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Biomedical subjects

A Sampson

Publications and source records attributed to A Sampson.

At least 19 recordsLinked to original sources
PubMed2005

Regional specificity of chandelier neuron axon terminal alterations in schizophrenia.

BACKGROUND: The axon terminals of GABAergic chandelier cells form linear arrays, termed cartridges, that synapse on the axon initial segment of neocortical pyramidal cells. These cartridges are immunoreactive for the GABA membrane transporter-1, and the density of GABA membrane transporter-1-immunoreactive cartridges in the prefrontal cortex has been reported to be reduced in schizophrenia. The goal of this study was to determine if reductions in the density of GABA membrane transporter-1-immunoreactive cartridges in schizophrenia are restricted to the prefrontal cortex. METHODS: Relative GABA membrane transporter-1-immunoreactive cartridge density was determined in auditory association area 42, a region previously implicated in the pathophysiology of schizophrenia, in 14 matched pairs of subjects with schizophrenia and normal comparison subjects. The results were compared with similar data from prefrontal area 46 in the same subjects. RESULTS: Mean GABA membrane transporter-1-immunoreactive cartridge density in area 42 was decreased by 9.8% in layers II-IIIa, and by 11.9% in layer VI in subjects with schizophrenia, although these differences did not achieve statistical significance. However, the magnitude of the reductions in the density of GABA membrane transporter-1-immunoreactive cartridges in area 42 of the subjects with schizophrenia was not significantly smaller than those in area 46. CONCLUSIONS: In subjects with schizophrenia, alterations in chandelier neuron axon cartridges appear to be more marked in the prefrontal cortex than in another cortical region implicated in the illness, although such changes might not be restricted to the prefrontal cortex.

Adult↗
PubMed2005

Massive myocardial calcification in second-trimester fetuses: antenatal detection and causes.

Massive myocardial calcifications were detected by antenatal ultrasound examination in four second-trimester fetuses. In one fetus, multiple cardiac rhabdomyomas were the initial diagnosis. One fetus presented with arthrogryposis and the brain and spinal cord showed severe hypoxic-ischemic damage. One fetus was hydropic and had severe cardiac malformations. The fourth fetus had congenital heart block and maternal serum was positive for anti-Ro and anti-La antibodies. Myocardial calcifications in the first three fetuses were most likely to be caused by hypoxic-ischemic damage to the heart, and immunological mechanisms were responsible in the other fetus. Antenatally detected myocardial echogenic foci in a fetus leading to a termination of pregnancy or associated with fetal death should be investigated with a full postmortem examination. It is important to confirm the presence of calcifications as distinct from a rhabdomyoma as genetic counseling is completely different. The demonstration of associated lesions in other organs also helps to explain the pathogenesis underlying this condition.

Adult↗
PubMed2001

Dopamine transporter immunoreactivity in monkey cerebral cortex: regional, laminar, and ultrastructural localization.

Dopamine (DA) influences a number of cognitive and motor functions that are mediated by the primate cerebral cortex, and the DA membrane transporter (DAT) is known to be a critical regulator of DA neurotransmission in subcortical structures in rodents. To gain insight into the possible functional role of cortical DAT, we compared the regional, laminar, and ultrastructural distribution of DAT immunoreactivity to that of tyrosine hydroxylase (TH), the rate-limiting enzyme in DA synthesis, in the cerebral cortex of macaque monkeys. DAT-immunoreactive (DAT-IR) axons were present throughout the cortical mantle, with substantial differences in density and laminar distribution across cytoarchitectonic areas. In particular, high densities of DAT-IR axons were present in certain regions (e.g., posterior parietal cortex, dentate gyrus) not previously thought to receive a substantial DA input. The laminar distribution of DAT-IR axons ranged from a restricted localization of labeled axons to layer 1 in lightly innervated regions to the presence of axons in all six cortical layers, with a particularly dense plexus in deep layer 3, in highly innervated regions. These regional and laminar patterns paralleled those of TH-IR axons, but several differences in fiber morphology and ultrastructural localization of DAT were observed. For example, in contrast to TH, DAT immunoreactivity in the cortex was localized predominantly to small-diameter profiles, whereas, in the dorsolateral caudate nucleus, DAT and TH immunoreactivities were present in both large-diameter and small-diameter profiles, which may represent varicose and intervaricose axon segments, respectively. Overall, the distribution of DAT-IR axons confirms and extends the results of previous reports, using other markers of DA axons, that the DA innervation of the primate cerebral cortex is global but specialized on both a regional basis and a laminar basis. In particular, these observations reveal an anatomical substrate for a direct and potent influence of DA over neuronal activity in posterior parietal cortex and in certain regions of the temporal lobe. However, due to its predominant distribution to small-diameter profiles, immunoreactivity for DAT may not be an appropriate ultrastructural marker for larger DA varicosities in the primate cortex. Moreover, this distribution of DAT suggests that cortical DA fibers may permit greater neurotransmitter diffusion than subcortical DA axons.

