Inverted duplication of 22pter----q11.21 in cat-eye syndrome.
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Biomedical subjects
Publications and source records attributed to A Robertson.
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Self-stimulation (SS) of both the medial prefrontal cortex (MPFC) and the dorsolateral hippocampus (HPC) is known to develop slowly, over a period of days. In both cases, the acquisition of bar-pressing can be markedly hastened by delivery of noncontingent electrical stimulation for several days prior to SS training. The similarity of these effects suggests that there might be a common substrate mediating the acquisition process. However, in the present experiment, pre-training noncontingent electrical stimulation of the MPFC had no effect on how rapidly rats acquired the bar-pressing response for HPC stimulation, or vice versa. A further dissociation of the elements governing the acquisition process for these two SS sites was suggested by the observation that pre-training noncontingent stimulation of the entorhinal cortex facilitated the speed of acquisition of SS of the HPC but not of the MPFC. It seems that the HPC and entorhinal cortex can be excluded from the subset of neural structures which are known to influence the acquisition process governing MPFC SS. These and other data suggest that the development of SS of the MPFC and HPC can be regarded, at least in part, as involving a process rooted in distinct substrates.
The effects of the atypical neuroleptics clozapine, thioridazine and sulpiride on behaviors induced by apomorphine were recorded, using a time-sampling observational paradigm. A low dose of apomorphine (0.1 mg/kg, SC) produced hypomotility. Of the neuroleptics tested, only sulpiride antagonized this hypomotility. Apomorphine in higher doses (0.2-1.0 mg/kg, SC) produced stereotyped behaviors (sniffing down and licking or gnawing). All three atypical neuroleptics antagonized stereotypy. The effects of sulpiride on apomorphine-induced hypomotility and stereotypy are consistent with the notion that this drug has strong presynaptic and weak postsynaptic blocking effects at dopamine receptors. The mechanisms of action of clozapine and thioridazine may be different from that of sulpiride. Perhaps the anticholinergic activities of these drugs mediate some of their behavioral effects. The effects of these atypical neuroleptics on apomorphine-induced stereotypy are opposite in direction to their effects on amphetamine-induced stereotypy, suggesting that these two behavioral patterns are not measures of the same neural process.
Rats were obtained at 21 days of age and were housed either in isolation or in groups of 4 for 6 weeks. They were then tested for their sensitivity to cocaine HCl (0.31, 0.62, 1.25 or 2.5 mg/kg) or d-amphetamine SO4 (0.031, 0.062, 0.125, 0.25 or 0.5 mg/kg) using a modified place preference paradigm. The isolated rats were insensitive to cocaine in this paradigm whereas the group-housed animals showed peak effects at the lowest dose of this drug. In contrast, there was no difference in sensitivity to amphetamine as a function of housing conditions. These data strengthen the notion that the effects of the early environment on drug sensitivity in the adult are specific to certain classes of drugs. Further, these data lend support to the notion that the effects of cocaine and amphetamine in the place preference paradigm are mediated by different neural systems.
Four experiments were performed to assess the nature of the contribution of the corticocortical projections between the prelimbic and sulcal divisions of the rat prefrontal cortex to self-stimulation (SS) of these sites. The first experiment showed that transection of these projections by parasagittal knife cuts or bilateral electrolytic lesions of the prelimbic cortex had no effect on SS of the sulcal cortex. The second experiment demonstrated that SS of the prelimbic cortex could be obtained after transection of the corticocortical projection path. The third experiment demonstrated that the deficit in prelimbic SS, seen to follow such bilateral transections, is a function of the amount of exposure to the stimulation given to the animals after the lesion. The fourth experiment showed that the stimulation-dependent process underlying the acquisition of prelimbic and sulcal SS could be dissociated by the knife cuts. The discussion focused on the implications of these findings for an account of prefrontal self-stimulation behavior.
The hypothesis that the anticholinergic properties of thioridazine can account for its ability to enhance amphetamine-induced stereotyped behaviors was tested. In one experiment, scopolamine-induced repetitive head movements were shown to be potentiated by thioridazine. In another experiment, subthreshold doses of scopolamine and thioridazine interacted to potentiate amphetamine-induced repetitive head movements. The data suggest that thioridazine, in addition to its neuroleptic activity, has significant anticholinergic effects in vivo and these effects may account for its potentiation of amphetamine-induced stereotypy.
