Molecular lesions in colorectal cancer: impact on prognosis? Original data and review of the literature.

BACKGROUND: In the Dukes' B and C stages of colorectal carcinoma there are considerable variations in the observed courses of the disease. Since post-operative chemotherapy in patients with Dukes' C (node-positive) colon carcinoma has been demonstrated to be effective in improving overall-survival, a more exact prognosis assessment gains additional significance and therapeutic relevance. DISCUSSION: One also hopes to derive improved prognostic factors from the clarification of the molecular pathogenesis. Because of its frequency and the accessibility and recognizability of its developmental stages colorectal carcinoma is among the best investigated of all solid tumors. Despite a multitude of suggested molecular candidate markers none of these changes has yet been able enter the everyday life of the clinic. However, it is to be expected that some of the molecular alterations presently discussed will gain importance before long in the clinical treatment of patients with colorectal carcinoma. CONCLUSION: Considering also our own findings, this review presents the latest developments in the scientific discussion of the tumor suppressor/oncogenes p53, k-ras, and DCC, biochemical determinants of the 5-fluorouracil metabolism, and defects of the DNA repair system.

Chymase expressing bone marrow mast cells in mastocytosis and myelodysplastic syndromes: an immunohistochemical and morphometric study.

BACKGROUND: Two cell specific neutral proteases, tryptase and chymase, are produced by human mast cells (MC). Tryptase is constitutively expressed by all MC, whereas chymase is found only in an MC subset. Very little is known about chymase expression in MC proliferative disorders (mastocytosis). AIMS AND METHODS: Routinely processed, formalin fixed, and paraffin wax embedded bone marrow trephine biopsy specimens obtained from patients with various subtypes of mastocytosis (n = 47) and myelodysplastic syndromes (MDS; n = 28) were immunostained with antibodies against chymase and tryptase. Normal/reactive bone marrow specimens with intact haemopoiesis (n = 31) served as controls. The numbers of chymase expressing (C+) and of tryptase expressing (T+) MC were assessed morphometrically using a computer assisted video camera system. RESULTS: In normal/reactive bone marrow, the numbers of C+ MC (median, 8/mm(2); maximum, 159/mm(2)) were in the same range as those of T+ MC (median, 4/mm(2); maximum, 167/mm(2)). Because normal MC express both chymase and tryptase, these findings indicate that the common phenotype of bone marrow MC in normal/reactive states is MC(TC) (MC expressing both tryptase and chymase). In contrast, in MDS and mastocytosis, the bone marrow exhibited far more T+ MC than C+ MC in almost all cases. CONCLUSIONS: According to these findings, the predominant MC type in the bone marrow in neoplastic states such as MDS and mastocytosis is MC(T) (MC expressing only tryptase). Although the pathophysiological basis of this apparent lack of chymase expression in most neoplastic MC in mastocytosis and MC involved in MDS remains unknown, this study has produced further evidence of the superior value of antitryptase antibodies in the diagnosis of mastocytosis.

Oxaliplatin, fluorouracil and leucovorin for advanced biliary system adenocarcinomas: a prospective phase II trial.

We studied the activity of combined oxaliplatin and fluorouracil-leucovorin in 16 consecutive patients with advanced biliary tract adenocarcinomas. The disease control rate (responses and stable disease) was 56% (95% confidence interval, 29-84%) and the median overall survival time was 9.5 months (range 0.9-26.8+). Therefore, this regimen might be active in biliary adenocarcinomas with further evaluation necessary.

Serum tryptase measurements in patients with myelodysplastic syndromes.

