Routine whole-body CT identifies clinically significant findings in patients supported with veno-venous extracorporeal membrane oxygenation.

AIM: To determine the yield of routine whole-body computed tomography (CT) following extracorporeal membrane oxygenation (ECMO) initiation and to assess the association of these findings with prognosis. MATERIALS AND METHODS: One hundred and ninety-eight consecutive patients with acute respiratory failure admitted for ECMO support between January 2015 and December 2019 who underwent whole-body CT performed within 48 h of ECMO initiation were examined in this single-institution retrospective study. CT findings were divided into three categories: clinically significant findings that may affect immediate management strategy or short-term outcomes; findings not related to hospital stay or outcome but require further workup; and benign findings that do not require further investigation. Logistic regression analysis was used to assess the association of CT findings with 7- and 30-day survival. RESULTS: Clinically significant findings were present in 147 (74%) patients, findings requiring further workup were found in 82 (41%) patients, and benign findings were identified in 180 (90%) of the patients. Patients with clinically significant neurological findings had an elevated risk of death at 7 days (odds ratio [OR] 3.58; 95% confidence interval [CI] 1.29; 9.93; p=0.01), but not 30 days. Increasing numbers of clinically significant findings were associated with greater odds of mortality at 7 days (OR 1.70; 95% CI 1.08; 2.67; p=0.02) and 30 days (OR 1.41; 95% CI 1.02; 1.96; p=0.04). CONCLUSIONS: Imaging patients at the point of admission for VV-ECMO with CT frequently identified clinically significant abnormalities with prognostic implications of these. These findings provide support for the use of more routine CT at the point of treatment escalation with prospective studies now required.

Measurement of extravascular lung water to diagnose severe reperfusion lung injury following pulmonary endarterectomy: a prospective cohort clinical validation study.

The measurement of extravascular lung water is a relatively new technology which has not yet been well validated as a clinically useful tool. We studied its utility in patients undergoing pulmonary endarterectomy as they frequently suffer reperfusion lung injury and associated oedematous lungs. Such patients are therefore ideal for evaluating this new monitor. We performed a prospective observational cohort study during which extravascular lung water index measurements were taken before and immediately after surgery and postoperatively in intensive care. Data were analysed for 57 patients; 21 patients (37%) experienced severe reperfusion lung injury. The first extravascular lung water index measurement after cardiopulmonary bypass failed to predict severe reperfusion lung injury, area under the receiver operating characteristic curve 0.59 (95%CI 0.44-0.74). On intensive care, extravascular lung water index correlated most strongly at 36 h, area under the receiver operating characteristic curve 0.90 (95%CI 0.80-1.00). Peri-operative extravascular lung water index is not a useful measure to predict severe reperfusion lung injury after pulmonary endarterectomy, however, it does allow monitoring and measurement during the postoperative period. This study implies that extravascular lung water index can be used to directly assess pulmonary fluid overload and that monitoring patients by measuring extravascular lung water index during their intensive care stay is useful and correlates with their clinical course. This may allow directed, pre-empted therapy to attenuate the effects and improve patient outcomes and should prompt further studies.

Association and expression of the antigen-processing gene PSMB8, coding for low-molecular-mass protease 7, with vitiligo in North India: case-control study.