The rate of acquisition of lever-pressing for electrical stimulation of the hippocampus (HPC) was compared in two strains of rat: barrier-sustained Wistar and Sprague-Dawley. Sprague-Dawley rats initially bar-pressed at very low rates and took a median of 11 days to self-stimulate, according to the criterion used. Wistar rats all reached the same criterion in the first test session. Differential sensitivity to the activating effects of stimulation as an explanation for this difference was ruled out by the observation that both strains decreased response rates at the same rate and to the same level if stimulation was made non-contingent on lever-pressing. Differential threshold for reward was ruled out by the observation that rate-intensity curves yielded the same threshold currents and peak rates in both strains. Finally, it was shown that the rate of development of kindled seizures in the two strains of rats is different: Wistars kindle to full seizures faster than do Sprague-Dawleys. The relationship between the quicker onset of self-stimulation and of kindled seizures in Wistars is discussed.
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The relation between dust exposure, retained lung dust, and pneumoconiosis have been examined in 430 dead coalminers who had participated in a large scale epidemiological survey of respiratory health. The men were divided into three groups depending on the presence of particular lesions in their lungs. Lungs containing no fibrotic lesions in excess of 1 mm were included in the "M" group, those with fibrotic lesions of between 1 mm and 9 mm in diameter were included in the "F" group, and those with any lesion 10 mm or more were categorised as having progressive massive fibrosis (PMF). The men were further divided into four groups according to the rank of coal mined at the colliery of employment. The mean weight of lung dust increased over the pathological range (M----F----PMF) regardless of the rank of coal mined. The men with PMF had not received unusually high exposures to dust in life but were found to have accumulated more dust in their lungs per unit of dust exposure than men without PMF, providing further evidence for differences in the patterns of deposition or clearance, or both, of dust in these men compared with those who do not develop PMF. For men who had mined the higher rank coals there was no difference in the composition of the lung dust between the pathological groups. Lungs from men mining low rank coal, however, showed a striking increase in the proportion of ash over the pathological groups (M, F, and PMF). In men who had mined low rank coal the proportion of ash in the airborne dust to which they had been exposed and in the dust retained in their lungs was, as expected, greater than in men who had worked with higher rank coals. For the same men, and particularly associated with the presence of some dust related fibrosis, the proportion of ash in retained dust was higher than that in the dust to which the men were exposed suggesting the occurrence of selective deposition or retention of the mineral components of dust in this group.
Bumetanide binding to human serum albumin was studied using ultrafiltration. The first stoichiometric binding constant for bumetanide is 6.4 X 10(4) M-1. Bumetanide competes with bilirubin for human serum albumin binding, having a KDispl (displacement constant) of 6.2 X 10(3) M-1 measured by the peroxidase method. This displacement effect is also observed using pooled umbilical cord serum and pooled adult serum employing a dialysis rate method. Bumetanide competes to a lesser degree with diazepam binding to human serum albumin. No competition with diazepam occurs using umbilical cord or adult serum. Pharmacologic concentrations of bumetanide would not significantly affect bilirubin-albumin binding and should not increase the risk of bilirubin encephalopathy in newborn infants.
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One hundred two patients with acute lower limb ischemia were treated with intra-arterial streptokinase. Thirty-seven patients had occluded vascular grafts and sixty-five had had no previous vascular surgery. Eighty-six limbs were acutely threatened. Intra-arterial streptokinase was given as an initial loading dose with a lower maintenance dose given afterward. The mean duration of therapy was 59 hours and hematologic monitoring was meticulous. Indications for intra-arterial streptokinase therapy were contraindication to surgery, anticipation of technically difficult surgery, and multiple occlusions that required separate surgical approaches. Seventy-two legs were saved (71%) and 30 amputated. Morbidity was low and only 1 of the 11 deaths was attributable to streptokinase. No leg was lost that would otherwise have been saved by straightforward surgery and no leg was lost that had not been previously threatened. In 46 patients for whom emergency femorotibial bypass would have been necessary, 35 legs (76%) were saved. Forty-three patients had vascular reconstruction immediately after streptokinase therapy was stopped, to bypass occlusive lesions that had been demonstrated by the thrombolytic therapy in 28 patients, and because streptokinase had produced no response in 15 patients. The advantages of intra-arterial streptokinase in the management of the acutely ischemic leg are that the leg may be saved without surgery, that surgery is not precluded, that the patient can be made as fit as possible for surgery during the streptokinase infusion, and that streptokinase can facilitate surgery by delineating underlying vascular pathologic conditions and clearing distal runoff vessels.
