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.     

Clinicopathological features of melanocytic skin lesions in Egypt.

Although melanocytic skin lesions have been recognized since antiquity, their literature was limited to Caucasians. To date, the clinicopathologic features of these lesions in Egyptians are still unknown. To define these features, diagnostic records of the melanocytic skin lesions received at the Pathology Department, Assuit University Hospitals (1989-2004) were reviewed. The lesions examined included 12 benign naevi (BN), 10 dysplastic naevi (DN), and 21 cutaneous malignant melanomas (CMMs). The DN and CMMs were more common in men than in women (2 : 1 and 1.5 : 1, respectively) while BN were more common in women (2 : 1). The average age incidence was 33+/-5, 38+/-7 and 54+/-3 years, for BN, DN and CMM, respectively. The lower limb (13/21, 62%), head and neck (7/21, 33%) were the most common sites for CMMs. The average size (mm) was 2+/-0.3, 4+/-0.6 and 21+/-0.3 for BN, DN and CMMs, respectively. Recurrence occurred in 10% of CMMs. Histologically, CMMs were of nodular type and composed of epithelioid (7/21, 33%), spindle cells (1/21, 5%), or mixed cells (13/21, 62%). The mean tumour thickness (Breslow) was 6+/-0.5 mm. CMMs included two of 21(9%), three of 21(14%), six of 21(38%), and 10 of 21(38%) with Clark level II, III, IV and V. In Egypt, CMM is the third most common cutaneous neoplasm following squamous and basal cell carcinomas. Compared with Western societies, melanoma has a male sex predilection, similar histological features but different topographical distribution and rare incidence. The striking difference from Western series is the incidence of nodular melanoma - in the West this represents 15-30% of melanomas, with superficial spreading being the majority. Another key difference from the West is the 'sun-bed' culture of the West and the desire to have suntans. This is the first study that reports the clinicopathologic features of melanocytic skin lesions in Egypt.     

Analysis of surgical management of calvarial tumours and first results of a newly designed robotic trepanation system.

This study was performed to evaluate the surgical strategy in patients with calvarial tumours, in order to design and modify a robot-assisted trepanation system. A total of 75 patients underwent craniectomy for the treatment of calvarial tumours during the 10-year period from 1993 to 2002. The patients' complaints, the size, location and histology of the tumour, and the various cranioplasty techniques used were analysed retrospectively. In a second procedure several craniectomies at typical locations according to the study's results were performed in a laboratory setting using a hexapod robotic tool, constructed at the Helmholtz-Institute, RWTH Aachen University, and plastic model heads. The workflow was documented and the reproducibility and the accuracy of the procedure were registered. A total of 83 surgical procedures were performed on 75 patients. The majority (87 %) of lesions treated surgically were located in the frontal, temporal and anterior parts of the parietal region. Histological examination revealed benign lesions in 66 % of the patients and dural involvement in 46 %. According to these results craniectomies were performed using the robotic system. Mean positioning accuracy of the robotic system while milling was 0.24 mm, with a standard deviation of 0.04 mm, and maximum error under 1 mm. Craniectomies leaving a 1-mm layer of the tabula interna intact to ensure a healthy dura were performed in several regions successfully. The majority of calvarial tumours, requiring surgical treatment in our patients, were located in cosmetically relevant areas in which drilling can be carried out with the robotic trepanation system. Consequently, the surgical approach had to be planned carefully in order to achieve a good cosmetic outcome.     

The importance of two-step tuberculin skin testing for newly employed healthcare workers.

At the time of hire, 4059 of 6522 healthcare workers required a 2-step tuberculin skin test; 114 workers (2.8%) demonstrated a boosted reaction after the second step. Boosted reactions were significantly associated with male sex and older age. A verbal history of previous tuberculin skin test results was not a reliable indicator of baseline tuberculin skin test status at the time of hire.     

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.     

Etanercept decreases tumor necrosis factor-α activity in chronic wound fluid

High levels of tumor necrosis factor-alpha (TNF-alpha), a pro-inflammatory cytokine, are present in the wound fluid of chronic nonhealing wounds. This leads to increased inflammation, cytokine expression, and ultimately results in impaired wound healing and tissue destruction. Etanercept is a recombinant fusion protein that consists of the soluble TNF receptor (p75) linked to the Fc portion of human IgG1. It is an effective inhibitor of TNF-alpha and has been shown to provide rapid and sustained improvement in rheumatoid arthritis by acting as a soluble receptor binding TNF-alpha and preventing its proinflammatory activities. Therefore, the aim of this study was to determine whether Etanercept could inhibit TNF-alpha activity in chronic wound fluid. Wound fluid was collected from the venous leg ulcers of 16 different patients. The effect of Etanercept on TNF-alpha activity was evaluated using both a TNF-alpha bioassay and an enzyme-linked immunoassay. Etanercept was found to reduce the cytotoxic effect of chronic wound fluid on L929 fibroblasts by approximately 30% and neutralized TNF-alpha binding in the enzyme-linked immunoassay by up to 80%. Direct application of Etanercept to chronic wounds may therefore reduce the inflammatory activity of TNF-alpha, which could reduce the chronicity of venous leg ulcers and thus aid in the healing of these wounds.     

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.