Mechanisms controlling theophylline release from ethanol-resistant coated pellets.

PURPOSE: To elucidate the mass transport mechanisms controlling drug release from recently proposed, ethanol-resistant, polymeric film coatings. METHODS: Theophylline matrix pellets were coated with ethylcellulose: guar gum blends. Drug release from single pellets and ensembles of pellets was measured in various release media. Changes in the systems' morphology, composition and mechanical properties were monitored using SEM, gravimetrical analysis and a texture analyzer. Based on the obtained experimental results a mechanistically realistic mathematical model was identified and used to quantitatively predict drug release from coated pellets in ethanol-free and ethanol-containing bulk fluids. RESULTS: Drug diffusion though the intact polymeric film coatings is likely to be the dominant mass transport mechanism in the investigated systems, irrespective of the ethanol content in the surrounding environment. An appropriate solution of Fick's law could be used to quantitatively predict theophylline release from pellets coated with different ethylcellulose:guar gum blends at different coating levels. Importantly, independent experiments confirmed the theoretical predictions. CONCLUSIONS: In silico simulations can help facilitating the optimization of the novel ethanol-resistant polymeric film coatings, avoiding time-consuming and cost-intensive series of trial-and-error experiments. The presence/absence of ethanol does not affect the underlying drug release mechanisms.

pH-sensitive film coatings: towards a better understanding and facilitated optimization.

The major aims of this study were: (i) to prepare and characterize polymeric film coatings with pH-dependent properties for oral administration; and (ii) to better understand the underlying mass transport mechanisms upon exposure to simulated gastric and intestinal fluids. Propylene glycol alginate (containing free carboxylic groups) was chosen as a pH-sensitive film former, which was blended with different amounts of ethylcellulose (being water-insoluble throughout the gastro-intestinal tract). The water uptake kinetics of thin free films in 0.1M HCl and phosphate buffer pH 7.4 were monitored gravimetrically and quantitatively described using an appropriate analytical solution of Fick's law of diffusion. Interestingly, the addition of only a low percentage (2.5-10%) of propylene glycol alginate to ethylcellulose significantly increased both, the rate and extent of the films' water uptake, irrespective of the pH of the release medium. Importantly, diffusion was found to be the pre-dominant mass transport mechanism for all system compositions and types of release media. The apparent water diffusivity in the polymeric films could quantitatively be determined as a function of the polymer blend ratio. It significantly increased with increasing pH of the release medium, due to the presence of the free carboxylic groups in propylene glycol alginate. Also the dry mass loss of the polymer networks was much more pronounced at high compared to low pH. The differences in both water uptake as well as dry mass loss resulted in a clear pH-dependence of the drug release kinetics from coated pellets. Importantly, desired pH-sensitive release rates can easily be adjusted by varying the propylene glycol alginate content.

Air pollution-derived PM2.5 impairs mitochondrial function in healthy and chronic obstructive pulmonary diseased human bronchial epithelial cells.

In order to clarify whether the mitochondrial dysfunction is closely related to the cell homeostasis maintenance after particulate matter (PM2.5) exposure, oxidative, inflammatory, apoptotic and mitochondrial endpoints were carefully studied in human bronchial epithelial BEAS-2B, normal human bronchial epithelial (NHBE) and chronic obstructive pulmonary disease (COPD)-diseased human bronchial epithelial (DHBE) cells acutely or repeatedly exposed to air pollution-derived PM2.5. Some modifications of the mitochondrial morphology were observed within all these cell models repeatedly exposed to the highest dose of PM2.5. Dose- and exposure-dependent oxidative damages were reported in BEAS-2B, NHBE and particularly COPD-DHBE cells acutely or repeatedly exposed to PM2.5. Nuclear factor erythroid 2-p45 related factor 2 (NRF2) gene expression and binding activity, together with the mRNA levels of some NRF2 target genes, were directly related to the number of exposures for the lowest PM2.5 dose (i.e., 2 µg/cm2), but, surprisingly, inversely related to the number of exposures for the highest dose (i.e., 10 µg/cm2). There were dose- and exposure-dependent increases of both nuclear factor kappa-B (NF-κB) binding activity and NF-κB target cytokine secretion in BEAS-2B, NHBE and particularly COPD-DHBE cells exposed to PM2.5. Mitochondrial ROS production, membrane potential depolarization, oxidative phosphorylation, and ATP production were significantly altered in all the cell models repeatedly exposed to the highest dose of PM2.5. Collectively, our results indicate a cytosolic ROS overproduction, inducing oxidative damage and activating oxygen sensitive NRF2 and NF-kB signaling pathways for all the cell models acutely or repeatedly exposed to PM2.5. However, one of the important highlight of our findings is that the prolonged and repeated exposure in BEAS-2B, NHBE and in particular sensible COPD-DHBE cells further caused an oxidative boost able to partially inactivate the NRF2 signaling pathway and to critically impair mitochondrial redox homeostasis, thereby producing a persistent mitochondrial dysfunction and a lowering cell energy supply.

