Onset of spinal block is more rapid with isobaric than hyperbaric bupivacaine

PURPOSE: To compare isobaric with hyperbaric 9.75 mg bupivacaine injected intrathecally, and to evaluate the effects of subsequent injection of lidocaine 2% into the epidural space. METHODS: Patients in group 1 (n = 30) received isobaric 9.75 mg bupivacaine and in group 2 (n = 30) hyperbaric 9.75 mg bupivacaine injected into the subarachnoid space in a combined spinal-epidural technique. They were undergoing urological, gynecological, orthopedic, gastro-intestinal or vascular surgery. Using a double blind technique, the followings parameters were measured: cutaneous analgesia to pinprick, motor blockade, time for two segment regression, time for complete regression of the motor block, quality of anesthesia. In 12 patients the effect of epidural injections of 3 ml lidocaine 2% was observed. RESULTS: Motor and sensory block developed more rapidly (five minutes) in the isobaric group (P<0.05). Maximum upper level (T7+/-2), two-segment regression (52 min in both groups), motor recovery (160 vs. 157 min), and quality of anesthesia did not differ between the two groups. Thirty nine epidural injections of 3 ml lidocaine 2% were given in 12 patients 10 min after spinal injection, 28 were in the hyperbaric group (P<0.05). Twenty six of the epidural injections produced an increase in sensory block of 0 or 1 dermatome, and 13, of 2 or more. CONCLUSION: The block developed more rapidly in the isobaric group, but both isobaric and hyperbaric 9.75 mg bupivacaine produced adequate upper levels of analgesia for surgery. The effect of epidural injections of 3 ml lidocaine 2% was usually minimal.     

Site-directed mutagenesis of the putative human muscarinic M2 receptor binding site.

Experimental probing of the model of the muscarinic M₂ receptor binding site proposed by Hibert et al. [Hibert, M.F., Trumpp-Kallmeyer, S., Bruinsvels, A., Hoflak, K., 1991. Three-dimensional models of neurotransmitter G-binding protein-coupled receptors. Mol. Pharmacol. 40, 8–15.] was achieved by mutating each amino-acid proposed to interact with muscarinic ligands. Pharmacological analysis of the different mutant receptors transiently expressed in human embryonic kidney (HEK/293) cells was performed with a variety of agonists and antagonists. D103A, Y403A and N404A mutations prevented binding of [³H] N-methylscopolamine and [³H] quinuclidinyl benzilate with a reduction in affinity greater than 100-fold, indicating essential contributions of these residues to the binding site for the radioligands. W400A and W155A mutations had very large effects on the binding of [³H] N-methylscopolamine (150-fold, 960-fold) but modest effects on the binding of [³H] quinuclidinyl benzilate (4-fold, 17-fold). In addition, binding of oxotremorine-M, oxotremorine, arecoline and pilocarpine to W155A resulted in a greater than 100-fold decrease in affinity. Threonine mutations (T187A and T190A) alter binding of most agonists but not of antagonists. W99 makes little contribution (<10-fold) to the binding site of the M₂ receptor. D103, W155, W400, Y403 and N404 are likely to be part of the binding site for N-methylscopolamine and also to contribute to the binding site for quinuclidinyl benzilate. Some of the predicted residues do not seem to be part of the M₂ receptor binding site but W155 is important for proper ligand binding on the muscarinic M₂ receptor, as predicted by the proposed model.     

Inferential confusion,obsessive beliefs and obsessive–compulsive symptoms: a multidimensional investigation of cognitive domains

Generally, research into the relationship between cognitive domains and obsessive–compulsive symptoms involves the use of scales that are highly intercorrelated with each other. The current study investigates the relationship between cognitive constructs and obsessive–compulsive symptoms using the item set of the Obsessive Beliefs Questionnaire and the Inferential Confusion Questionnaire. In order to create constructs that would not be excessively correlated with each other, factor scores were used to investigate the relationship between cognitive domains and obsessive–compulsive symptoms. Factor analysis followed by oblique rotation resulted in four moderately correlated cognitive constructs (importance/control of thoughts, inferential confusion/threat estimation, perfectionism/certainty and responsibility for preventing harm). With the exception of responsibility for preventing harm, the cognitive constructs under investigation were quite strongly related to obsessive–compulsive symptoms. In particular, hierarchical regression revealed the construct inferential confusion/threat estimation to be a global and strong predictor of obsessive–compulsive symptoms, followed by the constructs of perfectionism/certainty and the construct importance/control. Responsibility for preventing harm acted to be a negative predictor of obsessive–compulsive symptoms. It is concluded that the construct of inferential confusion acts as a more powerful predictor of obsessive–compulsive symptoms than any specific obsessive belief Copyright © 2008 John Wiley & Sons, Ltd.     

