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Biomedical subjects

M Häusler

Publications and source records attributed to M Häusler.

At least 19 recordsLinked to original sources
PubMed2003

Cerebrospinal fluid pterins and folates in Aicardi-Goutières syndrome: a new phenotype.

OBJECTIVE: To describe three unrelated children with a distinctive variant of Aicardi-Goutières syndrome (AGS) characterized by microcephaly, severe mental and motor retardation, dyskinesia or spasticity, and occasional seizures. RESULTS: Neuroimaging showed bilateral calcification of basal ganglia and white matter. CSF glucose, protein, cell count, and interferon alpha were normal. Abnormal CSF findings included extremely high neopterin (293 to 814 nmol/L; normal 12 to 30 nmol/L) and biopterin (226 to 416 nmol/L; normal 15 to 40 nmol/L) combined with lowered 5-methyltetrahydrofolate (23 to 48 nmol/L; normal 64 to 182 nmol/L) concentrations in two patients. The absence of pleocytosis and normal CSF interferon alpha was a characteristic finding compared to the classic AGS syndrome. Genetic and enzymatic tests excluded disorders of tetrahydrobiopterin metabolism, including mutation analysis of GTP cyclohydrolase feed-back regulatory protein. CSF investigations in three patients with classic AGS also showed increased pterins and partially lowered folate levels. CONCLUSIONS: Intrathecal overproduction of pterins is the first biochemical abnormality identified in patients with AGS variants. Long-term substitution with folinic acid (2-4 mg/kg/day) resulted in substantial clinical recovery with normalization of CSF folates and pterins in one patient and clinical improvement in another. The underlying defect remains unknown.

Basal Ganglia↗
PubMed2003

Reduced folate transport to the CNS in female Rett patients.

BACKGROUND: Previous CSF studies in Rett syndrome suggest reduced turnover of the biogenic monoamines serotonin and dopamine. Because diminished turnover may result from CNS folate depletion, the authors studied transport of folate across the blood-brain barrier. METHODS: In four patients with Rett syndrome, the authors measured CSF values of 5-methyltetrahydrofolate (5MTHF), biogenic monoamine end-metabolites, and pterins together with serum and red blood cell folate. In CSF, the overall folate binding capacity by the two soluble folate-binding proteins FBP1 and FBP2 (sFBP) was measured using a radioligand binding method for H3-labeled folate. A specific immunoreactive test (ELISA) detected sFBP1, which normally contributes to 30 to 35% of the total folate binding capacity. Genetic analysis included DNA sequencing of the MECP2, FBP1, and FBP2 genes. Empirical treatment with oral folinic acid was evaluated. RESULTS: Two patients without and two with mutations of the MECP2 gene had normal values for red blood cell folate, serum folate, homocysteine, and methionine. In CSF, all patients had low values for 5MTHF, neopterin, and the serotonin end-metabolite 5-hydroxyindoleacetic acid (5-HIAA). Genetic analysis of FBP1 and FBP2 genes had normal results. Compared to controls, patients with Rett syndrome had normal immunoreactive sFBP1 in CSF, whereas the total folate binding capacity was disproportionately lowered. Empirical treatment with oral folinic acid normalized 5-MHTF and 5-HIAA levels in CSF, and led to partial clinical improvement. CONCLUSION: Irrespective of the MECP2 genotype, 5MTHF transfer to the CNS is reduced in Rett syndrome. Folinic acid supplementation restores 5MTHF levels and serotoninergic turnover. The lowered folate binding capacity of FBP is not explained by a defect of the FBP1 or FBP2 gene, but most likely occurs as a secondary phenomenon in Rett syndrome.

Biogenic Monoamines↗
PubMed2002

Encephalitis related to primary varicella-zoster virus infection in immunocompetent children.

INTRODUCTION: Encephalitis is a rare complication of primary varicella-zoster virus (VZV) infection in immunocompetent children. METHODS: The clinical and laboratory findings of two girls with VZV-related encephalitis are reported. RESULTS: Both children presented with focal epileptic seizures, corresponding to cortical/subcortical as well as white matter lesions. The first showed a typical vesicular skin rash. She was easily diagnosed and made a rapid recovery during acyclovir and steroid treatment. In the second girl, a preceding measles-mumps-rubella virus vaccination and the absence of skin vesicles were misleading with respect to the diagnosis, which was finally proven by IgG seroconversion and intrathecal synthesis of IgG antibodies to VZV. She developed left parieto-occipital tissue necrosis and recovered only transiently during initial acyclovir/steroid treatment. Eight weeks after onset, progressive white matter demyelination and the occurrence of erythema nodosum in the lower limbs necessitated a second 4-month course of oral steroids. The VZV PCR from cerebrospinal fluid was negative in both children. CONCLUSIONS: Primary VZV infection may cause severe encephalitis that may occur without skin vesicles and lead to a chronic course with systemic vasculitis. The coincidence of vaccination and neurologic diseases offers no proof per se of a causal relationship.

