Analysis of cytopenia in geriatric inpatients.

BACKGROUND: Peripheral blood dyscrasias in older patients are repeatedly seen in geriatric clinical practice; however, there is substantial lack of data about the epidemiology, possible causes and treatment options in this patient group. Proton pump inhibitors (PPI) are extensively used in older patients and associated with leukopenia. The primary objective of this study was the assessment of encoded cytopenia prevalence in a geriatric patient cohort and the secondary objective was the assessment of putative causes and the analysis of PPI administration in patients with cytopenia. METHODS: Retrospective evaluation of patients admitted to the geriatric department of a German urban hospital between 2010 and 2012. Electronic patient data were screened for encoded diagnosis of cytopenia according to the International Classification of Diseases (ICD) 10. Inclusion criteria were ICD code D69.0-9 and/or D70.0-7, age ≥60 years and exclusion criteria were no ICD code D69.0-9 and/or D70.0-7 and age <60 years. Out of 9328 screened inpatients 54 patients remained for analysis. Study parameters included hemoglobin (Hb), red blood cell count (RBC), leucocytes, platelets, mean cell volume (MCV), mean corpuscular hemoglobin (MCH), mean corpuscular hemoglobin concentration (MCHC), red cell distribution width (RDW), presence of leukopenia (<4000/µl), presence of thrombocytopenia (<140,000/µl) and presence of anemia according to the World Health Organization (WHO). Substitution of blood products, medication with PPI and potential causes for dyscrasias were evaluated based on electronic patient records. RESULTS: The mean age was 78.3 ± 6.5 years (27 females, 27 males), anemia was seen in 78%, leukopenia was encoded in13% and thrombocytopenia in 44.4%. In most of the patients no substitution of blood products was documented. In most of the patients (20.4%) cytopenia was attributed to either heparin-induced thrombocytopenia (HIT) or hemato-oncologic (20.4%) diseases, followed by drug association in 18.5%. In 70.8% of the study patients PPIs were administered but the indication for PPI administration remained unclear in 20.4%. CONCLUSION: The results encourage accurate assessment of blood dyscrasias and appropriate documentation as well as indication check for PPI treatment in geriatric inpatients.

A Genetic Biomarker of Oxidative Stress, the Paraoxonase-1 Q192R Gene Variant, Associates with Cardiomyopathy in CKD: A Longitudinal Study.

Background. Oxidative stress is a hallmark of CKD and this alteration is strongly implicated in LV hypertrophy and in LV dysfunction. Methods and Patients. We resorted to the strongest genetic biomarker of paraoxonase-1 (PON1) activity, the Q192R variant in the PON1 gene, to unbiasedly assess (Mendelian randomization) the cross-sectional and longitudinal association of this gene-variant with LV mass and function in 206 CKD patients with a 3-year follow-up. Results. The R allele of Q192R polymorphism associated with oxidative stress as assessed by plasma 8-isoPGF2α (P = 0.03) and was dose-dependently related in a direct fashion to LVMI (QQ: 131.4 ± 42.6 g/m(2); RQ: 147.7 ± 51.1 g/m(2); RR: 167.3 ± 41.9 g/m(2); P = 0.001) and in an inverse fashion to systolic function (LV Ejection Fraction) (QQ: 79 ± 12%; RQ: 69 ± 9%; RR: 65 ± 10% P = 0.002). On longitudinal observation, this gene variant associated with the evolution of the same echocardiographic indicators [LVMI: 13.40 g/m(2) per risk allele, P = 0.005; LVEF: -2.96% per risk allele, P = 0.001]. Multivariate analyses did not modify these associations. Conclusion. In CKD patients, the R allele of the Q192R variant in the PON1 gene is dose-dependently related to the severity of LVH and LV dysfunction and associates with the longitudinal evolution of these cardiac alterations. These results are compatible with the hypothesis that oxidative stress is implicated in cardiomyopathy in CKD patients.

