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The article provides the results of minimally invasive direct revasculization of myocardium at the period from 2012 to 2014. Given method was used in 49 interventions. There weren't any lethal cases or myocardial infarctions. A mean hospital stay consisted of 8,6±2,7. Computer thomographic coronary bypass angiography was carried out after operation in terms of 6-48 months. The occlusion of mammary coronary shunt was revealed in 3 patients with minimally invasive revasculization of the myocardium in terms up to 48 months. There were noted a decrease' of hospital stay, bleeding during surgery and in early postoperative period, duration of artificial pulmonary ventilation, length of stay in intensive care unit for this group of patients.

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Increasingly, there are patients with concomitant coronary artery disease and aortic valve, especially in elderly patients, who often have severe comorbidities and high surgical risk, which is undoubtedly a certain effect on the choice of method and tactics of treatment. Today, there are several approaches to the treatment of patients in this category, and all of them have certain advantages and disadvantages.

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A novel triple neurokinin receptor antagonist (TNRA) could have pharmaceutical efficacy for asthma and/or chronic obstructive pulmonary disease. TNRA is potentially developed as inhalation medicine. The aim of this investigation was to evaluate the applicability of dry powder inhaler (DPI) formulation for TNRA. DPI formulation containing lactose was used for this feasibility study. Mechanofusion process for surface modification was applied on lactose particles to prepare four different DPI formulations. The mixture of TNRA and lactose was administered to rats intratracheally using an insufflator. The deposition pattern and blood concentration profile of TNRA were evaluated. Although there was no significant difference in deposition on deep lungs between the four formulations, DPI formulations containing mechanofusion-processed lactose showed longer T(max) and t(1/2) and higher AUC(0-infinity) and MRT compared to that containing intact lactose. On the other hand, the contact angle measurement showed that the mechanofusion process decreased the polar part of the surface energy of the lactose. Therefore, the prolongation of the wetting of the formulated powder mixture seemed to delay the dissolution of TNRA deposited in respiratory tract. It was concluded that DPI formulation containing mechanofusion-processed lactose could be suitable for inhalation of TNRA.

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Polyproline has recently been used as a spacer between donor and acceptor chromophores to help establish the accuracy of distances determined from single-molecule Förster resonance energy transfer (FRET) measurements. This work showed that the FRET efficiency in water is higher than expected for a rigid spacer and was attributed to the flexibility of the polypeptide. Here, we investigate this issue further, using a combination of single-molecule fluorescence intensity and lifetime measurements, NMR, theory, and molecular dynamics simulations of polyproline-20 that include the dyes and their linkers to the polypeptide. NMR shows that in water approximately 30% of the molecules contain internal cis prolines, whereas none are detectable in trifluoroethanol. Simulations suggest that the all-trans form of polyproline is relatively stiff, with persistence lengths of 9-13 nm using different established force fields, and that the kinks arising from internal cis prolines are primarily responsible for the higher mean FRET efficiency in water. We show that the observed efficiency histograms and distributions of donor fluorescence lifetimes are explained by the presence of multiple species with efficiencies consistent with the simulations and populations determined by NMR. In calculating FRET efficiencies from the simulation, we find that the fluctuations of the chromophores, attached to long flexible linkers, also play an important role. A similar simulation approach suggests that the flexibility of the chromophore linkers is largely responsible for the previously unexplained high value of R(0) required to fit the data in the classic study of Stryer and Haugland.

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The majority of patients with a unilateral cleft nasal deformity still benefit from additional nasal surgery in their teenage years, despite having undergone a primary nasal repair. However, the secondary nasal deformity of these patients stands in sharp contrast to those of children who have not benefited from primary repair. The authors' algorithm for the definitive correction of these secondary deformities considers the differences in these two patient groups and defines their indications for rib cartilage grafts and their method of using septal and ear cartilage in the repair. Balancing the muscle forces on the septum and alar cartilage is emphasized in both the primary and secondary repair. Both cartilage malposition and hypoplasia of the lower lateral cartilage complex have been identified as factors contributing to the deformity.

