Biomedical subjects
P Fleury
Publications and source records attributed to P Fleury.
[The clinical aspects and treatment of renal angiolipomas in patients with tuberous sclerosis].
The incidence of multiple and bilateral renal angiomyolipomas in tuberous sclerosis patients is 40-80%. These benign abundantly vascularised tumours are almost always asymptomatic. Most of the symptomatic renal angiomyolipomas measure more than 4 cm. These lesions are attended by a high risk of spontaneous rupture and massive haemorrhage. In our series of 23 tuberous sclerosis patients with renal angiomyolipomas 4 became symptomatic. Three of them were successfully treated wtih transcatheter selective embolization. Preventive embolization of renal angiomyolipomas appears indicated if these measure more than 4 cm. A fifth patient became symptomatic before the diagnosis of tuberous sclerosis was made. She had a forme fruste. She was also successfully treated by the same method.
Genetic heterogeneity in tuberous sclerosis.
Tuberous sclerosis (TSC) is an autosomal dominant disorder characterized by widespread hamartosis. Preliminary evidence of linkage between the TSC locus and markers on chromosome 9q34 was established, but subsequently disputed. More recently, a putative TSC locus on chromosome 11 has been suggested and genetic heterogeneity seems likely. Here we describe an approach combining multipoint linkage analysis and heterogeneity tests that has enabled us to obtain significant evidence for locus heterogeneity after studying a relatively small number of families. Our results support a model with two different loci independently causing the disease. One locus (TSC1) maps in the vicinity of the Abelson oncogene at 9q34 and a second locus (TSC2) maps in the region of the anonymous DNA marker Lam L7 and the dopamine D2 receptor gene at 11q23.
Renal angiomyolipomas: could the histology serve as a marker for tuberous sclerosis?
The histological features of 43 renal angiomyolipomas were studied in an attempt to evaluate whether the isolated forms and those that present as part of the tuberous sclerosis complex can be distinguished. In two patients the mass was classified as an angioleiomyoma, because no adipose tissue was present. All renal angiomyolipomas showed the same basic histological picture. The combined forms, however, showed additional features such as extension into pre-existent renal parenchyma, scattered foci of hamartomatous lesions, calcified spicules and tubular inclusions. The findings suggest that these features, in an otherwise classical angiomyolipoma, should alert the pathologist to the possibility of tuberous sclerosis.
Cerebrovascular disease in Ehlers-Danlos syndrome type IV.
We describe two patients with cerebrovascular complications of Ehlers-Danlos syndrome type IV. A 16-year-old girl with spontaneous internal carotid artery dissection and a 46-year-old woman with aneurysmal subarachnoid hemorrhage and multiple aortic dissections were both deficient in collagen type III, analyzed in cultured skin fibroblasts. To our knowledge, spontaneous carotid artery dissection associated with collagen type III deficiency has not been reported previously. Early clinical recognition of this syndrome is of great importance in view of the hazards of angiography and surgery. Collagen type III deficiency plays a role in the pathogenesis of intracranial saccular aneurysms and may also be involved in the pathogenesis of carotid cavernous fistulas and dissections of the cervical arteries.
Percutaneous transcatheter embolization of symptomatic renal angiomyolipomas: a report of four cases.
Successful percutaneous transcatheter embolization of renal angiomyolipoma is reported in four female patients. The angiomyolipomas measured more than 4 cm in diameter. Three patients had severe haemorrhage and one patient had a growing angiomyolipoma in a solitary kidney. This patient had percutaneous transcatheter embolization to prevent further deterioration of kidney function. Three patients had multiple renal angiomyolipomas as part of tuberous sclerosis. Two of them had selective transcatheter embolization of more than one angiomyolipoma. After embolization, one patient had partial loss of kidney function and one patient developed an abscess that could successfully be drained percutaneously under ultrasound guidance. The following conclusions can be drawn. All patients with tuberous sclerosis should be screened for renal angiomyolipomas. All symptomatic renal angiomyolipomas and all angiomyolipomas that measure more than 4 cm in diameter require treatment. Embolization should be considered as a primary therapeutic modality for multiple angiomyolipomas.
