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Biomedical subjects

J Haan

Publications and source records attributed to J Haan.

At least 37 records · Page 2Linked to original sources
PubMed2002

Episodic ataxia type 2. Three novel truncating mutations and one novel missense mutation in the CACNA1A gene.

We analysed the CACNA1A gene, located on chromosome 19p13, in three unrelated families and one sporadic case with episodic ataxia type 2 (EA-2). In two of the families and the sporadic patient, novel truncating mutations, which disrupt the reading frame and result in a premature stop of the CACNA1A protein, were identified in exons 14, 16 and 26. In the remaining family, a novel missense mutation (H253Y) was found. Of the twenty two EA-2 mutations identified thus far, including those of the present study, seventeen are truncating mutations and five are missense mutations, all resulting in an EA-2 clinical phenotype.

Adult↗
PubMed2002

Familial cyclic vomiting syndrome.

A family is described in which four members suffer from cycling vomiting syndrome (CVS), without additional symptoms. So far, only a few CVS families have been described in literature, and most patients belonging to these families had other symptoms in addition to CVS. We conclude that 'pure' CVS may also be a hereditary disorder. Its relation to migraine will be discussed.

Adolescent↗
PubMed2002

Comparison of coagulation activity tests in vitro for selected biomaterials.

Testing of coagulation induced by external communicating medical devices is an International Standardisation Organization (ISO) requirement for products exposed to human blood. Four categories of tests are indicated by ISO 10993/4: a clotting test (partial thromboplastin time; PTT), thrombin generation, fibrinogen deposition, or measurement of coagulation split products. We evaluated the specificity of these tests on various polymers and found only thrombin generation and fibrinogen binding sensitive and reproducible tests while thrombin generation correlated best with the classical PTT. The thrombin generation assay is therefore the method of choice for testing coagulation induced by biomaterials and medical devices.

Animals↗
PubMed2001

Cerebral microbleeds in CADASIL.

BACKGROUND: Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is a hereditary arteriopathy leading to recurrent cerebral infarcts and dementia. Intracerebral hemorrhage (ICH) has been described sporadically in patients with CADASIL, suggesting that the affected arteries in CADASIL are not bleed-prone. However, the presence of cerebral microbleeds, which often remain undetected on conventional MRI, has not been determined in CADASIL. OBJECTIVE: To determine whether cerebral vessels in patients with CADASIL are prone to microbleeding. METHODS: T2*-weighted gradient echo MRI, which is highly sensitive for visualizing microbleeds, was performed in patients with CADASIL and their family members (n = 63). Known risk factors for ICH were determined for all individuals. On an exploratory basis, the presence of cerebral microbleeds was correlated with demographic variables, vascular risk factors, disease progression, ischemic MR lesions, and genotype. RESULTS: Cerebral microbleeds were present in 31% of symptomatic CADASIL mutation carriers, predominantly in the thalamus. Vascular risk factors such as hypertension did not account for the microbleeds in these patients. Factors associated with microbleeds were age (p = 0.008), Rankin disability score (p = 0.017), antiplatelet use (p = 0.025), number of lacunae on MRI (p = 0.009), and the Arg153Cys Notch3 mutation (p = 0.017). After correction for age, only the Arg153Cys mutation remained significantly associated with the presence of microbleeds. CONCLUSION: Patients with CADASIL have an age-related increased risk of intracerebral microbleeds. This implies that they may have an increased risk for ICH, which should be taken into account in CADASIL diagnosis and patient management.

Adult↗
PubMed2001

[From gene to disease; amyloid-beta precursor protein gene instrumental in hereditary cerebral amyloid angiopathies].

Hereditary cerebral haemorrhage with amyloidosis-Dutch type (HCHWA-D) is an autosomal dominant disease caused by a mutation in the amyloid precursor protein gene on chromosome 21. The disease is characterised by amyloid deposition in cerebral blood vessels, which results in cerebral haemorrhages, leucencephalopathy, dementia and death. In the same gene, mutations have also been found for other rare diseases which also result in dementia and haemorrhages, as well as familial Alzheimer's disease (different mutations in different families). The majority of familial Alzheimer cases, however, are associated with mutations in the PS1 gene (more than 70 different mutations) or the PS2 gene (4 mutations).

Alzheimer Disease↗
PubMed2001

Hereditary vascular retinopathy, cerebroretinal vasculopathy, and hereditary endotheliopathy with retinopathy, nephropathy, and stroke map to a single locus on chromosome 3p21.1-p21.3.

We performed a genomewide search for linkage in an extended Dutch family with hereditary vascular retinopathy associated with migraine and Raynaud phenomenon. Patients with vascular retinopathy are characterized by microangiopathy of the retina, accompanied by microaneurysms and telangiectatic capillaries. The genome search, using a high throughput capillary sequencer, revealed significant evidence of linkage to chromosome 3p21.1-p21.3 (maximum pairwise LOD score 5.25, with D3S1578). Testing of two additional families that had a similar phenotype, cerebroretinal vasculopathy, and hereditary endotheliopathy with retinopathy, nephropathy, and stroke, revealed linkage to the same chromosomal region (combined maximum LOD score 6.30, with D3S1588). Haplotype analysis of all three families defined a 3-cM candidate region between D3S1578 and D3S3564. Our study shows that three autosomal dominant vasculopathy syndromes with prominent cerebroretinal manifestations map to the same 3-cM interval on 3p21, suggesting a common locus.

