J. H. Schuurmans Stekhoven

Extent, distribution, and mammographic/ histological correlations of breast ductal carcinoma in situ

To assess the potential of breast-conserving treatment for ductal carcinoma in situ (DCIS), 82 mastectomy specimens were studied by Egans serial subgross method. 42 (51%) of the tumours were larger than 50 mm and only 12 (15%) were smaller than 20 mm; the size distribution was not affected by the mode of detection (mammography 52 cases, clinical examination 30). All but 1 case showed only 1 region of tumour. 66% of tumours involved one breast quadrant, 23% extended over more than one quadrant, and 11% were centrally located. Mammographic estimates, based on the extent of microcalcifications, frequently underestimated the histological size of tumours, the extent of the discrepancy being related to the histological type--8/50 predominantly micropapillary/cribriform. In view of the frequently large size, adequate excision of many DCIS will require a wide excision involving up to a whole quadrant.

Ichthyosis bullosa of Siemens: Further delineation of the phenotype

SummaryWe report a third family affected with ichthyosis bullosa of Siemens, and we further delineate the clinical spectrum of this mild type of epidermolytic hyperkeratosis. Erythroderma had never been present in any of the affected individuals. All of them exhibited a brownish, rimpled hyperkeratosis, the main characteristic sites being the joints, the shins and the periumbilical region. Blistering occurred after slight mechanical trauma and even after sweating, resulting in superficially denuded areas. Two affected family members also suffered from chronic, relapsing pustular eruptions surrounded by a transient erythematous flare. Light- and electron-microscopic examination revealed epidermolytic hyperkeratosis limited to the upper part of the epidermis. The pustular lesions were found to be subcorneal blisters filled with neutrophils. Ichthyosis bullosa of Siemens can be clearly distinguished from bullous ichthyosiform erythroderma. The observation of subcorneal pustular dermatosis occurring in this phenotype provides further evidence for the genetic heterogeneity of epidermolytic hyperkeratosis.

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.

Are thrombocyte membranes altered in Alzheimer's disease? A morphometric and biochemical study

Morphometric analysis of thrombocytes from patients with Alzheimers disease, from patients with multi-infarct dementia, and from young and age-matched healthy control donors, did not reveal any Alzheimer-related increase in internal membranes. Biochemical analysis showed a reduced cholesterol content of thrombocyte membrane preparations from Alzheimer patients relative to age-matched controls, but not relative to multi-infarct dementia patients. Overall distribution of protein kinase C activity (PKC) between cytosol and membrane, in resting as well as in activated thrombocytes from Alzheimer patients, was similar to that in the control groups. However, both Alzheimer and multi-infarct dementia patients had lower cytosolic levels of basal kinase and PKC activities than age-matched controls, while only Alzheimer patients had lower cytoskeletal PKC activity than controls.

The usefulness of an endomyocardial biopsy in heart disease of unknown etiology

Light-, electron microscopic and enzyme histochemical examinations (phosphorylase, LDH, NADH:TR, SDH and 3-HBDH) were performed on endomyocardial biopsies of 26 patients with heart diseases of unknown etiology. On the basis of the clinical findings the patients were grouped into hypertrophic cardiomyopathy patients), dilated-congestive cardiomyopathy (8 patients), latent cardiomyopathy and small vessel disease (11 patients) and myocarditis (4 patients). Morphologic changes which might characterize the pathogenesis, were found in 7 patients: small vessel disease in 3 patients, nonspecific myocarditis in 1, iron storage disease in 1, adriamycin cardiomyopathy in 1 and cardiomyopathy with inclusions typical of Fabrys disease in 1 patient. In the other patients the morphologic changes were not sufficiently characteristic to be indicative of an etiopathogenesis. Several pathologic alterations did, nonetheless, appear to have a certain prognostic value such as endocardial and interstitial fibrosis, myofibrillolysis, myolysis, mitochondrial degeneration and increased lipid content in the muscle fibers. The frequency of these changes was evaluated partly semiquantitatively, partly by means of the point-counting method and graded with 1-3 points. Three patients with congestive cardiomyopathy scored at least 7 points. Two of them died within 8 weeks, 1 patient with adriamycin cardiomyopathy recovered after discontinuation of the therapy but he died 4 years after the biopsy. Six to 50 months after the biopsy (mean 31.5, median 6.5) the score was less than 7 in the other patients and all these patients were still alive. The histochemical changes manifested as an increase and/or a decrease of the enzymatic activities, involving scattered muscle fibers or their segments. A decrease of the activities of all dehydrogenases examined appeared to be prognostically ominous, correlating with a score of 7 or higher. A decrease of SDH activity in 7 cases, in combination with a decrease of the HBDH activity in 4 of them, was indicative of a disturbance in the Krebs cycle and lipid metabolism in the absence of ischemic damage. The alterations in the phosphorylase activity did not, however, appear to have a prognostic significance. Normal activity of the phosphorylase seemed to be prognostically favorable.

