Antitumor xenograft activity with a conjugate of a Vinca derivative and the squamous carcinoma-reactive monoclonal antibody PF1/D

The human squamous carcinoma-reactive murine monoclonal antibody PF1/D was used to derive a conjugate with the Vinca derivative 4-desacetylvinblastine-3-carboxyhydrazide (PF1/D-DAVLBHYD). This immunoconjugate was shown to be largely aggregate free and there was no loss of immunoreactivity postconjugation. When tested in vivo in a 3-day-established human squamous carcinoma nude mouse xenograft model, the PF1/D-DAVLBHYD conjugate eliminated tumor growth with three injections (days 3, 6, and 9) at 2 mg/kg Vinca content. Significant tumor suppression was also observed with 0.5 mg/kg conjugate doses. In contrast, free PF1/D antibody had minimal antitumor activity and no activity was seen with identical doses of a control non-tumor-binding IgG-DAVLBHYD conjugate. Together, these data demonstrate the specificity of the PF1/D-DAVLBHYD antitumor effects.     

FM sonography in diffuse liver disease: prospective assessment and blinded analysis

FM sonography - a signal-processing technique that uses frequency and phase information as well as amplitude data - shows promise in evaluation of patients with diffuse liver disease. In a prospective blinded review of 37 patients with biopsy-proved liver disease and 42 healthy volunteers, FM sonography was clearly superior to traditional amplitude-based (AM) sonography in distinguishing healthy from diseased subjects. Statistically significant differences were seen in accuracy (FM, 98.7%; AM, 84.8%), sensitivity (FM, 97.3%; AM, 70.3%), and negative predictive value (FM, 97.7%; AM, 78.8%). Our data also suggest that current FM sonographic techniques cannot differentiate among histologic findings associated with different hepatic parenchymal abnormalities. It is unclear, therefore, whether FM imaging can reduce the numbers of patients who require biopsy for diagnosis or the frequency of biopsy procedures in patients with known disease.     

Initial two-year results of the Oregon Liver Transplantation Program

During the first 24 months of the Oregon Liver Transplantation Program, which began in October 1988, 94 patients were formally evaluated and 47 adults underwent 54 liver transplantations. Thirty-four percent of patients were veterans. The recipient operation lasted a mean of 7.4 hours (range: 4 to 16 hours). Veno-venous bypass was used routinely at first but selectively later (7 of the last 26 cases), resulting in reduced operating time. Hepatic artery reconstruction was end-to-end anastomosis in 52 cases and iliac conduit in 2. No arterial thrombosis occurred. Biliary reconstruction was choledochocholedochostomy in 83% and choledochojejunostomy in 17%. Biliary complications occurred in 28%. Operative mortality was 2%, and 1-year actual survival was 80%. Patients with hepatitis B fared worse, with four of six dying at a mean of 7.6 months. Overall, the median hospital stay was 30 days. Patients surviving more than 3 months had a mean Karnofsky score of 82%. No significant difference in outcome was noted in patients receiving prophylactic OKT3 monoclonal antibody (used in 45%) versus conventional immunosuppressive therapy. Overall, allograft rejection occurred in 55% of patients. Retransplantation was required in seven patients, three for primary graft nonfunction, two for uncontrolled rejection during induction therapy with OKT3, and two for graft failure secondary to recurrent hepatitis B.     

Strut fixation of an extensive flail chest

The indications for and preferred approaches to operative stabilization of posttraumatic chest wall instability are uncertain. We suggest this simple, rapid, and effective approach to surgical stabilization by Luque rod strutting of the flail segment when operation is required.     

Brachial plexus injury: association with subclavian and axillary vascular trauma

Proximal upper extremity (subclavian and axillary) vascular injury (SAVI) and brachial plexus injury (BPI) occur uncommonly. However, BPI may be associated with SAVI and frequently is an important determinant of long-term disability. The medical records of patients with traumatic SAVI, BPI, or both over a 5-year period were reviewed. A total of 31 patients were identified. The group was predominantly male (28 men/3 women) with a mean age of 30.5 +/- 1.8 years (range, 15-63 years). Blunt trauma accounted for 43.5% of SAVI cases and 77.8% of BPI cases. Thirteen patients (41.9%) sustained SAVI alone (group I), 10 patients (32.2%) had combined SAVI and BPI (group II), and 8 patients (25.9%) had BPI alone (group III). Subclavian and axilliary vascular injury occurred in 10 of 18 patients (55.6%) with a BPI. Brachial plexus injury occurred in 10 of 23 patients (43.5%) with a SAVI. Patients with SAVI from blunt trauma were significantly more likely to have an associated complete BPI than patients with penetrating trauma. All patients with a complete BPI (6 patients) had an associated SAVI regardless of mechanism of injury. Only one patient with a partial BPI from blunt trauma had an associated SAVI. The Injury Severity Score was significantly higher for patients in group II. An average of 2.8 and 3.3 associated injuries were observed in patients with SAVI (groups I and II) versus patients without SAVI (group III), respectively. No patient who had a complete BPI showed an improvement in neurologic status during a mean follow-up of 7.2 months. No late vascular sequelae occurred in group-III patients.(ABSTRACT TRUNCATED AT 250 WORDS)     

Radical cystectomy after coronary artery bypass graft

Nine patients have undergone single-stage radical cystectomy and ileal conduit urinary diversion two to fifty-one months after coronary artery bypass procedures. Two patients presenting with intractable angina at the time their malignant disease was being evaluated required bypass surgery before cystectomy could be undertaken. No significant cardiac morbidity occurred postoperatively, and all remain alive without evidence of malignant disease.     

SQ 30,957, a new antibiotic produced by Penicillium funiculosum. Taxonomy, fermentation, isolation, structure determination, synthesis and antibacterial activity

A new antibiotic, SQ 30,957, 4-diazo-3-methoxy-2,5-cyclohexadien-1-one, has been isolated from fermentation broths of Penicillium funiculosum. The structure (1) was deduced from its spectroscopic properties and its degradation reaction. SQ 30,957 has excellent activity against anaerobic bacteria such as Clostridium and Bacteroides and has moderate activity against aerobic bacteria. The compound has an LD50 of less than 17 mg/kg in mice by intraperitoneal administration.     

Auer rod positive dysmyelopoietic syndrome

Twenty-five patients with refractory anemia with excess blasts (RAEB) were studied. Five of these patients showed Auer rods in their myeloblasts, but met other criteria for RAEB. Median survival of the Auer rod-positive group was 14 months (range 2–27) from diagnosis with survival of 7 months after Auer rods were first observed. Median survival for the Auer rod-negative group was 12 months. Two patients developed overt acute leukemia, both from the Auer rod-negative group. The clinical course of Auer rod-positive RAEB, like that of Auer rod-negative RAEB, was one of progressive bone marrow failure complicated by infection, serious bleeding and the development of absolute transfusion requirement. These findings suggest that Auer rod-positive RAEB is a morphologic variant dysmyelopoietic syndrome that may pursue a similar clinical course to Auer rod-negative disease. Formulation of a separate treatment approach for those RAEB patients who possess Auer rods would appear ill advised.