Simultaneous multiwavelength spectrophotometric quantitation of active components in analgesic formulations. Comparative study of three calculation methods

This work deals with the UV spectrophotometric quantitation of a mixture of compounds with overlapped spectra. The mixture spectrum is resolved by use of three computational programs based on different algorithms, namely Multicomponent Analysis (commercial software available from Hewlett-Packard), MULTIC (relying on multiple regression analysis) and SIMPLEX. The results obtained for mixtures of acetylsalicylic acid, acetaminophen and caffeine in commercial analgesic formulations, are compared.     

Development of novel dental cements. I. Formulation of aluminoborate glasses

Aluminoborate glasses were formulated as potential novel glass-ionomer cement components, and their reactivity with a polyalkenoic acid was assessed by means of working and setting time measurements. Of the 20 prepared formulations, some containing fluoride, eight were found to have acceptable manipulative characteristics, and three of these formed hard set materials.     

Steady-state pharmacokinetics of idebenone in patients with moderate renal impairment

Idebenone (45 mg twice daily) was administered to 7 patients with moderate renal impairment (creatinine clearance 21-40 ml/min) for 10 days. Standard pharmacokinetic parameters were computed on day 1 (single administration) and on day 10. On day 1 the mean of the maximum plasma concentration values (C(max)) was 364 ng/ml (standard deviation (S.D.) 100); time to C(max) (t(max)) was in the range of 1-2 h for 6 patients and 12 h for the remaining patient: the mean was 3 h (S.D. 3.99); the mean area under the plasma concentration vs. time curve (AUC) was 3005 ng h/ml (S.D. 1152). On day 10 the mean C(max) was 531 ng/ml (S.D. 355.3), the mean t(max) was 0.07 h (S.D. 0.19), the mean AUC was 3167 ng/ml (S.D. 2944) and the mean elimination half-life (t(1/2)) was 4.9 h (S.D. 1.1). Idebenone metabolites (QS-4, QS-6 and QS-10) showed a kinetic profile similar to the parent compound, with pharmacokinetic parameters comparable to idebenone for QS-4 and lower than idebenone for QS-6 and QS-10. Idebenone was metabolized and easily excreted and no accumulation was observed for the compound and its metabolites. No significant modification of the biohumoral indexes and vital signs and no adverse reactions were observed.     

Coronary occlusion secondary to blunt chest trauma: a first attempt at balloon angioplasty

There have been only 58 angiographically documented reports of transmural myocardial infarction due to closed-chest trauma. None of these cases has been treated by percutaneous transluminal coronary angioplasty. We report the case of a 40-year-old man who developed an anterior-wall myocardial infarction secondary to blunt chest trauma suffered in an automobile accident. Angiographic study performed 2 months after the injury revealed an isolated total obstruction of the left anterior descending coronary artery. The patient was judged a good candidate for balloon angioplasty, but total reocclusion occurred within 24 hours of the procedure and a 2nd attempt did not restore patency. Surgical revascularization was performed a week later. A year after his injury, the patient remains asymptomatic and is back at work. Despite the failure of percutaneous transluminal coronary angioplasty in its 1st application to coronary artery repair after blunt chest trauma, we believe it to be the treatment of choice in young patients and in single-vessel disease.     

Septicemias in cancer patients during parenteral nutrition: contributing factors and detection by weekly blood cultures

Infections constitute the main complication of parenteral nutrition, particularly in cancer patients, but prediction of catheter-related septicemias (CRS) has been little investigated. We have evaluated, in 200 consecutive episodes of parenteral nutrition (PN) in cancer patients, the factors contributing to infectious complications, and the predictive value of weekly blood cultures performed through the nutrition catheter. The median duration of PN was 22 days with a total of 5816 patient-days of PN, neutropenia (neutrophils < 1,000/mul) being present in 872 (15%). Catheters were placed either in a jugular vein (71% single-lumen silicone catheters, 18.5% double-lumen Hickman-Broviac catheters) or in a femoral vein (10.5%). We observed 62 episodes of septicemia of which 22 were CRS (11% incidence for the 200 cycles) and 40 were non-CRS (20% incidence); CRS were mostly due to Staphylococcus epidermidis (14 22 ). Neutropenic patients as a group did not suffer more CRS than non-neutropenic patients, but the risk of CRS was slightly increased when expressed per day of neutropenia (8 CRS/872 days vs 14 CRS/4942 days without neutropenia, P < 0.05). On the other hand, a femoral insertion site was associated with a much higher incidence of CRS (9 CRS/21 femoral catheters vs 13 CRS/179 jugular catheters, P < 0.0001). It was possible to evaluate 20 episodes of CRS for their predictability by weekly blood cultures: the sensitivity for detecting CRS due to Staphylococcus epidermidis was 67%, the specificity 92%, the negative predictive value 98% and the positive predictive value 36%. The simple and widely available procedure of routine surveillance blood cultures performed through the PN catheter should be further investigated, because it could help the clinician to determine the origin of recent fever, particularly to exclude CRS and avoid unnecessary removal of PN catheters.     

