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Biomedical subjects

A Scheuerle

Publications and source records attributed to A Scheuerle.

15 recordsLinked to original sources
PubMed2001

Limits of the genetic revolution.

The genetic revolution will touch all disciplines of medicine, much like the antibiotic discoveries in the last century did. However, genetic medicine is not an immediate "magic bullet" for all noninfectious conditions. Despite the sometimes melodramatic announcements by the lay media, there are hurdles to overcome before genetic treatments become as ubiquitous as antibiotics. These barriers fall into 3 categories: molecular, economic, and behavioral. First, the molecular difficulties include the biochemical complexity of genes and genetic disease, variation in pathogenesis among races, and gene-environment interaction. Second, economic disincentive to develop orphan drugs, and the expense of such medications, may hinder production of treatments for truly rare genetic diseases. Third, patients are unlikely to be any more compliant with new medications or recommendations than they are with the current ones. The "magic bullet" of folic acid is not used by the majority of women who are aware of its usefulness in preventing birth defects. While the genetic revolution has much potential, the complexity of genetics itself is difficult and the current barriers to useful treatment will not change. As with oncological and transplantation technology, great strides are likely to be made, but only at a measured pace.

Genetic Diseases, Inborn↗
PubMed1996

Association of the LHON 13,708 and 15,257 mitochondrial DNA mutations with neurodegenerative diseases distinct from LHON.

300 patients suffering from neurodegenerative diseases distinct from Leber hereditary optic neuropathy (LHON) were screened for the presence of mitochondrial DNA mutations. We report on nine patients, eight female and one male, who all harboured mutations at positions 13,708 and 15,257 of the mitochondrial DNA. Both mutations have previously been claimed to be associated with LHON. Based on our results, these mutations occur in a number of different neurodegenerative diseases and therefore cannot be regarded as "LHON" mutations.

Adolescent↗
PubMed1996

[Value of stereotaxy in neurosurgery. Indications and analysis of results of 71 cases].

CT- or MRI-guided stereotactic procedures should be a standard in a modern neurosurgical unit. Analysing 71 cases the indications and results of stereotactic neurosurgery are presented. In 53 patients stereotactic serial biopsies of different intraaxial lesions were performed, in 5 patients a spontaneous haemorrhage of the basal ganglia was removed by lysis with r-tPA. In 3 patients suffering from hydrocephalus due to diencephalic cysts a cystventricular shunt device was implanted. In 3 patients an intracerebral abscess was aspirated and drained. A stereotactic guided craniotomy and excision of small deep-seated lesions was performed in 6 cases. The accuracy of stereotactic tumour biopsies was 88.7% in our series, in accordance to other authors. The stereotactic aspiration and drainage of an intracerebral abscess provides accurate localization and minimal cortical damage and offers the possibility of intracavitary application of antibiotics. The stereotactic internal shunt implantation seems to be an alternative approach in the treatment of diencephalic cysts due to its minimal invasiveness and low operative risk. The aspiration of basal ganglia haematomas with insertion of an external drainage allows the lysis of the haematoma with r-tPA or urokinase. With stereotactic guidance small, deep-seated intraaxial lesions can be well localized and removed.

Aged↗
PubMed1995

Replication banding and molecular studies of a mosaic, unbalanced dic(X;15)(Xpter-->Xq26.1::15p11-->15qter).

We present a patient with a chromosomal mosaicism involving the X chromosome. One cell line is 45,X and the other has a de novo paternally derived dicentric X;15 translocation. Her karyotype is therefore 45,X/45,X,dic(X;15)(Xpter-->Xq26.1::15p11-->15 qter) based on G-banding. The presence of 2 centromeres on the derivative X was confirmed by fluorescence in situ hybridization (FISH) and a deletion of Xq26.1-->qter was confirmed by polymerase chain reaction (PCR) using DXS52 and DXYS154. Replication banding studies indicate that the derivative X is late replicating. Based on these studies, it is unclear whether inactivation has spread to proximal 15q. The patient has a unique phenotype distinct from Ullrich-Turner or Prader-Willi syndromes, but includes ataxia and language delay which are commonly seen in Angelman syndrome. These findings are contrary to those anticipated since deficiency of paternal genes at 15q12 typically leads to Prader-Willi syndrome. Molecular analysis of PCR-based polymorphisms of chromosome 15 and X indicates that uniparental disomy is not present for the X chromosome or chromosome 15 in either cell line. It is hypothesized that her phenotype results from the interaction of the 2 abnormal genotypes. Each abnormality may be diluted by the mosaicism and, in the derivative X line, by the possible variation among cells of inactivation spreading to chromosome 15.

Abnormalities, Multiple↗
PubMed1995

Dysmorphic features in patients with complex glycerol kinase deficiency.

Complex glycerol kinase deficiency is a contiguous gene syndrome consisting of a deletion of the glycerol kinase locus, together with the genes for adrenal hypoplasia congenita or Duchenne muscular dystrophy or both. We describe an infant with complex glycerol kinase deficiency and mildly dysmorphic features similar to those seen in other patients, including an "hourglass" appearance of the middle of the face; hypertelorism; rounded palpebral fissures; esotropia; wide, flattened earlobes; and a downturned mouth. The combination of medical history and characteristic facies should prompt the request for specific laboratory tests diagnostic for this potentially treatable condition.

Adrenal Insufficiency↗
PubMed1994

Mitochondrial complex I and III mutations and neutral-lipid storage in activated mononuclear macrophages and neutrophils: a case presenting with necrotizing myopathy, poikiloderma atrophicans vasculare, and xanthogranulomatous bursitis.

