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Biomedical subjects

I Yudelman

Publications and source records attributed to I Yudelman.

7 recordsLinked to original sources
PubMed1995

Chemotherapy rapidly alternating with twice-a-day accelerated radiation therapy in carcinomas involving the hypopharynx or esophagus: an update.

Laboratory studies have suggested that rapidly alternating chemotherapy and radiation therapy might act synergistically. We undertook this study to evaluate the toxicity and effectiveness of this approach in patients with carcinoma involving the hypopharynx or esophagus. Between 1987 and 1991, we treated 47 patients (23 with carcinoma involving the hypopharynx and 24 with carcinoma involving the esophagus) by three cycles of chemotherapy (during weeks 1, 4, and 7) rapidly alternating with twice-a-day radiation therapy (during weeks 2, 5, and 8). Chemotherapy consisted of cisplatin 100 mg/m2 and 5-fluorouracil 3-4 g/m2 given over 4 days. Radiation therapy consisted of 180-200 cGy twice each day to 2000 cGy/cycle, total 6000 cGy over 7 weeks. The histology was squamous cell carcinoma in 44 patients and adenocarcinoma in 3 patients with esophagus cancer. Median follow-up is 2 years (range 1-5 years). The observed survival rate for all 47 patients was 54% at 1 year and 38% at 2 years. Acute toxicity was considerable. Twelve patients (25%) died during therapy from toxicity, without tumor progression, leaving 35 patients (18 hypopharynx, 17 esophagus) evaluable for response. Among the hypopharyngeal patients, 83% had a complete response, 11% had a partial response, and 6% had no response. Among the esophageal patients, 94% had a complete response, and 6% had a partial response. Local control was better for the esophageal patients than the hypopharyngeal patients (98% vs. 52% at 2 years, p = 0.038). The incidence of distant metastases was 25% at 2 years and not significantly different between the two groups. A high rate of local control was achieved, particularly in esophageal cancer, by delivering chemotherapy and radiation therapy in a rapidly alternating fashion. This was achieved at a considerable cost in terms of toxicity, however. Although our response rates and local control compare favorably with those of other recently published studies of combined modality therapy in esophagus or head and neck cancer, much additional work is required to reduce the toxicity and, in hypopharyngeal cancer, to further improve the local control.

Adenocarcinoma↗
PubMed1987

Indices of fibrinogen proteolysis and platelet activation during the resolution of pulmonary embolism.

Indices of fibrinogen cleavage by thrombin (fibrinopeptide A, FPA); by plasmin (BB1-42 and serum FDP); of the platelet release reaction (beta thromboglobulin and platelet factor 4); and antithrombin III (AT III) levels were measured serially in 46 patients with pulmonary emboli in whom either substantial (SR) or impaired (IR) resolution was documented. The mean FPA level in the 25 patients with IR was significantly higher than the level in the 21 patients with SR (p less than 0.01). The increased thrombin activity in the IR group was not due to AT III deficiency or increased platelet reactivity but the elevated FPA levels in the presence of therapeutic levels of anticoagulation indicated that the dose of heparin was inadequate. The higher BB1-42 and FDP levels in this group reflected the increased plasmin activity that follows increased thrombin activity. In a multivariate discriminant analysis, only the FPA data could be used to predict the degree of resolution. Increased thrombin action impairs resolution presumably by producing greater amounts of accreted fibrin on the impacted embolus.

Antithrombin III↗
PubMed1982

Factors affecting fibrinopeptide-A levels in patients with venous thromboembolism during anticoagulant therapy.

The prompt reduction of elevated fibrinopeptide A (FPA) levels (normal less than 1.3 pmole/ml) by heparin therapy in patients with thromboembolism suggests that measuring the FPA level may provide a good index of disease activity and be a useful method of monitoring therapy. Sepsis or malignancy may elevate FPA levels and coexist with thromboembolism. FPA levels were surveyed in 51 patients with thromboembolism (including 15 with concurrent sepsis or malignancy) during heparin treatment in an attempt to distinguish the effects of coexistent disease and the progression of thromboembolism. The anticoagulant effect of heparin was within the therapeutic range for 81% of the study period. In patients with thromboembolism alone and marked resolution of emboli on repeat lung scan, the mean daily FPA levels were lower than the values in patients with minimal resolution (p less than 0.005). In patients with marked resolution of pulmonary embolism or venous thrombosis and a concurrent disorder, the mean FPA level remained elevated compared to normal values in patients with thromboembolism alone. These results suggest that FPA levels monitored during heparin therapy of thromboembolism may be useful as an index of disease activity except in the presence of coexisting sepsis or malignancy.

