Safety of GM-CSF in Patients with AIDS: A Review of the Literature

We performed a literature search for all clinical studies reporting outcomes in patients with the acquired immunodeficiency syndrome (AIDS) receiving granulocyte-macrophage colony-stimulating factor (GM-CSF) for any indication. Safety outcomes included human immunodeficiency virus replication, immune status, and frequency of opportunistic infections and neoplasms. Data were synthesized qualitatively. We identified 22 studies (274 patients): 12 addressed AIDS neutropenia, 8 AIDS cancer therapy, and 2 opportunistic infections. Viral burden was assessed by serum p24Ag in 15 studies. Nine reported no change in levels, three net decreases, and three net increases. All studies showing net increases involved patients receiving GM-CSF without a concurrent antiretroviral. The CD4 counts were unchanged in 5 studies, increased in 3, and not reported in 14. The incidence of neoplasms or new opportunistic infections was low. The literature suggests no increased risk of viral replication or clinical deterioration in patients with AIDS who take GM-CSF concurrently with zidovudine.     

A comparative analysis of radiological and surgical placement of central venous catheters

Purpose To compare the differences in practice and outcome of all radiologically and surgically placed central venous catheters retrospectively over a 2-year period simultaneously, at a single institution. Methods A total of 253 Hickman catheters were inserted in 209 patients; 120 were placed radiologically in 102 patients and 133 were placed surgically in 107 patients. The indication was chemotherapy in 76% of radiological and in 47% of surgical cases; the remainder were for total parenteral nutrition and venous access. Results There were 6 (4.5%) primary surgical failures and a further 17 (13%) surgical cases requiring multiple placement attempts. Pneumothorax occurred once (0.8%) surgically and four times (3.3%) radiologically. There were no radiological primary misplacements but there were five (3.7%) surgical ones. Catheter or central vein thrombosis occurred in four (3.3%) radiological and five (3.7%) surgical cases. The rate of infection per 1000 catheter-days was 1.9 in radiologically placed catheters and 4.0 in surgically placed ones (p<0.001). Average catheter life-span was similar for the two placement methods (100±23 days). Conclusion Radiological placement is consistently more reliable than surgical placement. There are fewer placement complications and fewer catheter infections overall.     

Case report 720

A man presented with a mass in the left first metacarpal bone. Later, his chest radiograph showed extensive, bilateral, rounded opacities in both lungs with enlarged hilar lymph nodes, and he developed expanding lesions in the left radius, ulna, and metacarpal bones. The pulmonary lesions were treated with radiotherapy and cytotoxic agents, and the tumor mass in the first metacarpal was debulked. All biopsies showed similar features of a mixed tumor (pleomorphic adenoma) with metastatic or embolic pulmonary involvement; ultrastructural and immunocytochemical investigations supported this unique diagnosis. The patient remains well 15 years after the initial diagnosis. It is possible that the myoepithelial elements in this case had been displaced intraosseously during development. We are not aware of a similar case in the literature.     

Immunological and respiratory reactions in workers exposed to organic dusts

The relationship of skin reactivity and serum immunoglobulin E (IgE) levels to the prevalence of chronic respiratory symptoms and to ventilatory capacity is examined in workers exposed to different organic aerosols. The results from group of control workers similarly tested are also presented. Workers exposed to occupational allergens had positive skin tests more frequently than did controls, except for soy bean workers. Workers with positive skin tests to occupational allergens had a higher prevalence of almost all symptoms than those with negative skin tests although the differences did not always reach statistical significance. Workers with positive skin reactions in general had significantly higher serum IgE levels than did workers with negative skin reactions. There were across-shift reductions of ventilatory capacity in all groups of exposed workers, varying for forced vital capacity from 1.7% to 13.3%, for forced expiratory volume from 0.4%–21.9%, for maximum flow rates at 50% from 1.5% to 16.1% and for maximum flow rates at the last 25% of control vital capacity from 0% to 24.9%. There was, however, no correlation between acute and chronic lung function changes and skin reactivity or IgE values. Our data suggest that although exposure to organic aerosols may be associated with frequent immunologic reactions, these findings do not predict objective respiratory impairment.The research was supported in part by grant no. JBP 733 from the National Institutes of Health, Bethesda, Md., USA, and by grant no. RO1 OHO-2593-04 from the National Institutes of Occupational Safety and Health, Centers for Disease Control, Atlanta, Ga., USA     

Mutations Affecting the Rossman Fold of Isoleucyl-tRNA Synthetase Are Correlated with Low-Level Mupirocin Resistance in Staphylococcus aureus

The isoleucyl-tRNA synthetase (ileS) gene was sequenced in toto from 9 and in part from 31 Staphylococcus aureus strains with various degrees of susceptibility to mupirocin. All strains for which the mupirocin MIC was greater than 8 microg/ml contained point mutations affecting the Rossman fold via Val-to-Phe changes at either residue 588 (V588F) or residue 631 (V631F). The importance of the V588F mutation was confirmed by an allele-specific PCR survey of 32 additional strains. Additional mutations of uncertain significance were found in residues clustered on the surface of the IleS protein.     

Role of nitric oxide in relaxation of the longitudinal layer of rectal smooth muscle

PURPOSE: This study was designed to investigate the role of nitric oxide in neurogenic relaxation of the longitudinal layer of human rectal smooth muscle. METHODS: Tissue was obtained from the mid rectum of patients undergoing anterior resection for carcinoma. Adjacent strips of longitudinal muscle were dissected and mounted in organ baths for isometric tension recording. In preliminary experiments to determine the response of strips to cholinergic, adrenergic, and potential excitatory agonists, strips were superfused with standard Krebs solution (37±0.5°C; pH, 7.4±0.05). Investigation of inhibitory, nonadrenergic noncholinergic responses required the addition of 3×10⁻⁶ M histamine to induce reproducible and stable tension for five-minute “test” periods, during which electrical field stimulation (EFS) and additional drugs were applied. In these experiments, strips were superfused with Krebs solution that contained atropine sulfate (3×10⁻⁶ M) and guanethidine (3×10⁻⁶ M). RESULTS: The response to cholinergic and adrenergic agonists was typical of nonsphincter specialized gastrointestinal smooth muscle. EFS elicited frequency-dependent, neurogenic (tetrodotoxin-sensitive) relaxations of precontracted strips, which were reduced in dose-dependent fashion by addition ofNω-nitro-l-arginine and restored by addition of 3×10 ⁻⁴ M l-arginine but not by d-arginine. Addition of exogenous nitric oxide (sodium nitroprusside) mimicked the relaxant response induced by EFS. CONCLUSION: Smooth muscle from the longitudinal layer of human rectum receives an intrinsic inhibitory innervation mediated by nitric oxide. Supported and financed by the Medical Research Council, United Kingdom. John Stebbing is in receipt of a Medical Research Council Clinical Training Fellowship. Read at the meeting of The American Society of Colon and Rectal Surgeons, Seattle, Washington, June 9 to 14, 1996.