Pain in sciatica depresses lower limb nociceptive reflexes to sural nerve stimulation.

The inhibitory effects of acute pain produced by the Lasègue's manoeuvre on the lower limb nociceptive flexion reflexes induced by electrical sural nerve stimulation were explored in patients complaining of sciatica as a result of an identified unilateral disc protrusion. Lassègue's manoeuvre on the affected side produced a typical radicular pain and resulted in a powerful depression of nociceptive reflexes elicited either in the normal or in the affected lower limb. Simultaneously, patients reported relief of the electrically-induced pain. In contrast, painless Lasègue's manoeuvre on the normal side had no effect on these parameters.     

Group A Streptococcus invasive infections: a review

The incidence of group A Streptococcus (GAS) invasive infections has been increasing worldwide, and there is no obvious explanation for this phenomenon. In 1993, a working group on severe GAS infections was established to define accurately what constitutes an invasive infection. Three types of infection are particularly feared: necrotizing fasciitis, myositis and a newly defined entity, named streptococcal toxic shock syndrome (STSS) because of a certain analogy with its staphylococcal counterpart. GAS produces many toxins responsible for its clinical manifestations. Some of them, labelled streptococcal pyrogenic exotoxins, have been characterized as superantigens. These proteins play a key role in initiating the immune response to GAS and are mostly responsible for the precipitous course of invasive infections. Death rates are high in streptococcal invasive infections, ranging from about 20% for necrotizing fasciitis to almost 100% for myositis. Therapy consists mainly of high doses of antibiotic combinations, aggressive surgery, and intravenous administration of immunoglobulins for STSS.     

The effects of pulse configuration on magnetic stimulation.

A study is presented in which the authors have examined the effects of pulse configuration, stimulation intensity, and coil current direction during magnetic stimulation. Using figure-8 and circular coils, the median nerve was stimulated at the cubital fossa and at the wrist of 10 healthy volunteers, and the response amplitude and site of stimulation were determined. The key findings of this study are in agreement with other researchers' findings and confirm that biphasic stimulating pulses produce significantly higher M-wave amplitudes than monophasic stimulating pulses for the same stimulus intensity. Mean response amplitudes for biphasic stimuli applied by both coils at the elbow and wrist are consistently higher for the normal current direction. Mean response amplitudes for monophasic pulses are almost always higher for reversed currents. The site for effective stimulation (the position of the virtual cathode) cannot be defined within a fixed distance from the center of the coil (3 to 4 cm), as has been suggested by other researchers, but was found to vary depending on the coil current amplitude and direction as well as the degree of inhomogeneity of the tissues surrounding the nerve. There is a statistically significant relationship between virtual cathode shift and stimulus intensity for biphasic and monophasic pulses. Reversing the coil current direction has no statistically significant effect on the virtual cathode position. Virtual cathode shifts can be measured for biphasic and monophasic stimulations using a figure-8 coil at the wrist and the elbow. However, such a shift is difficult to determine with a circular coil.     

The metabolic fate of an oral 14C-alanine load in the obese Zucker rat.

Following an oral 14C-alanine load, obese Zucker rats showed the same rate of intestinal amino acid absorption as their lean counterparts. Alanine absorption was unchanged by a 24 h starvation period. The whole-body oxidation of the absorbed tracer was lower in the fa/fa rats and was significantly decreased in both lean and obese groups when the animals were submitted to starvation. The incorporation of the 14C-tracer into 14C-lipid was significantly higher in the carcass, skeletal muscle, white adipose tissue and liver of the obese animals, while that of brown adipose tissue was decreased as compared to that of the lean rats. Starvation induced no variation in 14C-lipid incorporation in the lean (+/?) animals while it sharply decreased this parameter in the obese. The incorporation of the tracer into 14C-glycogen and 14C-protein was also increased in the liver of the obese rats while no changes in incorporation into these fractions were observed in skeletal muscle. It is concluded that dietary amino acids significantly contribute to the hyperlipogenesis found in the liver and adipose tissue of the fa/fa rats.     

Cochlear implants, which one to choose?]

The choice of a cochlear implant is a difficult one. A given type of implant does not yet correspond to a given type of patient. Our indications have to be refined by acquired experience and through the improvement of tests prior to implanting. The implants available present different features, but they all improve the communication of the profoundly deaf to different degrees, by attenuating their tinnitus.     

