Functional magnetic resonance imaging evidence for binocular interactions in human visual cortex

Using functional magnetic resonance imaging (fMRI), we explored the binocular interactions occurring when subjects viewed dichoptically presented checkerboard stimuli. A flickering radial checkerboard was presented to each eye of the subject, while T2*-weighted images were acquired over the visual cortex with gradient-echo, echoplanar sequences. We compared responses in striate and extrastriate visual cortex under four conditions: both eyes were stimulated at the same time (binocular condition), each eye was stimulated in alternation (monocular condition) or first the one eye then the other eye was stimulated (left eye first - right eye trailing, or vice versa). The results indicate that only the striate area, in and near the calcarine fissure, shows significant differences for these stimulation conditions. These differences are not evident in more remote extrastriate or associational visual areas, although the BOLD response in the stimulation-rest comparison was robust. These results suggest that the effect could be related to inhibitory interactions across ocular dominance columns in striate visual cortex.     

Neuronal apoptosis in the dentate gyrus in humans with subarachnoid hemorrhage and cerebral hypoxia

Apoptosis of dentate granule cells is a typical feature of several animal models of disease. In 20 autopsy cases of subarachnoid hemorrhage (SAH) and global cerebral hypoxia caused by protracted shock or respiratory failure, we evaluated by light microscopy and in situ tailing whether this pattern of neuronal damage also occurs in humans. In subarachnoid hemorrhage, 4.0/mm2 (0-13.0/mm2) apoptotic neurons were observed in the dentate gyrus, in cerebral hypoxia 3.6/mm2 (0-19.9/mm2) (p>0.05), and in 10 aged-matched control cases dying rapidly from non-neurological diseases 0/mm2 (0-0/mm2) (median [range]) (p<0.001 versus SAH and hypoxia). Neuronal apoptosis in the dentate gyrus was most frequent, when death occurred later than 24 hours and less than 11 days after disease onset. Neuronal damage in the hippocampus was always necrotic. It was more severe in hypoxia than in SAH (median neuronal damage score 3 [range: 0-3] versus 0 [0-3], p<0.001). Apoptosis appears to be the predominant mechanism of death in dentate granule cells irrespective of the underlying disease, whereas neuronal death in the hippocampus generally is of necrotic morphology.     

Role of ventricular assist devices in the German heart allocation system

The Eurotransplant (ET) allocation algorithm, newly implemented in 2000, gives priority for heart transplantation (HTx) to patients with high urgency (HU) status, but now this status is rescinded upon ventricular assist device (VAD) implantation and only regained if severe complications occur during mechanical circulatory support (MCS). We studied the effects of this change on the patients in our institute who were waiting for HTx with MCS. The median duration of MCS until HTx in adult patients gradually increased from 3.1 months in 1994, reaching a peak of 16.7 months in 2000, and then gradually decreased to 6.0 months in 2003. Among the patients with VAD implantation as a bridge to HTx, two patients were on MCS for more than 1 year (the longest duration of MCS being 1.6 years) at the end of 1999, and this figure increased to nine patients and a maximum MCS duration of 3.7 years at the end of 2003. These data imply that the patients in whom a complication occurred in the early phase of MCS and who had overcome this complication underwent HTx early with HU status, and those who were stable during MCS waited a long time for HTx. Furthermore, the number of patients in the latter group is increasing. The new allocation algorithm imposes on patients with MCS waiting for HTx who are relatively young and free from complications and serious coexisting disease, very long-term MCS without an end to VAD bridging, which is almost equivalent to destination therapy. Part of this paper was presented at the 42nd JSAO Conference (Tokyo, October 5–7, 2004)     

β1-Adrenoceptor gene variations: a role in idiopathic dilated cardiomyopathy?