Prognostic ability of nutritional assessment methods in surgical cancer patients

To identify patients at high-risk for post-operative infections, several methods have been proposed, including prognostic nutritional index (PNI), instant nutritional assessment (INA) and nutritional assessment (NA). Weight loss (WL) has also been related to post-operative morbidity. We have evaluated the prognostic ability of PNI, INA, NA and WL in a prospective study carried out in 94 patients affected by gastro-intestinal malignancy, who underwent major surgery. Post-operative infections occurred in 26 (27.7%) patients. PNI, INA and NA identified classes of patients with a progressive risk of septic complications. To determine the prognostic ability of PNI, INA, NA and WL, sensitivity, specificity, Youden index and predictive values were evaluated. All methods had a Youden index greater than one, with a positive predictive value ranging from 0.33 to 0.36. Since all the methods studied showed a similar predictive ability, it seems reasonable to identify the high-risk surgical patient by using weight loss in association with those nutritional parameters derived from routine hospital laboratory tests.     

Trajectory of contact region on the fingerpad gives the illusion of haptic shape

When one explores a solid object with a fingertip, a contact region is usually defined. When the trajectory of this region on the fingerpad is artificially controlled so as to resemble the trajectory that is normally present while exploring a real object, the experience of shape is created. In order to generate appropriate local deformation trajectories, we built a servo-controlled mechanism that rolled a flat plate on the fingerpad during the manual exploration of virtual surfaces so that the plate was kept tangent to a virtual shape at the point of virtual contact. An experiment was then designed to test which mode of exploration maximized the shape information gain: active versus semi-active exploration, where semi-active exploration is when one hand touches passively and the other moves the target object, and the use of single versus multiple points of contact. We found that subjects were able to perform curvature discrimination at levels comparable to those achieved when using direct manual contact with real objects, and that the highly simplified stimulus provided by the device was a sufficient cue to give the illusion of touching three-dimensional surfaces.     

Periaqueductal grey CB1 cannabinoid and metabotropic glutamate subtype 5 receptors modulate changes in rostral ventromedial medulla neuronal activities induced by subcutaneous formalin in the rat

This study was undertaken to analyze the involvement of periaqueductal gray (PAG) cannabinoid or group I metabotropic glutamate receptors in the formalin-induced changes on the rostral ventromedial medulla (RVM) ON- and OFF-cells activities. S.c. injection of formalin into the hind paw produced a transient decrease (4-6 min) followed by a longer increase (25-35 min) in tail flick latencies. Formalin also increased basal activity in RVM ON-cells (42+/-7%) and decreased it in OFF-cells (35+/-4%). Intra-PAG microinjection of (R)-(+)-[2,3-dihydro-5-methyl-3-(4-morpholinylmethyl) pyrrolo[1,2,3-de]-1,4-benzoxazin-6-yl]-1-naphthalenylmethanone mesylate (WIN 55,212-2) (2 nmol/rat), a cannabinoid receptor agonist, prevented the formalin-induced changes in RVM cell activities. Higher dosages of WIN 55,212-2 (4-8 nmol/rat) increased the tail flick latencies, delayed the tail flick-related onset to ON-cell burst, and decreased the duration of OFF-cell pause. Furthermore, WIN 55,212-2 at a dosage of 8 nmol/rat decreased RVM ON-cell (57+/-7%) and increased OFF-cell ongoing activities (26+/-4%). These effects were prevented by N-piperidino-5-(4-chlorophenyl)-1-(2,4dichlorophenyl)-4-methyl-3-pyrazolecarboxamide SR141716A, (1 pmol/rat), a CB1 cannabinoid receptor antagonist, or by 2-methyl-6-(phenylethynyl)pyridine (MPEP 20 nmol/rat), a selective mGlu5 glutamate receptor antagonist. T7-(hydroxyimino) cyclopropa[b]chromen-1alpha-carboxylate ethyl ester (CPCOOE/50 nmol/rat) and (S)-(+)-alpha-amino-4-carboxy-2-methylbenzeneacetic acid (LY367385, 20 nmol/rat), selective mGlu1 glutamate receptor antagonists, were ineffective in preventing the WIN-induced effects. This study suggests that s.c. injection of formalin modifies RVM neuronal activities and this effect is prevented by PAG cannabinoid receptor stimulation. Moreover, the physiological stimulation of PAG mGlu5, but not mGlu1 glutamate receptors, seems to be required for the cannabinoid-mediated effect.