[Teleangiectasia haemorrhagica hereditaria. Surgical therapy of malignant skin tumors (Osler-Weber-Rendu disease]. / Teleangiectasia haemorrhagica hereditaria. Operative Therapie maligner Hauttumoren (Morbus Osler-Weber-Rendu).

A 65 year old male patient was diagnosed with hereditary hemorrhagic telangiectasia at 30. During recent years he has suffered frequent, almost daily, nose bleeds causing anemia and making several blood transfusions necessary. In the past 2-3 years, the patient has developed multiple squamous cell carcinomas on the face. These unusually large tumours were treated by micrographic surgery using paraffin sections and the defects dosed with a variety of flaps and grafts. Several solar keratoses were also removed. If hemostasis parameters are normal, skin surgery can be performed without hesitation in hereditary hemorrhagic telangiectasia.

[Microangiopathic changes and functional disorders of nail fold capillaries in dermatomyositis]. / Mikroangiopathische Veränderungen und funktionelle Störungen an Nagelfalzkapillaren bei Dermatomyositis.

We report on a 70-year-old female patient with dermatomyositis. The connective tissue vascular bed was studied with capillaroscopy to evaluate morphological and functional changes of skin capillaries. Capillaroscopic findings showed morphological alterations such as rarefication of capillaries, avascular fields and tortuosity of nailfold capillaries. In addition, fluorescence-videomicroscopy showed pathologically increased transcapillary diffusion of dye in the apex region of nutritive skin capillaries. Increased capillary leakage probably contributed to the development of oedema in our patient. Immunosuppressive therapy combined with intensified manual lymphatic drainage was successful.

The long-term prognosis of the primary glomerulonephritides. A morphological and clinical analysis of 1747 cases.

Long-term studies of all types of primary glomerulonephritis (GN) taking into consideration the major morphological and clinical findings revealed the following: 1) Endocapillary GN, post-streptococcal type has a very good prognosis when only glomerulitis is present. The prognosis is significantly worse if either interstitial inflammation with fibrosis or nephrotic syndrome (NS) is present at the time of the biopsy. 2) The prognosis of the various types of mesangioproliferative GN (IgA nephritis, non-IgA nephritis, and immunohistologically negative GN) is very good if there is only glomerulitis. The prognosis is worse for all three types when the renal cortical interstitium exhibits inflammation with fibrosis at the time of the biopsy, and is worst of all when both interstitial fibrosis (IF) and the signs of acute renal failure (ARF) are present. Of this group, the type in which there are negative immunohistological findings exhibits the best prognosis. No difference in prognosis is found between IgA nephritis and non-IgA nephritis. 3) Minimal changes GN with NS has a very good prognosis when the interstitium is not involved. The presence of interstitial inflammation and fibrosis worsens the prognosis significantly. 4) Focal sclerosing GN has a much poorer prognosis than minimal changes GN with NS, even when there is glomerulitis only (5- and 10-year renal survival rates (RSRs) of 90% and 67%, respectively). If interstitial inflammation and fibrosis are present, the prognosis is significantly worse (5- and 10-year RSRs of 84% and 55%, respectively). The prognosis is worst when both ARF and IF are present at the time of the biopsy (5- and 10-year RSRs of 56% and 46%, respectively). From the clinical side, the prognosis is significantly worse if, at the time of the biopsy, NS is present or the serum creatinine concentration is elevated to more than 1.3 mg%. 5) Chronic membranous GN has a better prognosis than focal sclerosing GN if glomerulitis only is present (5-year RSR, 88%; 10-year RSR, 77%). If the renal cortical interstitium is also involved (in the form of IF), the prognosis is significantly worse (5-year RSR, 65%; 10-year RSR, 38%). The prognosis in this disease, too, is worst when both ARF and IF are present at the time of the biopsy (5-year RSR, 38%; 10-year RSR, 25%). 6) Membranoproliferative GN has a worse prognosis than any of the types of GN so far mentioned (5-year RSR, 51%; 10-year RSR, 32%).(ABSTRACT TRUNCATED AT 400 WORDS)

Determination of 2'-5'-oligoadenylate synthetase in serum and peripheral blood mononuclear cells before and after subcutaneous application of recombinant interferon beta and gamma.

