Tuberculous mastoiditis - a case series.

SUMMARY: Tuberculous mastoiditis (TBM) is a rare form of extrapulmonary tuberculosis (TB), which may result in catastrophic complications, including mastoid and ossicle destruction, hearing loss and intracranial spread if untreated. Diagnosis is challenging due to the paucibacillary nature of extrapulmonary TB, compounded by limited theatre access for specimen retrieval, resulting in delayed diagnosis and treatment initiation. In this case series, we discuss three cases of TBM (one paediatric and two adults) who presented to the public and private healthcare sectors in the Eastern Cape in 2022, underscoring that TB does not respect socioeconomic status.

Paediatric chronic suppurative otitis media in the Free State Province: clinical and audiological features.

BACKGROUND: Chronic suppurative otitis media (CSOM) is a chronic infection of the middle ear cleft. In sub-Saharan Africa >50% of cases occur in children <10 years of age. OBJECTIVES: To describe the otological, audiological and bacteriological findings in children with CSOM. METHODS: We conducted a prospective study at the Ear, Nose and Throat (ENT) Clinic at Universitas Academic Hospital between August 2009 and December 2010. We included all children with CSOM over this period. Patients underwent ENT and paediatric examination, and were tested for HIV. Pus swabs were taken after an ear toilet for routine microbiology, fungal and Mycobacterium tuberculosis culture. We performed audiological testing after the otorrhoea had resolved. RESULTS: Eighty-six children (113 ears) were included, with a median age of 4.6 years (range 1 - 12 years). The mean duration of otorrhoea was 161.7 weeks (range 4 - 572 weeks). Nine patients (10.5%) presented with coalescent mastoiditis and/or intracranial complications of CSOM. Of the 153 organisms identified; Gram-negative bacteria were present in 93 (82.3%) ears, with 94.8% of these being sensitive to quinolones. Only 1 case of tuberculous otitis media was identified. HIV infection was present in 54.6% of patients tested. There was a hearing loss in 44 (66.7%) of the tested affected ears. CONCLUSIONS: There was a long delay between the onset of symptoms and accessing ENT services. Most cases of CSOM were due to quinolone-sensitive Gram-negative aerobes. There was a high prevalence of cholesteatoma, hearing loss and other complications in children in this study.

Synthesis, structural characterization and in vitro inhibitory studies against human breast cancer of the bis-(2,6-di-tert-butylphenol)tin(IV) dichloride and its complexes.

Four new organotin(IV) complexes of bis-(2,6-di-tert-butylphenol)tin(IV) dichloride [(tert-Bu-)(2)(HO-Ph)](2)SnCl(2) (1) with the heterocyclic thioamides 2-mercapto-pyrimidine (PMTH), 2-mercapto-4-methyl-pyrimidine (MPMTH), 2-mercapto-pyridine (PYTH) and 2-mercapto-benzothiazole (MBZTH), of formulae {[(tert-Bu-)(2)(HO-Ph)](2)Sn(PMT)(2)} (2), {[(tert-Bu-)(2)(HO-Ph)](2)Sn(MPMT)(2)} (3), {[(tert-Bu-)(2)(HO-Ph)](2)SnCl(PYT)} (4) and {[(tert-Bu-)(2)(HO-Ph)](2)SnCl(MBZT)} (5), have been synthesized and characterized by elemental analysis, (1)H-, (13)C-, (119)Sn-NMR, EPR, FT-IR, Raman and Mössbauer spectroscopic techniques. The crystal and molecular structures of compounds 1­5 have been determined by X-ray diffraction. The geometries around the metal center adopted in complexes 1­5 varied between tetrahedral in 1, trigonal bipyramidal in 3, 4, 5 and distorted octahedral in 2. Two carbon atoms from aryl groups and two chlorine atoms form a distorted tetrahedron in the case of 1. Two carbon, two sulfur and two nitrogen atoms from thione ligands form a distorted octahedral geometry around tin(IV) with trans-C(2), cis-N(2), cis-S(2)-configurations in 2. However, in the case of 4 and 5 complexes two carbon, one sulfur, one nitrogen and one chloride atom form a distorted trigonal bipyramidal arrangement. Finally, in the case of 3 the trigonal bipyramidal geometry is achieved by two carbon, two sulfur and one nitrogen atom in a unique coordination mode of thioamides toward the tin(IV) cation. Compounds 1­5 were tested for their in vitro cytotoxicity against the human breast adenocarcinoma (MCF-7) cell line. Compound 3 exhibits strong cytotoxic activity against MCF-7 cells (IC(50) = 0.58 ± 0.1 µM).

