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Biomedical subjects

W Sperl

Publications and source records attributed to W Sperl.

At least 19 recordsLinked to original sources
PubMed2002

Screening for carnitine palmitoyltransferase II deficiency by tandem mass spectrometry.

Mitochondrial carnitine palmitoyltransferase II (CPT II) deficiency is the most common inherited disorder of lipid metabolism in adults. Currently the routine diagnosis is based on the determination of CPT enzyme activity in muscle tissue. We have analysed the tandem mass spectra of serum acylcarnitines of nine CPT II-deficient patients. These spectra were compared to those of a cohort of 99 patients with other neuromuscular disorders and metabolic conditions supposed to cause alterations of the long-chain acylcarnitines. The spectra in CPT II deficiency showed characteristic elevations of C16:0 and C18:1 acylcarnitines while acetylcarnitine C2 was not elevated. In the present study, the ratio (C16:0+C18:1)/C2 has detected all CPT II deficiencies and discriminated them from unspecific alterations of serum acylcarnitines. The ratios of CPT II-deficient patients showed virtually no overlap with those observed in patients with other neuromuscular disorders. We suggest mass spectrometry of serum acylcarnitines as a rapid screening test that should be included early in the diagnostic work-up of patients with recurrent myoglobinuria, recurrent muscular weakness and myalgia.

Adolescent↗
PubMed2001

Calvarial "doughnut lesions": clinical spectrum of the syndrome, report on a case, and review of the literature.

Many pathologic fractures, lumps on the head, elevated serum alkaline phosphatase (ALP) levels, and dental caries are the main characteristics of the rare autosomal dominantly inherited calvarial "doughnut lesions" (MIM 126550). We report the sporadic case of a 16-year-old patient who has had 10 pathologic fractures between age 6 weeks and 15 years. An elevated serum ALP level was found at age 11 and skull lumps at age 15; radiography showed frontal and parietal round radiolucencies surrounded by sclerotic bone comparable to doughnuts. Magnetic resonance imaging (MRI) showed skull lesions at an early stage. Because the findings are reminiscent of osteogenesis imperfecta (OI), collagen types I, III, and V were analyzed in fibroblasts and shown to be normal in terms of quantities, proportions, electrophoretic mobility, and thermostability. Thus, this rare syndrome can be distinguished from OI by collagen analysis and MRI of the skull at an early stage, even before palpable skull lesions appear.

Adolescent↗
PubMed2001

Epidemiology of sudden infant death syndrome (SIDS) in the Tyrol before and after an intervention campaign.

OBJECTIVE: We investigated the epidemiology of sudden infant death syndrome (SIDS) in the Tyrol before and after an intervention campaign. PATIENTS AND METHODS: Descriptive characteristics and risk factors of SIDS before the campaign were assessed in a retrospective case-control study (1984 to 1994). In April 1994 a country-wide information campaign on modifiable risk behaviours was initiated. Thereafter we prospectively collected data on child care practices four to six weeks after birth for all infants born in the Tyrol (participation rate 72%; n = 28,361) and evaluated new SIDS cases (1994 to 1998). For this purpose two questionnaires were used, one with 96 items for the evaluation of all SIDS cases and assessment of child care practices before 1994, and the other with 24 items for prospective data collection. RESULTS: The incidence of SIDS decreased from 1.83 (mean incidence, 1984-1994) to 0.4/1000 live births immediately after the campaign and remained low until 1998. The frequency of maternal smoking during pregnancy declined (22.9% vs. 14.5%, p < 0.01), as did the prevalence of the prone sleeping position (53.7% vs. 5.4%, p < 0.001) and of non-breastfeeding (21.3% vs. 6.7%, p < 0.001). All these variables were prominent risk factors for SIDS before the campaign and remained significant thereafter. On account of the markedly reduced prevalence of the prone sleeping position, smoking became the most common SIDS risk factor. The prevalence of sleeping on the side significantly increased (5.1% vs. 36.4%, p < 0.001) and the social status of mothers of SIDS infants tended to be lower than that before the campaign. The clear winter preponderance of SIDS which was evident before the campaign disappeared, or was even reversed. CONCLUSIONS: Our study documents the long-term efficacy of a low-cost intervention campaign by way of health education. Further efforts must be directed toward lower social classes, thereby focusing on maternal smoking and avoidance of the side sleeping position.

