Thymic carcinoma presenting with an unusual and delayed metastasis to the neural foramen, mimicking thoracic spinal radiculopathy.

We report a case of metastatic thymic carcinoma which presented as an enhancing mass located in the neural foramen of the thoracic spine. More common tumours which arise in the neural foramen would include a neurogenic tumour or developmental anomalies such as a foregut duplication cyst. This case is singular firstly because the lesion present as radiculopathy which mimics a neurogenic tumour. Secondly, the presentation was unusually delayed as the patient presented to our centre more than a decade after the resection of the primary tumour in another institution.

Cardiorenal syndrome - a new classification and current evidence on its management.

Patients with chronic kidney disease (CKD) are at high risk for major cardiovascular (CV) morbidity and mortality, especially when they range among the elderly. The co-existence of renal dysfunction is common in patients with chronic heart failure (CHF), and renal failure is among the strongest predictors of mortality in patients with heart failure. Approximately one-third of dialysis patients also suffer from heart failure. The term "cardiorenal syndrome" has been increasingly described in recent literature, as there is growing recognition of the frequent association of combined renal and cardiac dysfunction. The pathophysiology of the cardiorenal syndrome involves interrelated hemodynamic and neurohormonal mechanisms, including the sympathetic nervous system, the renin-angiotensin-aldosterone system, and endothelin and arginine vasopressin system activation. Recently, a new classification of cardiorenal syndrome has been proposed with five subtypes that reflect the pathophysiology, the bidirectional nature of heart and kidney interaction and the time-frame. The management of the cardiorenal syndrome remains a challenge in spite of the advances in medical therapy and novel agents. Novel agents such as B-type natriuretic peptide (BNP) derivative, endothelin antagonist, adenosine antagonist or vasopressin antagonist have been evaluated in randomized controlled trials, and their results are discussed in this review. Mechanical support like hemodialysis and ultrafiltration are found to be useful in acute cardiorenal syndrome. There has been renewed interest in b-blockers in chronic cardiorenal syndrome patients to prevent sudden cardiac death from arrhythmia. In this review, we discuss the evidence behind the definition, pathophysiology, new proposed classification and the various therapeutic measures available for acute cardiorenal syndrome as well as chronic cardiorenal syndrome.

Serological diagnosis of Mycobacterium avium complex lung diseases by enzyme immunoassay of IgA antibodies against MAC-specific glycopeptidolipid core antigen.

INTRODUCTION: There is an increasing trend worldwide in the incidence of Mycobacterium avium complex pulmonary diseases (MAC-PD) and the diagnosis is sometimes complicated. Recently, an enzyme immunoassay (EIA) kit that detects serum IgA antibody against MAC-specific glycopeptidolipid (GPL) core antigen had been developed and found to be useful in discriminating MAC-PD from other lung diseases. The antibody was subsequently also found to be elevated in patients suffering Mycobacterium abscessus pulmonary diseases (MAB-PD). This study is to evaluate this EIA kit in the serological diagnosis of MAC-PD in Hong Kong Chinese patients. METHODS: The study was conducted in Grantham Hospital, Hong Kong between July 2017 and July 2018. Assay of the IgA antibody level using the EIA kit was done on blood samples collected from patients suffering from MAC-PD, MAB-PD, pulmonary tuberculosis and other lung diseases. RESULTS: There were 100 subjects recruited into the study, among which 11 were excluded. By using the cut-off value 0.7 U/mL provided by the manufacturer, the sensitivity and specificity for diagnosis were 73.7% and 77.6% for MAC-PD; 50% and 77.6% for MAB-PD. By receiver operating characteristic curves analysis, new cut-off for MAC-PD and MAB-PD were calculated as 1.771 U/mL and 0.172 U/m, respectively. The sensitivity and specificity were 68.4% and 86.2% for MAC-PD, whereas 66.7% and 72.4% for MAB-PD. CONCLUSIONS: Our study showed that the enzyme immunoassay of IgA antibodies against MAC-specific glycopeptidolipid core antigen could help to distinguishing MAC and M. abscessus pulmonary diseases from pulmonary tuberculosis and other lung diseases among Hong Kong Chinese patients. Further larger scale studies in our local population for the usefulness of this antibody test in the diagnosis and monitoring of MAC and M. abscessus lung diseases might be warranted.

