Inhaled crocidolite mutagenicity in lung DNA

We used transgenic mice carrying the lacI reporter gene to study the mutagenesis potential of asbestos crocidolite. The animals were exposed by nose-only inhalation to an aerosol containing 5.75 mg/m(3) crocidolite dust for 6 hr/day and 5 consecutive days. After 1, 4, and 12 weeks, we examined four end points: the cytology of bronchoalveolar lavage, the lung load of crocidolite, the hydrophobic DNA adducts, and the mutations in the lacI reporter gene. Twelve weeks after exposure, nearly 10% of the inhaled fibers remained in the lung (227 +/- 103 ng/mg lung). There was evidence of a typical inflammatory response consisting of multinucleate macrophages at weeks 4 and 12, whereas immediately after the exposure, we observed numerous polymorphonuclear neutrophils. The mutant frequency significatively increased during the fourth week after the exposure: 13.5 [time] 10(-5) in the exposed group versus 6. 9 10(-5) in the control group. The induction factor, defined by the ratio of checked mutants of exposed mice to checked mutants of control mice, was 1.96. The mutation spectrum of control lung DNA and exposed lung DNA was similar, suggesting the possible involvement of a DNA repair decrease in crocidolite-treated animals. We used the (32)P-postlabeling method and did not detect any increase of either 5 mC or bulky adduct in treated mice. This is the first study that demonstrates asbestos mutagenicity in vivo after a nose-only inhalation.     

Phase II study of carminomycin in a human tumor cloning assay

Summary The anticancer activity of carminomycin was investigated in a human tumor cloning assay. No efficacy could be identified in the WiDr and the MCF7 cell lines which were highly responsive to doxorubicin. In addition, drug testing experiments were carried out in samples of various malignancies freshly obtained from 86 patients of whom 54 had not received prior anthracyclines. A reduction in the number of tumor colony forming units by 50% or more was seen in 1/26 breast cancers, 1/22 ovarian cancers and 1/7 melanomas. Cross-resistance studies indicated that eight tumors were responsive to doxorubicin only and one to carminomycin only whereas two were sensitive to both and 73 were resistant to both. This in vitro Phase II study corroborates the disappointing clinical results achieved with carminomycin.     

In vitro and in vivo characteristics of [iodine-125] 3-(R)-quinuclidinyl (S)-4-iodobenzilate

The radioiodinated muscarinic acetylcholine receptor antagonist, [125I] 3-quinuclidinyl 4-iodobenzilate, has two high affinity diastereomeric forms, the (R,R) and (R,S)-isomers. The (R,S)-diastereomer is only threefold lower in affinity than the (R,R)-isomer, but the kinetic properties are considerably different--the dissociation rate constant is 13-fold faster for the (R,S)-isomer and the association rate constant is two to threefold faster. The calculated affinity is therefore only fourfold lower. In vivo, the clearance of (R,S)-4IQNB from receptor-rich tissue is also more rapid than that of the (R,R)-isomer, that is a reflection of the more rapid in vitro kinetic properties since the physicochemical properties and the metabolic clearance of the diastereomers is the same.     

Ulnar-positive variance as a predictor of distal radioulnar joint ligament disruption

PURPOSE: Previous cadaveric data show that disruption of the triangular fibrocartilage complex (TFCC) at the wrist allows 0.5 to 3.0 mm of proximal radius migration. Anatomic studies have documented the presence of superficial and deep fibers of both the palmar and the dorsal distal radioulnar joint (DRUJ) ligaments. The aim of this study was to determine the contribution of the superficial and deep fibers of the DRUJ ligaments to longitudinal forearm stability as measured by ulnar-positive variance. METHODS: Eight fresh-frozen cadaver specimens were included in this study. Each specimen was secured with external fixation clamps to a sequential loading frame with the elbow in 90 degrees of flexion and the forearm and wrist in neutral pronation supination, neutral ulnar-radial deviation, and neutral volar-dorsal angulation. The radial head was resected and a force gauge was applied to the proximal radius. The peripheral TFCC was identified through an incision between the fifth and sixth extensor compartments and the dorsal capsulotomy of the DRUJ capsule. After baseline measurement sequential transection of the superficial and deep fibers of the TFCC was performed. Before and after each step load application and removal were performed by attaching an 88.90-N weight to the end of a force gauge and via longitudinal traction on the proximal part of the radius, and ulnar variance was measured with wrist fluoroscopy. RESULTS: Transection of the superficial TFCC fibers resulted in radius migration of 0.70 mm. This migration, however, was not significantly different from that observed at baseline. After both the superficial and deep TFCC fibers were transected the radius migrated proximately with load. This change of ulnar variance was significantly greater than that observed at baseline or after transection of only the superficial TFCC fibers. CONCLUSIONS: Traumatic injury to the TFCC with radiographic evidence of ulnar-positive variance may be an indication of disruption of the deep TFCC fibers.     

