Risk of Clostridium difficile-associated disease among patients receiving proton-pump inhibitors in a Quebec medical intensive care unit.

Our study was conducted to determine whether use of gastric acid-suppressive agents increased the risk of Clostridium difficile-associated disease (CDAD) in a medical intensive care unit of one of the first hospitals to be threatened by the current CDAD epidemic in Quebec, Canada. Our findings suggest that efforts to determine risk factors for CDAD should focus on other areas, such as older age and antibiotic use.     

Effects of nabilone, a synthetic cannabinoid, on postoperative pain

PURPOSE: Cannabinoids have been shown to have analgesic properties in animal studies, but a potential role for these drugs in acute pain management has not been established. It was hypothesized that nabilone, an oral cannabinoid synthetic tetrahydrocannabinol analogue, decreases morphine consumption, pain scores, nausea and vomiting following major surgery. METHODS: A double-blind, randomized, placebo-controlled, parallel-group pilot trial compared the effects of two different doses, 1 mg (n = 11) and 2 mg (n = 9) of nabilone, ketoprofen 50 mg (n = 11) or placebo (n = 10), given at eight-hour intervals for 24 hr. Outcomes included morphine consumption, pain scores and emesis after major surgery. Secondary outcomes included patient tolerability of the study medication. RESULTS: Forty-one patients (mean age 52 +/- 2 yr) undergoing gynecologic (46%), orthopedic (44%), or other (10%) surgery were recruited. Cumulative 24-hr morphine consumption was not different between the four groups, but pain scores at rest and on movement were significantly higher in the 2 mg nabilone group compared to the other groups. There were no significant differences between groups with respect to episodes of nausea and vomiting, quality of sleep, sedation, euphoria, pruritus, or the number and severity of adverse events. No serious adverse event was recorded. CONCLUSIONS: Contrary to the main hypothesis, high dose nabilone in the presence of morphine patient controlled analgesia is associated with an increase in pain scores in patients undergoing major surgery.     

Enrichment of glutamate in zinc-containing terminals of the cat visual cortex.

The presence of glutamate and GABA was examined in zinc-containing terminals of the cat visual cortex using a post-embedding immunogold method. The surface density of immunogold-labelling was also evaluated in morphologically defined ultrastructural elements, namely terminals having round synaptic vesicles and making asymmetrical synapses (RA boutons), terminals with flat vesicles and symmetrical synapses (FS) and glial cell processes. Glutamate immunoreactivity was highest in RA terminals and in zinc-containing boutons. It was lower in FS terminals and lowest in glial cell processes. GABA immunoreactivity was highest in FS terminals and low in all other ultrastructural elements analysed, including zinc-containing terminals. Therefore, zinc-containing terminals show an enrichment of glutamate and they are likely to use this amino acid as their neurotransmitter. Moreover, the fact that many RA terminals that are negative for zinc show an enrichment of immunoreactive glutamate suggests that zinc-containing fibres represent a subpopulation of the glutamate axonal network.     

Numerical data on neocortical neurons in adult rat, with special reference to the GABA population

The disector method was used to estimate the numerical density of neurons (number per unit volume) and their actual number per column (number under a given area of pial surface), in the occipital (monocular segment of the primary visual area, Oc1M), the parietal (somatosensory barrelfield area, Par1) and the frontal cortex (primary motor area, Fr1) of adult rat. Values were first obtained for all neurons in each layer, and then for GABA neurons as identified with postembedding immunocytochemistry on semithin sections. The numerical density of neurons in the frontal cortex (34,000/mm³) was significantly lower than in the two other neocortical areas (occipital: 52,000; parietal: 48,000/mm³). The GABA population showed a similar difference and consequently represented an equivalent proportion of total (15%) in the three cortical areas. Across layers, there was an alternate distribution of low and high density of neurons from layers II–III to VI in the three cortical areas, with the highest density in layer IV of the two sensory areas. The laminar changes in density of the GABA neurons were not as pronounced as those of the overall population. Consequently, the layers with the highest overall neuronal densities tended to have a lower proportion of GABA neurons and vice versa. There were more neurons under 1 mm² of surface in the parietal (90,000) than the occipital or the frontal cortex (71,000), which was also true of the GABA neurons. The greater number of neurons per column in the parietal cortex was mostly imputable to layer IV, the main recipient of thalamic axons. Comparing these values from the rat with those previously obtained in cat and monkey, it seemed that the number of neurons per cortical column was the highest in the sensory area preferentially used by each species.     

Frameshift mutation in the survival motor neuron gene in a severe case of SMA type I

Recently, a spinal muscular atrophy (SMA) determining gene, termed survival motor neuron (SMN) gene, has been isolated from the 5q13 region and found deleted in most patients. A highly homologous copy of this gene has also been isolated and located in a centromeric position. We have analyzed 158 patients (SMA types I-IV) and found deletions of SMN exon 7 in 96.8%. Mutations other than gross deletions seem to be extremely rare. In one of the undeleted SMA type I patients, a newborn who survived for only 42 days, we detected a maternally inherited 5 bp microdeletion in exon 3, resulting in a premature stop codon. By RT-PCR and long range PCR amplification we were able to show that the deletion belongs to the SMN gene, rather than to the centromeric copy, and that the proposita had no paternal SMN gene. Analysis of the neuronal apoptosis inhibitor protein (NAIP) gene, which maps close to SMN and has been proposed as a SMA modifying gene, suggests the presence of at least one full-length copy. Haplotype analysis of closely linked polymorphic markers suggests that the proposita also lacks the maternally derived copy of the centromeric homologue of SMN supporting the hypothesis that the severity of the phenotype might depend on the reduced number of centromeric genes in addition to the frameshift mutation.      