Acyclovir↗
PubMed2002

Absent or reversed end-diastolic blood flow in the umbilical artery and abnormal Doppler cerebroplacental ratio--cognitive, neurological and somatic development at 3 to 6 years.

UNLABELLED: The objective of this study was to examine the cognitive, neurological and somatic developments of children who had in utero an absent or reversed end-diastolic blood flow (ARED) in the umbilical artery or an abnormal cerebroplacental ratio (ABF). METHODS: 16 children with ARED blood flow and 15 children with ABF were each matched to children with the same gestational age, appropriate for gestational age, the same sex and born within 4 months. Data were assessed at the age of 3-6 years. Children with asphyxia, neonatal infection, malformation or major surgical interventions in the neonatal period were excluded. Each child underwent a neuropediatrical examination; furthermore, a Kaufman Assessment Battery for Children, a Snijders-Oomen Intelligence Scale for Children and a Man-Drawing Test were used to evaluate cognitive development. The socioeconomic status was also assessed. RESULTS: Children in the ARED group remained lighter and had a higher frequency of microcephaly. In the Kaufman Assessment Battery for Children and the Snijders-Oomen Intelligence Scale for Young Children, cognitive development was impaired in the ARED and the ABF groups compared to the control group. The ARED and the ABF groups, however, showed no differences. The Man-Drawing Test and the Denver Development Test did not show any differences. DISCUSSION: ARED blood flow and ABF showed impaired cognitive development. The degree of impairment was the same in the ARED and the ABF groups. Long-term follow-up studies until adulthood are necessary to see if impaired cognitive development remains significant in these groups of patients.

Adult↗
PubMed2002

Peripheral decrease and pulmonary homing of CD4+CD45RO+ helper memory T cells in cystic fibrosis.

Interstitial lung disease, although of prognostic impact for patients with cystic fibrosis (CF), remains difficult to assess without histopathologic investigations. As changes of peripheral blood lymphocyte subsets (LS) may accompany severe systemic lymphocyte immune responses, we compared peripheral LS of 44 patients with CF, 23 non-CF patients with recurrent pulmonary infections and 83 healthy controls (flow cytometry; CD3, CD19, CD16, CD56, CD4, CD8, CD11b, CD45RA, CD45RO, HLA-DR and CD25 antigens). Additional immunohistochemistry was performed on lung tissue of four CF patients aged 0.5, 12, 17 and 20 years, respectively. Patients with CF showed low absolute counts of CD4+CD45RO+ memory helperT cells, CD16+CD56+ NK cells, CD8+ and interleukin-2 receptor-positive T cells in peripheral blood (P < 0.001). Similar changes were registered in the non-CF patients with pulmonary infections, indicating that those were not specific for CF. Immunohistochemistry showed activation of bronchus-associated lymphoid tissue with interstitial accumulation of CD4+CD45 RO+ T cells in the three older patients. Patients with CF show marked changes of peripheral blood LS which are presumably not CF-specific and may mirror homing to lung tissue in the course of interstitial lung disease. Further research should evaluate its usefulness in monitoring progression of lung disease in CF.

Adolescent↗
PubMed2002

Psychomotor retardation, spastic paraplegia, cerebellar ataxia and dyskinesia associated with low 5-methyltetrahydrofolate in cerebrospinal fluid: a novel neurometabolic condition responding to folinic acid substitution.

