PubMed Health⌕ Search

Biomedical subjects

G Heimann

Publications and source records attributed to G Heimann.

At least 19 recordsLinked to original sources
PubMed1998

Permutational distribution of the log-rank statistic under random censorship with applications to carcinogenicity assays.

In the random censorship model, the log-rank test is often used for comparing a control group with different dose groups. If the number of tumors is small, so-called exact methods are often applied for computing critical values from a permutational distribution. Two of these exact methods are discussed and shown to be incorrect. The correct permutational distribution is derived and studied with respect to its behavior under unequal censoring in the light of recent results proving that the permutational version and the unconditional version of the log-rank test are asymptotically equivalent even under unequal censoring. The log-rank test is studied by simulations of a realistic scenario from a bioassay with small numbers of tumors.

Animals↗
PubMed1997

Nasopharyngeal carcinoma in childhood and adolescence: concept and preliminary results of the cooperative GPOH study NPC-91. Gesellschaft für Pädiatrische Onkologie und Hämatologie.

BACKGROUND: The increasing use of chemotherapy has improved the prognosis of patients with nasopharyngeal carcinoma (NPC), and the authors demonstrated the beneficial effect of adjuvant interferon (IFN)-beta in a previous pilot study of children with advanced stage NPC. The current multi-institutional, cooperative GPOH (Gesellschaft für Pädiatrische Onkologie und Hämatologie) study NPC-91 was begun in 1992 to determine the efficacy of preradiation chemotherapy, radiotherapy, and adjuvant IFN-beta, in the treatment of advanced stage NPC. METHODS: Of a total of 22 patients, 21 had American Joint Committee on Cancer Stage III or IV disease, and 1 had Stage II disease. The median age was 12 years (range, 8-16 years). Twenty of 22 received 3 courses of preradiation chemotherapy consisting of methotrexate 120 mg/m2 on Day 1, cisplatin 100 mg/m2 on Day 1, and 5-fluorouracil 1000 mg/m2 for five days as well as 6 doses of leucovorin 25 mg/m2 every six hours beginning on Day 2. The Stage II patient received no chemotherapy, and chemotherapy was terminated for another during the first course. All patients had radiation therapy, stratified by stage. The cumulative dose to the primary sites was 59.4 gray (Gy), with single doses of 1.8 Gy. A total of 45 Gy was delivered to the neck area. Finally, all patients were treated with recombinant IFN-beta (10(5) U per kg of body weight) 3 times a week for 6 months. RESULTS: The response rate was 91%. These patients stayed in first remission during a median follow-up of 32 months. With the exception of one reversible cardiotoxicity, moderate chemotherapy-related toxicity was observed. CONCLUSIONS: In this study, patients with advanced stage NPC had a good prognosis with treatment consisting of neoadjuvant cisplatin and 5-fluorouracil, radiotherapy, and adjuvant IFN-beta. It is particularly noteworthy that distant metastases did not develop.

Adenocarcinoma, Clear Cell↗
PubMed1997

Diagnostic yield of noninvasive high spatial resolution electromyography in neuromuscular diseases.

High Spatial Resolution electromyography (HSR-EMG), a new kind of noninvasive surface EMG based on a spatial filtering technique, was evaluated with respect to the diagnosis of neuromuscular diseases. HSR-EMG measurements were recorded from 61 healthy subjects and 72 patients with different neuromuscular diseases and analyzed quantitatively. The results indicate that a few parameters such as muscular conduction velocity, dwell time over root mean square, autocorrelation function, and chi-value are sufficient to recognize and classify specific signal alterations due to neuromuscular disorders. A diagnostic evaluation procedure calculating automatically the most probable diagnosis from the parameter results could assign the correct diagnosis to about 81% of the investigated patients and healthy subjects. Myopathic disorders were recognized with a sensitivity of 85% (specificity: 97%), neuropathic disorders with a sensitivity of 68% (specificity: 98%). We conclude that HSR-EMG shows a diagnostic validity similar to that described in literature for needle EMG. Moreover, the noninvasive technique provides the advantage of a simple and painless application.

