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Biomedical subjects

A Mercatello

Publications and source records attributed to A Mercatello.

At least 19 recordsLinked to original sources
PubMed1992

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.

Adult↗
PubMed1992

[Treatment of renal cancer in adults with interleukin 2].

Interleukin 2 is active in metastatic renal adenocarcinoma which is usually considered as a chemoresistant tumour; 20 to 30% objective responses, including 5 to 10% complete remissions, are reported using various treatment schedules. Toxicity, though of great concern, is now controlled and IL2 is mostly used in standard oncology units or as an out-patient subcutaneous treatment. Even if IL2 is now a registered drug in France, many questions remain however, regarding the optimal schedule and dose, the interest of combining IL2 with interferon alpha or the predictive factors of response of this therapy.

Adult↗
PubMed1992

[Acute respiratory insufficiency in sickle cell disease].

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.

Acute Disease↗
PubMed1992

Intravenous interleukin-2 in patients over 65 with metastatic renal carcinoma.

The present study was designed in order to evaluate the response rate and the toxicity of continuous infusion of Interleukin 2 (IL2) in patients over 65 with metastatic renal cell carcinoma. Twenty-five patients, median age 69 (range 65-77), without any prior systemic anticancer therapy received a continuous infusion of IL2 at a dose of 18 x 10(6) iu m-2 d-1 for 2 periods of 5 days separated by a 6 day break. Toxicity was not different compared with younger patients (e.g. fever, hypotension, rise in creatinine level), except for cardiac toxicity which was of great concern. Despite normal cardiac tests prior to inclusion into the study, abnormalities of the cardiac rhythm ranging from tachycardia to ventricular extrasystoles occurred in 44% of the patients and IL2 cardiac toxicity was responsible for one toxic death. Three objective responses, i.e. one partial and two complete persistent responses, were seen in 22 evaluable patients. Thus, if age does not seem to modify the potential for response to IL2 therapy, cardiac toxicity appears as a limiting factor for intravenous schedules of IL2.

Aged↗
PubMed1992

Phase I trial of recombinant interleukin-2 followed by recombinant tumor necrosis factor in patients with metastatic cancer.

In this Phase I trial, the feasibility of sequential administration of continuous intravenous recombinant interleukin-2 (rIL-2) at 18 x 10(6) IU/m2/day for 6 days, followed by three daily bolus intravenous recombinant tumor necrosis factor (rTNF) infusions at doses escalating between 10 and 120 micrograms/m2/day, was investigated in 31 patients with metastatic malignancies. Prophylactic use of indomethacin prior to and during rTNF administration was found to significantly reduce toxicity. However, despite prophylactic indomethacin, a maximum tolerated dose of rTNF of 120 micrograms/m2 was reached. The limiting toxicity was hypotension. Predictable flu-like toxicities (i.e., fever/chills, hypotension, gastrointestinal toxicity, edema, malaise) were seen in most patients. These started during the rIL-2 infusion and continued during rTNF administration, particularly in the absence of indomethacin. Hematological, renal, and hepatic toxicities were not dose limiting. These toxicities were all reversible after treatment interruption. Pulmonary toxicity [i.e., anaphylactic-like reactions, bronchospasms, and adult respiratory distress syndrome (ARDS)] was seen in several patients immediately after rTNF infusions, irrespective of the rTNF dose or treatment cycle, and mainly in patients with extensive pulmonary metastases. The combined effect of treatment-related ARDS, lung metastases, and a Guillain-Barré syndrome led to the death of one patient. Two partial responses were seen in this study (i.e., breast and renal cancer). Based on these results, a Phase II trial of rIL-2 followed by rTNF has been initiated in metastatic breast cancer patients.

Adolescent↗
PubMed1992

[Analysis of changes in serum levels of TNF, IL-1 and IL-6 during administration of IL-2. Correlation with clinical response to treatment].

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.

Adenocarcinoma↗
PubMed1991

Recombinant interleukin-2 in metastatic renal cell carcinoma--a European multicentre phase II study.

This multinational, multicentre study represents the introduction of recombinant interleukin-2 (rIL-2) in Europe. From December 1987 to June 1989, 57 eligible patients with metastatic renal cell cancer were treated with rIL-2 administered as continuous intravenous infusion. 8 out of 51 evaluable patients responded (16%), 2 complete remission (CR) and 6 partial remission (PR). 10 patients had no change (20%). The response duration for CR was 209 and 394+ days. The median response duration for PR was 371 (range 140-506+) days. Dose-limiting grade 3-4 toxicities were hypotension in 52% of the patients, arrhythmia (4%), dyspnoea (8%), creatinine rise (4%), peripheral neurotoxicity (10%) and central neurotoxicity (10%). Toxicities most often recovered solely on interrupted therapy. 2 patients died due to catheter-related septicaemia and one patient died of rIL-2 induced renal failure. The study confirmed the antitumour efficacy of rIL-2 in renal cell cancer. Toxicities were numerous, but manageable by close observation in a normal oncology ward without routine use of an intensive care unit.