Differences in cardiac structure assessed by echocardiography between renal transplant recipients and chronic kidney disease patients.

BACKGROUND: Cardiovascular disease (CVD) is the leading cause of death in predialysis chronic kidney disease (CKD) and dialysis patients as well as in renal transplant recipients (RTRs). Left ventricular hypertrophy (LVH) starts early during the course of CKD and is a strong predictor of CVD in this population. Regression of LVH after a successful renal transplantation remains a debatable issue among investigators, whereas there is little data comparing echocardiographic measurements between patients with predialysis CKD and RTRs. AIM: The aim of this study was to compare echocardiographic measurements of LV structure and function between predialysis CKD patients and RTRs of similar renal function level. PATIENTS AND METHODS: We conducted a case control study with individual (1:2) matching from the Renal Transplant and the predialysis CKD Outpatient Clinic. For each of the 36 RTRs, two matched for gender, age and estimated glomerular filtration rate (eGFR) predialysis CKD outpatients (72 patients) were included. All patients underwent transthoracic echocardiography and LV mass, LV mass index [LVM and LVMI = LVM/BSA g/m(2)] and indices of systolic function were measured. In a subgroup of 12 RTRs we retrospectively assessed and compared the LVMI measurements at three different time points, during predialysis, dialysis and post transplant period. RESULTS: The prevalence of LVH was 33% in RTRs and 52% in CKD patients (ns). RTRs had significantly lower LVM and LVMI levels compared with predialysis CKD patients (P = .006 and P = .008) while the other echocardiographic indices did not differ. In the subgroup of 12 RTRs, post-transplant LVMI levels (105 ± 25 g/m(2)) were significantly lower in comparison with predialysis (147 ± 57 g/m(2)) and dialysis LVMI levels (169 ± 72 g/m(2)) (P = .01, P = .01, respectively). CONCLUSION: RTRs had significantly lower LVMI compared with predialysis CKD patients of similar age, renal function, hemoglobin and blood pressure level.

Cardiac troponin I versus creatine kinase-MB in the detection of postoperative cardiac events after coronary artery bypass grafting surgery.

AIM: Several studies suggest that postoperarive concentrations of cardiac troponin-I (cTnI) may increase in patients undergoing aorto-coronary bypass grafting (CABG). The degree and pattern of release appears to be associated with perioperative myocardial damage. METHODS: This was a prospective observational study with serial sampling conducted at the Departments of Cardiothoracic Surgery and Anesthesiology, University Hospital of Ioannina, Ioannina, Greece. The levels of cTnI and creatine kinase-MB (CK-MB) preoperatively, upon admission to the intensive care unit and at 12, 24, 36 and 48 hours after surgery, as well as daily from postoperative days 3-7 were determined in 41 consecutive patients (33 males and 8 females, aged 64.8+/-6.1 years) who underwent CABG with cardiopulmonary bypass. The Authors compared the patterns and variation of cTnI and creatine kinase (CK)-MB after CABG in patients with or without postoperative cardiac events (PCEs). RESULTS: Eleven patients experienced a PCE (postoperative ventricular and supraventricular arrhythmia, need for intra-aortic balloon pump (IABP) for >12 hours, or postoperative myocardial infarction, [MI]). In patients without PCE the elevation of cTnI peaked at 24 hours after surgery, while in patients with PCE maximal values of cTnI occurred after 36 hours. CTnI levels correlated with CK-MB after the procedure. Receiver-operating characteristic (ROC) curve analysis indicated that cTnI is superior to CK-MB with regard to PCE diagnosis following CABG (area under the ROC curve, 0.73, 95% CI (0.53-0.93) versus 0.54, 95% CI, (0.25-0.83). CONCLUSION: CTnI seems to be more valuable compared to CK-MB in the detection of PCEs in patients undergoing coronary surgery.

An epidemiologic study of acute coronary syndromes in northwestern Greece.

