Schistosomiasis, in contrast to alcoholic liver disease, leads to presinusoidal hepatic fibrosis, which determines the prognosis of the disease. Because conventional liver function tests and liver biopsy specimens provide little information about the dynamics of the fibrotic process, we measured the serum concentrations of procollagen type III N-propeptide and procollagen type I C-propeptide, believed to mainly reflect collagen synthesis, and procollagen type IV C-propeptide and collagen type VI, two presumptive markers of collagen degradation. Determinations were performed in 15 healthy control subjects, 69 patients with various stages of infection with Schistosoma mansoni/Schistosoma haematobium (28 with an early active infection and no organ involvement, 27 with hepatosplenic involvement and 14 with complications of portal hypertension) and 16 patients with alcoholic cirrhosis. In addition, liver biopsy specimens were obtained from 30 schistosomal patients (18 with hepatosplenic involvement and 12 with complications of portal hypertension for histopathological grading and collagen histochemistry. Procollagen type III N-propeptide was significantly elevated in the three patient groups with schistosomiasis when compared with controls (p less than 0.01). Also, patients with higher histological grading showed significantly higher procollagen type III N-propeptide values (p less than 0.05). In alcoholic patients, procollagen type III N-propeptide was even higher and increased parallel to the severity of the disease, determined by using a combined clinical and laboratory index. Procollagen type I C-propeptide was only elevated in early infection (p less than 0.05) and steadily decreased with disease progression.(ABSTRACT TRUNCATED AT 250 WORDS)

Hepatic fibrosis in alcoholic liver disease often heralds progression to cirrhosis and, therefore, noninvasive parameters are required for early diagnosis and follow-up. Collagens VI and XIV, procollagen-III-N-propeptide, hyaluronic acid, and active transforming growth factor-beta1 (TGF-beta1) were measured in healthy volunteers, patients with alcoholic cirrhosis, and heavy drinkers without cirrhosis. Noncirrhotic alcoholics were assigned to two groups with either normal aspartate aminotransferase or levels > or = 2 normal. Collagens VI and XIV were elevated in all alcoholic patients compared to controls (P < 0.0001, all instances). Procollagen-III-N-propeptide and hyaluronic acid levels were higher in alcoholic patients with elevated liver enzymes and in cirrhotics as compared to controls. Procollagen-III-N-propeptide revealed a significant correlation with serum levels of TGF-beta1 (P < 0.0001). Collagens VI, and XIV, procollagen-III-N-propeptide, and hyaluronic acid appear to be sensitive markers indicating fibrotic transformation in alcoholics. The correlation between procollagen-III-N-propeptide and TGF-beta1 emphasizes its role in hepatic fibrogenesis.

S Si im mu ul lt ta an ne eo ou us s m me ea as su ur re em me en nt t o of f c co ol ll la ag ge en n t ty yp pe e--V VI I--r re el la at te ed d a an nt ti ig ge en n a an nd d p pr ro oc co ol ll la ag ge en n t ty yp pe e--I II II I--N N--p pr ro op pe ep pt ti id de e l le ev ve el ls s i in n b br ro on nc ch ho oa al lv ve eo ol la ar r l la av va ag ge e Biochemical parameters which are correlated with collagen synthesis and degradation may be helpful to monitor fibrosis. In this study, we compared the sensitivity and specificity of procollagen type-III-N-propeptide (PIIINP) and collagen type-VI (C-VI) related antigen levels, as well as a ratio of both parameters (PIIINP/C-VI), in bronchoalveolar lavage fluid (BALF) from patients with diffuse and localized lung disease. We investigated 45 patients with diffuse lung disease (idiopathic pulmonary fibrosis (IPF), n=21; sarcoidosis, n=13; and lymphangitic carcinomatosis (LC), n=11); 58 control subjects; and 92 patients with localized lung disease (bronchial carcinoma, n=37; pulmonary tuberculosis, n=31; and pneumonia, n=24). C-VI and PIIINP were measured by immunoassay in concentrated BALF.Although the PIIINP and C-VI levels were increased in diffuse lung disease, the sensitivity of the individual parameters PIIINP and C-VI was low ( Simultaneous measurement of C-VI and PIIINP in BALF from patients with diffuse chronic lung diseases may be a more sensitive approach to assess disturbances in collagen metabolism than the determination of each single parameter. Eur Respir J., 1994Respir J., , 7, 1221Respir J., -1226

The interval required for haematological reconstitution following myelosuppressive chemotherapy can be reduced by the infusion of autologous peripheral blood progenitor cells (PBPCs). When carboplatin (C) and paclitaxel (P) are followed by granulocyte colonystimulating factor (GCSF), multiple courses can be given at 10-day intervals with the autologous PBPCs from a unit of whole blood with each cycle. We extended this approach and defined the dose-limiting toxicity and maximum-tolerated dose for the addition of gemcitabine (G) to CP for patients (pts) with EOC in a phase I -II study of increasing doses of G (0, 800, 1000 and 1250 mg m À2 ) over four cohorts with C at area under curve (AUC) 6, plus P at 175 mg m À2 3 h À1 every 10 days for six cycles. Granulocyte colonystimulating factor 5 mg kg À1 day À1 was given s.c. days 1 -10 and 450 ml whole blood was venesected before each treatment, stored untreated at 41C and reinfused 24 h later. In all, 17 patients with EOC either bulky stage IV or recurrent after treatment-free interval 412 months were treated over 30 months. Of the 17 patients, 13 completed six cycles (one patient stopped early with PD, three with toxicity), interdose interval 9 -28 (median 10) days. Delays occurred in four patients due to infection or malaise, and there were no dose reductions. Haematological toxicity was not considered to be dose limiting. Febrile neutropenia was uncommon (2 patients), but grade III/IV thrombocytopenia was seen across all cohorts. Treatment was not delayed for thrombocytopenia and no bleeding complications occurred. Grade III transaminitis was seen in all patients in cohort 4 and grade IV toxicity, considered to be dose limiting, occurred in one. Responses were observed at all dose levels with six CR, seven PR, three SD and one PD. Dose intense GCP was deliverable over six cycles with manageable haematological toxicity, but with dose-limiting hepatic toxicity in cohort 4. The MTD was gemcitabine 1000 mg m À2 , carboplatin AUC 6, paclitaxel 175 mg m À2 given every 10 days for six cycles.

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