Defective opsonization in multiple myeloma

The mechanisms responsible for the unusual susceptibility of multiple myeloma (MM) patients to infections are incompletely defined. Since MM is associated with decreased production of normal serum proteins, we investigated the possibility that the production of opsonins might also be impaired. The neutrophil chemiluminescence assay of opsonization was used to evaluate the ability of serum from patients with MM to opsonize zymosan. It was found that sera from 18 MM patients exerted only 50% +/- 2.5% (mean +/- SEM) of the opsonic activity found in 18 control sera (p less than 0.001). In mixture experiments, untreated normal serum completely restored the opsonic activity of MM serum, suggesting a deficiency of opsonic factors rather than an inhibitor. In other mixture experiments, heat-inactivated normal serum only partially corrected the opsonic defect in MM serum. Serum from three patients had low C3 levels, and treatment of particles with these resulted in a greater opsonic defect than the patient population as a whole (p less than 0.02). No correlation between the opsonic defect and infections was established over an 18-mo period. These data suggest that MM serum lacks both heat-stable and heat-labile opsonic activity, the direct clinical significance of which remains to be clarified. However, these studies support the concept that defective host resistance in MM may be multifactoral, combining opsonic abnormalities with other defects previously described.     

Synergistic cytotoxic effect of azidothymidine and recombinant interferon alpha on normal human bone marrow progenitor cells

Azidothymidine (AZT) and interferon alpha (IFN-alpha) are among the drugs showing strong in vitro activity against the human immunodeficiency virus type-1 (HIV-1). Each drug, however, has significant toxicity against normal marrow progenitor cells that frequently proves dose-limiting in patients. In this study, AZT and recombinant IFN-alpha 2a (rIFN-alpha 2a) were tested as single agents and in combination against normal myeloid (CFU-GM) and erythroid (BFU- E) colony forming cells in a standard methylcellulose culture assay. The data were analyzed using a quantitative computerized analysis based on the median-effect principle and the isobologram equation as described by Chou and Talalay (Adv Enz Regul 22:27, 1984). The ED90 for BFU-E and CFU-GM inhibition was then compared with previously measured in vivo plasma levels of each drug and the ED90 for the anti-HIV-1 effect in vitro. We demonstrate that (a) the drugs are strongly synergistic in inhibiting marrow progenitor cell growth and that this synergism occurs at drug levels that are within the range of measured plasma levels in phase I clinical trials, (b) BFU-E are more sensitive than CFU-GM to the inhibiting effects of AZT, rIFN-alpha 2a or both drugs in combination, (c) the drug concentrations in combination that synergistically inhibit bone marrow progenitors are much higher than those required to inhibit HIV-1 replication in vitro, and (d) the anti- HIV-1 effect for the combination of AZT and rIFN-alpha 2a was clearly superior to the effect of AZT or rIFN-alpha 2a alone as indicated by the combination index and the dose-reduction index. These data suggest that substantially lower doses of AZT and rIFN-alpha than those currently being tested in clinical trials might not only maintain a strong synergistic anti-HIV-1 effect but might also avoid significant hematologic toxicity.     

Disseminated coxsackievirus B fulminant myocarditis in an immunocompetent adult: A case report: Case of disseminated coxsackievirus myocarditis

Coxsackieviral myocarditis is associated with systemic involvement in neonates; however, fulminant coxsackieviral myocarditis is rare in adults, and its dissemination with fatal myocarditis involving kidneys, liver, and adrenal is further rarely reported. We report a case of fulminant myocarditis along with dissemination of coxsackievirus, which was clinically unrecognized.     

Palliative side-to-side oesophagogastrostomy for unresectable carcinoma of the oesophagus and cardia.

The distressingly low resectability rate of carcinoma of the oesophagus and gastric cardia emphasises the need for palliative restoration of the act of swallowing. Side-to-side oesophagogastrostomy was performed in 10 cases of unresectable tumours. Eight anastomoses were made low in the left chest for lower third oesophageal and cardiac lesions and two high on the right for midoesophageal tumours. There were no anastomotic leaks or other complications, and no postoperative deaths. All patients swallowed well for an average of five months until their deaths. The decision to use this procedure is made at the time of thoracotomy when resection of the cancer is impossible because of local invasion and when sufficient proximal oesophagus is available for the anastomosis. The operation involves a single suture line only. It provides immediate palliation of dysphagia and makes unnecessary additional technical manoeuvres such as preparation of colonic or jejunal loops insertion of endoluminal tubes, or even transection of the oesophagus, pyloroplasty, gastrostomy or cervical oesophagostomy. It does not interfere with any subsequent radiotherapy or chemotherapy.