NIH conference. Membranous nephropathy.

Membranous nephropathy is a worldwide problem that accounts for about 20% of the cases of the adult-onset nephrotic syndrome. This disease places many patients at risk for both end-stage renal failure and the complications of hyperlipidemia. Immune-mediated injury to the glomerular capillary wall in patients with membranous nephropathy is characterized by subepithelial immune complex formation and generation of the membrane attack complex of complement. Glomerular capillary hypertension, hyperlipidemia, and possibly cytokines could contribute to the glomerular sclerosis seen in the advanced stages of the disorder. In some cases, production of pathogenic antibody can be suppressed by treating the underlying condition. The mechanisms of action of immunosuppressive agents are being investigated and treatments are being tested in clinical trials to optimize the balance of efficacy and toxicity. Alternate-day treatment with corticosteroids is often recommended for nephrotic patients with idiopathic membranous nephropathy, but this approach has not been proved beneficial. Ongoing studies are evaluating whether cytotoxic drugs or cyclosporin A combined with prednisone is more effective than treatment with corticosteroids alone. Lipid-lowering drug therapy is warranted in cases of the persistent nephrotic syndrome to avert the cardiovascular sequelae of hyperlipidemia.     

Fine-needle aspiration cytology of an endometrioid-like variant of yolk sac tumor.

A 36-year-old male with a history of immature teratoma and embryonal carcinoma of the testis was admitted to the hospital for abdominal pain and fever. A CT scan revealed a large right abdominal mass. The patient's serum alpha-fetoprotein (AFP) was 46.8 ng/ml (reference < 25 ng/ml). Fine-needle aspiration (FNA) of the mass revealed malignant glandular cells. Chemotherapy was instituted, followed by resection of the large abdominal mass. The tumor was grossly encapsulated, consisting of large areas of necrotic, hemorrhagic tissue surrounded by smaller, multiloculated cysts. Microscopically, the tumor had a villoglandular pattern and variably stratified tall columnar cells. A prominent feature of the columnar cells was supranuclear and subnuclear vacuolization. Intracytoplasmic PAS-positive, diastase-resistant hyaline globules were occasionally present. AFP by immunoperoxidase was prominent within the tumor. This recurrence of the previously diagnosed testicular teratoma with embryonal carcinoma represents a yolk sac tumor with components strongly resembling endometrioid carcinoma, a variant only recently described in eight cases of ovarian origin (Clement et al.: Am J Surg Pathol 1987; 11(10):767-778). We believe this is the first reported case of an endometrioid-like variant of testicular yolk sac tumor and also the first report of the FNA cytology findings in this variant.     

Nonuniform blood flow in the canine left ventricle

In order to investigate the relationship between coronary perfusion pressure and blood flow distribution in the left ventricle (LV), we measured myocardial blood flow in small regions using radioactive microspheres in six anesthetized, open-chest dogs. Mean coronary perfusion pressure (CPP) was controlled with a femoral artery to left main coronary artery shunt which included a pressurized, servo-controlled blood reservoir. In each dog, we measured flow in 192 regions of the LV free wall (mean weight per region = 206 +/- 38 mg) at different perfusion pressures. At CPP = 80 mm Hg, blood flow to individual regions varied fourfold (0.30 to 1.18 ml/min/g; relative dispersion (RD) = 21.8 +/- 2.3%). At CPP = 50 mm Hg, flow varied over sevenfold (0.08 to 0.60 ml/min/g; RD = 42.8 +/- 10%; P less than 0.01 vs 80 mm Hg). This relationship between flow variability and CPP was present within individual LV layers as well between layers and is much higher than the error associated with the microsphere technique. We conclude that blood flow to small regions of the LV is markedly nonuniform. This heterogeneity becomes more profound at lower CPP. These findings suggest that (1) global measurements of coronary flow must be interpreted with caution, and (2) even in hearts with normal coronary arteries some regions of the LV are more susceptible to ischemia than others. In addition, these findings may help explain the patchy nature of myocardial damage that occurs following periods of low coronary pressure or inadequate myocardial protection during cardiopulmonary bypass.     