INTRODUCTION: Normal brain development and function depend on the active transport of folates across the blood-brain barrier. The folate receptor-1 (FR 1) protein is localized at the basolateral surface of the choroid plexus, which is characterized by a high binding affinity for circulating 5-methyltetrahydrofolate (5-MTHF). PATIENTS AND METHODS: We report on the clinical and metabolic findings among five children with normal neurodevelopmental progress during the first four to six months followed by the acquisition of a neurological condition which includes marked irritability, decelerating head growth, psychomotor retardation, cerebellar ataxia, dyskinesias (choreoathetosis, ballism), pyramidal signs in the lower limbs and occasional seizures. After the age of six years the two oldest patients also manifested a central visual disorder. Known disorders have been ruled out by extensive investigations. Cerebrospinal fluid (CSF) analysis included determination of biogenic monoamines, pterins and 5-MTHF. RESULTS: Despite normal folate levels in serum and red blood cells with normal homocysteine, analysis of CSF revealed a decline towards very low values for 5-methyltetrahydrofolate (5-MTHF), which suggested disturbed transport of folates across the blood-brain barrier. Genetic analysis of the FR 1 gene revealed normal coding sequences. Oral treatment with doses of the stable compound folinic acid (0.5-1 mg/kg/day Leucovorin(R)) resulted in clinical amelioration and normalization of 5-MTHF values in CSF. CONCLUSION: Our findings identified a new condition manifesting after the age of 6 months which was accompanied by low 5-MTHF in cerebrospinal fluid and responded to oral supplements with folinic acid. However, the cause of disturbed folate transfer across the blood-brain barrier remains unknown.

Blood-Brain Barrier↗
PubMed2001

Stw 441/465: a new fragmentary ilium of a small-bodied Australopithecus africanus from Sterkfontein, South Africa.

In 1986 and 1987, a hominid left ilium fragment consisting of a spina iliaca anterior superior and crista iliaca was discovered during excavations at Sterkfontein, South Africa. Although the specimen is small it gives valuable hints for muscle insertions and origins at the pelvis of Australopithecus africanus. It indicates that the anatomy of the abdominal muscles and of the mm. glutei medius et minimus of A. africanus was quite different from that of the great apes and more similar to that of modern humans. This has major implications for the interpretation of the bipedalism and locomotor efficiency of the early South African hominids.

Animals↗
PubMed2001

A novel neurodevelopmental syndrome responsive to 5-hydroxytryptophan and carbidopa.

Tryptophan hydroxylase (TPH; EC 1.14.16.4) catalyzes the first rate-limiting step of serotonin biosynthesis by converting l-tryptophan to 5-hydroxytryptophan. Serotonin controls multiple vegetative functions and modulates sensory and alpha-motor neurons at the spinal level. We report on five boys with floppiness in infancy followed by motor delay, development of a hypotonic-ataxic syndrome, learning disability, and short attention span. Cerebrospinal fluid (CSF) analysis showed a 51 to 65% reduction of the serotonin end-metabolite 5-hydroxyindoleacetic acid (5HIAA) compared to age-matched median values. In one out of five patients a low CSF 5-methyltetrahydrofolate (MTHF) was present probably due to the common C677T heterozygous mutation of the methylenetetrahydrofolate reductase (MTHFR) gene. Baseline 24-h urinary excretion showed diminished 5HIAA values, not changing after a single oral load with l-tryptophan (50-70 mg/kg), but normalizing after 5-hydroxytryptophan administration (1 mg/kg). Treatment with 5-hydroxytryptophan (4-6 mg/kg) and carbidopa (0.5-1.0 mg/kg) resulted in clinical amelioration and normalization of 5HIAA levels in CSF and urine. In the patient with additional MTHFR heterozygosity, a heterozygous missense mutation within exon 6 (G529A) of the TPH gene caused an exchange of valine by isoleucine at codon 177 (V177I). This has been interpreted as a rare DNA variant because the pedigree analysis did not provide any genotype-phenotype correlation. In the other four patients the TPH gene analysis was normal. In conclusion, this new neurodevelopmental syndrome responsive to treatment with 5-hydroxytryptophan and carbidopa might result from an overall reduced capacity of serotonin production due to a TPH gene regulatory defect, unknown factors inactivating the TPH enzyme, or selective loss of serotonergic neurons.

5-Hydroxytryptophan↗
PubMed2001

Evaluation of prenatal ultrasound diagnosis of fetal abdominal wall defects by 19 European registries.

OBJECTIVES: To evaluate the current effectiveness of routine prenatal ultrasound screening in detecting gastroschisis and omphalocele in Europe. DESIGN: Data were collected by 19 congenital malformation registries from 11 European countries. The registries used the same epidemiological methodology and registration system. The study period was 30 months (July 1st 1996-December 31st 1998) and the total number of monitored pregnancies was 690,123. RESULTS: The sensitivity of antenatal ultrasound examination in detecting omphalocele was 75% (103/137). The mean gestational age at the first detection of an anomaly was 18 +/- 6.0 gestational weeks. The overall prenatal detection rate for gastroschisis was 83% (88/106) and the mean gestational age at diagnosis was 20 +/- 7.0 gestational weeks. Detection rates varied between registries from 25 to 100% for omphalocele and from 18 to 100% for gastroschisis. Of the 137 cases of omphalocele less than half of the cases were live births (n = 56; 41%). A high number of cases resulted in fetal deaths (n = 30; 22%) and termination of pregnancy (n = 51; 37%). Of the 106 cases of gastroschisis there were 62 (59%) live births, 13 (12%) ended with intrauterine fetal death and 31 (29%) had the pregnancies terminated. CONCLUSIONS: There is significant regional variation in detection rates in Europe reflecting different policies, equipment and the operators' experience. A high proportion of abdominal wall defects is associated with concurrent malformations, syndromes or chromosomal abnormalities, stressing the need for the introduction of repeated detailed ultrasound examination as a standard procedure. There is still a relatively high rate of elective termination of pregnancies for both defects, even in isolated cases which generally have a good prognosis after surgical repair.