Adolescent↗
PubMed1997

Combined pituitary deficiencies of growth hormone, thyroid stimulating hormone and prolactin due to Pit-1 gene mutation: a case report.

UNLABELLED: A child exhibited postnatal obstipation and icterus together with severe growth failure during the 1st year of life, a small facial skull and a prominent forehead. Endocrine work-up established the diagnosis of combined pituitary deficiencies of growth hormone, TSH and prolactin. Subsequently, the Pit-1 gene was analysed in the patient and both parents. A single point mutation was detected in exon 6 of the child: a C to G transversion on one allele, causing arginine in position 271 to be substituted by tryptophan (R271 W). This position is known as a "hot spot" for mutations. The inheritance is autosomal-dominant, as the mutated gene product interferes with DNA-binding of the wild-type protein. In contrast, other mutations in the PIT-1 gene are inherited in an autosomal-recessive mode. CONCLUSION: Diagnosing Pit-1 gene mutations as a rare cause of combined pituitary deficiency is important both for genetic counselling as well as for predicting the future course in the patient (spontaneous puberty, no glucocorticoid substitution necessary during stress periods).

Arginine↗
PubMed1997

Central pontine myelinolysis associated with acquired folate depletion.

After long-standing malnutrition a 15-month-old boy with signs of kwashiorkor was admitted in a moribund state with serious hyponatraemic dehydration, hypothermia, somnolence, and signs of a pontine disconnection syndrome. Folic acid levels were below the detection level in the presence of normal cobalamin levels. MRI of the brain showed global volume loss and signal abnormalities on the T2-weighted images suggestive for central pontine myelinolysis (CPM). Brainstem acoustic evoked responses have remained normal. The serious metabolic and nutritional derangements required substitution of folic acid, vitamins and trace elements as well as slow correction of hyponatraemic dehydration with return of the sodium level over a period of four days. This therapeutic regimen resulted in complete neurological recovery. Follow-up MRI documented normalisation of the initial pathologic findings. The hypothesis was put forward linking the pathogenesis of CPM with the combination of folate depletion and superimposed hyponatraemic dehydration. The previously acquired folate depletion could affect normal appositional function of myelin basic protein molecules due to insufficient methylation of arginine in position 107. The subsequent development of intramyelinic edema and CPM will then be triggered by the superimposed hyponatraemic dehydration. The verification of this hypothesis requires further investigations.

Dehydration↗
PubMed1997

Genetic disorders and cerebellar structural abnormalities in childhood.

Amongst 78 patients with either unilateral or bilateral (ponto-) cerebellar hypoplasia, atrophy or lesions on neuro-imaging (CT and/or MRI), 16 showed unilateral hypoplasia or lesions, 15 vermis defects, nine pontocerebellar hypoplasia, 10 non-progressive conditions with bilateral cerebellar hemisphere hypoplasia or lesions and 28 progressive cerebellar atrophy. Known genetic conditions did not occur with unilateral cerebellar involvement, whereas a high incidence of mostly autosomal recessively inherited diseases could be diagnosed in more than half of the patients with either pontocerebellar hypoplasia or progressive bilateral cerebellar atrophy. A minority of patients with vermis defects or non-progressive cerebellar hypoplasia suffered from genetic conditions. An overview of the literature is presented describing genetic and non-genetic syndromes, or metabolic disorders associated with cerebellar structural abnormalities. From these data, new proposals for improved diagnostic investigations will be presented.

Adolescent↗
PubMed1997

GH and TSH deficiency.

