INAUGURAL ARTICLE by a Recently Elected Academy Member:The cell surface metalloprotease/disintegrin Kuzbanian is required for axonal extension in Drosophila

It has long been suspected that proteolytic activity associated with advancing growth cones may be required for axon extension. We have isolated mutations in the kuzbanian (kuz) gene, which is expressed in the nervous system and encodes a putative zinc metalloprotease with a disintegrin domain. Drosophila embryos with loss-of-function mutations in kuz have dramatic defects in the development of central nervous system axon pathways, with many axons stalling and failing to extend through the nerve cord. This phenotype is rescued by panneural expression of kuz mRNA in the embryo. These results show that the Kuz metalloprotease is required for axon extension, suggesting a requirement for proteolytic activity at the growth cone surface.     

Immunotherapy and whole-body hyperthermia as combined modality treatment of a subcutaneous murine sarcoma

Interleukin–2 and hyperthermia have been used individually to treat a variety of tumors in both experimental and human trials. Combined adoptive immunotherapy and hyperthermia is an exciting new line of investigation. Previous work in our laboratory has shown that combined local hyperthermia and rIL-2 therapy can significantly decrease the rate of tumor growth. In this study, we investigated the effect of combined whole-body hyperthermia (WBHT) and rIL-2 on the growth of subcutaneous MCA-105 murine tumors in C57BL/6 mice. Treatment of both microscopic (day 3) and macroscopic (day 10) tumors was evaluated. In the treatment of microscopic tumors, animals received either no treatment; rIL-2 (3 × 10⁵ IU ip tid) on days 3–7; plus WBHT(41°C for 30 min) on days 3, 5, and 7; or WBHT only on days 3, 5, and 7. In treating macroscopic tumors, animals received either no treatment; rIL-2 on days 10–14; plus WBHT on days 10, 12, and 14; or WBHT only on days 10, 12, and 14. While combined treatment and WBHT alone had no significant effect on the growth of microscopic tumors, combined IL-2 and WBHT significantly reduced the rate of tumor growth of macroscopic tumors. These results suggest that the tumor microenvironment plays a critical role in combined WBHT and rIL-2 therapy, and may be due to effects of WBHT on the tumor vasculature. © 1993 Wiley-Liss, Inc.     

Avoiding complications in arthroscopic subacromial space and instability surgery

Arthroscopic shoulder surgery has become a safe tool for evaluation and treatment of a wide range of shoulder problems with few complications. With ever-improving technology (and commitment to motor skill development among arthroscopists), we can expect to maintain this low rate despite increasing procedure complexity. Avoiding complications in arthroscopic shoulder surgery requires careful preoperative planning, judicious patient selection, a thorough understanding of arthroscopic anatomy, and facility with arthroscopic techniques.     

Indoor nitrogen dioxide and childhood respiratory illness

Abstract: Nitrogen dioxide is produced from the combustion of fossil fuels and as an emission from gas-fired appliances, and is also a component of tobacco smoke. Nitrogen dioxide has been shown in experimental animals to be toxic to the respiratory tract. A number of recent studies have suggested that children exposed to significant levels of nitrogen dioxide in the home may be more susceptible to respiratory illness than children exposed to normal ambient levels. Respiratory illness is a major cause of morbidity in children everywhere. Here, we review the available evidence of this association and explore methodological issues in measurement of nitrogen dioxide exposure— misclassification of subjects, symptom bias and confounding. It has recently been shown that some New South Wales school rooms, where unflued gas heaters are often used as a source of warmth, have nitrogen dioxide levels which are above recommended ambient levels for outside air. This has underlined the need for setting standards for indoor levels of various pollutants, and cohort studies are suggested, to include personal monitoring and prospective data collection techniques.     

Percutaneous transluminal angioplasty of tibial arteries for limb salvage

Percutaneous transluminal balloon angioplasty (PTA) was performed in 17 tibial arteries with an average cross-sectional area stenosis of 92% (range 75–99%) in 13 patients (14 limbs) for limb salvage. In 4 of 14 lower extremities, PTA of femoropopliteal arteries was also performed. Technical success with 50% or less residual stenosis was achieved in all 17 tibial vessels. At approximately 2 months after PTA, clinical improvement had occurred in 10 of 14 limbs; no patient was made worse. Most recent follow-up (mean 19 months, range 8–34 months) revealed continued satisfactory clinical success with no further vascular intervention in 9 of these 10 limbs (one patient died). Short segmental stenoses, residual stenoses less than 40% following PTA, and absence of diabetes or gangrene appear to be predictors of favorable clinical outcomes. Our results suggest that PTA of focal tibial stenosis is an effective and safe treatment modality in properly selected patients and that wider use of PTA may be justified.     

Allergy to barium sulfate suspension with angioedema of the stomach and small bowel

Hypersensitivity reactions occurring during barium studies of the gastrointestinal tract are rare. A case is presented with radiographically demonstrated angioedema in the stomach and small bowel accompanied by allergic rhinitis, which was apparently an allergic response to the barium sulfate suspension. The reaction was documented twice during separate challenges to the barium suspension performed several months apart.