Tree-in-Bud Opacities: Not only tuberculosis.

We report a clinical case of mentally challenged young gentleman who was repeatedly hospitalized for respiratory symptoms. Contrast-enhanced CT (computed tomography) thorax revealed tree-in-bud (TIB) opacities. Provisional diagnosis of pulmonary tuberculosis was made and was referred to the respiratory team. However, after listening to patient's voice and reviewing the images on CT thorax, the diagnosis was confirmed as aspiration bronchiolitis.

Personalised management of Chronic Obstructive Pulmonary Disease (COPD): Malaysian consensus algorithm for appropriate use of inhaled corticosteroid (ICS) in COPD patients.

BACKGROUND: Regarding the long-term safety issues with the use of inhaled corticosteroids (ICS) and the clinical predominance of dual bronchodilators in enhancing treatment outcomes in chronic obstructive pulmonary disease (COPD), ICS is no longer a "preferred therapy" according to the Global Initiative for Chronic Obstructive Lung Disease except on top of a dual bronchodilator. This has necessitated a change in the current therapy for many COPD patients. OBJECTIVE: To determine a standardised algorithm to reassess and personalise the treatment COPD patients based on the available evidence. METHODS: A consensus statement was agreed upon by a panel of pulmonologists in from 11 institutes in Malaysia whose members formed this consensus group. RESULTS: According to the consensus, which was unanimously adopted, all COPD patients who are currently receiving an ICS-based treatment should be reassessed based on the presence of co-existence of asthma or high eosinophil counts and frequency of moderate or severe exacerbations in the previous 12 months. When that the patients meet any of the aforementioned criteria, then the patient can continue taking ICS-based therapy. However, if the patients do not meet the criteria, then the treatment of patients need to be personalised based on whether the patient is currently receiving long-acting beta-agonists (LABA)/ICS or triple therapy. CONCLUSION: A flowchart of the consensus providing a guidance to Malaysian clinicians was elucidated based on evidences and international guidelines that identifies the right patients who should receive inhaled corticosteroids and enable to switch non ICS based therapies in patients less likely to benefit from such treatments.

A review of the clinical approach to persistent pain following total hip replacement.

Total hip arthroplasty is effective in reducing pain and improving functional outcome for a variety of hip pathologies. Approximately 27% patients, however, complain of pain at 6 months' follow-up following surgery. The pain may worsen over time and can become severe and chronic in around 4% of patients who ultimately require revision surgery. Therefore, it is important for clinicians to comprehensively assess patients undergoing total hip arthroplasty in order to identify the underlying pathology of a painful hip and then offer prompt treatment. Causes of hip pain after total hip arthroplasty are analysed in this article, as well as the systematic approach to evaluation and appropriate diagnostic investigations.

One-step convergent synthesis of the steroid ring system via the coupling of gamma,delta-unsaturated Fischer carbene complexes with o-ethynylbenzaldehyde.

[reaction: see text]. Simultaneous and stereoselective construction of the steroid B and C rings is observed in a tandem process involving the coupling of o-ethynylbenzaldehyde with 2-alkenylcyclopentylcarbene-chromium complexes.

Guest and subunit exchange in self-assembled ionophores.

[reaction: see text] Self-assembled ionophores, formed by hydrogen bonding of isoG 1 around a cation, are dynamic structures. Multinuclear NMR spectroscopy in CD(3)CN-CDCl(3) showed that cation exchange is >10(4) faster than exchange of isoG 1 ligand in (isoG 1)(10)-Cs(+) Ph(4)B(-). The cationic guest also affected the kinetic stability of the complex. 2D-EXSY NMR experiments in CDCl(3) showed that ligand exchange was 2 orders of magnitude faster for the Li(+)-decamer than for the Cs(+)-decamer.

Reduced haloperidol/haloperidol ratios after oral haloperidol and decanoate administration in schizophrenics.

1. Haloperidol and reduced haloperidol plasma concentrations were measured in thirteen stable schizophrenic patients that received both oral haloperidol and haloperidol decanoate. 2. Significant correlations between reduced haloperidol/haloperidol ratios from oral haloperidol and haloperidol decanoate occurred at week two and week 16, respectively. 3. The formation of RH was consistent during haloperidol decanoate treatment.