Adult↗
PubMed2001

A case of Ohtahara syndrome with olivary-dentate dysplasia and agenesis of mamillary bodies.

We report a patient with early infantile epileptic encephalopathy (EIEE) with suppression-burst (Ohtahara syndrome) associated with olivary-dentate dysplasia and agenesis of mamillary bodies is reported. Although those with Ohtahara syndrome are a heterogeneous group, virtually all reported cases are secondary to neuronal migrational disorders, sometimes only identified by detailed neuropathologic examination, as in this case report, which describes mamillary body agenesis as a not-yet-recognized anomaly associated with Ohtahara syndrome. All children with Ohtahara syndrome should have high-resolution magnetic resonance imaging (MRI) and detailed postmortem neuropathologic examinations.

Cerebellar Nuclei↗
PubMed2001

Poor storage and handling of tissue mimics mitochondrial DNA depletion.

Analysis of the mitochondrial DNA (mtDNA) is an important part in the diagnosis of mitochondrial disorders. Besides point mutations and deletions in the mitochondrial genome a reduction in the amount of mtDNA molecules (mtDNA depletion) can also be the reason for mitochondrial defects. The DNA stability in clinical samples is essential for proper performance and interpretation of DNA based diagnosis. The stability of mtDNA was compared with that of nuclear DNA under poor handling and storage conditions. Fresh and thawed muscle tissue specimens were kept at different temperatures for a certain period of time before DNA isolation. Quantitative Southern blot analysis revealed a time-dependent decrease in the amount of mtDNA compared with nuclear DNA in thawed tissue specimens. Therefore, the current study demonstrates that proper specimen storage is a critical issue in quantitative mtDNA analysis and that poor handling and storage of tissue may mimic a severe mtDNA depletion.

Blotting, Southern↗
PubMed2001

Clinical and experimental results on cardiac troponin expression in Duchenne muscular dystrophy.

BACKGROUND: Because of controversial earlier studies, the purpose of this study was to provide novel experimental and additional clinical data regarding the possible reexpression of cardiac troponin T (cTnT) in regenerating skeletal muscle in Duchenne muscular dystrophy (DMD). METHODS: Plasma from 14 patients (mean age, 7.5 years; range, 5.7-19.4 years) with DMD was investigated for creatine kinase (CK), the CK MB isoenzyme (CKMB), cTnT and cardiac troponin I (cTnI), and myoglobin. cTnT concentrations were measured by an ELISA (second-generation assay; Roche) using the ES 300 Analyzer. cTnI, myoglobin, and CKMB were measured by an ELISA using the ACCESS System (Beckman Diagnostics). Troponin isoform expression was studied by Western blot analysis in remnants of skeletal muscle biopsies of three patients with DMD and in an animal model of DMD (mdx mice; n = 6). RESULTS: There was no relation of cTnT and cTnI to clinical evidence for cardiac failure. cTnI concentrations remained below the upper reference limit in all patients. cTnT was increased (median, 0.11 microg/L; range, 0.06-0.16 microg/L) in 50% of patients. The only significant correlation was found for CK (median, 3938 U/L; range, 2763-5030 U/L) with age (median, 7.5 years; range, 6.8-10.9 years; r = -0.762; P = 0.042). Western blot analysis of human or mouse homogenized muscle specimens showed no evidence for cardiac TnT and cTnI expression, despite strong signals for skeletal muscle troponin isoforms. CONCLUSIONS: We found no evidence for cTnT reexpression in human early-stage DMD and in mdx mouse skeletal muscle biopsies. Discrepancies of cTnT and cTnI in plasma samples of DMD patients were found, but neither cTnT nor cTnI plasma concentrations were related with other clinical evidence for cardiac involvement.

Adolescent↗
PubMed2000

[SIDS prevention program in Tyrol].

