Cerebellar abscess and syringomyelia due to isoniazid-resistant Mycobacterium tuberculosis.

A 19-year-old immunocompetent man was admitted to hospital with diplopia, nausea, vomiting and change in mental status. The patient had a history of tuberculous meningitis that was diagnosed at another hospital 6 months before the present admission, and at that time anti-tuberculosis treatment was initiated using a first-line drug combination. A computed tomography (CT) scan of the brain revealed non-communicating hydrocephalus. A ventriculo-peritoneal shunt was inserted surgically. Two months later, the patient was hospitalized again for fever, dysphagia and left hemiparesis. At that time, his cranial CT findings were within normal limits; however, magnetic resonance imaging (MRI) revealed an irregular multilocular peripheral contrast-enhancing lesion in the posterior fossa. The abscess was surgically drained. The presence of acid-fast bacilli in the abscess material was demonstrated by Ziehl-Neelsen staining. Mycobacterium tuberculosis grew on Lowenstein-Jensen culture medium, and the strain was found to be resistant to isoniazid. One month after the operation, the patient became quadriparetic. Cervical MRI revealed a cervico-thoracic syringomyelitic cavity, after which a syringoperitoneal shunt was placed. Treatment with four drugs was continued for 10 months, and then treatment with three drugs for a total period of 18 months. The patient recovered, with residual quadriparesis. Even though very rare, isoniazid-resistant M. tuberculosis may be the causative agent of progressive tuberculosis.     

Detection and genotyping of Epstein-Barr virus by polymerase chain reaction in tissues obtained from cases with Hodgkin's disease in Turkey.

In order to determine the positivity rate and genotype of Epstein-Barr virus (EBV) in cases with Hodgkin's disease (HD) in Turkey, 40 tissue specimens from HD patients were analysed. Ten non-lymphoid tissue samples from individuals without any evidence for lymphoma were used as controls. The cases with HD included 33 males and 7 females with a mean age of 28 years. Nodular sclerosis was the most prevalent histological subtype (16/40) followed by mixed cellularity (10/40), lymphocyte predominance (9/40), and lymphocyte depletion (5/40). After histopathological evaluation, deparafinisation and lysis of the specimens, one-stage polymerase chain reaction (PCR) and two-stage (nested) PCR assays were performed with the primers common for both EBV genotypes and the primers specific for EBV types 1 and 2, respectively. EBV DNA was detected in 22 of 40 (55%) cases with HD and in 1 of 10 (10%) control specimens. The distribution of EBV DNA positivity according to the histological subtypes was as follows: 10 of 16 (62.5%) for nodular sclerosis, 3 of 5 (60%) for lymphocyte depletion, 5 of 9 (55.6%) for lymphocyte predominance, and 4 of 10 (40%) for mixed cellularity. Although most of the HD patients were males of 15-34 years of age, there were no significant differences between EBV positivities obtained from different sex and age groups. The rates of EBV genotypes were 82% for type 1, 9% for type 2, and 9% for both types, respectively.     

Polyether Synthesis through Reductive Etherification Reaction Strategy

The reductive etherification reaction (RER) of carbonyl groups (aldehydes or ketones) through silane as a reducing agent together with Bronsted or Lewis acid affords the synthesis of symmetrical and unsymmetrical ethers. This strategy is applied at the macromolecular level for the first time in 1993, and isophthalaldehyde is self-polymerized in the presence of triethylsilane (Et₃SiH)/ tritylperchlorate (TrClO₄) to yield polyethers with low to moderate molecular weights. Next, the polyethers with alternating structures are achieved by reacting isophthalaldehyde with bis(trimethylsilyl) ethers or diols as comonomers using reducing agent silane and Lewis acid. Moreover, in recent years, it is shown that polyether synthesis and post-polymerization modification (PPM) of polymers proceeds smoothly and effectively with the RER strategy in the presence of chlorodimethylsilane (CDMS), which acts as both a reducing agent and a Lewis acid.     

Effect of water extract of Turkish propolis on tuberculosis infection in guinea-pigs.

Mycobacterium tuberculosis (H(37)R(v))-infected guinea-pig model was used to investigate the effect of water extract of propolis (WEP). After subcutaneous inoculation of tubercle bacilli, each animal received oral WEP (n=9), isoniazid (n=5) or saline (n=6) as placebo and were sacrificed 30 days later. Formation of necrosis was less prominent in the group treated with WEP, but was not statistically significant (P>0.05). The granuloma formation in the same group was more prominent than the placebo and isoniazid groups; however, this finding failed to reach statistical significance by the Kruskal-Wallis test (P>0.05). These findings suggest that Turkish WEP may have a limited effect on the development of tuberculosis infection in this guinea-pig model.     