[Neurofibromatosis; genetic and clinical aspects].
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[Cholesteatoma of the ear].
Cholesteatoma of the ear is characterized by the presence of a keratinizing squamous epithelium in the cavities of the middle ear. The epithelium invades the ear either by direct migration or by retraction of the eardrum. Owing to is potentials for migration, desquamation, bone erosion and infection, it is for most of the complications of chronic otitis and fully justifies the adjective "dangerous" applied to chronic cholesteatomatous otitis. The clinical diagnosis rests on microscope otoscopy. Audiometry informs on the degree of hearing loss and on the state of the contralateral ear. Standard radiography and computerized tomography of the petrous bone evaluate the extent of the lesion. Treatment is purely surgical: it consists of excision of the entire epithelium that has entered the middle ear and, secondarily, conservation or improvement of hearing. Whatever the surgical technique used, the frequency of recurrences calls for long-term follow-up.
Tuberous sclerosis and the relation with renal angiomyolipoma. A genetic study on the clinical aspects.
Renal angiomyolipomas were present in 23 out of a series of 38 patients with proven tuberous sclerosis (60.5%). Multiplicity and bilateral localization of combined renal angiomyolipomas were important differences between this category and the isolated, usually solitary, angiomyolipomas. One of the parents of a patient with tuberous sclerosis had small renal angiomyolipomas without signs of tuberous sclerosis. This indicates that renal angiomyolipomas might be a forme fruste of tuberous sclerosis. Two patients with suspected isolated renal angiomyolipomas proved to have tuberous sclerosis. From this study we can conclude that multiple angiomyolipomas, or a combination of a single renal hamartoma with one of the signs suggestive of tuberous sclerosis, warrant a thorough examination to exclude tuberous sclerosis.
Neonatal behavior after drug dependent pregnancy.
Neurobehavioural development of 35 infants of drug dependent mothers was compared with the development of 37 reference infants as part of a prospective longitudinal research project. Infants of drug dependent mothers had more poor responses than the other children on neurological examination. This difference is significant only when data of infants of drug dependent mothers born at full term are analysed. Two tailed testing indicated that significantly more infants of drug dependent mothers than reference children had electro-encephalograms rated as suspect or abnormal. By the end of the first month the infants of drug dependent mothers tended to be more active, and they had worse scores than the reference children on the neonatal behavioural assessment scale. Analysing data only of infants born at full term, the groups differ significantly on the interactive items. The results of this study show that even after treatment for the neonatal abstinence syndrome, infants of drug dependent mothers seem to differ from comparison children, which could indicate later developmental problems.
Behaviour in first year after drug dependent pregnancy.
Neurobehavioural development of a group of 35 infants of drug dependent mothers and of a reference group of 37 infants was compared. Two tailed testing showed that at the age of 3 months the infants of drug dependent mothers seemed to be more active than the reference group; at 6 months, however, no difference was found. On the infant behaviour temperament questionnaire, infants of drug dependent mothers tended to have slightly better scores for 'duration of orienting' at the age of 9 months; five other dimensions of behaviour did not differ between the groups. The Bayley scales of infant development and neurological examination according to the method of Touwen did not show any significant differences among the groups at the ages of 6 or 12 months. At 12 months infants of drug dependent mothers had slightly but not significantly worse results on electroencephalography. Studied with multidisciplinary measurements, the development of infants of drug dependent mothers does not seem to diverge particularly from the development of the reference group.
Evidence for genetic heterogeneity in tuberous sclerosis.
The question of genetic heterogeneity in tuberous sclerosis (TSC) was addressed by genetic linkage studies in eight affected families using nine polymorphic markers (EFD126.3, MCT136, ABO, ABL, AK1, and MCOA12 from distal 9q, and PBGD, MCT128.1, and 1CJ52.208M from distal 11q). The data as a whole supported a TSC locus on distal 9q, the peak lod score on multipoint analysis being 3.77 at 6 cM proximal to the Abelson oncogene locus (ABL). However, analysis of two point lod scores using the HOMOG programs showed significant evidence for genetic heterogeneity (p = 0.01), linkage to ABL being unlikely in one family. After exclusion of the unlinked family, multipoint analysis gave a peak lod score of 6.1 in the vicinity of ABL. The family unlinked to ABL showed no recombinants with two chromosome 11 probes, but was too small to provide significant evidence for linkage. Genetic heterogeneity in TSC will complicate efforts to clone the causative genes and severely limit the use of linked probes for carrier detection and prenatal diagnosis.