BACKGROUND: Vitiligo is a multifactorial, autoimmune, depigmenting disorder of the skin where aberrant presentation of autoantigens may have a role. OBJECTIVES: To study the association of two antigen-processing genes, PSMB8 and PSMB9, with vitiligo. METHODS: In total 1320 cases of vitiligo (1050 generalized and 270 localized) and 752 healthy controls were studied for the PSMB9 exon 3 G/A single-nucleotide polymorphism (SNP), PSMB8 exon 2 C/A SNP and PSMB8 intron 6 G/T SNP at site 37 360 using polymerase chain reaction (PCR)-restriction fragment length polymorphism. Real-time PCR was used for transcriptional expression of PSMB8 and cytokines. Expression of ubiquitinated proteins and phosphorylated-p38 (P-p38) was studied by Western blotting. RESULTS: Significant increases in PSMB8 exon 2 allele A (P < 2.07 × 10-6 , odds ratio 1·93) and genotypes AA (P < 1.03 × 10-6 , odds ratio 2·51) and AC (P < 1.29 × 10-6 , odds ratio 1·63) were observed in patients with vitiligo. Interferon-γ stimulation induced lower expression of PSMB8 in peripheral blood mononuclear cells of cases compared with controls, suggesting impaired antigen processing, which was confirmed by accumulation of ubiquitinated proteins in both lesional and nonlesional skin of patients with vitiligo. Expression of proinflammatory cytokines - interleukin (IL)-6, IL-1ß and IL-8 - was higher in the lesional skin. P-p38 expression was variable but correlated with the amount of ubiquitinated proteins in the lesional and nonlesional skin, suggesting that the inflammatory cytokine responses in lesional skin could be a result of both P-p38-dependent and -independent pathways. CONCLUSIONS: The PSMB8 exon 2 SNP is significantly associated with vitiligo. Accumulation of ubiquitinated proteins in skin of cases of vitiligo suggests their aberrant processing, which may promote the development of the disease.

Correlation of renin angiotensin system (RAS) candidate gene polymorphisms with response to Ramipril in patients with essential hypertension.

BACKGROUND: The renin-angiotensin system (RAS) is an important facet of blood pressure regulation physiology. Treatment of essential hypertension targets the RAS using Angiotensin Converting Enzyme Inhibitors (ACEIs). However, ACEIs are not uniformly effective and show inter-individual pharmacodynamic variations. AIM: To assess the correlation between genetic polymorphisms in the genes coding for RAS components (angiotensin converting enzyme (ACE I/D), α-adducin (ADD1) and ß1 -adrenoreceptor (ß1-ADR)) and response to Ramipril. MATERIALS AND METHODS: We recruited 120 patients with essential hypertension who were administered Ramipril monotherapy initially, followed by combination therapy, if needed, based on their responses. Relationship between genotypes of the three candidate genes and decrease in the blood pressure (BP) was analyzed. RESULTS: One hundred and six patients were evaluable at the end of the study period and 21 different genotypes were observed among them. Seven of them were classified as responders after 8 weeks and at the end of 12 weeks, an additional 77 (72.64%) were deemed responders. 19/22 non-responders were treated with combination therapy and 7/19 (36.84%) showed a response to the same. There was a significant difference between the proportions of responders and non-responders among the genotypes of the ADD1 and ß1-ADR genes (P=0.005 and 0.003, respectively). The best predictors of response to Ramipril 5 mg daily were the II/GG/SS, II/TG/SS, II/GG/SG, ID/GG/SS, ID/GG/SG and ID/TT/SS and DD/GG/SS; II/GG/GG, II/TT/SG, ID/TG/SG, ID/TT/SG, DD/GG/SG and DD/GG/GG were moderately predictive and II/TT/SS, II/TG/GG, ID/TG/GG, DD/TG/SG and DD/TG/GG were poorly predictive of response. DISCUSSION: Variable responses to Ramipril may be the result of genetic factors. CONCLUSION: Pre-prescription genotyping may help individualize treatment.

Determining the density content of symmetry energy and neutron skin: an empirical approach.

The density dependence of nuclear symmetry energy remains poorly constrained. Starting from precise empirical values of the nuclear volume and surface symmetry energy coefficients and the nuclear saturation density, we show how in the ambit of microscopic calculations with different energy density functionals, the value of the symmetry energy slope parameter L along with that for neutron skin can be put in tighter bounds. The value of L is found to be L=64±5 MeV. For 208Pb, the neutron skin thickness comes out to be 0.188±0.014 fm. Knowing L, the method can be applied to predict neutron skin thicknesses of other nuclei.

Cancer-associated MUC1 mucin inhibits human T-cell proliferation, which is reversible by IL-2.