Acute coronary syndromes (ACS) represent the most common cause of morbidity and mortality in the Western world. Relative epidemiologic data for Greece, a Mediterranean country, are sparse. The aim of the study was to determine the incidence and the clinical presentations of ACS. Over a 1-year period we conducted a prospective, population-based survey of ACS cases in an isolated area of northwestern (NW) Greece with 170,000 inhabitants. Every patient living in the study area, aged <80 years, without history of coronary artery disease, who presented with symptoms suspicious for ACS and was hospitalized for at least 24 hours was eligible for inclusion in the study. For sudden cardiac deaths, relative information was obtained from the autopsy report or the physician who documented death. Additional information regarding timing and associated conditions was obtained from relatives. The diagnosis and classification of the studied cases was performed according to World Health Organization and European Society of Cardiology criteria. The authors identified 352 patients (265 men, 87 women, mean age 62.5 +/-10 and 68 +/-9.5 years, respectively) with first-appeared ACS (174 non-ST elevation, 105 ST elevation, 73 sudden cardiac deaths). Fifty-six patients with other forms of ischemic heart disease (stable angina, heart failure, and silent ischemia) were not included in the analysis. Moreover, 154 patients with chest pain and normal appearing EGG at rest, normal values for enzymes (CK, troponin), and negative exercise testing, as well as 77 patients with normal findings from coronary angiography studies, were also excluded. The annual incidence for the age group of 30-79 was 39/10,000 inhabitants (60.6 for men and 19 for women). The incidence of ACS increased with age in both sexes and was higher in men even after the age of 70. About one third of the ACS and half of the sudden cardiac deaths occurred in the age group of 70-79. Only 3 patients were successfully resuscitated. ACS are common in this area of NW Greece and the majority of them present in a form amenable to therapeutic manipulations. Twenty percent of patients died suddenly, and a very small percentage of these were successfully resuscitated. Preventive measures and acute management facilities need to be improved, even in a Mediterranean country where the incidence of ischemic heart disease is relatively lower than in northern European countries.

Presence of hydroxysteroid dehydrogenase type 10 in amyloid plaques (APs) of Hsiao's APP-Sw transgenic mouse brains, but absence in APs of Alzheimer's disease brains.

This immunocytochemical study using two anti-amyloid beta-protein (Abeta) monoclonal antibodies, 4G8 and 6E10, revealed the presence of Abeta in both amyloid plaques (APs) and blood vessels of brains of Hsiao's APP-Sw transgenic mice (also known as Tg2576) and human Alzheimer's disease (AD) brains. Further study using both monoclonal (5F3) and polyclonal (R-228) antibodies to hydroxysteroid dehydrogenase type 10 (HSD-10) [formerly called SCHAD (short-chain L-3-hydroxyacyl-CoA dehydrogenase); also called ERAB (endoplasmic-reticulum-associated amyloid beta-peptide-binding protein)] indicated that HSD-10 was present in the APs of Tg2576 mice but was absent or immunocytochemically undetectable in the APs of AD brains. Our observations also revealed that HSD-10 was present in the blood vessels of both Tg2576 mice and AD brains. Immunogold electron microscopy also indicated that HSD-10 was present in the amyloid fibers (AFs), mitochondria, nuclear heterochromatin, and nucleolus of Tg2576 mouse brains but was absent in APs of AD brains. These results suggest that the human APP gene transferred to mice may induce overexpression of HSD-10 in mouse APs and in various other cellular components of mouse brains. It is also possible that the human APP gene responsible for HSD-10 deposition in APs of these Tg2576 mice brains is different from that of AD brains. Alternatively, the HSD-10 gene and APP gene may function independently in AD brains. Despite these differences, the Tg2576 mouse, as shown in this study, is a proper animal model for the study of AD and also for the investigation of HSD-10.

Clinical pregnancy in a woman of 45 years after gamete intrafallopian transfer (GIFT).

