Spongiform encephalopathies (prionoses) in animals

Transfection of plasmid DNAs containing b-galactosidase gene (pQE-LacZ) or alkaline phosphatase (pCSEAP) into L929 cell line using was studied. The complexes between plasmid DNA and liposomes containing Ca ions and glycyrrhizic acid or &-tocopherol caused successful transfection of functional genes into L929 cells. The efficiency of transfection of plasmid DNAs into L929 cells using polynucleotide-metallo(II)-liposome complexes were 30-50% from the efficiency value of calcium phosphate coprecipitation transfection.     

Flight paramedic scope of practice: current level and breadth

This study's objective was to determine the current level and breadth of flight paramedic scope of practice. A six-item survey of lead flight paramedics in 158 air medical programs addressed five issues: 1) Certifications required above state certification; 2) Procedures included in scope of practice; 3) Medications flight paramedics are allowed to administer; 4) Requirements needed to expand scope of practice; and 5) Views on establishing a National Flight Paramedic Certification to alter their scope of practice. Eighty programs out of the 90 respondents (89%) stated that they utilize flight paramedics. Of these 80 programs that use flight paramedics, 76 programs (95%) require certification in ACLS, 65 (81%) in PALS, and 50 (63%) in BCLS. Paramedics are allowed to perform cricothyroidotomy in 68 programs (85%), pericardiocentesis in 24 (30%), and tube thoracostomy in 23 (29%). Medications approved for administration include streptokinase in 37 programs (46 %), r-TPA in 48 (60%), and succinylcholine in 50 (63%). In 61 programs (76%), the scope of practice is determined solely by the air medical director. Eighteen respondents (23%) believe that the development of a National Flight Paramedic Certification Program would alter their scope of practice. In conclusion, flight paramedic scope of practice varies enormously. Since most medical directors have the authority to alter flight paramedic scope of practice and few programs believe that a National Flight Paramedic Certification would alter their practice, medical directors should work directly with flight paramedics to expand their scope of practice.     

Does blood flow through holmium:YAG transmyocardial laser channels?

BACKGROUND: Early reports indicate that transmyocardial laser revascularization improves symptoms in patients with refractory angina. However, there is little experimental evidence of whether blood flow through channels is the mechanism of action. METHODS: Endocardial channels were made in the distribution of the left anterior descending coronary artery in canine hearts (n = 5) using a holmium:yttrium-aluminum garnet laser. Hearts were excised acutely while perfused in a retrograde fashion from a second dog so that the aortic valve always remained closed. The proximal left anterior descending coronary artery was ligated. To measure direct transmyocardial blood flow, colored microspheres were injected into the left ventricular chamber. RESULTS: The number of spheres per gram of tissue in the channel region was significantly higher than in the control region (low load, 302.5 +/- 169.0 versus 41.8 +/- 59.4; high load, 208.4 +/- 138.3 versus 5.8 +/- 11.7; both, p < 0.05). However, the estimated regional blood flow through the channels was extremely low (<0.01 mL/g/min. In the chronic setting (n = 4) (2-week survival), no flow as detected through the channels, and the endocardial entry points were closed. CONCLUSIONS: Transmyocardial blood flow does not appear to occur through channels made with the holmium:yttrium-aluminum garnet laser. It remains to be determined whether this is the case with other types of lasers.     

Interactive image directed neurosurgery: patient registration employing the Laitinen stereo-adapter

Fiducial markers visible on both imaging scans and the patient are a convenient and accurate method to register the patients head in stereotactic space preceeding an interactive image directed neurosurgical procedure. We have been using the Laitinen non-invasive relocatable stereo-adapter to carry the fidcucial markers both during the imaging and patient registration process. Since the adapter can be accurately remounted the surgical procedure can take place at any time interval after the imaging study. To compare registration accuracy studies were performed using a phantom carrying both surface fiducial markers and fiducial markers mounted on the stereo adapter. We have found that total system accuracy using either surface or adapter mounted markers and an optical tracking system is in the range of 3-5 mm and is acceptable for a broad range of neurosurgical applications.     

