severe right heart failure with abnormal umbilical venous pulsations. After immediate delivery none had signs of persistent pulmonary hypertension. However, they have echocardiographic evidence of right ventricular dysfunction 2 to 6 months after delivery. CONCLUSIONS: Occlusion of the fetal ductus arteriosus may also occur in the absence of treatment with nonsteroidal antiinflammatory agents. Immediate delivery resulted in good clinical outcome, although right ventricular dysfunction may persist.

Constriction, Pathologic↗
PubMed1996

Insulin, insulin-like growth factor-binding protein-1, and sex hormone-binding globulin in patients with Turner's syndrome: course over age in untreated patients and effect of therapy with growth hormone alone and in combination with oxandrolone.

We have studied the course over age of fasting insulin, sex hormone-binding globulin (SHBG), and insulin-like growth factor (IGF)-binding protein-1 (IGFBP-1) in untreated children with Turner's syndrome (TS) and measured the course of these parameters during therapy with GH alone and in combination with oxandrolone. Forty patients with TS, aged 3.7-16.4 yr, were investigated before any therapy. Fasting insulin levels increased significantly with chronological age, whereas SHBG and IGFBP-1 decreased with chronological age, and serum concentrations of these parameters were in the normal range. SHBG and IGFBP-1 were not coregulated by insulin in TS as previously reported under physiological conditions; IGFBP-1 was inversely correlated with insulin, but SHBG was not, and neither parameter was correlated with the other. Twenty-eight patients were further investigated 3, 6, 9, and 12 months after the start of GH monotherapy (12-18 IU/m2-week) and 3, 6, 9, and 12 months after the addition of oxandrolone (0.0625 mg/kg.day; n = 16). There was a significant increase in insulin levels during GH monotherapy and a further increase during combination therapy, with peak levels 3 months after the start of GH and combination therapy, respectively. Both SHBG and IGFBP-1 levels decreased significantly during GH monotherapy, with a further dramatic decrease after the addition of oxandrolone. Levels of free testosterone were unaffected by both treatment regimens. IGFBP-1 was inversely correlated with insulin concentrations at all time points after the start of therapy. SHBG was inversely correlated with IGF-I concentrations, but showed no relation to insulin concentrations during GH monotherapy. In conclusion, there were no abnormalities in serum concentrations of insulin, SHBG, and IGFBP-1 in untreated patients that could help to explain the retarded growth in patients with TS. All effects of combined GH and oxandrolone therapy on endocrine parameters such as insulin, SHBG, IGFBP-1 and IGF-I mimic the endocrine pattern normally observed during the pubertal growth spurt. Our data confirm the importance of insulin in the regulation of IGFBP-1, but do not point to a coregulation of IGFBP-1 and SHBG by insulin in patients with TS.

Adolescent↗
PubMed1996

Attention in direct and indirect memory tasks with short- and long-term probes.

In two experiments, college students verified the answers to addition problems as their primary task while simultaneously viewing a word or nonword. The degree of attention allocated to the verbal stimulus varied depending on the difficulty of the problem and the instructions given. After each problem, a test probe assessed either a direct test of recognition memory or an indirect test of repetition priming in lexical decision at lags of 0, 1, or 8 intervening trials. The degree of attention at encoding and lag strongly affected recognition sensitivity (d'), but only lag affected recognition latencies. The repetition-priming effect neither declined with lag nor varied with the degree of attention. The degree of attention at encoding thus affects direct and indirect test performance differentially, a finding consistent with the distinction between explicit and implicit systems of long-term memory.

Attention↗
PubMed1995

Early detection of doxorubicin and daunorubicin cardiotoxicity by echocardiography: diastolic versus systolic parameters.

Doxorubicin and daunorubicin are effective anticancer agents in children, however, their therapeutic value is limited by myocardial cardiotoxicity. In 14 children (median age 5.0 years, range 3-12) prospective studies were performed using pulsed Doppler echocardiography to assess the changes in left ventricular systolic and diastolic filling dynamics. None of these children developed cardiomyopathy. M-mode echocardiographic systolic parameters and Doppler transmitral flow velocities were analysed at baseline, after a cumulative anthracycline dose of 138 +/- 26 mg/m2 (second examination) and after 240 +/- 15 mg/m2 (third examination). At the second examination the acceleration time/ejection time ratio was significantly reduced (P < 0.01), but this was no longer evident at the third examination. There was no significant change of peak velocity over aortic valve, pre-ejection period and change of velocity over time. In contrast, three diastolic parameters changed significantly; the late over early inflow velocity (P < 0.05), mitral valve late time velocity integral (P < 0.01 at the second and P < 0.05 at the third examination) and the ratio A-TVI/TVI (P < 0.025 and P < 0.01). At the third examination the velocity of the A wave was also significantly increased. CONCLUSION In anthracycline treated children left ventricular diastolic function deteriorates before systolic function. Diastolic function parameters should be used rather than systolic parameters to monitor these patients.

Cardiomyopathies↗
PubMed1995

Treatment of patients with Ullrich-Turner syndrome with conventional doses of growth hormone and the combination with testosterone or oxandrolone: effect on growth, IGF-I and IGFBP-3 concentrations.

