Anatomical variation of the vertebral artery clinically mimicking myasthenia gravis

Cranial nerve palsy, most commonly trigeminal, abducens, or facial, caused by compression of an ectatic or elongated intracranial artery is a well-known phenomenon. Symptoms of brain stem compression by an abnormal artery have rarely been reported (Tomasello et al. Neurosurgery 56(suppl 1):117–124, 2005). The authors present a 59-year-old woman with intermittent ptosis of the right eye, diplopia and swallowing disturbances, enhanced after physical effort, implying myasthenia gravis. Typical diagnostic procedures, e.g. repetitive nerve stimulation tests, acetylcholine receptor antibodies level were within normal limit. Neurogenic changes from the orbicularis oculi muscle were found in EMG. MRI and angio-CT revealed anatomical variation of the vertebral artery (elongated and arcuate route), causing intermittent signs of brain stem lesion. We point out the similarity of the clinical symptoms of myasthenia gravis and vascular brain stem compression by abnormal vertebral artery. The two diseases require completely different therapeutic proceedings.     

Syrian hamster infected with Leishmania infantum: A new experimental model for inflammatory myopathies

Idiopathic inflammatory myopathies (IIMs) are inflammatory disorders of unknown origin. On the basis of clinical, histopathological, and immunological features, they can be differentiated into three major and distinct subsets: dermatomyositis; polymyositis; and inclusion‐body myositis. Although a few animal models for IIM are currently available, they lack several characteristic aspects of IIMs. The aim of our study was to examine skeletal muscle involvement in an experimental animal model of visceral leishmaniasis, a disseminated infection caused by the protozoan parasite Leishmania infantum, and to compare features of associated inflammation with those of human IIM. Syrian hamsters infected intraperitoneally with amastigotes of L. infantum were killed at 3 or 4 months post‐infection, and the skeletal muscles were studied. Focal inflammation was predominantly observed in the endomysium and, to a lesser extent, in perivascular areas. Degenerating muscle fibers were also found, as well as myonecrosis. Immunofluorescence with confocal laser scanning microscopy was used to characterize the phenotype of inflammatory infiltrates and the distribution of MHC class I and II in muscle biopsies. The infiltrating inflammatory cells consisted mainly of T cells, and CD8⁺ T cells were found in non‐necrotic muscle fibers that expressed MHC class I on the sarcolemma. In addition to T cells, several macrophages were present. The model we are proposing closely resembles polymyositis and may be useful in studying certain aspects of this disease such as the role of T cells in muscle inflammation and myocytotoxicity, while also providing novel therapeutic targets. Muscle Nerve, 2009     

Integrin expression in the dermis during scar formation in humans

To evaluate changes leading to human wound reorganization we examined by immunohistochemistry the expression of several extracellular matrix (ECM) receptors (alpha2 chain of VLA-2, alpha3 chain of VLA-3, alpha6 chain of VLA-6, alphav, and beta1/beta3 chains of integrins) in a series of biopsies of human skin wounds healing by primary intention. The first time point investigated in this study was day 6 after injury, i.e. when a fibrin clot has been almost completely replaced by the granulation tissue. Gradual changes in integrin expression in granulation tissue and in the dermal scar were observed from the first time point investigated and were characterized by an up-regulation of alpha2beta1 complex, alphav integrin subunit, and beta1 integrin subunit. At day 27, the expression of the alpha2 chain of VLA-2 in the scar decreased. The expression of alphav and beta1 integrin subunits decreased but was still detectable by day 35. Vitronectin expression from day 7 onwards was also increased and colocalized to the area of the wounded dermis, and decreased by day 27. Our data suggests that, during the remodelling of the provisional matrix of the wound, dermal fibroblasts express transiently mainly alpha2 and alphav subunits of integrins associated with up-regulation of the beta1 subunit. It seems that up-regulation of some chains of integrins may be involved in the control of deposition of ECM components associated with wound healing.     