Quantitative imaging of the structural changes of osteoarthritis: An exciting challenge for the new millennium

Conclusions The progression of structural changes, including cartilage degradation in knee OA, over time is an extremely important parameter that must not be overlooked in the study of therapeutic interventions for this disease. Existing radiologic methods used to evaluate the disease progression are useful and allow for several clinical trials to take place. However, these methods are imperfect and time consuming. A faster and more accurate method to evaluate the efficacy of various medications on the progression of OA is required. Current tools lack sensitivity to change over short periods of observation (plain and standardized radiographs) or are invasive (arthroscopy). Due to its greater sensitivity to change, evaluation by MRI is promising and appears to surpass the other available technologies in measuring the structural changes of knee OA, including the gradual loss of cartilage. The development of the new software tool will allow for the MRI technology to provide quantitative measurement, and the evaluation of the efficacy of new therapeutic interventions in a more accurate and rapid fashion, dramatically changing the way knee OA clinical trials are conducted. Studies will be performed in a time-wise fashion, allowing for the testing of a larger number of molecules having the potential to retard or stop progression of the disease.     

Transluminal angioplasty of failing infrainguinal arterial by-pass grafts: Initial and long-term results in 13 patients

Thirteen stenotic infrainguinal arterial bypasses (12 venous, 1 Gore-tex graft) were treated by transluminal angioplasty, either percutaneously (10 patients) or surgically (3 patients). Eleven procedures were immediately successful (two at the proximal portions of femoropopliteal grafts, six near the distal anastomoses, and three at the distal parts of femoroinfrapopliteal grafts) and dilated stenoses are still patent with a mean duration of 24 months in all patients except 2 who died during the follow-up period. The calculated cumulative patency rate is 85% at 36 months. Two procedures were followed by immediate disruption near the distal end of anin situ saphenous bypass graft where balloon inflation was performed. These required immediate surgical repair. Dilatation of the distal ends ofin situ saphenous femoropopliteal bypasses may not be as safe as in other locations.     

Hypothyroid neuropathy

Two cases of polyneuropathy in patients with hypothyroidism are reported. In both cases, the polyneuropathy involved the lower limbs and was predominantly distal. It was sensorimotor in the first patient and purely sensory in the second one. Electrophysiological findings were consistent with an axonopathy. Symptoms and electrophysiological parameters improved with thyroid therapy. Neuropathy in such cases is probably related to the duration of hypothyroidism.     

Is the mechanisms of fipronil-induced thyroid disruption specific of the rat: Re-evaluation of fipronil thyroid toxicity in sheep?

In rat, fipronil treatment increases the elimination of thyroid hormones (TH). Relevance of this mechanism for the risk of fipronil for human health is subject to controversy because of the specificities of adult rat for TH plasma binding properties which often lead to the assumption that rats are more sensitive than human to thyroid disruption. This study aimed at determining if the mechanism of fipronil-induced thyroid disruption is altered in sheep a species more relevant to human from the standpoint of TH plasma binding. TSH, total triiodothyronine and free and total tetra-iodothyronine 24 h secretory profiles were not modified by fipronil treatment (5 mg/kg every 4 days per os) in rams. In euthyroid-like thyroidectomised ewes, the effect of this treatment was limited to a moderate increase in free T4 clearance. In contrast with the rat, fipronil treatment (0.5 mg/kg/day, IV for 14 days) had no effect on antipyrine clearance, a marker for hepatic cytochrome activity, in ewes. The differences between rat and sheep for the potential of fipronil as a thyroid disruptor might be related to the difference in the exposure to the toxicant, the actual exposure to the sulfone metabolite of fipronil being lower in sheep than in rat.     

Climate associated size and shape changes in Aedes aegypti (Diptera: Culicidae) populations from Thailand

In spite of the adult body size variability of Aedes aegypti (Linnaeus) and its likely association with life history and vectorial capacity, the causes of size variation itself have been only partially identified. In particular, possible important factors such as climatic variation have not received much attention.The objective of this 2-year study was to describe from field collections the relationship of Ae. aegypti metric properties with available climatic data. The study took place in a dengue hyperendemic area of Thailand. Fourth instar larvae (L₄) and pupae were collected from the same breeding places allowing the comparisons between seven successive collections, four in 2007 and three in 2008. Climatic data were relative humidity (RH) and temperature (T). They were considered for the periods covering either the pre-imaginal development or, assuming heritability of size, the previous generation. The pre-imaginal period was further subdivided into embryonic and larval phases of development. Size was estimated by traditional and geometric techniques, the latter based on 18 landmarks collected at the intersections of veins also allowing estimation of shape.The shape variation of the wing followed similar patterns as for size and was shown to be a passive allometric change. No significant correlation of size or shape could be disclosed with T. In contrast, significant correlation with RH was found during two periods of examination: (i) the period affecting the generation previous to the time of collection, suggesting possible selective mechanisms on genitors, and (ii) the one occurring during pre-imaginal development. The subdivision of the latter into embryonic and larval phases allowed to evidence a possible selecting effect on embryonic development. The selection would act through the resistance to water loss which is known to depend on the relative surface of the cuticle.In conclusion, our data highlight the importance of the emerged period of Ae. aegypti eggs as a critical time for the size of future adults, and point to the relative humidity as the likely selecting factor.