Structural motifs and biological studies of new antimony(III) iodide complexes with thiones.

Eight new antimony(III) iodide complexes of the heterocyclic thioamides, 2-mercapto-1-methylimidazole (MMI), 2-mercaptobenzimidazole (MBZIM), 5-ethoxy-2-mercaptobenzimidazole (EtMBZIM), 2-mercaptothiazolidine (MTZD), 3-methyl-2-mercaptobenzothiazole (NMeMBZT), 2-mercapto-3,4,5,6-tetrahydropyrimidine (tHPMT), 2-mercaptopyridine (PYT), and 2-mercaptopyrimidine (PMT) of formulas {[SbI(3)(MMI)(2)].MeOH} (1), [SbI(3)(MBZIM)(2)] (2), {[SbI(2)(mu(2)-I)(EtMBZIM)(2)](2).H(2)O} (3), [SbI(3)(MTZD)] (4), [(NMeMBZT)SbI(2)(mu(2)-I)(2)(mu(2)-S-NMeMBZT)SbI(2) (NMeMBZT)] (5), {[SbI(3)(tHPMT)(3)].MeOH} (6), [SbI(3)(PYT)] (7), and [SbI(3)(PMT)(2)] (8), have been synthesized and characterized by elemental analysis, FT-IR spectroscopy, FT-Raman spectroscopy, and TG-DTA analysis. The crystal structures of 3, 4, 5, 6, and 7 were also determined by X-ray diffraction. The complexes show interesting structural motifs. Complex 6 is a monomer, with octahedral (Oh) geometry around the metal ion formed by three sulfur and three iodide atoms. Complexes 3 and 5 are dimers, with a square pyramidal (SP) geometry in each monomeric unit, while complexes 4 and 7 are polymers with pseudotrigonal bipyramidal (psi-TBP). Two or three sulfur atoms from thioamide ligands and three iodide atoms are bound to Sb atoms forming building blocks for the dimers and polymers. Strong intramolecular interactions between mu(2)-I and/or mu(2)-S and Sb atoms stabilize both structures. In dimer complex 5, two terminal iodide and one terminal sulfur atom are bonded to the Sb ion, while two mu(2)-I and one mu(2)-S bridging atoms bridge the metal ions forming psi-Oh geometry. Computational studies using multivariant linear regression (MLR) and artificial neural networks (ANN) and considering biological results (50% inhibitory concentration, IC(50)) as dependent variables derived a theoretical equation for IC(50) values of the complexes studied. The calculated IC(50) values are compared satisfactorily with the experimental inhibitory activity of the complexes measured. Complexes 3-7 were used to study their influence upon the catalytic peroxidation of linoleic acid by the enzyme Lipoxygenase (LOX). Compounds 1-8 were also tested for in vitro cytotoxicity, and they showed mostly a moderate cytostatic activity against a variety of tumor cell lines but comparable with those found for the antimony(III) chloride and bromide complexes, reported earlier [Ozturk et al. Inorg. Chem. 2007, 46, 2861-2866; Ozturk et al. Inorg. Chem. 2009, 48, 2233-2245].

Coordination chemistry of tetra- and tridentate ferrocenyl polyphosphines: an unprecedented [1,1'-heteroannular and 2,3-homoannular]-phosphorus-bonding framework in a metallocene dinuclear coordination complex.

PalladiumII and nickelII halide complexes of the ferrocenyl polyphosphines 1,1',2,3-tetrakis(diphenylphosphino)ferrocene (1), and 1,1',2-tris(diphenylphosphino)-4-tert-butylferrocene (5) were prepared and characterized by multinuclear NMR. The metallo-ligand 1, the palladium [Pd2Cl4(1)] (3b) and nickel [NiCl2(5)] (6) coordination complexes were additionally characterized by X-ray diffraction crystallography. The behavior of 1 toward coordination to nickel and palladium was surprisingly different because the coordination of a second metal center after the initial 1,2-phosphorus-bonding of nickel was markedly difficult. The preference of nickel for 1,2-P coordination on 1,1'-bonding was confirmed by the exclusive formation of 6 from 5. The changes noted between the solid state structure of the ligand 1 and the structure obtained for the dinuclear palladium complex 3b reveal the rotational flexibility of this tetraphosphine. This flexibility is at the origin of the unique framework for a metallocenic dinuclear metal complex in which both coexist a 1,1'-heteroannular chelating P-bonding and a 2,3-homoannular chelating P-bonding with two palladium centers. Some reported specimens of ferrocenyl polyphosphines of constrained geometry have previously revealed that phosphorus lone pair overlap can lead to very intense "through-space" 31P31P nuclear spin-spin coupling constants (JPP) ( J. Am. Chem. Soc. 2004, 126 (35), 11077-11087] in solution phase. In these cases, an internuclear distance between heteroannular phosphorus atoms below 4.9 A, with an adequate orientation of the lone-pairs in the solid state and in solution, was a necessary parameter. The flexibility of the new polyphosphines 1 and 5 does not allow that spatial proximity (internuclear distances between heteroannular phosphorus above 5.2 A in the solid state); accordingly the expected through-space nuclear spin-spin coupling constants were not detected in any of their coordination complexes nor in 1.