The effect of increasing distraction on digital motion after external fixation of the wrist

PURPOSE: Although several factors have been related to the development of digital stiffness after external fixation of distal radius fractures, distraction can be considered one of the most important. This study determined a threshold for distraction during external fixation of distal radius fractures and documented the effect of distraction of the wrist on metacarpophalangeal (MCP) joint motion. METHODS: Eight fresh-frozen cadaveric forearms were mounted on a testing frame and the flexor digitorum superficialis (FDS) tendon of each finger was pulled individually until a 90 degrees flexion at the MCP joint was generated. A load cell was used to record the force applied on the tendons. Tendon displacement was calculated by using a linear potentiometer. Sequential distraction across the wrist was applied through a distraction outrigger on the external fixator and was measured both on the external fixator in millimeters and on fluoroscopic images. Finger motion was captured by using a 2-dimensional motion tracking system. The experiment was repeated at different levels of wrist distraction (increments of 2 mm to a maximum of 14 mm). RESULTS: There was a significant difference in the effect of distraction on the individual fingers. For the index finger the load required for the FDS to produce a 90 degrees flexion at the MCP joint was increased linearly between 0 and 8 mm of wrist distraction. For the other fingers a threshold of distraction was found. A significant increase in the load was noticed after 5 mm of wrist distraction. CONCLUSIONS: More than 5 mm of wrist distraction increases the load required for the FDS to generate MCP joint flexion for the middle, ring, and small fingers. For the index finger, however, as much as 2 mm of wrist distraction significantly increases the load required for flexion at the MCP joint.     

Distal radius fractures: a comparison of tension band wiring versus ulnar outrigger external fixation for the management of distal radioulnar instability

PURPOSE: To retrospectively compare the results of immobilization of the forearm in supination with the results of tension band fixation of the ulnar styloid in 35 patients with distal radius fractures, fracture of the base of the ulnar styloid, and distal radioulnar joint instability treated with external fixation. METHODS: Thirty-five patients with fractures of the distal radius, fracture of the base of the ulnar styloid, and unstable distal radioulnar joint had external fixation with adjunctive percutaneous pins and allograft bone to reduce and stabilize the distal radius fracture anatomically. Only those patients with an associated ulnar styloid base fracture displaced over 2 mm with gross distal radioulnar joint instability relative to the contralateral wrist were included in this study. Group 1 consisted of patients in whom the ulnar styloid base fracture was treated with conventional tension band wiring techniques. Group 2 patients were treated with a supplemental outrigger from the external fixator to the ulna and locked in 60 degrees of forearm supination. Groups 1 and 2 had an average follow-up period of 40 and 36 months, respectively. RESULTS: Group 2 had significantly better supination than group 1. In terms of functional outcome it was found that there was no significant difference for the Disabilities of the Arm, Shoulder, and Hand and the Gartland and Werley scores between the 2 treatment groups. There was a lower rate of complications and fewer secondary procedures were required in group 2. The incidence of distal ulna resection was 4 of the 35 patients (2 patients in each group). CONCLUSIONS: Our results indicate that patients in whom the ulnar styloid can be reduced and maintained in supination can be treated effectively with fixed supination outrigger external fixation. This method resulted in a statistically significant improvement in supination and a lower rate of distal radioulnar joint complications, and it required fewer secondary procedures.     

Treatment of infrarenal aortic aneurysm by minimally invasive retroperitoneal approach: use of a video-assisted technique

We propose a technique for treating abdominal aortic aneurysm in which first a minilaparotomy (retroperitoneal) is performed to make a conventional arterial dissection; then, video assistance is used to control the left lumbar arteries and to make the aortic anastomosis. This technique can be performed with no significant laparoscopic capability.The patient was installed in a 20-degree right lateral decubitus. A transverse left 8- to 10-cm abdominal incision was made, followed by separation of the muscular structures. Retroperitoneal control of the proximal aortic neck and of both common iliac arteries was obtained by digital and instrumental dissection. A 30-degree laparoscope was then introduced through a 8- to 12-mm trocar and provided the light and magnification that facilitated the dissection of the posterior wall of the aortic neck and of the left flank of the aneurysm, looking for the lumbar arteries to be clipped. A suspended running suture to make the aorto-prosthetic anastomosis was facilitated by the magnification of the camera, especially during the passage of needles. Between March and September 2001, 32 patients fulfilled the anatomic conditions: an infrarenal aortic neck length of 2 cm or more, absence of hypogastric artery aneurysm, and no need for inferior mesenteric artery reimplantation. In 30 patients, the surgery was performed by using the planned minimally invasive approach, and extension of the incision was necessary in two patients.