Clinical pregnancy in women over 44 years is rare in assisted reproductive technology (ART). A case of a 45-year-old woman with clinical pregnancy after GIFT is described.

The successful use of hatched blastocysts in assisted reproductive technology.

This retrospective study was undertaken to determine the value of blastocyst culture and transfer as a tool in assisted reproductive technology. Six hundred and fifty-five cycles in patients undergoing IVF treatment for infertility were involved. All patients were aged < 40 years. Day-2 embryos were transferred to 427 (group 1) and day-6 embryos (blastocysts) were transferred to 228 patients (group 2). Pronucleate oocytes obtained from IVF were cultured in vitro for 2 or 6 days. One to five embryos were transferred. A total of 10,146 oocytes were retrieved, 6,105 oocytes were fertilized, 2,222 embryos were transferred and 197 clinical pregnancies were achieved in all groups. Blastocystes were transferred to almost 90% of group 2 patients. The pregnancy rate per cycle and implantation rate per transferred embryo was 42.1% and 19.4%, respectively, in the blastocyst group compared to 23.6% and 8.6%, respectively, when embryos were transferred on day 2. Even though in the blastocyst group there was an increased number of oocytes fertilized at the same time there was a significant reduction in the number of embryos being replaced (3.2 vs 3.8). This study demonstrate that transfer of blastocysts increases the success of IVF when compared with day-2 transfers and reduces the number of embryos to be transferred.

ISZm1068: an IS5-like insertion element from Zymomonas mobilis.

A new insertion sequence, designated ISZm1068, was isolated from Zymomonas mobilis strain CP4. This element consists of 1,068 bp and contains one major ORF which shows similarities both at the nucleotide and at the amino acid sequence level with the corresponding ORFs encoding the transposases of many IS5 family elements, in particular the IS1031 group. Moreover, the Z. mobilis ORF shares the conserved N2, N3 and C1 signature motifs of the IS4 and IS5 families. Six out of seven Z. mobilis wild-type strains were shown by hybridisation to contain a single copy of the ISZm1068 element. Nucleotide sequences of the insertion elements from these strains exhibited extremely high levels of identity, varying from 94.25 to 99.25%. ISZm1068 was shown to be active in Escherichia coli cells and led to plasmid replicon fusions within the host cell. Sequence analysis of rare cointegration and resolution derivatives suggests that ISZm1068 has putative imperfect inverted repeats at its extremities of 18 bp (IR-right) and 14 bp (IR-left), and that a 3-bp (5'-TCA-3') target sequence is duplicated upon insertion.

Cryopreservation of embryos, blastocysts, and pregnancy rates of blastocysts derived from frozen-thawed embryos and frozen-thawed blastocysts.

PURPOSE: To evaluate the development of cryopreserved embryos when thawed and subsequently cultured to the blastocyst stage in comparison to transferring cryopreserved blastocysts. METHODS: In this retrospective clinical study, we have evaluated 170 cycles in patients undergoing IVF treatment for infertility. Cryopreserved embryos were thawed and were subsequently cultured and transferred at the blastocyst stage. Cryopreserved blastocysts (Day 6) were thawed and transferred immediately. RESULTS: Five hundred and sixty embryos and 444 blastocysts have been thawed. In the embryos group, the survival rate was 89% while in the blastocyst group the survival rate was 56%. In the embryos group the blastocyst development rate was 24.5%. The implantation rate in the embryos group was 20.6% per group blastocyst transferred compared to 5.3% in the blastocyst group. CONCLUSIONS: The ability of cryopreserved embryos to develop to blastocysts and their implantation potential does not seem to be greatly affected by the cryopreservation procedure.

Relatively low red cell folate levels and acute coronary syndromes.