Coordination properties of Cu(II) and Ni(II) ions towards the C-terminal peptide fragment -TYTEHA- of histone H4.

In order to reveal more information about the toxicity caused by metals and furthermore their influence to the physiological metabolism of the cell, the hexapeptide model Ac-ThrTyrThrGluHisAla-am representing the C-terminal 71-76 fragment of histone H4 which lies into the nucleosome core, was synthesized. A combined pH-metric and spectroscopic UV-VIS, EPR, CD and NMR study of Ni(II) and Cu(II) binding to the blocked hexapeptide, revealed the formation of octahedral complexes involving imidazole nitrogen of histidine, at pH 5 and pH 7 for Cu(II) and Ni(II) ions respectively. In basic solutions a major square-planar 4 N Ni(II)-complex, adopting a {N(Im), 3N(-)} coordination mode, was formed. In the case of Cu(II) ions, a 3 N complex, involving the imidazole nitrogen of histidine and two deprotonated amide nitrogens of the backbone of the peptide, at pH 7 and a series of 4 N complexes starting at pH 6.5, were suggested. In addition Ni(II)-mediated hydrolysis of the peptide bond-Tyr-Thr was evident following our experimental data.

Mutations in the neurofilament light chain gene (NEFL) cause early onset severe Charcot-Marie-Tooth disease.

Neurofilament light chain polypeptide (NEFL) is one of the most abundant cytoskeletal components of the neuron. Mutations in the NEFL gene were recently reported as a cause for autosomal dominant Charcot-Marie-Tooth type 2E (CMT2E) linked to chromosome 8p21. In order to investigate the frequency and phenotypic consequences of NEFL mutations, we screened 323 patients with CMT or related peripheral neuropathies. We detected six disease associated missense mutations and one 3-bp in-frame deletion clustered in functionally defined domains of the NEFL protein. Patients have an early onset and often a severe clinical phenotype. Electrophysiological examination shows moderately to severely slowed nerve conduction velocities. We report the first nerve biopsy of a CMT patient with a de novo missense mutation in NEFL, and found an axonal pathology with axonal regeneration clusters and onion bulb formations. Our findings provide further evidence that the clinical variation observed in CMT depends on the gene mutated and the specific type of mutation, and we also suggest that NEFL mutations need to be considered in the molecular evaluation of patients with sporadic or dominantly inherited CMT.

Brain plasticity for sensory and linguistic functions: a functional imaging study using magnetoencephalography with children and young adults.

In this report, the newest of the functional imaging methods, magnetoencephalography, is described, and its use in addressing the issue of brain reorganization for basic sensory and linguistic functions is documented in a series of 10 children and young adults. These patients presented with a wide variety of conditions, ranging from tumors and focal epilepsy to reading disability. In all cases, clear evidence of reorganization of the brain mechanisms of either somatosensory or linguistic functions or both was obtained, demonstrating the utility of magnetoencephalography in studying, completely noninvasively, the issue of plasticity in the developing brain.

Pulmonary hypoplasia in the myogenin null mouse embryo.

