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Biomedical subjects

G Nitenberg

Publications and source records attributed to G Nitenberg.

At least 55 records · Page 3Linked to original sources
PubMed1996

[Gastroduodenal ulcers in intensive care units].

In intensive care units, gastroduodenal ulcers may occur in a context of aggression or multiple organ failure or result from iatrogenic causes. Thus it is difficult to construct a unique theory of pathogenesis and consequently define a precise therapeutic target. The mechanisms which disrupt the protective digestive mucosa occur as the consequences of "intensive care stress". Factors favoring the development of these stress lesions of the gastroduodenal mucosa include multiple trauma, surgery, extensive burns, acute renal failure, acute respiratory failure, shock or severe infection. These factors should be distinguished from the recently defined risk factors for hemorrhage: defective hemostasis, respiratory failure requiring prolonged ventilation assistance. The first objective in preventing stress bleeding in the intensive care unit is thus to correct these favoring factors. The only target for drug prophylaxy is gastric oversecretion which can be well controlled with anti-H2 agents but also with sucralfate. These often expensive treatments improve the rate of complications but do not decrease overmortality related to this complication. Curative treatment is difficult in these severely ill patients. It is thus necessary to define high-risk patients who could benefit significantly from these treatments.

Critical Care↗
PubMed1996

Exotoxin A stimulates fluid reabsorption from distal airspaces of lung in anesthetized rats.

To determine whether exotoxin A may affect the transport of fluid across the lung epithelium, two isogenic strains of Pseudomonas aeruginosa PA103 (10(8) colony-forming units), one (PA103 tox omega) with a structural gene mutation in exotoxin A, were instilled into the distal airspaces of anesthetized rats. PA103 parental strain, but not its mutant, stimulated the removal of fluid from the distal airspaces of the lung. Instillation of exotoxin A alone caused a dose-dependent increase in the fluid transport across the lung epithelium. Instillation of amiloride (10(-3) M) with exotoxin A demonstrated that this effect partially depended on increased uptake of sodium across the lung epithelium. The absence of stimulation after instillation of an exotoxin A mutant (PE delta Glu553) without ADP-ribosyltransferase activity demonstrated that the effect of exotoxin A depended on its ADP-ribosyltransferase activity. Finally, the instillation of exotoxin A in rats depleted of macrophages indicated that the effect of exotoxin A was not secondary to the activation of alveolar macrophages by this toxin. In conclusion, these results indicate that the in vivo release of exotoxin A by live airspace P. aeruginosa directly stimulates the fluid removal from the airspaces by the lung epithelium. This may alter the volume or composition of airway secretions, and may contribute to the lung disease in patients infected with P. aeruginosa.

ADP Ribose Transferases↗
PubMed1996

Transforming growth factor-alpha increases alveolar liquid clearance in anesthetized ventilated rats.

The effect of transforming growth factor-alpha (TGF-alpha) on alveolar liquid clearance was examined in ventilated, anesthetized rats. An isosmolar Ringer lactate solution with 10, 50, or 200 ng/ml TGF-alpha and 125I-labeled albumin as the alveolar protein tracer was instilled into the right lower lung lobe; the rats were studied for 1 and 4 h. Compared with control rats, addition of 50 ng/ml TGF-alpha to the instilled fluid increased alveolar liquid clearance by 47% over 1 h and by 66% over 4 h (P < 0.05). This increase was similar to the 50% increase in alveolar liquid clearance over 1 h in rats instilled with a beta-adrenergic agonist, salmeterol (28). There was a dose-dependent effect of TGF-alpha (10, 50, 200 ng/ml) on alveolar liquid clearance. The combination of both TGF-alpha and salmeterol did not have an additive effect on alveolar liquid clearance. The TGF-alpha-stimulated increase in alveolar liquid clearance was inhibited by amiloride (10(-4) M), indicating that the increase in clearance depended on increased Na+ uptake across the alveolar epithelium. There was only a twofold increase in intracellular cAMP levels in isolated rat alveolar epithelial type II cells after stimulation with TGF-alpha. In contrast, beta-adrenergic agonist treatment increased intracellular adenosine 3',5'-cyclic monophosphate (cAMP) levels more than tenfold. Genistein (10(-6) M), a tyrosine protein kinase inhibitor, inhibited the TGF-alpha-stimulated increase in alveolar liquid clearance. In summary, TGF-alpha can stimulate in vivo alveolar liquid clearance at a rate similar to beta-adrenergic stimulation by increasing Na+ uptake by alveolar epithelial type II cells. However, the effect may be mediated by a non-cAMP dependent mechanism. Because genistein blocked the increase in alveolar fluid clearance, the signal transduction may involve genistein-dependent phosphorylation.