Adult↗
PubMed1991

[Cerebral aspergillosis in immunocompromised patients].

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.

Adult↗
PubMed1991

Acute renal failure with preserved renal plasma flow induced by cancer immunotherapy.

Adoptive immunotherapy in patients with advanced cancer produces significant regression of metastatic disease in selected patients, but it is complicated by severe side effects. Prevention of these complications is still limited because their precise mechanisms remain unknown. For this reason we have investigated renal function and hemodynamic parameters in 16 patients with renal cell carcinoma before and during treatment with a combination of high doses of both recombinant interleukin-2 (rIL2) and recombinant alpha-interferon. After patients had received three injections of combined immunotherapy, there was a decrease in mean blood pressure (-20%), glomerular filtration rate (-25%), urine output (-50%), and fractional sodium excretion (-0.8%). This was associated with an increase in heart rate (+30%), plasma creatinine level (+30%), fractional potassium excretion (+14%) and microalbuminuria (+130%). However, renal plasma flow remained constant. The increment in microalbuminuria may reflect an alteration of glomerular capillary permeability. The reduction in GFR may be accounted either for a decrease in efferent to afferent arteriolar resistance ratio, leading to a decrease in glomerular capillary pressure, or for a decrease in ultrafiltration coefficient, or both. Nonsteroidal antiinflammatory drugs, such as ketoprofen, used to minimize side effects, could considerably worsen renal function and should be avoided in patients treated by rIL2. Our results bring new insights into the pathogenesis of functional acute renal failure and provide a rational basis for the use of vasopressors in the treatment of cytokine-induced acute renal failure.

Acute Kidney Injury↗
PubMed1991

Microalbuminuria is acutely increased during anesthesia and surgery.

Microalbuminuria is known to increase in various diseases with potential repercussion on the kidneys and indicates an increase in glomerular intracapillary pressure or changes in permeability characteristics. In this study, we measured whether albumin excretion is affected in patients undergoing anesthesia and surgery, which are both known to induce dramatic changes in renal function and in the release of vasoactive substances such as catecholamines, vasopressin, angiotensin, and prostaglandins. Seven patients with normal renal function and physiological microalbuminuria prior to surgery were studied. Urine samples were collected before anesthesia, just before the beginning of surgery, and thereafter 30 min following incision, and 30 min after the end of surgery. Anesthesia induced a significant increase in microalbuminuria, which further increased during surgery. After the end of surgical procedure, microalbuminuria decreased but remained significantly higher than control. This phenomenon may be due to an increase in intracapillary glomerular pressure and/or an alteration in glomerular permeability induced by a direct effect of drugs, or to the action of vasoactive substances on the glomerular structure.

Adult↗
PubMed1991

[Adverse effects of interleukin 2].

Interleukin 2, has frequent and important side effects. Toxic effects observed are systemic (fever, chills, malaise), hemodynamic (capillary leak syndrome, hypotension), cardiac (arrhythmia, infarction), renal (renal dysfunction), infectious (septicemia), cutaneous, hematologic, gastrointestinal, endocrinologic and metabolic. Side effects are dose-dependent, generally reversible, with a mortality from 1 to 3%. Regimens of administration and other cytokine combinations affect interleukin 2 toxicity. If the treatment of these side effects is well known, selection of patients and specialized care unit remain always necessary.

Animals↗
PubMed1990

Correlation between clinical response to interleukin 2 therapy and sustained production of tumor necrosis factor.

Twenty-five previously untreated patients with metastatic renal cell carcinoma were treated with 5-day cycles of continuous infusion of interleukin 2 (IL2) and lymphokine-activated killer cell reinfusion. Five achieved a partial response. Three patients were found to have detectable tumor necrosis factor (TNF) in serum before initiation of therapy. On the fifth day of therapy, 24 patients had circulating TNF with immunoradiometric assay whereas 13 had detectable biological activity. Two days after the end of IL2 therapy, TNF concentration (immunoradiometric assay) decreased in most cases but was still detectable in 17 patients. Thirteen patients had still circulating TNF bioactivity. Although there was no significant difference between TNF levels observed on the fifth day of therapy in the responder and nonresponder groups, 48 h after the end of IL2 infusion, both the TNF concentration and the biological activity were significantly higher in the group of responder patients. This result suggests that the clinical response to IL2 therapy in patients with metastatic renal cell carcinoma is correlated to a sustained production of TNF after the end of IL2 infusion.