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To obtain quantitative information on the size and dynamics of unfolded proteins we combined single-molecule lifetime and intensity FRET measurements with molecular simulations. We compared the unfolded states of the 64-residue, alpha/beta protein L and the 66-residue, all-beta cold-shock protein CspTm. The average radius of gyration (Rg) calculated from FRET data on freely diffusing molecules was identical for the two unfolded proteins at guanidinium chloride concentrations >3 M, and the FRET-derived Rg of protein L agreed well with the Rg previously measured by equilibrium small-angle x-ray scattering. As the denaturant concentration was lowered, the mean FRET efficiency of the unfolded subpopulation increased, signaling collapse of the polypeptide chain, with protein L being slightly more compact than CspTm. A decrease in Rg with decreasing denaturant was also observed in all-atom molecular dynamics calculations in explicit water/urea solvent, and Langevin simulations of a simplified representation of the polypeptide suggest that collapse can result from either increased interresidue attraction or decreased excluded volume. In contrast to both the FRET and simulation results, previous time-resolved small-angle x-ray scattering experiments showed no collapse for protein L. Analysis of the donor fluorescence decay of the unfolded subpopulation of both proteins gives information about the end-to-end chain distribution and suggests that chain dynamics is slow compared with the donor life-time of approximately 2 ns, whereas the bin-size independence of the small excess width above the shot noise for the FRET efficiency distributions may result from incomplete conformational averaging on even the 1-ms time scale.

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Epignathus is an extremely rare, benign, congenital teratoma that arises from within the oral cavity and may be attached to the mandible, palate, or base of the skull. Because of its location, it can cause airway and feeding problems, as well as secondary defects due to the presence of an intraoral tumor. This tumor usually causes death in neonates, due to airway obstruction. Surgical removal is usually impossible, especially in large tumors (Stone, 1951; Bennett, 1970). A patient with a neonatally diagnosed nonobstructive palatopharyngeal epignathus is described. It was associated with a shortened palate, cleft uvula, and velopharyngeal insufficiency, and was successfully excised surgically.

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This report documents the successful elimination of disfiguring sebaceous adenomas from the face of a 21-year-old male patient with mechanical dermabrasion.

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Ultrafast protein dynamics of the CO adduct of a myoglobin mutant with the polar distal histidine replaced by a nonpolar valine (H64V) have been investigated by spectrally resolved infrared stimulated vibrational echo experiments and molecular dynamics (MD) simulations. In aqueous solution at room temperature, the vibrational dephasing rate of CO in the mutant is reduced by approximately 50% relative to the native protein. This finding confirms that the dephasing of the CO vibration in the native protein is sensitive to the interaction between the ligand and the distal histidine. The stimulated vibrational echo observable is calculated from MD simulations of H64V within a model in which vibrational dephasing is driven by electrostatic forces. In agreement with experiment, calculated vibrational echoes show slower dephasing for the mutant than for the native protein. However, vibrational echoes calculated for H64V do not show the quantitative agreement with measurements demonstrated previously for the native protein.

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Poor wound healing remains a critical problem in our daily practice of surgery, exerting a heavy toll on our patients as well as on the health care system. In susceptible individuals, scars can become raised, reddish, and rigid, may cause itching and pain, and might even lead to serious cosmetic and functional problems. Hypertrophic scars do not occur spontaneously in animals, which explains the lack of experimental models for the study of pathologic scar modulation. We present the results of three clinical comparative prospective studies that we have conducted. In the first study, secondary healing and cosmetic appearance following healing of partial thickness skin graft donor sites under dry (semi-open Sofra-Tulle dressing) and moist (moist exposed burn ointment, MEBO) was assessed. In the second study, healing of the donor sites was evaluated following treatment with Tegaderm or MEBO, two different types of moisture-retentive dressings. In the third study, 3 comparable groups of primarily healed wounds were evaluated. One group was treated by topical antibiotic ointment, the second group was treated by Moist Exposed Burn Ointment (MEBO), and the third group did not receive any topical treatment. In the second study, secondary healing of partial thickness skin graft donor sites was evaluated following treatment with Tegaderm or MEBO, two different types of moisture-retentive dressings. In the second and third studies, healed wounds were evaluated with the quantitative scale for scar assessment described by Beausang et al. Statistical analysis revealed that for both types of wound healing, scar quality was significantly superior in those wounds treated with MEBO.