Shunt component of alveolar-arterial oxygen pressure difference and atelectasis☆

The possible influence ofatelectasis on the alveolar-arterial O2 pressure difference, (A-a)Do2, and the shunt computed therefrom was studied under a variety of circumstances by creating five different conditions of counteracting or favoring atelectasis, followed by anatomical and histological examination at autopsy. 1) Ventilation during 8 hours with a frequency of 12/min and a tidal volume adjusted to get an alveolar CO2 pressure of about 35 mm Hg (30 min with pure O2, 512 hours on room air, 2 hours with pure O2) increased the hyperoxic (A-a)Do2 from 30 to 60 mm Hg but left the shunt unchanged at about 2 % of cardiac output. 2) Before, during, and after artificial ventilation with increased continuous positive pressure for 10–15 min the respective values of the hyperoxic (A-a)Do2 were 49,40, and 46 mm Hg, and the shunts 2.6,1.8, and 2.5 % (differences of “during” against “before” and “after” not significant). 3) Hyperventilation during 3–6 respiratory cycles and subsequent increase of the intratracheal pressure by expiratory clamping during 10–20 sec did not produce any significant change in arterial PO2,. 4) Continuous hyperventilation during 10–15 min left the (A-a)Do2; without significant change at 87 mm Hg as against 77 mm Hg before and after. 5) Hypoinflation of the lungs during 112 to 5 hours did not systematically alter the (A-a)Do2 and left the shunt in the normal range of about 2–4 % in most cases. Anatomical and histological examination did not reveal any considerable atelectasis in most cases. This seems to indicate that the present experimental conditions were appropriate for the determination of the anatomical veno-arterial shunting from the (A-a)Do, at hyperoxia and of the O2 diffusing capacity from the O2 diffusion gradient at hypoxia as reported in two companion papers.

Alveolar-arterial O2 and CO2 pressure differences in the anesthetized, artificially ventilated dog

Abstract The alveolar-arterial pressure differences of O 2 and CO 2 , (A-a)Do 2 and (a-A)Dco 2 , were determined in the artificially ventilated dog in pentobarbital anesthesia over a wide range of oxyganation. The alveolar P CO 2 , was between about 30 and 38 nun Hg. The (A-a)Do 2 was 21.4±9.1 mm Hg (± = standard deviation) at normoxia, 10.0±3.8 nun Hg at deep hypoxia, and 54.8+-46.4 or 70.7+-43.8 mm Hg at 60 or 100% O 2 , resp., the difference between the two levels ofhyperoxia being highly significant. The (a-A)Dco 2 showed a tendency to increase from 1.0±1.1 mm Hg at deep hypoxia to 3.8 ±2.5 mm Hg at normoxia and to 5.6 ±2.9 mm Hg at hyperoxia, but the differences between hypoxia and normoxia or between normoxia and hyperoxia were not significant. The shunts computed from the (A-a)Do 2 , at the two levels of hyperoxia were 3.2±3.1 % and 4.5-2.9%, resp., the difference being significant. There seems to exist an alveolar dead space component over the whole range of oxygenation as demonstrated by the (a-A)Dco,. Since an appreciable contribution of atelectasis to the shunt measured at hyperoxia could be ruled out on the basis of systematic investigations reported in a companion paper, the difference between the two levels of hyperoxia probably reflects a change in anatomical extrapulmonary veno-arterial shunting. The (A-a)Do 2 at normoxia could largely be accounted for by the alveolar dead space component and by the extrapulmonary anatomical venoarterial shunting. The (A-a)Do 2 showed a gradual decrease with deeper hypoxia but became constant in the range of 40 to 20 mm Hg Pao 2 .