Methicillin-resistant Staphylococcus aureus. Nosocomial acquisition and carrier state in a wound care center

OBJECTIVE: To assess methicillin-resistant Staphylococcus aureus (MRSA) nosocomial acquisition and carrier state in a wound care center. DESIGN AND SETTING: The results of an intervention to control MRSA were compared with those of historical controls at the wound care center of university-based H?pital Broussais, Paris, France. PATIENTS: Patients admitted for specific care of chronic ulcers and surgical wounds. MAIN OUTCOME MEASURES: Incidence rates of MRSA carriers and acquisition in wounds. RESULTS: Of 88 patients admitted during a 3-month preintervention period in 1993, 18 (21%) were MRSA carriers. Of 334 patients admitted in 1994 and 395 in 1996, 65 (19.5%) and 81 (20.5%) were MRSA carriers, respectively (P=.80). In 1993, 6 (9%) of 70 patients without MRSA acquired MRSA wound infections; the corresponding numbers were 6 (2.2%) of 269 in 1994 and 3 (0.9%) of 314 in 1996. Despite that the number of MRSA carriers remained stable at admission to the wound care center, the rate of MRSA infections in wounds per 100 noncarriers decreased significantly between the preintervention period and subsequent years: 1994 (P=.02) and 1996 (P=.002). CONCLUSIONS: Although our results are limited by the use of historical controls, they showed that simple infection control measures, such as the use of soap and water and barrier precautions associated with staff education, seemed to significantly reduce MRSA infection rates in patients with chronic skin breaks.     

Spread of old and new clones of epidemic methicillin-resistant Staphylococcus aureus in Poland

Objective: To study the relatedness among methicillin-resistant Staphylococcus aureus (MRSA) isolates originating from two regions of Poland using different epidemiologic typing methods.
Methods: Forty-five MRSA isolates (19 from Warsaw and 26 from the Grajewo region) were collected between 1995 and 1996. For phenotypic epidemiologic analysis, antimicrobial susceptibility testing (AST) with a panel of 19 antibiotics was performed. For genotypic epidemiologic analysis, pulsed-field gel electrophoresis (PFGE) of Smal-digested chromosomal DNA, restriction endonuclease analysis of plasmid (REAP) DNA digested by Hin dIII, random amplification of polymorphic DNA (RAPD) and binary typing (BT) of genomic DNA by hybridization with five different RAPD-generated strain-specific DNA probes, were used.
Results: Six clusters of clonally related strains were found among the MRSA isolates analyzed. Three of these, identified in both regions, were related to previously described Polish epidemic clones, designated HeEMRSA-Pol1 (heterogeneously methicillin resistant—18 isolates) and HoEMRSA-Pol1 (homogeneously resistant—two clones, six isolates each). The remaining three clones, identified in the Grajewo region only, are previously undescribed. One of these, represented by 11 isolates, appears to be new epidemic heterogeneous MRSA clone (HeEMRSA-Pol2). Results of PFGE and BT in general showed good correlation, and, in some cases, RAPD using AP1 and AP7 primers could discriminate between isolates belonging to single PFGE or BT types. Broad AST and REAP can provide useful additional information concerning relatedness.
Conclusion: Evidence for the spread of previously recognized epidemic MRSA clones in Poland and the presence of a new epidemic heterogeneously resistant clone of MRSA in hospitals outside Warsaw is documented.     

Polymorphisms of the XRCC3 C722T and the RAD51 G135C genes and the risk of head and neck cancer in a Polish population

