Serum level of interleukin 6 as a prognosis factor in metastatic renal cell carcinoma.

Interleukin (IL) 6 was measured in the serum of 138 patients with metastatic renal carcinoma before the initiation of IL-2 treatment. IL-6 was detectable in 66 patients with renal cancer (48%) and in only 8 of 70 normal adults (11%). Serum C reactive protein (CRP) and IL-6 levels are correlated, suggesting that IL-6 is involved in CRP increase in these patients. The interval between diagnosis of the primary tumor and metastasis was shorter in patients with a detectable serum IL-6 and/or serum CRP level greater than 50 mg/liter. Serum IL-6 and CRP levels were higher in subgroups of patients previously defined as having a poor life expectancy according to the Eastern Cooperative Oncology Group criteria. Pretreatment concentrations of IL-6 and CRP were higher in patients who experienced progressive disease after IL-2 treatment. Patients with detectable IL-6 had a shorter survival from the beginning of IL-2 treatment than patients without circulating IL-6 (median, 8 versus 16 months). Similarly, the median survival from the beginning of IL-2 therapy of patients with CRP levels greater than 50 mg/liter was 6 months, compared to 16 months in those with CRP levels below this threshold. None of the 21 patients with serum IL-6 concentrations greater than 300 pg/ml achieved response to any of the three IL-2 regimens. This subgroup has a median survival of 5 months after IL-2 treatment and consisted of 15% of the patients in our series. These results indicate that serum IL-6 and CRP levels are adverse prognosis factors in patients with metastatic renal cell carcinoma. Serum IL-6 level could help in the selection or stratification of the patients in future IL-2 trials.

Clinical application of retroviral gene transfer in oncology: results of a French study with tumor-infiltrating lymphocytes transduced with the gene of resistance to neomycin.

PURPOSE: Adoptive immunotherapy with tumor-infiltrating lymphocytes (TIL) and interleukin-2 (IL-2) has been reported to mediate tumor regression in some human cancers. To define better the biologic characteristics of TIL, especially survival and distribution in vivo, we performed a gene-marker study in patients with advanced malignancies. PATIENTS AND METHODS: We treated five patients with metastatic melanoma or renal cell carcinoma with adoptive immunotherapy. TIL were genetically modified, before their infusion, using a recombinant retroviral vector that contained the marker gene coding for resistance to neomycin (NeoR). RESULTS: All of the patients tolerated the treatment well and none of the theoretic safety hazards due to the retroviral gene transduction was observed. The presence of the NeoR gene in TIL was detected by Southern blot analysis, with an efficiency of transduction that ranged from 1% to 26%. With polymerase chain reaction (PCR) analysis, we demonstrated that gene-modified TIL can survive for several months after reinjection, since positive blood samples were observed up to day 260 following reinjection. Eight malignant biopsy specimens were obtained from three patients after cell infusion. TIL were detected in only four of these eight tumor deposits on days 7 and 260. CONCLUSION: These results confirm the feasibility and safety of using in vitro retroviral gene transduction in human lymphocytes to analyze their in vivo distribution for further therapeutic applications. However, a selective and prolonged retention of TIL at the tumor site was not found in this study.

Myocardiotoxicity of 5 fluorouracil.

We report a case of specific myocardiotoxicity due to 5 F.U. not previously described in man. A 41-year-old man was admitted to the ICU for heart and renal failure, appearing 24 h after 5 days treatment with 5 F.U. and cis-platinum. Dopamine was necessary to maintain blood pressure. Two-D echocardiography and a right heart catheterisation confirmed the alteration of myocardial contractility. After 2 weeks a complete cardiac recovery occurred.

In situ decontamination of medical wastes using oxidative agents: a 16-month study in a polyvalent intensive care unit.