Adenocarcinoma↗
PubMed1979

Sequence of fibrinogen proteolysis and platelet release after intrauterine infusion of hypertonic saline.

Plasma fibrinopeptide B (Bbeta1-14 or FPB) immunoreactivity was studied by radioimmunoassay in patients who received intrauterine infusion of hypertonic saline to terminate pregnancy. FPB immunoreactivity increased with thrombin treatment (TIFPB) suggesting the presence of a larger FPB-containing peptide, since purified FPB is not altered by thrombin, whereas thrombin increases the immunoreactivity of Bbeta1-42 (which includes FPB) 10-fold. TIFPB immunoreactivity in plasma, drawn 4 h after hypertonic saline infusion eluted from Sephadex G-50 similarly to isolated Bbeta1-42. Streptokinase, incubated with normal plasma progressively generated TIFPB immunoreactivity, which showed a major component which eluted from Sephadex G-50 similarly to Bbeta1-42. Streptokinase generated TIFPB much more rapidly in reptilase-treated plasma that contains fibrin I, (which still includes FPB), indicating that fibrin I is preferred over fibrinogen as a substrate for plasmin cleavage of arginine (Bbeta42)-alanine (Bbeta43). Serial studies were then made in 10 patients receiving intrauterine hypertonic saline. Fibrinopeptide A (FPA) levels rose immediately, reached a peak between 1 and 2 h, were declining at 4 h, and were normal at 24 and 48 h. TIFPB levels rose slightly in the 1st h, reached a peak at 4 h, and had returned to base-line values at 24 h. Serum fibrinogen degradation product levels were unchanged at 1 h, reached their highest level at 4 h, and were still markedly elevated at 24 and 48 h. Fibrinogen levels dropped slightly being lowest at 4 and 24 h. Platelet counts declined in parallel with the fibrinogen levels over the first 4 h, but continued to decrease through 48 h. Beta thromboglobulin (betaTG) levels generally paralleled FPA levels whereas platelet factor 4 (PF4) levels showed only slight changes. The data indicate that immediately after intrauterine hypertonic saline infusion thrombin is formed that cleaves FPA from fibrinogen to produce fibrin I and releases betaTG and PF4 from platelets. Later plasmin cleaves Bbeta1-42 from fibrin I to produce fragment X, which is further degraded to form serum fibrinogen degradation products. This sequence of proteolysis indicates that plasmin action on fibrin I serves as a mechanism that regulates fibrin II formation by removing the Bbeta chain cleavage site, which is required for thrombin action in converting fibrin I to fibrin II.

Abortion, Induced↗
PubMed1974

Measurement of fibrinopeptide A in human blood.

Since thrombin cleaves fibrinopeptides A (FPA) and B from the NH(2)-terminal end of the fibrinogen molecule, measurement of fibrinopeptide levels in plasma may provide a direct index of thrombin action. Recently a radioimmunoassay for FPA has been developed, and in the present paper, we describe the application of this assay to the measurement of FPA levels in clinical blood samples. Since fibrinogen cross-reacts with antibodies to FPA, dialysis was used to extract the peptide from plasma. In vitro generation of FPA was prevented by removing the fibrinogen from the plasma by precipitation with ethanol before dialysis. The processing technique permitted recovery of 75% of FPA added to blood in vitro. Evidence that the immunoreactivity measured in plasma is due to FPA was provided by the results of experiments in which two antisera to FPA with different specificities showed comparable results and addition of thrombin caused no change in immunoreactivity. In contrast, extracts of streptokinasetreated plasma showed a five-fold increase in activity when treated with thrombin and markedly different immunoreactivity with the two antisera. Plasma FPA levels in 30 normal men were below 2 ng/ml, with a mean of 0.5 ng/ml. FPA levels in 12 patients with reduced fibrinogen levels or reduced platelet counts or both ranged between 4 and 289 ng/ml. FPA levels in 13 patients with normal or elevated fibrinogen levels, including 6 patients with clinical evidence of venous thrombosis or pulmonary embolism or both, ranged between 5 and 23 ng/ml. FPA and fibrinogen degradation product levels did not correlate, and in several patients, elevated FPA levels were found in the presence of normal fibrinogen degradation product levels. After infusion of FPA-containing solutions in four normal individuals, FPA showed a disappearance rate from the plasma consistent with a t((1/2)) of 3-5 min. Heparin infusions in six patients with venous thrombosis or pulmonary embolism or both and elevated FPA levels were followed by a prompt decline in FPA level at a mean rate equivalent to a 3-5 min t((1/2)).

Anticoagulants↗