In April 1994, an intervention campaign to reduce the incidence of sudden infant death syndrome (SIDS) was established in the Tyrol. The campaign was intended to increase knowledge concerning risk factors for SIDS in the general community and to improve individual care for infants at risk. In contrast to interventional programmes in other federal states of Austria (i.e. Vorarlberg, Styria), this programme did not utilise polysomnography for identifying infants at risk. A part of the intervention programme was the "Styrian risk questionnaire", a standardised questionnaire concerning risk factors for SIDS. Individual instructions for health care of children at risk (risk score > or = 7) were provided and, if necessary, subscription of home monitoring was performed at the out-patient department (SIDS out-patient service) of the Department of Paediatrics in Innsbruck and other paediatric departments throughout the Tyrol. The educational programme also included information concerning basic life support. Psychological support was offered to parents of SIDS infants. Risk factors for SIDS in the Tyrol before the campaign were assessed in a retrospective case-control study (time period 1984-1994; 99 SIDS infants, 136 controls). The risk of SIDS was markedly reduced when parents had detailed knowledge of the risk factors of SIDS (odds ratio (OR) 0.03; p < 0.001), which emphasises the importance of information and educational programmes. The incidence of SIDS declined after the beginning of the intervention campaign from 1.83/1000 live births (average incidence from 1984-1994) to 0.4/1000 live births and remained at this level thereafter. Post-neonatal mortality also declined from 3.9 to 1.3/1000 live births. The prevalence of the prone sleeping position declined immediately after the campaign (53.7% vs. 5.4%, p < 0.001), as did the frequency of maternal smoking during pregnancy (22.9% vs. 14.5%, p < 0.01). Breast feeding became more popular. In all, the low-cost intervention programme in the Tyrol proved to be highly efficient in reducing the risk of SIDS and in maintaining this effect for several years.

Adult↗
PubMed2000

Magnetic resonance spectroscopy (MRS) in five patients with treated propionic acidemia.

Propionic acidemia is an inherited disorder caused by a defect of propionyl CoA carboxylase. Untreated, propionic acidemia leads to metabolic decompensation and toxic encephalopathy. We report on the magnetic resonance imaging (MRI) and magnetic resonance spectroscopy (MRS) findings in five children who were properly treated by protein restriction and carnitine supplementation, during a phase of clinically and metabolically stable conditions. The examinations were performed on a whole-body 1.5 T scanner. During the observation period, from 1992 to 1996 we employed long echo time single-voxel spectroscopy and chemical shift imaging in addition to a conventional MRI protocol. The two children with the longest delay before onset of therapy showed cerebral atrophy. MRS yielded elevated lactate peaks in four of the children. These results indicate that MRS can detect metabolic alterations in the brains of children with propionic acidemia during metabolically stable conditions. The presence of lactate could be caused by hampered aerobic oxidation within the citrate cycle due to intracellular elevated propionic metabolites.

Amino Acid Metabolism, Inborn Errors↗
PubMed2000

Oral creatine supplementation in Duchenne muscular dystrophy: a clinical and 31P magnetic resonance spectroscopy study.

The decrease in intracellular creatine concentration in Duchenne muscular dystrophy may contribute to the deterioration of intracellular energy homeostasis and may thus be one of the factors aggravating muscle weakness and degeneration. Oral creatine supplementation should have potential in alleviating the clinical symptoms. To test this hypothesis, creatine was orally administered over a period of 155 days to a 9-year-old patient with Duchenne muscular dystrophy. In accordance with previous investigations on normal subjects and trained athletes, the patient experienced improved muscle performance during creatine supplementation. Further evidence supporting this hypothesis derived from plasma creatine kinase and lactate dehydrogenase activities and repeated 31P magnetic resonance spectroscopy of the gastrocnemius muscle. These preliminary observations indicate a potential role for creatine supplementation in the symptomatic therapy of patients with muscle disease.

Administration, Oral↗
PubMed2000

Lactobacilli and acidosis in children with short small bowel.