A simple and traceless solid phase method simplifies the assembly of large peptides and the access to challenging proteins.

Chemical protein synthesis gives access to well-defined native or modified proteins that are useful for studying protein structure and function. The majority of proteins synthesized up to now have been produced using native chemical ligation (NCL) in solution. Although there are significant advantages to assembling large peptides or proteins by solid phase ligation, reports of such approaches are rare. We report a novel solid phase method for protein synthesis which relies on the chemistry of the acetoacetyl group and ketoxime ligation for the attachment of the peptide to the solid support, and on a tandem transoximation/rearrangement process for the detachment of the target protein. Importantly, we show that the combination of solid phase and solution ligation techniques facilitates the production of a challenging and biologically active protein made of 180 amino acids. We show also that the solid phase method enables the purification of complex peptide segments through a chemoselective solid phase capture/release approach.

Correction: A simple and traceless solid phase method simplifies the assembly of large peptides and the access to challenging proteins.

[This corrects the article DOI: 10.1039/C7SC01912B.].

Genetic and epigenetic alterations in normal and sensitive COPD-diseased human bronchial epithelial cells repeatedly exposed to air pollution-derived PM2.5.

Even though clinical, epidemiological and toxicological studies have progressively provided a better knowledge of the underlying mechanisms by which air pollution-derived particulate matter (PM) exerts its harmful health effects, further in vitro studies on relevant cell systems are still needed. Hence, aiming of getting closer to the human in vivo conditions, primary human bronchial epithelial cells derived from normal subjects (NHBE) or sensitive chronic obstructive pulmonary disease (COPD)-diseased patients (DHBE) were differentiated at the air-liquid interface. Thereafter, they were repeatedly exposed to air pollution-derived PM2.5 to study the occurrence of some relevant genetic and/or epigenetic endpoints. Concentration-, exposure- and season-dependent increases of OH-B[a]P metabolites in NHBE, and to a lesser extent, COPD-DHBE cells were reported; however, there were more tetra-OH-B[a]P and 8-OHdG DNA adducts in COPD-DHBE cells. No increase in primary DNA strand break nor chromosomal aberration was observed in repeatedly exposed cells. Telomere length and telomerase activity were modified in a concentration- and exposure-dependent manner in NHBE and particularly COPD-DHBE cells. There were a global DNA hypomethylation, a P16 gene promoter hypermethylation, and a decreasing DNA methyltransferase activity in NHBE and notably COPD-DHBE cells repeatedly exposed. Changes in site-specific methylation, acetylation, and phosphorylation of histone H3 (i.e., H3K4me3, H3K9ac, H3K27ac, and H3S10ph) and related enzyme activities occurred in a concentration- and exposure-dependent manner in all the repeatedly exposed cells. Collectively, these results highlighted the key role played by genetic and even epigenetic events in NHBE and particularly sensitive COPD-DHBE cells repeatedly exposed to air pollution-derived PM2.5 and their different responsiveness. While these specific epigenetic changes have been already described in COPD and even lung cancer phenotypes, our findings supported that, together with genetic events, these epigenetic events could dramatically contribute to the shift from healthy to diseased phenotypes following repeated exposure to relatively low doses of air pollution-derived PM2.5.

The utility of non-HDL in managing dyslipidemia of stage 5 chronic kidney disease.

