Morphometric quantification of myocyte dimensions validated in normal growing rat hearts and applied to hypertrophic human hearts.

To obtain quantitative information on changes in myocyte size in hearts with increased myocardial mass light microscopical morphometry was used in fixed and stained myocardial tissue sections. A modification of the azan staining procedure made longitudinal (sarcolemma) and transverse (intercalated discs) boundaries visible with a contrast that allowed morphometric analysis. The method was validated in left ventricular tissue of rats ranging in age from 4 to 17 weeks. Myocyte width, cut surface area, length, and volume were significantly correlated with left ventricular weight with residual errors of 5%, 5%, 6%, and 8% respectively. The method was applied to 21 human hearts, nine of which had left ventricular hypertrophy. Myocyte width, area, length, and volume both in subepicardial and subendocardial left ventricular tissue were significantly greater in hypertrophic than in normal hearts. Although the mean weight of the hypertrophic hearts exceeded that of normal hearts by 40%, myocyte volumes in subepicardial and subendocardial left ventricular tissue of hypertrophic hearts were higher by 78% and 43% respectively, indicating a transmural difference in the extent of myocyte hypertrophy. The method is accurate and reproducible and gives useful quantitative information on changes in myocyte dimensions during normal cardiac growth as well as in cardiac hypertrophy.

Evaluation of the cuticle bleeding time in canine haemophilia A.

In this paper we describe our clinical experience and results with the cuticle bleeding time test in a colony of cross-bred Labrador retrievers with severe haemophilia A. The dogs have a severe bleeding tendency with a high incidence of fatal haemorrhages in the central nervous system. Homozygous females appeared to be especially prone to this lethal complication. Factor VIII recovery and half-life determinations yielded results similar to the data from human studies. The cuticle bleeding time proved to be a good measure of the coagulation defect. The prolongation of the bleeding time could be completely abolished by administration of 10 to 15 units of canine factor VIII per kg body weight. We conclude that the cuticle bleeding time in canine haemophilia provides us with a suitable model for the in vivo study of new therapeutic materials.

HLA-B27 as a relative risk factor in ankylosing enthesopathy in transgenic mice.

HLA-B27 is a risk factor for several human diseases through a mechanism that is not yet understood. This article describes a naturally occurring joint disease in laboratory mice, ANKENT. ANKENT begins with mild inflammation and culminates in irreversible stiffening of the ankle and/or tarsal joints in one or both hind paws. The macroscopic and histologic features of ANKENT, its relationship to age, gender, and environment, and some immunologic aspects are considered. With respect to genetics, it is demonstrated that an HLA-B27 transgene is a relative risk factor for ANKENT. Its impact depends on the H-2 haplotype, reaching a relative risk value of 9.4 for C57Bl/10, H-2b males (p < 0.025). Several features of ANKENT are reminiscent of human AS: joint pathology, age and gender distribution, the presence of non-MHC as well as MHC risk factors (including HLA-B27), and the suspicion that environmental factors are involved.

Multilocular renal cyst associated with transposition of the inferior vena cava and malrotation of the bowel.

A case is presented of an adult male patient with a heavily calcified multilocular renal cyst (Permann's tumor), transposition of the inferior vena cava and reversed rotation (malrotation) of the bowel. Because of the synchronous embryological development of the forementioned structures, a possible congenital etiology of the multilocular renal cyst is suggested.

Histopathology of murine ankylosing enthesopathy.

Ankylosing enthesopathy is a spontaneously occurring progressive stiffening of the ankle and/or tarsal joints in mice of C57Black background. In C57BL/10 mice and mice of the same genetic background that had been made transgenic for HLA-B27, the start of the disease was detected by weekly testing for decreased mobility in the ankle/tarsus region. Ankylosing enthesopathy was found to begin with a short phase of proliferative inflammation of the joints and adjacent tissues, with some fibrinous exsudation, some leucocytic infiltration and slight bone erosion. This inflammation is soon accompanied and followed by proliferation of cartilaginous cells at the bone insertions of joint capsule ligaments (entheses). Ossification of the cartilage proliferations and some desmal ossification lead to large osteophytes that inhibit mobility. Fusion of osteophytes occasionally leads to marginal ankylosis. The histopathology of the successive stages of murine ankylosing enthesopathy and the preponderance in males and HLA-B27 transgenic mice are reminiscent of ankylosing spondylitis in man. The spine, however, was not affected.

Changes in nonmyocyte tissue composition associated with pressure overload of hypertrophic human hearts.