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Spectrally resolved infrared stimulated vibrational echo data were obtained for sperm whale carbonmonoxymyoglobin (MbCO) at 300 K. The measured dephasing dynamics of the CO ligand are in agreement with dephasing dynamics calculated with molecular dynamics (MD) simulations for MbCO with the residue histidine-64 (His64) having its imidazole epsilon nitrogen protonated (N(epsilon)-H). The two conformational substate structures B(epsilon) and R(epsilon) observed in the MD simulations are assigned to the spectroscopic A(1) and A(3) conformational substates of MbCO, respectively, based on the agreement between the experimentally measured and calculated dephasing dynamics for these substates. In the A(1) substate, the N(epsilon)-H proton and N(delta) of His64 are approximately equidistant from the CO ligand, while in the A(3) substate, the N(epsilon)-H of His64 is oriented toward the CO, and the N(delta) is on the surface of the protein. The MD simulations show that dynamics of His64 represent the major source of vibrational dephasing of the CO ligand in the A(3) state on both femtosecond and picosecond time scales. Dephasing in the A(1) state is controlled by His64 on femtosecond time scales, and by the rest of the protein and the water solvent on longer time scales.

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Toxic epidermal necrolysis (TEN) is a rare condition that was described by Lyell in 1956. It is a severe, acute, adverse, primarily drug-induced, potentially fatal, cutaneous reaction that is characterized by large areas of skin desquamation and sloughing, similar in many aspects to second-degree burns. The treatment of cutaneous drug reactions rests essentially on immediate diagnosis and recognition of the disease process, accurate history, thorough physical examination, prompt discontinuation of the offending drug, and supportive care. TEN patients are best managed in specialized burn units. Nevertheless, the management remains very much individualized, based on the clinical setting. Topical wound care remains an essential factor in the treatment of burn-like syndromes and is a main determining parameter for morbidity and mortality. As the value of moist environment in wound healing is being fully appreciated, we report on the use of a newly introduced ointment, the Moist Exposed Burn Ointment (Julphar; Gulf Pharmaceutical industries, Ras El-Khaymah, United Arab of Emirutes), a moisture-retentive ointment, in the successful management of a case of TEN.

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BACKGROUND: There is growing evidence of improved healing of full- and partial-thickness cutaneous wounds in wet and moist environments. Retention of biologic fluids over the wound prevents desiccation of denuded dermis or deeper tissues and allows faster and unimpeded migration of keratinocytes over the wound surface. It allows also the naturally occurring cytokines and growth factors to exert their beneficial effect on wound contracture and re-epithelialization. Despite all of these documented benefits, applying the moist healing principles to large surface areas, in particular to large burns, is hindered by the major technical handicap of creating and maintaining a sealed moist environment over these areas. METHODS: From January to September 2001, healing of partial-thickness skin graft donor sites was studied in a prospective comparative study of two types of moist dressings, Tegaderm (3M Health Care, St. Paul, MN), a semipermeable membrane occlusive dressing, and moist exposed burn ointment (MEBO) (Julphar; Gulf Pharmaceutical Industries, United Arab of Emirates), an ointment that can provide a moist environment without the need of an overlying occlusive dressing. Healing was assessed both clinically and with serial measurements of transepidermal water loss (TEWL) and moisture. Following healing, scar quality was evaluated by two members of the team separately using a visual analog scale. Results were statistically analyzed. RESULTS: Faster healing was observed clinically with MEBO application. Physiologic healing as determined by TEWL measurements occurred at an extremely significant earlier stage for MEBO, and this was associated with better scar quality, demonstrating a positive relationship between function and cosmetic appearance. Moreover, the ointment is definitely easier to apply than the occlusive self-adhesive membrane, which requires some degree of dexterity and expertise. CONCLUSION: MEBO application is an effective and valid alternative to conventional occlusive dressings. Moreover, the observed improved anatomic and physiologic healing indicates that MEBO may have a positive effect on healing more that the mere fact of passive moisture retention.

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The history of wound care and management closely parallels that of military surgery which has laid down the principles and dictated the practices of wound cleansing, debridement and coverage. From a treatment standpoint, there are essentially two types of wounds: those characterized by loss of tissue and those in which no tissue has been lost. In the event of tissue loss it is critical to determine whether vital structures such as bone, tendons, nerves and vessels have been exposed. It is also important to determine the amount of soft tissue contusion and contamination. In any case primary wound healing by early closure either primarily or with the help of grafts or flaps is preferred to secondary healing and wound contraction with subsequent contractures which interfere with range of motion and function. Whether the wound is acute or chronic, essential principles of wound care must be observed in order to avoid wound sepsis and achieve rapid and optimal wound healing. - Tissues must be handled gently. - Caustic solutions capable of sterilizing the skin should never be applied to the wound. It is desirable never to put anything in the wound that cannot be tolerated comfortably in the conjunctival sac. - All devitalized tissues must be debrided either hydrodynamically, chemically, mechanically or surgically. - All dead space must be obliterated. - Exposed vital structures must be covered by well vascularized tissues. An essential part of any wound management protocol is wound dressing. It cannot be too strongly emphasized that a wound dressing may have a profound influence on healing particularly of secondary type healing, a critical feature being the extent to which such dressing restricts the evaporation of water from the wound surface. A review of available dressing materials is reported with emphasis on the newly developed concept of moist environment for optimal healing. a practical guide for dressing selection is also proposed.