BACKGROUND: The Kidney Disease Outcomes Quality Initiative (K/DOQI) treatment guidelines for managing dyslipidemia in patients with chronic kidney disease (CKD) designate CKD as a high-risk category for coronary heart disease and, in Stage 5 CKD patients, recommend maintaining low-density lipoprotein (LDL) < 100 mg/dl and, for patients with hypertriglyceridemia (> or = 200 mg/ dl), non-high-density lipoprotein (non-HDL) < 130 mg/dl, the latter to achieve very low-density lipoprotein (VLDL) < 30 mg/dl. More recently, the National Cholesterol Education Program has recommended an LDL target of < 70 mg/dl for high-risk patients. AIMS: The purposes of this study were: to document the point prevalence of dyslipidemia in CKD patients at hemodialysis inception, prior to potential impact of dialysis treatments; to assess the hypothesis that non-HDL serves as a reliable surrogate marker for elevated VLDL; to examine the performance of K/DOQI guidelines in treating dyslipidemia; and to evaluate the utility of non-HDL as an alternative primary trigger/target of lipid-lowering therapy in Stage 5 CKD patients. METHODS: Consistent with K/DOQI guidelines, lipid levels drawn immediately prior to hemodialysis sessions, thus possibly non-fasting, were analyzed in 21,893 incident dialysis patients by laboratory measurements of triglycerides, total cholesterol, and HDL and from calculated values of non-HDL, LDL, VLDL and intermediate-density lipoprotein. RESULTS: Prevalence of dyslipidemia, by guideline definitions, was 82%, predominantly manifested by elevated triglycerides (52%) and VLDL (52%) and decreased HDL (51%), with less frequent elevations of LDL (40%) and total cholesterol (24%). Non-HDL > or = 130 mg/dl was neither a sensitive (61%) nor specific (75%) marker for elevated VLDL. There was a striking disparity between the high prevalence of dyslipidemia and the percentage of dyslipidemic patients qualified by K/DOQI guidelines for therapy. Non-HDL > or = 130 mg/dl was as effective in qualifying dyslipidemic patients for lipid-lowering therapy (54%) as the entire K/DOQI treatment algorithm (57%). Lowering the trigger of non-HDL to > or = 100 mg/dl would qualify 81% of dyslipidemic patients for treatment while offering the important advantage of being uninfluenced by the non-fasting state. CONCLUSIONS: In Stage 5 CKD patients at hemodialysis inception, dyslipidemia is highly prevalent with predominance of the atherogenic triad (hypertriglyceridemia, elevated VLDL and reduced HDL). Non-HDL is a poor surrogate marker for VLDL. As a valid non-fasting lipid parameter, non-HDL alone at the level of > or = 130 mg/dl qualifies dyslipidemic Stage 5 CKD patients for therapy as effectively as the K/DOQI guidelines. Setting the non-HDL trigger/target cut-off at 100 mg/dl overcomes the insensitivity of non-HDL as a marker for atherogenic lipoproteins represented by the VLDL designation while ensuring more aggressive lipid-lowering therapy for Stage 5 CKD patients at high risk for cardiovascular events. Accordingly, non-HDL of 100 mg/dl is proposed as the all-encompassing primary trigger/target of lipid-lowering therapy in high-risk Stage 5 CKD patients, particularly those patients on dialysis in whom lipid samples obtained before dialysis cannot be guaranteed to be fasting.

Differential responses of healthy and chronic obstructive pulmonary diseased human bronchial epithelial cells repeatedly exposed to air pollution-derived PM4.

While the knowledge of the underlying mechanisms by which air pollution-derived particulate matter (PM) exerts its harmful health effects is still incomplete, detailed in vitro studies are highly needed. With the aim of getting closer to the human in vivo conditions and better integrating a number of factors related to pre-existing chronic pulmonary inflammatory, we sought to develop primary cultures of normal human bronchial epithelial (NHBE) cells and chronic obstructive pulmonary disease (COPD)-diseased human bronchial epithelial (DHBE) cells, grown at the air-liquid interface. Pan-cytokeratin and MUC5AC immunostaining confirmed the specific cell-types of both these healthy and diseased cell models and showed they are closed to human bronchial epithelia. Thereafter, healthy and diseased cells were repeatedly exposed to air pollution-derived PM4 at the non-cytotoxic concentration of 5 µg/cm2. The differences between the oxidative and inflammatory states in non-exposed NHBE and COPD-DHBE cells indicated that diseased cells conserved their specific physiopathological characteristics. Increases in both oxidative damage and cytokine secretion were reported in repeatedly exposed NHBE cells and particularly in COPD-DHBE cells. Diseased cells repeatedly exposed had lower capacities to metabolize the organic chemicals-coated onto the air-pollution-derived PM4, such as benzo[a]pyrene (B[a]P), but showed higher sensibility to the formation of OH-B[a]P DNA adducts, because their diseased state possibly affected their defenses. Differential profiles of epigenetic hallmarks (i.e., global DNA hypomethylation, P16 promoter hypermethylation, telomere length shortening, telomerase activation, and histone H3 modifications) occurred in repeatedly exposed NHBE and particularly in COPD-DHBE cells. Taken together, these results closely supported the highest responsiveness of COPD-DHBE cells to a repeated exposure to air pollution-derived PM4. The use of these innovative in vitro exposure systems such as NHBE and COPD-DHBE cells could therefore be consider as a very useful and powerful promising tool in the field of the respiratory toxicology, taking into account sensitive individuals.