BACKGROUND: Low folate levels are related to increased risk for coronary artery disease in humans, while experimental work has shown that folate deficiency is thrombogenic. We hypothesized that relatively low folate levels are related to the development of acute coronary syndromes in patients with previously stable coronary artery disease. METHODS: One hundred and forty-one men were studied: 53 consecutive patients with acute coronary syndromes, 41 with stable coronary artery disease and 47 control participants. Known clinical and lipid risk factors were identified in all subjects and in addition plasma B12, plasma and red cell folate levels were measured. RESULTS: Red cell folate levels were significantly lower in patients with acute coronary syndromes (510+/-178 nmol/l) than in both stable coronary artery disease patients (638+/-264 nmol/l, P< 0.005) and controls (615+/-193 nmol/l, P< 0.05 respectively). Plasma folate and B12 levels were similar in all three groups. Multiple logistic regression analysis identified red cell folate levels as the only independent predictor of acute coronary events in the whole population of patients with known coronary artery disease and in the subgroup of non-smokers (P=0.010 and P=0.031). CONCLUSIONS: The present study suggests that relatively low red cell folate levels are associated with acute coronary syndromes and are an independent predictor of acute coronary events.

Metabolic management of coronary heart disease: adjunctive treatment with trimetazidine decreases QT dispersion in patients with a first acute myocardial infarction.

PURPOSE: The metabolic management of ischemic heart disease represents a promising new therapeutic approach for acute coronary syndromes. Trimetazidine has been suggested to exert anti-ischemic properties on myocardium without affecting myocardial oxygen consumption or supply. The aim of this study was to investigate whether the administration of trimetazidine, as an adjunct to conventional treatment, decreases QT dispersion in patients with acute myocardial infarction (AMI). METHODS AND RESULTS: The study was prospective, randomized, double-blind and included 55 out of 86 consecutive patients aged < or = 80 years, admitted with a first AMI. Excluded from the study subjects with atrial fibrillation or pacing-rhythm, bundle branch block, pericardial or valvular heart disease or cardiogenic shock. Also were excluded patients treated with inotropic and antiarrhythmic agents, except for beta blockers. Enrolled patients were randomized into 2 groups: Trimetazidine group (n=29) and control group (n = 26). All patients were treated conventionally and, in addition, trimetazidine group patients were received trimetazidine 20 mg orally every 8 hours started after randomization and continued throughout hospitalization. The QT and QTc (corrected QT) dispersion were measured manually on 3 and 7 post-AMI days. The mean values of QT and QTc dispersion were significantly lower in trimetazidine group on both days, compared to control group: Day 3, QTD = 52+/-24 ms vs 68+/-30 ms (p = 0.034), QTcD = 52+/-21 ms vs 75+/-34 ms (p = 0.004). Day 7, QTD = 39+/-17 ms vs 60+/-20 ms (p < 0.0001), QTcD 40+/-17 ms vs 62+/-20 ms (p < 0.0001). Between days 3 and 7 the mean values of QT (p = 0.003) and QTc dispersion (p = 0.002) were decreased significantly only in trimetazidine group. An analysis with respect to the use of thrombolysis revealed that trimetazidine sub-groups had lower QT and QTc dispersion mean values on day 7, both in patients treated (p < 0.05) and non-treated (p = 0.001) with thrombolysis. CONCLUSIONS: It is concluded that trimetazidine decreases QT and QTc dispersion after acute myocardial infarction. Further investigation is needed to evaluate the mechanism and the clinical implications of this effect.

Treatment of refractory unstable angina in geographically isolated areas without cardiac surgery. Invasive versus conservative strategy (TRUCS study).