The effects of the atypical neuroleptic sulpiride (0-20 mg/kg s.c.) and the classical neuroleptic metoclopramide (0-4 mg/kg s.c.) on behaviours produced by D-amphetamine (0-5 mg/kg i.p.) were measured in a time-sampling observational paradigm in rats. Sulpiride had one clear dose-dependent effect: it enhanced amphetamine-induced stereotyped behaviours (repetitive head movements, sniffing down and some gnawing). In contrast, metoclopramide dose-dependently decreased amphetamine-induced stereotypy, locomotion, rearing, and sniffing up, and concurrently antagonized the suppression of lying down produced by amphetamine. Sulpiride's facilitatory effects on amphetamine-induced stereotypy follow a pattern previously observed for two other atypical neuroleptics: clozapine and thioridazine. This may be a common effect of atypical neuroleptics. Since these neuroleptics are antipsychotic, amphetamine-induced stereotypy appears to be a poor animal model for human psychoses. It is suggested that sulpiride's effects may be mediated through a preferential presynaptic versus postsynaptic action on dopamine neurons in the nigrostriatal bundle.
Vertebral mineral density, measured by computerized axial tomography, radiocalcium absorption, serum dehydroepiandrosterone (DHA), and serum cortisol (C) were measured in 98 postmenopausal women aged 56-70 yr. On the basis of spine radiographs and fracture history, the women were classified into 49 normal subjects (mean age, 60.5 yr) and 49 with osteoporosis (mean age, 63.1 yr). Vertebral mineral density (VMD), radiocalcium absorption (alpha), serum DHA, and the ratio of DHA to cortisol (DHA/C) were all significantly lower in the osteoporotic than in the normal subjects. DHA was significantly related to C in both groups but the regression was significantly flatter in the osteoporotic than in the normal subjects. Calcium absorption did not fall significantly with age in either group. In the normal group VMD, DHA, and DHA/C fell with age but VMD was not related to alpha, DHA, or DHA/C. In the osteoporotic group, VMD did not fall significantly with age but was significantly related to alpha and DHA/C. Stepwise regression analysis showed that in the normal subjects, age was the only variable significantly related to VMD (P less than 0.05). In the osteoporotic group, calcium absorption was the main determinant of VMD, with age and DHA/C contributing much less to the variance. Discriminant function analysis showed a theoretical misclassification of 45% of cases using DHA, 39% using DHA/C, 32% using alpha, and 18% when alpha and DHA or DHA/C were both taken into account. It is concluded that malabsorption of calcium is a significant risk factor for postmenopausal osteoporosis, probably because of a secondary increase in bone resorption to maintain serum calcium. The severity of the osteoporosis is directly related to the severity of the calcium malabsorption. Low serum DHA appears to represent a further risk factor, either because of its role as estrogen precursor or (possibly) because it promotes bone formation. However, the severity of the osteoporosis was not related to the serum DHA level and only weakly to the DHA/C ratio.
This study reports an evaluation of care given at an urban multidisciplinary community family practice clinic. By means of an "indicator-condition" approach, the criteria and rating system developed for the Burlington Randomized Controlled Trial (BRCT) were applied to 103 randomly selected charts demonstrating 124 episodes of care given for seven specific "conditions": otitis media, hypertension, prenatal care, care of the newborn up to the age of 12 months, immunization up to the age of 24 months, depression and urinary tract infection. Overall, 83 (67%) of the episodes of care studied were rated adequate or superior. The proportion of such episodes varied from 33% for hypertension to 81% for care of the newborn. No statistically significant differences were found between these results and those of the BRCT. A total of 48 instances of inadequate care were noted, of which 21 (44%) were omissions in patient management. Inadequate preventive care and care of chronic diseases was more common than inadequate care of acute infectious diseases. The method of primary care assessment used was found to be both practical and inexpensive.