Animals↗
PubMed2001

Decreased somal size of deep layer 3 pyramidal neurons in the prefrontal cortex of subjects with schizophrenia.

BACKGROUND: Schizophrenia is associated with deficits in working memory, a cognitive function that depends on the connections of the prefrontal cortex (PFC) with the thalamus and other cortical regions. Pyramidal neurons in PFC deep layer 3 play a central role in both thalamocortical and corticocortical circuitry. Given that somal size tends to be associated with both the dendritic and axonal architecture of a neuron, abnormalities in these circuits in schizophrenia may be associated with a change in the somal size of deep layer 3 pyramidal neurons. METHODS: We used design-based stereology to estimate the somal volume of pyramidal neurons in deep layer 3 of PFC area 9 in 28 subjects with schizophrenia, each of whom was matched to 1 normal comparison subject for sex, age, and postmortem interval. RESULTS: The geometric mean of the somal volume estimates in the subjects with schizophrenia was significantly (P =.02) decreased by 9.2%. This decrease was associated with a shift in the distribution of somal volumes toward smaller sizes. Neither antipsychotic medication treatment history nor duration of illness was associated with somal size. CONCLUSIONS: These findings independently replicate previous reports of decreased somal size in the PFC in schizophrenia. The reduction in size of deep layer 3 pyramidal neurons is consistent with abnormalities in thalamocortical and corticocortical circuitry, suggesting that disruption of these circuits may contribute to cognitive abnormalities in schizophrenia.

Adult↗
PubMed2001

GABA transporter-1 mRNA in the prefrontal cortex in schizophrenia: decreased expression in a subset of neurons.

OBJECTIVE: Within the prefrontal cortex of schizophrenic subjects, alterations in markers of gamma-aminobutyric acid (GABA) neurotransmission, including decreased immunoreactivity for the GABA membrane transporter GAT-1, may be most prominent in a subset of inhibitory neurons. In the present study, the authors sought to determine whether the alterations in GAT-1 protein could be attributed to a reduction in GAT-1 mRNA expression. METHOD: Tissue sections containing prefrontal cortex area 9 from 10 matched pairs of schizophrenic and comparison subjects were processed for in situ hybridization histochemistry with (35)S-oligonucleotide probes for GAT-1 mRNA. RESULTS: In the schizophrenic subjects, the relative density of labeled neurons was 21%-33% lower in layers 1-5 of the prefrontal cortex but was unchanged in layer 6. In contrast, cellular levels of GAT-1 mRNA expression, as reflected in grain density per labeled neuron, did not differ by more than 11% between subject groups in any layer. These findings indicate that GAT-1 mRNA expression is relatively unaltered in the majority of prefrontal cortex GABA neurons in schizophrenic subjects but is reduced below a detectable level in a subset of GABA neurons. Furthermore, the magnitude and laminar pattern of these results were strikingly similar to those found in a previous study of mRNA expression for the synthesizing enzyme of GABA, glutamic acid decarboxylase(67), in the same subjects. CONCLUSIONS: Both GABA synthesis and reuptake appear to be altered at the level of gene expression in a subset of GABA neurons, and the resulting changes in GABA neurotransmission may contribute to prefrontal cortex dysfunction in schizophrenia.

Adult↗
PubMed1998

Cyclo-oxygenase.

Explore the source record for details and available documents.

Anti-Inflammatory Agents, Non-Steroidal↗
PubMed1998

Comparison of meta-analysis versus analysis of variance of individual patient data.

Meta-analysis is a method of synthesizing the results of independent studies. We consider the case in which there are multiple treatments and a control, with the goal of estimating the relative effect of each treatment based on continuous outcomes. Even when all data are available, rather than only summary data, it has become common to use meta-analytic estimators of treatment contrasts. Alternatively, we could use a two-way analysis of variance model with no interaction in which one factor is study and one factor is treatment. For the unbalanced case, we obtain the surprising result that the standard meta-analysis estimates of treatment contrasts are identical to the least squares estimators of treatment contrasts in the linear model. Because a meta-analysis of individual patient data can be considerably more costly in terms of data retrieval than a meta-analysis of summary data, this equivalence provides for cost-efficient analysis.

