Pretreatment plasma levels of fibrinopeptide-A (FPA), D-dimer (DD), and von Willebrand factor (vWF) in patients with ovarian carcinoma.

The preoperative plasma levels of fibrinopeptide-A (FPA), D-dimer (DD), and von Willebrand Factor (vWF) were measured in 125 patients with ovarian masses undergoing laparotomy and in 88 healthy nonpregnant women as controls. FPA, DD, and vWF levels were significantly higher in the 58 patients with ovarian carcinoma than in the 67 patients with benign ovarian disease or controls. FPA and DD values were significantly higher in advanced (FIGO stage III-IV) than in early ovarian carcinoma. Among patients with advanced disease, FPA and DD levels correlated with none of the common clinicopathological prognostic variables; conversely, vWF values were related to FIGO stage (IV versus III, P < 0.02) and size of residual disease after initial surgery (> 2 cm versus < or = 2 cm, P < 0.05). In conclusion, increased fibrin production and degradation occur in patients with ovarian carcinoma.

Treatment of amiodarone iodine-induced thyrotoxicosis with plasmapheresis and methimazole.

The present report illustrates the clinical and biochemical outcome in two amiodarone iodine-induced thyrotoxicosis (AIIT) patients submitted to plasmapheresis. Amiodarone was discontinued, and treatment with MMI (40 mg/day) was started. In addition, patients were submitted to two sessions of plasma-exchange, with a one-day interval between the two session. In both patients serum total T3 (TT3) and free T3 (FT3) concentrations decreased promptly but in contrast to the serum TT3, FT3 levels remained steadily above the normal range. A similar behaviour was observed for total T4 and free T4 plasma concentrations. Interestingly, a clearcut clinical amelioration was observed in both patients even before a reduction of circulating free thyroid hormone concentrations could be documented. In conclusion, our experience indicates that plasmapheresis may be useful in order to obtain a rapid amelioration of severe clinical picture of thyrotoxicosis, but cannot be considered as a definite therapy in AIIT. It should be considered that plasmapheresis is not devoid of risks and is also a very expensive procedure.

Pretreatment plasma levels of fibrinopeptide-A (FPA), D-dimer (DD), and von Willebrand factor (vWF) in patients with operable cervical cancer: influence of surgical-pathological stage, tumor size, histologic type, and lymph node status.

The preoperative plasma levels of fibrinopeptide A (FPA), D-dimer (DD), and von Willebrand Factor (vWF) were measured in 38 patients with cervical cancer undergoing radical hysterectomy with pelvic lymphadenectomy. The surgical-pathological stage of disease was Ib in 17 patients, IIa in 9 patients, and IIb in 12 patients. The tumor size was < or = 4 cm in 20 patients and > 4 cm in 18 patients. The histologic type was squamous cell carcinoma in 32 patients and adenocarcinoma in 6 patients. Positive pelvic lymph nodes were found in 10 patients. When compared to controls, FPA, DD, and vWF levels were significantly raised in patients with surgical-pathological stage IIb disease but not in patients with stage Ib or IIa disease. The values of FPA, DD, and vWF were related to surgical-pathological stage (stage IIb vs stage Ib-IIa: P < 0.005, P < 0.001, and P < 0.001, respectively) and tumor size (> 4 cm vs < or = 4 cm: P < 0.05, P < 0.005, and P < 0.02, respectively), but not to histologic type. vWF values were also related to lymph node status (positive vs negative lymph nodes: P < 0.02). FPA and DD levels were higher in patients with positive lymph nodes than in patients with negative lymph nodes, but the difference did not reach the statistical significance even due to the small number of patients involved. In conclusion, increased fibrin production and degradation seem to occur in patients with stage IIb cervical cancer. The biological meaning of this hemostasis activation deserves further investigation.

Antibodies to hepatitis C virus in patients with mixed cryoglobulinemia.

The prevalence of antibodies to hepatitis C virus (HCVAb) was investigated in 52 unselected patients with mixed cryoglobulinemia and in 84 patients with other systemic immunologic diseases. HCVAb were detected by an enzyme-linked immunosorbent assay, and their specificity was evaluated by a recombinant-based immunoblot assay. The presence of HBV-related markers was investigated in the same samples. HCVAb were found in 54% of mixed cryoglobulinemia patients, and the finding was confirmed by recombinant-based immunoblot assay in all cases. HCVAb and/or HBV markers were present in 70% of the patients. HCVAb seropositivity was significantly more frequent in mixed cryoglobulinemia patients with biopsy-proven liver involvement (P less than 0.01) and with increased serum transaminase levels (P less than 0.01). HCVAb were virtually absent in control patients with other immunologic diseases. These results support the notion that viral agents, i.e., HCV and possibly HBV, have a role in the pathogenesis of mixed cryoglobulinemia patients.

Antibodies against hepatitis C virus in mixed cryoglobulinemia patients.

The prevalence of antibodies against hepatitis C virus (anti-HCV) in an unselected series of 45 mixed cryoglobulinemia patients was assessed by an enzyme linked immunosorbent assay (Chiron ELISA HCV, Second Generation). The anti-HCV specificity was evaluated by a recombinant based immunoblot assay (Chiron RIBA HCV, Second Generation Assay). HBV-related markers and HIVAb were detected in the same samples. The prevalence of anti-HCV observed in mixed cryoglobulinemia was compared with 80 patients with other immunological systemic diseases. Anti-HCV were found in 91% of mixed cryoglobulinemia patients, and confirmed by RIBA in all cases; on the other hand, anti-HCV were practically absent in other control diseases. HBV markers were recorded in 49% of mixed cryoglobulinemia subjects; while HIVAb were constantly absent. These data give us new insights into the etiopathogenesis of mixed cryoglobulinemia.