To investigate whether pressure-overloaded left ventricular hypertrophy is associated with changes in tissue composition of left ventricular subendocardial (ENDO) and subepicardial (EPI) myocardium, we studied post-mortem 19 normal hearts, 17 hearts of patients with systemic hypertension, and 5 hearts of patients with aortic stenosis. Coronary artery disease was present in 9 hearts of the hypertension group and all 5 hearts of the aortic stenosis group. By means of a grid-point method, volume percentages of nonmyocyte tissue were measured. In ENDO and EPI, nonmyocyte tissue contributed to 27 +/- 8% and 27 +/- 12% for normal hearts, 35 +/- 7% and 32 +/- 7% for hearts in the hypertension group without coronary disease, 40 +/- 10% and 29 +/- 8% for hearts in the hypertension group with coronary artery disease, and 38 +/- 9% and 40 +/- 7% for hearts with aortic stenosis, respectively. For the total group of 41 hearts the volume percentage of nonmyocyte tissue correlated with heart weight index in ENDO (r = 0.59: P less than 0.001), but not in EPI (r = 0.10; not significant). Hearts from patients with hypertension showed a significant increase in microscopical scar fibrosis in ENDO compared to normal, and this increase was amplified by the presence of coronary artery disease. Hearts from patients with aortic stenosis showed an increase in diffuse, non-scar interstitial tissue compared to normal, and occurred in ENDO and EPI. We conclude that the volume fraction of nonmyocyte tissue in ENDO increases as heart weight increases, independent of the type of pressure-overload. Only in the aortic stenosis group this increase of nonmyocyte tissue fraction was observed in EPI as well.

Subtotal liver calcification due to epithelioid hemangioendothelioma.

A hepatic epithelioid hemangioendothelioma leading to almost complete calcification of the right and left liver lobes in a 75-year-old female is reported. Over a period of 16 years the liver progressively calcified, but its function remained normal by compensatory hypertrophy of the caudate lobe. Multiple partially calcified metastases were present in the lungs, peripancreatic region and along the left principal bronchus. Extreme liver calcification has only rarely been reported. The case presented here reflected slow tumor growth and subsequent long disease course. The vascular nature of the tumor was confirmed by immunohistochemical and ultrastructural analysis.

Renal cysts in premature children: occurrence in a family with polycystic kidney disease.

Discrete but typical renal lesions, probably representing the first stage of familial adult-type polycystic kidney disease, were found in two premature still-born daughters of a woman whose family had many cases of this autosomal dominant disease. Apparently, enough cysts were present to form polycystic kidneys of adult size solely by cyst dilation, without additional cyst formation.

Diffuse (eosinophilic) fasciitis. A series of six cases.

Six patients with diffuse fasciitis are described. Their ages range from 12 to 45 years. Five had a typical clinical illness which responded well to corticosteroid therapy but one patient relapsed a year after discontinuation of corticosteroids. One patient had severe skin ulceration resistant to corticosteroids, cytotoxics and plasma exchange and was further complicated by the development of life threatening local and generalised sepsis. Eosinophilia of the blood was not present in any of the cases and not unduly prominent in biopsies of the affected tissue, but characteristic fascial thickening and infiltration by chronic inflammatory cells was diagnostic when a full-thickness biopsy was examined. The natural history and optimal treatment of this condition remain unclear.

Cryptosporidiosis leading to an unsuspected diagnosis of AIDS.

We describe a 68-year-old woman with an episode of diarrhoea, malaise and weight loss, caused by infection with Cryptosporidium. The diagnosis was hampered because this patient had a low risk of HIV infection, a two-year history of Crohn's disease, and a simultaneous candidal infection. An infection with Cryptosporidium was demonstrated with electron microscopic examination, and subsequent tests revealed positive HIV serology. AIDS was probably contracted through her husband.

Villous tumors of the duodenum. Presentation of five cases.

Five cases of villous tumors of the duodenum are reported. These tumors have a predilection for the periampullary region and tend to present with jaundice or obstruction of the duodenal lumen. In four of these patients, malignant transformation was seen. Endoscopy and biopsy play a major rôle in attempting to obtain an accurate preoperative diagnosis. Unfortunately, the diagnosis of malignant degeneration is frequently missed, even when multiple biopsies are taken. For this reason villous tumors should always be resected, and the strategy of treatment must depend on pre-, intra- and postoperative histological evaluation, location in the duodenum and intra-operative findings.

[How accurate is the clinical diagnosis in skin tumors removed by the family physician, surgeon or dermatologist?]. / Hoe juist is de klinische diagnose bij huidtumoren verwijderd door huisarts, chirurg en dermatoloog?

