Nonimmune hydrops fetalis: a challenge in perinatal pathology

Autopsies were performed in 40 cases of nonimmune hydrops fetalis during the period from 1975 to 1983. In 25 cases specific anatomic diagnoses, including hematologic disorders, infections, chromosomal abnormalities, congenital anomalies, and tumors, were made. In the majority the diagnosis of hydrops fetalis was made prenatally by ultrasonography. The mean gestational age at delivery was 30 weeks; 23 infants were stillborn, and 17 died during the neonatal period. Body weights were consistently increased; peripheral edema and ascites were present in all cases and pleural effusions in all but two cases. Hepatosplenomegaly, cardiomegaly, and pulmonary hypoplasia were frequent findings. The most consistent microscopic changes involved endocrine organs. Islet cell hyperplasia and Leydig cell hyperplasia were common, and thyroid hyperplasia was found occasionally. The fetal zone of the adrenal cortex was often thick and composed of swollen, vacuolated cells. Enhanced extramedullary erythropoiesis was observed in all cases. Thirty-nine placentas were examined; 34 were edematous (mean weight, 547 g), with villous edema, excess erythroblastemia and normoblastemia, and occasional intravillous hematopoiesis. Nonimmune hydrops fetalis has a range of known causes. Thorough autopsy, including placental examination, is the most useful approach for determining the etiology. In 23 cases the probable or possible cause was established in this manner. Antibody studies should also be performed in all cases to exclude an immunologic etiology. Synthesis of clinical, serologic, and pathologic data offers prospects for rational management and prediction of recurrence.     

Diagnostische Bedeutung von Muskelbiopsien bei metabolischen Myopathien

Summary In the diagnosis of metabolic myopathies the use of biochemical methods, in addition to morphological examination of muscle biopsies, is often necessary in order to identify a specific metabolic defect. In order to narrow down the spectrum of biochemical methods, extensive clinical investigation and morphological examination, including histology, enzyme histochemistry and electromicroscopy if necessary have to be done beforehand. Patients are classified in the following groups: 1) progressive muscular weakness and/or muscle wasting with storage of a) glycogen, b) lipid or c) mitochondrial alterations; 2) recurrent rhabdomyolysis induced by fasting or exercise a) with glycogen storage or b) without any specific morphological alterations. The spectrum of metabolic defects comprises disorders of glycogen and glucose metabolism (deficiency of acid maltase, debranching and branching enzyme, phosphorylase, phosphofructokinase and other glycolytic enzymes), lipid metabolism (carnitine deficiency, carnitine palmitoyl transferase deficiency), mitochondria (respiratory chain disorders, pyruvate dehydrogenase deficiency) and others such as adenylate deaminase deficiency. In some of these e.g. infantile acid maltase deficiency and mitochondriopathies, it is clinically more important when organs other than muscle are affected; however, muscle biopsy is a useful substrate for diagnosis of these metabolic disorders.

Mit Unterstützung durch die DFG und die Friedrich Baur Stiftung, München     

Cytogenetic studies of bone marrow and extramedullary tissues and clinical course during metamorphosis of chronic myelocytic leukemia

Of 33 consecutive patients with chronic myelocytic leukemia, examined during metamorphosis, 82% showed chromosome abnormalities in addition to the Ph1. Aberrations most frequently encountered were +8 (39%), +22q - (30%), and i(17q) (18%). Translocations other than the Ph1 were observed in four cases and - Y clones in four cases. Discrepancies in the cytogenetic pattern between bone marrow and extramedullary tissues or blood were noted in a total of 15 patients. In six cases, transformation occurred in extramedullary organs at a time when it was not present in the marrow. In three cases the bone marrow transformation was preceded by a lymph node blastic infiltrate; in one case, by a skin infiltrate; and in one case, by a subdural blastoma. Clonal abnormalities additional to the Ph1 were identified in the tumor tissue from all these cases. Patients with primary extramedullary transformation tended to have a lower median age at onset of metamorphosis, shorter survival, and higher incidence of chromosome abnormalities than the cases without extramedullary involvement. Patients with only Ph1-positive cells and no other anomalies had a slightly longer duration of metamorphosis and longer total survival. Basophilia and thrombocytopenia were more marked in cases with i(17q) than in the rest of the series.     