Rapidly deteriorating renal function with membranoproliferative glomerulonephritis Type 1 associated with hepatitis C treated successfully with steroids and antiviral therapy: a case report and review of literature.

INTRODUCTION: The hepatitis C virus (HCV) infection is associated with several renal diseases including mixed essential cryoglobulinemia, membranoproliferative glomerulonephritis (MPGN) and less frequently membranous nephropathy and crescentic glomerulonephritis. We present a case of HCV-associated cryoglobulin-negative, MPGN Type 1 with features of early crescents and rapidly deteriorating renal function requiring urgent treatment. CASE: A 35-year-old male was admitted with history of arthralgia and erythematous rash. His past medical history included being an intravenous drug abuser. Biochemistry test showed raised serum creatinine of 150 micromol/l. He had nephrotic range proteinuria of 6 g/day and a serum albumin of 23 g/l. Viral serology for hepatitis B and HIV was negative but confirmed evidence of HCV infection with genotype 3A and viral load of 151,014 copies. He had a renal biopsy and histology demonstrated features of crescentic MPGN Type 1. His renal function deteriorated rapidly with his serum creatinine rising to 300 micromol/l over 2 days. We commenced treatment with intravenous methylprednisolone, 500 mg once daily (o.d.) for 3 days, followed by oral prednisolone 40 mg o.d. Concurrently, pegylated Interferon- (IFN) I+/- was commenced. After a 2-week treatment, his renal function showed remarkable recovery with creatinine reduced to 140 micromol/l. After 3 months, ribavirin was added when his renal function remained stable. He had tolerated his treatment without any major side effects. At 6 months follow-up clinic, his renal function was normal with serum creatinine of 69 micromol/l, 24-h urinary protein had dropped to 0.35 g/day, serum albumin increased to 38 g/l and HCV PCR was negative. DISCUSSION: The current treatment strategy of HCV-associated renal diseases includes targeting viral trigger HCV with interferon and ribavirin. Both IFN-I+/- and ribavirin have their limitation and adverse effects. In a clinical scenario where there is evidence of rapidly deteriorating renal function with crescentic glomerulonephritis, cautious use of immunosuppressive therapy may well be essential in the acute stage to halt the progression of kidney damage. Literature review of the treatment strategy for MPGN Type 1, cryoglobulin-negative with early features of crescents associated with HCV showed that there was no report or guideline available. CONCLUSIONS: To our knowledge, this is the first case in the literature of rapidly progressing MPGN Type 1 associated with HCV and nephrotic syndrome treated successfully with antiviral drugs and steroids concurrently. Our case highlights an important treatment strategy and may be beneficial to nephrologists facing this clinical scenario in the future. However, a randomized controlled trial is required to evaluate the efficacy of this treatment combination before it can be a standard treatment.

Technetium myocardial perfusion scanning in prerenal transplant evaluation in the United kingdom.

Because death with a functioning graft remains one of the most important causes of long-term renal transplant failure, cardiac risk stratification and screening for coronary artery disease are essential components of pretransplant assessment. Pretransplant screening for occult coronary artery disease in a subset of these patients may improve outcome. The UK follows the European Best practice guideline 1.5.5 E. Although echocardiography, thallium myocardial perfusion scanning (MPS), dobutamine stress echocardiography, and coronary angiography have been suggested as means of cardiovascular assessment, the best means of assessment remains undetermined. Therefore, we investigated the role of 99m technetium sestamibi myocardial perfusion scanning as an assessment tool for identifying those patients with end-stage renal failure at high risk of cardiovascular death after renal transplantation. Retrospectively, we studied 126 patients that had a MPS as part of their pretransplant assessment. Overall unadjusted survival was 65% at 3 years. Twelve deaths resulted from cardiovascular causes. A reversible defect on MPS was associated with a fatal cardiac event and all-cause mortality. The unadjusted hazard ratio of cardiac event with reversible defect on MPS was 3.1 (95% confidence interval, 1.1 to 18.2) and hazard ratio of death with reversible defect on MPS was 1.92 (95% confidence interval, 1.1 to 4.4). Thus, MPS may be a useful tool in cardiac risk stratification and in selecting patients with a favorable outcome after renal transplantation. Our patients with a reversible defect in particular have increased cardiac mortality. This group may benefit from coronary angiography.