Over a 16-month period from September 1997 to December 1998, a prospective study was made of an on-site treatment of medical wastes in a 10-bed intensive care unit. First, the wastes were ground and then, a high concentration of ozone in air was repeatedly injected into the ground wastes. The study analysed the practical application of the system and its microbiological efficiency. Inactivation experiments were made with reference strains of Staphylococcus aureus, Enterococcus hirae, Pseudomonas aeruginosa, Escherichia coli, Mycobacterium smegmatis, Bacillus subtilis var niger, Bacillus stearothermophilus, Candida albicans and Aspergillus niger. Two thousand eight hundred treatment cycles, i.e. 84,000 grindings and 140,000 ozone injections gave a treatment capacity of 50 kg of waste per day with a good staff acceptability. All kinds of medical devices used in an intensive care unit were treated. In untreated ground wastes, the median bacterial load was 105.86 (range 10(2.35)-10(8.05)) cfu/g. After ozone treatment, bacteria and fungi were reduced by a factor of 10(5). Aero-contamination of the ward was unchanged. Computer control allowed all events to be tracked. On-site medical waste treatment appears to be an efficient alternative to the usual centralized collection and treatment.

[Analysis of changes in serum levels of TNF, IL-1 and IL-6 during administration of IL-2. Correlation with clinical response to treatment]. / Analyse des modifications des concentrations sériques de TNF, d'IL-1 et d'IL-6 au cours de l'administration d'IL-2. Corrélation avec la réponse au traitement.

We have investigated the serum concentrations of TNF, IL-1 and IL-6 in 49 patients with metastatic renal carcinoma receiving interleukin 2 (IL-2) or a combination of IL-2 and interferon alpha (IFN). Our results demonstrate that IL-2 and/or IFN induce an increase of serum concentrations of IL-1 and TNF in 95% and 75% of the patients respectively. Serum IL-6 levels increase in 44% of the patients. Serum concentrations of IL-1 and TNF remain elevated 48 hours after the end of IL-2 infusion. IL-1 and TNF levels are higher in patients receiving a combination of IL-2 and IFN. TNF and IL-1 levels in serum are significantly higher in responders to IL-2 treatment 48 hours after the end of IL-2 infusion. These two biological criteria enable a subgroup of patients with a very low response rate to IL-2 to be defined. The persistent increase of these cytokines in serum indicates a persistent activation of the immune system lasting after the end of IL-2 treatment which could be involved in the antitumor response.

[Propofol versus etomidate in short-time urologic surgery]. / Propofol versus étomidate en chirurgie urologique de courte durée.

Thirty patients, scheduled for short urological surgical procedures and ranked ASA 1 or 2, were randomly assigned to two homogenous groups. In group P, they were given a 2 mg.kg-1 bolus of propofol and 10 micrograms.kg-1 of alfentanil, followed by a continuous infusion of propofol (5 mg.kg-1.h-1) and 5 micrograms.kg-1 doses of alfentanil. In group E, they were given a 0.3 mg.kg-1 bolus of etomidate, followed by an infusion (1.5 mg.kg-1.h-1). The doses of alfentanil were the same as in group P. Further doses of either propofol (0.5 mg.kg-1) or etomidate (0.2 mg.kg-1) were used should anaesthesia prove not to be deep enough. The patients were not intubated, and breathed spontaneously. Surgery lasted a mean of 18.3 +/- 11.8 min (group P) and 18.8 +/- 9.4 min (group E). The following parameters were studied: the amount of each agent required for maintenance of anaesthesia, the duration of apnoea at induction, the quality of anaesthesia and of muscle relaxation, adverse effects (coughing, trismus, restlessness, nausea, vomiting), the time required for recovery, and its quality. In group P, there was a 27% decrease in arterial pressure, without any tachycardia or hypoxia, together with a quick recovery of excellent quality. On the other hand, in group E, there was little or no haemodynamic alteration, but there often was a trismus at induction. Hypoxia also occurred during induction with etomidate, being severe enough in one case to require tracheal intubation and artificial ventilation. The reasons for this hypoxia seemed to be the apnoea and the trismus, which tends to hinder assisted ventilation.(ABSTRACT TRUNCATED AT 250 WORDS)

[Acute respiratory insufficiency in sickle cell disease]. / Insuffisance respiratoire aigu au cours de la crise drépanocytaire.