The interferon-inducible enzyme, 2'-5'-oligoadenylate synthetase, was estimated in healthy donors and in patients before and after subcutaneous application of recombinant interferon beta and gamma. Tests were carried out with lysates of peripheral blood mononuclear cells, using an established radioenzymatic assay, and in serum samples, using a new radioimmunoassay. Both test systems substantially yielded the same results: after a single injection of interferon beta (1-5 x 10(6) IU), 2'-5'-oligoadenylate synthetase increased in a dose-dependent manner reaching maximal catalytic concentrations in most patients after 24-48 hours (leukocytes) and 48-72 hours (serum). In contrast, interferon gamma (2-4 x 10(6) IU) caused only a small induction of 2'-5'-oligoadenylate synthetase. However, daily application of interferon gamma for 7 days led to a distinct time-dependent increase of 2'-5'-oligoadenylate synthetase activity concentration during this observation period. Characteristically, even during daily application, the 2'-5'-oligoadenylate synthetase activity concentration dropped just 48-72 hours after the first injection of interferon beta. The determination of 2'-5'-oligoadenylate synthetase proved to be useful for optimizing and monitoring subcutaneous therapy with interferon. The new radioimmunoassay which allows the determination of this enzyme in serum is superior to other methods used in the past.

[Intralesional therapy of melanoma metastases with recombinant interferon-beta]. / Intraläsionale Therapie von Melanommetastasen mit rekombinantem Interferon-beta.

In ten patients with metastasizing melanomas, discontinuous intratumoral treatment with recombinant interferon beta (rIFN-beta) was administered into 19 cutaneous or palpable subcutaneous metastases. Among the 16 metastases treated with 5 x 10(6) IU per injection, 8 showed partial or complete remission. No recurrence was observed during the 4-9-month follow-up period. There was no regression in 3 metastases treated with 3 x 10(6) IU rINF-beta per injection. No systemic antineoplastic effects were observed in any of the cases. The IFN-beta serum levels were measurably increased following intratumoral application. Local treatment led to a significant increase in (2'-5')oligoadenylate synthetase in the mononuclear blood cells and in the serum. Side-effects of the treatment were moderate; there was a temporary increase in transaminases, a decrease in thrombocytes and influenza-like symptoms. The results show that IFN-beta has a dose-dependent antitumour effect on malignant melanomas.

The pathogenesis of chronic renal failure in diabetic nephropathy. Investigation of 488 cases of diabetic glomerulosclerosis.

Investigation of renal biopsy specimens from 488 patients with diabetic glomerulosclerosis (DGS) of varying severity revealed the following: 1) The severity of DGS increases with the duration of the diabetes. 2) As the severity of DGS increases, it is complicated with increasing frequency by exudative changes, which correspond in detail to hyperperfusion lesions described in the literature. 3) As the severity of DGS increases, the severity of arteriolosclerosis and the incidence of nephrotic syndrome increase significantly. 4) The 5- and 10-year renal survival rates are highest for those diabetic patients in whom the tubules and renal cortical interstitium are of normal appearance. These survival rates are diminished if any of the following are present at the time of biopsy: a) interstitial fibrosis; b) hyperperfusion lesions; c) nephrotic syndrome; d) elevation of the serum creatinine concentration to more than 1.3 mg%. 5) No significant correlation was found between renal survival rate and age, sex, or type of diabetes. 6) The inflammation of the renal interstitium seen in diabetes does not differ from that seen in chronic glomerulonephritis. Monocytes, macrophages, T lymphocytes, fibroblasts and fibrocytes play the major role in this inflammation. This inflammatory process is considered to represent not pyelonephritis, but rather an auto-immune process. In other words, it is proposed that the diabetic kidney fails not only as a result of non-specific glomerular lesions (hyperperfusion lesions) but also because of non-specific tubulointerstitial changes, whereas diabetic glomerulosclerosis alone does not lead to chronic renal failure.

The consequences of tubulo-interstitial changes for renal function in glomerulopathies. A morphometric and cytological analysis.

