Genotype/phenotype correlation of the G85E mutation in a large cohort of cystic fibrosis patients.

In this European study, the phenotype in 68 patients, homozygous or compound heterozygous for the G85E mutation, was investigated. Each index case was compared with two cystic fibrosis (CF) patients from the same clinic, matched for age and sex: one with pancreatic sufficiency (PS) and one with pancreatic insufficiency (PI). When comparing 31 G85E/F508del and F508del/F508del patients, there were no differences in median age at diagnosis, mean sweat chloride value, most recent weight for height, most recent forced expiratory volume in one second % predicted, prevalence of chronic Pseudomonas aeruginosa colonisation and typical CF complications. However, PI was less frequent in the G85E/F508del group. Comparison of 55 G85E patients (with second mutation known and not classified as mild) with PS controls (n=44) showed that the G85E patients had a significantly higher sweat chloride, more often failure to thrive at diagnosis, higher prevalence of PI, worse current weight for height, higher prevalence of chronic P. aeruginosa colonisation and liver cirrhosis. Pulse-chase experiments revealed that G85E cystic fibrosis transmembrane conductance regulator failed to mature on a M470 as well as on a V470 background. Therefore, G85E is a class II mutation. Although there is variability in its clinical presentation, G85E mutation results in a severe phenotype.     

Nefopam, a Nonsedative Benzoxazocine Analgesic, Selectively Reduces the Shivering Threshold in Unanesthetized Subjects

Background: The analgesic nefopam does not compromise ventilation, is minimally sedating, and is effective as a treatment for postoperative shivering. The authors evaluated the effects of nefopam on the major thermoregulatory responses in humans: sweating, vasoconstriction, and shivering.

Methods: Nine volunteers were studied on three randomly assigned days: (1) control (saline), (2) nefopam at a target plasma concentration of 35 ng/ml (low dose), and (3) nefopam at a target concentration of 70 ng/ml (high dose, approximately 20 mg total). Each day, skin and core temperatures were increased to provoke sweating and then reduced to elicit peripheral vasoconstriction and shivering. The authors determined the thresholds (triggering core temperature at a designated skin temperature of 34[degrees]C) by mathematically compensating for changes in skin temperature using the established linear cutaneous contributions to control of each response.

Results: Nefopam did not significantly modify the slopes for sweating (0.0 +/- 4.9[degrees]C [middle dot] [mu]g-1 [middle dot] ml; r2 = 0.73 +/- 0.32) or vasoconstriction (-3.6 +/- 5.0[degrees]C [middle dot] [mu]g-1 [middle dot] ml; r2 = -0.47 +/- 0.41). In contrast, nefopam significantly reduced the slope of shivering (-16.8 +/- 9.3[degrees]C [middle dot] [mu]g-1 [middle dot] ml; r2 = 0.92 +/- 0.06). Therefore, high-dose nefopam reduced the shivering threshold by 0.9 +/- 0.4[degrees]C (P < 0.001) without any discernible effect on the sweating or vasoconstriction thresholds.     

Esthesioneuroblastoma: endonasal endoscopic treatment.

Objectives: To illustrate endoscopic techniques used in the treatment of esthesioneuroblastoma and to advocate this method of management followed by radiation therapy in selected cases. Methods: A retrospective case series of 10 patients with esthesioneuroblastomas treated between 1999 and 2004 at a tertiary referral center using endonasal techniques. Results: Mean age of patients at presentation was 56.2 years (median 57 years). Seven patients were female and 3 patients were male. Kadish staging at presentation was: A - 3 patients, B - 5 patients, C - 2 patients. Dulguerov stage at presentation was: T1 - 4 patients, T2 - 4 patients, T3 - 2 patients. The period of follow-up ranged from 11 months to 74 months (mean 38.1 months, median 39 months). To date no recurrence has developed in any patient. Conclusions: Our experience suggests that endoscopic surgery can be an effective method of management. Strict attention to selection criteria, careful surgical techniques, and regular follow-up are key elements for success.     

Historical overview of analytical methods for the measurement of transthyretin.