Adrenergic beta-Agonists↗
PubMed1995

Early tracheotomy in neutropenic, mechanically ventilated patients: rationale and results of a pilot study.

Despite substantial advances in the management of such patients, the prognosis of ventilated neutropenic patients remains grim. The objective of our study was to evaluate the benefit of tracheotomy in this category of patients, in terms of mortality while they were in the intensive-care unit and nosocomial pneumonias. The charts of 53 consecutive, ventilated, neutropenic patients, or those destined to be imminently neutropenic, admitted to our intensive-care unit during a 4-year period, have been retrospectively reviewed. Tracheotomy was performed at the bedside or in the operating room: 20 patients underwent tracheotomy within 48 h of mechanical ventilation (ET group), while 33 were tracheotomized later or remained intubated (INT group). The two groups were comparable with regard to the underlying disease, respiratory failure, mechanical ventilation patterns and severity scores, but neutropenia was more profound in the ET group. Mortality while in the intensive-care unit was similar (ET: 70%; INT: 78.8%). However, the survival curves showed a trend towards longer survival in the ET group, even after adjustment for the degree of neutropenia (log-rank test: P = 0.07). The incidence of pneumonias was similar in both groups. No major complications of tracheotomy were reported. These findings suggest that a tracheotomy could be proposed for neutropenic patients requiring mechanical ventilation, in order to prolong their survival beyond the end of the neutropenic period. A prospective study is underway to confirm these preliminary results.

Adolescent↗
PubMed1995

Totally implanted catheters to reduce catheter-related infections in patients receiving interleukin-2: a 2-year experience.

A high incidence of bacterial infections has been previously reported during interleukin-2 (IL-2) treatment, mainly due to catheter-related infections. Antibiotic prophylaxis has been successfully used to decrease such infections. The goal of this study was to evaluate an alternative way to reduce catheter-related infections in IL-2-treated patients by the use of totally implanted catheters. A total of 74 patients with metastatic renal cell carcinoma, referred to our institution to receive IL-2 from March 1989 to July 1991, were included in this prospective study. IL-2 was given on a 2-days-a-week schedule (24 x 10(6) IU m-2 day-1) either alone (41 patients) or in association with interferon gamma (33 patients). All these patients were prospectively evaluated for fever, bacteremia and line-site infection. Seven patients (9.5%) had one (2 patients) or more (5 patients) positive blood cultures with Staphylococcus aureus. Antibiotics were used only in 5 patients, and the catheter had to be removed in only 2 of these patients. In the other patients, no further infection developed despite the lack of antibiotics. Moreover, 9 patients had positive blood cultures with Staphylococcus epidermidis (1.9% of total number of blood cultures). In conclusion, a totally implanted catheter appears to reduce the incidence of infections in IL-2-treated patients, at least on a 2-days-a-week schedule.

Antineoplastic Agents↗
PubMed1995

Safety of tracheotomy in neutropenic patients: a retrospective study of 26 consecutive cases.