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Visible scarring remains a considerable concern for patients seeking augmentation mammaplasty. We describe an intra-areolar infra-nipple incision that provides a good surgical access in most cases and allows inflatable as well as prefilled implant insertion with limited subcutaneous tunneling over the inferior glandular quadrants. The resultant scar is minimal and can be easily camouflaged by the pigmented and contractile areolar skin.

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Two-dimensional (2D) infrared vibrational echoes were performed on horse heart carbonmonoxymyoglobin (MbCO) in water over a range of temperatures. The A(1) and A(3) conformational substates of MbCO are found to have different dephasing rates with different temperature dependences. A frequency-frequency correlation function derived from molecular dynamics simulations on MbCO at 298 K is used to calculate the vibrational echo decay. The calculated decay shows substantial agreement with the experimentally measured decays. The 2D vibrational echo probes protein dynamics and provides an observable that can be used to test structural assignments for the MbCO conformational substates.

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Following traumatic or surgical injury to the skin, wounds do not heal by tissue regeneration but rather by scar formation. Though healing is definitely a welcomed event, the resultant scar, very often, is not aesthetically pleasing, and not infrequently, may be pathologic causing serious deformities and contractures. Management of problematic scars continues to be a frustrating endeavor with less than optimal results. Prophylactic methods of wound management to minimize serious scarring are being developed. In a previously published study, we have demonstrated improved healing of split thickness skin graft donor sites following treatment with Moist Exposed Burn Ointment (MEBO, Julphar Gulf Pharmaceutical Industries, Ras Al-Khaimah, UAE). At present, we are reporting the results of a comparative clinical prospective study evaluating scar quality following primary healing of elective surgical and traumatic facial wounds with prophylactic MEBO application, topical antibiotic ointment application, and no topical therapy at all. Scars were evaluated according to the Visual Analogue Scale for scar assessment. Statistical analysis of scar assessment scores demonstrated marked prevention of unfavorable scars with improved cosmetic results following MEBO prophylactic therapy.

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Orally administered dosage forms receive a destructive force in the gastrointestinal (GI) tract due to peristalsis. In this study, the destructive force was measured with a 'destructive force-dependent release system' (DDRS). DDRS is a press-coated tablet with an extremely brittle outer layer composed of highly hydrophobic Teflon(R) powder, which is molded with a weak compression force. Teflon(R) powder forms a porous but water-impermeable layer around the core tablet. A marker drug contained in the core tablet is released only when the tablet receives a force larger than its pre-determined crushing strength. A comparison of the physiological conditions in the GI tract of dogs with those of humans, including the destructive force against tablets in the stomach, helps us to understand their difference in bioavailability of oral dosage forms. With DDRS, it is possible to evaluate the destructive force of both human and dog stomach using the same method. Therefore, the destructive force data from human and dog can be directly compared. The destructive force in the dog stomach was evaluated to be 3.2 N, which was considerably stronger than that of humans.

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High-resolution mass spectrometry has been routinely used for structural confirmation and identification; however, it has mostly been applied to relatively pure samples. Exact mass measurement of minor components such as impurities, degradation products or metabolites in complex mixtures has been difficult without prior separation and isolation. Here we report the utilization of on-line liquid chromatography in combination with high-resolution mass spectrometry for the identification of impurities and base degradation products of Sch 27899, a member of the everninomicin class of antibiotics. Nine Sch 27899-related impurities and degradation products were detected by negative ion electrospray ionization using a magnetic sector mass spectrometer. Exact mass measurements were obtained at a resolution of 5000 using polyethylene glycol (PEG) sulfates as internal standards. Corresponding elemental compositions were determined within a 2 ppm error tolerance and structures were proposed for all components.

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