Hepatic manifestations of Wilson's disease: frequency and pattern in Saudi patients

Seven symptomatic patients with Wilson's disease have so far been diagnosed at King Khalid University Hospital (KKUH), Riyadh, over the last six years. On family screening, another three asymptomatic patients were found to be affected. Five of the symptomatic patients had clinical features of liver disease on initial presentation and was preceded by renal dysfunction in another patient. The remaining patient presented with neurological features. Six patients had Kayser-Fleisher ring. Abnormal liver function tests were found in half of the patients. Ceruloplasmin was reduced in 7 of 10 patients. Serum copper and urinary copper estimations were most useful diagnostic laboratory tests. Morphological alteration was found in all 9 patients who had a percutaneous liver biopsy. All patients were treated initially with D-penicillamine and clinical response was noted in seven, of whom one developed neurological manifestations while receiving the treatment. D-penicillamine was replaced by zinc sulfate in 3 patients who developed thrombocytopenia. The data suggest that Wilson's disease may not be rare in Saudi Arabia. For early detection and prompt treatment, the disease should be suspected under appropriate clinical circumstances especially in young patients with liver diseases. Close relatives of such index patients should be routinely screened.     

Thoracic outlet syndrome--a myofascial variant: Part 3. Structural and postural considerations

Thoracic outlet syndrome involves more than just local neurovascular compression. Myofascial release treatments and stretching exercises may be only partially or temporarily successful unless all related components of somatic dysfunction, including craniosacral mechanisms, are addressed. Structural and postural abnormalities in the frontal plane, as with a short leg, and in the sagittal plane, such as lumbopelvic imbalances, as well as neural involvement all contribute to thoracic outlet syndrome symptoms. Once segmental restrictions are treated and symptoms diminish, postural correction and strengthening exercises may be initiated. Osteopathic diagnosis and treatment of the local, regional, and remote structural problems is necessary for optimal treatment of thoracic outlet syndrome and the maintenance of a symptom-free status.     

Optimized microvessel density analysis improves prediction of cancer stage from prostate needle biopsies

During angiogenesis in the chorioallantoic membrane (CAM) of the chick, capillary proliferation occurs primarily by intussusceptive growth. Previously, we reported that such growth in the CAM proceeded without substantial macromolecular extravasation. Neovascularization involving capillary sprout formation, on the other hand, has been associated with a concomitant loss of endothelial selectivity. Thus, the present study tested the hypothesis that endothelial selectivity during angiogenesis is dependent on the mode of microvascular growth. Capillary sprout formation occurs in peripheral regions of the CAM, in addition to the more centrally located areas of intussuceptive growth. In this study, angiogenic endothelial permselectivities were evaluated in these respective areas of CAM microvascular growth by intravital fluorescent microscopy of a graded series of FITC-dextrans. In both cases, the angiogenic endothelia restricted extravasation of macromolecules > or = 20 kDa. Furthermore, capillary sprout endothelia, like the intussusceptive CAM endothelia, remained tightly sealed at the junctional clefts. Thus, angiogenic endothelial permselectivity in the CAM is not dependent on the mode of microvascular growth. Whether distinct cellular mechanisms are operable in capillary endothelial sprouts of the CAM, relative to those of other proliferating sprout endothelia, remains to be tested.     

Development of monoclonal gammopathy precedes the development of Epstein-Barr virus-induced posttransplant lymphoproliferative disorder

Epstein-Barr virus (EBV)-induced posttransplant lymphoproliferative disorder (PTLD) develops in 3% to 10% of solid organ transplant recipients with a resultant mortality of up to 70%. Unfortunately, there is no current marker which identifies patients who will develop this disease. We therefore conducted a risk factor analysis of variables that might predict the development of PTLD. Specifically, since EBV may cause both PTLD and the development of monoclonal proteins (M protein), we sought to determine if the development of an M protein preceded and therefore might serve as a predictive marker of subsequent PTLD. Before and after liver transplantation, 201 patients were evaluated for the presence of urine and serum M proteins. Patients were followed to monitor the development of PTLD for a mean of 1,733 days. PTLD developed in seven patients (3.5%), three (43%) of whom died from disseminated PTLD. PTLD was classified as polymorphous in six patients and monomorphous in one patient. Fifty-seven patients (28%) developed an M protein after transplantation: five of seven patients (71%) with PTLD and 52/194 (27%) of patients without PTLD. Multivariate risk factor analysis for the development of an M protein after transplantation identified cytomegalovirus (CMV) donor seropositivity (P = 0.0002) and postoperative symptomatic CMV infection (P = 0.019) as risk factors. Whereas EBV serostatus of either the donor or recipient was not found to be a risk factor for the occurrence of either an M protein or PTLD, the development of a serum immunoglobulin M (IgM) M protein (P = 0.04) and of any urine M protein (P = 0.01) was identified by univariate analysis as being associated with the development of PTLD. Further studies are needed to determine the predictive value of M proteins as a marker for PTLD. Until such time, the development of serum or urine M protein should heighten the suspicion of developing PTLD.     

Uptake of tetracycline in otoconia of the guinea pig

Calcium ion turnover in the otoconia of adult guinea pigs was investigated by observing the uptake of tetracycline. Oral administration of tetracycline resulted in the deposition of tetracycline (fluorescence) on the outer surface of otoconia, indicating the occurrence of dynamic exchange and/or uptake of calcium ions in the otoconia. Prolonged administration of tetracycline induced with fluorescence deposition in the central portion as well as on the surface of the otoconia. These findings suggest the occurrence of neogenesis, regeneration and/or growth of otoconia even in adult animals.     

Sequence specificity in the interaction of the four stereoisomeric benzo[c]phenanthrene dihydrodiol epoxides with the supF gene

The shuttle vector pS189 was treated with each of the four configurational isomers of benzo[c]phenanthrene 3,4-dihydrodiol 1,2-epoxide, and the modified DNA was used as a template in a polymerase arrest assay examining the supF gene. Sites at which polymerase (Sequenase, version 2.0) progress along the template was blocked were presumed to be at or near sites of adduct formation. The polymerase arrest sites were compared with recently reported mutation hotspots induced by these agents in this gene (Bigger et al., Proc. Natl. Acad. Sci. USA, 89: 368-372, 1992). For 31 of 32 mutation hotspots, a polymerase arrest band was present at or 1 or 2 nucleotides 3'- to that site, indicating that adduct formation tended to be associated with mutation hotspots. However, the arrest bands near mutation hotspots were not particularly prominent in all cases, and there were many sites of substantial polymerase arrest that were not in the vicinity of mutation hotspots. Thus, factors in addition to chemical selectivity must play key roles in determining sites of mutation.