Transplantation treatment of spinal cord injury patients.

The minimally manipulated cells from fetal nervous and hemopoietic tissues (gestational age 16-22 weeks) were subarachnoidally implanted into 15 patients (18-52 years old) with severe consequences of traumatic spinal cord injury (SCI) at cervical or thoracic spine level. The times after SCI were from 1 month to 6 years. Each patient underwent from one to four cell transplantations (CT) with various time intervals. In 11 of 15 cases, CT was combined with an operative partial disruption of a connective tissue cyst and with implantation into a spinal cord lesion of a spinal cord fragment together with olfactory ensheathing cells. Before CT the patients showed complete motor and sensory function disorder consistent with a grade A of SCI according to Frankel classification. With CT treatment, six patients improved their neurological status from A to C grade of SCI, exhibiting incomplete restoration of both motor and sensory function. The status of other five CT-treated patients became consistent with SCI grade B and was characterized by appearance of contracting activity in some muscles and incomplete restoration of sensitivity. The remaining four patients did not exhibit any clinical improvements. No serious complications of CT were noted. The results suggest a clinical relevance of the CT-based approach to treating severe consequences of SCI.     

Antimicrobial resistance of nosocomial strains of Staphylococcus aureus in Russia: results of a prospective study

A total of 879 Staphylococcus aureus clinical isolates from 17 medical institutions in different regions of Russia were tested. Susceptibility to 18 antimicrobials was determined by agar dilution in accordance with the NCCLS recommendations. The most potent antimicrobials were glycopeptides, linezolid, and fusidic acid, to which no resistance was found. Other antimicrobials with low frequency of non-susceptibility were mupirocin (0.3%), trimethoprim/sulfamethoxazole (0.8%), quinupristin/dalfopristin (1.8%) and rifampicin (7.0%). Fluoroquinolones displayed moderate activity (5.8% of non-susceptible strains to moxifloxacin, 9.1% to levofloxacin, 13.1% to ciprofloxacin). High rates of non-susceptibility were found to clindamycin (27.1%), gentamicin (30.7%), tetracycline (37.1%), erythromycin (39.6%) and chloramphenicol (43.1%). The prevalence of oxacillin-resistant S. aureus (ORSA) was 33.5% and varied from 0% to 89.5% in different hospitals. ORSA were isolated most frequently in the burn units (77.5%), intensive care units (54.8%), trauma and orthopedics units (42.1%). This is the first multicenter study published of antimicrobial resistance of S. aureus in Russia which meets international standards.     

Non-mammalian “big” neurophysins — complete amino acid sequence of a two-domain MSEL-neurophysin from goose

Vasotocin-associated neurophysin (MSEL-neurophysin) has been purified from goose neurohypophysis through molecular sieving and high-pressure reverse-phase liquid chromatography (HPLC). The protein has a molecular mass (measured by SDS-polyacrylamide gel electrophoresis) of 17kDa in contrast to 10kDa found for the mammalian MSEL-neurophysins. Complete amino acid sequence (131 residues) has been determined mainly through tryptic or staphylococcal proteinase peptides derived from carboxyamido-methylated neurophysin, isolated by HPLC and microsequenced. N- and C-terminal sequences have been established by Edman degradation or action of carboxypeptidase Y, respectively, applied on the native protein. Goose MSEL-neurophysin is homologous to the two-domain “big” MSEL-neurophysin previously identified in the frog. It appears that in non-mammalian tetrapods, namely birds and amphibians, the proteolytic processing of the pro-vasotocin involves only one cleavage, releasing the hormone moiety and a “big” neurophysin with two domains homologous to mammalian MSEL-neurophysin and copeptin, respectively. Comparison of the avian protein with its mammalian and amphibian counterparts reveals that the first half of the polypeptide chain is evolutionarily much less variable than the second and that the goose protein resembles the frog protein much more than the mammalian one.     

Cell therapy of brain stroke

Cell suspension consisting of cells from immature nervous and hemopoietic tissues was subarachnoidally transplanted to 10 patients with brain stroke consequences. Clinical effect of different degree was attained in all patients. Six months after cell therapy functional activity significantly increased in contrast to clinically comparable control group. No serious complications of cell therapy were observed. Presumably, cell therapy is a more or less safe method of treatment, which can be effectively used in the treatment of brain stroke consequences.__________This revised version was published online in July 2005 with the addition of the issue title and article categoryTranslated from Kletochnye Tekhnologii v Biologii i Meditsine, Vol. 1, No. 1, pp. 25–28, January, 2005     

Results of surgical treatment of bleeding gastric tumors

The results of surgical treatment of 132 patients with gastric tumors complicated by bleeding are presented. In 58.4% of the patients, the radical intervention was performed, in uncomplicated course of a disease--in 73.2%. Lethality after the emergency operations was 38.1% and considerably exceeded that after the elective interventions (7.8%). This dictates the necessity to improve the conservative hemostatic measures.     