Abnormal differentiation and maturation of hemopoietic cells are characteristic features of myelodysplastic syndromes (MDS). Tryptases (alpha- and beta-type) are lineage-restricted serine proteases primarily expressed in mast cells (MC). We have analyzed expression of tryptase in 89 de novo MDS patients (refractory anemia (RA), n = 30; RA with ringed sideroblasts (RARS), n = 21; RA with excess of blasts (RAEB/RAEB-t), n = 27; chronic myelomonocytic leukemia (CMML), n = 11). Serum levels of total tryptase (alpha - protryptase + beta - tryptase) were measured by FIA. The numbers of tryptase+ cells were determined in paraffin-embedded bone marrow (bm) sections by immunohistochemistry and morphometry. In healthy individuals, serum total tryptase levels ranged between < 1 and 15 ng/ml (5.6 +/- 2.8 ng/ml). Tryptase levels of > 20 ng/ml were detected in 5/22 patients with RA (22.7%), 4/17 with RARS (23.5%), 0/16 with RAEB/RAEB-t, and 3/8 with CMML (37.5%). Thus, serum tryptase concentrations were higher in RA (16.6 +/- 14.3 ng/ml), RARS (12.9 +/- 8.2), and CMML (16.5 +/- 7.6) compared to RAEB/-t (8.7 +/- 3.8). By morphometry, elevated numbers of tryptase+ bm cells were detected in all MDS groups (RA: 139 +/- 131; RARS: 118 +/- 98; RAEB/RAEB-t: 80 +/- 79; CMML: 105 +/- 114 cells/mm2) compared to controls (54 +/- 51 cells/mm2). As assessed by Northern blotting and protein analysis, bm cells in MDS primarily produced alpha-(pro)tryptase, but little or no beta-tryptase. Together, our data show that elevated levels of tryptase are detectable in a group of patients with MDS probably because of an increase in neoplastic (mast) cells producing the enzyme(s). In addition, serum tryptase levels appear to correlate with MDS variants. Follow up studies should clarify whether an elevated tryptase concentration in MDS is of prognostic significance.

Prophylaxis of restenosis with (186)re-labeled stents in a rabbit model.

BACKGROUND: Intraluminal beta-irradiation has been shown to decrease neointimal proliferation after angioplasty in experimental models. The purpose of this study was to test the technical feasibility and biological effects of (186)Re-labeled stents. METHODS AND RESULTS: Thirty-four New Zealand White rabbits were fed a 0.5% cholesterol diet before balloon angioplasty and insertion of Palmaz stents in the infrarenal aorta. The animals were killed 7 weeks after stent implantation. Two of 34 animals died prematurely (aortic leak, pneumonia). Control stents (n=7) were compared with (186)Re stents (2.6 MBq [n=6], 8.1 MBq [n=5], 16.0 MBq [n=6], and 25.3 MBq [n=8]). Stent application was successful in all cases. No thrombus occlusion was observed. After 7 weeks, neointima formation was 2.2+/-0.2 mm(2) in the control group. In the treatment groups, a dose-dependent neointima reduction was detectable (0.5+/-0.5 mm(2) [2.6 MBq], 0.4+/-0.4 mm(2) [8.1 MBq], and 0 mm(2) [16.0 MBq, 25.3 MBq]). No induction of neointimal formation was observed at the edges of the stents. Radiation resulted in delayed reendothelialization. CONCLUSIONS: (186)Re stents were capable of reducing neointima formation in a dose-dependent fashion. (186)Re stents did not cause late thrombosis or neointimal induction at the stent margins in the observation period of 7 weeks.

Primary cardiac leiomyosarcoma originating from the pulmonary valve. Case report and review of the literature.

Primary cardiac tumours are rare findings (incidence 0.02% according to a recent meta-analysis) with dismal prognosis. Approximately 25% are malignant, mostly represented by sarcomas. Among these, leiomyosarcomas are exceptional. Treatment for primary cardiac leiomyosarcomas consists of radical surgical resection followed by adjuvant radiation therapy and/or chemotherapy. The mean survival after surgery and adjuvant therapies is 6.8 months. We present a rare case of a 40- year-old male patient with a primary cardiac leiomysarcoma originating from the pulmonary valve. This patient died after surgery and implantation of a homograft of the pulmonary trunk. Furthermore, the literature has been reviewed.

Aortico-pulmonary paraganglioma associated with bilateral carotid body tumors. Diagnostic presentation and clinical implications.

A case of mediastinal paraganglioma in association with bilateral carotid body tumors is presented. Characteristic radiological findings included a hypointense signal in T1-weighted, a hyperintense signal in T2-weighted magnetic resonance (MR) images and a vascular enhancement pattern in dynamic contrast enhanced MR imaging. Thus, feeding vessels could be depicted noninvasively. The importance of family screening in affected individuals is stressed, as a hereditary form of the disease exists in which multiple paragangliomas are common.

Acute lymphoblastic leukaemia: correlation between morphological/immunohistochemical and molecular biological findings in bone marrow biopsy specimens.