A number of adenocarcinomas abundantly express and secrete underglycosylated MUC1 mucin. Underglycosylation exposes tandem repeat peptide sequences on cancer-associated MUC1 mucin that are normally cryptic. High levels of MUC1 mucin are correlated with a poor prognosis and immunosuppression in adenocarcinoma patients. In this report we show that cancer-associated MUC1 mucin, affinity-purified from ascites fluids of cancer patients, and synthetic tandem repeats of MUC1 mucin core peptide can suppress human T-cell proliferative responses. This MUC1 mucin-induced suppression of T-cell responses can be reversed by the addition of exogenous IL-2 or anti-CD28 monoclonal antibody. These results are consistent with other studies showing that lymphocytes present in the vicinity of tumor cells are anergic and can be reactivated with exogenous interleukin-2. Overcoming MUC1 mucin-induced immunosuppression with IL-2 combined with active specific immunotherapy might be an effective immunotherapeutic strategy against human adenocarcinomas.

Oscillatory metallic behaviour of carbon nanotube superlattices-an ab initio study.

We study the structural, electronic and optical properties of the (n,n)/(2n,0);n = 3 and 6 superlattices of carbon nanotubes (CNs) by employing the first principles pseudo-potential method within density functional theory (DFT) in the generalized gradient approximation (GGA). There occur pentagon-heptagon defects along the circumference of the heterojunction of these superlattices. The role of the length of the superlattice unit cell on the electronic and optical properties has been investigated. The curvature effects on the various properties are also discussed. The heterojunctions of the small diameter n(3,3)/n(6,0) superlattices which possess a threefold rotational symmetry exhibit an oscillatory behaviour in terms of the fundamental energy bandgaps which vanish whenever the integer n is a multiple of 3. These results indicate that a similar oscillatory behaviour in the fundamental gap energy having a periodicity of 6 may be observed in the case of the large diameter n(6,6)/n(12,0) superlattices whose heterojunctions reveal a sixfold symmetry. The system energy of the 3(6,6)/3(12,0) superlattice shows a minimum. The electronic structure and optical absorption of a superlattice are quite different from those of its constituent carbon nanotubes. The present results obtained after employing all the s-, p- and d-orbitals of the atoms (although the d-orbital contributions are quite small) are quite different from the findings of earlier workers who have employed a phenomenological tight-binding formulation considering only one pi orbital or four orbitals. We find that most of the states are extended resonance states and are quite delocalized in contrast to the earlier finding of the occurrence of the completely localized states in sections of the constituent nanotubes. The metallic superlattices exhibit a high density of states (DOS) at the Fermi level (E(F)). For the large diameter n(6,6)/n(12,0) superlattices, the electron energy gap vanishes for n = 1 and 2 but increases up to a maximum value of 0.344 eV for n = 3 and decreases thereafter for larger n, a result which is in disagreement with earlier workers. These new facts have not been reported in the literature so far.

Growth inhibition of Mycobacterium bovis, Mycobacterium tuberculosis and Mycobacterium avium in vitro: effect of 1-beta-D-2'-arabinofuranosyl and 1-(2'-deoxy-2'-fluoro-beta-D-2'-ribofuranosyl) pyrimidine nucleoside analogs.

The resurgence of tuberculosis and the emergence of multiple-drug-resistant strains of Mycobacteria necessitate the search for new classes of antimycobacterial agents. We synthesized a series of 1-beta-D-2'-arabinofuranosyl and 1-(2'-deoxy-2'-fluoro-beta-D-ribofuranosyl) pyrimidine nucleosides possessing diverse sets of alkynyl, alkenyl, alkyl, and halo substituents at the C-5 position of the uracil and investigated their effect on activity against M. tuberculosis, M. bovis, and M. avium. Among these molecules, 5-alkynyl-substituted derivatives emerged as potent inhibitors of M. bovis, M. tuberculosis, and M. avium. Nucleosides 1-beta-D-2'-arabinofuranosyl-5-dodecynyluracil (5), 1-(2'-deoxy-2'-fluoro-beta-D-ribofuranosyl)-5-dodecynyluracil (24), and 1-(2'-deoxy-2'-fluoro-beta-D-ribofuranosyl)-5-tetradecynyluracil (25) showed the highest antimycobacterial potency against M. bovis and M. tuberculosis. The MIC90 exhibited by compounds 5, 24, and 25 was similar or close to that of the reference drug rifampicin. The most active compounds 5, 24, and 25 were also found to retain sensitivity against a rifampicin-resistant strain of M. tuberculosis H37Rv at similar concentrations. Some of these analogs also revealed in vitro antimicrobial effect against several other gram-positive pathogens.

