Barbara A. Burke

Anomalous inferior vena cava with azygos continuation (infrahepatic interruption of the inferior vena cava). Report of 15 new cases.

Summary Fifteen new cases of anomalous inferior vena cava with azygos or hemiazygos continuation are presented, together with a review of 26 cases previously published. The incidence of this anomaly approximates 0.6 per cent in patients with congenital heart defects. The commonly encountered cardiac defects include cor biloculare, atrioventricular canal, anomalously connecting pulmonary veins, double outflow right ventricle, large atrial septal defect, pulmonary stenosis or atresia, or combinations of these. Abnormal positions of the heart and abdominal viscera are often present. An antemortem diagnosis can be established by cardiac catheterization or angiocardiography. A typical “candy cane” appearance of the anomalous venous pathway occurs when angiocardiography is performed from the leg veins. The most common pattern is azygos continuation with normal position of the heart and abdominal viscera. There is no evident relationship between the subtypes of this anomaly and the intracardiac defects that may be present. The embryologic development of the venous system is discussed, particularly in regard to the origin of the anomalies under discussion. Anomalous inferior vena cava with azygos or hemiazygos continuation is best interpreted as interruption or failure of fusion of the hepatic and prerenal segments of the inferior vena cava, combined with persistence of either the right lumbar azygos vein or left lumbar hemiazygos vein. Thus, a better term for the anomaly would be “infrahepatic interruption of the inferior vena cava with azygos (hemiazygos) continuation.”

Transcutaneous angioplasty of experimental aortic coarctation.

A dilatable form of juxtaductal aortic coarctation was surgically created in 29 newborn lambs. Of the 17 long‐term survivors, four lambs served as controls and 13 underwent transcutaneous balloon dilation angioplasty with either polyvinylchloride or polyethylene catheters after 7‐10 weeks of recovery. During growth before dilation, there was little change in the systolic gradient across the coarctation (36.6‐35.3 mm Hg) despite an increase in animal weight from 3.8 to 19.3 kg. This systolic gradient remained constant in undilated lambs throughout a 6-month follow-up. Dilation produced an immediate 65% increase in the diameter of the coarctation and a 68% decrease in the systolic gradient across the coarctation site. Successful dilation required very high (6-8 atmospheres) dilating pressures. This gradient relief persisted throughout a follow-up of up to 1 year. Although no late sequelae could be attributed to the ngioplasty, one lamb suffered an anterior aortic tear limits and optimal protocols for dilating human coarctations are not known.

Total or near total pancreatectomy and islet autotransplantation for treatment of chronic pancreatitis.

Total or near total pancreatectomy is the surest way to relieve the pain of chronic pancreatitis but is rarely applied because the metabolic consequences are so severe. For most patients drainage procedures are applicable, but pancreatectomy may be the only alternative for small duct disease or where procedures to improve duct drainage have failed. Preservation of endocrine function is a major problem in patients who require pancreatectomy. Experiments in pancreatectomized dogs have shown that intrasplenic or intraportal transplantation of unpurifled pancreatic islet tissue dispersed by collagenase digestion can prevent diabetes. We have applied this technique to ten patients with chronic pancreatitis, small ducts, and intractable pain. The entire pancreas or >95% of the pancreas was excised, minced, dispersed by collagenase digestion and infused into the portal vein <2½ hours after removal. Mean (±SD) rise in portal pressure was 17 ± 8 cm of water. Liver function tests were altered minimally. All patients were relieved of pain. One patient died of a complication not related to the islet autotransplant; viable islets were identified in the liver at autopsy. Of the remaining nine patients, three have been insulin independent for 1, 9, and 38 months. One patient was insulin independent for 15 months and now takes 12 units of insulin daily. Three have nonketosis prone diabetes (tested by insulin withdrawal) and take 15–30 units of insulin per day. C-peptide studies in these patients show that functioning islets are present. Two patients are diabetic and require 35 and 60 units of insulin per day. In eight of nine patients tested serum insulin concentrations fell to undetectable levels during the interval between pancreatectomy and islet transplantation. Serum insulin levels during the first few hours after islet transplantation predicted success. In the insulin independent or in the patients with mild diabetes, insulin levels were persistently ≤6 μU/ml. In the other two patients, the increase in insulin concentration was not sustained. Islet tissue preparation from a diseased pancreas is difficult. The surgeon and the patient must still be willing to accept diabetes for relief of pain when performing this operation. In some patients, however, islet autotransplantation can prevent or partially ameliorate diabetes after pancreatectomy, and preservation of endocrine function is worthwhile.

Endocrine pancreas in cystic fibrosis: An immunohistochemical study

The pancreases of 17 patients who had cystic fibrosis with and without diabetes mellitus were evaluated at autopsy by routine staining and immunohistochemical methods for insulin, glucagon, somatostatin, and pancreatic polypeptide. Qualitative assessment of the number of islets of Langerhans and the degrees of exocrine pancreatic atrophy, fibrosis, and fat replacement was made for each pancreas. Quantitative assessment of islet composition was performed in 15 of the 17 based on the immunochemical reactivity of each cell type. Nondiabetic patients with cystic fibrosis in the latter part of the first decade of life have classic fibrocystic changes of the pancreas, with some persisting exocrine tissue, islets that appear normal, and prominent nesidioblastosis. The latter process may protect these patients from glucose intolerance. Young adult diabetic patients with cystic fibrosis have total loss of exocrine pancreas with fat replacement, lack of nesidioblastosis, a qualitative decrease in the number of islets, fibrosis of and amyloid deposits in islets, decreased numbers of insulin-containing cells in each islet, and atrophy of islet cells, probably resulting from progressive ischemia. Although the potential exists for an increasing incidence of diabetes mellitus in patients with cystic fibrosis as their life spans increase, individual variation occurs in this disease.

