Development of miotic cross-tolerance between pyridostigmine and sarin vapor.

The organophosphorous nerve agent sarin (GB) and the carbamate pyridostigmine bromide (PB) both inhibit acetylcholinesterase (AChE), leading to overstimulation of muscarinic receptors. Both GB and PB produce miosis through stimulation of ocular muscarinic receptors. This study investigated 2 hypotheses: (1) that the miotic response to PB would decrease following repeated injections; and (2) that repeated administration of PB would result in tolerance to the miotic effect of GB vapor. Rats were injected intramuscularly with saline, 0.04 mg/kg, 0.5 mg/kg, or 1.4 mg/kg of PB twice daily for 8 consecutive days. After day 3, animals injected with 1.4 mg/kg PB developed miotic tolerance. Twenty-four (24) h following the final PB injection, the rats were exposed to GB vapor (4.0 mg/m(3)). A similar magnitude of miosis was observed in all groups after GB exposure. However, the rate of recovery of pupil size in animals pretreated with 0.5 and 1.4 mg/kg PB was significantly increased. Twenty (20) h following exposure to GB vapor, the pupils of animals pretreated with 1.4 mg/kg PB had recovered to 77% +/- 4% of their pre-exposure baseline, whereas the saline-injected controls had recovered to only 52% +/- 2% of their pre-exposure baseline. The increased rate of recovery does not appear to be a result of protection of pupillary muscarinic receptors by the higher doses of PB, as there was no longer PB present in the animal at the time of GB exposure. These results demonstrate the development of tolerance to the miotic effect of PB following repeated exposures, and also suggest that cross-tolerance between PB and GB occurs. However, because the magnitude of the response was not reduced, the PB pretreatment and its associated miotic cross-tolerance does not appear to diminish the effectiveness of miosis as a biomarker of acute exposure to nerve agent vapor.     

Application of an augmented reality tool for maxillary positioning in orthognathic surgery – A feasibility study

BACKGROUND: An augmented reality tool for computer assisted surgery named X-Scope allows visual tracking of real anatomical structures in superposition with volume rendered CT or MRI scans and thus can be used for navigated translocation of bony segments. METHODS: In a feasibility study X-Scope was used in orthognathic surgery to control the translocation of the maxilla after Le Fort I osteotomy within a bimaxillary procedure. The situation achieved was compared with the pre-operative situation by means of cephalometric analysis on lateral and frontal cephalograms. RESULTS: The technique was successfully utilized in 5 patients. Maxillary positioning using X-Scope was accomplished accurately within a range of 1mm. The tool was used in all cases in addition to the usual intra-operative splints. A stand-alone application without conventional control does not yet seem reasonable. CONCLUSION: Augmented reality tools like X-Scope may be helpful for controlling maxillary translocation in orthognathic surgery. The application to other interventions in cranio-maxillofacial surgery such as Le Fort III osteotomy, fronto-orbital advancement, and cranial vault reshaping or repair may also be considered.     

Synthesis of 1-alkyl-3,4-dihydroisoquinoline derivatives and study of their effect on arterial pressure

A series of 1-alkyl-3,4-dihydroisoquinolines and the related 4-alkyl-1,2-dihydro-benzo[f]isoquinolines was synthesized using reactions of dialkylbenzylcarbinols and their naphthyl analogs with alkylcyanides. Experiments showed that 1-alkyl-6,7-dimethoxy-3,4-dihydroisoquinolines typically produce a hypotensive action, while the benzo-annelated structures usually exhibit a hypertensive effects. The most active compound decreases the arterial pressure in cats by 52 Torr and the effect lasts for about 4 hours. __________ Translated from Khimiko-Farmatsevticheskii Zhurnal, Vol. 40, No. 3, pp. 15–17, March, 2006.     

Management of asthma in patients supervised by primary care physicians or by specialists.

French asthma patients may be supervised by general practitioners (GPs) and/or specialists. Therefore, this study examined asthma management in patients exclusively supervised by specialists (SPE), GPs, (GP) and both (GP+SPE group), and compared the findings. Asthma patients were consecutively recruited in 348 pharmacies. Each patient completed a questionnaire providing data on personal characteristics, asthma management, perception of disease and asthma supervision. Asthma control was measured using the Asthma Control Test. Questionnaires were linked to computerised records of medications which had been dispensed before inclusion in the study. From the 1,256 patients (mean age = 36.1 yrs, 54.3% females), 11.4, 36.6, and 52.0% were placed in the SPE, GP, and GP+SPE groups, respectively. During the previous 4 weeks, most patients in the SPE group were properly controlled (52.2 versus 26.4 and 21.5% in GP and GP+SPE groups, respectively). The SPE group made more use of fixed combinations of long-acting beta agonist and inhaled corticosteroid, while receiving less short-acting beta agonists, antitussives and antibiotics. Striking differences in symptoms and asthma management were observed according to the type of asthma supervision. The current results strongly support the need to improve the management of asthma in primary care, and the coordination of care between general practitioners and specialists.     

Lack of a rationale for the Task Force recommendation regarding re-administration of streptokinase

Dear Sir In the recently published Task force report, under section ‘Fibrinolyticregimens’, the authors recommend not to re-administerstreptokinase for at least 10 years. The reference supportingthis statement is Ref. 51. After evaluating this paper and lookinginto the literature my comments     

Coccidioidomycosis After Renal Transplantation in an Endemic Area

Coccidioidomycosis is an endemic fungal infection of the desert southwestern United States of particular concern for immunosuppressed renal transplant recipients. The clinical course of coccidioidomycosis can be severe in immunosuppressed patients, with high rates of dissemination and mortality, and antifungal prophylaxis is routinely administered to high-risk patients. We sought to determine the impact of coccidioidomycosis on patients who received their renal transplant at our hospital in Phoenix, Arizona. A retrospective records review of the first 205 patients who received a renal transplant between June 1999 and December 2003 identified 6 patients (3%) who had contracted coccidioidomycosis after transplantation. All six cases occurred more than 6 months after transplantation. Two of these six patients had disseminated coccidioidomycosis. Two patients, one with pulmonary infection and one with disseminated infection, died. None of the six patients with coccidioidomycosis after transplantation had identified risk factors before transplantation. No high-risk patient who received targeted antifungal prophylaxis had a reactivation of coccidioidomycosis after transplantation. Treatment for acute rejection and induction with antithymocyte globulin did not appear to increase the risk of subsequent coccidioidomycosis.     

Spinocerebellar ataxia types 2 and 3 segregating simultaneously in a single family.

Spinocerebellar ataxia (SCA) types 2 and 3 are autosomal-dominant neurodegenerative disorders caused by mutations in two different genes. We identified mutations for SCA2 and SCA3 segregating simultaneously in a single Brazilian family. The index patient had SCA2, whereas her two second-degree cousins had SCA3. Disease was more rapidly progressive in the SCA2 patient, who presented severe brainstem and pancerebellar atrophy, as opposed to the two SCA3 patients, who had only mild cerebellar vermian atrophy. In such situations, molecular confirmation of all patients may avoid misdiagnosis of SCA subtypes and eventual errors in predictive testing of unaffected family members.