MACULAR HAEMORRHAGE IN ADULT ACUTE LEUKAEMIA PATIENTS AT PRESENTATION AND THE RISK OF SUBSEQUENT INTRACRANIAL HAEMORRHAGE

Glycoprotein (GP)-specific platelet-associated IgG (PA-IgG) may be demonstrable in autoimmune-mediated thrombocytopenia. We studied 159 consecutive patients with histories of thrombocytopenia by a modified direct monoclonal antibody-specific immobilization of platelet antigens (direct MAIPA) assay, which immobilizes GP IIb/IIIa, GP Ib/IX and GP Ia/IIa simultaneously. This modification requires smaller quantities of platelets than standard measurements performed separately. PA-IgG was present in 84/159 (53%) patients, as shown by the direct platelet immunofluorescence test (PIFT) with flow cytometry as a reference. PA-IgG against GP IIb/IIIa and/or GP Ib/IX and/or GP Ia/IIa was noted in 46 patients (29%), of whom 93% (43/46) were also PA-IgG positive. The amount of PA-IgG detected by PIFT correlated directly with that detected by direct MAIPA ( r =0.71; P <0.0001). Only three patients 12548 with negative direct PIFT had GP-specific PA-IgG. GPV-specific PA-IgG was detected in 13 (10%) of the 125 patients, in whom further studies could be performed. In the subgroup of patients with GP-specific PA-IgG, the median fluorescence intensities of direct PIFT were higher than in patients with no GP-specific PA-IgG ( P <0.001). Direct PIFT and direct MAIPA divided the patients into asymmetric subgroups. However, the relative roles of these tests in the diagnosis of autoimmune-mediated thrombocytopenia await further studies.     

Arthrographic imaging of post-traumatic temporomandibular joint disorders.

Clinical, arthrographic and surgical findings in 20 patients who showed persisting TMJ-pain or dysfunction after an acute traumatic event were reviewed and compared to findings in a control group of 65 patients who did not remember an acute post-traumatic onset of symptoms. Anterior disk displacement (82%), disk perforation (65%) and rotational anteromedial disk displacement (34%) were the most common abnormalities encountered. Other important abnormalities were joint adhesions and capsule perforation. When compared with the control group, all these abnormalities occurred more often in traumatised joints. Arthrography was found to be highly accurate in detecting most types of abnormalities found during surgery. Arthrography is reported to be more effective than MRI in detecting disk perforations, adhesions and capsule perforations, which points to its continuing importance as an imaging tool for evaluating post-traumatic temporomandibular joint disorders.     

Incidence of arm swelling following axillary clearance for breast cancer.

Arm swelling was measured using volume determination in 118 patients following mastectomy (n = 60) or wide excision (n = 58), both with axillary clearance. The mean age was 60.5 years and the median follow-up was 22.5 months. Axillary clearance removed level III nodes. Axillary irradiation was given to only three patients with extensive (more than 75 per cent) nodal involvement. The incidence of early postoperative complications was 18.6 per cent. The incidence of lymphoedema was 7.6 per cent (nine patients). Three of these patients had early lymphoedema within 6 months of treatment. Arm circumference differences correlated poorly with volume differences. The incidence of lymphoedema following axillary clearance is low and comparable to that for sampling or no axillary surgery.     

Cardiovascular malformations in Malaysian neonates with Down's syndrome

A prospective study was done to determine the incidence of cardiovascular malformations in neonates with Down's syndrome. 17/34 (50%) of the babies with Down's syndrome born at the Maternity Hospital, Kuala Lumpur, Malaysia had congenital heart defects. These included 7 cases of ventricular septal defect (VSD), 3 cases of patent ductus arteriosus (PDA), 2 cases of atrio-ventricular canal defect, 2 cases of ventricular septal defect with patent ductus arteriosus, 1 case of hypertrophic cardiomyopathy, 1 case of hypertrophic obstructive cardiomyopathy and 1 case of complex cyanotic heart. Only 8/17 (47%) of these babies had any clinical signs suggesting underlying cardiac defects. In view of the common occurrence of cardiac anomalies, it is recommended that echocardiographic screening should be carried out on all neonates with Down's syndrome.     

Antegrade double J ureteral stenting for ureteric strictures: use of silicone stents

In 16 patients with ureteric strictures, silicone double J ureteral stents were inserted antegradely following percutaneous nephrostomy. In 9 patients prior attempt at retrograde placement of a stent had failed. Balloon dilatation of the stricture using angiographic catheters was also performed in 5 patients. The ureteric strictures were most commonly caused by malignant infiltration, post operative fibrosis, infection and ureteric calculi. Most previous reports have described the use of polyethylene and polyurethrane stents. Technical problems with the use of silicone stents are discussed. Although silicone stents are better tolerated by patients and associated with low complication rates, in 5 of 18 stents inserted (28%) the procedure failed. Suboptimal positioning of the stent due to poor radio-opacity and premature occlusion were the causes. With the availability of co-polymer stents, it is likely that these will replace silicone stents as the stent material of choice for antegrade insertion.     

