High-dose venlafaxine treatment in a depressed patient with a genetic CYP2D6 deficiency.

A female patient (47 years) who suffered from a severe episode of a recurrent depression with psychotic symptoms (F33.3) firstly underwent several unsuccessful treatments. She was then submitted to a combined treatment with 2×300 mg/day extended-release venlafaxine (VEN) and lithium (0.7 mmol/l). She responded within 7 weeks and, after 9 weeks, she showed full remission. Moreover, she tolerated this medication well. Steady-state plasma concentrations of VEN and its metabolites and their enantiomers were measured. The concentrations of VEN and its metabolite O-demethyl-VEN (ODV) were 1024 and 234 ng/ml, respectively. The unusually high concentration of the parent compound in comparison to the metabolite is mainly explained by an impaired metabolism of R-VEN in this patient, who by genotyping was shown to have a genetic deficiency of CYP2D6. In conclusion, in patients suffering from non-response to an antidepressant treatment, an individualised treatment strategy should be developed, and stereoselective therapeutic drug monitoring and genotyping may be recommended.

Glomerulopathy associated with predominant fibronectin deposits: a newly recognized hereditary disease.

A newly recognized type of familial glomerulopathy observed in patients of both sexes in six families is reported. Proteinuria, often within the nephrotic range, microscopic hematuria, hypertension and a slowly decreasing renal function over several years were common. No underlying systemic diseases were identified. Generally, light microscopy showed enlarged glomeruli with minimal hypercellularity and with extensive deposits in the mesangium and subendothelial space. By electron microscopy, granular deposits with some admixture of fibrils were most common. In one family, the deposits were predominantly fibrillary. Immunoglobulins and complement factors were inconstant or lacking. A main finding was a strong immune reactivity to fibronectin, corresponding to the distribution of the deposits. In one patient, the deposits recurred in a renal transplant. There was no indication of systemic deposition. Abnormalities in the metabolism of circulating fibronectin may play a pathogenetic role in this disease of probably autosomal dominant inheritance.

[Medial necrosis of the pulmonary artery in ruptured aneurysm]. / Medianekrosen der Arteria pulmonalis bei Aneurysmaruptur.

Fifty years ago the first author of this paper described the entity known as idiopathic medial necrosis of the aorta. The present report describes two cases of ruptured aneurysm of the main pulmonary artery. The histologic alterations of the arterial wall were the same as in the much more common aneurysms of the aorta, viz. severe medial necrosis and mucoid degeneration. The findings are discussed and compared with 20 cases documented in the literature. Physical (hypertension) as well as biochemical factors appear to play an essential role in the pathogenesis of medial necrosis.

Immunosialadenitis (Sjögren's syndrome) and lymphoproliferation.

The association of primary salivary gland non-Hodgkin's lymphoma (NHL) and immunosialadenitis (myoepithelial sialadenitis, MESA) is well recognized. Within MESA the whole spectrum of lymphoproliferation starting with a prelymphoma transforming into an early lymphoma and later on into a manifest lymphoma can be observed. These lymphomas represent so-called low grade B-cell lymphomas of mucosa associated lymphoid tissue (MALT), an entity also including lymphoplasmocytoid immunocytoma according to the Kiel classification of NHL. In a few patients a transition into a high grade B-cell lymphoma may occur. The recognition of early stages of lymphomas and their distinction from reactive MESA is only possible by application of immunohistological methods.

[Chronic pyelonephritis and its differential diagnosis. A disease changing with time]. / Die chronische Pyelonephritis und ihre Differentialdiagnose. Ein Krankheitsbild im Wandel der Zeit.

