Isolation and properties of an abnormal Hageman factor (Factor XII) molecule in a cross-reacting material-positive hageman trait plasma.

We have previously described two unrelated individuals with homozygous Hageman trait (Factor XII deficiency) whose plasmas contained nonfunctional material immunologically indistinguishable from normal Hageman factor (HF). Abnormal HF from the plasma of one these subjects has now been purified to homogeneity, as judged by sodium dodecyl sulfate-polyacrylamide gel electrophoresis, alkaline disc gel electrophoresis, and immunoelectrophoresis. Purified abnormal HF had no clot-promoting activity, but showed the same specific antigenicity as purified normal HF by an immunoassay. The abnormal HF was of a single chain polypeptide with the same molecular weight (80,000) as normal HF and was positively stained by periodic acid-Schiff reagent. Both normal and abnormal HF had similar amino acid compositions and isoelectric points (pI 6.5 approximately 7.1). When 125I-labeled abnormal HF and 131I-labeled normal HF were mixed with normal plasma and exposed to glass, both HF underwent an identical pattern of cleavage, yielding 52,000- and 30,000-mol wt fragments. Similarly, abnormal HF was fragmented by trypsin in the same way as normal HF, but no prekallikrein-activating activity was generated after cleavage. [3H]Diisopropyl phosphorofluoridate was incorporated into a 29,000-mol wt fragment of the trypsin-cleaved normal HF, but not into that of the trypsin-cleaved abnormal HF. These data suggest that the molecular defect in this abnormal HF resides at or near the active site serine residue in the 30,000-mol wt part of the molecule.

Alterations in platelet surface sialytransferase activity and platelet aggregation in a group of cancer patients with a high incidence of thrombosis.

Platelet aggregation, platelet surface sialic acid, and platelet surface sialytransferase activity were studied in a group of 12 cancer patients with a high incidence of thrombosis. These patients demonstrated accelerated coagulation, increased Factor VIII antigen and restocetin cofactor, and enhanced adenosine 5'-diphosphate-induced platelet aggregation. Platelet exogenous sialytransferase activity was increased in cancer patients (117.6 +/- 14 pmol/10(9) platelets) as compared to controls (59.0 +/- 4.3 pmol/10(9) platelets, p less than 0.01). Platelet exogenous sialytransferase activity and platelet aggregation were inhibited by aspirin. Thrombosis and bleeding have complicated the clinical course of half of these patients. This platelet membrane analysis provides additional data which may be related to current observations of increased levels of plasma sialytransferase activity and serum sialic acid in cancer patients.

A study of infusional cisplatin and infusional fluorouracil for locally advanced or metastatic non-small-cell lung cancer: a Mid-Atlantic Oncology Program study.

A combination of cisplatin administered as a 24-hour infusion and fluorouracil administered as a 5-day infusion was used to treat 97 patients with non-small-cell lung (NSCLC) cancer in a phase II trial. Thirty patients had stage IIIB disease; 67 patients, stage IV disease (new international classification). Patients with stage IIIB disease also received thoracic radiation after chemotherapy. The regimen was well tolerated, with 24% or less grade 3 or greater toxicities of all types. One toxic death was attributed to fluid overload. The response rate, partial and complete, was 43% (95% confidence interval, 27% to 63%), and median survival was 13.8 months for patients with stage IIIB disease. Response rates refer to the chemotherapy response. For patients with stage IV disease, the response rate was 34% (95% confidence interval, 24% to 47%), and median survival was 6.2 months. On this regimen, stable-disease patients with stage IV disease had survivals at least equal to responders.

Alveolar rhabdomyosarcoma associated with disseminated intravascular coagulation and a unique factor VIII antigen.

Disseminated intravascular coagulation (DIC) has been described in association with many tumors. We describe a patient with alveolar rhabdomyosarcoma in whom DIC developed with the initiation of chemotherapy. The patient achieved complete remission of his tumor for 14 months. An unusual factor VIII antigen was identified on crossed immunoelectrophoresis that was present at initial diagnosis, disappeared with remission, and returned with relapse of the tumor.

Heparin monitoring by activated partial thromboplastin time. Comparison of ex vivo measurement and in vitro standardization.

Twenty patients were studied prospectively during heparin therapy. Three activated partial thromboplastin time (APTT) reagents were used to compare APTT values with plasma heparin levels during induction of heparin and transition of heparin to coumadin. A heparin in vitro dose APTT response curve and a heparin ex vivo curve were established. The in vitro sensitivity curves using different reagents were varied at therapeutic heparin levels. In contrast, the APTT reagents did not differ ex vivo. The in vitro curves demonstrated poor performance. Sixty percent of the patients did not adequately compare by APTT estimation of plasma heparin levels. An APTT ratio (1.5 to 2.5) using the patient's baseline APTT as the denominator demonstrated better representation of heparin levels. The in vitro APTT curves are inappropriate for heparin monitoring.

Endobronchial metastatic plasmacytoma.