Hypothyroidism is a recognised complication of GH therapy in GH deficient children. The mechanisms involved include direct effects on thyroid function but also result from the close interrelationship of pituitary cell-lines that differentiate during embryonic development of the anterior pituitary gland. Among numerous pituitary transcriptionfactors that orchestrate pituitary organogenesis Pit-1 was the first to be recognised and is the most extensively studied. Mutations in the Pit-1 gene account for a form of combined pituitary hormone deficiency for GH, Prolactin (Prl) and TSH (CPHD). Despite the variability of the clinical presentation of this syndrome at the time of initial diagnosis, all forms finally result in severe retardation of growth and development due to GH-deficiency and hypothyroidism. More than half of the families with a combined pituitary hormone deficiency have not disclosed any Pit-1 abnormalities. Evidence is accumulating that Prop-1, a transcriptionfactor expressed temporarily in the fetal anterior pituitary, could be a candidate for patients with a Pit-1 phenotype without any Pit-1 gene abnormalities.

DNA-Binding Proteins↗
PubMed1996

Gastroesophageal reflux in infants: evaluation of a new intraluminal impedance technique.

In this study, pH metry was simultaneously applied with a new technique, the intraluminal multiple electrical impedance (IMP) procedure, for measuring gastrointestinal motility for gastroesophageal reflux (GER) detection. Seventeen infants with clinical symptoms of GER disease such as recurrent apnea, aspiration pneumonia, wheezing, and failure to thrive were investigated during two feeding periods. A single catheter combining a pH electrode with seven electrodes for impedance measurements over a distance of 8.5 cm was used for the investigation. In all patients, 185 acid episodes were detected by pH metry. In 106 of these 185 acid episodes, a unique pattern in the IMP readings was noted, indicated by a retrograde esophageal volume flow. These episodes were regarded as acid GER episodes. Seventy-one of the 185 acid episodes occurred during the clearance process of a preceding acid GER characterized by typical IMP readings of an anterograde bolus transport. Eight of 185 acid episodes were missed in the IMP readings for technical reasons. The IMP pattern described as characteristic for a GER was observed in 490 other episodes not detected by pH metry. More than 75% of all GER detected by IMP reached the pharyngeal space; 73% of all GER occurred during feeding and the first 2 postprandial hours and 27% occurred during the remaining time until the next feeding. Even during the latter period, 34% of GER were detected by IMP only; they were missed by pH metry. Volume clearance indicated by IMP was always completed earlier than acidity clearance. The results show that IMP technique facilitates the detection of all GER, whereas pH metry is confined to the measurement of acid GER. Therefore, this technique might improve the evaluation of GER disease and detection of GER in conditions with gastric hypoacidity.

Electric Impedance↗
PubMed1996

Pit-1: clinical aspects.

Pit-1 is a transcription factor which is expressed in the somatotrope, lactotrope, and thyrotrope cell population of the anterior pituitary gland from early fetal development throughout life. Mutations in the Pit-1 gene result in insufficient expression of this factor, accounting for a form of combined pituitary hormone deficiency for growth hormone (GH), prolactin, and thyroid-stimulating hormone. Clinical presentation at diagnosis can be variable, although all forms finally result in severe growth retardation due to GH deficiency and hypothyroidism. The clinical variability is due to other factors than the exact location of the mutation; however, the type of inheritance seems to correlate well with the genotype. Early detection of Pit-1 abnormalities might prevent the sequelae associated with some early and severe presentations of this disorder.

Animals↗
PubMed1994

Physicochemical parameters of x-ray contrast media.