Chronic pyelonephritis (c.p.) is by definition an infectious tubulo-interstitial nephritis. It has to be differentiated from other etiologic forms of tubulo-interstitial nephritis. Therefore strict morphological criteria are needed for diagnosis. The characteristic lesion is a large cortico-medullary scar overlying a dilated chronically inflammed calyx. The macroscopic aspect and the histologic survey picture are more important than histologic details. A diagnosis on renal biopsies is therefore not warranted. Vesico-renal reflux and papillary morphology play an important pathogenetic role. Beside the more common focal scar a diffuse form of scarring can be observed. A limited number of conditions only have to be considered in differential diagnosis. The Ask-Upmark kidney seems to be a special form of c.p. related to urinary tract infection and reflux in early infancy. Pelvi-calyceal lithiasis without superimposed infection causes a picture very similar to a pyelonephritic scar. A reliable differentiation between c.p. and analgesic nephropathy may cause problems in endstage kidneys with sloughed off papillae. Various mechanisms of renal damage such as bacterial infection, immunological mediated inflammation, leakage of urinary constituents into the interstitium especially Tamm-Horsfall-protein and ischemia have to be considered. Despite the frequency of urinary tract infections chronic progressive pyelonephritis is rare. Predisposing factors are needed for progression of the disease. These include congenital or acquired urinary tract obstruction, vesico-renal reflux and papillary damage with intrarenal obstruction to the urinary flow. Other important factors are focal and segmental glomerulosclerosis and hypertension.

Immunostaining in atypical fibroxanthoma of the skin.

We have studied 12 cases of cutaneous atypical fibroxanthoma using immunohistochemistry to demonstrate lysozyme, alpha-1-antitrypsin, S-100-protein, receptors for peanut agglutinin, and intermediate filaments. Results were compared with immunostaining in 24 cases of other so-called fibrohistiocytic tumours. In addition 2 cases of atypical fibroxanthoma and 6 cases of fibrohistiocytic tumours were stained by monoclonal antibodies specific for the monocyte cell lineage (Ki-M1, Ki-M2, Ki-M6, Ki-M7, Ki-M8, OKM-1 and Leu-M1) and double-stained by monocyte-markers and Ki-67. The immunophenotype of atypical fibroxanthoma was rather similar to the marker profile found in malignant fibrous histiocytoma. All atypical fibroxanthomas were positive for vimentin and negative for epithelial markers. Monocyte lineage-specific determinants could be demonstrated in varying amounts in cells suggestive of being reactive. In contrast proliferating--Ki-67 positive--cells did not express monocyte/macrophage related antigens in atypical fibroxanthoma and malignant fibrous histiocytoma both. As to the histogenesis of these tumours our findings speak in favour of a derivation from primitive mesenchymal cells rather than from histiocytes.

[Sarcoidosis of the kidney]. / Sarkoidose der Niere.

Of 123 patients with sarcoidosis observed from 1971 to 1986, 4 had histologically proven renal involvement. Hypercalcemia was present in all of these 4 patients, hypercreatinemia in 3 and urolithiasis in one. Histologically renal interstitial nephritis or fibrosis was found in all 4 cases, and 3 cases showed sarcoid-like renale granulomas. In addition, nephrocalcinosis or mesangioproliferative glomerulonephritis was present in one patient each. Corticosteroid therapy corrected hypercalcemia in 3 patients and improved renal function in the patient with glomerulonephritis and in the case with interstitial fibrosis. One patient died of granulomatous myocarditis, renal insufficiency having been unaffected by corticosteroids.

[Predictive value of additional immunohistochemical studies in histological diagnosis]. / Aussagekraft immunhistochemischer Zusatzuntersuchungen in der histologischen Diagnostik.

No exact information exists on the diagnostic value of immunohistochemistry applied to the routine material of an institute of surgical pathology. For this reason 390 cases additionally investigated by immunohistochemistry were analyzed retrospectively. This method was applied to 0.5% of all biopsies studied morphologically. On average 4.4 antisera per case were used. 352 cases (90.3%) initially diagnosed by morphology alone (16 benign lesions of debatable type, 111 lesions not clearly defined as benign or malignant, 225 malignant tumours of unknown subtype) could be clarified by immunohistochemistry. To obtain reliable results specific application of immunohistology and a clearcut formulation of the question are necessary. If these criteria are fulfilled immunohistochemistry represents a powerful tool in surgical pathology.

[Renal involvement in Legionnaires' disease]. / Renale Mitbeteiligung bei der Legionärskrankheit.

9 consecutive cases of Legionnaires' disease are presented, all of which involved either a pathological urinary sediment or acute renal insufficiency. Diabetic glomerular sclerosis and terminal septic shock in one patient accounted per se for the urinary findings and terminal oliguric renal failure. In the remaining 8 patients the renal abnormalities are interpreted as manifestations of Legionnaires' disease: these were acute renal insufficiency in 6, requiring dialysis treatment in 4, proteinuria in 7, hematuria in 5, leukocyturia in 5 and cylindruria in 3 patients. One patient died of pneumonia and one patient, without Legionella-related renal involvement, of septic shock. Renal histology of 5 patients showed acute interstitial nephritis in one and diffuse sclerosing interstitial nephritis in a second patient, whose biopsy was obtained after 3 months' hemodialysis treatment. In 3 patients renal biopsy findings were explained by preexisting renal pathology, i.e. diabetic nephropathy, chronic transplant rejection and shock kidney respectively. Renal failure requiring hemodialysis and urinary abnormalities were largely reversible.