Morphologic evaluation of the liver in hereditary angioedema patients on long-term treatment with androgen derivatives

17 alpha-Alkylated androgens are highly effective in preventing attacks in HAE patients. These drugs, however, seem to be implicated in the development of cholestatic jaundice, peliosis hepatis, and liver tumors. In order to assess the risk-benefit balance of the long-term therapy with androgen derivatives, a follow-up investigation was performed in 13 HAE patients. The results of this study indicate that long-term treatment (15 to 47 mo) with low doses of danazol or stanozolol does not induce significant hepatic damage detectable by laboratory tests or liver biopsy. However, the limited number of patients, although in a rather long period of observation, still suggests a careful control and the use of minimal effective doses.     

3q−, 3q+ anomaly in malignant proliferations in humans

Anomalies of both No. 3 chromosomes, of the t(3q?; 3q+) type can be observed in human malignancy as reported previously. It is our experience that this anomaly is found predominantly in myeloproliferative disorders, as a rather rare event, though occurring more frequently than similar exchanges between other homologous chromosomes. Previous claims about a relationship between this anomaly and thrombocytosis could not be confirmed, but the features found in a few patients indicate that further research should be undertaken to clarify this point.     

Neuronal connection of the cortex and reconstruction of the visual space

The distributions of retrograde labeled cells in fields 17 and 18 and the fields 17/18 transitional zone were studied in both hemispheres of cats after microiontophoretic administration of horseradish peroxidase into individual cortical columns in fields 17, 18, 19, and 21a. The clustered organization of the internal connections of the cortical fields, the asymmetrical locations of labeled callosal cells relative to the injected columns, and the defined distribution of labeled cells in layers A of the lateral geniculate body suggested that eye-specific neuronal connections support binding of the visual hemifields separately for each eye. Application of marker to columns in fields 19 or 21a demonstrated disparate inputs from fields 17 and 18 and the fields 17/18 transitional zone. It is suggested that these connections may support the extraction of loci and stereoscopic boundaries located in the central sectors of the visual space.Translated from Rossiiskii Fiziologicheskii Zhurnal imeni I. M. Sechenova, Vol. 89, No. 10, pp. 1281–1290, October, 2003.     

Direct estimation of the frequency of human cytotoxic T lymphocytes and their precursors following in vitro allosensitization

Cell mediated lympholysis (CML) has been proposed as an in vitro model of the rejection process that results from transplantation of allogeneic tissue. To date, the absolute frequencies of cytotoxic T lymphocytes (CTL) and their precursors (CTL.P) have not been directly estimated in man because of technical difficulties. Through optimizing the conditions for radiometric detection of 51Cr release and the attendant improvement in CML sensitivity, direct CTL frequency estimates have been determined in peripheral blood (PBL), spleen (SPL), and lymph nodes (LNC) after in vitro allostimulation using unrelated human cells and limiting dilution assays. The mean frequency of CTL generated from PBL is 1 in 826 cells (0.121% +/- 0.101%) which, from preliminary experiments, is significantly greater than that generated from either LNC or SPL (p less than 0.05). With restimulation of primed cells on day 10, the frequency of CTL generated from PBL was increased 400%. The CTL.P frequency (0.0064% +/- 0.0050%) was approximately 5% of the corresponding CTL frequency. The CTL.P frequencies were found to be minimal estimates as both accessory "filler" cells and T cell growth factors increased the level of detection of CTL.P an average of threefold. The limiting cell dilution assay as detailed in this report should be a powerful tool for defining the cellular requirements and related factors necessary for optimal induction of a CTL response and should provide the means for determination of the immunogenetic requirements and the allospecificity of human cytotoxic lymphocytes.     

Effect of prostaglandin D2 and I2 on the airways of rhesus monkeys

Prostaglandin (PG) D2 and PGI2 were evaluated to determine their effect on pulmonary function parameters when aerosolized in anesthetized rhesus monkeys. PGD2 resulted in an increase in frequency (f) and pulmonary resistance (rl) and a decrease in peak expiratory flow rate (PEFR), tidal volume (VT), and dynamic compliance (Cdyn), with the major effect on RL. PGI2 primarily effected an increase in f and a decrease in PEFR and VT. PGI2 had a variable effect, generally a decrease, on RL. The metabolite of PGI2, 6-keto-PGF 1 alpha, had no effect on the rhesus airway. PGF 2 alpha responses were similar to PGD2 except that the PGF 2 alpha produced a less strikingly consistent increase in RL. When PGI2 and PGD2 were aerosolized simultaneously, they simulated previously described antigen responses. Further, PGI2 plus PGD2 produced an airway response at 1/10 the concentration of either agent alone.