Treatment of chronic hypertension with intravenous enalaprilat and transdermal clonidine.

We report an 11-year-old boy with hypertension and chronic intestinal pseudo-obstruction, which renders him totally dependent on parenteral nutrition and prevents the use of oral medications. Here we report the feasibility of utilizing chronic i.v. enalaprilat and transdermal clonidine on a chronic basis to control hypertension. Over the last 10 months, the patient's hypertension has been well controlled by 1.25 mg i.v. enalaprilat every 8 h and a 0.2-mg clonidine patch every 6 days, with no apparent side-effects. There are no reports of i.v. enalaprilat usage exceeding 3 weeks' duration. Therefore we believe that it is possible to effect reasonable management of chronic hypertension with the use of chronic i.v. enalaprilat and transdermal clonidine therapy.

Serum beta2-microglobulin and immunoglobulin levels in young hemodialysis patients.

Amyloidosis is a complication of long-term hemodialysis treatment. The major histological feature of hemodialysis-associated amyloidosis (HAA) is the deposition of amyloid fibrils in the affected lesions, due, in part, to elevated serum beta2-microglobulin (beta2M) levels. In vitro studies reveal that serum immunoglobulin light and heavy chains co-deposit with beta2M in tissues affected by HAA. Only one study of HAA has been performed in young dialysis patients. We therefore assessed risk factors for HAA in a group (n=30) of young (18.7+/-0.9 years) patients receiving chronic, uninterrupted hemodialysis using cellulose acetate membranes. All patients initiated dialysis before reaching 18 years of age. The pre-dialysis serum beta2M level was 49.7+/-3.9 mg/l (normal 0-2.4 mg/l). Since serum albumin was normal (4.3+/-0.1 mg/dl) and serum protein/albumin was elevated (1.7+/-0.0, normal 1.2-1.5), indicating increased circulating protein, we assayed immunoglobulins in the same patients. The serum immunoglobulin levels (expressed as a percentage of the total level of serum proteins) were elevated (21.3+/-0.9%, normal 11.1%-21.0%). The Kt/v was 1.37+/-0.03, suggesting that the high levels of serum beta2M and immunoglobulins were not due to inadequate dialysis in these patients. Patients with residual renal function (Kr) did display significantly lower serum levels of beta2M (33.2+/-2.3, P=0.03). Furthermore, improved clearance of beta2M correlated with higher values of Kr (r=0.914). In contrast, serum levels of immunoglobulin (22.6+/-3.7, P=0.5) were unaffected by Kr. In addition, there was no correlation between older age at onset of dialysis and serum levels of either beta2M (r=0.107) or immunoglobulins (r=0.321). Finally, the length of time on dialysis had no effect on serum levels of either beta2M (r=0.105) or immunoglobulins (r=0.092). Taken together, these results indicate that young hemodialysis patients may be at risk for HAA.

A 1-Mb BAC/PAC-based physical map of the autosomal recessive polycystic kidney disease gene (PKHD1) region on chromosome 6.

The PKHD1 (polycystic kidney and hepatic disease 1) gene responsible for autosomal recessive polycystic kidney disease has been mapped to 6p21.1-p12 to an approximately 1-cM interval flanked by the markers D6S1714/D6S243 and D6S1024. We have developed a sequence-ready BAC/PAC-based contig map of this region as the next step for the positional cloning of PKHD1. This contig comprising 52 clones spanning approximately 1 Mb was established by content mapping of 44 BAC/PAC-end-derived STSs, 3 known genetic markers, 5 YAC-end-derived STSs, 3 random STSs, 1 previously mapped gene, and 1 EST. The average depth per marker is 6.3 clones, and the average STS density is 20 kb. The genomic clone overlaps were confirmed by restriction fragment fingerprint analysis. A high-resolution BAC/PAC-based contig map is essential to the ultimate goal of identifying the PKHD1 gene.