Previously, polymerase chain reaction (PCR) technology has been hampered by its inability to generate quantitative results, a drawback inherent to the high degree of amplification taking place in the ...reaction. Recently, PCR techniques have been described with the potential of quantifying the amount of mRNA or DNA in biological samples. In this study quantitative PCR was used to investigate the role of the EGF (epidermal growth factor) system in cancer both for measurements of mRNA concentrations and for measurements of the number of copies of specific genes. It is shown that the mRNA expression of a subset of ligands from the EGF system is increased in bladder cancer. Furthermore, measurement of the mRNA concentration gives important information such as the expression of these ligands correlated to the survival of the patients. In addition to the alterations at the mRNA level, changes also can occur at the DNA level in the EGF system. Thus, it has been demonstrated that the number of genes coding for the human epidermal growth factor receptor 2 (HER2) is increased in a number of breast tumors. It is now possible to treat breast cancer patients with a humanized antibody reacting with HER2, and the treatment is considered to be justified if the tumor displays an increased amount of HER2. For this reason there is a need for techniques suitable for HER2 measurements. A LightCycler real-time PCR method used for HER2 neu DNA quantification was evaluated and the results compared with those obtained by immunohistochemistry (IHC) and fluorescence in situ hybridization (FISH). Tumor biopsies were collected from 112 patients diagnosed with early breast cancer from January 1990 to March 1994. The samples were analyzed for HER2 DNA amplification by real-time PCR on LightCycler and by FISH and for HER2 protein expression by IHC. Inter-assay variation for HER2 measured by LightCycler was 10% (×=3.1; n=17). Amplification ≥2 was observed in 19% of the patients. Concordance rates between real-time PCR and the other methods were 91% (IHC) and 92% (FISH). The correlation between real-time PCR and FISH was highly significant (p<0.001). The "LightCycler-HER2 neu DNA quantification kit" produces results with a high level of reproducibility and its ease of use allows rapid screening for amplification of HER2. In this paper useful information is given on how real-time PCR compares with FISH and IHC. The data show that results obtained for amplification of HER2 by real-time PCR on the LightCycler instrument are comparable to results obtained by IHC and FISH.
Abstract Sickle cell anemia (SCA) is characterized by hemoglobin polymerization that results in sickle-shaped red blood cells. The vascular obstruction by sickle erythrocytes is often inflammatory, ...and purinergic system ecto-enzymes play an important role in modulating the inflammatory and immune response. This study aimed to evaluate the E-NTPDase and E-ADA activities in lymphocytes of SCA treated patients, as well as verify the cytokine profile in this population. Fifteen SCA treated patients and 30 health subjects (control group) were selected. The peripheral lymphocytes were isolated and E-NTPDase and E-ADA activities were determined. Serum was separated from clot formation for the cytokines quantification. E-NTPDase (ATP and ADP as substrate) and E-ADA (adenosine as substrate) activities were increased in lymphocytes from SCA patients ( P < 0.001). The TNF-α and IL-6 serum cytokines showed decreased on SCA patients comparing to control ( P < 0.001). The regulation of extracellular nucleotides released in response to hypoxia and inflammation through E-NTPDase and E-ADA enzymes represent an important control of purine-mediated in the SCA disease, avoiding elevated adenosine levels in the extracellular medium and consequent organ injuries in these patients. The pro-inflammatory cytokines decreased levels by use of hydroxyurea occur in attempt to reduce the pro-inflammatory response and prevent vaso-oclusive crisis.
About 15% of patients with haematological malignancy develop acute respiratory failure (ARF), necessitating admission to intensive care where their mortality is of the order of 50%.
The prognosis of ...these patients is not determined by the pathological characteristics of the malignancy but by the cause of the acute respiratory failure. In effect, the need to resort to mechanical ventilation in the presence of dysfunction of other organs dominates the prognosis. Even if the use of non-invasive ventilation in these patients has reduced the need for intubation and reduced the mortality, its prolonged use in the most severely affected patients prevents the optimal diagnostic and therapeutic management.
Fibreoptic bronchoscopy with broncho-alveolar lavage (BAL) is considered the cornerstone of aetiological diagnosis but its diagnostic effectiveness is poor, at best 50%, and this has led to increasing interest in high resolution CT scanning and regularly reawakens a transitory enthusiasm for surgical lung biopsy. Furthermore, in hypoxaemic patients, fibreoptic bronchoscopy with BAL may be the origin of the resort to mechanical ventilation, and thus increased mortality. The place of recently developed non-invasive tools is under evaluation. In effect, though the individual performance of diagnostic molecular techniques on sputum, blood, urine or naso- pharyngeal secretions has been established, the combination of these tools as an alternative to BAL has not yet been reported.