BACKGROUND: In patients with a short small bowel, D-lactic acidemia and D-lactic aciduria are caused by intestinal lactobacilli. The purpose of this study was to obtain a detailed picture of the metabolic acidosis in young children with short small bowel. METHODS: Feces, blood, and urine of children with short small bowel and acidosis were studied microbiologically and/or biochemically. RESULTS: Previous findings were confirmed that more than 60% of the fecal flora of patients with small short bowel, who are not receiving antibiotics, consists of lactic acid-producing lactobacilli. In blood, D-lactic acid was the most prominent metabolite: the highest serum D-lactate (15.5 mmol/l) was observed in a sample taken immediately after the onset of hyperventilation. The highest D-lactate excretion was in urine collected some hours after the onset of hyperventilation, and amounted to 59 mol/mol creatinine. Acidosis in the patients with short small bowel was related to strongly increased serum D-lactate and anion gap and to strongly decreased serum bicarbonate and pH. CONCLUSION: In children with small short bowel and acidosis, the common intestinal flora of mainly lactobacilli abundantly produces D-lactic acid from easily fermentable carbohydrates. Thus, these bacteria directly cause shifts of bicarbonate, pH, and base excess and indirectly cause shifts of the anion gap, as well as hyperventilation. These kinetic parameters are strongly associated.

Acidosis↗
PubMed1999

Spectrum of CFTR mutations in the Middle North of Spain and identification of a novel mutation (1341G-->A). Mutation in brief no. 252. Online.

We have analyzed 39 unrelated cystic fibrosis (CF) families by denaturing gradient gel electrophoresis (DGGE) and direct sequencing in order to determine the spectrum of CF mutations in our population. This approach has allowed us to detect 72 out of the 78 CF chromosomes (92.3%). The DF508 mutation was found to be present in 51/78 (65.4%) CF chromosomes, in accordance with the predicted Northwest-Southeast gradient within the European population. Another 14 known mutations, and the novel 1341G-->A mutation were identified. Nine out of fifteen non DF508 mutations were present in a single chromosome. The 1341G-->A mutation, found in 2 unrelated patients, is a new mutation associated to severe phenotype, causing pancreatic insufficiency and chronic lung infections. Our data suggest a different distribution of non-DF508 mutations in our population when compared with previous studies carried out in Spanish CF families. Six out of the 14 non-F508 in our study were not present in a recent study carried out in 640 Spanish families with CE These six mutations account for 29.6% non DF508 chromosomes in our sample.

Cystic Fibrosis↗
PubMed1998

Sudden infant death syndrome: risk factor profiles for distinct subgroups.

The authors investigated risk profiles of sudden infant death syndrome (SIDS) as a function of age at death. A case-control study carried out in the Tyrol region of Austria enrolled 99 infants who died of SIDS between 1984 and 1994 and 136 randomly selected controls. Early and late SIDS (< 120 days of age vs. > or = 120 days) were defined according to the clear-cut bimodal age-at-death distribution. Inadequate antenatal care, low parental social and educational level, and the prone sleeping position were risk conditions that applied to both early and late SIDS. A marked seasonal variation (winter preponderance) was the most outstanding feature of late SIDS. A gestational age of < 37 weeks (odds ratio (OR) = 8.4, 95% confidence interval (CI) 2.6-26.0), repeated episodes of apnea (OR = 5.7, 95% CI 1.2-27.0), low birth weight (< 2,500 g) (OR = 3.4, 95% CI 1.1-11.0), a family history of sudden infant death (OR = 2.9, 95% CI 1.1-7.5), and maternal smoking during pregnancy (OR = 2.2, 95% CI 1.0-4.5) were associated with early SIDS. This study identified two distinct subgroups of SIDS infants characterized by different risk conditions and ages at death. These results underline a multiple-cause hypothesis for SIDS etiology which involves a genetic predisposition, immaturity in the first months of life, and environmental factors acting at various ages.

Adult↗
PubMed1998

The therapeutic potential of oral creatine supplementation in muscle disease.

The decrease in intracellular creatine concentration observed in a number of muscle diseases may deplete energy homeostasis and may, therefore, be one of the factors determining and/or aggravating muscle weakness and degeneration. Two hypotheses are put forward in the present communication to explain: (i) the mechanisms leading to the disturbances in creatine metabolism found in various muscle diseases; and (ii) the potential of oral creatine supplementation in alleviating the clinical symptoms.

Animals↗