Chromosome Mapping↗
PubMed2001

Involvement of the CACNA1A gene containing region on 19p13 in migraine with and without aura.

OBJECTIVE: To assess the involvement of the 19p13 familial hemiplegic migraine (FHM) locus in migraine with and without aura. BACKGROUND: Migraine with and without aura are likely to be polygenetic multifactorial disorders. FHM is a rare dominantly inherited type of migraine with aura. In about 50% of families, FHM is caused by mutations in the P/Q-type calcium channel alpha(1A)-subunit (CACNA1A) gene on chromosome 19p13. The CACNA1A gene is thus a good candidate gene for "nonhemiplegic" migraine with or without aura. METHODS: The authors performed an affected sibpair analysis using flanking and CACNA1A intragenic markers. The authors assessed the occurrence of shared parental marker alleles among 189 affected siblings from 36 extended families with typical migraine with or without aura. RESULTS: Sibling pairs with any form of migraine had inherited the same 19p13 CACNA1A-containing region significantly more frequently than expected by chance (maximum multipoint lod score = 1.22). This result was almost exclusively dependent on the increased sharing found in sibling pairs with migraine with aura (maximum multipoint lod score = 1.41). The locus-specific relative risk for a sibling (lambda(s)) to suffer from migraine with aura, defined as the increase in risk of the trait attributable to the 19p13 locus, was lambda(s) = 1.56. When combining migraine with and without aura, lambda(s) was 1.22. CONCLUSIONS: The increased allele sharing in the CACNA1A gene region on 19p13 is consistent with an important involvement of this region in migraine, especially migraine with aura.

Alleles↗
PubMed2001

[From gene to disease; from CACNA1A to migraine].

Familial hemiplegic migraine (FHM) is a rare autosomal dominant subtype of migraine with aura. FHM is associated in half the families with mutations in the CACNA1A gene on chromosome 19P13, encoding the alpha-1A subunit of brain-specific P/Q-type calcium channels. P/Q-type calcium channels are important in neurotransmitter release. The first functional studies indicate that mutations causing FHM result in a gain or loss of function of P/Q-type calcium channels. Affected sib-pair analysis in families with migraine with and without aura indicates involvement of the CACNA1A gene in these more frequent types of migraine.

Calcium Channels↗
PubMed2001

Dementia in hereditary cerebral hemorrhage with amyloidosis-Dutch type is associated with cerebral amyloid angiopathy but is independent of plaques and neurofibrillary tangles.

Cerebral amyloid angiopathy is frequently found in demented and nondemented elderly persons, but its contribution to the causation of dementia is unknown. Therefore, we investigated the relation between the amount of cerebral amyloid angiopathy and the presence of dementia in 19 patients with hereditary cerebral hemorrhage with amyloidosis-Dutch type. The advantage of studying hereditary cerebral hemorrhage in amyloidosis-Dutch type is that patients with this disease consistently have severe cerebral amyloid angiopathy with minimal neurofibrillary pathology. The amount of cerebral amyloid angiopathy, as quantified by computerized morphometry, was strongly associated with the presence of dementia independent of neurofibrillary pathology, plaque density, or age. The number of cortical amyloid beta-laden severely stenotic vessels, vessel-within-vessel configurations, and cerebral amyloid angiopathy-associated microvasculopathies was associated with the amount of cerebral amyloid angiopathy and dementia. A semiquantitative score, based on the number of amyloid beta-laden severely stenotic vessels, completely separated demented from nondemented patients. These results suggest that extensive (more than 15 amyloid beta-laden severely stenotic vessels in five frontal cortical sections) cerebral amyloid angiopathy alone is sufficient to cause dementia in hereditary cerebral hemorrhage with amyloidosis-Dutch type. This may have implications for clinicopathological correlations in Alzheimer's disease and other dementias with cerebral amyloid angiopathy.

Aged↗
PubMed2001

Delayed cerebral edema and fatal coma after minor head trauma: role of the CACNA1A calcium channel subunit gene and relationship with familial hemiplegic migraine.

Trivial head trauma may be complicated by severe, sometimes even fatal, cerebral edema and coma occurring after a lucid interval ("delayed cerebral edema"). Attacks of familial hemiplegic migraine (FHM) can be triggered by minor head trauma and are sometimes accompanied by coma. Mutations in the CACNA1A calcium channel subunit gene on chromosome 19 are associated with a wide spectrum of mutation-specific episodic and chronic neurological disorders, including FHM with or without coma. We investigated the role of the CACNA1A gene in three subjects with delayed cerebral edema. Two subjects originated from a family with extreme FHM, and one subject was the previously asymptomatic daughter of a sporadic patient with hemiplegic migraine attacks. In all three subjects with delayed severe edema, we found a C-to-T substitution resulting in the substitution of serine for lysine at codon 218 (S218L) in the CACNA1A gene. The mutation was absent in nonaffected family members and 152 control individuals. Haplotype analysis excluded a common founder for both families. Neuropathological examination in one subject showed Purkinje cell loss with relative preservation of granule cells and sparing of the dentate and inferior olivary nuclei. We conclude that the novel S218L mutation in the CACNA1A calcium channel subunit gene is involved in FHM and delayed fatal cerebral edema and coma after minor head trauma. This finding may have important implications for the understanding and treatment of this dramatic syndrome.