Although fetal breathing movements are required for normal lung development, there is uncertainty concerning the specific effect of absent fetal breathing movements on pulmonary cell maturation. We set out to evaluate pulmonary development in a genetically defined mouse model, the myogenin null mouse, in which there is a lack of normal skeletal muscle fibers and thus skeletal muscle movements are absent in utero. Significant decreases were observed in lung:body weight ratio and lung total DNA at embryonic days (E)14, E17, and E20. Reverse transcriptase/polymerase chain reaction, in situ immunofluorescence, and electron microscopy revealed early lung cell differentiation in both null and wild-type lungs as early as E14. However at E14, myogenin null lungs had decreased 5'-bromo-2-deoxyuridine incorporation compared with that of wild-type littermates, whereas at E17 and E20, increased Bax immunolabeling and terminal deoxyribonucleotidyl transferase-mediated dUTP-biotin nick-end labeling staining were detected in the myogenin null mice but not in the wild-type littermates. These observations highlight the importance of skeletal muscle contractile activity in utero for normal lung organogenesis. Null mice lacking the muscle-specific transcription factor myogenin exhibit a secondary effect on lung development such that decreased lung cell proliferation and increased programmed cell death are associated with lung hypoplasia.

In vivo microdialysis and gas chromatography/mass spectrometry for studies on release of N-acetylaspartlyglutamate and N-acetylaspartate in rat brain hypothalamus.

Microdialysis and gas chromatography/mass spectrometry was used for the measurement of extracellular N-acetylaspartate (NAA) and N-acetylaspartylglutamate (NAAG) in rat hypothalamus. The sensitivity of the method for each of these compounds was approximately 5 pmol/30 microliters of dialysate. Baseline NAA concentrations in dialysate were estimated to be approximately 25 pmol/36 microliters, while that for NAAG was at or below the detection limit of 5 pmol/ 36 microliters. In vivo and in vitro calibrations of microdialysis probes showed that the recovery for NAA was approximately 10 percent. For NAAG, the in vitro recovery was 6.3%, and in vivo recovery, 11%. Depolarization stimulation using 100 mM KCl in the microdialysis perfusate was employed to measure extracellular NAA and NAAG concentrations. Extracellular NAA was elevated to approximately 70 pmol/36 microliters dialysate following depolarization. No significant elevation of NAAG was observed. By infusing known amounts of stable isotopically labeled NAAG-d3 via the microdialysis probe and measuring the isotopically labeled catabolic product, NAA-d3, in collected microdialysate, we were able to confirm the existence of one or more hydrolytic enzymes active towards NAAG in the hypothalamus. This finding suggest the possible involvement of active metabolic processes in the relationship between NAAG and NAA releases.

Amoxapine overdose in a young man: a transient mitochondrial abnormality?

Amoxapine is a second-generation tricyclic antidepressant structurally related to the neuroleptic loxapine. It was previously marketed as an alternative to traditional tricyclic antidepressants because of alleged shorter onset of action and fewer cardiotoxic effects. However, various adverse reactions, including cardiac dysrhythmias, renal failure, coma, seizures, and neuroleptic malignant syndrome, were reported during therapy or after acute overdose. A 14-year-old boy ingested 1900 mg of amoxapine and developed seizures, hypertension, hyperpyrexia, altered mental status, myoglobinuria, renal failure, and transient magnetic resonance imaging (MRI) changes suggestive of hypertensive encephalopathy and neuroleptic malignant syndrome. Since mitochondrial disorders can cause multisystem failure, including encephalopathy, renal tubular dysfunction, and myopathy, a transient, toxic disorder of mitochondrial function was considered as the basis for the patient's clinical and MRI changes.

Proton magnetic resonance imaging and spectroscopic studies of the pathogenesis and treatment of juvenile dermatomyositis.

Juvenile dermatomyositis is an inflammatory disorder of muscle, skin, and connective tissue. Immune vasculopathy is central to the pathophysiology. We studied a 13-year-old boy with juvenile dermatomyositis using proton magnetic resonance imaging (MRI) with short tau inversion recovery (STIR), and proton magnetic resonance spectroscopy (MRS) to quantitate lipid and water in affected regions of muscle. Tissue perfusion was assessed by measuring tissue water concentration changes during isometric exercise of the tibialis anterior muscle. During sequential studies over 3 months of steroid treatment, STIR image abnormalities, resting water concentrations, and diminished perfusion returned to normal. Resting lipid concentrations increased during this period. MRI serves to guide muscle biopsy and monitor progress of the disease state. MRS demonstrates the vasculopathy and provides noninvasive assessment of steroid therapy in juvenile dermatomyositis.

Xeroderma pigmentosum and Cockayne syndrome: overlapping clinical and biochemical phenotypes.