This review deals with acute respiratory failure in patients with haematological malignancy. It includes a review of the recent literature and considers the current controversies, in particular the risk-benefit balance of fibreoptic bronchoscopy with BAL in severely hypoxaemic patients.
Acute respiratory failure (ARF) in patients with cancer is frequently a fatal event. To identify factors associated with survival of cancer patients admitted to an intensive care unit (ICU) for ARF, ...we conducted a prospective 5-year observational study in a medical ICU in a teaching hospital in Paris, France. The patients were 203 cancer patients with ARF mainly due to infectious pneumonia (58%), but also noninfectious pneumonia (9%), congestive heart failure (12%), and no identifiable cause (21%). We measured clinical characteristics and ICU and hospital mortality rates.ICU mortality was 44.8% and hospital mortality was 47.8%. Noninvasive mechanical ventilation was used in 79 (39%) patients and conventional mechanical ventilation in 114 (56%), the mortality rates being 48.1% and 75.4%, respectively. Among the 14 patients with late noninvasive mechanical ventilation failure (>48 hours), only 1 survived. The mortality rate was 100% in the 19 noncardiac patients in whom conventional mechanical ventilation was started after 72 hours. By multivariable analysis, factors associated with increased mortality were documented invasive aspergillosis (odds ratio OR, 2.13; 95% confidence intervals CI, 1.05-14.74), no definite diagnosis (OR, 3.85; 95% CI, 1.26-11.70), vasopressors (OR, 3.19; 95% CI, 1.28-7.95), first-line conventional mechanical ventilation (OR, 8.75; 95% CI, 2.35-35.24), conventional mechanical ventilation after noninvasive mechanical ventilation failure (OR, 17.46; 95% CI, 5.04-60.52), and late noninvasive mechanical ventilation failure (OR, 10.64; 95% CI, 1.05-107.83). Hospital mortality was lower in patients with cardiac pulmonary edema (OR, 0.16; 95% CI, 0.03-0.72). Survival gains achieved in critically ill cancer patients in recent years extend to patients requiring ventilatory assistance. The impact of conventional mechanical ventilation on survival depends on the time from ICU admission to conventional mechanical ventilation and on the patient's response to noninvasive mechanical ventilation.
We determined the prevalence and indicators of infection in intensive care unit (ICU) patients with diabetic ketoacidosis (DKA) by performing a retrospective analysis of 123 episodes of DKA (in 113 ...patients) managed in a medical ICU between 1990 and 1997. In univariate analysis, features associated with infection were female sex, neurological symptoms at admission, fever during the week before admission, a need for colloids, a high blood lactate level at admission, and lack of complete clearance of ketonuria within 12 h. Multivariate analysis identified 3 independent predictors of infection: female sex (odds ratio OR, 2.31; confidence interval CI, 1.05-5.35), neurological symptoms at admission (OR, 2.83; CI, 1.18-6.8), and lack of complete clearance of ketonuria within 12 h (OR, 3.73; CI, 1.58-9.09). Infection is the leading trigger of DKA in ICU patients. Neurological symptoms at admission and lack of complete clearance of ketonuria within 12 h are useful warning signals of infection.
To identify predictors of 30-day mortality in critically ill cancer patients with septic shock.
Retrospective study over a 6-year period.
Twelve-bed medical intensive care unit (ICU).
Eighty-eight ...patients (55 men, 33 women) aged 55 (43.5-63) years admitted to the ICU for septic shock.
None.
Eighty (90.9%) patients had hematological malignancies and eight (9.1%) had solid tumors; 47 patients (53.4%) were neutropenic, 19 (21.6%) were hematopoietic stem cell transplantation (HSCT) recipients, and 27 (30.7%) were in remission. Microbiologically documented infections were found in 60 (68.2%) patients. The Simplified Acute Physiologic Score II (SAPS II) and Logistic Organ Dysfunction (LOD) scores at ICU admission were 66 (47-89) and 7 (5-10), respectively, and the LOD score on day 3 was 8 (4-10). Sixty-eight (78.1%) patients received invasive mechanical ventilation (MV), 12 (13.6%) noninvasive MV, 22 (25%) dialysis. Thirty-day mortality was 65.5% (57/88). By multivariable analysis, mortality was higher when time to antibiotic treatment was >2 h odds ratio (OR), 7.05; 95% confidence interval (95% CI), 1.17-42.21 and when DLOD (day 3-day 1 LOD score/day 3 LOD score) was high (OR, 3.47; 95% CI, 1.44-8.39); mortality was lower when admission occurred between 1998 and 2000 (OR, 0.23; 95% CI, 0.05-0.98) and when initial antibiotics were adapted (OR, 0.24; 95% CI, 0.06-0.09).
