Errors enacted during endoscopic surgery--a human reliability analysis

PURPOSE: Current knowledge on central nervous system sarcoidosis. CURRENT KNOWLEDGE AND KEY POINTS: Sarcoidosis is localized in the central nervous system in 5 to 16% of the cases. Various neurological manifestations are observed, including: seizures, cognitive or psychic manifestations, hypothalamic and pituitary involvement, local pseudotumors, and hydrocephalus very frequently associated with asymptomatic lymphocytic meningitis and with cranial nerve palsy, particularly palsy of the seventh nerve, occurring less regularly. CNS localization is most often an early manifestation of the disease, unmasking sarcoidosis. It is often part of primary or secondary systemic polyvisceral sarcoidosis. The diagnosis is mainly based on two arguments: confirmation of the existence of systemic sarcoidosis and clinical and paraclinical compatibility of neurological abnormalities (particularly at magnetic resonance imaging [MRI]). Neurological histopathology is rarely necessary to confirm the diagnosis. Corticotherapy is indicated in all symptomatic cases and most often leads to a more or less complete clinical response evidenced by regression of active lesions identified on MRI. The treatment must often be prolonged for several years, and clinical and MRI evolution help guide therapeutical choices for dosages and threshold doses. CNS involvement is potentially severe with mortality and morbidity rates that are not insignificant. Limiting of iatrogenic risks requires adequate follow-up. PERSPECTIVES AND PROJECTS: Multicenter studies are necessary to determine factors influencing the incidence and long-term prognosis of CNS sarcoidosis treated with corticotherapy. The efficacy of treatments other than corticotherapy must be evaluated.     

Hyperbaric oxygen and thrombolysis in myocardial infarction: the ''HOT MI'' randomized multicenter study

Reactions mediated by the brain are part of the response to intraperitoneal administration of endotoxin, a model of gram-negative bacterial infection. To test the hypothesis that a compromised blood-brain barrier (BBB) may contribute to these reactions, the integrity of the BBB was measured following lipopolysaccharide administration. Rats received intraperitoneal injections of 50 microg/kg or 2 mg/kg of endotoxin. Brain uptake of a macromolecular vascular marker, 3H-labelled rat serum albumin, and of a poorly permeable low molecular weight substance, [14C]sucrose, was then measured with the intravenous bolus injection method. Compared to controls, neither dose of endotoxin affected the BBB permeability for these tracers. This was true when brain uptake was measured 5 min or 2 h after lipopolysaccharide injection. It is concluded that intraperitoneal endotoxin even at a high dose does not acutely disrupt the BBB.     

Topical clindamycin versus systemic tetracycline in the treatment of hidradenitis suppurativa

BACKGROUND: Antibiotics are often used to treat hidradenitis, but only topical clindamycin has been shown to be effective in a randomized controlled trial. The paucity of these trials may be the result of difficulties in disease assessment. OBJECTIVE: We compare topical clindamycin with systemic tetracycline in the treatment of hidradenitis suppurativa, and study clinical disease assessment. METHODS: A total of 46 patients with stage 1 or 2 hidradenitis suppurativa were treated in a double-blind, double dummy controlled trial. RESULTS: No significant difference was found between the two types of treatment. Patients' global assessment of disease was significantly worse than physician's assessment in 3 of 5 evaluations (P = .0096 to .015), but the correlation between patients' and physicians' assessments was satisfactory after only one visit (rs = .761 to .895). Soreness was the key factor in patients' overall assessment of the disease. CONCLUSION: Systemic therapy with tetracyclines did not show better results than topical therapy with clindamycin. Subjective factors, particularly soreness, appear to be a key factor in patients' assessment of the disease and should, therefore, be included as an outcome variable in future therapy studies.     

Morphine stimulates nitric oxide release from invertebrate microglia

Analysis of chromosomal DNA restriction patterns produced by pulsed field gel electrophoresis (PFGE) was used to investigate an outbreak of human salmonellosis caused by Salmonella enterica ssp. enterica serovar Infantis (S. Infantis) involving more than 500 registered human cases. The outbreak had been tentatively traced back to a single pig slaughterhouse. A total of 135 isolates from various sources produced 21 different PFGE patterns with the restriction endonuclease XbaI. All human isolates from the outbreak belonged to a single type, the 'EPI-type', whereas human isolates recovered before and after the outbreak belonged to several different types. All isolates investigated from the suspect pig slaughterhouse and its supplier pig herds belonged to the EPI-type. Isolates from pork from the central meat market in Copenhagen, which received most of the carcasses from the suspect slaughterhouse, also belonged to the EPI-type. This was furthermore, the case for isolates from beef from the same market, indicating that cross-contamination had taken place. All isolates from pork and some, but not all, isolates from beef, collected in butchers' shops during the outbreak belonged to the EPI-type. The typing results supported that the outbreak was a common source outbreak, probably originating from a limited number of supplier pig herds supplying animals to a single slaughterhouse.     