Acute tumor lysis syndrome due to mono-therapy with a corticosteroid in a patient with non-Hodgkin lymphoma

A 20-year-old man was hospitalised because he nearly suffocated when lying on his back. After bronchoscopy which revealed severe external compression of the airways, suddenly respiratory insufficiency developed. Because a malignant lymphoma was suspected chemotherapy was started, using monotherapy with prednisolone as the risk of acute tumour lysis syndrome (ATLS) is high with polychemotherapy of bulky tumours. Nevertheless ATLS developed, for which haemodialysis had to be applied. The tumour, a T-cell lymphoblastic non-Hodgkin lymphoma with high grade malignancy, was treated successfully with cyclophosphamide, doxorubicin, vincristine en prednisone. ATLS is characterized by hyperkalaemia, hyperuricaemia, hyperphosphataemia, hypocalcaemia, lactate acidosis and acute renal failure. It can occur in the course of aggressive cytoreductive therapy in rapidly growing lymphoproliferative malignancies with large tumour size, due to massive tumour cel lysis. Corticosteroid monotherapy is a very rare cause of ATLS.     

Acyclovir given as prophylaxis against oral ulcers in acute myeloid leukaemia: randomised, double blind, placebo controlled trial

OBJECTIVES: To evaluate (a) the prophylactic effect of the antiherpetic drug acyclovir on oral ulcers in patients with acute myeloid leukaemia receiving remission induction chemotherapy and thus (b), indirectly, the role of herpes simplex virus in the aetiology of these ulcers. DESIGN: Randomised, double blind, placebo controlled trial. SUBJECTS: 74 herpes simplex virus seropositive patients aged 18-84. Thirty seven patients received acyclovir (800 mg by mouth daily) and 37 placebo. The patients were examined daily for 28 days. MAIN OUTCOME MEASURES: Occurrence of herpes labialis, intraoral ulcers, and acute necrotising ulcerative gingivitis. RESULTS: The two populations were comparable in age, sex, type of antineoplastic treatment, and history of herpes labialis. Acute oral infections occurred in 25 of the acyclovir treated patients and 36 of the placebo treated patients (relative risk 0.69 (95% confidence interval 0.55 to 0.87)). This difference was due to a reduction in the incidence of herpes labialis (one case versus eight cases; relative risk 0.13 (0.02 to 0.95)), intraoral ulcers excluding the soft palate (one case versus 13 cases; relative risk 0.08 (0.01 to 0.56)), and acute necrotising ulcerative gingivitis (one case versus eight cases; relative risk 0.13 (0.02 to 0.95)). However, ulcers on the soft palate were diagnosed with similar frequency in the two groups. Isolation of herpes simplex virus type 1 in saliva was reduced from 15 cases in the placebo group to one case in the acyclovir group (relative risk 0.07 (0.01 to 0.48)). CONCLUSION: Intraoral ulcers excluding the soft palate are most often due to infection with herpes simplex virus, whereas ulcers on the soft palate have a non-herpetic aetiology. The findings suggest that acute necrotising ulcerative gingivitis may also be due to herpes simplex virus. Prophylaxis with acyclovir should be considered for patients with acute myeloid leukaemia during remission induction therapy.     

Hereditary angio-oedema: new clinical observations and autoimmune screening, complement and kallikrein-kinin analyses

