Natural killer cells in highly exposed hepatitis C-seronegative injecting drug users.

Injecting drug use remains the major risk factor for hepatitis C (HCV) transmission. A minority of long-term injecting drug users remain seronegative and aviraemic, despite prolonged exposure to HCV - termed highly exposed seronegative subjects. Natural killer (NK) cells have been implicated in this apparent protection. A longitudinal nested, three group case-control series of subjects was selected from a prospective cohort of seronegative injecting drug users who became incident cases (n = 11), remained seronegative (n = 11) or reported transient high-risk behaviour and remained uninfected (n = 11). The groups were matched by age, sex and initial risk behaviour characteristics. Stored peripheral blood mononuclear cells were assayed in multicolour flow cytometry to enumerate natural killer cell subpopulations and to assess functional activity using Toll-like receptor ligands before measurement of activation, cytokine production and natural cytotoxicity receptor expression. Principal components were derived to describe the detailed phenotypic characteristics of the major NK subpopulations (based on CD56 and CD16 co-expression), before logistic regression analysis to identify associations with exposed, seronegative individuals. The CD56(dim) CD16(+) (P = 0.05, OR 6.92) and CD56(dim) CD16(-) (P = 0.05, OR 6.07) principal components differed between exposed, seronegative individuals and pre-infection samples of the other two groups. These included CD56(dim) CD16(+) and CD56(dim) CD16(-) subsets with CD56(dim) CD16(+) IFN-γ and TNF-α on unstimulated cells, and CD56(dim) CD16(-) CD69(+) , CD107a(+) , IFN-γ and TNF-α following TLR stimulation. The cytotoxic CD56(dim) NK subset thus distinguished highly exposed, seronegative subjects, suggesting NK cytotoxicity may contribute to protection from HCV acquisition. Further investigation of the determinants of this association and prospective assessment of protection against HCV infection are warranted.

TAK1-regulated expression of BIRC3 predicts resistance to preoperative chemoradiotherapy in oesophageal adenocarcinoma patients.

BACKGROUND: About 20% of resectable oesophageal carcinoma is resistant to preoperative chemoradiotherapy. Here we hypothesised that the expression of the antiapoptotic gene Baculoviral inhibitor of apoptosis repeat containing (BIRC)3 induced by the transforming growth factor ß activated kinase 1 (TAK1) might be responsible for the resistance to the proapoptotic effect of chemoradiotherapy in oesophageal carcinoma. METHODS: TAK1 kinase activity was inhibited in FLO-1 and KYAE-1 oesophageal adenocarcinoma cells using (5Z)-7-oxozeaenol. The BIRC3 mRNA expression was measured by qRT-PCR in 65 pretreatment frozen biopsies from patients receiving preoperatively docetaxel, cisplatin, 5-fluorouracil, and concurrent radiotherapy. Receiver operator characteristic (ROC) analyses were performed to determine the performance of BIRC3 expression levels in distinguishing patients with sensitive or resistant carcinoma. RESULTS: In vitro, (5Z)-7-oxozeaenol significantly reduced BIRC3 expression in FLO-1 and KYAE-1 cells. Exposure to chemotherapeutic agents or radiotherapy plus (5Z)-7-oxozeaenol resulted in a strong synergistic antiapoptotic effect. In patients, median expression of BIRC3 was significantly (P<0.0001) higher in adenocarcinoma than in the more sensitive squamous cell carcinoma subtype. The BIRC3 expression significantly discriminated patients with sensitive or resistant adenocarcinoma (AUC-ROC=0.7773 and 0.8074 by size-based pathological response or Mandard's tumour regression grade classifications, respectively). CONCLUSIONS: The BIRC3 expression might be a valid biomarker for predicting patients with oesophageal adenocarcinoma that could most likely benefit from preoperative chemoradiotherapy.

[Studies of the architecture and functions of human skeletal muscles with the use ultrasonic scanning].

Architecture of m. triceps with the neutral ankle positioning (O degrees) was studied in vivo in essentially healthy male subjects (n = 8) and patients with motor disorders of varying etiology (4 males and 4 females). Ultrasonic scanning produced real-time images of m.gastrocnemius medialis, m. gastrocnemius lateralis and m.soleus both during relaxation (passive state) and isometric effort at 50% of maximal voluntary force (active state). Length, myofiber pinnation angle and muscle thickness were measured.

[Echocardiographic indices of cardiac function and systemic hemodynamics in patients with cardiac fibrillation paroxysms and their dynamics as affected by disopyramide phosphate]. / Ekhokardiograficheskie pokazateli funktsii serdtsa i sistemnaia gemodinamika u bol'nykh s paroksizmami mertsatel'noi aritmii i ikh dinamika pri vozdeistvii dizopiramida fosfata.

Clinical and echocardiographic studies in 25 chronic coronary patients with atrial fibrillation paroxysms following intravenous administration of 0.61-3.8 mg/kg Rhythmilen or its single oral dose (1.25-2.5 mg/kg), as well as during prolonged treatment with 400-600 mg Rhythmilen daily, demonstrated that their myocardial contractility parameters were reduced in the absence of an attack. Contractility parameters were not basically affected where the drug had no effect. Rhythmilen is an effective anti-arrhythmic agent: it arrests atrial fibrillation paroxysms in 73% and maintains the sinus rhythm when used preventively in 82% of cases.