Analysis of Variance↗
PubMed1997

Safety and effectiveness of homemade and reconstituted packet cereal-based oral rehydration solutions: a randomized clinical trial.

OBJECTIVES: Parents may be deterred from obtaining commercial oral rehydration solutions (ORS) for their young children with acute diarrheal disease because of its availability and/or cost, especially if they are poor. We conducted a randomized clinical trial to determine 1) whether low-income parents could safely mix and administer cereal-based ORS (CBORS) both from ingredients commonly found in the home and from a premixed packet; 2) whether these CBORS were as effective in maintaining hydration as commercial glucose-based ORS; and 3) whether CBORS were more effective in reducing severity and duration of illness. METHODS: Children 4 to 36 months of age discharged from emergency departments and health centers with acute diarrheal disease were randomized to receive either homemade CBORS, reconstituted packet CBORS, or Pedialyte. A study nurse saw the child at home each day until the illness resolved, and obtained capillary blood for serum sodium at enrollment and at 24 to 48 hours; a sample of CBORS for sodium concentration; stool for pathogen analysis; and daily fluid intake, stool frequency, and weight. RESULTS: A total of 232 children were enrolled, of whom 203 (88%) completed the study. Two parents (3%) in the homemade CBORS group and one parent (1%) in the packet CBORS group made mixing errors resulting in a high sodium concentration (>100 mEq/L); their children refused the solution and had normal serum sodium values. Mean CBORS sodium concentration for the remainder of the homemade CBORS group was 60 +/- 10 mEq/L, and for the packet CBORS group, 54 +/- 13. Eighteen children (11%) had abnormal serum sodium values at presentation, which returned to normal in all groups in most cases. Three children (4.5%) in the homemade CBORS group, 4 (6%) in the packet CBORS group, and 1 child (1.4%) in the Pedialyte group failed therapy. Children refused to take homemade CBORS and packet CBORS (43% and 32%, respectively) more often than Pedialyte (9%), and those in the CBORS groups tended to take less ORS and total fluids. There were no significant differences among the three groups in incidence of daily vomiting or stooling, duration of diarrhea, or weight gain. CONCLUSIONS: CBORS do not offer a clinically significant advantage over glucose-based ORS. Homemade CBORS represent a treatment option in carefully selected cases, but it is not the safest alternative for regular clinical use.

Acute Disease↗
PubMed1996

Statistical analysis of possible bias of clinical judgements due to observing an on-therapy marker variable.

In certain double-blind clinical trials there is the possibility that certain 'marker variables' observable during the trial may in part unblind the trial, even at a subliminal level. At issue is whether or not this potential unblinding biases the investigators' clinical efficacy assessments. This issue arose after the completion of three clinical trials that compared tretinoin emollient cream (TEC) 0.05 per cent to its vehicle in patients with photodamaged skin. The question raised was whether or not possible 'subliminal unblinding' of the investigators and patients, due to the cutaneous irritation associated with topical tretinoin, might have caused a treatment bias in the study. To address this issue, we undertook a reanalysis of these three clinical trials. In doing so, we develop in this paper a statistical modelling approach to address issues of possible bias introduced by the ability to observe such marker variables. The approach utilizes a linear discriminant analysis to introduce an auxiliary categorical variable for the efficacy analysis. A suitable categorical data model permits the estimation of relevant bias effects. We illustrate this approach with data from the three TEC 0.05 per cent trials.

Bias↗
PubMed1996

Antepartum and postpartum complications of twin-twin transfusion.

