Experimental investigation on histocompatibility of bovine collagen in rat tongue.

Authors injected a 1.5-2 cc Gax-Collagen into the tongue of 13 rats in order to examine the reactivity of the tissues around the graft and its attitude and duration. The research had practical purposes as the material is mainly used in E.N.T. for reconstructing the vocal cords. The animals have been sacrificed from 1 day to 9 months and the tongue subjected to the ordinary histologic methods. Our conclusions are as follows: a) a moderate inflammatory reaction following the introduction of the foreign body, then it attenuates and disappears at the third month; b) the implant is well tolerated, does not cause structural alterations in the surrounding tissues, in particular in the musculature where it is placed; c) a neovascularization appears, it lessens over the time, keeping itself only at the edge of the graft; d) in the formed fissures, fibroblasts, traces of collagen and neocollagen are present. All these conditions allow for taking root and the persistence of the implant. It is remarkable that the spherical form of the Gax-Collagen does not modify even if it has been implanted into a muscular organ and therefore subjected to severe and continuous mechanical stress.     

Inhibition of angiotensin converting enzyme by ramipril in serum and tissue of man.

Studies in animal models have indicated that ramipril is a potent inhibitor of angiotensin converting enzyme (ACE) in serum and tissue. In our study, the normal range of ACE activity and the inhibitory effect of short-term oral administration of ramipril on ACE activity in human serum and tissue samples of renal cortex, heart and blood vessels were determined. ACE activity in the renal cortex (125.2 +/- 11.5 nmol/mg per min) was greater than 600 times that of the heart (0.20 +/- 0.01 nmol/mg per min), greater than 500 times that of the veins (0.23 +/- 0.09 nmol/mg per min) and greater than 150 times that of the arteries (0.80 +/- 0.23 nmol/mg per min). ACE activity in the renal cortex and arteries 2 h after last dosing was almost completely inhibited by ramipril whereas ACE activity in the veins and heart was inhibited to a lesser extent. Our results demonstrate in man, for the first time, an inhibition of tissue ACE following short-term oral treatment with an ACE inhibitor.     

The imprecision of stereopsis

In comparison to lateral judgments of distance, stereoscopic judgments are not precise. Although stereoacuity thresholds for targets presented in the fixation plane can equal the best thresholds for the monocular hyperacuities, i.e. a few sec arc, the increment thresholds for disparity are substantially larger than the increment thresholds for lateral separation (width). We measured the minimum detectable change in the three-dimensional distance separating two features, one presented in the fixation plane, and the other some distance in front of it, i.e. with a significant standing disparity between the two features. For briefly-presented targets (150 msec), the Weber fraction for disparity was 10-20% over the range from 1 to 20 min arc, while the Weber fraction for width was only 2-3% under comparable conditions. The disparity thresholds were substantially improved for a longer duration target (1000 msec), but they were still a factor of two worse than the monocular width thresholds. In a related experiment, the vernier acuity for a standard vernier target was profoundly degraded by pairing the offset upper line presented to one eye with a disparate line in the other eye; the vernier threshold was elevated for disparities ranging from 3 to 30 min arc. This finding shows that the more precise monocular signals are actively suppressed in fused or partially-fused stereoscopic images.     

Corticosteroids reduce regenerative repair of epithelium in experimental gastric ulcers.