Inhibition of Mycobacterium tuberculosis, Mycobacterium bovis, and Mycobacterium avium by novel dideoxy nucleosides.

The prevalence of tuberculosis (TB) and mutidrug-resistant tuberculosis (MDR-TB) has been increasing, leading to serious infections, high mortality, and a global health threat. Here, we report the identification of a novel class of dideoxy nucleosides as potent and selective inhibitors of Mycobacterium bovis, Mycobacterium tuberculosis, and drug-resistant Mycobacterium tuberculosis. A series of 5-acetylenic derivatives of 2',3'-dideoxyuridine (3-8) and 3'-fluoro-2',3'-dideoxyuridine (22-27) were synthesized and tested for their antimycobacterial activity against M. bovis, M. tuberculosis, and M. avium. 2',3'-Dideoxyuridine possessing 5-decynyl, 5-dodecynyl, 5-tridecynyl, and 5-tetradecynyl substituents (4-7) exhibited the highest antimycobacterial activity against all three mycobacteria. In contrast, in the 3'-fluoro-2',3'-dideoxyuridine series, a 5-tetradecynyl analogue (26) displayed the most potent activity against these mycobacteria. Among other derivatives, 5-bromo-2',3'-dideoxycytidine (11), 5-methyl-2',3'-dideoxycytidine (12), and 5-chloro-4-thio-2',3'-dideoxyuridine (19) exhibited modest inhibition of M. bovis and M. tuberculosis. In the series of dideoxy derivatives of adenosine, guanosine, and purines, 2-amino-6-mercaptoethyl-9-(2,3-dideoxy-beta-d-glyceropentofuranosyl)purine (32) and 2-amino-4-fluoro-7-(2,3-dideoxy-beta-d-glyceropentofuranosyl)pyrrolo[2,3-d]pyrimidine (35) were the most efficacious against M. bovis and M. tuberculosis, and M. avium, respectively.

Structural, electronic and vibrational properties of small Ga(x)N(y) (x+y = 2-5) nanoclusters: a B3LYP-DFT study.

An ab initio study of the stability, structural and electronic properties has been made for 49 gallium nitride nanoclusters, Ga(x)N(y) (x+y = 2-5). Among the various configurations corresponding to a fixed x+y = n value, the configuration possessing the maximum value of binding energy (BE) is named as the most stable structure. The vibrational and optical properties have been investigated only for the most stable structures. A B3LYP-DFT/6-311G(3df) method has been employed to optimize the geometries of the nanoclusters fully. The binding energies (BEs), highest-occupied and lowest-unoccupied molecular orbital (HOMO-LUMO) gaps and the bond lengths have been obtained for all the clusters. We have considered the zero-point energy (ZPE) corrections ignored by the earlier workers. The adiabatic and vertical ionization potentials (IPs) and electron affinities (EAs), charge on atoms, dipole moments, vibrational frequencies, infrared intensities (IR Int.), relative infrared intensities (Rel. IR Int.) and Raman scattering activities have been investigated for the most stable structures. The configurations containing the N atoms in majority are seen to be the most stable structures. The strong N-N bond has an important role in stabilizing the clusters. For clusters containing one Ga atom and all the others as N atoms, the BE increases monotonically with the number of the N atoms. The HOMO-LUMO gap and IP fluctuate with the cluster size n, having larger values for the clusters containing odd number of N atoms. On the other hand, the EA decreases with the cluster size up to n = 3, and shows slow fluctuations thereafter for the larger clusters. In general, the adiabatic IP (EA) is smaller (greater) than the vertical IP (EA) because of the lower energies of the most stable ground state of the cationic (anionic) clusters. The optical absorption spectrum or electron energy loss spectrum (EELS) is unique for every cluster, and may be used to characterize a specific cluster. All the predicted physical quantities are in good agreement with the experimental data wherever available. The growth of these most stable structures should be possible in experiments.