BACKGROUND: Although numerous antibodies suitable for use on paraffin wax embedded sections are available for the subtyping of acute leukaemia (acute myelogenous leukaemia (AML) and acute lymphoblastic leukaemia (ALL)) in bone marrow biopsy sections, unequivocal identification of the cell line involved is sometimes impossible. METHODS: Forty eight formalin fixed, paraffin wax embedded bone marrow biopsy specimens that had been decalcified in EDTA were investigated, including 42 thought to exhibit ALL on the basis of bone marrow smears. Five specimens exhibited AML and one biphenotypic leukaemia, as diagnosed immunohistochemically in bone marrow biopsies. Immunostaining was performed with antibodies against relatively specific B and T cell antigens. The blasts were investigated for rearrangements of the immunoglobulin heavy chain (IgH) and the T cell antigen receptor (TCR) genes. RESULTS: Amplifiable DNA was obtained from all 48 specimens. An IgH gene rearrangement was detected in 20 of 23 c-ALL specimens. Four of seven T cell ALL (T-ALL) specimens had a TCR-gamma gene rearrangement, and the one B cell ALL (B-ALL) specimen exhibited a clonal IgH gene. Three of four cases of unclassifiable ALL could be assigned to the B cell lineage on the basis of gene rearrangement analysis. Seven cases originally diagnosed in smears as ALL were rediagnosed as AML (n = 5) or biphenotypic leukaemia (n = 2) because of immunohistochemical reactivity for myeloperoxidase or lysozyme. Two of these AML cases and two of three cases of biphenotypic leukaemia exhibited a monoclonal IgH gene rearrangement. CONCLUSIONS: Acute leukaemia can be subtyped in bone marrow sections with a limited panel of antibodies suitable for use on paraffin wax embedded sections (against CD3, CD10, CD20, CD79a, myeloperoxidase, and lysozyme). In patients with ALL and a diagnostically equivocal immunophenotype, gene rearrangement analysis might indicate whether the B or T cell lineage is involved.

Reactive and neoplastic lymphocytes in human bone marrow: morphological, immunohistological, and molecular biological investigations on biopsy specimens.

BACKGROUND: Slight, diffuse or focal lymphocyte proliferation is relatively common in bone marrow biopsy specimens. It may be impossible to determine whether this represents a reactive lymphocytosis or low grade non-Hodgkin lymphoma (NHL) on the basis of routine investigations alone. AIM: To investigate the supplementary use of molecular biological techniques in this situation. METHODS: 529 formalin fixed, paraffin embedded bone marrow biopsy specimens from the iliac crest were subjected to histological and immunohistochemical staining to determine the number and nature of the lymphocytes present. The cases were divided into three groups according to the lymphocyte count: normal (< 10% of nucleated bone marrow cells), slightly increased (10-30%), and markedly increased (> 30%). All of the last group could be diagnosed as NHL from the morphological findings alone. The clonality of rearrangements of the IgH and TCR gamma genes was investigated by polymerase chain reaction (PCR). RESULTS: Monoclonality was observed in 7.5% of the 372 cases with a normal lymphocyte count, in 50% of the cases with a modest increase in lymphocyte numbers (suggesting a diagnosis of low grade NHL not detected by immunostaining), and in 77% of the cases with markedly increased lymphocyte numbers. CONCLUSIONS: If PCR is used in addition to the immunohistochemical investigation of bone marrow biopsies, considerably more cases of NHL can be identified, making this of particular use in staging and detection of recurrences.

Diagnostic significance of nuclear p53 expression in the surveillance of Barrett's esophagus--a longitudinal study.

The efficacy of currently performed surveillance in patients with Barrett's esophagus (BE) is substantially compromised by shortcomings of dysplastic lesions as diagnostic markers. The aim of this study was to evaluate the possible role of p53 protein expression as complementary method in the diagnosis of neoplastic transformation in BE. A longitudinal study was performed. 41 patients were enrolled. The median time of surveillance was 46 months. 234 archival paraffin blocks containing a total of 627 biopsies were retrieved. p53 protein immunostaining by application of the monoclonal antibody DO-1 was performed. The results of immunohistochemistry were compared with the exact histopathological diagnosis and grading of dysplasia (no dysplasia, indefinite for dysplasia, low-grade dysplasia, high-grade dysplasia, carcinoma). In merely four of 206 nondysplastic mucosal sites p53 expression was found. However, p53 expression was detected with increasing frequency in sites indefinite for dysplasia (2/9), specimens with low-grade dysplasia (9/15), high-grade dysplasia (3/3) and the one with a carcinoma. This study shows a close association of nuclear p53 protein expression to the process of neoplastic transformation in Barrett's epithelium. However, it apparently does not precede the appearance of dysplasia significantly. Thus, nuclear p53 expression as detected by immunohistochemistry may serve to confirm a suspected diagnosis of dysplasia in BE.