[Early stomach carcinoma]. / Das Magenfrühkarzinom.

Geographical and epidemiologic investigations in recent years have thrown light on the determining factors in chronic atrophic gastritis and the intestinal type of gastric carcinoma. It is now proven that the majority of early gastric cancers have the exact symptoms of the ulcer type. Diagnosis is by endoscopy and biopsy. Uncritical therapy of an ulcer-like symptomatology by H2-receptor blockers must be rejected.

[Rare stomach tumor--cystic leiomyoma in childhood]. / Seltener Magentumor--Zystisches Leiomyom im Kindesalter.

We report about a rare gastric tumour of a child and discuss the important literature.

[Bronchial cancer from the viewpoint of 2 neighboring regional cancer registers]. / Das Bronchialkarzinom aus der Sicht zweier benachbarter regionaler Krebsregister.

From follow-up examinations on 460 male and 67 female patients with bronchial cancer during the years 1981 and 1982 in the cantons of St. Gallen and Appenzell/Switzerland, as well as from the region of Vorarlberg/Austria various morphological and clinically registered parameters of importance to oncology were comparatively analysed. These regional clinical cancer registers have existed for many years and are recognized legitimately and clinically as an important partial aspect in diagnostic, therapy and prophylaxis of malignant tumours.

[Malignant pericardial effusion--a sign of unfavorable prognosis?]. / Maligner Perikarderguss--ein prognostisch ungünstiges Zeichen?

Malignant pericardial effusion (MPE) resulting in cardiac tamponade is a rare complication in neoplastic disease. From January 1975 to December 1984 the authors observed 22 patients with cytologically verified malignant pericardial effusion. The most frequent primary tumors were non-small cell lung cancer (6), breast cancer (5), non-Hodgkin lymphoma (4) and mesothelioma (4). 50% of the patients presented with MPE as the initial manifestation of the tumor. In the other group of patients MPE appeared after an average of 11 months following the diagnosis of malignant disease. The most frequent symptoms and clinical findings were dyspnea (100%), jugular venous distention (91%), and tachycardia (82%). During the first 24 hours after pericardiocentesis a median volume of 675 ml of predominantly serosanguinous effusion was drained. Besides intrapericardial drug instillation, patients also received local radiotherapy and systemic chemotherapy. At the time when MPE was diagnosed 77% of the patients exhibited advanced malignant disease. Mean survival time was 140 days. Malignant pericardial effusion is therefore regarded as an unfavorable prognostic factor.

[Polar resection in double kidneys in childhood]. / Zur Problematik der Polresektion bei Doppelnieren im Kindesalter.

78 cases of double kidneys without vesico-uretero-renal reflux, in which a heminephrectomy was done, were histologically investigated. The histopathological results were compared with the clinic and the urogram. It could be demonstrated that the results did not correspond in some cases. As a consequence of these discrepancies, we conclude that intravenous urography is not sufficient to indicate a primary heminephrectomy. Therefore, additional studies, such as a diethylenetriaminopentaacetate-T-99m scintigram and a preoperative kidney biopsy under sonographic control, are suggested.

The adenoma-carcinoma sequence of the colon and rectum.

Morphological and epidemiological arguments in favour of an adenoma-carcinoma concept of evolution in the development of colorectal cancers are presented. It is highly probable that most colorectal cancers arise in adenomas. Therefore detection and endoscopic removal of adenomas is a means of reducing the incidence of colorectal carcinomas.

Colorectal cancer: the relationship of staging to survival. A cancer registry study of 800 cases in St. Gallen-Appenzell.