Effect of lycopene from tomatoes (cooked) on plasma antioxidant enzymes, lipid peroxidation rate and lipid profile in grade-I hypertension.

BACKGROUND: Results from observational studies suggest that the oxidative stress and hyperlipidemic status, which prevails in hypertension, plays an important role in causation of secondary complications. So the aim of the present study is to evaluate the beneficial effect of tomatoes, which are a rich source of lycopene, a relatively new carotenoid known to play an important role in human health and disease. METHODS: In this study lipid peroxidation rate was measured by estimating malondialdehyde (MDA) and the activity of plasma enzymes involved in antioxidant activities like superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), glutathione reductase (GR), reduced glutathione (GSH), and serum lipid profile which includes total cholesterol and triglycerides were estimated in a grade I hypertensive group (n = 40) and an age-matched control group (n = 50). RESULTS: Significantly lower plasma antioxidant enzyme activity, very high lipid peroxidation rate and very high serum total cholesterol, triglycerides in the grade I hypertensive group was observed when compared to the control group (p < 0.001). Sixty days of tomato supplementation in the hypertensive group (n = 30) showed a significant improvement in the levels of serum enzymes involved in antioxidant activities and decreased lipid peroxidation rate (F value highly significant), but there were no significant changes in lipid profile (F value insignificant). CONCLUSION: These findings suggest that tomato lycopene may have considerable natural therapeutic potential as an antioxidant but may not be used as a hypolipidemic agent in hypertension.

Effect of short term supplementation of tomatoes on antioxidant enzymes and lipid peroxidation in type-II diabetes.

The objective of the present study is to evaluate the beneficial effect of tomatoes, which are rich source of Lycopene, relatively a new carotenoid known to play an important role in human health and disease. In this study lipid peroxidation rate was measured by estimating Malondialdehyde and the levels of serum enzymes involved in antioxidant activities like Super Oxide Dismutase, Glutathione Peroxidase, Glutathione Reductase, Reduced Glutathione, in type-II diabetic group (n=40) and age matched control group (n=50), and observed significantly lower levels of antioxidant enzymes and very high lipid peroxidation rate in type-II diabetes when compared to control group (p<0.001). Short term supplementation with tomatoes (cooked) to diabetic group for a period of 30 days, showed a significant improvement in antioxidant enzyme levels (p<0.001) and decreased lipid peroxidation rate (p<0.001) suggesting the supplementation with tomato lycopene may serve as the best method of preventing the oxidative stress in diabetic patients.

Inhibition of hepatitis B virus (HBV) replication by pyrimidines bearing an acyclic moiety: effect on wild-type and mutant HBV.

Chronic hepatitis B virus (HBV) infection remains a major health problem worldwide. The main clinical limitation of a current antiviral drug for HBV, lamivudine, is the emergence of drug-resistant viral strains upon prolonged therapy. A group of 5-, 6-, or 5,6-substituted acyclic pyrimidine nucleosides with a 1-[(2-hydroxyethoxy)methyl] moiety were synthesized and evaluated for antiviral activities. The target compounds were prepared by the reaction of silylated uracils possessing a variety of substituents at the C-5 or C-6 positions or both with 1,3-dioxolane in the presence of potassium iodide and chlorotrimethylsilane by a convenient and single-step synthesis. Among the compounds tested, 5-chloro and 5-bromo analogues possessing an acyclic glycosyl moiety were the most effective and selective antiviral agents in the in vitro assays against wild-type duck HBV (EC50=0.4-2.2 and 3.7-18.5 microM, respectively) and human HBV-containing 2.2.15 cells (EC50=4.5-45.4 and 18.5-37.7 microM, respectively). These compounds were also found to retain sensitivity against lamivudine-resistant HBV containing a single mutation (M204I) and double mutations (L180M/M204V). The compounds investigated did not show cytotoxicity to host HepG2 and Vero cells, up to the highest concentration tested. The results presented here confirm and accentuate the potential of acyclic pyrimidine nucleosides as anti-HBV agents and extend our previous observations. We herein report the capability of acyclic pyrimidine nucleosides to inhibit the replication of both wild-type and drug-resistant mutant HBV.