Further characterization of insulin secretion from the perfused duodenum-pancreas of chicken: a comparison of insulin release in chickens selected for high and low abdominal fat content.

Insulin release from the perfused pancreas was studied in genetically selected fat and lean chickens. The previously described glucose insensitivity of the chicken pancreas cannot be overcome by 5 or 10 mM D-glyceraldehyde, suggesting that the resistance is not related to glucose metabolism before the triose phosphate step. At 42 mM, glucose induced a biphasic insulin release which was specific, since 42 mM mannitol did not elicit insulin release. Arginine (10 mM) or acetylcholine (0.1-1 microM), which in themselves do not cause insulin release, generated a biphasic insulin release in the presence of a low nonstimulating glucose concentration (14 mM); the effect was synergistic. In contrast to the glucose tolerance test observed in vivo, the pancreas from the fat line chicken in response to glucose or glucose plus arginine released significantly less insulin during the first phase. The significance of this defect awaits further elucidation. On the other hand, acetylcholine, a more potent secretagogue, did not reveal any significant difference between fat and lean chickens.

Prognostic factors for neutropenic patients in an intensive care unit: respective roles of underlying malignancies and acute organ failures.

The admission of neutropenic patients to an intensive care unit (ICU) is still controversial, especially if mechanical ventilation is required. To avoid useless stays in ICU, the evaluation of the respective role of the underlying malignancy and acute organ failures might be useful for better definition of the categories of patients who could benefit from aggressive ICU support. For this purpose, we carried out a retrospective study of the charts of 107 consecutive neutropenic patients admitted to an ICU in a comprehensive cancer centre over a four-year period. The following characteristics were recorded within 24 h of admission: patient data, characteristics of neutropenia and the underlying malignancy, the type and number of organ system failures (OSFs) and simplified acute physiological scores (SAPS and SAPS II). The impact of each variable on outcome in the ICU was studied by univariate and multivariate (logistic regression) analysis. 59 patients died in the ICU (mortality rate: 55%). Patients with a haematological malignancy (n = 57, 53%) were more likely to experience respiratory failure, an underlying malignancy deemed rapidly fatal, and to have longer lasting neutropenia than patients with a solid tumour (n = 50, 47%). However, the mortality rate did not differ in the two groups (haematological malignancy 61% versus solid tumour 48%, p = 0.16). Respiratory and cardiovascular organ failure (p < 0.001 for both) correlated with mortality in the ICU. In the multiple logistic regression model, only the number of organ system failures and respiratory failure remained predictive of ICU mortality. In conclusion, the characteristics of the underlying malignancy are not relevant when deciding whether or not neutropenic patients should be admitted to an ICU. The main risk factors for death in an ICU are the number of organ failures on admission, and among them the presence of respiratory failure.

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.

Technetium-99m-tetrofosmin myocardial imaging: a comparison with thallium-201 and angiography.

UNLABELLED: Images recorded after intravenous administration of 99mTc-tetrofosmin were compared to those obtained with 201Tl in a series of 40 patients with angiographically documented coronary artery disease. These patients were part of a Phase II tetrofosmin study and presented anamnestic or laboratory evidence suggestive of ischemic heart disease. METHODS: Thirty-seven patients had one or more coronary obstructions greater or equal to 70% of luminal diameter. Three patients studied after bypass surgery or angioplasty had patent grafts, absence of disease progression or no significant restenosis. Twenty-six patients had evidence of previous myocardial infarction. All images were processed into a common display format by a core laboratory. They were identified by code and read by concensus of four investigators. Each segment was classified as normal or abnormal and these readings were combined and categorized into normal, reversible, fixed or mixed regional defects. RESULTS: There was good segmental correspondence between thallium and tetrofosmin (kappa values ranged from 0.43 to 1.00). The ability of thallium and tetrofosmin to recognize and localize myocardial infarction was excellent, since corresponding abnormalities were present in respectively 24 and 25 of the 26 patients with previous myocardial infarction. Abnormalities in noninfarcted territories were recognized with both tracers in 16 of 28 patients presenting with coronary lesions involving vessels unrelated to the infarct. CONCLUSION: In comparison to rest tetrofosmin, thallium redistribution shows more reversibility in areas with myocardial infarction but less reversibility in areas of myocardial ischemia. Current Phase II results suggest that tetrofosmin is a sensitive and reliable tracer for detecting myocardial infarction and ischemia. Results should be confirmed in a larger group of patients.