Endobronchial nocardiosis associated with broncholithiasis.

Pulmonary nocardiosis is a rare respiratory infection which commonly affects immunocompromised patients but also in immunocompetent hosts. The clinical manifestation is variable and endobronchial nocardiosis is a very rare condition. We report a case of endobronchial nocardiosis associated with the presence of a broncholith. The pathogenesis and the treatment of this condition are discussed below.

Bronchiolitis obliterans organising pneumonia (BOOP) in a lung cancer patient after lobectomy.

A 79 year-old patient with lung cancer underwent a standard thoracotomy and lobectomy. Postoperatively, he developed low-grade fever and dyspnoea. Chest X-rays showed progressive lung infiltrates, which was subsequently diagnosed to be Bronchiolitis Obliterans Organizing Pneumonia (BOOP) by transbronchial lung biopsy. He responded well to corticosteroid therapy. The case report is followed by a brief discussion on BOOP in association with lung cancer and thoracotomy.

Primary spinal oligoastrocytoma mimicking longitudinally extensive transverse myelitis.

Longitudinally extensive transverse myelitis (LETM) is most commonly associated with neuromyelitis optica spectrum disorders (NMOSD). However, a wide range of etiologies may produce longitudinally extensive spinal cord lesions (LESCLs) on imaging. We highlight the case of a patient with a spinal cord tumor whose imaging showed LESCL and was diagnosed with LETM. He did not respond to immunosuppression and subsequently developed a progressive and protracted clinical course. Thoracic cord biopsy performed 6 years after symptom onset showed primary spinal oligoastrocytoma. We discuss the features that should raise suspicion of a neoplasm in the context of LESCL and serve a reminder that not all LESCLs are inflammatory.

Computational analysis of PKA-balanol interactions.

Protein kinases are important targets for designing therapeutic drugs. This paper illustrates a computational approach to extend the usefulness of a single protein-inhibitor structure in aiding the design of protein kinase inhibitors. Using the complex structure of the catalytic subunit of PKA (cPKA) and balanol as a guide, we have analyzed and compared the distribution of amino acid types near the protein-ligand interface for nearly 400 kinases. This analysis has identified a number of sites that are more variable in amino acid types among the kinases analyzed, and these are useful sites to consider in designing specific protein kinase inhibitors. On the other hand, we have found kinases whose protein-ligand interfaces are similar to that of the cPKA-balanol complex and balanol can be a useful lead compound for developing effective inhibitors for these kinases. Generally, this approach can help us discover new drug targets for an existing class of compounds that have already been well characterized pharmacologically. The relative significance of the charge/polarity of residues at the protein-ligand interface has been quantified by carrying out computational sensitivity analysis in which the charge/polarity of an atom or functional group was turned off/on, and the resulting effects on binding affinity have been examined. The binding affinity was estimated by using an implicit-solvent model in which the electrostatic contributions were obtained by solving the Poisson equation and the hydrophobic effects were accounted for by using surface-area dependent terms. The same sensitivity analysis approach was applied to the ligand balanol to develop a pharmacophoric model for searching new drug leads from small-molecule libraries. To help evaluate the binding affinity of designed inhibitors before they are made, we have developed a semiempirical approach to improve the predictive reliability of the implicit-solvent binding model.

A case of concomitant tuberculosis and sarcoidosis with mycobacterial DNA present in the sarcoid lesion.

A 35-year-old Chinese woman initially presented with histologically and bacteriologically confirmed tuberculous lymphadenitis. She was also found to have thrombocytopenia, elevated serum alkaline phosphatase, and bilateral lung infiltrates. After 15 months of antituberculosis treatment, despite resolution of the cervical lymphadenopathy, she started to experience dyspnea. Chest radiograph appearance, thrombocyte count, and liver biochemistry had all deteriorated as well. Histologic findings from tissues obtained via transbronchial biopsy and open lung biopsy were consistent with sarcoidosis but also showed the presence of mycobacterial DNA by the polymerase chain reaction. She subsequently achieved a very good response clinically, radiographically, hematologically, and biochemically with 1-year of corticosteroid treatment for her sarcoidosis, and she remained relapse-free afterwards. The concomitant presence of tuberculosis and sarcoidosis in this patient together with the presence of mycobacterial DNA in the sarcoid lesion reiterate the possibility that mycobacteria or some of its components may be capable of inducing the immune response and the pathologic changes of sarcoidosis.

