The Potential of F-18-FDG PET in Breast Cancer. Detection of Primary Lesions, Axillary Lymph Node Metastases, or Distant Metastases.

This retrospective study was done to evaluate the utility of 2-[F-18]fluoro-2-deoxy-D-glucose positron emission tomography (F-18-FDG PET) in identifying primary and recurrent breast cancer and lymph node metastases. One hundred whole-body PET scans of 87 patients were reviewed. PET results obtained with F-18-FDG and an ECAT/EXACT-921 or an ECAT-931 (Siemens/CTI) were based on visual interpretation, or standardized uptake values (SUVs), related to histology and also compared to computerized tomography (CT) and mammography results. The sensitivity for PET in detecting primary (N = 35 studies) and recurrent breast cancer (N = 65 studies) was 96% and 85% with a specificity of 91% and 73%. The sensitivity for lymph node metastases at the time of initial diagnosis was 100% with a specificity of 100%. Quantitative SUV information did not improve the accuracy of F-18-FDG PET in identifying primary breast cancers. The results suggest that whole-body PET is useful in detecting recurrence or metastases, may be useful in detecting lymph node metastases prior to initial axillary lymph node dissection, but is less sensitive in excluding axillary lymph nodes metastases later in the course of the disease.

The use of intermediate and high purity factor VIII products in the treatment of von Willebrand disease.

Since 1985, viral-attenuated blood products have been available for the treatment of patients with hemophilia. Unfortunately, similar viral-attenuated blood products, enriched for von Willebrand factor (vWF), have not been readily available for the treatment of patients with von Willebrand disease (vWD). In the current study, we examined the clinical efficacy and in vivo properties of two viral-attenuated factor VIII products, Koate-HS and Koate-HP, in the treatment of patients with vWD. Twenty-one (21) infusions were evaluated in 17 different vWD patients (4 with type IA; 8 with Type IIA; 1 with Type IID; 4 with type III). Seven (7) patients received Koate-HS and 12 patients received Koate-HP (2 patients received both products; 1 patient was studied three times). Von Willebrand factor antigen, ristocetin cofactor, bleeding time, and the multimeric composition of vWF were determined pre- and post-infusion. Complete or partial correction of prolonged bleeding times was observed in 2 of the 6 patients tested following treatment with Koate-HS and in 7 out of 11 patients tested following treatment with Koate-HP. Surgery was performed on five of these patients, two of whom were treated with Koate-HS and three of whom were treated with Koate-HP. In the surgical patients, clinical hemostasis was achieved regardless of whether the bleeding time was corrected. We conclude that both Koate-HS and Koate-HP can be utilized successfully in the treatment of patients with vWD in spite of the lack of high molecular weight multimers of vWF in these products.(ABSTRACT TRUNCATED AT 250 WORDS)

Analysis of the relationship of von Willebrand disease (vWD) and hereditary hemorrhagic telangiectasia and identification of a potential type IIA vWD mutation (IIe865 to Thr).

Reports of families with members affected with both von Willebrand disease (vWD) and hereditary hemorrhagic telangiectasia (HHT) suggest a possible relationship between these two disorders. vWD, the most common inherited bleeding disorder in humans, is due to either a quantitative or qualitative defect in von Willebrand factor (vWF). The gene for vWF has been cloned and mapped to chromosome 12 (12p12----12pter). HHT, an uncommon inherited bleeding disorder, is characterized by malformed, dilated, fragile blood vessels. The chromosomal location of the gene for HHT is unknown. We studied two families by RFLP analysis to determine whether there is a molecular basis for the association of vWD and HHT. Family A is affected with both type IIA vWD and HHT; family B is affected with HHT alone. Linkage of HHT to the vWF gene was not detected, and vWF was ruled out as a candidate gene for HHT. The vWF gene was found to be tightly linked to type IIA vWD in family A (lod score 3.61 at recombination fraction .00). By PCR and DNA sequence analysis of vWF exon 28, a single T----C transition resulting in the substitution of Thr for Ile865 was identified. This substitution is located immediately adjacent to two previously identified type IIA vWD mutations.

Spurious polycythemia and renal malignancy.

We have described a 19-year-old woman with polycythemia. Based on a normal red cell mass and decreased plasma volume, spurious polycythemia was diagnosed. CT scan of the abdomen revealed a 4 cm mass in the right kidney. Upon right nephrectomy, the mass was found to be an unusual neoplasm of the renal tubular epithelium. Four weeks postoperatively, both the hemoglobin and hematocrit values were normal.

1-Deamino-8-D-arginine vasopressin and cryoprecipitate in variant von Willebrand disease.

The effect of infusing DDAVP and cryoprecipitate either singly or in combination was studied in a patient with variant von Willebrand disease. Both DDAVP and cryoprecipitate caused only partial correction in the hemostatic defect when used as a single agent. A combination of DDAVP and cryoprecipitate induced a complete correction of the hemostatic defect as well as factor VIII related properties.

