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Biomedical subjects

W Hecker

Publications and source records attributed to W Hecker.

At least 19 recordsLinked to original sources
PubMed1997

Wolfram (DIDMOAD) syndrome and Leber hereditary optic neuropathy (LHON) are associated with distinct mitochondrial DNA haplotypes.

Because Wolfram (or DIDMOAD) syndrome is supposed to be a mitochondrial (mt)-mediated disease, we investigated a group of eight DIDMOAD patients with respect to point mutations of the mtDNA thus far described as being associated with defined mitochondrial disorders such as MELAS, MERRF, and LHON. Furthermore, to screen DIDMOAD patients for other mtDNA defects we used Southern blot analysis to detect mtDNA length mutations and rearrangements as well as PCR-SSCP and direct sequencing to screen all ND genes (complex I of the respiratory chain), the 22 tRNAs, and a part of the cyt b gene for unknown mutations. As a disease control group, 17 LHON patients (harboring one of the primary LHON mutations) were included in this study because of the overlapping clinical symptoms (optic atrophy) in both syndromes. We compared mtDNA variants identified in DIDMOAD patients with those found in LHON patients as well as in a control group consisting of 67 healthy German blood donors. In total, the control group was characterized by 29 polymorphic sites in ND and tRNA genes that define certain major Caucasian haplotypes. We found that a cluster of nucleotide exchanges at nucleotide positions (nps) 4216 and 11,251 roughly discriminates controls (12/67 controls, 18%) from the disease groups (6/8 DIDMOAD patients, 75%; 10/17 LHON patients, 59%). All 4216-positive LHON patients (10 patients) were concentrated in a haplogroup defined by additional exchanges at nps 10,398, 12,612, and 13,708 (haplogroup A), while the bulk of 4216-positive DIDMOAD patients (5 patients) were found in a distinct haplogroup consisting of nucleotide exchanges at nps 4917, 10,463, 13,368, 14,233, and 15,928. The frequencies of both haplogroups were significantly lower in the control group versus the respective disease groups. A more detailed analysis was performed by sequencing the two hypervariable regions of the non-coding D-loop region from patients and controls and corroborated the ranging in the two major haplogroups. Thus, the different clinical features of the mitochondrial disease groups investigated here corresponded to different clusters of mtDNA variants, which might act as predisposing haplotypes, increasing the risk for disease.

Adult↗
PubMed1996

Molecular genetic analysis and human chorionic gonadotropin stimulation tests in the diagnosis of prepubertal patients with partial 5 alpha-reductase deficiency.

UNLABELLED: Reduced conversion of testosterone (T) to dihydrotestosterone (DHT) results in defective virilization in karyotypic males. Different mutations in the 5 alpha-reductase type 2 gene cause the phenotypic variability of the disease. In this report we describe four prepubertal patients with a predominantly male phenotype who carry homozygous point mutations in the 5 alpha-reductase type 2 gene and address the specific T and DHT response to different human chorionic gonadotropin (hCG) stimulation tests. For molecular genetic analysis, DNA from peripheral blood leucocytes was studied. The coding region of the 5 alpha-reductase type 2 gene was characterized by exon-specific polymerase chain reaction amplification, non-radioactive single strand polymorphism analysis, and direct sequencing. Three different homozygous point mutations (Gly196-Ser, Arg227-Gln and Ala228-Thr) were identified in the patients. In contrast, in the DNA from 100 phenotypically normal males only two heterozygous abnormalities (Ile196-Ile, delta Met157) were characterized. For hormonal studies, T and DHT were measured in serum before and after hCG stimulation employing different protocols. HCG stimulation with 5000 IU/m2 once and prolonged stimulation with seven injections of 1500 IU hCG per single dose every other day were used. CONCLUSION: While abnormal T/DHT ratios were identified with both hCG protocols in the patients, prolonged stimulation lead to higher T values and to higher T/DHT rations, and hence to a better discrimination of pathologic results.

3-Oxo-5-alpha-Steroid 4-Dehydrogenase↗
PubMed1995

Impaired glucose tolerance leads to delayed diagnosis of Alström syndrome.

OBJECTIVE: To emphasis the need for timely diagnosis of Alström syndrome. CASE: We report a case of late-detected Alström syndrome in a boy 15 1/2 years of age who was admitted because of poor wound healing and hyperglycemia. RESULTS: Diagnosis was made and the patient's impaired glucose tolerance improved by diet. CONCLUSIONS: Regular follow-ups are needed to recognize and possibly prevent late-appearing complications.