Two cases are reported of acute respiratory failure occurring during sickling crises. In the first one, the crisis was characterised by priapism, and in the other one, by abdominal pain. The different causes of these respiratory effects are discussed: infection, fat embolism, pulmonary infarct, haemodynamic pulmonary oedema, as was probably the case in the first patient, or non haemodynamic pulmonary oedema due to sickling, as during conventional treatment of a sickling crisis (oxygen, antibiotics, blood transfusion, cytapheresis). Invasive investigations may contribute to keeping up the clinical picture, because of hypoxic sickling. The water equilibrium of these patients must be monitored with great care. Worsening of the patient's condition despite 48 h of correct treatment must lead to the search for a specific cause.

[Cerebral aspergillosis in immunocompromised patients]. / Aspergillose cérébrale chez l'immunodéprimé.

Three cases of central nervous system (CNS) aspergillosis in immunocompromised patients are reported. All three had neurological symptoms with normal cerebrospinal fluid (CSF). The CT scan showed poorly defined low density lesions which were not enhanced by contrast medium. They also had pulmonary signs and fever despite antibiotic treatment. Aspergillus fumigatus was isolated from bronchoalveolar lavage fluid. Antifungal therapy was started promptly, associating amphotericin B, itraconazole and flucytosine. Unfortunately, they died within 2 days to 2 weeks after admission in the intensive care unit. Postmortem examinations revealed disseminated aspergillosis with colonization of brain, lung, heart and kidney. The CT scan signs were quite different from those seen with the more usual bacterial ring lesions. In immunocompromised patients, the agents responsible for producing these findings are Aspergillus, Nocardia, Cryptococcus, Toxoplasma and Mycobacterium tuberculosis. Signs involving organs other than the CNS, and an examination of the CSF, should provide elements for establishing a differential diagnosis. Early antifungal treatment is the only chance of survival. Recrudescent fever and pulmonary signs occurring in neutropenic patients after antibacterial antibiotic treatment has been started are sufficient criteria for empirically starting amphotericin B administration unless clinical judgement dictates otherwise.

[Can hydroxyethylamidon be used during intensive care of brain-dead organ donors?]. / L'hydroxyéthylamidon peut-il être utilisé lors de la réanimation des sujets en état de mort cérébrale pour don d'organe?

In France, most of the kidney grafts are obtained from brain dead organ donors. Brain death induces numerous changes, especially in haemodynamic status, requiring the infusion of large volumes of fluid. The aim of this study was to evaluate the effect of hydroxyethyl starch (HES) on the organ donors and the kidney graft function in recipients. We compared two groups of brain dead organ donors and the kidney grafts, differing by the infused solutions: either a combination of HES (Elohes, Biosedra) and 4% human albumin solutions (HES group), or albumin alone in the control group (Albumin group). In the two groups, sex-ratio, age, cause of brain death and duration of therapy were similar. Fluid requirements were identical in the two groups: respectively 2,211 +/- 1,512 mL in the Albumin group vs 2,452 +/- 1,094 mL in the HES group (p = 0.17). However, the volume of albumin was significantly decreased in the HES group: 711 +/- 822 mL (p = 0.0001). Therefore the cost was lower in the latter: 638 +/- 633 vs 1766 +/- 788 FF. The coagulation status was not significantly different between the two groups. Amylasemia was higher in the HES group, but the difference was not significant. In the Albumin group, urinary output increased, but not significantly and creatinemia was decreased: 113.9 +/- 62 vs 131.5 +/- 44 mumol.L-1 (p < 0.05). The two groups of recipients were also similar for sex-ratio, age, kind of graft, cause of the chronic renal failure and ischaemia times.(ABSTRACT TRUNCATED AT 250 WORDS)

[The value of anesthesia consultation in relation to the single preanesthetic visit]. / Intérêt de la consultation d'anesthésie par rapport à la seule visite préanesthésique.