[Cardiac arrhythmia and myocardial contraction in opium and ephedrone addiction]. / Narusheniia ritma serdtsa i sokratimost' miokarda pri opiinoi i éfedronovoi narkomanii.

Sixty-two patients with opium and ephedrone abuse were studied. They underwent 24-hour Holter monitoring, resting ECG and echocardiography, 18 of them having volumetric loading with polyglucine, 400.0 ml, i.v. Sinus tachycardia was detected in 67.4%, ventricular extrasystole in 4.7%, supraventricular extrasystole with infrequent paroxysms of supraventricular tachycardia in 11.6%. Despite the fact that signs of heart failure were absent and myocardial contractility was normal at rest, echocardiography along with volume loading allow one to reveal in patients some abnormal contractile alterations in the left ventricle. These include its increased volumes, decreased ejection fraction and circulatory shortening rate of myocardial fibers, which suggests that the compensatory potentials of the myocardium are reduced in drug abuse.

Styloid, velar, and pharyngeal muscles in cleft palate. Anatomical findings in elderly cadaver with unrepaired cleft palate.

Dessection of the musculature of the palate, pharynx, and styloid process was carried out in a cadaver aged 78 years with an unrepaired complete cleft palate. A new muscle named "the accessory stylohyoid" was found to be attached to the styloid process and the lesser cornu of the hyoid bone bilaterally. Anatomical changes in other muscles especially the stylopharyngeus and palatopharyngeus are described. The functions of these muscles are discussed on the basis of the anatomical findings and previous observations of other investigators.

Closure of nasal septal perforations.

Many surgical procedures have been described in the literature for the closure of nasal septal perforations. The results of most procedures have not been encouraging. In this paper, we present our experience of closure of nasal septal perforations using the mucoperichondrial/mucoperiosteal rotational flap on one side and the temporalis fascia graft on the other. In 13 of 14 cases, we were able to achieve complete closure of the perforations: one case failed because of continuous nose picking. The details of the procedure are described.

Office myringotomy and ventilation tube insertion using 10% Xylocaine aerosol.

Acquiring adequate, safe and painless local anesthesia of the tympanic membrane for the purpose of myringotomy with or without insertion of a middle ear ventilating tube has been a challenge for the otologist. A simple technique using 10% Xylocaine aerosol has been successfully employed in 74 adults to perform this procedure in the office. No complications or side-effects were encountered. This method not only avoids the pain associated with local infiltration of anesthetics, but has made iontophoresis unnecessary.

ENT abnormalities associated with Fraser syndrome: case report and literature review.

Fraser syndrome is an uncommon genetic disorder characterized by multiple congenital abnormalities. Newborns afflicted with this syndrome have abnormalities of the eyes, ears, nose, larynx, palate, extremities and urogenital system. A review of the literature shows a deficiency in the description of the ENT abnormalities. Most articles have appeared in the ophthalmologic literature with emphasis on the obvious ocular abnormalities. In this paper we will describe in detail, the ear, nose and throat abnormalities in a two-year-old child with Fraser syndrome.

[Determination of fructosamine in the early diagnosis of disorders of carbohydrate metabolism]. / Opredelenie fruktozamina v rannei diagnostike narushenii uglevodnogo obmena.

Blood serum fructosamine level were measured on an empty stomach in 97 normal subjects and subjects with various disorders of carbohydrate metabolism (the so-called "pre-diabetes" and changed glucose tolerance) in order to elucidate the significance of this factor as a marker of such disorders. Fructosamine concentrations were for the first time measured in children whose parents suffered from insulin-dependent or noninsulin-dependent diabetes mellitus. The content of fructosamine on an empty stomach was found to depend on the degree of carbohydrate metabolism disorders, increasing with the progress of these disorders. The findings permit a conclusion on the possibility of using fructosamine as a marker for the diagnosis of "pre-diabetes" in subjects with its levels of 2.5 to 2.99 mmol/l and of disordered glucose tolerance in those with its levels over 3 mmol/l and glucose level on an empty stomach no more than 6 mmol/l.

[Ethacizine in the treatment of psoriasis]. / Etatsizin v terapii psoriaza.

Ethacizine (2-carbethoxyamino-10 (3-diethylaminopropionyl) phenothiazine hydrochloride) has been administered in a daily dose of 150-200 mg for 8-10 weeks to 46 patients with diffuse psoriasis. The treatment has been effective in 84.8% of the patients. Late results, followed up over a year in 40 patients, are fine.

[Pharmacodynamics and pharmacokinetics of disopyramide phosphate]. / Farmakodinamika i farmakokinetika dizopiramida fosfata.

Based on pharmacodynamic and pharmacokinetic studies in 42 patients with paroxysmal and extrasystolic abnormalities of the rhythm it was established that disopyramide phosphate (ritmilen) is an effective antiarrhythmic agent for atrial fibrillation paroxysms. The drug exerts negative, chronotropic, dromotropic and inotropic effects, especially upon intravenous injections for removal of atrial fibrillatin paroxysms. Ritmilen moderately reduces the blood pressure. When used for removal of atrial fibrillation paroxysms ritmilen is effective in doses of 1.2-1.7 mg/kg intravenously and in doses of 2.5-3.8 mg/kg per os. In patients with chronic ventricular premature heart beat the single effective drug doses amount to 0.61-1.7 mg/kg. After oral use the ritmilen concentration in blood plasma is lower than after intravenous use in adequate doses. No relationship has been found between the drug antiarrhythmic effect and blood plasma concentration.