Variant of congenital dyserythropoietic anemia.

Nonspherocytic hemolytic anemia was diagnosed in a 34-year-old man with jaundice since childhood. Splenectomy at the age of 8 had no influence on the anemia. Bronze diabetes was diagnosed at age 31, presumably due to hemosiderosis and secondary hemochromatosis. Iron chelation was unsuccessful in controlling iron overload, but phlebotomies proved effective without aggravating the anemia. We believe the anemia represents a variant of congenital dyserythropoietic anemia, type I.

Radioimmunoassay of fragment E-related neoantigen: validation studies and clinical application.

Measurement of fibrinogen-fibrin degradation products (FDP) levels in plasma may provide a direct index of plasmin action, and increased levels of FDP would indicate coagulopathy. We have established an E-neoantigen radioimmunoassay ( Eneo RIA) that can determine normal and pathological plasma levels of E-related FDP. The assay employs rabbit antiserum produced against fragment E derived from a plasmin digest of fibrinogen and subsequently absorbed with fibrinogen. The absorbed antiserum contains antibodies which are equally reactive with fibrinogen derived E (Fg-E) and fibrin derived E (Fb-E) but not with fibrinogen at 1 mg/ml. The Eneo RIA was validated by assay parallelism and by recovery experiments. Plasma Eneo immunoreactivities in 14 normals were 4-22 ng/ml (mean 12.7 ng/ml). Plasma Eneo levels in 23 of 24 patients with neoplastic and haematological diseases were elevated above normal (range 27-2027 ng/ml). Unusually high Eneo values were observed with three patients whose diseases were complicated by either disseminated intravascular coagulation (DIC) or deep vein thrombosis. After heparin therapy, the Eneo level of a patient with chronic DIC declined. A pathological plasma was eluted from a Sephadex G-200 column and Eneo immunoreactivity was determined on the eluates. The gel filtration pattern of Eneo indicates that E-related FDP is a family of plasmic fragments derived from crosslinked fibrin.

Renal disease after mitomycin C therapy.

Fourteen patients with adenocarcinoma of the gastrointestinal tract and pancreas treated with mitomycin C(MMC) and 5-fluorouracil (5-FU) had renal impairment 6-11 months from the beginning of MMC therapy. Two clinical entities were recognized: an acute fulminating renal failure that was rapidly fatal and a chronic slowly progressive renal impairment. The first entity showed a microangiopathic hemolytic profile with anemia, thrombocytopenia, and erythrocyte fragmentation. Light microscopy and electron microscopy examination of the kidney revealed a primary vascular disease with musculomucoid intimal hyperplasia of arteries and rare fibrin thrombi in arterioles. Interstitial fibrosis, tubular atrophy, and widespread glomerular necrosis were also seen. The disease was ultimately fatal within three to four weeks. The second entity showed a chronic course of renal failure with similar pathologic findings but less pronounced, and a microangiopathic hemolysis was absent. The course in the second group was ultimately fatal between three to eight months.

Activated factor IX complex in treatment of surgical cases of hemophilia A with inhibitors.

Three patients with severe hemophilia A with inhibitors to factor VIII were treated with activated factor IX complex. Bleeding was controlled adequately during surgical procedures involving each of the three. Partial thromboplastin times showed a variable shortening and prothrombin times were significantly shortened to values less than normal. Hemostasis was substantiated by the use of epsilon aminocaproic acid. Neither anamnestic responses nor thrombotic complications were observed. A transient hypertension developed in two patients shortly after infusion with the activated factor IX complex.

Psychogenic purpura (autoerythrocyte sensitization).

A 41-year-old woman has had a long history of repeated episodes of recurrent painful ecchymotic lesions. Results of coagulation tests were normal other than a slight decrease in antithrombin III. Skin tests were positive in response to the patient's own washed red cells. Light and electron microscopy of both the spontaneous and the induced lesions showed nonspecific changes but failed to reveal immunologic vasculitis. Psychologic evaluation showed hysterical and masochistic traits, depression, anxiety, and inability to deal appropriately with hostile impulses. Placebo was successful on several occasions in controlling or modifying the severity of the ecchymotic lesions.

A simulation of human heart function.

A simulation of the function of the human heart and heart muscle has been developed in the form of a digital computer code. For a given set of values for the input variables, realistic values of the cardiac output variables are predicted. A detailed discussion of the simulation and some results obtained from its application are presented. This simulation represents a unique combination of what was known in muscle mechanics, muscle thermodynamics, and of the structure, size, and shape of the heart, into an engineering model to improve the understanding of human heart muscle function. The left ventricle (LV) is treated as a thick-walled sphere whose wall is composed entirely of muscle fibers. Force-length velocity relationships are used to determine the tension in each fiber. The pressure in the LV is computed from fiber tension and fiber structure in the LV. A lumped-parameter simulation of the arterial tree provides a load impedance for the LV. Results are presented for simulation of normal human LV performance.