AIMS: We compared invasive (on-site coronary angioplasty or emergency air-ambulance transfer for bypass grafting surgery) vs conservative (persistent medical treatment) strategies in the management of refractory unstable angina in geographically isolated hospitals without cardiac surgical facilities. METHODS AND RESULTS: One hundred and forty eight randomized patients with refractory unstable angina were compared on an intention-to-treat basis. Outcomes (invasive vs conservative): (a) in hospital: stabilization (96% vs 43%, P=0.0001), non-fatal myocardial infarction (2.6% vs 4.2%, P=ns), death (1.3% vs 8.3%, P=0.046), combined outcome (3.9% vs 12.5%, P=0.053) and hospitalization (11.4+/-6.3 vs 12.4+/-8.0 days, P=ns). (b) 30-days follow-up: non-fatal myocardial infarction (2.6% vs 4.2%, P=ns), death (2.6% vs 11.1%, P=0.030) and combined outcome (5.3% vs 15.3%, P=0.031). (c) 12 month follow-up: non-fatal myocardial infarction (3. 9% vs 4.2%, P=ns), death (3.9% vs 12.5%, P=0.053), combined outcome (7.9% vs 16.7%, P=ns), re-admissions for unstable angina: (17.1% vs 23.6%, P=ns), late coronary angioplasty: (15.8% vs 11.1%, P=ns) and (d) late coronary bypass grafting: (7.9% vs 12.5%, P=ns). CONCLUSION: Invasive treatment of patients with refractory angina in remote areas without surgical back-up results in significant in-hospital stabilization and a reduction in major events in-hospital and at 30 days. Coronary angioplasty in stand-alone units and air-transfer of these patients seems safe.

Characterization and replication properties of the Zymomonas mobilis ATCC 10988 plasmids pZMO1 and pZMO2.

The complete nucleotide sequences of two small cryptic Zymomonas mobilis ATCC 10988 plasmids (pZMO1 and pZMO2) were determined. The plasmids showed 67% homology to each other at their nucleotide level. Plasmid pZMO1 was 1651 bp long with 38% G + C content and contained an open reading frame (ORFZMO1) of 1044 nucleotides. ORFZMO1 is predicted to encode a polypeptide of 348 amino acids and shows a high degree of homology with gram-negative replication proteins of rolling circle replicating plasmids, which belong to the pC194/pUB110 family. Plasmid pZMO2 was found to be 1669 bp long, with a 38.5% G + C content, and it contained an ORF of 552 nucleotides (ORFZMO2) encoding a putative polypeptide of 184 amino acids. This polypeptide also shows a high degree of homology with the replication proteins of RCR plasmids of gram-negative bacteria, but only at their N-termini. The region necessary for replication of both plasmids was determined by stability tests under nonselective conditions, following cloning in pBR325 and introduction in Z. mobilis ATCC 10988 by pRK2013 assisted conjugation. Double- and single-strand origin regions were predicted by sequence analysis. Detection of single-stranded DNA in the extract of exponentially growing cells confirmed experimentally the rolling circle replication mode of at least pZMO2.

A double-blind, placebo-controlled study of the effectiveness and safety of nizatidine in the prevention of postprandial heartburn.

BACKGROUND: Heartburn is frequently associated with overindulgence in food and drink, meal-stimulated gastric acid secretion, and a gastroesophageal reflux with a pH of 4 or lower. Nizatidine is a selective histamine2 receptor antagonist that effectively suppresses gastric acid secretion at lower than prescription doses and has been approved for nonprescription use in the prevention of postprandial heartburn. OBJECTIVE: To examine the relative effectiveness of 3 dose levels of nizatidine (225 mg, 75 mg, and 25 mg) in preventing postprandial heartburn. METHODS: Four hundred thirteen subjects with documented moderate to severe heartburn following a standard meal that provoked heartburn were randomized to receive a single dose of nizatidine at 225 mg (n = 104), 75 mg (n = 101), or 25 mg (n = 105), or placebo (n = 103) 30 minutes before the meal, at 30 minutes (immediately after completing the meal), and at 60, 90, 120, 150, 180, and 210 minutes (from beginning the meal), subjects assessed the presence or absence of heartburn (yes or no) and the severity of heartburn (100-mm visual analog scale). RESULTS: The use of both 225 mg and 75 mg of nizatidine were significantly better than placebo in preventing heartburn in the proportion of subjects with complete prevention of heartburn (15 [14.4%] and 15 [14.9%], respectively, vs 3 [2.9%]; P < .001); the effects of nizatidine, 25 mg, in 7 subjects (7%) were not distinguishable from placebo. Similar results for nizatidine, 225 mg and 75 mg, were seen for longest duration of no heartburn, total duration of no heartburn, the average severity of heartburn, and the peak heartburn severity. All 3 doses of nizatidine were superior to placebo (P < .001) in reducing average and peak heartburn severity and were well tolerated. CONCLUSIONS: Single doses of 225 mg and 75 mg of nizatidine administered 30 minutes before a standard meal intended to provoke heartburn are significantly more effective than placebo for the prevention and/or reduction of postprandial heartburn.