Adolescent↗
PubMed1994

Thyroid carcinoma in childhood: management and follow up of 11 cases.

Eleven patients under 16 years of age, 5 males and 6 females were diagnosed with thyroid carcinoma in our hospital between 1974 and 1992. Median age at diagnosis was 9.5 years (range: 5.2-15.7 years). The presenting sign was a single thyroid nodule in 5, multiple thyroid nodules in 1, cervical adenopathy in 3, and thyroid nodules in conjunction with cervical adenopathy in 2 patients. Histological diagnosis was papillary carcinoma in 5 cases, follicular carcinoma in 2, mixed papillary-follicular carcinoma in 3, and anaplastic carcinoma in one. Only 4 patients had no extrathyroidal metastases at diagnosis. All but one subjects underwent total thyroidectomy, either one-stage or two-staged. If metastases were present, ablative radio-iodine therapy followed. Two patients died within a few months, one from complications of lung metastases, another from diffuse spread of anaplastic carcinoma. Two patients were lost to follow up; 7 patients have been followed for 9.0-18.0 years. Of these, one patient with initial lung metastases has had six recurrences which were successfully treated each time with radio-iodine although thyroglobulin levels remained elevated; another patient who had an initial subtotal thyroidectomy incurred a relapse 12 years later during pregnancy but is doing well now after more intensive surgery. We propose that children with differentiated thyroid carcinoma should undergo total thyroidectomy and selective lymph node extirpation by a skilled surgeon followed by whole body radio-iodine scan and ablative radio-iodine treatment if necessary. Plasma thyroglobulin can then be used as a tumour marker and suppressive levothyroxine does should be given.

Adenocarcinoma, Follicular↗
PubMed1991

[Impression management in behavior toward handicapped patients].

A previous study (Tröster, 1989) showed that nonhandicapped persons preferred a physically handicapped interaction partner to a nonhandicapped partner in an attributionally unambiguous situation. In order to test whether this "sympathy effect of physical handicap" is based on tendencies of impression management, 48 female subjects had to choose to sit next to either a physically handicapped or nonhandicapped female interaction partner in order to view a film together. Attributional ambiguity was varied by either confounding the choice of an interaction partner with a second, socially acceptable alternative (attributionally ambiguous situation: a choice between two films) or not confounding it (attributionally unambiguous situation: no choice between films). Public responsibility was manipulated by informing the subjects about their freedom to choose where they wished to sit either in public (public responsibility) or in private (no public responsibility). The results supported the impression management hypothesis: The handicapped interaction partner (in a wheelchair) was only preferred when the subjects had to anticipate that observers would deduce a preference of the chosen partner from the subjects' choices because of the attributionally unambiguous situation and the public announcement of their freedom of choice. Results suggest that the nonhandicapped strive to exhibit positive and nondiscriminative behavior toward the handicapped in order to avoid creating a disadvantageous impression in an observer.

Adult↗
PubMed1990

[Invagination in childhood].

This paper is a retrospective study of all children with intussusception, who were treated in the pediatric surgical clinic in the Dr. v. Hauner'sches Kinderspital of the University of Munich from 1970 to 1988. In this time we evaluated 99 cases out of 101 children. Points of interest were epidemiological data, such as sex ratio, average age, place of residence, exact documentation of the anamnesis typical of this pediatric surgical entity, of diagnosis, site of intussusception as well as of frequency of conservative barium enema reduction and surgical treatment respectively. 68 patients of these evaluated 99 cases had to be operated. As far as postoperative courses are concerned bowel obstruction occurs in 6 patients, 4 cases developed a relapse of intussusception and one child died.

Adolescent↗
PubMed1990

[Schönlein-Henoch purpura. A clinical study of 119 patients with special reference to unusual complications].

119 patients with Schönlein-Henoch purpura from 1 to 17 years were investigated. All patients had a rash, 76% joint affections, 76% gastrointestinal symptoms, 54% renal involvement, 17% of the boys orchitis, 2% intramuscular bleeding and 2% coagulation disorder. 1 boy showed perforation of the nasal septum, to our knowledge not described in Schönlein-Henoch purpura up to now. The mean age was 6.4 years. The seasonal peak was in October, 63% of our patients had a preceding infection, mostly of the upper respiratory tract, pointing to various infectious agents as a trigger of this disease. Patients with abdominal pain had a 4-fold, patients with bloody stools a 7.5-fold increased risk of renal involvement. 13/38 Patients had a serum albumin level below 3.5 g/dl that may have been caused either by renal or gastrointestinal losses.