Sinus cavities are often a major obstacle to the placement of dental implants in the posterior maxilla, especially when early tooth loss has occurred. Several grafting procedures aimed at reducing the expanded volume of these pneumatic cavities have been routinely utilized since 1979. Essentially, these techniques have consisted of recreating the necessary viable bone volume at the floor of sinus cavities by placing different bone substitute materials to allow for the insertion of endosseous implant devices. The progress achieved in the refinement of the surgical procedures and the knowledge acquired in the field of patient screening and selection, choice of biomaterials, management of complications, etc., have made sinus graft surgery highly codified and predictable. A comprehensive statistical study by multifactorial procedures was carried out to establish a Burt Contingency Chart. This chart visualizes the frequencies of all the "modality combinations" among the selected "qualitative parameters" and, by a " factorial analysis", the "multiple correlations", so that the "statistical affinities" that may exist among the same variables can be determined. This critical study endeavors to search for and reveal the favorable clinical, biologic and scientific parameters necessary for the success of sinus graft surgery on short-, medium-, and long-term bases (more than nine years). It is a particularly homogenous study, since all the operative procedures have been carried out exclusively by the author under standardized conditions. The wide variety of biomaterials utilized by the author since 1979 shows the development of bone substitute biomaterials as they have been introduced into the market during the past 15 years. The large number of patients treated, the variety of grafting materials, the important success rate obtained, and the long duration of patient follow-up have been instrumental in enabling us to establish scientifically significant results. Autogenous bone and its combinations with calcium- and phosphorus-containing biomaterials remain undoubtedly the best all-purpose biomaterials. The synthetic biomaterials have their own specific indications according to their stable (non-resorbable) or unstable (resorbable) nature and their rates of metabolic "turnover". Differently treated bones from the tissue bank (if not contaminated or immunologically questionable) behave in a fashion not unlike autogenous bone. Root-form implants are by far the best implants in the reconstructed sinus sites, while other implant types (subperiosteal implants, etc.) inserted beneath the reinforced osseous sinus floor, buccal wall, and pyramidal process, also have their indications.     

Unpacking Pandora from Its Box: Deciphering the Molecular Basis of the SARS-CoV-2 Coronavirus

An enigmatic localized pneumonia escalated into a worldwide COVID-19 pandemic from Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2). This review aims to consolidate the extensive biological minutiae of SARS-CoV-2 which requires decipherment. Having one of the largest RNA viral genomes, the single strand contains the genes ORF1ab, S, E, M, N and ten open reading frames. Highlighting unique features such as stem-loop formation, slippery frameshifting sequences and ribosomal mimicry, SARS-CoV-2 represents a formidable cellular invader. Hijacking the hosts translational engine, it produces two polyprotein repositories (pp1a and pp1ab), armed with self-cleavage capacity for production of sixteen non-structural proteins. Novel glycosylation sites on the spike trimer reveal unique SARS-CoV-2 features for shielding and cellular internalization. Affording complexity for superior fitness and camouflage, SARS-CoV-2 challenges diagnosis and vaccine vigilance. This review serves the scientific community seeking in-depth molecular details when designing drugs to curb transmission of this biological armament.     

Ca2+ Signalling Induced by NGF Identifies a Subset of Capsaicin-Excitable Neurons Displaying Enhanced Chemo-Nociception in Dorsal Root Ganglion Explants from Adult pirt-GCaMP3 Mouse

Nociceptors sense hazards via plasmalemmal cation channels, including transient receptor potential vanilloid 1 (TRPV1). Nerve growth factor (NGF) sensitises TRPV1 to capsaicin (CAPS), modulates nociceptor excitability and induces thermal hyperalgesia, but cellular mechanisms remain unclear. Confocal microscopy was used to image changes in intracellular Ca²⁺ concentration ([Ca²⁺]_i) across neuronal populations in dorsal root ganglia (DRG) explants from pirt-GCaMP3 adult mice, which express a fluorescent reporter in their sensory neurons. Raised [Ca²⁺]_i was detected in 84 neurons of three DRG explants exposed to NGF (100 ng/mL) and most (96%) of these were also excited by 1 μM CAPS. NGF elevated [Ca²⁺]_i in about one-third of the neurons stimulated by 1 μM CAPS, whether applied before or after the latter. In neurons excitable by NGF, CAPS-evoked [Ca²⁺]_i signals appeared significantly sooner (e.g., respective lags of 1.0 ± 0.1 and 1.9 ± 0.1 min), were much (>30%) brighter and lasted longer (6.6 ± 0.4 vs. 3.9 ± 0.2 min) relative to those non-responsive to the neurotrophin. CAPS tachyphylaxis lowered signal intensity by ~60% but was largely prevented by NGF. Increasing CAPS from 1 to 10 μM nearly doubled the number of cells activated but only modestly increased the amount co-activated by NGF. In conclusion, a sub-population of the CAPS-sensitive neurons in adult mouse DRG that can be excited by NGF is more sensitive to CAPS, responds with stronger signals and is further sensitised by transient exposure to the neurotrophin.