Myocardial imaging with technetium-99m-tetrofosmin: comparison of one-day and two-day protocols.

UNLABELLED: There is no evidence of myocardial redistribution after tetrofosmin injection, therefore, two separate injections are needed to differentiate scar from ischemia with this tracer. The injections can be given on the same day (one-day protocol) or on separate days (two-day protocol). As part of a Phase II clinical study, a one-day protocol was compared with a two-day protocol. METHODS: Fifty-five patients with suspected coronary artery disease were studied according to the following protocol: on the first day at rest, anterior, left lateral, left anterior oblique 40 degrees and 70 degrees images were acquired 30 min after injection of 8 mCi of tetrofosmin for 5 min each. Two days later, exercise and rest images were acquired on the same day. At peak exercise, 8 mCi of tetrofosmin were injected and 30 min later the same four standard planar images were recorded as on Day one. Four hours after the exercise injection, 24 mCi of tetrofosmin were injected at rest and imaging was repeated 30 min later. Qualitative comparisons between the one- and two-day protocols were performed in 50 patients in whom all data were available following blinded evaluation of images by three readers. RESULTS: All three readers reported identical results for the 26 patients. A difference in extent or location between the observers was found in seven patients, differences between normal and abnormal in eight patients, while discrepancies between ischemia and necrosis were noted in four patients. In five patients, an ischemic area was found according to the one-day protocol, but according to the data of the two-day protocol, this area was judged to be necrotic. One observer reported the opposite in one patient. These discrepancies between the reversibility of defects were restricted to the inferior wall. Comparison with 201Tl data showed no systematic pattern of variation. CONCLUSION: Tetrofosmin can be used in a one-day protocol. However, in planar imaging, the inferior wall should be reported with caution.

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.

Diagnosis of nosocomial pneumonia in cancer patients undergoing mechanical ventilation: a prospective comparison of the plugged telescoping catheter with the protected specimen brush.

STUDY OBJECTIVES: Quantitative culture of protected samples of lower respiratory tract secretions obtained by a fiberoptic protected specimen brush (PSB) is widely accepted for the diagnosis of ventilator-associated pneumonia (VAP), but this diagnostic procedure is time consuming, expensive, and may give rise to iatrogenic complications, especially in cancer patients who often present with thrombocytopenia. The plugged telescoping catheter (PTC) could be a satisfactory alternative to the PSB in this setting. The aim of the present study was to evaluate the interest of the PTC to diagnose VAP in ventilated cancer patients. DESIGN: A prospective observational study. SETTING: A 15-bed medical-surgical ICU in a comprehensive cancer center. PATIENTS AND INTERVENTIONS: Over a 9-month period, 42 patients suspected of having bacterial VAP during mechanical ventilation underwent 69 bronchial samplings: a blinded PTC and a fiberoptic PSB were performed successively in each case. A positive culture for both sampling procedures was defined as the recovery of > or = 10(3) cfu/mL of at least one potential pathogen. The PSB result was taken as the reference standard. MEASUREMENTS AND RESULTS: The overall agreement between the techniques was 87% (60/69). PTC had a sensitivity of 67%, a specificity of 93%, a positive predictive value of 71%, and a negative predictive value of 91%. CONCLUSIONS: We conclude that the accuracy of the blinded PTC compares well with that of the PSB for the diagnosis of VAP in cancer patients. The sensitivity of the PTC observed herein, which is slightly lower than that described in previous studies, may be due to the blinded nature of the method: the indications for initial or secondary coupling with a directed sampling method in patients with suspicion of localized pneumonia remain to be determined.

Effectiveness of simple measures to control an outbreak of nosocomial methicillin-resistant Staphylococcus aureus infections in an intensive care unit.

Between June 1985 and March 1986, 14 cases of severe nosocomial methicillin-resistant Staphylococcus aureus (MRSA) infection, including septicemia, were observed in the intensive care unit (ICU) of a 400-bed cancer reference center. Simple control measures including contact isolation of colonized patients and reinforcement of handwashing practices among personnel were followed by a sharp decrease in the rate of infection and colonization. An epidemiological investigation showed that a single serophage variant MRSA strain was involved; peak incidence of infection was 17 per 100 ICU patient discharges; the index case was identified as a patient admitted from another hospital and the epidemic strain was then transmitted from patient-to-patient in the ICU; risk factors for acquiring infection were length of prior hospitalization, invasive procedures and number of antibiotic treatments; dissemination of the strain to other wards was only anecdotal. These results stress the effectiveness of simple measures to control outbreaks of MRSA nosocomial infections even in immunocompromised cancer patients.

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.

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.

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.