The association between corticosteroid treatment and gastric ulcer healing is controversial. The effects of corticosteroids on experimental ulcer healing in the rat were studied and the effect of coadministration of a prostaglandin E1 analogue was determined. Forty male adult rats were divided into five groups and pretreated for 10 days as follows: (a) control, (b) prednisolone (10 mg/kg), (c) prednisolone and misoprostol (300 micrograms/kg), (d) misoprostol, and (e) indomethacin (2 mg/kg) Gastric ulcer was induced by applying a cryoprobe to the serosal surface of the stomach. Healing was assessed by determining the ulcer size at three and six days. Mucosal regenerative activity at the ulcer edge was assessed by quantitating DNA synthesis in cells by immunohistochemical techniques using monoclonal antibodies to detect expression of proliferating cell nuclear antigen (PCNA) and incorporated 5-bromo-5-iododeoxyuridine (BrdU). Compared with control rats, the rate of healing and the mucosal regenerative activity were significantly reduced in rats treated with prednisolone and indomethacin (p < 0.05). Coadministration of misoprostol and corticosteroids reversed the delay in healing and the reduction in mucosal regeneration induced by corticosteroids alone. With misoprostol alone, the ulcer size and the number of epithelial cells that actively synthesised DNA did not differ from control animals. A comparison between the two immunohistochemical markers of cell proliferation showed a highly significant correlation between the two techniques (r = 0.64, p < 0.005), indicating that the simpler PCNA technique should prove valuable in assessing regeneration in experimental ulcer disease.     

Surveillance for stage I non-seminomatous germ cell tumours of the testis: the optimal protocol has not yet been defined

Forty-six patients with clinical stage I testicular non-seminomatous germ cell tumours were followed up according to a protocol of active surveillance between 1979 and 1987. The median follow-up time was 40+ months. Thirteen patients (28%) relapsed, predominantly in retroperitoneum and/or lung. Ten of these relapses (76%) occurred within 8 months of orchiectomy. Relapses occurred in 7/35 T1 tumours and 5/10 T2 to T4 tumours. No correlation was detected between the histological type and relapse rate. Three late relapses were diagnosed at 23, 29 and 36 months. Eleven of the relapsed patients remain in prolonged complete remission after PVB chemotherapy +/- surgery; one patient, who initially refused treatment at the time of relapse, has died. Another relapsed with predominant elements of rhabdomyosarcoma intermingled with malignant teratoma in a bone metastasis. He had a partial response to PVB chemotherapy but subsequently died. Thirty-four patients (74%) did not undergo lymphography (LG) and had a higher relapse rate (11/34) than those who had LG (2/12); this was not a statistically significant difference in this small series. The policy of active surveillance is not yet the "state of the art" and should be under constant scrutiny with respect to safety and practice.     

The application of trend surface models to the analysis of time factors in Swiss cancer mortality

To study different temporal components on cancer mortality (age, period and cohort) methods of graphic representation were applied to Swiss mortality data from 1950 to 1984. Maps using continuous slopes ("contour maps") and based on eight tones of grey according to the absolute distribution of rates were used to represent the surfaces defined by the matrix of various age-specific rates. Further, progressively more complex regression surface equations were defined, on the basis of two independent variables (age/cohort) and a dependent one (each age-specific mortality rate). General patterns of trends in cancer mortality were thus identified, permitting definition of important cohort (e.g., upwards for lung and other tobacco-related neoplasms, or downwards for stomach) or period (e.g., downwards for intestines or thyroid cancers) effects, besides the major underlying age component. For most cancer sites, even the lower order (1st to 3rd) models utilised provided excellent fitting, allowing immediate identification of the residuals (e.g., high or low mortality points) as well as estimates of first-order interactions between the three factors, although the parameters of the main effects remained still undetermined. Thus, the method should be essentially used as summary guide to illustrate and understand the general patterns of age, period and cohort effects in (cancer) mortality, although they cannot conceptually solve the inherent problem of identifiability of the three components.     

"Weber's law" for position: unconfounding the role of separation and eccentricity

Bisection thresholds are approximately proportional to the separation/eccentricity of the targets. This "Weber's law" for position has been invoked over the past century. It is the separation of the reference targets, or their eccentricity which determines the threshold? In previous studies separation and eccentricity are confounded. In the present report we have pitted separation against eccentricity. Bisection thresholds were measured for stimuli presented on an isoeccentric arc, so that separation could be varied while holding the eccentricity of the test lines constant. We used a 5-fold range of separations from 2-10 deg. In this regime, the present results provide strong evidence against Weber's law. When separation is varied but eccentricity held constant, there is no Weber's law. Rather the thresholds are approximately constant. Our results suggest that the judgement of the separation of widely separated objects is similar to a distance measurement using a ruler on the cortex, in that the error of measurement is independent of the separation between objects. The results imply that when we attempt to gauge the distance between widely separated objects it is unlikely that we do so on the basis of the outputs of large spatial filters; rather it appears that we make such judgements by estimating the cortical distance which separates the targets of interest.     