Bromine-76 and carbon-11 labelled NNC 13-8199, metabolically stable benzodiazepine receptor agonists as radioligands for positron emission tomography (PET)

NNC 13-8241 has recently been labelled with iodine-123 and developed as a metabolically stable benzodiazepine receptor ligand for single-photon emission computed tomography (SPECT) in monkeys and man. NNC 13-8199 is a bromo-analogue of NNC 13-8241. This partial agonist binds selectively and with subnanomolar affinity to the benzodiazepine receptors. We prepared ⁷⁶Br labelled NNC 13-8199 from the trimethyltin precursor by the chloramine-T method. Carbon-11 labelled NNC 13-8199 was synthesised by N-alkylation of the nitrogen of the amide group with [¹¹C]methyl iodide. Positron emission tomography (PET) examination with the two radioligands in monkeys demonstrated a high uptake of radioactivity in the occipital, temporal and frontal cortex. In the study with [⁷⁶Br]NNC 13-8199, the monkey brain uptake continued to increase until the time of displacement with flumazenil at 215 min after injection. For both radioligands the radioactivity in the cortical brain regions was markedly reduced after displacement with flumazenil. More than 98% of the radioactivity in monkey plasma represented unchanged radioligand 40 min after injection. The low degree of metabolism indicates that NNC 13-8199 is metabolically much more stable than hitherto developed PET radioligands for imaging of benzodiazepine receptors in the primate brain. [⁷⁶Br]NNC 13-8199 has potential as a radioligand in human PET studies using models where a slow metabolism is an advantage. Received 19 April and in revised form 10 June 1997     

Acute psychotropic effects of bilateral subthalamic nucleus stimulation and levodopa in Parkinson's disease.

High-frequency deep brain stimulation (DBS) of the subthalamic nucleus (STN) improves the motor symptoms of Parkinson's disease (PD). Opposite changes in mood, such as mania or depression, have been reported after surgery, but it is not known whether these side effects are specifically related to STN DBS. To learn whether STN DBS also influences the limbic loop, we investigated acute subjective psychotropic effects related to levodopa or bilateral STN DBS. After a median postoperative follow-up of 12 months, 50 PD patients completed the Addiction Research Center Inventory (ARCI), assessing subjective psychotropic effects in four conditions: off-drug/on-stimulation; off-drug/off-stimulation; on-drug/off-stimulation; and on-drug/on-stimulation. Both levodopa and STN DBS improved all the ARCI subscales, indicating subjective feelings of well being, euphoria, increase in motivation, and decrease in fatigue, anxiety, and tension. A suprathreshold dose of levodopa was significantly more effective than STN DBS, using the same electrical parameters as for chronic stimulation, on four of the five ARCI subscales. We concluded that 1) both STN DBS and levodopa have synergistic acute beneficial psychotropic effects in PD, 2) the psychotropic effects of both treatments need to be considered in the long-term management of chronic STN DBS, and 3) the results indicate an involvement of the limbic STN in mood disorders of PD.     

A three step supercritical process to improve the dissolution rate of eflucimibe.

The aim of this study is to improve the dissolution properties of a poorly-soluble active substance, Eflucimibe by associating it with gamma-cyclodextrin. To achieve this objective, a new three-step process based on supercritical fluid technology has been proposed. First, Eflucimibe and cyclodextrin are co-crystallized using an anti-solvent process, dimethylsulfoxide being the solvent and supercritical carbon dioxide being the anti-solvent. Second, the co-crystallized powder is held in a static mode under supercritical conditions for several hours. This is the maturing step. Third, in a final stripping step, supercritical CO(2) is flowed through the matured powder to extract the residual solvent. The coupling of the first two steps brings about a significant synergistic effect to improve the dissolution rate of the drug. The nature of the entity obtained at the end of each step is discussed and some suggestions are made as to what happens in these operations. It is shown the co-crystallization ensures a good dispersion of both compounds and is rather insensitive to the operating parameters tested. The maturing step allows some dissolution-recrystallization to occur thus intensifying the intimate contact between the two compounds. Addition of water is necessary to make maturing effective as this is governed by the transfer properties of the medium. The stripping step allows extraction of the residual solvent but also removes some of the Eflucimibe which is the main drawback of this final stage.