Rapid diagnosis of smear-negative pulmonary tuberculosis via fibreoptic bronchoscopy: utility of polymerase chain reaction in bronchial aspirates as an adjunct to transbronchial biopsies.

Fibreoptic bronchoscopy was performed on 190 patients with chest radiographic lesions and negative sputum smears for acid-fast bacilli. Aside from obtaining transbronchial biopsies for histological examination, bronchial aspirate specimens were also tested for Mycobacterium tuberculosis complex DNA by a conventional polymerase chain reaction (PCR) technique. Of 177 transbronchial biopsies performed, a diagnosis was found in 64 cases [43 cases of tuberculosis (TB), 17 cases of lung carcinoma and four cases of other infective/inflammatory diseases] giving a diagnostic yield of 36.2%. PCR was positive in 105 of 108 finally diagnosed cases of TB and 22 of 82 non-TB cases. The sensitivity, specificity, positive predictive value and negative predictive value of PCR when applied to bronchial aspirate specimens for diagnosing smear-negative pulmonary TB were 97.2%, 73.2%, 82.7% and 95.2% respectively. Therefore, detection of M. tuberculosis complex DNA in bronchial aspirates by PCR might have an adjunctive place to transbronchial biopsies in the rapid diagnosis of smear-negative pulmonary tuberculosis.

Measuring and modeling vocal source-tract interaction.

The quality of synthetic speech is affected by two factors: intelligibility and naturalness. At present, synthesized speech may be highly intelligible, but often sounds unnatural. Speech intelligibility depends on the synthesizer's ability to reproduce the formants, the formant bandwidths, and formant transitions, whereas speech naturalness is thought to depend on the excitation waveform characteristics for voiced and unvoiced sounds. Voiced sounds may be generated by a quasiperiodic train of glottal pulses of specified shape exciting the vocal tract filter. It is generally assumed that the glottal source and the vocal tract filter are linearly separable and do not interact. However, this assumption is often not valid, since it has been observed that appreciable source-tract interaction can occur in natural speech. Previous experiments in speech synthesis have demonstrated that the naturalness of synthetic speech does improve when source-tract interaction is simulated in the synthesis process. The purpose of this paper is two-fold: 1) to present an algorithm for automatically measuring source-tract interaction for voiced speech, and 2) to present a simple speech production model that incorporates source-tract interaction into the glottal source model. This glottal source model controls: 1) the skewness of the glottal pulse, and 2) the amount of the first formant ripple superimposed on the glottal pulse. A major application of the results of this paper is the modeling of vocal disorders.

Polymeric films as vehicle for buccal delivery: swelling, mechanical, and bioadhesive properties.

PURPOSE: To investigate the suitability of an SCMC (sodium carboxymethyl cellulose/polyethylene glycol 400/carbopol 934P) and an HPMC (hydroxypropylmethyl cellulose/polyethylene glycol 400/carbopol 934P) films as drug vehicle for buccal delivery. METHODS: The mechanical and in vitro bioadhesive strength properties of the films were investigated using texture analyzer equipment, while swelling behavior was studied in different media, namely, distilled water and simulated saliva solution. In addition, the in vivo bioadhesion of the film was studied by estimating the film residence time on buccal mucosa of human volunteers. RESULTS: Increase in carbopol 934P content was found to elevate the elasticity, softness and bioadhesive strength but decrease the strength and degree of swelling of both SCMC and HPMC films. SCMC films swelled more extensively in distilled water while HPMC films in simulated saliva solution. HPMC films exhibited greater in vivo bioadhesion although the in vitro bioadhesive strength was lower than SCMC films. Correlation existed between the in vivo and in vitro bioadhesion data within the polymer, but no rank correlation was observed between the two polymers. CONCLUSION: HPMC films may be preferred over SCMC films as drug vehicle for buccal delivery as the former was tougher, more elastic, more bioadhesive in vivo and swelled in a more tolerable manner in the oral cavity than the latter.

An in-vitro method for buccal adhesion studies: importance of instrument variables.