Abortion, Induced↗
PubMed2001

Application of virus-specific immunoglobulin M (IgM), IgG, and IgA antibody detection with a polyantigenic enzyme-linked immunosorbent assay for diagnosis of Epstein-Barr virus infections in childhood.

The Enzygnost anti-Epstein-Barr virus enzyme-linked immunosorbent assay (ELISA) system, which is based on a defined antigen mixture and on detection of antibodies of the immunoglobulin G (IgG), IgM, and IgA classes, was evaluated for its reliability in diagnosing Epstein-Barr virus infections in childhood. With samples from 66 children, the Epstein-Barr virus status and the infection phase were defined by indirect immunofluorescence and anticomplement fluorescence assays: 11 children were seronegative, 8 had a primary infection, 20 had a recent primary or past infection, and in 27 a reactivated Epstein-Barr virus infection was diagnosed. When applying the Enzygnost ELISAs, 15 serum samples (22.7%) were not interpretable due to indeterminate results in at least one of the assays used and were therefore excluded from further evaluation. The respective sensitivities and specificities for the diagnosis of seronegativity were 100 and 100%, those for the diagnosis of primary infection were 100 and 97%, those for the diagnosis of recent primary or past infection were 100 and 52%, and those for the diagnosis of reactivated infection were 10 and 100%. This poor performance of the Enzygnost system with reactivated infections is due to the prerequisite of an IgG antibody value of >650 IU/ml for the diagnosis of viral activity, which was fulfilled in only two of the children. Despite the high rate of indeterminate results, the Enzygnost system is useful in diagnosing acute and past Epstein-Barr virus infection in childhood. For serological diagnosis of viral activity in childhood, a supplementary assay is necessary.

Antibodies, Viral↗
PubMed2001

Long term complications of inferior vena cava thrombosis.

AIM: To evaluate the long term outcome after paediatric inferior vena cava (IVC) thrombosis. METHODS: A combined retrospective and prospective study on infants and children with IVC thrombosis treated at Aachen and Maastricht University Hospitals between 1980 and 1999. RESULTS: Forty patients were enrolled, including four with preceding cardiac catheterisation, 18 with central venous saphenous lines, and an additional eight with umbilical venous catheters. Six patients died within three months of diagnosis; one patient was lost to follow up. Twelve of the remaining 33 patients had suffered from limited IVC thrombosis; during follow up (for up to nine years) none showed persisting caval obstruction (successful thrombolysis, n = 2; spontaneous recanalisation, n = 10). The remaining 21 patients presented with extensive IVC thrombosis. During follow up (for up to 18 years) complete restitution was found in only four cases (one thrombolysis, two surgery, one spontaneous recanalisation). Persisting iliac and/or caval venous obstruction occurred in 17 patients, including six with thrombolysis. Varicose veins were found in 12, and post-thrombotic syndrome in seven of these cases. According to Kaplan-Meier analysis, 30% of patients with persisting venous disease will develop post-thrombotic syndrome within 10 years of the thrombotic event. CONCLUSIONS: Infants and children with extensive IVC thrombosis are at high risk for persisting venous disease and serious long term complications. Prospective trials are urgently needed to establish effective treatment strategies and to improve long term prognosis. Central venous catheters, contributing to IVC thrombosis in the majority of cases reported here, should be inserted only if essential.

Adolescent↗
PubMed2000

Partial liquid ventilation with surfactant: effects on gas exchange and lung pathology in surfactant-depleted piglets.