Twin-twin transfusion is a condition that was previously associated with close to a 100% perinatal mortality. Recent reports suggest that a survival rate of about 60% can be achieved with serial amniocentesis and modern neonatal care. However, it is now apparent that the survivors of this condition have multisystem complications that can result in neonatal mortality and long-term morbidity. Fourteen cases of twin-twin transfusion were examined to determine the antenatal findings that may predict the postnatal outcomes of these infants. The overall survival was 61% (17 of 28). The mean gestation at diagnosis was 23.0 weeks (range 18-34 weeks) and the mean gestation at delivery was 29.0 weeks (range 23-37 weeks). The mean number of amniocenteses was 2.9 and the average total volume of amniotic fluid removed was 6,114 mL. Different patterns of complications were seen in the donor and recipient twins. Hypertrophic cardiomyopathy affected 9 of the recipient twins. Anuria/oliguria was found in 4 of the donor twins and none of the recipients. Periventricular leukomalacia was found in 8 twins and 7 also had mild ventriculomegaly; of the surviving 17 twins, 5 had either periventricular leukomalacia, mild ventriculomegaly or both. Amniotic fluid leakage and perforation of the intervening membrane subsequent to serial amniocentesis were seen in 5 cases. Severe intrauterine growth retardation and abnormal cardiotocographs were a common feature. These complications directly resulted in neonatal mortality and long-term morbidity in the survivors. Not all complications were detected antenatally and the severity was not able to be anticipated.

Anuria↗
PubMed1995

Reinforcing effects of triazolam in sedative abusers: correlation of drug liking and self-administration measures.

Six male subjects with histories of sedative abuse were allowed to orally self-administer a maximum of 18 color-coded triazolam and placebo capsules during daily 3-h sessions. The schedule of reinforcement was a signaled fixed-interval 10-min schedule in which triazolam and placebo were concurrently available as mutually exclusive choices. Triazolam was shown to be a reinforcer in four of the six subjects. The two subjects who did not self-administer triazolam in preference to placebo also had lesser histories of drug dependence. Self-administration of triazolam (0.125 or 0.25 mg per capsule) was generally stable over 7-10 days. Manipulations of triazolam dose (0.0312-0.25 mg) per capsule in two subjects showed that the number of capsules self-administered was inversely related to capsule dose. Subject ratings of drug liking obtained from experimenter-administered doses of triazolam were correlated with self-administration behavior occurring 1-7 days later. Of the subject ratings, next day ratings obtained on the day after dosing resulted in significant correlations whereas same day ratings obtained while subjects were under the influence of triazolam did not. These results have important implications for abuse liability prediction and suggest that next day ratings have greater predictive validity than measures collected while subjects are under the influence of benzodiazepines.

Adult↗
PubMed1995

Amnion rupture in the second trimester.

Two cases of amnion rupture are presented in 'low-risk' pregnancies. One case ended in fetal death in utero at 21 weeks. The other resulted in the preterm delivery of an otherwise normal male with mild amniotic band syndrome.

Amnion↗
PubMed1992

Vanishing twins: the frequency of spontaneous fetal reduction of a twin pregnancy.

This study examines the outcome of 126 twin pregnancies diagnosed by ultrasound examination at 6-16 weeks' gestation. Fifty-nine patients conceived by in vitro fertilization (IVF) and embryo transfer and had a routine scan. The 67 non-IVF pregnancies had a scan for other clinical indications including threatened abortion. When live twins were detected prior to 7 weeks'gestation, only 71% of pregnancies resulted in live twin neonates. Each fetus of a multiple pregnancy had a 19% chance of dying in utero or in the neonatal period of diagnosed prior to 7 weeks, and 11% if both were found to be alive between 7 and 10 weeks. The fetal loss rate was similar for IVF and non-IVF pregnancies.

Journal Article↗
PubMed1989

Mecamylamine increases nicotine preference and attenuates nicotine discrimination.

Eight subjects evaluated various qualities of cigarette smoke after being given a range of doses (0, 2.5, 10 and 20 mg) of the nicotinic receptor blocker mecamylamine. In one test condition, subjects were given either high or low nicotine tobacco smoke to determine the effects of mecamylamine on their subjective responses. In another test condition, subjects were allowed to adjust the nicotine dose level of the smoke to determine the effects of mecamylamine on dose preference. When the subjects evaluated puffs of smoke with high and low nicotine content, mecamylamine caused a dose-related decrease in the self-rated strength and harshness of the high nicotine dose level smoke. In contrast, there was little effect on the low dose smoke. At the highest mecamylamine dose (20 mg) there was no significant difference in the ratings of high and low nicotine cigarettes. Low doses of mecamylamine decreased the reported desire for a cigarette, and also attenuated the reduction in desire for a cigarette caused by smoking. When the subjects were allowed to select their preferred level of nicotine intake using a smoke mixing device, the 10 and 20 mg doses of mecamylamine caused a significant increase in self-administered nicotine dose level. Despite this compensatory increase in nicotine self-administration, the reduction in desire for a cigarette after smoking was still less than after placebo.

Adult↗