A method using a texture analyzer equipment and chicken pouch as the biological tissue was investigated for measuring the bioadhesive properties of polymers under simulated buccal conditions. The method was evaluated using two polymers, namely Carbopol 974P and Methocel K4M while the instrument variables studied included the contact force, contact time and speed of withdrawal of the probe from the tissue. The parameters measured were the work of adhesion and peak detachment force. Longer contact time and faster probe speed not only gave better reproducibility of results, but also better sensitivities for both parameters measured. On the other hand, a certain level of contact force was found essential for achieving good bioadhesion, above which there was no further contribution to the bioadhesion process. When the method was applied to determine the bioadhesiveness of several polymers, the values obtained for the work of adhesion and peak detachment force were quite consistent in the ranking of the polymers. The Carbopols were found to have the highest values, followed by gelatin, sodium carboxymethyl celluloses and hydroxypropylmethyl celluloses. On the other hand, Alginic acid, Eudragit RLPO and RSPO, and Chitosan appeared to have low bioadhesive values.

Formulation and evaluation of controlled release Eudragit buccal patches.

Controlled release buccal patches were fabricated using Eudragit NE40D and studied. Various bioadhesive polymers, namely hydroxypropylmethyl cellulose, sodium carboxymethyl cellulose and Carbopol of different grades, were incorporated into the patches, to modify their bioadhesive properties as well as the rate of drug release, using metoprolol tartrate as the model drug. The in-vitro drug release was determined using the USP 23 dissolution test apparatus 5 with slight modification, while the bioadhesive properties were evaluated using texture analyzer equipment with chicken pouch as the model tissue. The incorporation of hydrophilic polymers was found to affect the drug release as well as enhance the bioadhesiveness. Although high viscosity polymers can enhance the bioadhesiveness of the patches, they also tend to cause non-homogeneous distribution of the polymers and drug, resulting in non-predictable drug-release rates. Of the various bioadhesive polymers studied, Cekol 700 appeared to be most satisfactory in terms of modifying the drug release and enhancement of the bioadhesive properties.

Preparation and properties of gem-dichlorocyclopropane derivatives of long-chain fatty esters.

Methyl oleate (18:1) and linoleate (18:2) were readily transformed to the corresponding gem-dichlorocyclopropane derivatives in high yield, using triethylbenzylammonium chloride as the phase-transfer catalyst in the presence of aqueous NaOH and CHCl3. Reaction of dichlorocarbene with methyl 12-hydroxystearate furnished methyl 12-chlorostearate (49%) and 12-O-formylstearate (19%). The hydroxy group in methyl ricinoleate was protected (O-tetrahydropyran-2'-yl) prior to dichlorocyclopropanation of the ethylenic bond. Removal of the protecting group allowed the hydroxy group to be converted to a chloride, O-acetyl, azido or O-formyl function. Treatment of methyl ricinoleate with thionyl chloride, followed by the reaction with dichlorocarbene gave the corresponding 12-chloro-dichlorocyclopropane derivative. The dichlorocyclopropane derivative of oleic acid was transformed to a C19 allenic fatty acid when treated with t-butyl lithium. However, the remaining dichlorocyclopropane derivatives containing an additional functional group in the alkyl chain, failed to yield the corresponding allenic derivatives. All derivatives were characterized by a combination of spectroscopic and chromatographic techniques, including infrared, 1H nuclear magnetic resonance (NMR), and 13C NMR spectroscopy.

Determination of 1-benzo[b]thien-2-ylethanone and related impurities by high performance liquid chromatography.

1-Benzo[b]thien-2-ylethanone (2-acetylbenzothiophene, 2-ABT) and related impurities were determined using a reverse-phase high performance liquid chromatography system and UV detection at 254 nm. Separation was achieved isocratically on a 4.6 mm x 25 cm, 5 microns Zorbax Rx-C8 column using an eluent which is 0.2% perchloric acid/THF in a ratio of 60:40 (v/v). The chromatographic system resolved 2-ABT and known impurities in less than 45 min with near baseline resolution. Known impurities were quantitated versus 2-ABT with corrections made for differences in detector response at the specified wavelength. Linearity for 2-ABT was demonstrated with a correlation coefficient > 0.9999. Assay precision (RSD values) for impurities at 0.5% ranged from +/- 1.8% to +/- 14%, while precision (RSD values) for the 2-ABT determination ranged from +/- 0.81% to +/- 1.1%. A variety of different chromatographic columns and conditions are discussed for the application.