Atranones A-G, from the toxigenic mold Stachybotrys chartarum.

Atranones A-G have been isolated from the toxigenic fungus Stachybotrys chartarum. These compounds contain several unusual features including an enol-lactone as part of a 3,7-dioxabicyclo[3.3.0]octane-2-one ring system fused to an 11-membered ring. Two new dolabellane diterpenes, related in structure to the atranones were also isolated, which suggests a diterpenoid origin for the C24 atranones.

Refeeding syndrome: the danger of feeding a starving man.

Refeeding syndrome is a potentially fatal clinical condition characterized by severe electrolyte and fluid shifts associated with metabolic abnormalities in severely malnourished or starved patients undergoing oral, enteral or parenteral refeeding. We here present a case of a 50-year-old Indian male with a background of depression and alcoholic liver disease presented with alleged ingestion of a detergent. He subsequently developed an oesophageal stricture resulting in severe malnutrition. He developed refeeding syndrome following commencement of TPN associated with clear biochemical alteration. This was immediately identified and rectified. This case report highlights the prevalence of refeeding syndrome in a typical hospital setting that can easily be overlooked and stresses the importance of early recognition as this is a preventable disorder.

Nuclear magnetic resonance relaxation time studies on the manganese(II) ion complex with succinyl coenzyme A synthetase from Escherichia coli.

Nuclear magnetic resonance, as well as electron paramagnetic resonance, experiments were carried out in a study of the Mn(II) ion complex with phosphorylated succinyl-CoA synthetase. For high specific activity enzyme samples, there are 3.5 +/- 0.7 metal ion binding sites per enzyme molecule with indistinguishable dissociation constants (KD = 6.9 X 10(-4) M). However, for enzyme samples with a lower specific activity yet equivalent purity, there are 1.6 strong metal ion binding sites (KD = 6.6 X 10(-4) M) and 2.0 weak metal ion binding sites (KD = 4.0 X 10(-3) M), a result that is easily reconciled with the alpha2beta2 subunit structure of the enzyme. Water proton relaxation rate measurements indicate that each strongly bound Mn(II) ion is coordinated to three water molecules. The present results strongly suggest that the existence of nearly 4 high-affinity metal binding sites per enzyme molecule is related to the integrity or configuration of that portion of the molecule which interacts with substrates.

Homodimeric and heterodimeric aryl sulfotransferases catalyze the sulfuric acid esterification of N-hydroxy-2-acetylaminofluorene.

Three aryl sulfotransferases (ASTs) isolated from rat liver catalyze the sulfuric acid esterification of the carcinogen N-hydroxy-2-acetylaminofluorene (N-OH-2AAF). These three ASTs were separated by high resolution anion exchange chromatography and were designated Q1, Q2, and Q3. Q1 and Q2 had high N-OH-2AAF sulfonation activity, whereas Q3 showed low activity. Reversed phase high performance liquid chromatography/mass spectrometry analysis showed Q1-Q3 to be comprised of 33,945- and 35,675-Da protein subunits. Q1 contained only the 35,675-Da protein subunit, Q2 contained equal quantities of 33,945- and 35,675-Da subunits, and Q3 contained only the 33,945-Da subunit. The subunit compositions of Q1-Q3 were confirmed by immunochemical analysis. Size exclusion high performance liquid chromatography confirmed that the active quaternary structure of the three isoenzymes was dimeric. Analysis of liver cytosols for the relative contributions of Q1-Q3 to total cytosolic N-OH-2AAF sulfotransferase activity indicated the Q1, Q2, and Q3 accounted for 44, 46, and 10% of the activity, respectively. These results demonstrate the existence of both homodimeric and heterodimeric aryl sulfotransferases and show that two ASTs, a homodimer of 35,675-Da subunits and a heterodimer of a 33,945- and a 35,675-Da subunit, are primarily responsible for hepatic N-OH-2AAF sulfotransferase activity.