Morphometric investigation of the structures of the cortex in kidneys exhibiting various types of glomerulopathy revealed the following: 1. In various types of glomerulonephritis, diabetic glomerulosclerosis, and glomerular amyloidosis there are significant correlations between the severity of fibrosis of the renal cortical interstitium and tubular atrophy resulting from chronic interstitial inflammation, and the serum creatinine concentration, creatinine clearance, inulin clearance and PAH clearance. 2. As illustrated with the example of membranoproliferative glomerulonephritis type I, if glomerulopathy alone is present, there is no elevation of the serum creatinine concentration, even if the glomerular inflammatory changes are severe; neither are severe renal amyloidosis that is confined to the glomeruli and severe isolated diabetic glomerulosclerosis associated with elevation of the serum creatinine concentration. 3. There is a significant negative correlation between the severity of interstitial fibrosis resulting from chronic inflammation and the total number and cross-sectional area of the intertubular capillaries; i.e., the total cross-sectional area and number of capillaries per unit area decrease as the fibrosis of the cortical interstitium increases. 4. Cases of glomerulonephritis in which there is accompanying fibrosis of the renal cortical interstitium have a significantly worse long-term prognosis than those in which there is only severe glomerulitis. 5. Obliteration of the post-glomerular capillaries leads to an increase in the cross-sectional area of the glomerular capillary convolution, the morphological equivalent of an increase in intraglomerular pressure. 6. The cause of the disease of the renal cortical interstitium that may accompany the various types of glomerulonephritis is not known. It is considered possible, as a working hypothesis, that this inflammation represents a T-cell stimulated autoimmune process in which fibroblast proliferation occurs, leading to an increase in numbers of fibrocytes in the renal cortical interstitium and thus to increased production of collagen.

IgA nephritis: on the importance of morphological and clinical parameters in the long-term prognosis of 239 patients.

This study is concerned with the correlation between tubulointerstitial changes (interstitial fibrosis, acute renal failure, and interstitial fibrosis with acute renal failure), glomerular changes (focal and segmental lesions, hyperperfusion lesions), vascular changes, clinical data at the time of biopsy (serum creatinine concentration, creatinine clearance, hematuria, proteinuria, and hypertension) and first symptoms (hematuria, proteinuria and hypertension) and the kidney survival rate in 239 patients with IgA nephritis without nephrotic syndrome. The morphological and clinical parameters were subjected to multivariate analysis in order to examine their significance with regard to the prognosis. The interstitial fibrosis was proven to be the most important morphological parameter, and the most important clinical parameters were the serum creatinine concentration and the creatinine clearance.

Long-term prognosis of chronic idiopathic membranous glomerulonephritis. An analysis of 334 cases with particular regard to tubulo-interstitial changes.

A retrospective long-term study (average follow-up time 5.2 years) of 334 patients with idiopathic membranous glomerulonephritis (MGN) was carried out with the following results: 1) MGN was found to have a relatively good prognosis when all cases were considered together: 5-year kidney survival rate (KSR) -88%, and 10-year KSR -77%. 2) Univariate survivorship analysis showed the following morphological and clinical parameters to be associated with an increased risk of terminal renal insufficiency or death from renal disease: a) tubulo-interstitial changes; b) glomerular stage III as opposed to stages I and II; c) elevation of serum creatinine concentration at the time of the biopsy; d) arterial hypertension at the time of the biopsy. 3) Multivariate analysis showed that only tubulo-interstitial changes (interstitial fibrosis and/or acute renal failure) found at the time of the biopsy and their clinical correlate, serum creatinine concentration, were significant and therefore of definite prognostic importance. 4) Unsystematic therapy with steroids and/or cytostatic agents does not improve the long-term prognosis of MGN. 5) The cause of disease in the tubulo-interstitial system in MGN is discussed. Interstitial fibrosis is considered to develop possibly as a consequence of unresorbed interstitial edema which can develop during an episode of acute renal failure. Coexisting T-cell-mediated disease in the region of the intertubular capillaries is also considered as a possible factor in the development of interstitial fibrosis.

[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.

Prognostic value of preoperative serum CEA level compared to clinical staging. IV. Histological grading and tumor type in colorectal and gastric cancer.

In a clinical investigation of observed postoperative survival, 410 patients with colorectal cancer and 269 patients with stomach cancer have been registered for primary surgical treatment connected with a long-term follow up. Histologic grading and tumor typing were examined as potential prognostic factors and compared with the prognostic information covered by operability, tumor extension, and the preoperative CEA level. Statistical treatment of the data revealed no prognostic significance of the tumor types adenocarcinoma, mucinous, and anaplastic tumours in gastric cancer. Histologic grading specified ranges associated with significant differences in survival of gastric and colorectal cancer patients. However, histologic grading did not provide prognostic information in addition to operability and tumor extension. However, histologic grading gave additional prognostic information to preoperative CEA levels in the range of 0-5 micrograms CEA/1 serum but not in the range greater than 5 micrograms CEA/1. The results indicate that the prognostic information of preoperative serum CEA level is not directly linked to the histologic grade of a tumor.