UNLABELLED: Thirty-nine girls with Ullrich-Turner syndrome (UTS) (median age 9.5 years) were treated with growth hormone (GH) with either 12 or 18 IU/m2 per week for 12 months followed by combination therapy with either oxandrolone (Ox) (0.0625 mg/kg/day po) or low-dose testosterone (T) (5 mg in every 2 weeks). Growth velocity improved significantly after 12 IU/m2 per week (6.4 +/- 1.7 cm/year vs 4.0 +/- 1.3 cm/year, x +/- SD, P < 0.001) and 18 IU/m2 per week of GH (6.5 +/- 1.3 cm/year vs 4.5 +/- 1.4 cm/year, P < 0.001). Ox, but not T was effective in maintaining growth velocity during the 2nd year of therapy (6.9 +/- 1.3 vs 5.3 +/- 1.5 cm/year). Basal insulin-like growth factor-I (IGF-I) concentrations were in the lower normal range and increased significantly in patients treated with 18 IU/m2 per week (357 +/- 180 ng/ml vs 160 +/- 84 ng/ml) and 12 IU/m2 per week (273 +/- 121 ng/ml vs 140 +/- 77 ng/ml). IGF-I concentrations increased further after addition of Ox (533 +/- 124 ng/ml, P < 0.001) or T (458 +/- 158, P < 0.05). IGFBP-3 concentrations were in the upper normal range before therapy and increased only moderately in both GH dosage groups. However, IGF binding protein-3 (IGFBP-3) concentrations were not affected by additional Ox or T treatment. CONCLUSIONS: 1. Conventional GH doses are effective in increasing growth velocity in UTS, especially, when combined with Ox.(ABSTRACT TRUNCATED AT 250 WORDS)

Age Determination by Skeleton↗
PubMed1995

Nephropathy with Wilms tumour or gonadal dysgenesis: incomplete Denys-Drash syndrome or separate diseases?

UNLABELLED: We report three children, one presenting with nephropathy, bilateral Wilms tumour (WT) and cryptorchism, one with combined nephropathy and gonadal dysgenesis and one with nephropathy which developed 13 years after a WT. The first case was recognized as typical Denys-Drash syndrome (DDS) which is characterized by the combination of nephropathy, intersex disorders and WT. The two other patients, who did not express the full spectrum of the syndrome, were older than 10 years, when they reached and stage renal failure. The fact that nephropathy in childhood is combined with such rare diseases like gonadal dysgenesis and/or WT, supports the concept of a common aetiology with DDS. Therefore, the patients were analysed for possible Wilms tumour suppressor gene (WT1) mutations. In all three individuals mutations in the heterozygous configuration could be demonstrated. CONCLUSION: These results provide evidence that incomplete and complete DDS are diseases of the same spectrum. WT1 analysis of more children with two symptoms of the triad of DDS should be helpful in establishing genotype-phenotype correlations and in understanding differences in the clinical picture of DDS.

Adolescent↗
PubMed1995

Aldosterone and testosterone producing adrenal adenoma in childhood.

An 8-year-old boy presented with precocious puberty and hypertension. He had hypokalemia, increased serum aldosterone and testosterone levels and low plasma renin activity. An adrenal adenoma was found using imaging methods and was removed. Postoperatively aldosterone, testosterone and blood pressure returned to normal. Renal ultrasonography findings were consistent with nephrocalcinosis, which might be explained by long lasting hypokalemic metabolic alkalosis and hypercalciuria. Precocious pseudopuberty progressed into true puberty due to the maturational effect of testosterone. Nephrocalcinosis was still present 8 years later and hypertension was recurring obviously as a consequence of increased peripheral resistance.

Adenoma↗
PubMed1995

First experience with prognostic factors in unselected neuroblastoma patients. The Austrian Neuroblastoma 87 Study.

Between January 1987 and December 1993, 117 patients were registered in the Austrian A-NB87 study. The male/female ratio was 1.18, with 50 patients below the age of 1 year at diagnosis. Patients were assigned to stage according to the result of primary surgery in localised disease. Age, ferritin and neuron specific enolase were used in addition in stage III disease for risk-adapted treatment. Adrenal or pelvic primary tumour sites were mainly associated (81%) with advanced disease. The median observation time of the study is 3.5 years. The overall survival at 3 years was excellent in low stage disease and IVs patients, i.e. 100% for stage I and IIA (20 patients), 92% in stage IVs (13 patients), 81% in stage IIIA (18 patients) and 69% in stage IIB (8 patients). Stage IV (38 patients) showed a survival rate of 51%, whereas stage IIB (10 patients) had the worst outcome in this study, i.e. 20%, due to treatment-related toxicity. Significant unfavourable prognostic factors were neuron specific enolase (NSE) > 100 ng/ml, ferritin > 300 micrograms/ml and amplified MYCN. This study achieved a better survival rate in stage IV patients and a subgroup of stage III in comparison to our previous study (Pädiatrie und Pädologie 1986, 21, 269) and gives the basis to further reduce treatment intensity in low-risk disease based on biological factors. However, prognosis for high-risk cases was still poor in spite of a very aggressive treatment concept.