Two siblings are described whose clinical presentation of cutaneous photosensitivity and central nervous system dysfunction is strongly reminiscent of the DeSanctis-Cacchione syndrome (DCS) variant of xeroderma pigmentosum. An extensive clinical evaluation supported a diagnosis of DCS and documented previously unreported findings. In vitro fibroblast studies showed UV sensitivity that was two to three times that of normal controls. However, neither a post-UV-irradiation DNA excision-repair defect indicative of XP nor a semiconservative DNA replication defect indicative of XP variant was found. Rather, a failure of RNA synthesis to recover to normal levels after UV exposure was observed, a biochemical abnormality seen in Cockayne syndrome (CS), one of the premature-aging syndromes with clinical UV sensitivity. These patients, therefore, clinically have XP, but their biochemical characteristics suggest CS. The reason(s) for the severe neurologic disease, in light of the relatively mild cutaneous abnormalities, is unclear. Other cases with unusual fibroblast responses to irradiation have been noted in the literature and, along with the data from our patients, reinforce the notion of the complexity of DNA maintenance and repair.

A congenital myasthenic syndrome refractory to acetylcholinesterase inhibitors.

We studied 4 siblings (3 men and 1 woman), ages 22 to 43 years, with congenital ptosis, external ophthalmoplegia, proximal muscle weakness and fatigability unresponsive to acetylcholinesterase (AChE) inhibitors. Repetitive nerve stimulation showed a significant compound muscle action potential (CMAP) area decrement at 2 or 3 Hz. Nerve conduction studies and concentric needle electromyography were normal, and repetitive CMAPs to single nerve stimulation were not observed. Voluntary single fiber electromyography (SFEMG) showed increased jitter and blocking. Assessment of individual end-plates using SFEMG with intramuscular axonal microstimulation showed no uniform relationship between jitter and the rate of stimulation, consistent with a postsynaptic defect of neuromuscular transmission. Edrophonium eliminated the decremental response to repetitive nerve stimulation, but caused no significant clinical improvement, suggesting an additional mechanism for weakness in these patients.

Proton magnetic resonance of exercise-induced water changes in gastrocnemius muscle.

Exercise-induced water concentration changes have been determined in the medial gastrocnemius muscle noninvasively with image-guided in vivo proton magnetic resonance spectroscopy (MRS). These measurements were performed on seven normal male volunteers during and after isometric and ischemic-isometric exercise at 5, 10, and 20% maximum voluntary contraction (MVC). The observed water flux changes during different phases of exercise have been interpreted in terms of fluid transfer between the vasculature and exercising muscle. Good correlation between individual MVC and changes in water fluxes and the decay of water content was observed after 20% MVC exercise level. MRS results have been found to be consistent with those reported in the literature based on invasive biopsy techniques.

Neurologic morbidity associated with achondroplasia.

Neurologic morbidity has long been appreciated in adults with achondroplasia and has recently been recognized to be common in children. Neurologic complications result from bony stenosis involving the entire vertebral column and the base of the skull. These complications are reviewed with special attention to the findings in children.

Organometallic estrogens: synthesis, interaction with lamb uterine estrogen receptor, and detection by infrared spectroscopy.

As an integral part of the development of a new technique using organometallic markers for the detection of hormone receptors by FT-IR spectroscopy, a series of estradiol derivatives labeled with Cr(CO)3 or Cr(CO)2CS fragments on the A ring has been synthesized. The stereochemistry of one of these steroids, alpha-[3-(dimethyl-tert-butylsiloxy)-17 beta-estradiol]dicarbonyl(thiocarbonyl)chromium(0), has been established by X-ray diffraction. The organochromium-labeled steroids are stable in aqueous methanol solution, and their relative binding affinities to estrogen receptor have been determined; these values vary from 0.4 to 28%. The complex exhibiting the strongest affinity, [3-O-(3-hydroxypropyl)-17 beta-estradiol]-chromium tricarbonyl complex, has been prepared in a tritiated form with a high specific activity (4.1 Ci/mmol). This tritiated hormone binds reversibly to the estradiol receptor in lamb uterine cytosol with an affinity (Kd = 0.85 nM) and number of binding sites (n = 770 fmol/mg of protein) close to the values observed for estradiol itself. The level of nonspecific binding is low, and the hormone is not bound significantly to other nontarget tissues. The observation that the binding affinity of the steroid depends on which side of the steroidal A ring the organometallic label is bound demonstrates the nonequivalence of the two sides of the A ring with respect to the receptor site. The FT-IR spectra of the organochromium markers in the v(CO) region can be used for the detection of the estradiol receptor in lamb uterine cytosol.