OBJECTIVE: Checking the agreement of clinical and histopathological diagnoses of skin tumours sent in by general practitioners, surgeons and dermatologists in connection with the desirability of general practitioners removing skin tumours. DESIGN: Retrospective descriptive study. SETTING: Diagnostic Centre SSDZ, Delft. MATERIAL AND METHOD: The clinical diagnoses on application forms and the histopathological diagnosis of skin tumours sent in during the first half of 1993 were compared. A discrepancy was scored if these diagnoses differed considerably. The discrepancies between the diagnoses were classified according to the clinical and histopathological diagnoses: malignant, premalignant or benign conditions. RESULTS: Discrepancies were present in 31% (specimens from general practitioners), 32% (surgical specimens) and 17% (specimens from dermatologists). The longer differential diagnoses list of the dermatologists flattered this difference. In 9 out of 381 discrepancies a malignant tumour was underrated, in 37 a benign tumor had clinically been regarded as malignant. Dermatologists contributed more malignant and premalignant tumours than the other two groups, more often operated radically (punch biopsies excluded), and made fewer mistakes when they regarded a lesion as benign, but regarded more lesions incorrectly as malignant. Selection of specimens sent in for histopathology may have played a role in this connection. CONCLUSION: General practitioners and surgeons had about the same number of discrepancies between clinical and histopathological diagnoses. The benefit of histopathological examination of skin tumours was clearly demonstrated.

[Diagnostic image (52). Metallosis of a lymph gland]. / Diagnose in beeld (52). Metallose van een lymfklier.

Parailiacal lymph node metallosis in a 62-year-old man with a hip prosthesis who had lymph node resection at prostate cancer operation.

[Diagnostic image (54). Sinus thrombosis and hemorrhagic infarction in puerperium ]. / Diagnose in beeld (54). Sinustrombose en hemorragische infarcering in het kraambed ('kraamhoofd').

A 28-year-old woman developed puerperal sinus sagittalis superior thrombosis that caused hemorrhagic cerebral infarction and death by cerebral herniation.

[Tubercular granulomas of the liver in a Somalian patient notwithstanding a chronic hepatitis C]. / Granulomen in de lever bij een Somalische patiënt met chronische hepatitis C toch veroorzaakt door tuberculose.

A 44-year-old male Somalian immigrant was admitted to hospital for evaluation of upper abdominal pain and painful joints (neck and shoulders). Chronic active hepatitis caused by hepatitis C virus was diagnosed. Further examination was instituted because of the simultaneous finding of granulomas in a liver biopsy. In hepatitis C liver granulomas may be found. Infection by Mycobacterium tuberculosis was established, however, after extensive investigation. Treatment was started with tuberculostatic drugs, after which the complaints of the patient disappeared, liver enzyme levels decreased and granulomas in the liver disappeared. No side effects of the tuberculostatic treatment were seen on the course of the hepatitis C.

[Gas gangrene of ischemic myocardial tissue caused by Clostridium septicum]. / Gasgangreen van ischemisch hartspierweefsel door Clostridium septicum.

A 86-year-old woman hospitalized for analysis of persistent abdominal discomfort died, apparently of myocardial infarction, shortly after admission. Autopsy revealed extensive myocarditis caused by infection with Clostridium septicum. As a portal of entry a carcinoma of the colon was found. The association of colon carcinoma and bacteraemia with C. septicum is well established while colon carcinoma can lead to cardiac hypoxia through blood loss and anaemia. However, myocarditis caused by this organism is extremely rare.

[Less operations required due to perioperative frozen section examination of sentinel nodes in 275 breast cancer patients]. / Minder operaties vereist door peroperatief vriescoupeonderzoek van schildwachtklieren bij 275 patiënten met mammacarcinoom.

OBJECTIVE: To determine the reliability of a peroperative frozen section examinations of sentinel lymph nodes in mammary carcinoma. DESIGN: Retrospective. METHOD: In the Reinier de Graaf Hospital and Diagnostic Centre SSDZ Delft, the Netherlands, the results of frozen section from sentinel lymph node investigations of mammary carcinomas from 1997-2000 were compared with the final pathological results. If axillary dissection had been performed on these patients, the histopathological findings of the dissected lymph nodes were also studied. RESULTS: Frozen sections were made of 287 sentinel lymph nodes from 275 patients. A tumour was found in the sentinel lymph nodes of 64 patients and these patients immediately underwent a complete axillary lymph node dissection. For 31 of these patients a tumour was also found in the other lymph nodes. In 29 of these 31 patients, histological examination had shown extranodal extension. The frozen sections from the sentinel nodes of the remaining 211 patients were considered negative. However, in 13 of these patients, the paraffin sections of the sentinel node nevertheless showed a tumour and the remaining axillary lymph nodes were removed in a second operation. In the last 89 patients studied, the sentinel lymph nodes were cut at four levels and stained immunohistochemically at one level for cytokeratins. Accordingly micrometastases were found in the sentinel lymph nodes of 4 of the 13 patients with (false-)negative frozen sections. False-positive results did not occur. CONCLUSION: The major advantage of the sentinel node method in breast cancer is that for women without metastasis present in the sentinel node, axillary dissection is avoided. By means of a peroperative examination of frozen sections, 83% of the patients with a metastasis in the sentinel lymph node (or about one quarter of all patients) were spared from having a second operation for axillary dissection at a later stage.