Animals↗
PubMed1990

[Electrophoresis of cholinesterases of the cerebrospinal fluid in the Guillain-Barré syndrome].

Polyacrylamide gel electrophoresis of cholinesterase from cerebrospinal fluid was performed in 22 patients with Guillain-Barré syndrome. Fifteen of these patients had an abnormal cerebrospinal fluid with emergence of a second electrophoretic migration band corresponding to non-specific cholinesterase. Among 182 patients with a variety of diseases who served as controls, only one presented with this abnormality. From these data the sensitivity and specificity of cerebrospinal fluid cholinesterase electrophoresis were calculated at 68 and 99 percent respectively. The second migration band seems to appear early in the course of the disease and disappears when the patient is cured. Moreover, the occurrence of this band is correlated with the severity of the condition, as shown by a greater number of patients under artificial ventilation and by a longer stay in intensive care unit. Cerebrospinal fluid electrophoresis could be used as a prognosis factor.

Adolescent↗
PubMed1990

[Changes in renal function induced by anesthesia].

The rate of urine formation and its composition are influenced by the different drugs used during surgery. Anaesthetics act on renal function, not only directly, but also by producing changes in cardiovascular function and in neuroendocrine activity. Many factors may be incriminated: lowered blood pressure and cardiac output, increased sympathetic outflow (renal nerve stimulation and increased plasma catecholamines), increased release of renin, angiotensin and vasopressin. The effects of anaesthetics on the kidney go beyond a simple change in basal haemodynamics and include, for some drugs, an alteration in the ability for the kidney to autoregulate its blood flow and glomerular filtration rate. Studies on toad bladders showed a decrease in transport of water, sodium and organic anions. But, in fact, renal effects of anaesthetics in man and animals depend on the species, the anaesthetic and the method used to study the effect. Most barbiturates and inhalational anaesthetics tend to decrease renal blood flow (RBF) and glomerular filtration rate (GFR). These trends are gradually reversed during recovery. The effects of ketamine and diazepam are not clearly defined. Morphine and fentanyl decrease urine flow and GFR, whilst RBF increases or decreases, depending on whether a direct or indirect measurement technique was used. Muscle relaxants have little effect on renal function. Spinal and epidural anaesthesia only slightly decrease GFR and RBF in proportion to the decrease in mean arterial pressure. Obviously, the preexisting intravascular volume and the quantity of intravenous fluids given strongly influence the renal response to spinal and epidural anaesthesia. Some studies have shown that urine flow rate, creatinine clearance, urinary sodium excretion and RBF are reduced during mechanical ventilation with positive end-expiratory pressure. Surgery itself influences renal function by inducing alterations in prerenal haemodynamics. Operative stress leads to an increase in circulating catecholamines and angiotensin. Significant fluid shifts, excessive blood loss and redistribution of a third space may lead to a prerenal oliguric state, increasing secretion of vasopressin. Acute renal failure (ARF) is a frequently lethal complication of critical surgical illness, due to a variety of factors which interfere with glomerular filtration and tubular reabsorption, such as renal hypoperfusion or nephrotoxic insults. In fact, the initiating aggression ultimately culminates in the development of one or more of the maintenance factors (decreased tubular function, tubular obstruction, decreased GFR and RBF) that reduce urine flow and osmolar excretion. Good management during the perioperative period tends to minimize the risk of developing ARF.

Acute Kidney Injury↗
PubMed1990

Functional and immunophenotypic modifications induced by interleukin-2 did not predict response to therapy in patients with renal cell carcinoma.

Twenty-five patients with renal cell carcinoma were treated with continuous infusion of IL-2 (3 x 10(6) units/m2/day) with or without lymphokine-activated killer (LAK) cells; 5 responded to therapy. Functional and immunophenotypic modifications of the peripheral blood lymphocytes (PBLs) did not predict response to therapy. Systemic administration of interleukin-2 (IL-2) during 5 days caused a preferential proliferation of natural killer (NK) cells, although CD4+ T cells remained the predominant circulating population, in particular in three of the five responding patients. The IL-2 low-affinity receptor was induced only on CD4+ T cells. B cells did not proliferate and immunoglobulin levels were not modified by IL-2. In the peripheral blood, the NK function increased but the LAK function in vivo remained low. The T-cell proliferative response in mixed lymphocyte cultures (MLCs) decreased after therapy. Four days of ex vivo culture of PBLs with IL-2 did not modify T and NK distributions, but increased the coexpression of CD8 on NK cells and NKH1 density; it decreased the coexpression of CD16 and induced LAK cell function. Three weeks after the end of the first course of therapy and before the second course was started, all immunological parameters returned to baseline levels, except the T-cell proliferative response in MLCs. The second course of IL-2 therapy induced the same modifications as the first one, with the exception of a higher CD4+ T-cell proliferation.

Adult↗