We report the case of a 57-year-old woman suffering from xanthogranulomatous bursitis, necrotizing myopathy, and poikiloderma atrophicans vasculare, which are associated with marked accumulation of neutral-lipid storage phagocytes. The observed lipid storage was restricted to activated phagocytes independent of the presence of tissue necrosis and was not seen either in circulating blood leukocytes or in muscle fibers. The patient's daughter disclosed xanthomatous inflammatory reaction with profound delay of wound healing secondary to pelviscopy. Examination of the mitochondrial DNAs of the patient, her daughter, and her two grandchildren revealed two homoplasmic mutations at positions 13708 and 15257 of the mitochondrial genome. We discuss the involvement of these mutations in the pathogenesis of xanthomatous and xanthogranulomatous inflammation. Further investigations are required to test whether impairment of aerobic energy production independent from mitochondrial DNA mutations (eg, by hypoxia or microbial toxins) similarly can cause the accumulation of lipid-laden macrophages and explain the persistency of xanthogranulomatous inflammation.

Base Sequence↗
PubMed1994

Facilitating diagnosis, prognosis, and management: distinguishing isolated and syndromic anomalies.

Birth defects comprise a significant percentage of craniofacial abnormalities, particularly in infants and children. A patient in whom these anomalies represent part of a larger syndrome may have features, such as a congenital heart defect and a urogenital malformation, which complicate pre- and post-operative management. Distinguishing isolated anomalies from syndromic anomalies is important. Appropriate diagnosis, referral, and prognosis is facilitated by examining specific parts of the body. The embryonic face develops coincident with the limbs, so their malformations can often be found concurrently. Two common considerations in dysmorphologic diagnosis are: 1) malformations of midline structures (brain, palate, heart, genitalia) tend to occur together; and 2) an underlying diagnosis may be present in a patient with two major or three minor anomalies. Presented herein are definitions of major and minor anomalies, and some of the syndromes in which they can be found. It is suggested that children with a craniofacial anomaly, isolated or syndromic, should be evaluated by a geneticist, and that patients with two or more major anomalies should have a chromosome analysis performed.

Abnormalities, Multiple↗
PubMed1993

In situ autolysis of mouse brain: ultrastructure of mitochondria and the function of oxidative phosphorylation and mitochondrial DNA.

The effect of in situ autolysis on cerebral mitochondrial structure and function has been investigated. Mice (n = 9) were sacrificed and stored for up to 24 h under unfavorable post-mortem conditions at 25 degrees C. At different time intervals groups of three animals were submitted to post-mortem dissection and tissue from different regions of the brain was used for the preparation of "free" and synaptosomal mitochondria. On electron microscopic examination, the post-mortem period had no significant influence on mitochondrial morphology and enzymatic activities of complexes I-V of the mitochondrial oxidative phosphorylation system were still present in all the mitochondrial preparations from different regions of the brain, albeit at a reduced levels. Degradation of mitochondrial DNA was virtually absent from mitochondrial preparations during the 24-h period of autolysis, as shown by the presence of intact DNA by Southern blot and PCR analysis. Based on these results, alterations in mitochondrial DNA and deficiencies of mitochondrial respiratory complexes I-V can be recognized in cerebral tissue even after 24 h of unfavorable post-mortem storage conditions.

Animals↗
PubMedDate not supplied

[Olivo-ponto-cerebral hypoplasia--case report of a neurodegenerative disease manifesting at birth with a fatal outcome].

We report on a boy with pontocerebellar hypoplasia Type II according to the classification of Barth. The clinical signs were noted at birth and consisted of muscular hypertonus, central hypopnoe requiring artificial ventilation, chorea, hyperthermia above 40 degrees C and myoclonic seizures resistant to all therapeutic modalities. At birth, the boy was noted to have macrocephaly, but was microcephalic by 3 months of age. He failed to develop any mental or motor facilities. After cessation of all therapy the child died at the age of 3 1/2 months. Postmortem examination of the brain revealed loss of neurons and gliosis affecting the olivo-ponto-cerebellar system, signs characteristic of PCH.

Child Development↗
PubMedDate not supplied

Disseminated neocortical and subcortical encephalopathy (DNSE) with widespread activation of brain macrophages: a new dementia disorder? Autopsy reports of two postmenopausal women from families with mitochondrial DNA mutations.

In this study we present 2 postmenopausal women who showed clinical symptoms that resembled those of a rather well-defined group of vascular dementia disorders, termed subcortical dementia (Binswanger disease, CADASIL). Patient 1 exhibited mitochondrial DNA (mtDNA) variants in the ND5 gene at position 13,708 and the Cytb gene at position 15,257. These DNA variants have been described in a number of neurologic disorders, but their pathogenetic potential is unclear. Patient 2 showed the same DNA alterations and an additional mtDNA variant at position 15,812 in the Cytb gene. The principal neurohistologic features of the 2 atrophic brains presented here include: subtotal selective neuronal cell loss in the cortex and, to a lesser degree, in the basal ganglia (claustrum, putamen, globus pallidus), sparing palaeocortex and periarchaeocortex, and a very characteristic and diagnostic feature was detachment of astrocytic processes from capillary walls resulting in pericapillary space formation. These pericapillary spaces were partially filled with macrophages. The spaces were not associated with total breakdown of the blood vessel walls as demonstrated by the absence of erythrocytes, lymphocytes, or polymorphonuclear leukocytes outside the vascular bed of the brain; progressive subcortical encephalopathy, as it is seen in subcortical dementia (Binswanger), but lacking arterial lipohyalinosis. The cerebral grey and white matter revealed cuffing of arteries and arterioles by adventitial macrophages. The neocortical and subcortical changes were accompanied by myriads of activated macrophages filled with lipids. The pathology of our 2 cases differs from that of other neurodegenerative disorders and we suggest the term of "disseminated neocortical and subcortical encephalopathy (DNSE) with widespread activation of brain macrophages".

Basal Ganglia↗