Genetic variations in DNA repair genes may affect an individual's susceptibility to head and neck cancer. We performed a case–control study to test the association between head and neck cancer risk and two polymorphisms: the C722 T of the XRCC3 and the G135C of the RAD51 —genes of DNA double strand break (DSB) repair by homologous recombination (HRR). Genotypes were determined by PCR-restriction fragment lenght polymorphism (PCR-RFLP). DNA was isolated from peripheral blood lymphocytes of a group of 288 patients consisting of 97 subjects with precancerous hyperplastic laryngeal lesions (PHLL) and 191 subjects with head and neck squamous cell carcinoma (HNSCC) as well as 353 healthy control donors. We found an association between PHLL and the 722CT (OR 6.67; 95% CI 3.02–14.74) as well as 722 TT (OR 4.65; 95% CI 2.30–9.43) variants of the XRCC3 gene. Similar relation was observed between these genotypes and HNSCC (OR 2.59; 95% CI 1.61–4.16 and OR 5.54; 95% CI 3.22–9.52, respectively). Moreover, we also observed an association between PHLL (OR 6.04; 95% CI 3.69–9.90) and HNSCC (OR 6.04; 95% CI 3.69–9.90) and the135GC variant of the RAD51 gene. The gene–gene interaction between XRCC3 and RAD51 polymorphic variants may contribute to higher prevalence of PHLL. The increased risk of this disease was observed in case of the combination of the 722CT/135GC (OR 3.81; 95% CI 1.55–9.75) as well as the 722 TT/135GC genotypes (OR 5.33; 95% CI 1.96–14.47). The presence of the same genes combinations plays a part in higher probability of HNSCC occurrence (OR 2.42; 95% CI 1.22–4.79 for 722CT/135GC and OR 3.63; 95% CI 1.69–7.76 for 722 TT/135GC). We also found an association between these XRCC3 or RAD51 polymorphic variants and smoking status in PHLL (ORs 2.85–10.28 and 1.82–7.35, respectively) and HNSCC patients (ORs 2.94–13.93 and 1.36–3.94, respectively) as well as alcohol intake among PHLL (ORs 3.44–6.12 and 3.52–8.43, respectively) and HNSCC subjects (ORs 2.71–7.01 and 2.33–4.62, respectively). In conclusion our data showed that the C722 T and the G135C polymorphisms of the XRCC3 and the RAD51 genes might be associated with HNSCC. Finally we suggested that these polymorphisms might be used as predictive factor of precancerous lesion for head and neck cancer in a Polish population.     

Modulation of the Effect of Endothelin-3 on Blood Pressure by Atrial Natriuretic Peptide in Conscious Spontaneously Hypertensive (SHR) and Normotensive (WKY) Rats

Endothelin (ET) exerts direct vasoconstrictory effects and stimulates release of vasoactive substances. It has been demonstrated that ET stimulates the release of atrial natriuretic peptide (ANP) both under in vitro and in vivo conditions. The present study aimed at elucidating whether the cardiovascular effects of endothelin-3 (ET-3) in normotensive (WKY) and spontaneously hypertensive (SHR) rats are modulated by ANP. The experiments were performed on 17 conscious WKY and 17 SHR rats. The effects of i.v. administration of 1 μg of ET-3 on blood pressure (BP) and heart rate (HR) were investigated under control conditions and during ANP infusion (0.3 μg/kg/min). In both strains ET-3 elicited a transient significant hypotensive effect followed by an increase in BP. BP fall was significantly greater and pressor effect significantly smaller in SHR than in WKY. In WKY, but not in SHR rats, both hypotensive and pressor phases were significantly attenuated during ANP administration. The results are evidence of differential involvement of endogenous blood pressure regulating factors in the cardiovascular effects of ET-3 in WKY and SHR rats during ANP infusion.     

Primary amenorrhea in a young Polish woman with complete androgen insensitivity syndrome and Sertoli-Leydig cell tumor: identification of a new androgen receptor gene mutation and evidence of aromatase hyperactivity and apoptosis dysregulation within the tumor.

Primary amenorrhea in 46,XY females can be due to complete androgen insensitivity syndrome (CAIS), pure gonadal dysgenesis, 17-hydroxysteroid dehydrogenase deficiency, or mixed gonadal dysgenesis. The present paper describes a new de novo non-sense mutation in exon 1 (K141Z) of the androgen receptor gene (AR) and the expression in CAIS testis of aromatase, estrogen receptors, as well as proliferation- and apoptosis-associated proteins. CAIS is a rare disease characterized by absent virilization in 46,XY individuals and the development of a female phenotype despite normal or even elevated androgen levels. CAIS is usually caused by a mutation in AR, which leads to organ resistance to androgens. Testicular tumors such as Sertoli-Leydig cell tumor often develop in patients with CAIS. The immunohistochemical findings in the testes of our CAIS patient suggest that the high expression of aromatase and other molecular changes in the testis may be responsible for pubertal breast development and the increased risk of testicular tumor.