Tridimensional structure of the Golgi apparatus in type A ganglion cells of the rat

The three-dimensional structure of the whole Golgi apparatus and of its components in type A ganglion cells was examined in thin and thick sections by low- and high-voltage electron microscopy. At low magnification, in 10-μm-thick sections of osmicated cells, the Golgi apparatus formed a broad, continuous perinuclear network. At higher magnification and in thinner sections of cells impregnated with uranyl acetate-lead-copper citrate or postfixed in K-ferrocyanide-reduced osmium, the Golgi apparatus appeared as a heterogeneous structure in which saccular regions characterized by stacks of saccules alternated with intersaccular regions made up of branching membranous tubules which bridged the saccules of adjacent stacks. The saccular regions consisted of the following superimposed elements: (1) a cis-osmiophilic element made up of anastomosing tubules; (2) two or three saccules negative for the phosphatases tested (i.e., nicotinamide adenine dinucleotide phosphatase = NADPase, thiamine pyrophosphatase = TPPase, and cytidine monophosphatase = CMPase); (3) two saccules showing TPPase activity; and (4) one to three trans-sacculotubular elements showing a “peeling-off” configuration, one of which showed CMPase activity. The saccules (phosphatase-negative) on the cis-side of the Golgi stacks showed, in addition to small circular pores, larger perforations in register. The cavities thus formed in the stacks of saccules, called “wells,” always associated with small 80-nm vesicles, had a pan shape with the mouth directed toward the cis-face and the bottom closed by a TPPase-positive saccule. In face views of the saccules, the smallest of these perforations showed either a crescent shape, due to the presence of a bud on one side of the perforation, or a circular shape with a single small 80-nm vesicle in the center which was occasionally attached to the saccule by a filiform stalk. Such smaller cavities were considered as the precursors of the larger perforations and eventually of the wells. The small 80-nm vesicles seen in the small cavities or in the wells appeared to form in situ and possibly migrate toward the cisternae of endoplasmic reticulum seen proximal to the cis-face of the stack of saccules. Small 80-nm vesicles were also numerous in the intersaccular regions, along the lateral- and trans-aspects of the Golgi stacks, while larger, 150-to 300-nm vesicles, coated and uncoated, were seen only on the trans-face of the Golgi stacks in proximity to the trans-sacculotubular elements which appear to “peel off” from the Golgi stacks.     

SMN gene analysis of the spinal form of Charcot-Marie-Tooth disease.

The spinal form of Charcot-Marie-Tooth disease (spinal CMT) is a rare genetic disorder of the peripheral nervous system, the genetic basis of which remains unknown. To test the hypothesis that a defect of survival motor neuron (SMN), the determining gene for spinal muscular atrophy (SMA), would result in spinal CMT, 18 unrelated spinal CMT patients were studied. Nine of them were sporadic cases and the other nine belonged to unrelated autosomal dominant pedigrees. None of the 18 patients showed deletions involving SMN exons 7 or 8, the most frequent gene alteration found in SMA. In addition, haplotype analysis in two large autosomal dominant pedigrees showed that the 5q13 locus was not segregating with the spinal CMT locus. Therefore, neither the sporadic nor the familial cases of spinal CMT are associated with a SMN gene deletion, nor are the familial cases linked to the 5q13 region, indicating that this neuropathy is genetically different from SMA.     

Degeneration of germ cells in normal,hypophysectomized and hormone treated hypophysectomized rats

In normal adult rats some germ cells degenerate at several vulnerable steps of spermatogenesis. These are the type A spermatogonia, midpachytene spermatocytes, primary and secondary spermatocytes which degenerate during their respective maturation divisions and step 7 and 19 spermatids. In the present study, these degenerating cells were examined under the electron microscope, and their frequency was determined in toluidine blue stained semithin sections of testes from normal, hypophysectomized (at 5.5 days after operation) and hypophysectomized rats injected with FSH and LH separately or in combination. With the exception of the step 19 spermatids, the degenerating germ cells underwent necrosis in vacuolated spaces delimited by Sertoli cells. In the case of the affected step 19 spermatids, an apical cytoplasmic process of the Sertoli cell initially ensheathed a long segment of their flagellum, and then each degenerating cell was drawn deep in the seminiferous epithelium where it was phagocytozed by the Sertoli cell. Soon after hypophysectomy the incidence of degenerating mid-pachytene spermatocytes, step 7 and 19 spermatids which are present in stages VII or VIII of the cycle of the seminiferous epithelium, increased significantly. In contrast the number of degenerating primary or secondary spermatocytes during the meiotic divisions seen in stage XIV of the cycle or of any other germinal cell was not significantly modified. While the injection of FSH alone had no influence on the number of degenerating cells in hypophysectomized rats, injections of LH at the two doses administered (0.7 μg or 20 μg) reduced significantly the number of degenerating cells seen in stages VII-VIII of the cycle; combined injections of FSH and LH (20 μg) reduced the number of these degenerating cells to the normal low values. Thus it appeared that the mid-pachytene spermatocytes and the step 7 and 19 spermatids, all present in the adluminal compartment of the seminiferous epithelium in stages VII or VIII of the cycle, were more sensitive to the presence of absence of gonadotropic hormones than the other germ cells present in the seminiferous epithelium.