OBJECTIVE: To evaluate the effects of 24 h partial liquid ventilation (PLV) with and without surfactant (S) treatment on gas exchange and lung injury in a newborn animal model of S deficiency. DESIGN: A prospective, controlled, in vivo animal laboratory study. SETTING: Research laboratory in a university setting. SUBJECTS: Twenty-four pathogen-free, male piglets (mean weight 1.9 kg, age 1-3 days). INTERVENTIONS: The animals were randomised in four groups: PLV with FC-77 combined with conventional ventilation (PLV/CV) versus S + PLV/CV and PLV combined with high frequency oscillatory ventilation (PLV/HFOV) versus S + PLV/HFOV. The piglets were anaesthetised, intubated and instrumented with vascular catheters. Thirty minutes after lung injury had been induced with repeated saline lavage, S animals received natural S. Thirty minutes after surfactant substitution PLV with FC-77 was started. The oxygenation index (OI), PaO(2)/FIO(2) ratio, PaCO(2) and the ventilatory efficacy index were determined before and during PLV. After 24 h the lungs were removed for histopathological examination. MEASUREMENTS AND MAIN RESULTS: Within 60 min after the initiation of PLV, all animals demonstrated improvements of the OI and PaO(2)/FIO(2) ratio compared to the values after lung injury. However, at 18 and 24 h of PLV, the OI and PaO(2)/FIO(2) ratio were significantly worse in the S + PLV/CV and S + PLV/HFOV groups compared to the groups without S. PaCO(2) was higher at 18 and 24 h when S was used in PLV/HFOV (p < 0.05). A semi-quantitative lung injury score revealed most severe lung damage in the S + PLV/HFOV group. CONCLUSIONS++: The combination of S and PLV with FC-77 led to an impaired gas exchange and did not further protect the animal from lung injury.

Animals↗
PubMed2000

Severe cytomegalovirus-triggered autoimmune hemolytic anemia complicating vertically acquired HIV infection.

The association of acute cytomegalovirus infection with severe autoimmune hemolysis has not yet been reported in patients with HIV infection. The case is described of a 9-month-old infant with congenital HIV-1 infection who presented with severe autoimmune hemolysis and a high cytomegalovirus viral plasma load. Alternative causes of the hemolysis, such as drugs or other infections, were ruled out. After birth and after successful therapy of hemolysis, cytomegalovirus was not detected in the plasma, strongly suggesting a causal relationship between the hemolysis and cytomegalovirus infection. Severe autoimmune hemolysis should thus be considered as a cytomegalovirus-associated complication in HIV infection.

AIDS-Related Opportunistic Infections↗
PubMed2000

Effects of prolonged partial liquid ventilation, high frequency ventilation and conventional ventilation on gas exchange and lung pathology in newborn surfactant-depleted piglets.

Partial liquid ventilation (PLV) improves oxygenation in various animal models of respiratory insufficiency. The aim of this study was to compare the effects of conventional ventilation (CV), high frequency oscillatory ventilation (HFOV), and PLV combined with CV or HFOV on gas exchange and histopathology. Thirty anaesthetised newborn piglets (mean weight 1.94 kg, age 1-3 days) were randomized in five groups of six animals: CV, CV + surfactant (S), HFOV+S, PLV/CV, and PLV/HFOV. Thirty min after lung injury had been induced with repeated saline lavage, specific ventilatory treatment was initiated. Three animals of the CV group died within the 24 h study period, whereas none died in any of the other groups. The oxygenation index (OI) and the PaO2/FIO2 ratio improved significantly within 30 min in all groups, but not in the CV group. After 24 h all oxygenation parameters were better in the PLV groups than in CV or CV+S (P < 0.05). No differences in gas exchange were noted between HFOV+S and PLV/CV. The combination of PLV with HFOV led to an increased PaO2/FIO2 ratio when compared with PLV/CV and with HFOV+S (P < 0.05). All PLV treated animals had significantly less lung injury in the upper and lower lobes compared with gas-ventilated animals by histologic semi-quantitative lung injury score (P < 0.01) and in the lower lobes by morphometry (P < 0.001). In conclusion, HFOV+S and PLV either with CV or HFOV are effective techniques to provide adequate gas exchange in S-deficient lungs compared with CV with and without S. However, lung injury was significantly improved in both PLV treated groups compared with HFOV+S and the CV groups.

Animals↗
PubMed2000

Bronchiolitis obliterans organizing pneumonia: a distinct pulmonary complication in cystic fibrosis.

Organizing pneumonia in cystic fibrosis has hitherto been considered a nonspecific reparative process. We report on an adult patient with cystic fibrosis and histologically proven bronchiolitis obliterans organizing pneumonia, who experienced sustained clinical improvement under corticosteroid therapy. This case suggests that bronchiolitis obliterans organizing pneumonia may be a distinct pulmonary complication in cystic fibrosis and improve with specific therapy.

Adult↗