Plasmacytomas are rare tumors and an endobronchial presentation has not been previously described. A 64-year-old white woman with metastatic involvement by plasmacytoma is presented. A review of the literature indicates the difficulty in distinguishing this lesion from benign plasma cell tumors of the lung and the prolonged follow-up often necessary to reveal metastatic behavior. Careful observation in this case led to the demonstration of metastatic lung and endobronchial lesions without the development of abnormal proteinuria or overt myeloma. The literature would suggest a key role for radiation therapy in treatment. The role of chemotherapy remains to be defined.

Functional recovery in cancer rehabilitation.

OBJECTIVE: To assess the impact of inpatient rehabilitation on the motor and cognitive functional status of cancer patients, and to determine whether cancer diagnosis, rehabilitation impairment, physician-determined rehabilitation goals, and active cytotoxic treatment affect the magnitude of functional improvement. DESIGN AND SETTING: A retrospective, case series of patients with an oncology diagnosis undergoing inpatient rehabilitation at a rehabilitation hospital. PARTICIPANTS: A sample of 200 patients admitted for rehabilitation services due to disability resulting from impairments caused by cancer or its treatment. INTERVENTION: Comprehensive multidisciplinary inpatient rehabilitation. OUTCOME MEASURES: Function status was measured using the motor and cognitive measures of the Functional Independence Measure. RESULTS: All patients made significant gains in motor function regardless of diagnostic group, rehabilitation impairment group, rehabilitation goal group, and cytotoxic treatment status. The magnitude of motor function gain was not equivalent across all impairments and rehabilitation goals. Significant gains in cognitive function were made by all patients except those with intracranial neoplasms, central nervous system dysfunction, and palliative rehabilitation goals. CONCLUSION: Inpatient rehabilitation can improve both motor and cognitive function in patients with disability resulting from impairments caused by cancer or its treatment.

Acquired platelet dysfunction following mithramycin therapy.

The administration of mithramycin to patients with testicular tumors has been accompanied by a hemorrhagic diasthesis, often in the absence of thrombocytopenia. Bleeding time, platelet aggregation, platelet adenine nucleotide levels, and coagulation factor assays were studied in three patients receiving mithramycin for embryonal testicular carcinomas. These studies demonstrated a drug dependent, reversible hemorrhagic diathesis associated with (1) prolongation of bleeding time, (2) decreased platelet aggregation responses to ADP, collagen, and epinephrine, and (3) depleted platelet stores of ADP in the absence of thrombocytopenia. These abnormalities were temporally correlated with the onset of mucocutaneous bleeding in all patients.

Molecular heterogeneity of Hageman trait (factor XII deficiency): evidence that two of 49 subjects are cross-reacting material positive (CRM+).

We have studied plasmas of 49 individuals with homozygous Hageman trait from 42 kindreds, all of which contained less than 1% of the Hageman factor (factor XII) clotting activity of pooled normal plasmas. Forty-seven plasmas contained less than 1% of Hageman factor antigen. In two other, unrelated individuals with Hageman trait, nonfunctional material immunologically indistinguishable from normal Hageman factor was detected in plasma by radioimmunoassay at concentrations of 39% and 80%, respectively. These plasmas did not contain circulating anticoagulants against Hageman factor and, as in ordinary Hageman trait, displayed impaired surface-mediated plasma reactions such as fibrinolysis and kinin generation. Upon immunodiffusion against anti-Hageman factor serum, these plasmas formed a single precipitin line of complete identity with normal plasma or purified Hageman factor. Upon immunoelectrophoresis, the precipitin line had the same mobility as normal Hageman factor. Nonfunctional Hageman factor and normal Hageman factor behaved identically on a Sephadex G-150 column (apparent MW = 100,000) and on sucrose density-gradient centrifugation (4.5S). Nonfunctional Hageman factor was adsorbed to kaolin as readily as normal Hageman factor, suggesting that the binding site to negatively charged surfaces is different from functional sites. Antiserum raised against Hageman factor-like material in a CRM+ Hageman trait plasma specifically inactivated Hageman factor activity in normal plasma. The plasmas of three heterozygotes in these families contained approximately twice as much Hageman factor antigen as Hageman factor activity, whereas those of 16 heterozygotes in ordinary (CRM-) Hageman trait families contained approximately equal amounts of activity and antigen. The present study indicates that rarely homozygous Hageman trait may be CRM+ and that this defect is genetically determined.

A heparin-like anticoagulant as part of global abnormalities of plasma glycosaminoglycans in a patient with transitional cell carcinoma.

A patient is described in whom a circulating heparin-like anticoagulant developed during the terminal course of metastatic transitional cell carcinoma. The anticoagulant, which was identified as heparan sulfate, was the clinical sign of global abnormalities in the patient's plasma glycosaminoglycans. Subsequent analysis disclosed increased amounts of chondroitin sulfate as well as heparan sulfate. In addition, the charge density and molecular weight of the patient glycosaminoglycans and their organization into proteoglycans differed significantly from glycosaminoglycans isolated from normal plasma samples.