Mechanism of erectogenic effect of the selective phosphodiesterase type 5 inhibitor,DA-8159

DA-8159, a new Phosphodiesterase (PDE) 5 inhibitor, has exhibited potent erectogenic potential in a penile erection test in rats and anesthetized dogs. In this study, we investigated the mechanism of its erectogenic activity by measuring the activity of DA-8159 against a various PDE isozymes and assessing cGMP and cAMP formation in a rabbit corpus cavernosum in vitro. DA-8159 inhibited the PDE 5 activity in rabbit and human platelets, which the IC50 was 5.84 +/- 1.70 nM and 8.25 +/- 2.90 nM, respectively. The IC50 of DA-8159 on PDE 1, PDE 2, PDE 3 and PDE 6 were 870+/- 57.4 nM, 101 +/- 15 microM, 52.0 +/- 3.53 microM and 53.3 +/- 2.47 nM, respectively. This suggests that DA-8159 is a potent, highly selective, competitive inhibitor of PDE 5-catalyzed cGMP hydrolysis. The rates of cGMP hydrolysis catalyzed by human platelets-derived PDE 5 as a function of the cGMP concentration (5-100 nM) and two-fixed DA-8159 concentration (11.3 and 18.8 nM) were investigated in order to characterize the mode of PDE 5 inhibition by DA-8159. DA-8159 increased the apparent Km value for cGMP hydrolysis but had no effect on the apparent Vmax, indicating a competitive mode of inhibition. DA-8159 increased the cGMP concentrations in the rabbit corpus cavernosum dose dependently. In the presence of sodium nitroprusside (SNP), DA-8159 significantly stimulated the accumulation of cGMP when compared to the control level. This indicated that the enhancement of a penile erection by DA-8159 involved the relaxation of the cavernosal smooth muscle by NO-stimulated cGMP accumulation. In conclusion, DA-8159 is a selective inhibitor of PDE 5-catalyzed cGMP hydrolysis and the enhancement of a penile erection by DA-8159 is mediated by the relaxation of the cavernosal smooth muscle by the NO-stimulated cGMP accumulation.     

Molecular cytogenetic analysis of gene rearrangements in childhood acute lymphoblastic leukemia

The aims of this study were to estimate the incidences of BCR/ABL, MLL, TEL/AML1 rearrangements, and p16 deletions in childhood acute lymphoblastic leukemia (ALL), to identify new abnormalities, and to demonstrate the usefulness of interphase fluorescence in situ hybridization (FISH). We performed G-banding analysis and FISH using probes for BCR/ABL, MLL, TEL/AML1 rearrangements, and p16 deletions on 65 childhood ALL patients diagnosed and uniformly treated at a single hospital. Gene rearrangements were identified in 73.8% of the patients using the combination of G-banding and FISH, while the chromosomal abnormalities were identified in 49.2% using G-banding alone. Gene rearrangements were disclosed by FISH in 24 (72.7%) of 33 patients with normal karyotype or no mitotic cell in G-banding. Among the gene rearrangements detected by FISH, the most common gene rearrangement was p16 deletion (20.3%) and the incidences of others were 14.1% for TEL/AML1, 11.3% for MLL, and 1.8% for BCR/ABL translocations. Infrequent or new aberrations such as AML1 amplification, MLL deletion, ABL deletion, and TEL/AML1 fusion with AML1 deletion were also observed. We established the rough incidences of gene rearrangements in childhood ALL, found new abnormalities and demonstrated the diagnostic capability of interphase FISH to identify cryptic chromosome aberrations.     

Ultrastructure of human embryonic stem cells and spontaneous and retinoic acid-induced differentiating cells

Ultrastructural and immunohistochemical studies of 4 groups of cells-(human embryonic stem cells (hES), embryoid bodies (EB), and spontaneously and retinoic acid (RA)-induced differentiating cells)-were carried out to investigate their detailed phenotype. Immunohistochemically, the EB cells showed strong immunoreactivity for CD34, CD117, and nestin. Differentiating cells expressed pancytokertin, vimentin, CD31, CD56, GFAP, nestin, and NeuN as well as CD34, and c-Kit. However, synaptophysin and neurofilaments were not present in these same differentiating cells. Transmission electron microscopy showed that hES and EB cells were very similar to germ cells or cells of the inner cell mass. Spontaneously and RA-induced differentiating cells exhibited epithelial, mesenchymal, endodermal, and neuronal phenotypes. The perikarya of the neuronal cells had rich RERs (Nissl substance) and long cytoplasmic processes filled with numerous neural tubules. However, neither synaptic junctions nor synaptic vesicles were developed. In our study, RA treatment with brain-derived growth factor and TGFalpha in neuron differentiation medium induced not only neuronal differentiation but also pluripotential differentiation. Full neuronal differentiation did not occur after 2 weeks in culture, as no synaptic junctions and synaptic vesicles developed.