A phosphorus-31 nuclear magnetic resonance investigation of intracellular environment in human normal and sickle cell blood.

Intracellular pH and 2,3-diphosphoglycerate concentration in sickle cell amenia and normal human blood samples were measured by means of phosphorus-31 nuclear magnetic resonance spectroscopy. To monitor the concentrations of various internal phosphorylated metabolites of intact red blood cells, heparinized blood samples were used and were incubated at 37 degrees C with 5.6% C92, 25% O2, and 69.4% N2. The 31P chemical shifts of phosphorylated compounds, such as 2,3-diphosphoglycerate, adenosine 5'-triphosp-ate, and inorganic phosphate, depend on pH, and by using an appropriate calibration curve, the intracellular pH of intact erythrocytes can be obtained. The intracellular pH values in fresh sickl cell blood and normal blood were found to be 7.14 and 7.29, respectively. However, the whole-blood pH, as measured by a standard pH meter, was found to be 7.54 for both types of blood. The initial concentration of 2,3-diphosphoglycerate in sickle cell blood was about 30% higher, but it was depleted much faster during incubation than that in normal blood. The difference in intracellular pH between these two types of blood samples remained constant during incubation, even after depletion of 2,3-diphosphoglycerate. These results suggest that there are differences in intracellular environment between normal and sickle cell blood. Thus, 31P nuclear magnetic resonance spectroscopy provides a fast, direct, continuous, and noninvasive way to monitor the intracellular environment of intact erythrocytes.

2'-Deoxyguanosine reacts with a model quinone methide at multiple sites.

Quinone methides and related intermediates have been implicated in a range of beneficial and detrimental processes in biology and effectively alkylate a variety of cellular components despite the ubiquitous presence of water. As a prerequisite to understanding the origins of their specificity, the major products generated by DNA and its components with an unsubstituted ortho quinone methide under aqueous conditions were recently characterized [Pande, P., Shearer, J., Yang, J., Greenberg, W. A., and Rokita, S. E. (1999) J. Am. Chem. Soc. 121, 6773-6779]. Investigations currently focus on the complete range of derivatives formed by deoxyguanosine (dG) and guanine residues in duplex DNA through product isolation and structure determination using reversed-phase chromatography and a range of one and two-dimensional NMR techniques. Previous construction of a synthetic standard for dG alkylation is now shown to have yielded the N1-linked adduct rather than the N(2)-linked adduct. This later adduct has also now been characterized and confirmed to be the major product of reaction between the quinone methide and both duplex DNA and dG under neutral conditions. An N7 adduct of guanine has additionally been identified under these conditions and appears to result from spontaneous deglycosylation of the corresponding N7 adduct of dG. A combination of steric and electronic properties of duplex DNA likely contribute to the enhanced selectivity of the quinone methide for its guanine N(2) position (7.8:3.2:1.0 for adducts of N(2):N7:N1) relative to that of dG (4.7:3.5:1.0 for adducts of N(2):N7:N1).

Phosphorus-31 nuclear magnetic resonance studies of human red blood cells.