Resection of a large right atrial hemangioma in a neonate after prenatal diagnosis.

Cardiac hemangiomas are extremely rare benign tumors. We describe the case of a right atrial hemangioma in a neonate diagnosed prenatally and successfully operated 10 days after spontaneous delivery. This unusual case illustrates the importance of prenatal diagnosis and delivery of the baby next to a pediatric center with a department of appropriately specialized cardiovascular surgery.

Human glomerular structure under normal conditions and in isolated glomerular disease.

Investigation of the human glomerulus in health and disease shows that the human glomerulus comprises seven lobule-like structures with numerous anastomoses. The total length of the capillaries in a single glomerulus is 0.95 cm, making a total of 19 km for all 2-million glomeruli. The total surface area of all glomerular capillaries is 6,000 cm2. The total filtration surface area is 516.1 cm2. Severe isolated disease of the glomerulus, as seen in acute endocapillary glomerulonephritis, membranoproliferative glomerulonephritis types I and II, membranoproliferative glomerulonephritis plus chronic membranous glomerulonephritis, diabetic glomerulosclerosis, and glomerular amyloidosis, does not lead to elevation of serum creatinine concentration, even if the filtration area is reduced to about 20% (as in diabetes) of the normal value. It is concluded that isolated glomerular disease does not lead to elevation of the serum creatinine concentration. Glomerulopathies in which there is acute or chronic elevation of the serum creatinine concentration are accompanied by acute renal failure or involvement of the renal cortical interstitium, respectively.

Renal morphology in essential hypertension: analysis of 1177 unselected cases.

Morphological and clinical analysis of 1177 renal biopsies from nonselected patients with essential hypertension revealed compensated benign nephrosclerosis in 775 cases. Decompensated benign nephrosclerosis was found in 251 cases, and secondary malignant nephrosclerosis was found in 151 cases. This article describes the morphological and clinical features of decompensated benign nephrosclerosis, which has received little recognition until now. The morphological and clinical features of secondary malignant nephrosclerosis, which is induced by hypertension, are also considered. There is also a discussion of the differentiation of the latter from primary malignant nephrosclerosis, in which stenosis of the preglomerular vessels develops in the presence of normal blood pressure and leads secondarily to renal hypertension.

[Giant cell tumor of bone. Morphological, immunohistochemical, morphometric and DNA flow cytometric findings]. / Der Riesenzelltumor des Knochens. Morphologische, immunhistochemische, morphometrische und DNA durchflusszytometrische Befunde.

Giant cell tumour (GCT) of bone is a locally aggressive tumour with a high rate of recurrence if not completely excised. The present study was undertaken to clarify whether flow cytometric, immunohistochemical and morphometric studies can be a useful tool to assess the prognosis of patients with GCT. DNA flow cytometry, cell cycle studies and immunohistochemical investigations with antibodies against CD 68, CD 34, p53 and Ki67 were performed on paraffin embedded tissue of 10 cases of GCT. As a further possible prognostic parameter angiogenesis within the tumour was investigated using an automatic image analysis system. Histologically 4 cases were grade 1 tumours and 6 cases grade 2. Among the Grade 1 cases, all were diploid. Of the Grade 2 cases, 4 were diploid and 2 were aneuploid. Both of the patients with an aneuploid tumour developed a loval recurrence. All GCT revealed large numbers of CD 68 positive giant cells, but mononuclear tumour cells exhibiting CD 68 immunoreactivity were also present. Corresponding to the immunohistochemical findings with MIB-1 the flow cytometric DNA histogram revealed high proliferation rates (mean value 14.9%). None of the tumours exhibited p53 immunoreactive cells. All cases showed high content of vessels with on the average relative vessel area of 7.7%. No correlation between clinical outcome and vascular parameters (number of vessels, vessel area, perimeter) was found. Our findings suggest that DNA flow cytometry is useful in predicting tumour behaviour in some cases. GCT exhibits extensive angiogenesis, but none of the vascular parameters investigated was found to be of prognostic value.

[Free transplanted, microvascular reanastomosed forearm flap for reconstruction of the mouth cavity and oropharynx. Clinical and morphologic findings with special reference to reinnervation]. / Frei transplantierte, mikrovaskulär reanastomosierte Unterarmlappen zur Rekonstruktion in Mundhöhle und Oropharynx. Klinische und morphologische Befunde unter besonderer Berücksichtigung der Resensibilisierung.

