Genetics of Hunter Syndrome: carrier detection, new mutations, segregation and linkage analysis

We have investigated 31 families segregating for Hunter Syndrome in order to advance our understanding of the genetics of this disease. The hair root test for the diagnosis of carriers of Hunter Syndrome was improved by the adoption of a new diagnostic index that distinguishes between carrier and normal females better than previous methods of analysis. One hundred and eleven female relatives of the affected children were tested by such procedures. This showed that seven out of 31 mothers were not carriers (22.6%), thus suggesting a small deficit of new mutations relative to the expectation that 33 % of lethal, recessive alleles arise anew in a population at equilibrium at a sex-linked locus with equal mutation rates in male and female gametogenesis. The difference, however, is not statistically significant. The age of the parents of new mutants was slightly but significantly raised. Nevertheless, the independent increase in the age of the fathers of new female mutants was not statistically significant. Finally, a deficit of affected males was observed. This was significant and suggests the possibility of intrauterine loss of some affected males.
Linkage analysis between the Hunter Syndrome locus, three polymorphisms in the Factor IX gene and the anonymous polymorphic probes 52A and DX13 showed that the Hunter locus is fairly closely linked to DX13, and hence distal to the Factor IX gene, while no linkage was observed with the 52A polymorphic site.
The maximum lod score for the linkage between factor IX and the Hunter Syndrome locus was 0.424 at θ = 025; and that for the linkage between the Hunter Syndrome locus and DX13 was 3.01 at θ= 01.     

Left Ventricular Outflow Tract Obstruction Following Mitral Valve Replacement with Carpentier-Edwards Prosthesis

Left ventricular outflow tract (LVOT) obstruction is a rare complication of mitral valve replacement. In this article, we describe three patients in whom left ventricular outflow tract obstruction occurred following Carpentier-Edwards porcine mitral valve replacement. All three patients presented with symptomatic mitral regurgitation (angiographic grade 3–4) requiring mitral valve replacement. Preoperatively there was no evidence of hypertrophic obstructive cardiomyopathy by physical exam, echocardiography, or by cardiac catheterization. At the time of surgery all three were shown to have severe mitral valve prolapse. The native anterior mitral leaflet was left intact and pledgeted to the mitral annulus. Following surgery a new systolic murmur was appreciated. Echocardiographic exam visualized obstruction of the left ventricular outflow tract by the prosthetic strut in two cases and by a flail anterior leaflet in one case. Continuous-wave Doppler measured a calculated peak gradient of 72 to 81 mmHg across the left ventricular outflow tract. In one case simultaneous Doppler and cardiac catheterization confirmed the diagnosis and severity of left ventricular outflow tract obstruction. Mechanisms of left ventricular outflow tract obstruction following Carpentier-Edwards porcine mitral valve replacement are discussed. These three cases highlight the importance of echo-Doppler techniques in understanding the mechanism of newly detected systolic murmurs following mitral valve replacement.     

Malignant osteoclastoma-like giant cell tumour of the renal pelvis

We report the fourth case of an osteoclastoma-like giant cell tumour of the renal pelvis. A special feature was that although thorough sampling of the tumour showed an osteoclastoma-like pattern throughout, it was intimately associated with carcinoma in situ change of the adjacent transitional epithelium and this provides further support for the view that these tumours are of epithelial derivation. However, immunohistological and ultrastructural studies failed to reveal epithelial features within the tumour cells and the possible significance of this finding is discussed.     

Pacemaker Electrode Repositioning Using the Loop-Snare Technique

Using a percutaneous femoral vein approach under fluoroscopic control, a malpositioned ventricular pacemaker electrode was released from the right ventricular wall by hooking the lead with a deflecting wire inserted into a RIM catheter. A closed loop was formed by tightening the handle of the wire allowing the electrode to be dislodged and pulled into the inferior vena cava. The electrode was then snared using a loop formed by an exchange wire advanced through an 8 French catheter with a J-curve steamed at its tip. The electrode was advanced to the right ventricular apex and released by advancing one end of the snare wire while pulling the other end to open the loop.     

Impact of Arteriogenesis in Plastic Surgery: Choke Vessel Growth Proceeds via Arteriogenic Mechanisms in the Rat Dorsal Island Skin Flap

Objective: We examined the molecular mediators of postoperative choke‐vessel growth. Our focus was the possible overlap between choke‐vessel growth and arteriogenesis. Methods: A rat perforator flap model, encompassing four vascular territories, was used. Flaps were surgically elevated, re‐inset, and allowed to survive for one, three, five, or seven days. Tissue samples for Western and histological analyses were collected from the choke zone along the dorsal midline. Tissue from territories linked by the choke zone was analyzed to distinguish between global and local effects. The proteins examined included CD11b, ICAM‐1, and MMP‐2, three markers associated with arteriogenesis, as well as Hsp70 and vascular endothelial growth factor, markers of physiological stress and hypoxia/ischemia. Results: Arteriogenesis markers, as shown by Western analysis, increased at three and five days after flap elevation, and the increase was localized by immunohistochemistry to the growing arteries and veins. The marker of physiological stress increased at Days 5 and 7. The hypoxia‐ischemia marker did not increase in the choke zone. Conclusions: The growth of choke arteries and veins proceeds in an inflammatory environment that resembles arteriogenesis. Ischemia did not appear to play a role in choke‐vessel changes.     

Delayed pressure urticaria, objective evaluation of a variable disease using a dermographometer and assessment of treatment using colchicine

A randomized double-blind placebo controlled trial of colchicine in the treatment of 13 patients with delayed pressure urticaria enabled us to assess some of the variables in this disorder. We have modified a previously described method of pressure testing using a calibrated dermographometer and shown a pressure induced papular dose response curve. Assessment of disease activity was based on the number of pressure weals which occurred, the size of delayed pressure induced papules using a dermographometer calibrated at 9.75 x 10(5) pascals for five separate time periods on the back and estimations of erythrocyte sedimentation rate and the acute phase protein levels. We have been unable to show a therapeutic effect using colchicine 0.5 mg bd for I week.