Genetic testing for hearing loss: different motivations for the same outcome

Autism is a complex genetic disorder. Chromosome 15 is of particular interest in this disorder, because of previous reports of individuals with autism with chromosomal abnormalities in the 15q11-q13 region. Transmission disequilibrium between polymorphisms in this region and autism has been also been reported in some, but not all studies. Recently, a novel maternally expressed gene, ATP10C, was characterized and mapped to the chromosome 15q11-q13 region, 200 kb distal to UBE3A. It encodes a putative aminophospholipid translocase likely to be involved in the asymmetric distribution of proteins in the cell membrane. Preferential maternal expression has been demonstrated in fibroblasts and brain. Because of its physical location and imprinting pattern, ATP10C was considered to be a candidate gene for chromosome 15-associated autism. In an effort to find the genes responsible for autism in this chromosomal region, 1.5 kb of the 5' flanking region, as well as the coding and splicing regions of ATP10C, were screened for sequence variants. Several polymorphic markers including five nonsynonymous SNPs were identified. To investigate transmission disequilibrium between ATP10C and autism, a family-based association study was conducted for 14 markers in 115 autism trios. No significant transmission disequilibrium was found, suggesting ATP10C is unlikely to contribute strongly to susceptibility to autism in these families. However, due to limited power to detect genes of modest effect, the possible functional role of the nonsynonymous SNPs and the functional implications of the SNPs identified from 5' flanking region and intron 2 splicing region may be evaluated in further studies.     

Role of the alveolar macrophage in host defense and immunity to Legionella micdadei pneumonia in the guinea pig

Guinea pigs develop a lethal pneumonia after intratracheal infection with Legionella micdadei, and the lung displays pathological changes similar to those observed in humans. To investigate the role of the resident alveolar macrophage in the pathogenesis of L. micdadei pneumonia, guinea pig alveolar macrophages obtained by bronchoalveolar lavage were cultured in vitro and infected with L. micdadei. In the absence of opsonins L. micdadei was phagocytized by, and multiplied within, alveolar macrophages with greater than a 100-fold increase in cell-associated colony forming units over 20 h. L. micdadei opsonized with complement or antibody multiplied within alveolar macrophages at the same rate as unopsonized bacteria. Guinea pigs which were treated with antimicrobials after infection with L. micdadei and recovered from the pneumonia were immune to challenge with an otherwise lethal inoculum of L. micdadei. However, the growth curve of both unopsonized and opsonized L. micdadei in the alveolar macrophages from immune animals was essentially identical to that in macrophages from susceptible animals. Thus, the resident alveolar macrophage is not capable of limiting the growth of Legionella. Rather, the alveolar macrophages appear to be the primary site of Legionella multiplication within the lung. Although alveolar macrophages may participate in other aspects of pulmonary immunity to the legionellae, these data indicate that the alveolar macrophage alone does not act as an effector cell in cell-mediated immunity to Legionella.     

The essential role of stimulus temporal patterning in enabling perceptual learning

Little is known about how temporal stimulus factors influence perceptual learning. Here we demonstrate an essential role of stimulus temporal patterning in enabling perceptual learning by showing that 'unlearnable' contrast and motion-direction discrimination (resulting from random interleaving of stimuli) can be readily learned when stimuli are practiced in a fixed temporal pattern. This temporal patterning does not facilitate learning by reducing stimulus uncertainty; further, learning enabled by temporal patterning can later generalize to randomly presented stimuli.