Proper classification of colorectal cancer has been critical in determining prognosis. Dukes' staging and its modifications have created considerable confusion. The TNM system has never been widely accepted because of its complexity. The Australian clinico-pathological staging (ACPS) system corresponds closely to Dukes' A, B, C-classification, but it differs from Dukes' in separating a stage D for incurable metastatic disease. Evaluating the compatibility of these 3 different staging systems, a survival analysis is presented of a group of 800 non-selected patients, resected in curative or palliative intention and compiled from the cancer registry of St. Gall-Appenzell. The prognostic importance of accurate staging for colorectal cancer is confirmed. No matter which system is used, in order to give realistic statements it must be based on tumor penetration, lymph node involvement and distant metastasis.

Evidence of vascular differentiation in anaplastic tumours of the thyroid--an immunohistological study.

Sixteen cases of anaplastic carcinoma (ACA) and 4 cases of malignant haemangioendothelioma (HAE) of the thyroid were studied by light microscopy and immunohistochemistry. Seven cases of ACA and 3 cases of HAE were characterized by coexpression of immunohistological features of epithelial and vascular endothelial cells. Expression of vimentin was common to all tumours investigated. The present study provides evidence that ACA and HAE are partially closely related tumours showing alternating differentiation. This speaks in favour of a common neoplastic cell with the potential for epithelial and vascular endothelial differentiation.

Identification of types and primary sites of malignant tumors by examination of exfoliated tumor cells in serous fluids. Comparison with the diagnostic accuracy on small histologic biopsies.

The accuracy of identification of tumor type and primary site of malignant tumors by examination of exfoliated tumor cells was cytologically studied in 448 malignant effusions from 366 patients for whom the primary tumor site had been confirmed by histology. Ninety-seven corresponding small biopsies from metastases were separately reviewed histopathologically. In four fluids, the cells were too scanty or too poorly preserved for tumor typing. The cytologic tumor typing was performed with nearly 100% accuracy in the remaining 444 fluids, except for those of intermediate-cell anaplastic carcinomas (0 of 3) and poorly differentiated squamous (epidermoid) carcinomas (1 of 5). Adenocarcinoma was correctly identified in 98% of 285 fluids, large-cell carcinoma in 97% of 108 fluids, oat-cell carcinoma in 94% of 16 fluids, well-differentiated (keratinizing) squamous carcinoma in 100% of 3 fluids, malignant lymphoma in 100% of 22 fluids and sarcoma in 100% of 2 fluids. The criteria and the failures are discussed at length. In the investigation of the accuracy of cytologic and histologic diagnoses with respect to the primary tumor site, tumors with variable sites of origin (sarcomas and lymphomas) and those with usually singular sites of origin (e.g., small-cell anaplastic carcinoma of the lung) were excluded, leaving 387 cytologic and 83 histologic specimens available for review. The breast as a primary site was correctly identified in 70% of both the cytologic and histologic specimens; the primary cytodiagnostic criteria included a uniform cell pattern, finely granular chromatin, dense cytoplasm and cell balls with smooth borders. Ovarian primaries were correctly identified in 70% of the fluids and 83% of the biopsy samples on the basis of very irregular clusters of large pleomorphic tumor cells, large nucleoli and psammoma bodies. Lung primaries, identified in 50% of the fluids and 29% of the biopsy samples, showed quite variable cell patterns, most often including large pleomorphic cells with or without mucus formation and prominent multinucleation. Gastric cancers of the diffuse type were accurately identified in 52% of the corresponding fluids, which showed mainly isolated cells with dense cytoplasmic rims, occasional signet-ring cells, "embryo-shaped" nuclei, marked hyperchromasia and densely granular chromatin.(ABSTRACT TRUNCATED AT 400 WORDS)

[Significance of kidney papillae in the pathogenesis of pyelonephritis and reflux nephropathy]. / Die Bedeutung der Nierenpapillen in der Pathogenese von Pyelonephritis und Refluxnephropathie.

The role of the renal papillae in the pathogenesis of pyelonephritis and reflux nephropathy was studied by endoscopy and histology in adult autopsy kidneys. Compound papillae with a concave area cribrosa of the "reflux type" were found in greater frequency in adults than in children. Acute purulent inflammation in the renal parenchyma or coarse pyelonephritic scars were seen almost always overlying "refluxing" papillae or overlying papillae altered by papillary necrosis, obstructive atrophy and other changes of papillary shape. Intrapapillary tubular obstruction in early analgesic nephropathy, gout, myeloma and medullary cystic disease is an other factor favouring bacterial infection to occur. Without an underlying renal papillary damage renal injury attributable to urinary infection seems to be rare.