Adolescent↗
PubMed1989

[The value of MRT of the thorax in congenital tracheal stenoses].

MRI of the thorax was performed in 24 children aged between six weeks and five years, in whom a tracheal stenosis had been demonstrated by bronchoscopy. Since bronchoscopy can only demonstrate the interior of the trachea, various imaging methods, such as CT and angiography, were used to demonstrate the topography and cause of the tracheal stenosis. MRI has shown that the most common cause of a stenosis in the central section of the trachea is focal compression by an aberrant brachiocephalic trunk (10 cases). Stenosis of the distal trachea could be due to anomalies of the aortic arch (5 cases), a dilated pulmonary artery (4 cases) or a soft tissue mass (3 cases). In all these patients, MRI was greatly superior to the conventional methods. By using a special technique, MRI made it possible to clarify the cause and localisation of a tracheal stenosis by a non-invasive examination.

Aorta, Thoracic↗
PubMed1984

Innominate artery compression of the trachea in infancy and childhood: is surgical therapy justified?

We reviewed innominate artery compression of the trachea in 10 medically treated patients (group I) and 6 children who underwent innominate arteriopexy (group II). The symptoms were as follows: (1) stridor (80% in group I, and 66% in group II), (2) recurrent bronchopulmonary infections (40% in group I, 66% in group II) and (3) apneic attacks (10% in group I and 100% in group II). Diagnosis was made in all cases by tracheobronchoscopy . It revealed severe tracheal stenosis (narrowing more than 2 thirds) in all children treated by surgery. In group I the tracheal stenosis was mild (narrowing less than one third) in 5 cases, moderate (narrowing from one third to 2 thirds) in 4 cases and severe in only one case. The indication for surgery was based on a history of apneic attacks. In this study innominate arteriopexy has proven to be a reliable and low risk procedure which relieved reflex apnea and recurrent bronchopulmonary infections in all 6 children operated upon.

Apnea↗
PubMed1983

Phase I metabolism of imipramine by microsomes of small intestine in comparison with metabolism by liver microsomes.

The metabolism of imipramine was investigated by the incubation of C-14 labelled compound in Krebs-Ringer bicarbonate buffer with microsomes of small intestine and of liver from guinea pigs. Imipramine and its metabolites were extracted with chloroform, separated by TLC and determined quantitatively by direct scanning with a TLC Linear Analyzer. With intestinal microsomes, the following metabolites could be identified: DMI, 2-OH-IMP, IMP-N-oxide. DMI is the main metabolite. The same metabolites appeared after incubation with liver microsomes, but the proportions were different: the N-oxide formation was predominant, followed by N-demethylation and hydroxylation. The formation of DMI and 2-OH-IMP seems to follow Michaelis-Menten kinetics, both in assays with intestinal and with liver microsomes. The liver/intestine ratio of DMI and 2-OH-IMP formation is proportional to the cytochrome P-450 ratio in the microsomes, in contrast to N-oxide formation.

Animals↗
PubMed1983

[Comparative studies of gelatin and cellulose ester membrane filters for their suitability in determining the microorganism count in the air].

Filtration is one of the classical methods for the determination of the microbial content of the air or the number of microbe-bearing particles in the ambient air. Hereby, the opinion prevails that gelatin foam filters yield better results than filters made of cellulose esters. Since gelatin filters are themselves by no means free from disadvantages, several tests were carried out under the conditions encounted in practice in two packaging rooms used for pharmaceutical preparations. The objective was to ascertain whether the customary cellulose ester filters really are less suitable for determination of the microbial content of the air than the filters made of soluble gelatin. Based on the results of various preliminary experiments, gamma-irradiated filters of cellulose nitrate, with a pore size of 0,45 micron, were selected from a range of tested membrane filters (Tables 1,2,4-6 and Fig. 1) and compared directly with the gelatin filters. The statistical evaluation of these tests showed that, under the chosen experimental conditions, both filters yielded the same count of organisms (Tables 3, 9 and 10, Figs. 2 and 3). Moreover, by means of further tests, it could be proved that neither cellulose nitrate filters with a pore size of 0,8 micron, which had undergone gamma-radiations, nor filters made of the mixed esters of cellulose, which had been treated with ethylene oxide or autoclaved, differed significantly from the selected type (Tables 5-8). This study therefore clearly demonstrates that - in addition to gelatin filters - a whole range of membrane filters made of cellulose esters yield equally good results and may be used for supervision of the microbial content of the air in closed rooms.

