Impact and Predictors of Noncircular Left Ventricular Outflow Tract Shapes on Estimating Aortic Stenosis Severity by Means of Continuity Equations

Determining aortic stenosis (AS) severity is clinically important. Calculating aortic valve (AV) area by means of the continuity equation assumes a circular left ventricular outflow tract (LVOT). The full impact of this assumption in calculating AV area is unknown. Predictors of noncircular LVOT shape in patients with AS are undefined.In 109 adult patients with AS who underwent multiplanar transesophageal echocardiography, we calculated AV area by means of the standard continuity method and by a modified method involving planimetric LVOT area.We found 54 circular, 37 horizontal-oval, 8 vertical-oval, and 10 irregular LVOTs. Area derived by direct planimetry correlated better with the modified than the standard continuity method (r=0.89 vs r=0.85; both P=0.0001). Valve areas of patients with mild, moderate, or severe AS by planimetry were more often mischaracterized with use of the standard than modified method (29 vs 18; P <0.0001). Horizontal-oval AV area derived by planimetry (1.28 ± 0.55 cm²) was underestimated by the standard method (1.05 ± 0.47 cm²; P=0.001), but not by the modified method. Congenital AV morphology and low cardiac index were the only multivariate predictors of horizontal-oval shape. Low cardiac index was the only predictor of noncircular shape.More than half our patients with AS had noncircular LVOTs. Using the modified method reduces mischaracterizations of AS severity. Congenital AV morphology and low cardiac index predict horizontal-oval or noncircular shape. These data suggest the value of direct LVOT measurement to calculate AS severity in patients who have congenital AV or a low cardiac index.     

Stones, bones, and heredity

Genetic disorders of mineral metabolism cause urolithiasis, renal disease, and osteodystrophy. Most are rare, such that the full spectrum of clinical expression is difficult to appreciate. Diagnosis is further complicated by overlap of clinical features. Dent's disease and primary hyperoxaluria, inherited causes of calcium urolithiasis, are both associated with nephrocalcinosis and urolithiasis in early childhood and renal failure that can occur at any age but is seen more often in adulthood. Bone disease is an inconsistent feature of each. Dent's disease is caused by mutations of the CLCN-5 gene with impaired kidney-specific CLC-5 chloride channel expression in the proximal tubule, thick ascending limb of Henle, and the collecting ducts. Resulting hypercalciuria and proximal tubule dysfunction, including phosphate wasting, are primarily responsible for the clinical manifestations. Low-molecular-weight proteinuria is characteristic. Definitive diagnosis is made by DNA mutation analysis. Primary hyperoxaluria, type I, is due to mutations of the AGXT gene leading to deficient hepatic alanine–glyoxylate aminotransferase activity. Marked overproduction of oxalate by hepatic cells results in the hyperoxaluria responsible for clinical features. Definitive diagnosis is by liver biopsy with measurement of enzyme activity, with DNA mutation analysis used increasingly as mutations and their frequency are defined.

Conclusion

These disorders of calcium urolithiasis illustrate the value of molecular medicine for diagnosis and the promise it provides for innovative and more effective future treatments.     

Parents' Views about Special Provision for their Child with Severe or Profound and Multiple Learning Difficulties

This paper reports on the findings of a research study, conducted via a postal questionnaire, which aimed to elicit the wishes, needs and satisfaction with special educational provision of parents of children with severe or profound and multiple learning difficulties. Parents' views regarding services received, type of housing and employment preferred for their child, present and future concerns are also reported. The results indicated that the majority of parents in the sample are generally satisfied with their child's current special school placement and do not want a change of placement. However, one in five parents did indicate a desire for a change of placement, with the preferred option being a special class in an ordinary school. A priority for their child's learning is communication skills. A desire for a high level of involvement in their child's education was indicated but, on the whole, parents did not achieve as high a level as they would wish. Parents were generally satisfied with services received but a significant proportion expressed a desire for additional services. In terms of the future, the majority of parents expect that their child is unlikely to live or work independently or semi-independently as an adult. The paper concludes by discussing ways of enhancing parents' involvement in the decision-making process regarding special provision for their child.     

Familial expansile osteolysis: a morphological, histomorphometric and serological study.

Biopsies from the diseased bones of patients with familial expansile osteolysis (FEO) were examined by light and electron microscopy. Focal concentrations of multinuclear osteoclasts were present, and these contained viral-like microcylindrical inclusions which appeared exclusive to their nuclei. No consistent relationship was found between osteoclast size and the number of osteoclast nuclei containing microcylindrical inclusions. Quantitative histomorphometry showed evidence of increased bone remodelling with high bone cell densities and a decrease of the reversal period in bone remodelling. The lesions contained prominent woven bone and fibrovascular tissue, together with mononuclear cells and adipocytes. Little bone was found in the most radiolucent lesions, which were almost totally occupied by adipocytes and fibrovascular tissue. Serology did not reveal any significant differences between the viral antibody titres of patients and their age- and sex-matched controls. The present study suggests that intranuclear viral-like microcylindrical inclusions of osteoclasts are not a specific feature of Paget's disease, and are found in other disorders of osteoclast function, including pycnodysostosis, osteopetrosis, giant cell tumours, and familial expansile osteolysis.     

Percutaneous management of lymphatic fluid collections

Eight lymphatic fluid collections were drained percutaneously. There were no immediate or late complications. Seven patients had follow-up; 1 required surgical drainage of a residual or recurrent lymphocele, and another had reaccumulated fluid in a lymphocele which was detected on autopsy. The remaining lymphatic collections responded to percutaneous drainage. Percutaneous drainage is safe and can be an effective tool in the management of lymphatic collections.     

Nucleotide Sequence of the ADH23 Gene Encoding the Human Alcohol Dehydrogenase β3 Subunit

All nine exons of the ADH2(3) allele, which encodes the human alcohol dehydrogenase beta 3 subunit, have been cloned and sequenced. Comparison of this sequence to the ADH2(1) nucleotide sequence revealed only a single difference that results in an amino acid change, thus proving that the significant kinetic differences between these two isozymes is due to the Cys for Arg substitution at position 369. There are also two silent polymorphisms, and two changes in noncoding regions.     

Progressive peripheral cone dysfunction

A 22-year-old man had a three-year history of progressive day blindness, most notably peripherally, and denied difficulty with central vision or color vision. Visual function studies demonstrated a diffuse dysfunction of the photopic system and normal scotopic function. The central cone function, however, was essentially normal. Visual acuity was 20/20 in each eye, results on AO-HRR and Ishihara color plate testing were normal, color naming visual fields demonstrated color discrimination in the central 10 degrees, and foveal adaptation was normal.