The history of prealbumin dates back to the early forties and may be divided into three parts, based on a chronological and functional approach. The first part--the discovery and the identification of prealbumin--was essentially based on classical protein chemistry methods. The second--the demonstration of prealbumin as a thyroid hormone-binding protein (thyroxine-binding prealbumin)--has greatly benefited from isotopic techniques. The third one--establishing prealbumin as a nutritional marker--was a result of field studies on nutrition. The discovery of the role of prealbumin in retinol binding led to a change in its name, prealbumin becoming transthyretin. Finally, structural studies and mutation analysis of transthyretin in patients with amyloid neuropathy have opened a new area of research.     

Effects of 2,4-dichlorophenoxyacetic acid on Rhizobium sp. in pure culture

The effects of 2,4-Dichlorophenoxyacetic acid on the growth rate, chemical composition, ¹⁴C-2,4-dichlorophenoxyacetic acid and ⁴⁵Ca²⁺ uptake by Rhizobium sp. M 4 able to nodulate Arachis hypogaea were determined. Cellular growth was diminished by the presence of 10^?3 M 2,4-dichlorophenoxyacetic acid in the medium. Alterations in cellular chemical composition, in ¹⁴C-2,4-dichlorophenoxyacetic acid and in ⁴⁵Ca²⁺ uptake were found.     

Pars plana vitrectomy in aphakic and pseudophakic retinal detachment

Eighty-two consecutive aphakic or pseudophakic retinal detachments were treated by buckling and vitrectomy procedures. Functional results (86.6%) and the incidence of proliferative vitreoretinopathy (11%) were comparable with reports of cases treated by the classic method.Presented at the 1984 meeting of the Club Jules Gonin in Lausanne, Switzerland     

Blood coagulation activation and fibrinolysis during a downhill marathon run.

Prolonged physical exercise is associated with multiple changes in blood hemostasis. Eccentric muscle activation induces microtrauma of skeletal muscles, inducing an inflammatory response. Since there is a link between inflammation and coagulation we speculated that downhill running strongly activates the coagulation system. Thirteen volunteers participated in the Tyrolean Speed Marathon (42,195 m downhill race, 795 m vertical distance). Venous blood was collected 3 days (T1) and 3 h (T2) before the run, within 30 min after finishing (T3) and 1 day thereafter (T4). We measured the following key parameters: creatine kinase, myoglobin, thrombin-antithrombin complex, prothrombin fragment F1 + 2, D-dimer, plasmin-alpha(2)-antiplasmin complexes, tissue-type plasminogen activator antigen, plasminogen-activator-inhibitor-1 antigen and thrombelastography with ROTEM [intrinsic pathway (InTEM) clotting time, clot formation time, maximum clot firmness, alpha angle]. Thrombin generation was evaluated by the Thrombin Dynamic Test and the Technothrombin TGA test. Creatine kinase and myoglobin were elevated at T3 and further increased at T4. Thrombin-antithrombin complex, prothrombin fragment F1 + 2, D-dimer, plasmin-alpha(2)-antiplasmin complexes, tissue-type plasminogen activator antigen and plasminogen-activator-inhibitor-1 antigen were significantly increased at T3. ROTEM analysis exhibited a shortening of InTEM clotting time and clot formation time after the marathon, and an increase in InTEM maximum clot firmness and alpha angle. Changes in TGA were indicative for thrombin generation after the marathon. We demonstrated that a downhill marathon induces an activation of coagulation, as measured by specific parameters for coagulation, ROTEM and thrombin generation assays. These changes were paralleled by an activation of fibrinolysis indicating a preserved hemostatic balance.     

Clinical trial comparing plasma arc and conventional halogen curing lights for orthodontic bonding.

The purpose of this clinical trial was to evaluate the reliability and time saved with a plasma arc curing unit (Apollo 95E, Dental/Medical Diagnostic Systems, Woodland Hills, Calif) compared with a conventional curing unit (Ortholux XL 3000, 3M Unitek, St Paul, Minn) for direct bracket bonding with resin adhesive. Forty-five patients were involved in the study, and 608 brackets were bonded in a contralateral quadrant pattern. The patients were followed for a mean (+/- standard deviation) period of 11 +/- 3.2 months. Survival analysis was carried out to compare the failure rate for the 2 techniques. The time required for bonding with each technique was also recorded. The mean survival time was 399 days, and there were no significant differences in survival time between the 2 bonding methods. Twelve bonding failures were reported with each technique. The curing time per bracket was significantly reduced with the plasma curing light compared with a conventional curing unit (65 +/- 19 vs 82 +/- 31 seconds). The plasma arc curing light can save chair-time without affecting the bonding failure rate.