OBJECTIVE: To evaluate the safety of tracheotomy in neutropenic ventilated cancer patients, in terms of infectious and haemorrhagic complications. DESIGN: Retrospective study. SETTING: A medical-surgical intensive care unit in a Cancer-hospital. PATIENTS AND PARTICIPANTS: 26 consecutive patients undergoing a tracheotomy in neutropenic period, from 1987 to 1990. INTERVENTIONS: Tracheotomy, performed at the bedside or in operating room. MEASUREMENTS AND RESULTS: In all neutropenic patients undergoing a tracheotomy, the characteristics and duration of both neutropenia and mechanical ventilation have been recorded. Stomal bleeding and infection, and infectious pneumonias and alveolar haemorrhage have been carefully reviewed. Platelets were transfused in 23 of the 26 patients at the time of the procedure; no local haemorrhage was observed. Neither stomal nor pulmonary infections secondary to tracheotomy were noted. No respiratory worsening was attributable to the tracheotomy. Nineteen patients (73%) died in ICU, without direct link between tracheotomy and death. CONCLUSIONS: These findings suggest that a tracheotomy can be safely performed in neutropenic patients requiring mechanical ventilation.

Decision Making↗
PubMed1994

Immunotherapy with interleukin-2 (IL2) and lymphokine-activated natural killer cells: improvement of clinical responses in metastatic renal cell carcinoma patients previously treated with IL2.

Treatment with interleukin-2 (IL2) induces clinical responses in 15-30% of metastatic renal cell carcinoma (MRCC) patients, with mainly partial responses. In order to improve clinical response, we decided to treat partial response patients from a previous IL2 treatment with a second course of IL2 associated with lymphokine-activated natural killer (LANAK) cells. 10 patients who underwent PR after an IL2 protocol (24 x 10(6) U/m2/day, 2 days a week for 5 weeks, either alone or with interferon-gamma) subsequently received a combination of high-dose IL2 (16-20 x 10(6) U/m2/day, 2 days a week) and LANAK cell infusions. Four complete responses were obtained, and 2 additional patients whose tumour mass was further reduced achieved complete response following surgery. These results support the view that initial responses obtained with primary IL2 courses can be improved by complementary treatments. The potential role of cellular immunotherapy and, more particularly, of LANAK cells as an effective procedure to further reduce tumour burden in patients responsive to IL2 will have to be assessed in randomised studies.

Adult↗
PubMed1994

Lack of oxygen supply dependency in patients with severe sepsis. A study of oxygen delivery increased by military antishock trouser and dobutamine.

BACKGROUND: During severe sepsis, the existence of a pathologic oxygen supply dependency remains controversial. STUDY OBJECTIVE: To evaluate the relationship between oxygen delivery (DO2) and oxygen consumption (VO2) during severe sepsis and to compare, in this respect, survivors and nonsurvivors and patients with normal or increased concentration of plasma lactate. STUDY DESIGN: Cohort analytic study. SETTING: Three European ICUs in university hospitals. PATIENTS: Seventeen mechanically ventilated patients with severe sepsis (six with high blood lactate levels) studied within the first day of diagnosis. INTERVENTIONS AND MEASUREMENTS: Pulmonary elimination of carbon dioxide, or carbon dioxide production (VCO2) and VO2 were measured by indirect calorimetry before and after two interventions designed to increase DO2 (calculated from the Fick equation): inflation of a military antishock trouser (MAST) and infusion of dobutamine. RESULTS: During MAST inflation, DO2 increased by 19% in patients with a normal concentration of plasma lactate (p < 0.01), but remained unchanged in patients with high lactate levels. During dobutamine infusion, DO2 increased in both groups by 16% (p < 0.01) and 20% (p < 0.05), respectively. In both groups, we found that the VO2 and VCO2 were not affected by either the MAST or the dobutamine-induced increase in DO2. There was no difference between survivors and nonsurvivors. CONCLUSION: There was no evidence of a pathologic oxygen supply dependency in patients with severe sepsis, even in those who had an elevated concentration of plasma lactate and in those who ultimately died. These results do not favor the conclusion that maximizing DO2 is a primary therapeutic objective in such patients.

Acute Disease↗
PubMed1993

Combination of interleukin-2 and gamma interferon in metastatic renal cell carcinoma.

