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Nitric oxide (NO), a biologically active mediator generated in many cell types by the enzyme NO synthase, may play an important role in cardiovascular toxicity that is frequently observed in cancer patients during intravenous (i.v.) interleukin 2 (IL-2) therapy. The induction of NO synthase and the production of NO seem to be involved in the pathogenesis of the vascular leakage syndrome, as well as in the regulation of myocardial contractility. In the present study, we evaluated the pattern of plasmatic NO changes during multiple cycles of continuous i.v. infusion (CIVI) of IL-2 in ten advanced cancer patients (five males, five females, median age 59 years, range 33-67 years; eight affected by renal cell cancer and two affected by malignant melanoma). The patients received IL-2 at 18 MIU m-2 day-1 (14 cycles) or 9 MIU m-2 day-1 (seven cycles) for 96 h, repeated every 3 weeks. Interferon alpha (IFN alpha) was also administered subcutaneously (s.c) during the 3 week interval between IL-2 cycles. For each cycle, plasma samples were collected before treatment (t0), 24 h (t1), 48 h (t2), 72 h (t3) and 96 h (t4) after the start of IL-2 infusion, and 24 h after the end of the cycle. NO concentration was determined spectrophotometrically by measuring the accumulation of both nitrite and nitrate (after reduction to nitrite). The following observations may be drawn from data analysis: (1) plasma nitrate + nitrite significantly raised during treatment (P = 0.0226 for t0 vs t3), but statistical significance was retained only when cycles administered with IL-2 18 MIU m-2 day-1 are considered (P = 0.0329 for t0 vs t3; P = 0.0354 for t0 vs t2 vs t4) (dose-dependent pattern); (2) during subsequent cycles a significant trend toward a progressive increase of plasma nitrate + nitrite levels, with increasing cumulative dose of IL-2, was observed (linear regression coefficient r = 0.62, P = 0.0141 for t0; r = 0.80, P = 0.0003 for t1; r = 0.62, P = 0.013 for t2; r = 0.69, P = 0.045 for t3); (3) plasma nitrate + nitrite levels peaked earlier in subsequent cycles than in the first cycle; (4) all patients experienced hypotension. The mean of the systolic blood pressure values was significantly lower at the time of plasma nitrate + nitrite peak than at t0 (P = 0.0004); (5) the two cases of grade III hypotension occurred in patients with the higher mean and peak plasma nitrate + nitrite values. We conclude that determination of plasma nitrate + nitrite levels during CIVI IL-2 can usefully estimate, in a dose-dependent pattern, the degree of peripheral vascular relaxation and capillary leakage associated with cytokine action, clinically manifested as hypotension. However, isolated cardiac toxicity that continues to represent a relevant problem during IL-2 therapy, does not appear to correlate with plasma nitrate + nitrite levels; therefore, further studies are required to understand adequately the mechanisms underlying IL-2-induced cardiac toxicity.

The case of a 64-year-old man who was admitted to hospital with fever, general deterioration and anorexia is reported. For the past 4 years, the patient had been receiving corticosteroid therapy for a chronic inflammatory demyelinating polyradiculoneuropathy. Soon after admission the patient developed respiratory insufficiency as a result of a massive pneumonitis, with severe hypoxia, acute anaemia, acute renal failure and a systemic inflammatory response syndrome (SIRS) requiring admission to the Intensive Care Unit (ICU). All faecal, bronchial, duodenal and urine samples showed Strongyloides stercoralislarvae. Despite antihelmintic therapy and cardiorespiratory support, the patient died from the consequences of irreversible shock. Strongyloidiasis is present worldwide and can be a chronic, essentially asymptomatic infection. This nematode can produce an overwhelming hyperinfection syndrome, especially in patients showing deficient cell-mediated immunity. Strongyloides hyperinfection syndrome is frequently fatal but is potentially a treatable clinical condition. Patients undergoing immunosuppressive therapy or with suspected immunity deficiency (HIV infection, malnutrition, lymphomas, leukaemias or other neoplasia treated with systemic radiotherapy or chemotherapy) must be also monitored for opportunistic Strongyloides stercoralisinfection, because clinical manifestation of the systemic hyperinfection syndrome can be rather non-specific.

Purpose:The aim of this work is to report the utility of the distal esophageal stump's circular myotomy in case of a long gap esophageal atresia repair. Methods:Between 1972 and 1999 the authors treated 192 patients who had esophageal atresia (EA). Among them, 6 patients with EA long gap underwent both a distal and proximal stump circular myotomy. Five cases were Gross type C, and 1 case was Gross type A. The gap (average 4.5 cm) did not permit a simple and direct end-to-end anastomosis. Results:One patient died 6 days after the operation because of a cardiac malformation. There was no mucosal tear during the myotomies or any anastomotic stricture later. Five patients survived. Three of them needed an antireflux procedure (60% of surviving patients). None of the 5 patients showed any mucosal outpouching, and their esophageal motility and swallowing were not different clinically compared with the patients who underwent an EA repair without a myotomy. Conclusions:Distal circular myotomy is a very useful, however, delicate, procedure that can help solve the problem given by long gap EA. It is mandatory not to tear the mucosa during the myotomy to avoid the shortening of the stump caused by its repair, which would lead to an increase in the size of the gap. J Pediatr Surg 36:855-857. Copyright © 2001 by W.B. Saunders Company.

Cardiovascular toxicity related to i. v. administration of Interleukin2 (IL-2) is the main cause of treatment withdrawal and it is unpredictable on the base of standard pre-treatment evaluations including history, physical examination and EKG. We performed this study to investigate the value of Cardiac Ultra Sono Scan (CUSS) in the detection and prediction of such toxicity. The study included 19 patients (15 males, 4 females, median age: 51, tumor type: 10 advanced renal cell cancer, 9 malignant melanoma) scheduled to receive multiple cycles of IL-2 by continuous i. v. infusion at the dose of 18MIU/m2/day for 96 hours. Data were recorded from 31 IL-2 infusions: a marked impairment of diastolic function was observed in all cases, but in a subset of cycles (12/31) this function was already impaired at the pre-treatment determination, and this was significantly correlated with the onset of major cardiovascular side-effects conditioning treatment discontinuation (P<0.05). Among the parameters studied, the ratio of maximal flow velocity in early diastole to that obtained in late diastole (E/A), as measured by transmitralic flow pattern analysis, resulted not only the most sensible index of impairment of the diastolic function induced by IL-2, but also an accurate predictor of cardiovascular toxicity when altered before treatment. An abnormal E/A was significantly correlated with a history of hypertension (P<0.05). We conclude that CUSS is an effective procedure and may contribute to identify patients with increased risk for cardiovascular toxicity due to IL-2.