Transposon mutagenesis and strain construction in Zymomonas mobilis.

Conjugative or mobilizable plasmids carrying the transposable elements Tn5, Tn501 or mini Mu were readily transferred from Escherichia coli donors into Zymomonas mobilis recipients with frequencies depending both on donor and recipient strain used. With the exception of pULB113 (RP4::mini Mu), all foreign plasmids exhibited high instability in Z. mobilis transconjugants under both selective and non-selective conditions. Transposition events and consequent mutagenesis occurred readily in Z. mobilis transconjugant strains, with Tn5 and Tn501 being far less successful than mini Mu. Transposon mutagenesis with the help of mini Mu resulted in the isolation of a large number of independent auxotrophs with polyauxotrophs, cysteine, methionine and isoleucine requiring-isolates being the most frequent. When chromosomal DNA from all these mutants was digested with various restriction enzymes and the resulting restriction patterns were hybridized with a mini Mu probe, the majority of these mutants appeared to have insertions at different sites of the chromosome. Thus, transposon mutagenesis by mini Mu is proven to be a simple and efficient tool for mutant production and the genetic analysis of Z. mobilis.

Respiratory effects of tracheal gas insufflation in spontaneously breathing COPD patients.

OBJECTIVE: To evaluate the effect of tracheal gas insufflation (TGI) in spontaneously breathing, intubated patients with chronic obstructive pulmonary disease (COPD) undergoing weaning from the mechanical ventilation. DESIGN: A prospective study in humans. SETTING: Polyvalent intensive care unit (14-bed ICU) in a 700-bed general university hospital. PATIENTS: Twelve patients with chronic obstructive pulmonary disease (COPD) who required intubation and mechanical ventilation were studied. All patients met standard criteria for weaning from mechanical ventilation. Seven patients (group 1) had been transorally intubated during episodes of acute respiratory failure. Five patients, all men (group 2), had previously undergone tracheostomy and had a transtracheal tube in place. INTERVENTIONS: Intratracheal, humidified, O2-mixture insufflation (TGI) was given via a catheter placed in distal or proximal position. Gas delivered through the intratracheal catheter was blended to match the fractional of inspired gas through the endotracheal tube. Continuous flows of 3 and 6 l/min in randomized order were used in each catheter position. Prior to data collection at each stage, an equilibration period of at least 30 min was observed, and thereafter blood gases were analyzed every 5 min. A new steady state was assumed to have been established when values of both PaCO2 and V CO2 changed by less than 5% between adjacent measurements. The last values of blood gases were taken as representative. The new steady state was confirmed within 35-50 min. Baseline measurements with zero Vcath were made at the beginning and end of the experiment. RESULTS: This study shows that VT, MV, PaCO2, and VD/VT are reduced in a flow-dependent manner when gas is delivered through an oral-tracheal tube (group 1). The distal catheter position was more effective than the proximal one. In contrast, when gas was delivered through tracheostomy (group 2), TGI was ineffective in the proximal position and less effective than in group 1 in distal position. CONCLUSION: Under the experimental conditions, tracheal gas insufflation decreased dead space, increased alveolar ventilation and possibly reduced work of breathing. From the preliminary data reported here, we believe that TGI may help patients experiencing difficulty during weaning.