OBJECTIVE: In France, a preanaesthetic assessment (PAA) several days prior to hospital admission for a scheduled surgical or diagnostic procedure under anaesthesia, associated with a preanaesthetic visit (PAV) the day before, are compulsory. This study aimed at comparing the benefits of PAA with those of a PAV not preceded by a PAA. STUDY DESIGN: Prospective, controlled, randomized study. PATIENTS: The study included 296 patients undergoing either a urologic, or ophthalmologic, or ENT procedure, randomly allocated either to a PAA (followed by a PAV) group or a PAV (without previous PAA) group. METHODS: The main criterion of comparison was the duration of preanaesthetic hospital stay and the secondary criteria were the incidence of procedure postponements and patients' satisfaction respectively. RESULTS: In the PAA group, the preanaesthetic hospital stay was shorter by 0.4 days (P = 0.001). Out of the 19 postponed procedures (7%), the cause of postponement was a medical one in 15 patients: 13 in the PAV group and 2 in the PAA group respectively (P = 0.009). The PAA was not considered as a constraint by most patients. CONCLUSION: The PAA shortens the duration of preanaesthetic hospital stay and decreases the incidence of procedures postponed for a medical cause.

[Pseudo-late onset cutaneous parphyria in haemodialysis patients. Clinical and histological features. 9 cases (author's transl)]. / La pseudo-porphyrie cutanée tardive des hémodialyses. Aspects cliniques et histologiques à propos de 9 cas

In the context of a study of cutaneous problems seen in chronic renal failure patients on intermittent haemodialysis, the authors noted bullous eruptions very similar to late onset cutaneous porphyria. The bullae occur during the summer and are situated on exposed areas, in particular the head and neck. There is skin fragility and the bullae are transient, giving place to erosions and later to atrophic scarring. Even pseudo-miliary cysts have been observed. Histology reveals a sub-epidermal bulla, the basis of which consists of spiky papillary dermis. Immunofluorescence show immunoglobulin deposits in the vessels and basal membrane. All porphyrin measurements are negative. This disorder may be due to the presence of a non-porphyrinogenic photo-sensitising substance, found in certain types of plastic tubing.

[Treatment of cancer of the kidney with interleukin 2 in adults, the Lyon experience]. / Traitement par l'interleukine 2 du cancer du rein de l'adulte, l'expérience lyonnaise.

Like interferon-alpha, interleukin 2 (IL2) is active on metastatic kidney cancers, which are regarded as chemoresistant tumors. Out of 20 to 30% objective responses, 5 to 10% complete remissions are reported with various IL2 delivery schedules. The considerable toxicity is well mastered at present, thus allowing treatment in non-intensive care departments, or even in an ambulatory mode for subcutaneous administration. Even though Interleukin 2 has been authorized for sale in France, optimal mode of administration, the role of the IL2-interferon-alpha combination or the predictive factors of response to treatment still raise many questions.

[Immunotherapy of metastatic kidney cancer]. / Immunothérapie du cancer du rein métastatique.

Interleukin 2 (IL2), like Interferon alpha (IFN), is active in metastatic renal cancer, considered to be a chemoresistant cancer. 20 to 30% of objective responses, including 5 to 10% of complete remissions are reported with various protocols of IL2 administration. The considerable toxicity is now well controlled, allowing treatments to be administered in standard wards or even on an outpatient basis by subcutaneous injection. IFN, generally given as long-term treatment, achieved average response rates of between 15 and 20%. Although IL2 and IFN have been granted Product Marketing Authorization in France, the modalities of optimal administration, the place of the combination of IL2-Interferon alpha and the factors predictive of response to treatment still remain unclear.

[Postoperative analgesia for nephrectomy]. / Analgésie postopératoire pour la néphrectomie.

The aim of this study of post-nephrectomy acute pain in 30 patients was to compare three methods of postoperative analgesia and determine which one could be the most satisfactory. Ten patients received epidural analgesia with pethidine (400 mg.24 h-1 for 48 hrs). Ten other patients received intrapleural analgesia with bupivacaine (0.2 mg.kg-1.h-1 of 0.5% bupivacaine with 1/200,000 epinephrine). The ten remaining patients received systemic IV analgesia (2 g of propacetamol every 6 hrs and 0.15 mg of buprenorphine every 6 hrs). According to results of pain evaluation score (VAS) epidural analgesia with pethidine (VAS less than 2.5) appeared to be the best tested analgesic method. IV systemic analgesia (VAS less than 5) was less effective. Intrapleural bupivacaine (VAS greater than 5) was ineffective but apparently not toxic (serum concentration less than 1,200 ng.ml-1).