Phosphorus-31 nuclear magnetic resonance spectroscopy is used to monitor the changes in the concentrations of 2,3-diphosphoglycerate and adenosine-5' triphosphate as a function of time and to measure the intracellular pH of normal and abnormal red blood cells in the presence of 25% oxygen, 5.6% carbon dioxide, and 69.4% nitrogen at 37 degrees C. Under these conditions, the intracellular pH values of normal AA, sickle SS, AS, SC, AC, and CC red cells are 7.24 +/- 0.07, 7.13 +/- 0.04, 7.15 +/- 0.03, 7.16 +/- 0.03, 7.24 +/- 0.05, and 7.14 +/- 0.03, respectively. The intracellular pH of SS red cells is about 0.1 pH unit more acidic than that of AA red cells. Time-dependent changes in the concentration of 2,3-diphosphoglycerate of normal human red cells show an initial lag phase, followed by a slow linear decrease. The duration of the initial lag phase decreases in the following order: AA approximately equal to AS approximately equal to AC greater than SC greater than SS approximately equal to CC red cells. The decay of 2,3-diphosphoglycerate is much faster in SS and CC red cells compared to other red cells studied. The time-dependent depletion of adenosine-5' triphosphate in these red cells is similar in nature to that of 2,3-diphosphoglycerate. The linewidths of 2-P and 3-P resonances of 2,3-diphosphoglycerate for fully oxygenated SS red cells are broader (approximately 20 Hz) than those for other red cells (approximately 10 Hz). However, the linewidths of 2-P and 3-P resonances of 2,3-diphosphoglycerate in the lysates of these red cells are narrower (approximately 4.5 Hz) than those in the intact red cells and are very similar in all types of red cells studied. The linewidths of the 31P resonances of adenosine-5' triphosphate are also similar (approximately 30-40 Hz) in all red cells studied. In addition, we have investigated the effect of carbamylation on the metabolism of 2,3-diphosphoglycerate and the intracellular pH in SS and AA red cells and have found that neither one is affected by this process. Our results provide further evidence that phosphorus-31 nuclear magnetic resonance spectroscopy offers a direct, non-invasive way to investigate the intracellular environment and the metabolism of phosphorylated metabolites in intact red blood cells.

Pharmacokinetics of SCH-39304 in human immunodeficiency virus-infected patients following chronic oral dosing.

The pharmacokinetics of SCH-39304, an investigational, orally active, broad-spectrum antifungal agent, were evaluated in 17 adult, human immunodeficiency virus-positive males. Patients were studied on days 1 and 16 and were divided into the following three treatment groups: (i) patients with culture-proven oropharyngeal candidiasis who were not receiving concurrent zidovudine therapy and who were treated with 50 mg of SCH-39304 daily (n = 6); (ii) patients with culture-proven oropharyngeal candidiasis who were receiving concurrent zidovudine therapy and who were treated with 50 mg of SCH-39304 daily (n = 5); and (iii) patients with or without oropharyngeal candidiasis who were receiving concurrent zidovudine therapy and who were treated with 200 mg of SCH-39304 daily (n = 6). All patients received a single daily dose of the study medication for 16 days. Plasma samples for SCH-39304 concentration measurement were collected for 6 h following the initial dose and for 504 h following the day 16 dose. Urine was collected for 24 h following SCH-39304 administration on days 1 and 16. All samples were assayed for SCH-39304 by gas chromatography. Wide intersubject variations in SCH-39304 plasma concentration-versus-time profiles were observed on each study day. Absorption appeared to be slow, with mean day 1 peak plasma SCH-39304 concentrations of 1.2 micrograms/ml at 2.1 h (50 mg) and 3.9 micrograms/ml at 4.0 h (200 mg) after drug administration. Mean peak plasma SCH-39304 concentrations on day 16 were 7.6 micrograms/ml at 4.3 h (50 mg) and 17.2 micrograms/ml at 3.2 h (200 mg) after drug administration. Mean elimination half-lives on day 16 for the 50- and 200-mg daily dosages were 100 and 89 h, respectively. SCH-39304 was cleared primarily unchanged in the urine. Mean areas under the plasma concentration-versus-time curve (from 0 to 24 h) on day 16 reflect a lower than expected increase with the 200-mg/day regimen (314.5 microgram.h/ml) compared with that for the 50-mg/day regimen (139.9 microgram.h/ml), suggesting the potential for reduced bioavailability at higher dosages. No significant effect of concurrent zidovudine therapy on the kinetics of SCH-39304 was observed.

Assay of progressive motion of boar spermatozoa.

The motility of ejaculated boar spermatozoa was assayed by measuring the number of organisms which have entered a capillary tube in an experimental setup with the spermatozoal suspension as well as the capillary content containing the same chemically defined motility medium. This medium, used both for washing and suspending spermatozoa, contained only an isotonic tris HCl (isotris) buffer at pH 7.0. The recommended assay conditions are the following: (1) wash the spermatozoa three times with isotris buffer, (2) suspend the spermatozoa in a concentration of 10(6) spermatozoa/ml, and (3) assay at 25 degrees C with an incubation period of 60 min.