Characterization and solubilization of vasoactive intestinal peptide receptors from rat lung membranes

Receptors for vasoactive intestinal peptide (VIP) were characterized in rat lung membranes by binding and covalent cross-linking of [125I]VIP using ethylene glycolbis-(succinimidylsuccinate). Binding studies indicated the presence of two classes of binding sites for VIP in rat lung membranes: 0.28 +/- 0.11 pmol/mg protein high affinity receptors (Kd = 79.2 +/- 26.4 pM) and 3.3 +/- 0.9 pmol/mg protein lower affinity receptors (Kd = 4.8 +/- 2.1 nM). Furthermore, binding of [125I]VIP to rat lung receptors was inhibited by micromolar concentrations of GTP analogs, guanosine-5'-O-(3-thiotriphosphate) GTP gamma S), and guanylylimidodiphosphate, suggesting that VIP receptors in rat lung membranes were tightly coupled to the guanine nucleotide regulatory protein (Ns). Scatchard analysis of VIP binding in the presence of GTP gamma S revealed selective inhibition of binding to high affinity sites. A 58K band was specifically labeled when membranes covalently labeled with [125I]VIP were analyzed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis under reducing conditions. The apparent size of this species was not altered when sodium dodecyl sulfate-polyacrylamide gel electrophoresis analysis was carried out in the absence of reducing agent. Unlabeled VIP inhibited the labeling, with an IC50 of about 1 nM. A related peptide, GH-releasing factor-(1-40)OH, exhibited a much lower binding affinity, and two unrelated peptides, insulin and atrial natriuretic factor, did not inhibit labeling of the 58K species, even at micromolar concentrations. Labeling of the 58K species was inhibited in a GTP gamma S-dependent manner, suggesting the involvement of this species in the coupling to Ns. These data collectively indicated that the 58K species was a VIP-binding unit of VIP receptors in rat lung membranes. Several nondenaturing detergents were tested for extraction of labeled receptors from the membrane; the best extraction was obtained using 1% n-octyl-beta-D-glucopyranoside.     

Epidemiology,pathophysiology and contemporary management of cardiogenic shock – a position statement from the Heart Failure Association of the European Society of Cardiology

Cardiogenic shock (CS) is a complex multifactorial clinical syndrome with extremely high mortality, developing as a continuum, and progressing from the initial insult (underlying cause) to the subsequent occurrence of organ failure and death. There is a large spectrum of CS presentations resulting from the interaction between an acute cardiac insult and a patient's underlying cardiac and overall medical condition. Phenotyping patients with CS may have clinical impact on management because classification would support initiation of appropriate therapies. CS management should consider appropriate organization of the health care services, and therapies must be given to the appropriately selected patients, in a timely manner, whilst avoiding iatrogenic harm. Although several consensus‐driven algorithms have been proposed, CS management remains challenging and substantial investments in research and development have not yielded proof of efficacy and safety for most of the therapies tested, and outcome in this condition remains poor. Future studies should consider the identification of the new pathophysiological targets, and high‐quality translational research should facilitate incorporation of more targeted interventions in clinical research protocols, aimed to improve individual patient outcomes. Designing outcome clinical trials in CS remains particularly challenging in this critical and very costly scenario in cardiology, but information from these trials is imperiously needed to better inform the guidelines and clinical practice. The goal of this review is to summarize the current knowledge concerning the definition, epidemiology, underlying causes, pathophysiology and management of CS based on important lessons from clinical trials and registries, with a focus on improving in‐hospital management.     

Can flow cytometry detect successful ticlopidine treatment in patients with VVI pacemakers?

An increased platelet activation status is present in patients with VVI pacemakers. With platelet activation, there is modulation of platelet surface molecule expression. In the current study, the expression of platelet surface markers in VVI patients before and after ticlopidine treatment and control subjects was investigated by means of flow cytometry. The study group consisted of 25 patients with VVI pacemaker, and 15 control subjects. CD42b, CD61, and CD62p expression were significantly increased in VVI patients compared with control subjects (CD42b p < 0.001, CD61 p< 0.005 and CD62p p < 0.001). In addition, after ticlopidine treatment, platelets showed a significant fall in expression of all these markers in VVI patients (CD42b p < 0.001, CD61 p < 0.005 and CD62p p< 0.001). Our data suggest an increase of the surface expression of all these markers on platelets and demonstrate the efficacy of ticlopidine in reducing them.     

Expression of claudin‐11 by tumor cells in cutaneous squamous cell carcinoma is dependent on the activity of p38δ

The incidence of cutaneous squamous cell carcinoma (cSCC) is rapidly increasing, and the prognosis of patients with metastatic disease is poor. There is an emerging need to identify molecular markers for predicting aggressive behaviour of cSCC. Here, we have examined the role of tight junction (TJ) components in the progression of cSCC. The expression pattern of mRNAs for TJ components was determined with RNA sequencing and oligonucleotide array‐based expression analysis from cSCC cell lines (n=8) and normal human epidermal keratinocytes (NHEK, n=5). The expression of CLDN11 was specifically elevated in primary cSCC cell lines (n=5), but low or absent in metastatic cSCC cell lines (n=3) and NHEKs. Claudin‐11 was detected in cell‐cell contacts of primary cSCC cells in culture by indirect immunofluorescence analysis. Analysis of a large panel of tissue samples from sporadic UV‐induced cSCC (n=65), cSCC in situ (n=56), actinic keratoses (n=31), seborrhoeic keratoses (n=7) and normal skin (n=16) by immunohistochemistry showed specific staining for claudin‐11 in intercellular junctions of keratinizing tumor cells in well and moderately differentiated cSCCs, whereas no staining for claudin‐11 was detected in poorly differentiated tumors. The expression of claudin‐11 in cSCC cells was dependent on the activity of p38δ MAPK and knock‐down of claudin‐11 enhanced cSCC cell invasion. These findings provide evidence for the role of claudin‐11 in regulation of cSCC invasion and suggest loss of claudin‐11 expression in tumor cells as a biomarker for advanced stage of cSCC.