Pulmonary diffusing capacity in the dog as influenced by anesthesia and ventilatory regime

Abstract Previous work by various groups of authors had shown disagreement concerning the magnitude of the pulmonary diffusing capacity in the dog and had led to suspect a possible influence of kind of anesthesia and ventilatory regime. In the present study, therefore, six experimental series were compared: A = pentobarbital and artificial ventilation, B = pentobarbital and spontaneous respiration, C = chloralose-urethane and artificial ventilation, D = chloralose-urethane and spontaneous respiration, E = unanesthetized dogs breathing spontaneously, and F = influence of CO2 breathing. The most important factors measured or calculated included O2 consumption, cardiac output, anatomical veno-arterial shunting, alveolar-arterial O2 and CO2 pressure differences as well as O2 diffusion gradient and pulmonary diffusing capacity for O2 at hypoxia. There was no noticeable difference between the different series with the exception of the shunt at hyperoxia, and of CO2 breathing in series F where the decrease of the alveolar-arterial O2 pressure difference by CO2 was confirmed. The values of the O2 diffusion gradient were again several mm Hg and those of the pulmonary diffusing capacity were confirmed to be of the order of about 10 ml O2/min mm Hg. In spite of this comprehensive effort no explanation for the disagreement with other authors could be found. Available data for the pulmonary diffusing capacity and the alveolar surface area were plotted against O2 consumption in a double-log plot with parallel regression lines for a number of species; most experimental values of the pulmonary diffusing capacity, with the exception of the high values reported for the dog by some other groups, but including the data from our laboratory, agreed well with the regression line. It was concluded that this combined evidence should lend considerable support to our experimental results.

Experimental autoimmune retinitis in the rat induced by immunization with rhodopsin: An ultrastructural study

Experimental autoimmune retinitis induced by immunization with rhodopsin was investigated in the Lewis rat using transmission electron microscopy and light microscopy. The first signs of retinitis consisted of scattered infiltrations of lymphocytes and other mononuclear cells, predominantly in the inner nuclear layer and outer plexiform layer. Occasionally, some macrophages were detected in the photoreceptor cell layer. Eyes exhibiting a clinically moderate or severe inflammation contained areas of normal retina coexistent with mildly to severely inflamed foci. The central retina was more frequently affected than the peripheral area. In moderately inflamed foci, macrophages infiltrated the photoreceptor cell layer, damaging and eliminating its structures. Inflammatory cells penetrated the photoreceptor outer segment layer which remained unaltered so far in spite of a high serum anti-(rhod)opsin antibody titer. In stages of severe inflammation, massive infiltrations of macrophages and polymorphonuclear cells destroyed the photoreceptor cells focally, leaving the retinal pigment epithelium virtually unaffected. Adjacent to these foci the pigment epithelial cells sometimes exhibited increased numbers of phagosomes and swelling. The locations of the cell infiltrations and lesions in progressive stages of development suggest that the rod outer segments are the target for the autoimmune damage. The described patterns of inflammation were compared with those of previous studies using other animal species and inciting antigens. Especially in rhodopsin-induced retinitis, the blood-retina barrier at the level of the Bruchs membrane/pigment epithelium appears to be highly resistant to cytotoxic cells. The present observations are in agreement with the concept that the cellular immune response plays a major role in the pathogenesis of (rhod)opsin-induced retinitis.

Unusual findings in the human renal glomerulus in multiple myeloma

SummaryIn a case of multiple myeloma, a number of glomeruli were found whose lumina were completely filled with a PAS-positive material. Electron-microscopic examination revealed that this material consisted of bundles of osmiophillic fibrils of two types: a massive type with a diameter of 790 A and a hollow type with a diameter of 460 Å.