Immunoprophylaxis and immunotherapy of gram-negative sepsis and shock with antibodies to core glycolipids and lipid a of bacterial lipopolysaccharides

Conclusions The results obtained by numerous investigators reveal the ability of antibodies to cross-reactive LPS antigens to protect against infections caused by various gram-negative pathogens and their endotoxins. Based upon experimental and clinical experience, one could postulate that these antibodies are a promising approach for the prophylaxis and therapy of sepsis. The recognition of high-risk patients would allow early start of combined therapy with appropriate immune preparations and antibiotics, which along with life-supporting measures (corticosteroids, electrolyte and nutrition infusions, etc.), would be a useful tool in the treatment of gram-negative sepsis and endotoxin shock.     

Retrosternal (intrathoracic) goitre--diagnosis and surgical treatment

For a period of 12 years (1987-1998) 2033 patients underwent surgical treatment of the thyroids in the surgical clinics of the Higher Medical Institute in Plovdiv. Retrosternal or intrathoracic goitre was found in 29 patients (p +/- Sp = 1.43 +/- 0.26%). Of these, seven were males and 22 females all aged 32 to 76 years. Twenty two of the patients were euthyroid and seven hyperthyroid (75.9 +/- 7.9% and 24.1 +/- 7.8%, respectively). Compression of adjacent organs was detected in 19 of the patients (65.5 +/- 8.8%) (P < 0.05). X-ray, ultrasonography, scintigraphy (gamma-chamber), computed tomography, and in cases of voice disorders, direct laryngoscopy were used in making the diagnosis. All patients underwent surgical treatment. Cervical collar incision was suitable in 27 patients and in one patient longitudinal sternotomy was used and in other, who had deep posterior mediastinal goitre, Hart's method of combined thoracotomy and cervicotomy was required. The weight of the resected glands varied from 50 to 1500 g. The results obtained are discussed in terms of the incidence, type, and site of the retrosternal (intrathoracic) goitre, capabilities of the contemporary methods of diagnostics, surgical necessities, surgical approach and compared with literature data.     

Evidence of the immunomodulatory role of dual PI3K/mTOR inhibitors in transplantation: an experimental study in mice

The PI3K/mTOR signaling cascade is fundamental in T‐cell activation and fate decisions. We showed the distinct regulation of PI3K/mTOR in regulatory and effector T‐cells and proposed the potential therapeutic benefit of targeting this pathway to control the balance between effector and regulatory T‐cell activities. Substantial adverse effects in long‐term clinical usage of rapamycin suggest the use of alternative treatments in restraining effector T‐cell function in transplant patients. We hypothesize that dual PI3K/mTOR inhibitors may represent an immunosuppressant alternative. Here we show that dual PI3K/mTOR PI‐103 and PKI‐587 inhibitors interfered IL‐2‐dependent responses in T‐cells. However, in contrast to the inhibitory effects in non‐Treg T‐cell proliferation and effector functions, dual inhibitors increased the differentiation, preferential expansion, and suppressor activity of iTregs. Rapamycin, PI‐103, and PKI‐587 targeted different signaling events and induced different metabolic patterns in primary T‐cells. Similar to rapamycin, in vivo administration of PI‐103 and PKI‐587 controlled effectively the immunological response against allogeneic skin graft. These results characterize specific regulatory mechanisms of dual PI3K/mTOR inhibitors in T‐cells and support their potential as a novel therapeutic option in transplantation.     

Perception time and spatial frequency.

The time of detection of a feature of square-wave gratings (orientation or a small difference in spatial frequency between two adjacent gratings) was studied as a function of stimulus spatial frequency. The relative perception time was measured by the reaction time method or by the method of masking. Perception time was found to increase at grating frequencies above 4–6 c/deg, the effect being partly due to the lower contrast sensitivity at these frequencies. However, a delay was also found when increased contrast at high frequencies compensated for the lower sensitivity. The result suggests the existence of a mechanism for processing a high spatial frequency stimulus which demands more time than that for processing a low spatial frequency.     

Intraoperative identification of recurrent laryngeal nerves in thyroid surgery by electrical stimulation

INTRODUCTION: Iatrogenic injury of the recurrent laryngeal nerve and its prevention is one of the controversial issues in thyroid surgery. The incidence of this operative complication ranges from 0.4% to 3.9%. PATIENTS AND METHODS: The authors analysed the results of the identification of 114 nerves in 60 patients who underwent thyroid surgery between July 9, 1999 and December 19, 2000 in the 3rd Surgical Clinic at the Department of Clinical Surgery and in the Department of Ear Nose and Throat Diseases of the Medical University in Plovdiv, Bulgaria. Nerve integrity monitor Neurosign 100 and specially designed EMG electrodes (Magstim Company Ltd., Wales, UK) were used. The patients were examined pre- and postoperatively for vocal cord paralysis by otolarygologist. RESULTS: In all patients electrical stimulation of the recurrent laryngeal nerve was successfully used for identification of the nerve and evaluation of its integrity during and at the end of the operation. No postoperative recurrent laryngeal nerve deficit was detected clinically. CONCLUSIONS: The results indicate that the identification of the recurrent laryngeal nerve by electromyography is a safe, effective and simple method for electrophysiologic monitoring during thyroid surgery. This method allows assessment of the neural integrity at the end of the procedure.     

Phenotypic and genotypic characteristics of non-invasive S. pneumoniae isolates recovered from PCV10-vaccinated children in Bulgaria

PurposeThe non-invasive pneumococcal disease (NIPD) is a common infection during childhood. We aimed to define the clonal spread of pediatric non-invasive isolates recovered during the PCV10-period in Bulgaria concerning the serotype and antimicrobial susceptibility.Materials and methodsSerogrouping/serotyping were performed using latex agglutination and capsular swelling reaction. Serogroup 6 strains were subjected to serotype-specific PCR's. The antibiotic susceptibilities were assessed by broth microdilution. MLST was performed to define the clonal composition.ResultsWe analyzed 154 pediatrics non-invasive S. pneumoniae isolates. The PCV10-vaccinated children were 94.1%. We disclosed 88% non-vaccine serotypes (NVTs) and 12% PCV10 - serotypes. All common serotypes among PCV10-vaccinated children (n ?= ?145) were non-vaccine types (NVTs): 19A (13.8%), 6C (11.7%), 3 (9.6%), 15A (8.3%) and 23A (5.5%). Antimicrobial non-susceptibility showed highest levels in erythromycin (50.0%), oral penicillin (49.4%), clindamycin (45.4%), trimethoprim-sulfamethoxazole (43.5%), tetracycline (42.2%), and ceftriaxone (14.3%). The multidrug-resistant strains (MDR) were 51.3%. MDR-serotypes were 6C (20.2%), 19A (17.7%), 15A (11.4%), 19F (10.1%), and 23A (8.9%). MLST presented 17 clonal complexes (CCs) with prevalence of CC320, CC386, CC505, CC8029 and CC2613 clustered 83% MDR isolates.ConclusionsAll emergent pediatric non-invasive serotypes in our geographic area during the studied PCV10-period were NVTs (19A, 6C, 3, 15A, and 23A). The fifth widespread CCs: CC320, CC386, CC505, CC8029 and CC2613 clustered 83% MDR isolates. Future surveillance of vaccine-induced changes in the clonality and the antimicrobial resistance of the pneumococcal population is needed.