The accelerated phase of Chediak‐Higashi syndrome. An expression of the virus‐associated hemophagocytic syndrome?

The clinical and pathologic findings of four patients with Chediak‐Higashi syndrome in the accelerated phase were studied in order to clarify the nature of this enigmatic process. Fever, lymphadenopathy, hepatosplenomegaly, and cytopenias were present in every patient. All cases demonstrated extensive parenchymal infiltrates in many organs composed of benign‐appearing histiocytes manifesting hemophagocytosis accompanied by lymphocytes and plasma cells. Studies in one patient suggested a viral etiology with the findings of a low blood lymphocyte OKT4 to OKT8 ratio, acquired loss of lymphocyte response to mitogens, the presence of Epstein‐Barr virus genome in the mononuclear cells of lymph node, blood, and bone marrow, and possible clinical responses to acyclovir. It is concluded that the accelerated phase of Chediak‐Higashi syndrome may be the clinicopathologic expression of the virus‐associated hemophagocytic syndrome.

Systemic lupus erythematosus within the first two decades of life

Forty-nine patients with systemic lupus erythematosus (SLE) during childhood and adolescence presenting over a period of 17 years were followed during treatment with prednisone and azathioprine. The average period of follow-up was 5.7 years. Detailed analyses of clinical parameters of renal function and sequential changes in glomerular abnormalities by percutaneous renal biopsy are reported. Therapy was directed towards normalizing the results of urinalysis and renal function, eliminating proteinuria and maintaining normal serology (normal serum complement and negative antiDNA titers). The 10 year survival of the entire group was 86 per cent. A survival of 73 per cent and 87 per cent over this interval in patients with diffuse and focal proliferative lupus nephritis, respectively, was achieved. The major cause of mortality in this series was infection. It appears that intensive observation and monitoring of serologic parameters in SLE, along with aggressive steroid and immunosuppressive therapy, lead to a prognosis in SLE more favorable than previously reported.

Antineutrophil cytoplasmic autoantibody-positive crescentic glomerulonephritis as a complication of treatment with propylthiouracil in children

Propylthiouracil, which is commonly used in the treatment of hyperthyroidism, has been associated in adults with antineutrophil cytoplasmic autoantibody, a serologic marker of vasculitis. Severe renal disease has not been reported as a complication of therapy with this drug. We report severe antineutrophil cytoplasmic autoantibody-positive vasculitis in children receiving propylthiouracil, as well as rapidly progressive crescentic glomerulonephritis after administration of this drug.

Transvenous angioplasty of experimental branch pulmonary artery stenosis in newborn lambs.

A dilatable form of bilateral branch pulmonary artery stenosis was created in 27 newborn lambs. Nine lambs were long-term survivors and were dilated with modified Gruntzig balloon dilation catheters. They were allowed to recover for 6-9 weeks, during which time there was no significant change in the mean systolic gradients across the narrowed sites. Thirteen arteries underwent dilation. Dilation was associated with a decrease in the systolic gradient in all cases (from 34.9 mm Hg to 8.1 mm Hg) and an increase in the diameter of the narrowed site (from 4.6 to 7.6 mm) as estimated by angiography. Flows and flow distribution were measured in four lambs before and after unilateral dilation using 15-p radiolabeled microspheres; in each case, the fraction of total flow to the dilated lung rose after dilation (19.2 to 45.4%), as did the total flow to the dilated lung (30.0 to 69.2 ml/kg-min). Four lambs were catheterized every 2-4 weeks for an average of 16 weeks after dilation; the average gradient in these lambs remained below 10 mm Hg despite considerable growth (from 9.6 to 25.9 kg). Gross pathologic examination showed an intact vascular adventitia in all cases; there were multiple linear tears in the intima in recently (less than 7 days) dilated cases, but complete intimal healing had occurred by 2 months after dilation. No significant morbidity could be attributed to the dilation procedure. These results indicate that clinical trials are warranted.

Early bladder outlet obstruction in fetal lambs induces renal dysplasia and the prune-belly syndrome

A model of posterior urethral valves in fetal lambs was developed in order to evaluate the effect of intrauterine urinary obstruction on the developing kidney. Complete urethral obstruction was induced in five fetal lambs at 43 to 45 days of gestation. Two control fetal lambs underwent sham operations. At full term (140 days), two of the five experimental lambs and both control lambs were available for postmortem examination. Results of gross and histological examination of the control lambs were normal. In contrast, the kidneys of the experimental lambs were markedly asymmetrical in size. Histological examination of the kidneys in experimental lambs showed cystic dilatation of the collecting ducts and occasional cystic dilatation of Bowmans spaces, features compatible with obstruction. Also noted were peripheral cortical cysts and primitive tubules lined with cuboidal epithelium and surrounded by fibromuscular collarettes, characteristic of renal dysplasia. One of the infant lambs had many characteristics of the prune-belly syndrome, including a wrinkled, markedly distended abdomen, deficient abdominal wall musculature, flared chest wall, limb deformities, and undescended testes. These results suggest that early in utero urethral obstruction (at the beginning of the second third of gestation) causes renal dysplasia. The results also support the hypothesis that the prune-belly syndrome results from abdominal distention that occurs early in gestation.

Inherited factor H deficiency and collagen type III glomerulopathy

A non-immune complex-mediated glomerulonephritis associated with persistent hypocomplementemia occurred in a young boy. Measurement of complement components revealed complete factor H deficiency, inherited as an autosomal recessive trait. Evaluation of the renal lesion revealed extensive deposition of type III collagen suggestive of collagen type III glomerulopathy, a recently identified cause of chronic renal insufficiency in children and adults. This report represents the first association of inherited factor H deficiency with collagen type III glomerulopathy.