Air Microbiology↗
PubMed1981

[Low-level challenge test for the examination of the microbiological susceptibility, during the period of use, of liquid and semi-solid dosage forms in multiple-dose containers (author's transl)].

In the case of preserved liquid and semi-solid pharmaceutical preparations in multiple-dose containers, the adequacy of protection against microbial contamination is examined by means of a strict microbiological preservation test (Table 1). On account of a reduction in the amount of preservative added, either for medical (allergies) or technological (solubility etc.) reasons, or on account of a decrease in the antimicrobial efficacy during storage due to degradation or adsorption of the preservative or incompatibility with other excipients, the requirements of the preservation test may in some cases no longer be fulfilled during use. In such cases, a so-called low level multi challenge test is used to examine whether, after first opening the package, microbial growth can be prevented, in spite of renewed slight contamination during the period of use. To this purpose, samples are contaminated with very small quantities of various test organisms and stored at room temperature during the entire testing period (twice the theoretical period of use). The count of organisms is determined after certain intervals of time and the samples contaminated anew (Table 2). If at some time during the entire testing period, the number of organisms determined before a fresh inoculation exceeds the sum of the microbial counts from all inoculations carried out beforehand, one can no longer preclude the possibility of microbial, proliferation during the normal period of use and thereby detriment to the dosage form or danger to the patient. In such cases, the maximal permissible period of use should be limited or the size of the package reduced accordingly. If very poor results are obtained for the test, a change in composition of the dosage from must be envisaged in certain cases.

Bacteria↗
PubMed1981

[Microbiological test for the determination of the maximum permissible standing time for non-sterilised ampoule solutions (author's transl)].

As opposed to most large volume parenterals (LVP), which on account of their composition provide good nutrient media for microbial growth, it can be expected that many ampoule solutions have an antimicrobial activity of their own, due to the high activity of their drug substances. It is therefore questionable as to whether the requirements laid down by the American Food and Drug Administration (FDA) for LVP, demanding a maximum time limit of 8 hours for the manufacture, filling and sterilisation, can simply be extrapolated to apply to small volume parenterals. A method is now described whereby the behaviour of various micro-organisms can be studied in non-sterilised ampoule solutions. The tests carried out show that only a negligible fraction of the ampoule solutions permit proliferation of contaminating organisms. On the contrary, the majority of the preparations examined had an inhibitory or even microbicidal effect. On the basis of the findings, it is proposed to make a generally valid classification of ampoule solutions into 5 different risk classes. While it is essential to adopt the rigorous FDA restrictions for the entire manufacturing period in the case of those preparations most susceptible to microbial proliferation, the standing times, i.e. the period of time between the manufacture of the solution and the subsequent antimicrobial treatment of the ampoules, can be prolonged without risk for the other groups. This maximum standing time, laid down specifically for each product, in many cases enables the manufacturer to produce larger batches or to improve exploitation of production capacity, yet at the same time maintain security for the product and the user.

Drug Contamination↗
PubMed1976

Studies of the kinetics and metabolism of 17 beta-heptanoyl-17 alpha-ethinyl-4-oestren-3-one-7-3H (norethisterone enanthate) in humans following intramuscular injection.

The kinetics and metabolism of 17 beta-heptanoyl-17 alpha-ethinyl-4-oestren-3-one-7-3H (7-3H-norethisterone enanthate, NET-En) after i.m. injection in two female subjects is described. 177.4 mg and 174.5 mg NET-En were injected. Maximum 3H-activity in plasma was reached 8 to 14 days after the injection. In terms of NET-En it amounted to 70-100 mug/100 ml. Maximum NET concentration was reached on the 4th to 8th day and amounted to about 1 mug/100 ml. After 4 weeks NET concentration was still about 0.05 to 0.1 mug/100 ml and even after 6 weeks NET was still detectable in plasma. In 14 days the two subjects excreted about 13% of the administered dose in the urine and about 15% and 21%, respectively, in the faeces. On the basis of a rough calculation, the subjects eliminated about 60% and 55% of the radioactivity with urine and faeces within 42 days.

Female↗