[Neurofibromatosis in pediatrics].
The diagnostic criteria and complications of neurofibromatosis (Von Recklinghausen's neurofibromatosis or peripheral neurofibromatosis) are summarized. Patients and their relatives were studied in pediatric departments of the University Hospitals at Amsterdam (n = 23) and Rotterdam (n = 39) using a multidisciplinary approach and a standardized protocol. This comprehensive evaluation enables improved detection of serious complications and their management, and information to the parents about this highly variable disorder. Also, more insight is obtained into the natural history of the disease. Genetic counseling and family studies will become more precise in the near future, now the gene for NF I has been localised on chromosome 17, and for NF II (central NF) on chromosome 22, enabling DNA-marker studies.
Schematic representation of NF-1 clinical features in Dutch.
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[Tuberous sclerosis, changes in the diagnostic and therapeutic approach].
In the last 15 years the diagnostic possibilities in tuberous sclerosis have considerably improved. Some new signs of this disorder have recently been described. The meaning of other signs became more evident. Investigation of large groups of patients made it possible to indicate which clinical features of tuberous sclerosis may be classified according to their diagnostic importance as pathognomonic or definitively diagnostic or as presumptive or provisionally diagnostic. It is sometimes difficult to determine the significance of a single nonspecific lesion. It is very important to know the meaning of the signs for those parents or more distant relatives who ask for genetic counseling. As long as the gene defect in tuberous sclerosis had not been determined it will remain possible that formes frustes will not be detected despite the most elaborate examination. Connected with the improvement of the diagnosis by imaging technics of especially the cerebral and renal features, the therapeutic possibilities have been changed. On one side this concerns neurosurgical removing of giant cell astrocytoma situated near the foramen of Monro and of cortical or subcortical tubers that cause therapy resistant partial epilepsy. On the other side it concerns embolisation of symptomatic renal angiomyolipomas or renal transplantation in the case of renal insufficiency due to cysts with or without angiomyolipomas.
[Localization of the gene defect in tuberous sclerosis].
Elucidation of the genetic defect in tuberous sclerosis (TS) awaits a precise chromosomal localization. At present two chromosomal regions, 9q34 and 11q23, are candidates for the site of a TS locus. Family studies using polymorphic DNA markers are carried out in other laboratories and in ours and are expected to disclose the existence of one TS gene that is localized on either chromosome 9 or 11, or the involvement of two genes, one on #9 and one on #11. Early postnatal and potentially prenatal diagnosis by means of DNA analysis may be offered to a family with TS after identification of the gene defect, but also after the identification of very closely linked DNA markers.
Gliomatosis cerebri, report of a clinically diagnosed and histologically confirmed case.
Pathological criteria for diffuse gliomatosis are clearly demarcated but its clinical diagnosis has always been hampered by the imaging techniques used. Although with the advent of CT scanning clinical possibilities were improved, isodense brain lesions are difficult to detect and in these cases the diagnosis gliomatosis cerebri can only be suspected from the clinical signs and the absence of radiological signs. We have studied a young patient with a peculiar clinical history, in whom comparison of the CT-scan and NMR scan yielded remarkable results. Our clinical diagnosis of (diffuse) gliomatosis was confirmed by biopsy.
The incidence of hepatic hamartomas in tuberous sclerosis. Evaluation by ultrasonography.
Our series of tuberous sclerosis patients consisted of 23 children between 6 and 16 years of age and of 13 patients between 16 and 48 years of age. In the former group the incidence of multiple hepatic haemangiomas, estimated by grey-scale ultrasonography, is 13%, whereas this incidence is 23% in the group of older patients. The sign might be important for genetic counselling in formes frustes.