Screening derivatized peptide libraries for tight binding inhibitors to carbonic anhydrase II by electrospray ionization-mass spectrometry

This paper describes the use of electrospray ionization-mass spectrometry (ESI-MS) to screen two libraries of soluble compounds to search for tight binding inhibitors for carbonic anhydrase II (EC 4.2.1.1). The two libraries, H2NO2SC6H4C(O)NH-AA1-AA2-C(O)NHCH2CH2CO2H where AA1 and AA2 are L-amino acids (library size: 289 compounds) or D-amino acids (256 compounds), were constructed by attaching tripeptides to the carboxyl group of 4-carboxybenzenesulfonamide. Screening of both libraries yielded, as the tightest binding inhibitor, compound 1 (AA1 = AA2 = L-Leu; binding constant Kb = 1.4 x 10(8) M-1). The ability of ESI-MS to estimate simultaneously the relative binding affinities of a protein to soluble ligands in a library, if general, should be useful in drug development.     

Circular YAC vectors containing a small mammalian origin sequence can associate with the nuclear matrix

Three different mammalian origins of DNA replication, 343, S3, and X24, have been cloned into a 15.8 kb circular yeast vector pYACneo. Subsequent transfection into HeLa cells resulted in the isolation of several stably maintained clones. Two cell lines, C343e2 and CS3e1, were found to have sequences maintained as episomes in long-term culture with a stability per generation of approximately 80%. Both episomes also contain matrix attachment region (MAR) sequences which mediate the binding of DNA to the nuclear skeleton and are thought to play a role in DNA replication. Using high salt extraction of the nucleus and fluorescent in situ hybridization, we were able to demonstrate an association of the 343 episome with the nuclear matrix, most probably through functional MAR sequences that allow an association with the nuclear matrix and associated regions containing essential replication proteins. The presence of functional MARs in small episomal sequences may facilitate the replication and maintenance of transfected DNA as an episome and improve their utility as small episomal constructs, potential microchromosomes.     

Pindolol does not act only on 5-HT1A receptors in augmenting antidepressant activity in the mouse forced swimming test

Hypocapnia produces cerebral vasoconstriction. The mechanisms involved in hypocapnia-induced elevation of vascular smooth muscle tone remain unclear. We addressed the hypothesis that, in cerebrovascular smooth muscle, increases in extracellular pH (pHo) cause increases in Ins(1,4,5)P3 and cytosolic calcium ([Ca2+]c). Superfused primary cultures of piglet cerebral microvascular smooth muscle cells were exposed to artificial CSF (aCSF) of control (pHo 7. 4, PCO2 36 mm Hg), metabolic alkalosis (pHo 7.7, PCO2 36 mm Hg), or respiratory alkalosis (pHo 7.7, PCO2 19 mm Hg). Intracellular pH (pHi) and [Ca2+]c were measured, using BCECF and fura-2, respectively, with dual wavelength spectroscopy. Ins(1,4,5)P3 was determined by a protein binding assay. Both metabolic and respiratory acidosis treatments increased pHi from the control value of about 7.2 to 7.35. Metabolic and respiratory alkalosis increased Ins(1,4,5)P3, as we showed previously. Metabolic and respiratory alkalosis increased [Ca2+]c about 80% and 110%, respectively. Neither Ins(1,4,5)P3 nor [Ca2+]c increased in cells treated with aCSF that produced control pHo with increased pHi (7.3). In contrast, when pHo increased (7.7), but pHi was maintained at control (7.2), Ins(1,4,5)P3 increased from 123 pmol/well to 307 pmol/well and [Ca2+]c increased 46%. However, the increase of [Ca2+]c was less than with either respiratory or metabolic alkalosis. Thus, hypocapnia-induced cerebral vasoconstriction could involve production of Ins(1,4,5)P3 with resultant elevation in [Ca2+]c. While the Ins(1,4,5)P3 signal appears to be dependent on an increase in extracellular pH, a role for intracellular pH cannot be completely excluded.     

Frameless stereotactic guidance for surgery of the upper cervical spine

OBJECTIVE: The goal was to evaluate and describe the use of a frameless, computed tomography-guided, stereotactic technique in complex procedures involving the craniocervical junction. METHODS: Eleven procedures, including transoral odontoid resection, posterior atlantoaxial fusion with transarticular C1-C2 screw fixation, and spinal tumor resection, were performed in the preceding 26 months. In each case, frameless stereotaxy was used to plan the incision, to define resection margins, and to determine the appropriate orientation of instrumentation. RESULTS: There were no intraoperative complications noted. Each patient underwent adequate resection of the pathological lesion and satisfactory placement of instrumentation. The stereotactic system provided detailed anatomic visualization, which increased the confidence of the surgeon during the procedure. The system limited the need for extensive surgical exposure, reduced fluoroscopy time, and decreased the risk of neurovascular injury. CONCLUSION: Frameless stereotaxy provided the surgeon with intraoperative information regarding the extent of bone and soft tissue resection. It provided a multidimensional view of anatomic relationships in the operative field, which significantly increased surgical accuracy and safety.     

Cryo-electron microscopy structure of yeast Ty retrotransposon virus-like particles

The virus-like particles (VLPs) produced by the yeast retrotransposon Ty1 are functionally related to retroviral cores. These particles are unusual in that they have variable radif. A paired mass-radius analysis of VLPs by scanning transmission electron microscopy showed that many of these particles form an icosahedral T-number series. Three-dimensional reconstruction to 38-A resolution from cryo-electron micrographs of T = 3 and T = 4 shells revealed that the single structural protein encoded by the TYA gene assembles into spiky shells from trimeric units.