Adolescent↗
PubMed2001

Incidental pregnancy in trauma patients.

BACKGROUND: The rate of incidental pregnancy in trauma patients and the incidence of associated fetal mortality, to our knowledge, have not been previously reported. The early diagnosis of pregnancy in trauma patients has become even more difficult because rapid pregnancy screens have been eliminated because of quality control issues. We determined the rate of incidental pregnancy and the sequelae of delayed diagnosis, including fetal radiation exposure and mortality. STUDY DESIGN: Data were analyzed retrospectively on all patients in whom pregnancy was diagnosed during a trauma admission during a 4-year period (1995 to 1999). Pregnancy was confirmed by beta-HCG testing and gestational age estimated by an obstetrician by ultrasonography. Pregnancy outcomes were determined by a prospective telephone survey. RESULTS: One hundred fourteen (2.9%) of the 3,976 women (age 15 to 40 years) admitted to the trauma center were found to be pregnant. Thirteen (11.0%) were incidental pregnancies, of which 9 (8.0%) were newly diagnosed. Mean gestational age was significantly lower in the newly diagnosed pregnancies (6.9 versus 20.5 weeks, p < 0.0005). Fetal mortality in this group was significantly higher (100% versus 25%, p < 0.0005). The mean initial radiation exposure of all patients was 4.5 rads. Cumulative radiation exposure exceeded 5 rads in 85% of patients. CONCLUSIONS: Trauma patients diagnosed with incidental pregnancy are routinely exposed to doses of radiation exceeding the recommendations of the American College of Obstetrics and Gynecologists. Reinstitution of the rapid pregnancy test should be considered in all female trauma victims of childbearing age. This may promote a reduction in fetal radiation exposure and perhaps influence a portion of the fetal mortality in those patients with newly diagnosed incidental pregnancy.

Adolescent↗
PubMed2001

No involvement of the calcium channel gene (CACNA1A) in a family with cluster headache.

It is very likely that genetic factors play a role in the pathophysiology of cluster headache (CH). As CH shares its paroxysmal character with migraine, and migraine has been described in coexistence with CH in some families, we hypothesized that both diseases might share a genetic aetiology. In this study, we tested whether the migraine CACNA1A gene on chromosome 19 is involved in CH in an extended pedigree. Haplotype analysis did not reveal an obvious disease haplotype, and SSCP analysis of all 47 exons of the CACNA1A gene did not reveal a causative mutation. CH in this family is not caused by mutations in the CACNA1A gene.

Calcium Channels↗
PubMed2001

Admission angiography for blunt splenic injury: advantages and pitfalls.

BACKGROUND: To analyze the use of admission angiography as a nonoperative adjunct for management of blunt splenic injury. METHODS: Retrospective chart review of all blunt splenic injuries to a Level I trauma center from March 1997 through July 1999. RESULTS: One hundred twenty-six patients underwent angiography for splenic injury. Eighty-six patients (68%) had a negative angiogram and were treated expectantly. Of these, seven patients (8%) required laparotomy, with a splenic salvage rate of 92%. Embolization was performed on 40 patients (32%) for evidence of vascular injury. Of these, three patients (8%) required laparotomy, for a total salvage of 92%. Repeat angiography was performed for suspicion of bleeding in 12 patients (10%), with 50% requiring embolization. Outcome based on CT grade demonstrated an average grade of 2.9, with a salvage rate of greater than 70% for grade IV and V injuries. CONCLUSION: Vascular injury increases with splenic injury grade. Embolization improves nonoperative salvage rates to 92%, even with high-grade injuries. Ten percent of patients require additional therapy including "second-look" angiography. A significant portion of patients with negative screening angiograms (10%) required either embolization or laparotomy to control delayed hemorrhage.

Adult↗
PubMed2000

Alternating hemiplegia of childhood: no mutations in the familial hemiplegic migraine CACNA1A gene.

INTRODUCTION: Alternating hemiplegia of childhood (AHC) is a rare disorder mainly characterized by attacks of hemiplegia and mental retardation. It has been often associated with migraine. The CACNA1A gene on chromosome 19 is involved in familial hemiplegic migraine and other episodic cerebral disorders, but also with progressive neuronal damage. METHODS: We performed mutation analysis in this gene in four AHC patients, using single strand conformation polymorphism analysis. RESULTS: We found nine polymorphisms, but no mutations in any of the 47 exons. CONCLUSIONS: Other cerebral ion channel genes remain candidate genes for AHC.

Adult↗