It remains a controversial question whether or not the anastomosis of sensory nerves is necessary in free transplants of microvascularly reanastomosed radial forearm flaps in the oral cavity and oropharynx. Some authors perform this routinely because they expect fewer complications in a skin with a sensory nerve supply. We carried out clinical and morphological examinations in 20 patients in order to determine the sensory innervation of the transplanted tissue. All patients received free transplants of microvasculary reanastomosed radial forearm flaps during a tumor operation in the oral cavity or oropharynx. Postoperative wound healing proceeded without complications in all but three cases, but these disturbances were insufficient to explain any deficit in sensation in the operated areas. Following surgery, sensation was determined clinically by two-point discrimination. Morphological studies of 20 flap biopsies using conventional colored light microscopy demonstrated nerve fibers in 14 of the biopsies. Immunohistochemical investigations also showed the presence of small nerve fibers by proving S-100 positive Schwann cells. We could not find a correlation between the demonstration of nerve fibers and the use of radiation (or an increased radiation dosage) following surgery. These findings suggest that nerve regeneration was completed just before the 6th postoperative month, which was the earliest time recorded in this study. Perivascular (vegetative) nerves showed a delayed regeneration and could be demonstrated only 36 months after operation. Histological investigations of the transplanted tissue showed a decrease in keratin with a partial increase in parakeratosis, a loss of skin structures and nearly always chronic inflammation. Our findings verify that a sensory innervation is possible in free transplanted radial forearm flaps by the regeneration of nerves coming from the transplantation bed and/or adjacent (oral) mucosa. This leads to a sensation comparable to that of healthy mucosa. These findings also indicate that there is no need for the anastomosis of sensory nerves during transplant surgery.

Desmoplastic fibroma of the bone. A report of two patients, review of the literature, and therapeutic implications.

BACKGROUND: Desmoplastic fibroma (DF) is an extremely rare bone tumor. The recommendations for therapy are often based on limited personal experience, and the rate of local recurrence in the published cases is very high. Therefore, an analysis of treatment results of published cases was performed. Furthermore, DNA analysis of the tumors from two patients was also performed. METHODS: The clinical, radiologic, and histologic data of two patients with DF of the long bones are presented. DNA flow cytometry was performed on both DFs, three cases of abdominal fibromatosis, and three cases of extraabdominal fibromatosis. One hundred eighty-nine patients analyzed in the literature and our own 2 patients were evaluated with regard to epidemiologic, clinical, and histologic data, with particular emphasis on treatment results. RESULTS: DNA analysis of the locally infiltrating tumors revealed indices of proliferation between 21.5% and 24%, noticeably elevated values in comparison with extraosseous desmoid tumors (8.04%). Magnetic resonance imaging (MRI) was most valuable for imaging the intraosseous and extraosseous extent of DF. The evaluation of 191 patients (189 from the literature, 2 of the authors) showed the numbers of males and females to be equivalent, with a mean age of 23 years. DF has been reported in almost all bones, with a tendency to occur in the mandible and the long bones. Approximately 12% of patients presented with a pathologic fracture (20 of 161 patients). Infiltrative growth in the soft tissue was documented in 48% of patients. Three patients developed metastases after local recurrence. Analyzing the treatment results, the authors found a recurrence rate of 55-72% after nonresection procedures, and 17% after resection. No recurrences are reported after resection with wide surgical margins. The recurrence rate of tumors of the extremities was 55%, and 25% of these patients eventually required an amputation. CONCLUSIONS: Considering the "semimalignant" character of this entity and the poor treatment results in patients with recurrent tumors, marginal or wide resection for primary treatment is recommended. The superior imaging quality of MRI greatly facilitates preoperative planning.

Nonspecific immunostaining of blast cells of acute leukemia by antibodies against nonhemopoietic antigens.