RATIONALE AND OBJECTIVES: Osmolality, including "dynamic osmolality," which is observed during dilution in the plasma, viscosity, density, and partition coefficient of 11 commercially available contrast media and two new nonionic monomers were determined. METHODS: Osmolality was measured by vapor pressure osmometry, viscosity by determining flow in microcapillaries, and partition coefficient in n-octanol or n-butanol/water mixtures by inductively coupled plasma mass spectroscopy or x-ray fluorescence analysis of iodine concentrations. RESULTS: For the commercially available contrast media, the following statistically significant ranking of osmolality was obtained at 300 mg iodine/mL: iotrolan << ioxaglate < iopromide < iopamidol < ioversol = iohexol < iopentol << meglumine diatrizoate. The novel nonionic monomers, ZK 119095 and ZK 139129, had very low osmolalities, and ZK 139129 was isotonic to blood. The partition coefficient for the system n-octanol/water was lowest for the ionic compounds ioxaglate and diatrizoate followed by the nonionic dimer iotrolan. In n-butanol, iotrolan showed the lowest partition coefficient. CONCLUSION: "Dynamic osmolalities" of contrast media may differ from static values possibly because of the formation of "quasi-oligomers." Especially for ZK 139129, disaggregation occurred during dilution and the osmolality increased slightly. However, osmolality was lower than for any other monomer during the whole dilution process.

Animals↗
PubMed1994

Midazolam and ketamine as premedication in colonoscopies: a pharmacodynamic study.

As colonoscopy is often painful, a premedication appears to be indispensable. Commonly, benzodiazepines, i.e. midazolam, alone or in combination with analgesic drugs are used. Besides all advantages, midazolam especially is known to have the risk of oversedation and respiratory depression. Therefore it should be used at minimal dose. In a double-blind, randomized study, three premedication-schedules of midazolam (mid) plus ketamine (ket) were compared in 33 patients, aged between 8 and 60 years, with regard to safety and acceptance by patients and endoscopist. I: ket 1 mg/kg+mid 0.1 mg/kg, max. 5 mg II: ket 1 mg/kg+mid 0.05 mg/kg, max. 2.5 mg III: ket 0.75 mg/kg+mid 0.1 mg/kg, max. 5 mg Oxygen-saturation, heart rate and blood pressure were recorded as well as the evaluations of sedation, cooperation and complaint of pain. To assess the recovery-time of the patients, the reaction time and the attention were evaluated by "Wiener's determination apparatus" and "test d2", respectively, before and at 1, 2, 3 and 4 hours after premedication. Medication I resulted in heavy sedation, good cooperation and amnesia but had the strongest tendency towards hypoxemia. Under schedule III, reduced cooperation and acceptance were seen due to a strong experience of pain. The best conditions during the examination with regard to cooperation, experience of pain and acceptance were found after premedication II without relevant depression of vital parameters. It can be concluded that midazolam can be used at minimal recommended doses as premedication for colonoscopy if combined with ketamine in a sufficient analgesic dosage.

Adolescent↗
PubMed1993

Increased physiological dead space during exercise after bronchodilation in cystic fibrosis.

Bicycle ergospirometry was performed on 14 patients with cystic fibrosis (CF), for evaluating the effects of salbutamol and theophylline on the ventilatory response to exercise. After 1 week without bronchodilator therapy the patients cycled at 1/3 and 2/3 of their individual maximal working capacity (Wmax). The test was repeated three times after treatment with salbutamol, theophylline, or both drugs, respectively. After the combined therapy, physiological deadspace, ventilation, ventilatory equivalent of oxygen, and end-expiratory oxygen pressure increased significantly during steady state exercise at 1/3 Wmax. Similar, although not statistically significant changes, were observed after monotherapy with salbutamol or theophylline and during exercise at 2/3 Wmax. These effects could not be predicted by any lung function tests at rest or by the Shwachman-Kulczycki score. The results indicate that in some patients with CF bronchodilators can impair lung function during exercise. In conclusion, the effects of medication on exercise performance of patients with CF have to be considered. Especially, the use of bronchodilators requires a careful evaluation of their real benefit in each individual patient.

Adolescent↗
PubMed1993

Recovery from neurological deficits following biotin treatment in a biotinidase Km variant.