A substantial body of evidence suggests involvement of the human beta1-adrenoceptor (beta1-AR) gene in the pathophysiology of dilated cardiomyopathy (DCM), a severe heart disease of significant public health impact. Beta1-AR-mediated signal transduction is dramatically altered due to downregulation, resulting in an impairment of myocardial response. The important role of genetic factors in idiopathic dilated cardiomyopathy (IDCM) recently recognized, we analyzed this prime candidate gene for genetic variation in carefully selected patients and controls. In this preliminary study, 18 single nucleotide polymorphisms were observed, 17 of which were located in the N-terminal and C-terminal region of the coding exon, resulting in 7 amino acid exchanges: Ser-49-Gly, Ala-59-Ser, Gly-389-Arg, Arg-399-Cys, His-402-Arg, Thr-404-Ala, and Pro-418-Ala. These mutations resulted in 11 different beta1-AR genotypes. Importantly, the genotypes carrying the Ser-49-Gly mutation in the N-terminus of the molecule in a heterozygous or homozygous form were observed significantly more frequently in the group of IDCM patients. The present results may provide a clue on the molecular mechanisms involved in IDCM, and add moreover interesting information on nature, distribution, and evolutionary aspects of sequence variation in human adrenergic receptor genes.     

Loads applied tangential to a fingertip during an object restraint task can trigger short-latency as well as long-latency EMG responses in hand muscles

Electrical stimulation of the digital nerves can cause short- and long-latency increases in electromyographic activity (EMG) of the hand muscles, but mechanical stimulation of primarily tactile afferents in the digits generally evokes only a long-latency increase in EMG. To examine whether such stimuli can elicit short-latency reflex responses, we recorded EMG over the first dorsal interosseous muscle when subjects (n=13) used the tip of the right index finger to restrain a horizontally oriented plate from moving when very brisk tangential forces were applied in the distal direction. The plate was subjected to ramp-and-hold pulling loads at two intensities (a 1-N load applied at 32 N/s or a 2-N load applied at 64 N/s) at times unpredictable to the subjects (mean interval 2 s; trial duration 500 ms). The contact surface of the manipulandum was covered with rayon—a slippery material. For each load, EMG was averaged for 128 consecutive trials with reference to the ramp onset. In all subjects, an automatic increase in grip force was triggered by the loads applied at 32 N/s; the mean onset latency of the EMG response was 59.8±0.9 (mean ± SE) ms. In seven subjects (54%) this long-latency response was preceded by a weak short-latency excitation at 34.6±2.9 ms. With the loads applied at 64 N/s, the long-latency response occurred slightly earlier (58.9±1.7 ms) and, with one exception, all subjects generated a short-latency EMG response (34.9±1.3 ms). Despite the higher background grip force that subjects adopted during the stronger loads (4.9±0.3 N vs 2.5±0.2 N), the incidence of slips was higher—the manipulandum escaped from the grasp in 37±5% of trials with the 64 N/s ramps, but in only 18±4% with the 32-N/s ramps. The deformation of the fingertip caused by the tangential load, rather than incipient or overt slips, triggered the short-latency responses because such responses occurred even when the finger pad was fixed to the manipulandum with double-sided adhesive tape so that no slips occurred.     

Genetic variation in locomotor activity rhythm among populations ofLeptopilina heterotoma (Hymenoptera: Eucoilidae), a larval parasitoid ofDrosophila species

The locomotor activity rhythm ofLeptopilina heterotoma, a parasitoid insect ofDrosophila larvae, was investigated under laboratory conditions. Under LD 1212, the locomotor activity of females shows a clear rhythm which persists under continuous darkness (circadian rhythm). However, comparative study of five populations indicates that both the rate of activity and the profile of the rhythm vary according to the origin of females. The Mediterranean populations (Tunisia and Antibes) show two peaks of activity, at the beginning and at the end of the photophase, whereas more northern populations (Lyon and the Netherlands) are mostly active during the afternoon. Females originating from the area of Lyon have a very low level of activity. Reciprocal crosses (F₁ hybrids and backcrosses) between the French and the Tunisian strains demonstrated the genetic basis of these variations and the biparental inheritance of the trait. This genetic variability is interpreted as a consequence of selective pressures and suggests a local adaptation of natural populations in host foraging behavior. The selective factors which could act on the daily organization of parasitoid behaviors are discussed.     

Identification of high risk patients with severe, but asymptomatic aortic stenosis

Whether asymptomatic patients with severe aortic stenosis benefit from surgery remains unclear. We report our data recently published in the New England Journal of Medicine on the natural history of this disease and predictors of outcome.     