Exploring the mechanisms of in vivo regulation of liver protein breakdown in the rat by the use of the new antilipolytic-agent model.

In this study, we explored the changes in the rate of protein degradation in liver cells in vivo, using a method based on the physiological stimulation of liver autophagy. Male albino rats 1, 2, 6, 12 and 24 months old were fasted overnight, and then received an injection of the antilipolytic agent 3,5-dimethylpyrazole (DMP) to evoke a sudden shortage of lipid fuel. A comparison was made with the in vivo effects of glucagon by giving the 2-month-old group an intraperitoneal injection of this hormone. Samples of liver were taken after 0, 15, 20, 30, 60 and 150 min and processed for electron microscopy, and groups of rats were subjected to short-term single pass liver perfusion. Results show that in the younger age-groups, the DMP stimulation of liver autophagy and amino acid release is highly significant, and compares favourably with the glucagon model of induction of the autophagic process. With older rats, an age-related longer time-lag of the autophagic response and a decrease in the effect of DMP were observed. In conclusion, hormones may activate autophagy, whereas levels of plasma amino acids may tune down the process to adjust the availability of the substrate to tissue needs.

Plasma exchange with prostaglandin I2 and ACD solution: comparative effects.

Discontinuous plasma exchange with prostaglandin I2 (5 ng/kg/min) and low dosage heparin (5-6 IU/kg/min) (treatment I), and ACD solution alone (treatment II) was studied. During both treatments the activated partial thromboplastin time remained within the normal range. After treatment I platelet count was not decreased but in vitro platelet aggregation was reduced (p less than 0.001). After treatment II platelet count was reduced and in vitro platelet aggregation unchanged. Prostaglandin I2 at this dosage caused no cardiovascular complications. The physiopathological implications of these differences are discussed.

Plasma-exchange in mixed cryoglobulinemia. Effects on renal, liver and neurologic involvement.

Prolonged plasma-exchange without addition of cytotoxic agents was employed in 16 patients with mixed cryoglobulinemia and kidney, liver or neurologic involvement. Patients with rapidly progressive renal failure or active and reversible lesions generally improved after plasma-exchange, as well as those with a recently occurring sensory-motor peripheral neuropathy. In 4 out of 6 patients with mixed cryoglobulinemia and chronic active hepatitis, plasma-exchange was followed by either normalization or significant reduction of liver enzymes and bromosulfophthalein retention. In all cases responding to plasma-exchange the beneficial effects were evident after the first 2-3 weeks of treatment, while symptoms did not generally recur when the procedures were either slowly tapered or discontinued. Although the pathogenetic mechanism(s) of action of plasma-exchange remains largely unknown, preliminary data indicate that these procedures induce quantitative as well as qualitative changes in the immune system.

Treatment of the renal involvement in mixed cryoglobulinemia with prolonged plasma exchange.

Nine patients with mixed cryoglobulinemia and severe membranoproliferative glomerulonephritis were treated with plasma exchange alone or in combination with medium to low amounts of corticosteroids, but never with cytotoxic drugs. In 5 patients renal function and/or proteinuria improved after plasma exchange, and no clinical relapse usually occurred when the procedures were reduced or discontinued. These procedures seemed of particular effect in the presence of histologically active and not irreversible lesions and rapid deterioration of renal function. While cryocrit almost invariably decreased, circulating immune complex or complement levels were unpredictably affected by plasma exchange. Cryocrit, but not immune complex or complement levels, was the serological parameter which most often closely correlated with signs of renal involvement (i.e., proteinuria and/or serum creatinine). Thus, plasma exchange might be a safe and useful tool in the treatment of an often drug-resistant and rapidly progressive renal involvement occurring in patients with mixed cryoglobulinemia.

Immune complex behaviour during prolonged plasma exchange in essential mixed cryoglobulinemia and systemic lupus erythematosus.

A number of immunological parameters were measured in 9 patients with essential mixed cryoglobulinemia and 12 patients with systemic lupus erythematosus undergoing plasma exchange alone or without cytotoxic drugs. Only cryocrit significantly decreased in the majority of patients with essential mixed cryoglobulinemia. In contrast, immune complex levels, measured in two different ways, did not change on the whole, although variable and unpredictable changes were often present in individual patients. Thus, these data do not support the view that the mechanism(s) of action of plasma exchange in these diseases is only due to the quantitative removal of circulating immune complexes, and qualitative changes in the immune complex moiety may also occur.

Prolonged plasma exchange in the treatment of renal involvement in essential mixed cryoglobulinemia.

Four men and 2 women with Essential Mixed Cryoglobulinemia and a membrano-proliferative glomerulonephritis were treated with prolonged Plasma Exchange without the addition of cytotoxic agents. All patients had Nephrotic Syndrome and Renal Insufficiency. Three of them presented a rapid deterioration of renal function just prior to Plasma Exchange treatment. Total number of procedures varied for each patients from 24 to 105. Serum creatinine decreased significantly in those patients with rapid deterioration of renal function, while it was not modified in the 3 with stable chronic renal failure. In no instance major side effects were recorded, and relapses of the disease did not occur, after gradually tapering of Plasma Exchange sessions. These data suggest that Plasma Exchange alone, if early instituted, may be an effective and safe treatment of Essential Mixed Cryoglobulinemia Glomerulonephritis.