A 15-year-old boy suffered from progressive bilateral optic neuropathy of acute onset at the age of 10 years. Subsequently he developed spastic paraparesis and a predominantly motor type neuro-axonal neuropathy in all limbs. The basic error has been elucidated to be due to an unusual biotinidase Km variant with biphasic enzyme kinetics causing systemic biotin depletion and consequent multiple biotin-dependent carboxylase deficiency. After daily oral substitution with 10 mg biotin metabolic derangements subsided rapidly. Follow-up studies over one year after substitution with biotin demonstrated remarkable recovery from part of the previously present neuro-ophthalmological, motor and cognitive deficits. The previously extinguished flash-evoked visual potentials now showed clear responses after six months of substitution with biotin. In contrast with reports in literature, these findings indicated that neurological damage associated with biotinidase deficiency, rather than being permanent, is to some extent reversible.

Administration, Oral↗
PubMed1992

Neonatal theophylline intoxication: pharmacokinetics and clinical evaluation.

The pharmacokinetics of theophylline and its metabolites, caffeine, 1,3-dimethyluric acid, 1-methyluric acid and 3-methylxanthine were studied in a 5-day old 1.3 kg premature neonate who accidentally received 180 mg theophylline in 26 h during treatment for bradycardia. Tachycardia, hyperventilation, increased diuresis, central nervous system excitation, an increase in blood glucose concentrations followed by a prolonged decrease and hypercalcaemia were the predominant clinical and laboratory manifestations. The patient responded to supportive care and survived without sequelae. The concentration time course of theophylline and its metabolites in plasma and the pattern of urinary and gastric elimination were determined over 95 h. Theophylline showed, in contrast to its metabolites, a log linear decline in plasma. Elimination of theophylline and caffeine, calculated from their urinary excretion rates, were both exponential during the entire observation period. Urine flow dependence of renal clearance was obvious for theophylline and caffeine. Implications of theophylline disposition in neonates are discussed with special regard to theophylline poisoning.

Drug Overdose↗
PubMed1992

[Juvenile optic neuropathy caused by Km variants of biotinidase].

A patient with a newly recognised variant of biotinidase deficiency presented with acute bilateral visual loss at the age of 10 years. A progressive optic neuropathy, a predominantly motor type neuropathy and spastic paraparesis developed over the following 5 years. Metabolic investigations revealed biotin depletion causing multiple biotin dependent carboxylase deficiency. The basic defect was a biotin recycling disorder due to a biotinidase Km variant with residual colorimetric activity of 4.4% of normal. Further investigations on plasma biotinidase showed biphasic kinetics with two different reduced Vmax values and two Km-values, one being almost normal and the other highly elevated. After a period of 2 months of oral substitution with biotin 10 mg per day the visual field defects improved as well as the distal spastic parapareses and motor neuropathy. We conclude that the differential diagnosis of unexplained bilateral optic neuropathy of juvenile onset, particularly when associated with upper and lower motor neuron disease should include biotinidase deficiency.

Adolescent↗
PubMed1992

A biotinidase Km variant causing late onset bilateral optic neuropathy.

A patient with a newly recognised variant of biotinidase deficiency presented with acute loss of vision at the age of 10 years. Progressive bilateral optic neuropathy, spastic paraparesis, and a predominantly motor type neuropathy developed over the next five years. Metabolic investigations revealed biotin depletion causing multiple carboxylase deficiency. The basic defect was a biotin recycling disorder due to a mutant biotinidase with residual activity of 4.4% assayed routinely. Biocytin excretion in urine was only slightly increased. Further investigations on plasma biotinidase revealed biphasic kinetics with two different reduced values for maximum reaction velocity (Vmax) and two for the Michaelis constant (Km), one being almost normal and the other considerably raised. In contrast to this patient, two age matched children with partial biotinidase deficiency (2.8% and 2.9% of normal), but with a normal Km for biocytin, remained asymptomatic. After six months of oral substitution with 10 mg biotin per day the coecocentral and peripheral scotomata regressed, the pyramidal signs in the lower limbs disappeared, and further progression of the motor neuropathy arrested. We conclude that the differential diagnosis of unexplained bilateral optic neuropathy of juvenile onset, particularly when associated with upper and lower motor neuron disease, should include biotinidase deficiency.

Adolescent↗