U.J.G. van Haelst

Nodular regenerative hyperplasia of the liver: an important cause of portal hypertension in non-cirrhotic patients.

In our hospital over the last 10 years a diagnosis of nodular regenerative hyperplasia was made for 13 patients. Sixty-nine percent of these patients had portal hypertension, representing 27% of all our patients with portal hypertension and a non-cirrhotic liver. Nodular regenerative hyperplasia was the second most frequent cause of portal hypertension in patients without cirrhosis. To make the diagnosis, a reticulin staining of a surgical biopsy is most helpful. However, the characteristic derangement of the liver architecture on histology may still be overlooked. In this study a suggestive relation was found between malignant disease (multiple myeloma, chronic myelogenous leukaemia, Leydig cell tumour and Hodgkins disease), the use of cytotoxic or immunosuppressive drugs and nodular regenerative hyperplasia. Furthermore, a high rate of symptomatic nodular regenerative hyperplasia was observed in patients following kidney transplantation. Liver function abnormalities developed in these patients after a period ranging from 8 months to 3 years of immunosuppressive- or chemotherapy. These liver function abnormalities were, however, usually mild. Since hepatic encephalopathy is not likely to develop in these patients with nodular regenerative hyperplasia a decompressive shunt operation is a good alternative approach, if not the treatment of choice, for the prevention of recurrent variceal haemorrhage.

Disturbances in bile acid metabolism of infants with the Zellweger (cerebro-hepato-renal) syndrome

The bile acid pattern in bile and serum from two infants with the cerebro-hepato-renal syndrome of Zellweger was severely disturbed. An increased concentration particularly of trihydroxycoprostanic acid and also of dihydroxycoprostanic acid could be demonstrated. A generalized mitochondrial defect could explain these increased concentrations. This hypothesis is supported by the abnormal structure of the mitochondria in the liver biopsy of one of our patients. It is possible that the abnormal bile acids contribute to the liver damage of infants with Zellweger syndrome.

Double‐blind comparison of 5‐aminosalicylic acid and acetyl‐5‐aminosalicylic acid suppositories in patients with idiopathic proctitis

Suppositories containing 300 mg 5‐aminosalicylic acid (1.96 mmol) or 425 mg acety1‐5‐aminosalicylic acid (1.96 mmol) were used in 40 patients with idiopathic proctitis to determine the efficacy of acetyl‐5‐aminosalicylic acid in treating this bowel inflammation. Each patient was treated with 5‐aminosalicylic acid or acetyl‐5‐aminosalicylic acid suppositories twice daily for 4 weeks in a double‐blind trial. Four patients were included twice in the trial. The second time they were treated with the alternative regimen. Six patients in the acetyl‐5‐aminoscylic acid group did not complete the trial, four of them because of diarrhoea. Complete clinical remission with normal rectal mucosa on sigmoidoscopy was achieved in 10 out of 18 patients on 5‐aminosalicylic acid and in only two out of 15 in the acetyl‐5‐aminosalicylic acid group (P= 0.03). A favourable histological improvement was demonstrated with 5‐aminosalicylic acid suppositories, but the difference with acetyl‐5‐aminosalicylic acid was not significant (P= 0.059). Three of the four patients who received both drugs recovered with 5‐aminosalicylic acid; in none of them was acetyl‐5‐aminosalicylic acid effective. The results from this study and from previous investigations show that acetyl‐5‐aminosalicylic acid is not superior to placebo.

Severe hepatotoxic reaction with progression to cirrhosis after use of a novel retinoid (acitretin)

We report the case of a 50-year-old female who suffered from severe palmar and plantar pustulosis. During treatment with acitretin, a novel oral retinoid, which is the main derivative of etretinate, the patient developed a severe hepatotoxic reaction. Subsequent histological studies strongly suggested the development of liver cirrhosis. Reversible elevation of serum aminotransferase values during treatment with acitretin has been reported. However, the present observation indicates that severe hepatotoxic injury may also follow treatment with this agent.

Features of a Syndrome With Congenital Cataract and Hypertrophic Cardiomyopathy

We studied 12 patients from six unrelated families with a syndrome that has an autosomal recessive pattern of inheritance and can be diagnosed from clinical, histologic, and biochemical characteristics. The four major symptoms are congenital cataract, hypertrophic cardiomyopathy, mitochondrial myopathy of voluntary muscles, and exercise-related lactic acidosis. The patients had bilateral and total cataract in the first weeks of life, underwent cataract surgery, and developed nystagmus and strabismus. Corrected visual acuity was lower than 20/40 in aphakic eyes. Patients were mentally normal, and at school age they visited a school for blind and visually impaired children. The majority of the patients developed axial myopia with myopic fundus changes; aphakic refraction usually was lower than 10.0 diopters after the first decade. The cardiac myopathy was progressive and the cause of premature death. Three of the 12 patients died in the neonatal period and six patients died in early adulthood.

