High-resolution human genome scanning using whole-genome BAC arrays.
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Chromosome Mapping↗
Biomedical subjects
B Bejjani
Publications and source records attributed to B Bejjani.
Idazoxan, an alpha-2 antagonist, and L-DOPA-induced dyskinesias in patients with Parkinson's disease.
Dyskinesia is a frequent and disabling side effect in patients with Parkinson's disease treated with chronic dopa-therapy. Preclinical data in the 1-methyl-4-phenyl-1,2,3,6,-tetrahydropyridine (MPTP) monkey suggest that alpha-2 antagonists may reduce dihydroxyphenylalanine (L-DOPA)-induced dyskinesia. We assessed, in a pilot randomised placebo-controlled study, the effects of single oral doses (10 mg, 20 mg, and 40 mg) of idazoxan, an alpha-2 antagonist, on motor parkinsonian disability and L-DOPA-induced dyskinesia following an acute oral challenge of L-DOPA in 18 patients with Parkinson's disease. The severity of L-DOPA-induced dyskinesia improved after 20 mg idazoxan pretreatment, while there was no concommittant deterioration in the antiparkinsonian response to L-DOPA. These results suggest that blocking alpha-2 receptors in patients with Parkinson's disease might improve L-DOPA-induced dyskinesia without the cost of a return of parkinsonian symptomatology. Further studies are required to assess whether this property could have potential therapeutic applications in the long-term management of dyskinetic patients with Parkinson's disease.
Administration, Oral↗
Normal expression of the Fanconi anemia proteins FAA and FAC and sensitivity to mitomycin C in two patients with Seckel syndrome.
Seckel syndrome is a rare autosomal recessive disorder. The classical presentation includes pre- and postnatal growth deficiency, mental retardation, and characteristic facial appearance. There have been several reports of associated hematological abnormalities and chromosomal breakage, findings suggestive of Fanconi anemia (FA). We tested for these findings in two Arabic patients with this syndrome. We compared the growth profile of lymphoblastoid cells from our patients and their parents with the FA group A cell line HSC72 in the presence and absence of mitomycin C (MMC). By Western analysis, we also determined the expression of FAA and FAC, two FA disease gene products that together account for approximately 80% of FA. Unlike HSC72 cells, cells from the patients were resistant to MMC, and both FAA and FAC proteins were expressed at similar levels in all cell lines. There is an increasing recognition of clinical variability and perhaps genetic heterogeneity in Seckel syndrome. Our results demonstrate that cross-link sensitivity comparable to FA is not a uniform finding in patients with Seckel syndrome.
Abnormalities, Multiple↗
Pallidal stimulation for Parkinson's disease. Two targets?
There has been renewed interest in functional surgery as treatment for Parkinson's disease (PD). Although pallidotomy and chronic pallidal stimulation are highly effective in suppressing levodopa-induced dyskinesia (LID), both methods also seem to be effective in reducing parkinsonian disability. However, the simultaneous improvement of LID and motor signs is hard to explain with the classic model of basal ganglia circuitry. Taking advantage of the fact that deep brain stimulation is reversible and that implanted electrodes contain four discrete stimulation sites, we investigated the effect of stimulation on different sites of the globus pallidus (GP) in five PD patients. Stimulation in the dorsal GP (upper contact) significantly improved gait, akinesia, and rigidity and could induce dyskinesia when patients were in the "off" state. In contrast, stimulation in the posteroventral GP (lower contact) significantly worsened gait and akinesia, although the reduction in rigidity remained. For patients in the "on" state, stimulation in the posteroventral GP dramatically reduced LID but, as in the "off" state, worsened gait and akinesia, thus canceling out the antiparkinsonian effect of levodopa. Our results indicate that stimulation had a striking different effect on parkinsonism and dyskinesia when applied at two different loci of the GP and that stimulation applied in the posteroventral GP produced opposite effects on rigidity and on akinesia. We conclude that parkinsonian signs and LID are a reflection of at least two different anatomofunctional systems within the GP and that this functional organization of the GP needs to be considered when determining the optimal target for surgical treatment of PD.
Adult↗
Genetic disorders that masquerade as multiple sclerosis.
There are many genetic disorders that have signs and symptoms suggestive of multiple sclerosis and that may easily be overlooked in the evaluation of both adult and pediatric multiple sclerosis patients. The recognition of a genetic disorder as the cause of a patient's "multiple sclerosis" phenotype has important implications not only for the patient, but often also for others in the patient's family who may be at risk for the same disease. We present here a review of single gene disorders that can masquerade as multiple sclerosis. For each disorder, the major clinical and biochemical characteristics are discussed, together with the appropriate testing to screen for and confirm the diagnosis. In addition, guidelines are presented for when to suspect an underlying genetic condition in a patient with a diagnosis of definite or probable multiple sclerosis. The great variety of genetic disorders that can masquerade as multiple sclerosis and the many implications of a genetic diagnosis underscore the importance of recognizing genocopies of multiple sclerosis.