Effect of long term supplementation of tomatoes (cooked) on levels of antioxidant enzymes, lipid peroxidation rate, lipid profile and glycated haemoglobin in Type 2 diabetes mellitus.

The objective of the present study is to evaluate the beneficial effect of tomatoes, which are a rich source of lycopene, a relatively new carotenoid known to play an important role in human health. In this study, the lipid peroxidation rate was investigated by estimating malondialdehyde (TBARS) levels of antioxidant enzymes like SOD, GSH-Px, GR, GSH, lipid profile, which includes total cholesterol, triglycerides, high density lipoprotein, low density lipoprotein, very low density lipoprotein, and glycated haemoglobin HbA1c in (n = 40) the Type 2 diabetic group (n = 40) and an age-matched control group (n = 50). Significantly lower levels of antioxidant enzymes and very high lipid peroxidation rate in the Type 2 diabetic group were observed when compared to controls (p < 0.001). Likewise, significantly higher levels of lipid profile and glycated haemoglobin (HbA1c) in the diabetic group were observed when compared with control (p < 0.001). Long term tomato supplementation in diabetes mellitus showed a significant improvement in the levels of antioxidant enzymes and decreased lipid peroxidation rate (p < 0.001), but there were no significant changes in lipid profile and glycated haemoglobin HbA1c levels (p > 0.10). These findings suggest that tomato lycopene may have considerable therapeutic potential as an antioxidant but there was no significant lipid lowering effect in Type 2 diabetes mellitus.

Does pregnancy immunize against breast cancer?

Multiparity has been linked with protection against breast cancer. T cells from biparous women, but not T cells from nulliparous women or men, specifically proliferated in response to core peptide sequences of a human breast cancer-associated mucin (MUC-1). Two of the nulliparous women were retested during the first trimester of their first pregnancy, and their T cells proliferated specifically in response to MUC-1 mucin. These observations support the hypothesis that there is a natural immunization against MUC-1 peptide epitopes during pregnancy which provides some protection against the development of breast cancer. These data also suggest that certain MUC-1 synthetic peptides might be effective components of "vaccines" for therapy or prevention of breast cancer.

Expression of MUC1 mucin on activated human T cells: implications for a role of MUC1 in normal immune regulation.

MUC1 mucin is expressed by normal and malignant epithelial cells and is thought to function through cell-cell interactions and transmembrane signal transduction events. Secreted cancer-associated MUC1 is immunosuppressive and inhibits human T-cell proliferation. We report here that newly synthesized MUC1 is expressed on the surface of mitogen-activated human T cells and is also found in soluble form in the supernatants from cultures of mitogen-activated human T cells. After removal of the mitogenic stimulus from the T-cell cultures, MUC1 expression is downregulated. The addition of anti-MUC1 monoclonal antibody to mitogen-activated cultures partially inhibits the T-cell proliferative response. These data suggest that MUC1 serves an immunodulatory function for human T lymphocytes.

The anti-MUC1 monoclonal antibody BCP8 can be used to isolate and identify putative major histocompatibility complex class I associated amino acid sequences.