Connatal Pelizaeus-Merzbacher Disease with congenital stridor in two maternal cousins

SummaryTwo maternal cousins are described with the connatal form of Pelizaeus-Merzbacher Disease (PMD) and congenital stridor. Study of brain biopsy material confirms the diagnosis of PMD. The neuropathological findings are suggestive for the transitional form of this disease. Quantitative morphology gives support to the hypothesis that PMD is a disturbance in maturation of neurons and in myelin formation rather than an active degenerative process. The hereditary transmission is most consistent with a sex-linked recessive pattern. Different X-linked signs seem combined in the presented cases.

An electron microscopic study of muscle in Werdnig-Hoffmann's disease

An ultrastructural study of the quadriceps muscle of a 6 1/2 month old infant with Werdnig-Hoffmans disease has been made. The diagnosis was established on the basis of clinical and laboratory findings, the electromyographic examination and the light microscopic post-mortem study of the spinal cord and different muscles of the extremities. The fine structural changes of denervation observed in the different components (myofibrils, nucleus, sarcolemmal sheath) of the muscle fibers proper are comparable with those previously described by other authors. The most striking feature in this study is the relative high number of cells which fulfil the criteria given by Mauro (1961) and which are designated satellite cells. Cells lying free in the interstitial spaces or in proximity of capillaries and showing great morphological resemblance to “pericytes” are thought to be precursors of the satellite cells. The findings further suggest that these satellite cells may assume myoblast-like properties and that regeneration or restoration could be brought about by activity of these cells. No sufficient evidence can be given that the presence of satellite cells and the submicroscopic changes of the contractile component of the muscle fibres in Werdnig-Hoffmanns disease are due to or represent arrest of maturation.

Ultrastructural study of the vacuoles in the peripheral lymphocytes in juvenile amaurotic idiocy

SummaryLymphocytes of the peripheral blood of 31 patients with juvenile amaurotic idiocy (juvenile form of ceroid lipofuscinosis) were examined with the electron microscope. In all cases, intracytoplasmic clear vacuoles were present, containing round hollow, fingerprint and highly electron dense structures. The combination of these structures, not necessarily in one and the same vacuole, was considered to be highly indicative for the diagnosis of juvenile amaurotic idiocy. In addition to these three structures, parallel tubular inclusion bodies, rectilinear profiles and rodshaped structures were found but in a number of the cases. The parallel tubular inclusion bodies were not regarded as having any diagnostic significance.

Giant cell tumor of soft parts

The light-microscopic and ultrastructural findings in a case of so-called giant cell tumor of soft parts, localized at the dorsal side of the left foot of a 23-years-old male are described. An amputation of the lower extremity was performed and subsequently chemotherapy with adriamycin was given for 3 months. Despite the histology and cytologic malignant appearance and the evident vascular invasion, already present at the time of the first excision, the last known status 2 years later seems favorable. There are no pathologic lymph nodes in the groins and no signs of metastases on chest X-rays. From the electron-microscopic study no definite conclusion can be drawn as regards the histogenesis of this tumor. We feel, as do others, that many of the principal mononuclear tumor cells are poorly differentiated mesenchymal cells. Some of the neoplastic cells, however, show ultrastructural features suggestive of chondro- or osteoblasts (a well-developed r.e.r. containing electron-dense material; multiple Golgi complexes; masses of glycogen; interdigitating cell membrane villi; cytoplasmic filaments; an extracellular amorphous matrix). Some of the larger tumor cells have the submicroscopic aspects of histiocytes as described in osseous, cutaneous, or pulmonary lesions of the histiocytosis X group. As yet undetermined cytoplasmic inclusion bodies constitute another rare observation in our material.

Chemical characterization of glomerular and tubular basement membranes of cattle of different ages.

Glomerular and tubular basement membranes were isolated from fetal, neonatal, young and adult bovine kidneys. An isolation method with sieves for both glomeruli and tubules from the same kidney was developed. A detergent procedure appeared to give purer glomerular and tubular basement membrane preparations than the generally used sonication method. No large differences were found in the composition of glomerular and tubular basement membrane of adult animals. Glomerular and tubular basement membrane preparations of the four age groups showed an increase with age of hydroxylysine and both 3- and 4-hydroxyproline. The most marked increases appeared at different stages of development, that of tubular basement membrane being between fetal and neonatal stages and glomerular basement membrane between 18 weeks old and adult animals. The ratio of 3- to 4-hydroxyproline increased considerably during development. Total imino acid content was higher for both types of basement membrane from adult than from young animals, while total content of hydroxylysine plus lysine remained fairly constant. The increase in hydroxylation of lysine was accompanied by a corresponding change in glucose and galactose content so that the ratio of galactose to hydroxylysine or glucose to galactose remained constant. Fucose content of both types of basement membranes was the same for all age groups but content of aminosugars and mannose gradually increased with age.