It is well known that some of the widely used antibodies directed against hemopoietic antigens exhibit cross-reactivity with normal and neoplastic nonhemopoietic cells. By contrast, relatively little is known about the immunoreactivity of hemopoietic cells with antibodies that detect nonhemopoietic antigens. In this study 43 routinely processed bone marrow biopsy specimens containing infiltrates of acute leukemia of different subtypes were stained with a panel of 20 antibodies that detect nonhemopoietic antigens in formalin-fixed and paraffin-embedded tissue. Thirteen of the antibodies applied (KL1; BMA 120; and antibodies against epithelial membrane antigen, alpha-fetoprotein, prostate-specific acid phosphatase, prostate-specific epithelial antigen, placental alkaline phosphatase, alpha-amylase, serotonin, bombesin, beta-human chorionic gonadotrophin, desmin, and S-100 protein) did not stain blast cells in any of the cases. However, anti-vimentin, HMB45, and anti-myoglobin stained blast cells in the majority of the cases; the antibodies against thyroglobulin, actin, and carcinoembryonic antigen stained blast cells in 10% to 25% of the cases; and anti-neuron-specific enolase stained blast cells in less than 10% of the cases. No correlation was found between the leukemia subtype and the pattern of immunoreactivity. The staining specificity, (i.e., the specificity of binding of the primary antibody--immunologic vs. nonimmunologic binding), was tested by increasing the dilution of the primary antibody and comparing the staining intensity in the bone marrow specimens and control tissue. Staining specificity was confirmed only for staining with the antibodies against neuron-specific enolase and vimentin. The findings show that immunoreactivity of tumor cells in bone marrow biopsy specimens for nonhemopoietic antigens does not exclude a diagnosis of acute leukemia.

Staging, grading and related histopathological techniques in local therapy of rectal tumours.

Today, local therapy is an established alternative to radical resection for the treatment of rectal tumours. Selection of the operative technique requires an exact perioperative estimation of risks, with both clinical and histopathological examination. Of crucial importance in making a decision to perform a local resection is exact and meticulous histopathological preparation of the tissue. The most important criterion is the estimation of risk of lymph node metastases. This risk is assessed on the basis of the depth of invasion of the tumour, the histological grade of differentiation and the presence or absence of invasion of lymphatic vessels.

[Clinical pathology of the glomerulus--from phenomenon to entity. The mesangial lesion]. / Klinische Pathologie des Glomerulus--vom Phänomen zur Entität. Die mesangiale Läsion.

The numerous findings discussed lead to the following conclusions: 1. The mesangial lesions, which may take a wide range of different forms, can be classified into two groups according to whether an underlying immunological pathomechanism is involved. Those that result from such a pathomechanism represent various types of glomerulonephritis. 2. Amongst these immunologically-mediated glomerulonephritides mesangioproliferative glomerulonephritis (and, of this group, IgA nephritis) is the most common. Membranoproliferative glomerulonephritis is the most severe of these diseases. Either may be idiopathic or secondary, or may occur in association with systemic disease. 3. The number of macrophages in the mesangial lesions in glomerulonephritis correlates with the severity of the glomerulonephritis, the localization of the immune complex deposits and the degree of proteinuria. If the immune complex deposits extend out of the mesangium into the subendothelial space, the number of macrophages is higher, the structural changes are more marked, and proteinuria is more severe. 4. Various pathomechanisms and nosologic entities can lead to mesangial lesions of the type seen in mesangioproliferative glomerulonephritis or membranoproliferative glomerulonephritis. On the other hand, the same entity may be associated with mesangial lesions of different severity, and consequently the prognosis varies. Differential diagnosis of the mesangial lesions, which represent heterogeneous nosologic entities, requires the use of light microscopic, immunohistochemical, and electron microscopic techniques. Exact diagnosis is necessary because of the differences in prognosis. 5. The course and prognosis of mesangial lesions are determined by immunological and nonimmunological factors. Long-term studies have demonstrated that prognostically relevant information can already be gained at the time of biopsy by the assessment of certain morphological features (e.g., immunohistological findings, severity of glomerulonephritis, the presence of focal/segmental lesions) and clinical parameters (e.g., proteinuria, hematuria, hypertension, and serum creatinine concentration). The decisive predictor of an unfavorable prognosis is the presence of interstitial fibrosis.

[Etiology and pathogenesis of osteochondrosis dissecans of the knee joint]. / Zur Atiologie und Pathogenese der Osteochondrosis dissecans des Kniegelenkes.

We report a clinical examination series on 72 knees with osteochondritis dissecans. The O.D. very often affected men employed in construction. An illness on both knees was usually found in younger patients. In those cases the osteochondritis was more often located in an area of lighter bearing. In cases involving only one knee the illness was confined to the area of heavy bearing. In patients seeking therapy up to 10 years after initiation of symptoms we found 50% to have a corpus librum. This rate rises significantly after 10 years to over 90%. In 7 of 10 cases we found a hyperlipoproteinaemia.