Age Factors↗
PubMed1995

[Is subconjunctival steroid administration in addition to local therapy after cataract operations necessary? A laser tyndallometric study].

UNLABELLED: Subconjunctival steroids are often injected at the end of cataract surgery. In the present laser flare-cell meter study, we investigated whether this procedure improves the anti-inflammatory effect of steroid eye drops. PATIENTS AND METHODS: Thirty patients (69-81 years of age) without preexisting deficiencies of the blood-aqueous barrier were investigated preoperatively and after ECCE with PC-IOL implantation. The laser flare-cell meter (model FC 1000; Kowa Company) used for examination permits sensitive and exact determination of aqueous flare. The patients were randomly assigned to one of the following two treatment groups: group A: topical therapy with prednisolone 1% eye drops (Inflanefran forte) 5 times per day; group B: subconjunctival injection of 4 mg dexamethasone (Fortecortin) immediately at the end of surgery; topical therapy as in group A. In addition, all patients received antibiotic therapy using gentamicin eye drops. Oral steroids were not administered. RESULTS: Under topical therapy with prednisolone 1% (group A), the aqueous flare (in photon counts/millisecond) increased from a preoperative value of 10.2 +/- 2.5 (mean +/- SD) to 37.3 +/- 11.1 in the afternoon after surgery (8 h postoperatively) and decreased to 30.9 +/- 38.7 and 27.8 +/- 3.2 on days 1 and 3 after surgery. With additional steroid injection (group B), the flare accounted to 31.7 +/- 8.7 in the afternoon after surgery and to 31.3 +/- 5.9 and 27.1 +/- 4.7 on days 1 and 3 after surgery, respectively. There was no significant group difference (P > 0.3). CONCLUSIONS: After uncomplicated cataract surgery, subconjunctival steroid injection (4 mg dexamethasone) does not improve the effect of potent anti-inflammatory topical therapy (prednisolone 1% eye drops).

Aged↗
PubMed1995

[Monotherapy vs combination therapy with topical prednisolone and indomethacin].

UNLABELLED: The anti-inflammatory effects of topical steroids and nonsteroidal anti-inflammatory drugs (NSAID) are claimed to be additive, according to fluorophotometric measurements. This finding was reevaluated using laser flare-cell photometry. PATIENTS AND METHODS: Thirty patients (61-79 years of age) without pre-existing deficiencies of the blood-aqueous barrier were investigated preoperatively as well as on day 1 and 3 after ECCE with IOL implantation. The laser flare-cell photometer (model FC-1000; Kowa Company) which was used for examination enables sensitive and exact in vivo determination of aqueous flare. The patients were randomly assigned to one of the following three treatment groups: group A, monotherapy with prednisolone 1% eyedrops (Inflanefran forte); group B, monotherapy with indomethacin 1% eyedrops (Chibro Amuno); group C, combination therapy with prednisolone 1% + indomethacin 1% eyedrops. One drop of either drug was administered five times per day to each patient, beginning immediately after completion of surgery. In addition, all patients received antibiotic therapy with gentamicin. Parabulbar or oral steroids were not administered. RESULTS: Under monotherapy with prednisolone, the flare (photon counts/ms) on days 1 and 3 postoperatively averaged 30.9 and 27.8, respectively. Under indomethacin monotherapy, the flare values were similar (no significant differences). Under combination therapy with prednisolone+indomethacin, however, the flare values were significantly lower both on day 1 (24.2) and on day 3 (20.6). CONCLUSIONS: Combination therapy with topical prednisolone+indomethacin thus seems superior to monotherapy with either of these agents. This confirms the previous fluorophotometric finding that the anti-inflammatory effects of topical steroids and NSAID are additive, a phenomenon attributable to different pharmacological sites of action.

Aged↗
PubMed1994

Frequent recombination in the human T-cell receptor beta gene complex.

Although individual TCRVBV gene segments exhibit limited polymorphism, human T-cell receptor beta (TCRB) haplotypes are characterized by multiple different combinations of allelic markers. This observation suggests that genetic recombination may have played a role in the generation of these haplotypes. Meiotic recombination in a region spanning approximately 250 kilobases (kb) at the 3' end of the TCRB gene complex was investigated by extended family studies and by analysis of single sperm. Segregation patterns of polymorphic TCRB markers in families allowed the assignment of TCRB alleles to parental haplotypes and detection of recombinants among the offspring. Among the 178 informative paternal meioses, four (approximately 2%) were recombinant, whereas no recombinants were found in the 199 maternal meioses. In addition, segregation of two allelic markers was examined in a total of 1101 individual sperm from two heterozygous donors to detect exchange events in this region. The results revealed a similar rate of recombination, approximately 1.3%, which, along with the family data, suggests that at, least in males, meiotic recombination in this 250 kb region may be six times higher than the "average" rate of 1% per 10(6) bases that has been estimated for the human genome.

Base Sequence↗