Diagnosis, Differential↗
The value of deletion analysis for carrier detection in Duchenne muscular dystrophy (DMD).
We performed genetic analysis for carrier detection for several at-risk females in a four-generation Duchenne muscular dystrophy (DMD) pedigree using deletion analysis. We demonstrated that dosage analysis is a suitable alternative method to determine the carrier status of female relatives of DMD patients shown to have a deletion within the DMD gene. Subsequently, we diagnosed an affected male fetus for an at-risk female shown to be a DMD carrier by deletion analysis. The usefulness of deletion and linkage analysis are compared. In this family, linkage analysis was complicated by the unavailability of key family members, two recombination events and by previously undisclosed nonpaternity. We found that dosage analysis was more efficient than linkage for carrier evaluation in this family.
Adult↗
Clinical findings and linkage studies in familial tuberous sclerosis.
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Calcium-Binding Proteins↗
Localization of one gene for tuberous sclerosis within 9q32-9q34, and further evidence for heterogeneity.
Tuberous sclerosis (TSC) is an autosomal dominant disorder with both neurological and cutaneous manifestations often resulting in significant disability. Although it has been studied clinically and biochemically for many years, the underlying pathophysiology remains unknown. Genetic linkage analysis provides an alternative strategy for understanding the genetic etiology of this disease. Genetic linkage of a gene for TSC to loci in 9q32-9q34 has been reported but has not been a universal finding, since absence of linkage to 9q loci, as well as linkage to loci on 11q, have also been reported. We present here data on 22 families (21 previously unreported) segregating TSC. Our results strongly support a TSC locus in the 9q32-34 region for approximately one-third of families and provide significant evidence for genetic heterogeneity. Application of newly described highly polymorphic dinucleotide repeat marker loci in TSC greatly enhanced the informativeness of our pedigrees and was vital for detecting the heterogeneity. No clear evidence of linkage to chromosome 11q22 markers was found, suggesting that a still unidentified TSC locus elsewhere in the genome may account for the majority of TSC families.
Chromosomes, Human, Pair 9↗
Ureteral seminal vesicle anomaly. Gross hematuria as presenting symptom.
An ectopic ureter ending in a seminal vesicle and associated with renal agenesis is a rare occurrence. There are no reports of this anomaly occurring with gross, total, painless hematuria as presenting symptom. Sonography and catheterization of the ejaculatory duct were the most helpful diagnostic studies used to demonstrate the abnormality. Surprisingly, on pathologic examination, the cystic area was not seminal vesicle but a dilated hemorrhagic ureter.
Adult↗
Calcification and bone marrow formation in ureteropelvic junction obstruction.
Abnormal deposits of calcium in ischemic and necrotic tissue is a common finding in human pathological conditions. Calcium is found in 1 to 2 per cent of renal cysts and 10 per cent of renal cell carcinomas. Calcification in hydronephrosis secondary to ureteropelvic junction obstruction is rare. No cases of bone marrow arising within a calcified renal mass have been reported.
Adult↗
Ureteropelvic junction obstruction in newborns and infants.
Of 11 patients less than 1 year old with ureteropelvic junction obstruction 9 presented with an abdominal mass. The ideal method evaluation of such patients with an abdominal mass includes sonography followed by isotope renal scan if the mass is determined to be urinary in origin. Visualization by excretory urography in this age group is often impaired by poor renal concentrating ability and excessive bowel gas. Repair was achieved successfully using a nonintubated, nonstented, dismembered pyeloplasty in 10 of 13 kidneys. The average postoperative hospital stay for this group was 4.8 days. Three kidneys were diverted temporarily by nephrostomy, leading to a complication in 1 that required secondary repair. Average postoperative hospital stay in the diverted group was 15 days. Renal function was excellent following repair in all patients, suggesting that early repair is highly desirable in this age group.
Female↗
Pyelocaliceal diverticulum presenting as a disappearing renal mass.
We report a rare case of a disappearing cystic mass of the kidney. Pyelocaliceal diverticulum has to be considered in the differential diagnosis of patients with pyelonephritis and a space-occupying lesion of the kidney. Initial conservative therapy with antibiotics helps to determine the definitive diagnosis. Surgical management is recommended to prevent sequelae of pain and infection.
Adult↗