Earlier ICU admission and antibiotic treatment of critically ill cancer patients with septic shock is associated with higher 30-day survival. The LOD score change on day 3 as compared to admission is useful for predicting survival.
Patients with newly diagnosed cancer responsible for organ failures may require intensive care unit (ICU) admission and immediate chemotherapy. Outcomes in this population have not been studied.
...Prospective observational cohort study.
Teaching hospital.
All patients admitted to the ICU, from January 1997 to June 2003, for organ failures due to newly diagnosed, untreated cancer and deemed necessary to receive immediate cancer chemotherapy.
None.
For the period of 6.5 yrs, 100 patients met the study criteria: 43 had acute leukemia, 37 lymphoma, and 12 solid tumors. Median Simplified Acute Physiology Score II was 39 (30-48) points, and median Logistic Organ Dysfunction score was 5 (3-7) points. Three variables were independently associated with 30-day mortality: need for vasopressor therapy (odds ratio, 6.01; 95% confidence interval, 1.86-19.4), mechanical ventilation (odds ratio, 6.36; 95% confidence interval, 1.76-22.94); and hepatic failure (odds ratio, 7.76; 95% confidence interval, 1.25-48.27). Overall survival was 60% after 30 days and 49% after 180 days.
Mortality was chiefly dependent on the nature and number of organ failures, not on the nature or stage of the malignancy. The 30-day and 180-day survival rates indicate that, in this selected group of patients, advanced disease at cancer diagnosis should not lead to refusal of ICU admission. Moreover, administration of chemotherapy in the intensive care unit is feasible, and although the mortality rate is high, routine ICU admission of patients with newly diagnosed cancer, specific organ failure, and the need for administration of chemotherapy in the ICU deserves evaluation.
When a cancer patient becomes critically ill, mechanical ventilation (MV) is often considered futile. However, recent studies have found that outcomes of critically ill cancer patients have been ...improving over the years and that classic predictors of high mortality have lost their relevance.
We retrospectively determined outcomes and predictors of 30-day mortality in 237 mechanically-ventilated cancer patients admitted to the intensive care unit (ICU).
The 132 (55.7%) patients who were admitted between 1990 and 1995 were compared with 105 (44.3%) patients who were admitted between 1996 and 1998. The malignancy was leukemia/lymphoma in 119 (50.3%) patients, myeloma in 50 (21%), and a solid tumor in 68 (28.7%). Forty-two (17.7%) patients had bone marrow transplantation, and 91 (38.4%) were neutropenic. Median Simplified Acute Physiology Score II (SAPS II) was 58 (range, 40-75). Reasons for MV were acute hypoxemic respiratory failure in 148 (62.5%) patients, coma in 54 (22.8%), and cardiogenic pulmonary edema in 35 (14.7%). Conventional MV was used first in 189 (79.8%) patients, and noninvasive MV (NIMV) was used in 48 (20.2%). Overall mortality rate was 72.5% (172 deaths).
Logistic regression identified three variables associated with mortality: ICU admission between 1996 and 1998 (odds ratio OR, 0.24; 95% confidence interval CI, 0.12-0.50) and the use of NIMV (OR, 0.34; 95% CI, 0.16-0.73) were protective, and the SAPS II was aggravating (OR, 1.04 per point; 95% CI, 1.02-1.06). To better define the impact of NIMV, we performed a pairwise-matched exposed-unexposed analysis. Forty-eight patients who did and 48 who did not receive NIMV as the first ventilation method were matched for SAPS II, type of malignancy, and period of ICU admission. Crude ICU mortality rates from exposed patients and controls were 43.7% and 70.8%, respectively. NIMV remained protective from mortality after adjustment for matching variables (OR, 0.31; 95% CI, 0.12-0.82).
Our results confirm that mortality has improved over the past decade in critically ill cancer patients, even those who require MV, and suggest that this may be, in part, because of a protective effect of NIMV.
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