The challenge of differentiating tuberculous meningitis from bacterial meningitis.

Tuberculous meningitis (TBM) is a rare but important differential diagnosis in patients with impaired consciousness. Here, we describe a case of TBM in an 83-year-old Japanese woman who presented to a local hospital with fever and decreased consciousness of 20 days' duration (from day -40). She was started on treatment for bacterial meningitis due to an increased cerebrospinal fluid cell count, but her condition did not improve. She was transferred to a second hospital on suspicion for cholecystitis, then to a university hospital when consciousness did not improve and finally to us at a fourth hospital. On day -2, diffuse granulation was seen in both lung fields on chest computed tomography, sputum Mycobacterium test was positive and adenosine deaminase was elevated in spinal fluid. We diagnosed TBM secondary to miliary tuberculosis and started treatment with steroids and anti-tuberculous drugs (day 0). However, her level of consciousness did not improve and she died at a sanatorium on day 178. Delayed treatment of TBM has a prognostic impact and should be kept in mind as a differential diagnosis for impaired consciousness.

Characterization of melanosomes and melanin in Japanese patients with Hermansky-Pudlak syndrome types 1, 4, 6, and 9.

Hermansky-Pudlak syndrome (HPS) is an autosomal recessive disorder characterized by oculocutaneous albinism (OCA), a bleeding tendency, and ceroid deposition. Most of the causative genes for HPS encode subunits of the biogenesis of lysosome-related organelles complex (BLOC). In this study, we identified one patient each with HPS4, HPS6, and HPS9 by whole-exome sequencing. Next, we analyzed hair samples from the three patients and representative patients with HPS1 and controls using electron microscopy and chemical methods. All HPS patients had fewer, smaller, and more immature melanosomes than healthy controls. Further, all patients showed reduced total melanin content and increased levels of benzothiazine-type pheomelanin. The results of this study demonstrate the impact of the dysfunctions of BLOCs on the maturation of melanosomes and melanin levels and composition through analysis of their hair samples.

Cryptococcal Pleuritis Presenting with Lymphocyte-predominant and High Levels of Adenosine Deaminase in Pleural Effusions Coincident with Pulmonary Tuberculosis.

Co-infection with cryptococcus and tuberculosis has rarely been reported. We herein report a case of an 80-year-old man with cryptococcal pleuritis concurrent with pulmonary tuberculosis. He was admitted for progression of left pleural effusion and consolidation in the left upper lobe. Culture for Mycobacterium tuberculosis was positive in sputum, and analyses of pleural effusion revealed lymphocyte-predominant high levels of adenosine deaminase (ADA). Medical thoracoscopy revealed massive infiltration of Cryptococcus neoformans in pleura without granuloma. This is the first case report of cryptococcal pleuritis coincident with pulmonary tuberculosis. Cryptococcal pleuritis should be ruled out when the adenosine deaminase levels are elevated in pleural effusion.

1,3-Diiodocalix[4]arene: synthesis by Ullmann-type iodination of 1,3-bistriflate ester of calix[4]arene, conformational analysis, and transformation into 1,3-dicarboxy-, diformyl-, and dialkylcalix[4]arenes.

A facile synthesis of 1,3-diiodocalix[4]arene 6 has been achieved by copper-catalyzed iodination of the 1,3-bistriflate ester 2a of p-tert-butylcalix[4]arene. After protection of the hydroxy groups with iodomethane, diiodide 6 is subjected to halogen­lithium exchange with butyllithium, followed by carbonation with CO2 or formylation with N-formylpiperidine and subsequent deprotection of the hydroxy groups to give novel dicarboxylic acid 11 or dialdehyde 16 in practical yields. The iodo groups of diiodide 6 pass through the calixarene macrocycle; the activation free energy for the conversion of the more stable syn conformer 6syn to the less stable anti conformer 6anti is ΔG(⧧) = 104 kJ mol(­1) at 298 K. Dialdehyde 16 shows fast self-exchange between two equivalent species with a cone conformation, ΔG(⧧), being 63.2 kJ mol(­1). Dicarboxylic acid 11 adopts a cone conformation and forms a dimer in solution as suggested by 1H NMR and X-ray crystallographic analyses. The arrangement of the iodide groups of compound 6 can be fixed predominantly to anti (17a and 17b) by introducing bulky alkyl groups (e.g., propyl groups) onto the hydroxy groups. The stereospecific alkylation of the iodo groups of the resulting di-O-alkylated anti-1,3-diiodides provides access to the anti-1,3-dialkylcalixarenes 19, which is otherwise difficult to obtain.