Effect of total parenteral nutrition with intravenous fat on lipids and high density lipoprotein heterogeneity in neonates

Plasma lipid concentrations and high density lipoprotein (HDL) subclass distributions were evaluated in 22 newborn infants nourished with intravenous (iv)-fat. The majority of infants were premature with respiratory distress syndrome. Based on baseline (prior to iv-fat) HDL subclass profiles determined by gradient gel electrophoresis (GGE), infants fell into two classes, one with two or more pronounced peaks within the normal HDL spectrum (group I, 17 subjects) and the other with highly unusual HDL distribution (group II, five subjects). Total plasma cholesterol increased in both groups during low and high fat intravenous feeding. HDL-cholesterol, however, did not change with iv-fat where mean values for groups I and II at baseline, iv-low fat and -high fat were: group I, 31.2 +/- 7.1, 30.0 +/- 8.8, and 36.6 +/- 16.7 mg/dl, respectively; and group II, 20.0 +/- 7.8, 20.2 +/- 7.4, and 19.8 +/- 8.8 mg/dl, respectively. Unlike HDL-cholesterol levels that remained constant with iv-fat, apolipoprotein (apo) AI concentrations increased significantly: group I, 73.0 +/- 11.0, 88.3 +/- 15.9, and 93.1 +/- 21.9 mg/dl, respectively; and group II, 31.8 +/- 10.5, 41.0 +/- 12.8, and 59.3 +/- 18.5 mg/dl, respectively. In group I infants, iv-fat is associated with an increase in larger-sized particles, particularly in the (HDL2b)gge range; in group II there is an increase in (HDL3b)gge and (HDL3c)gge components and a disappearance of particles that fall outside of the size range of normal HDL. In both groups, enteral feeding is associated with a further normalization of HDL subclass distribution. The aberrant GGE profiles and very low apoAI levels of group II infants at baseline were associated with unusual HDL morphology determined by electron microscopy where discoidal structures were prominent. With iv-fat, discoidal particles decline in number while normal spherical structures increase. Prevalence of discoidal HDL at baseline was associated with low concentrations of lecithin:cholesterol acyltransferase (LCAT) (1.12 +/- 0.5 micrograms/ml); with iv-fat this enzyme rose to 1.61 +/- 0.18 micrograms/ml. Increased LCAT is associated with the normalization of HDL morphology. It is likely that iv-fat improves the nutritional status of premature infants, thereby stimulating increased liver synthesis of important proteins, including apoAI and LCAT, associated with HDL metabolism.     

Narrative and procedural discourse in temporal lobe epilepsy.

It is well established that some individuals with temporal lobe epilepsy (TLE) demonstrate language deficits at the single word level. However, discourse production rarely has been examined quantitatively within this group. This study compared adult TLE patients with an early seizure onset (< or = age 14 years, n = 27) to a control group (n = 28) on narrative and procedural discourse tasks. As a group, the TLE patients performed normally on the procedural discourse task, but differed significantly from the controls on several narrative discourse variables. At the individual level, 30% of the TLE patients versus 4% of the controls demonstrated impaired discourse ability (p and 0.01). Within this early onset TLE group, discourse performance was not associated with demographic or seizure history variables. Considering the cognitive domain, discourse performance correlated significantly with working memory. In summary, mild discourse dysfunction was present in a significant minority of early onset TLE patients, but this deficit was not closely associated with other language measures. Discourse ability and its neuropsychological, neuroanatomical and conversational speech correlates deserve further study in TLE patients.     

Case Report: Giant choledochal cyst

We report an adult female with a rare giant choledochal cyst. The patient presented following a normal pregnancy with the classical triad of an abdominal mass associated with jaundice and right upper quadrant abdominal pain. The cyst was excised using an intramural technique and biliary reconstruction achieved with a Roux-en-Y hepaticojejunostomy. Our patient has remained well with no evidence of malignancy over a 12 year review period. The aetiology and current management of this condition are discussed.