The use of high-dose interleukin-2 (IL2), alone or in association with lymphokine activated killer cells in patients with metastatic renal cell carcinoma (MRCC) results in a 20-25% response rate. However, the toxicity of IL2 is substantial and despite many clinical trials, response rates initially reported have not been improved. The aim of this study was to evaluate a combination of IL2 and gamma interferon (IFN) in MRCC with respect to both efficacy and tolerance. IL2 was given by continuous intravenous infusion at a daily dose of 24 x 10(6) U/m2 for 2 consecutive days during 5 consecutive weeks. Gamma IFN was given subcutaneously at a daily dose of 5 x 10(6) U/m2 on the same days as IL2. 33 patients with MRCC entered the study. Clinical responses were comparable with other published series: 7 patients (21%) achieved partial response, 13 (39%) were stable and 13 had progression, despite therapy. Immunological profile observed with this regimen showed a major increase in natural killer cells which became the predominant lymphocyte population at the end of the therapy. Tolerance was good with 92.5% of the planned doses actually received by the patients. This was reflected by an early discharge from the hospital in 95% of the cycles, increasing acceptability of the regimen by the patients.

Adult↗
PubMed1991

Wegener's granulomatosis presenting as diffuse pulmonary hemorrhage.

A 35-year-old woman experienced diffuse intraalveolar haemorrhage with respiratory distress and acute renal failure. Renal histology and evolution confirmed Wegener's granulomatosis. Early use of immunosuppressive drugs allowed weaning from mechanical ventilation and temporary improvement of the renal failure. A review of the literature emphasizes the rarity of alveolar hemorrhage as an initial symptom of Wegener's granulomatosis and the necessity of aggressive management.

Adult↗
PubMed1991

Heat and moisture exchanger vs heated humidifier during long-term mechanical ventilation. A prospective randomized study.

Adequate humidification of inspired gases with HMEs during long-term MV remains controversial. In this study, a comparison is made between tracheal secretions during long-term MV either with HME or conventional HH. Both the HME and HH groups were similar with respect to age, sex, diagnosis, duration of MV, SAPS and mortality. Temperature of gases in the tracheal tube was lower and the amount of tracheal instillations was greater in the HME group than in the HH group. Tracheal secretions became thicker between day 1 (control) and day 5, in the HME group than in the HH group. Four and two tube occlusions occurred in HME and HH groups, respectively. Tracheal bacterial colonization was similar in the two groups. Given the advantages of HME (reduced nurses' work and financial cost), HME could be routinely used under cautious surveillance and replaced by HH if difficulty in suctioning occurs.

Female↗
PubMed1991

[Synchronous cancers of the esophagus and of the ORL area: results of combined treatments with esophagectomy (28 cases)].

Twenty-eight patients with synchronous esophageal and head and neck epidermoid cancers have been treated by a combined protocol including esophagectomy. Seventy-nine percent received pre-operative chemotherapy, 50% had resection of the head and neck lesion at the same time as the esophagectomy and 79% received post-operative irradiation. Two patients died during the post-operative period (7%), and 1, 2 and 3-yr survival rate (Kaplan-Meier) was respectively 64, 32 and 27%. Contrary to our initial assumption, there was no significant decrease in survival compared to patients operated on for an isolated esophageal cancer. The patients were divided into 4 very simple prognostic groups based on the T and N stages of the clinical pre-therapeutic TNM classification: T1 or T2 for esophageal lesions and different T or N stages according to the prognosis for head and neck lesions. A study of each group tended to show that esophagectomy was beneficial except in cases of synchronous T2 esophageal cancer and locally advanced head and neck cancer (there was 2-yr survival in this group). The 28 patients studied represent a particular population which presented 91 cancerous localisations during the duration of the study (mean: 3.25 localisations per patient).

Carcinoma, Squamous Cell↗
PubMed1990

Acute myocardiotoxicity during 5-fluorouracil therapy.

A 38-year-old man with a colonic carcinoma experienced cardiogenic shock during continuous intravenous treatment with 5-fluorouracil (5-FU), without clinical or electrical signs of coronary insufficiency and with a normal coronary angiogram. His symptoms resolved after eight days of inotropic and vasodilator therapy. Because of the severity of the shock, rechallenge was not performed. This is the first case of acute cardiac failure without coronary ischemia, associated with 5-FU monotherapy. Experimental studies suggest that this adverse effect could be due to myocardial accumulation of 5-FU leading to depletion of high energy phosphate compounds. This might also explain the more frequently seen acute coronary insufficiency due to 5-FU.

Adult↗