Expression and costimulatory effects of the TNF receptor superfamily members CD134 (OX40) and CD137 (4-1BB), and their role in the generation of anti-tumor immune responses

This study addresses the relative importance of CD134 (OX40) and CD137 (4-1BB) in the costimulation of CD4+ and CD8+ T cells under comparable conditions of antigenic stimulation. We demonstrate that CD134 is capable of directly costimulating CD8+ T cells. However, costimulation of CD8+ T cells by CD134 is less potent than that triggered by CD137. The higher costimulatory activity of CD137, when compared with CD134, correlates well with its faster expression kinetics and higher levels on CD8+ T cells. Furthermore, induction of CD137 expression on CD8+ T cells is highly sensitive to low levels of TCR stimulation, which is in contrast with CD134. Conversely, CD134 is more effective than CD137 in costimulating CD4+ T cells. This, however, could not be attributed to differential expression. We also demonstrate that the transient nature of CD134 and CD137 expression on activated CD4+ T cells is the resultof proteolytic shedding. Consistent with the greater ability of CD137 to costimulate CD8+ T cells, stimulation of CD137 in vivo is considerably more effective than CD134 in augmenting anti-tumor immune responses. Therefore, agents that stimulate signaling via CD137 are likely to be more useful in clinical conditions where highly effective CD8+ CTL responses are required.     

Retrograde (Ventriculoatrial) Conduction

Ľinterêt dans la conduction VA rétrograde a été renouvelé depuis la découverte de tachycardies induites par les stimulateurs cardiaques de type physiologique qui incorporent le recueil des potentiels auriculaires. Seule ľétude de la conduction VA rétrograde associée à une parfaite connaissance de son comportement électrophysiologique dans dif-ferents cos, permettra de dépister les malades susceptibles de faire une tachycardie induite par le stimulateur.
Interest in retrograde VA conduction has been renewed with the advent of tachycardias induced by physiologic pacemakers with atrial sensing capabilities. Accurate representation of ventriculoatrial conduction requires detailed electrophysiologic analysis during sinus rhythm, during tachycardias whether or not associated with accessory pathways, and during ventricular pacing studies. Retrograde conduction should be assessed in patieifts considered for implantation of atrial sensing and tracking pacemakers (VAT, VDD, DDD), until technologic advances overcome the problems of endless loop tachycardias.     

Inspecting Insulin Products Using Water Proton NMR. I. Noninvasive vs Invasive Inspection

Background:There is a clear need to transition from batch-level to vial/syringe/pen-level quality control of biologic drugs, such as insulin. This could be achieved only by noninvasive and quantitative inspection technologies that maintain the integrity of the drug product.Methods:Four insulin products for patient self-injection presented as prefilled pens have been noninvasively and quantitatively inspected using the water proton NMR technology. The inspection output is the water proton relaxation rate R₂(¹H₂O), a continuous numerical variable rather than binary pass/fail.Results:Ten pens of each product were inspected. R₂(¹H₂O) displays insignificant variation among the 10 pens of each product, suggesting good insulin content uniformity in the inspected pens. It is also shown that transferring the insulin solution out of and then back into the insulin pen caused significant change in R₂(¹H₂O), presumably due to exposure to O₂ in air.Conclusions:Water proton NMR can noninvasively and quantitatively inspect insulin pens. wNMR can confirm product content uniformity, but not absolute content. Its sensitivity to sample transferring provides a way to detect drug product tampering. This opens the possibility of inspecting every pen/vial/syringe by manufacturers and end-users.     

Sudden Death as a Presenting Symptom of Hypertrophic Cardiomyopathy: Treatment with an Implantable Cardioverter Defibrillator

Aborted sudden death as the presenting manifestation of hypertrophic Cardiomyopathy in a 14-year-old child is reported. Documented ventricular fibrillation was the cause of cardiac arrest. No ventricular arrhythmia was induced during programmed electrical stimulation. An implantable cardioverter-defibrillator was indicated. As the patient had a family history of myocardial disease, he had undergone a cardiovascular evaluation 4 years before the major event, and was found normal. It is suggested that normal physical examination, ECG, echocardiogram should not rule out the diagnosis of hypertrophic Cardiomyopathy when a family history is present. Left ventricular hypertrophy may develop during childhood in patients with hypertrophic Cardiomyopathy.