Enzyme-linked immunosorbent assay (ELISA) for antibodies to Clostridium difficile toxins in patients with pseudomembranous colitis and antibiotic-associated diarrhoea

Enzyme-linked immunosorbent assay (ELISA) was established with purified toxins from Clostridium difficile as antigene to measure antibody response in patiensts with pseudomembranous colitis (PMC) and prolonged antibiotic-associated diarrhoea (AAD). Positive ELISA titres were defined in a control population. Antibodies of IgG class against toxin B were demonstrated in 6/88 (7%) control sera and in 31/61 (51%) sera from 11/19 (58%) patients. Antibodies of IgA class were found in one patient while antibodies of IgM class were not demonstrated. ELISA antibodies against toxin A were not demonstrated. For comparison a neutralization test was performed and neutralizing antibodies to toxin B but not to toxin A were demonstrated in 10/61 (16%) sera from 4/19 (21%) patients and in none of the controls. ELISA was found to be a more sensitive assay than neutralization. ELISA antibodies were detected from the third week of the disease while neutralizing antibodies appeared after 5 weeks. Lack of an antibody response in ELISA seemed to correlate to a more severe colitis.     

Onset of action of pimecrolimus cream 1% in the treatment of atopic eczema in infants

BACKGROUND: Data on the efficacy of pimecrolimus cream 1% within the first days of treatment are scarce, as in previous studies, the first postbaseline assessment was performed only after 1 week. OBJECTIVE: We sought to investigate the onset of action of pimecrolimus cream 1% in infants with mild to very severe atopic eczema. METHODS: We used pimecrolimus cream 1% (n = 129) or vehicle cream (n = 66) administered in a double-blind manner for 4 weeks and then open-label pimecrolimus cream 1% for 12 weeks, with a 4-week follow-up period. RESULTS: Pimecrolimus cream 1% reduced the mean Eczema Area and Severity Index at 4 weeks by 71.5% compared with an increase of 19.4% with vehicle ( P < .001). The reduction in the Eczema Area and Severity Index with pimecrolimus cream 1% was significant at day 4 (38.5% vs 17.6% increase with vehicle). Significant improvements in caregivers' assessments of pruritus and sleep loss were observed with pimecrolimus cream 1% by day 2 ( P < .03) and day 3 ( P = .002), respectively, compared with vehicle. Responses to pimecrolimus cream 1% were sustained during the open-label phase, and pimecrolimus cream 1% was well tolerated. Symptoms of atopic eczema returned gradually after discontinuation. CONCLUSION: Pimecrolimus cream 1% was well tolerated and effective in patients with mild to very severe atopic eczema, with rapid onset of action and no disease rebound after discontinuation.     

Numerical and structural chromosomal abnormalities detected in human sperm with a combination of multicolor FISH assays

A pair of multicolor FISH assays (X-Y-21 and A-M-16) was developed for human sperm to simultaneously measure sex ratios; aneuploidies involving chromosomes 1, 16, 21, X, and Y; meiotic diploidies; and structural aberrations involving chromosome 1p. Sex ratios in sperm were not significantly different from unity among healthy men. Baseline frequencies of disomic sperm for chromosomes 1, 8, and 21 were similar (6.7 per 10(4) sperm, 95% CI of 5.6-8.1), suggesting that among these three chromosomes, chromosome 21 was not especially prone to nondisjunction. Frequencies of disomy 16 sperm were significantly lower, however (3.5 per 10(4) sperm, 95% CI of 2.0-6.2; P < 0.02). The baseline frequencies of sperm disomy by FISH for chromosomes 16 and 21 were validated against aneuploidy data obtained by the hamster-egg technique for human sperm cytogenetics. The frequencies of X-X, Y-Y, X-Y ("Klinefelter") sperm and sex-null ("Turner") sperm were 5.5, 5.1, 5.5, and 7.8 per 10(4) sperm, respectively. For chromosomes 16 and 21, the frequencies of nullisomic and disomic sperm were similar, suggesting that gain and loss events occurred symmetrically. However, more gain than loss was reported for chromosomes 1, X, and Y. The frequency of MI and MII diploid sperm (with flagella) was approximately 12 per 10(4) (range 8.3-16.7 per 10(4) sperm). Based on flagella data, the frequency of somatic cells in the semen was estimated to be approximately 1.8 per 10(4) sperm. Loss or gain of a portion of chromosome-arm 1p occurred in 5.5 per 10(4) sperm, and the percentage of sperm carrying structural aberrations within the haploid genome as calculated from FISH (1.4%), was similar to that obtained with the hamster-egg technique. These complementary sperm FISH assays have promising applications in studies of chromosomally abnormal sperm after exposure to occupational, medical, and environmental toxicants.