MHC class I molecules were isolated from the MUC1-positive human breast adenocarcinoma cell line MCF-7 by immunoaffinity using the panreactive anti-class I monoclonal antibodies (MAb) W6/32. Acid-eluted peptides from the class I molecules were separated twice by high-performance liquid chromatography and tested for reactivity with the MAb BCP8, which reacts with the minimal MUC1 core peptide sequence PDTRPA. A peak with strong and specific BCP8 reactivity was found in fractions eluting at 16.5-17.5 min. The protocol used for the MUC1+ pancreatic adenocarcinoma cell line CAPAN-1 (HLA.A2) was to perform sequential affinity purifications of class I molecules using MAb W6/32, followed by affinity purification of HLA.A2 molecules by the HLA.A2.1-specific MAb, MA2.1, and high-performance liquid chromatography fractionation of the acid-eluted material. A single peak with MAb BCP8 reactivity was noted at 18-19 min. The protocol for the MUC1+ breast adenocarcinoma cell line SKBr-3 (HLA.A11,B40), which used A11- and B40-specific MAbs, also resulted in the detection of BCP8-specific peaks at approximately 18-19 min. A preliminary mass spectral analysis of BCP8 affinity-purified class I associated material surprisingly revealed the presence of two 3-mer MUC1 amino acid sequences and one 6-mer sequence. A synthetic 9-mer MUC1 peptide, TSAPDTRPA, containing the isolated fragments was found to cause strong class I up-regulation in T2 cells as well as to serve as an epitope for CTL generated in a primary in vitro immune response. These studies suggest that MUC1-derived peptides are processed and presented in the context of MHC class I molecules on the surface of tumor cells and support the use of MAb BCP8 to further define MHC class I associated MUC1 motifs.

Percutaneous dilational tracheostomy: an initial experience in community based teaching hospital.

UNLABELLED: Percutaneous dilational tracheostomy (PDT) is frequently performed in the intensive care unit to prevent the long term complications associated with prolonged endotracheal intubation. OBJECTIVE: To report the analysis of our experience with percutaneous dilation tracheostomy. STUDY DESIGN: A prospective documentation of 40 patients who received percutaneous dilational tracheostomy in a multidisciplinary intensive care unit during a 12-month period. METHOD: The patients demographic, indications of intubation and PDT, time required to perform the procedure, complications and the outcome of these patients in the intensive care unit were noted. RESULT: Among 425 patients, 40 underwent percutaneous dilational tracheostomy that included 22 females and 18 males with the median age of 35 years. Prolonged ventilatory support was the most common indication for tracheostomy. The average duration of intubation before PDT was 5 days. Median procedure time was 20 minutes. Complications included minor bleeding in two (5%), subcutaneous emphysema with pneumothorax in two patients (5%), tracheal stenosis in three (7.5%), tracheo-esophageal fistula and glottic granuloma in one patient each (2.5%). Among forty patients, 28 (70%) were discharged to the ward, 8 died in intensive care unit and 4 left hospital against medical advice. CONCLUSION: Percutaneous dilational tracheostomy is a safe, quick and effective way for long term airway management in critically ill patients.

Design and studies of novel 5-substituted alkynylpyrimidine nucleosides as potent inhibitors of mycobacteria.

We herein report a new category of 5-substituted pyrimidine nucleosides as potent inhibitors of mycobacteria. A series of 5-alkynyl derivatives of 2'-deoxyuridine (1-8), 2'-deoxycytidine (9-14), uridine (15-17), and 2'-O-methyluridine (18, 19) were synthesized and evaluated for their antimycobacterial activity in vitro. 5-Decynyl, 5-dodecynyl, and 5-tetradecynyl derivatives showed the highest antimycobacterial potency against M. bovis and M. avium, with the 2'-deoxyribose derivatives being more effective than the ribose analogues. Nucleosides bearing short alkynyl side chains 5-ethynyl, 5-propynyl, 5-pentynyl, and 5-heptynyl were mostly not inhibitory. Incorporation of a phenylethynyl function at the 5-position diminished the antimicrobial effect. Furthermore, related bicyclic analogues (20-24) were devoid of antimycobacterial activity, indicating that an acyclic side chain at the C-5 position of the pyrimidine ring is essential for potent activity. Compounds 1-17 were synthesized by the Pd-catalyzed coupling reactions of respective alkynes with 5-iodo derivatives of 2'-deoxyuridine, 2'-deoxycytidine, and uridine. Intramolecular cyclization of 1 and 3-6 in the presence of Cu afforded the corresponding bicyclic compounds 20-24. The investigated nucleosides are recognized here for the first time to be potent inhibitors of mycobacteria. This class of compounds could be of interest for lead optimization as antimycobacterial agents.