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Biomedical subjects

M Diamond

Publications and source records attributed to M Diamond.

At least 19 recordsLinked to original sources

Temporal trends of organochlorine contaminants in burbot and lake trout from three selected Yukon lakes.

Historical studies have demonstrated that organochlorine (OC) concentrations in top predators can vary considerably from lake to lake within a small geographic region but temporal trends of these contaminants have rarely been monitored in a sub-Arctic area for a long period of time. This study examined OC concentrations, including chlordane (CHL), DDT, hexachlorocyclohexane (HCH), toxaphene (CHB), PCB and chlorinated benzenes (CBz) in lake trout and burbot, from three Yukon lakes (Laberge, Kusawa, Quiet), over a span of 11 years (1992-2003). Temporal and spatial differences continue to exist in the OC concentrations of burbot and lake trout between these lakes. There is strong evidence that these contaminants are declining at various rates in lake trout (Salveninus namaycush) in Laberge, Kusawa and Quiet Lakes. For example, SigmaDDT concentrations have decreased 39%, 85% and 84% in Kusawa, Quiet and Laberge Lakes, respectively. Conversely, no consistent trends were observed in OC concentrations for burbot (Lota lota). For example, there is no evidence of a decline in toxaphene concentrations of Kusawa burbot yet a 58% decrease was observed in Laberge samples. Increases were also observed in the SigmaHCH levels of Kusawa Lake burbot, as well as increases in all OC groups (except SigmaHCH) for the Quiet Lake burbot samples. Decreases in burbot were evident in SigmaHCH and SigmaCHB for Lake Laberge fish and in SigmaCHL for Kusawa Lake samples. Spatial variations in OC levels are quite evident as Lake Laberge trout and burbot continued to maintain the highest levels over the eleven-year period from 1992 to 2003 followed by Kusawa Lake and then Quiet Lake. These differences were related to a variety of factors especially the species morphological characteristics such as log age, log weights and fish lipid content. A decreasing trend in Quiet and Laberge Lake trout lipid content, coupled with fluctuating condition factors and increases in body masses, suggest biotic changes may be occurring within the food webs due to fish population variations related to the cessation of commercial fishing or potentially an increase in lake plankton productivity related to annual climate variation. It is suspected that biotic factors rather than atmospheric inputs are the primary factors affecting the contaminant concentrations in lake trout and burbot in the study lakes.

Animals↗

Randomized, placebo-controlled trial of rofecoxib in the acute treatment of migraine.

OBJECTIVE: To investigate the clinical profile of rofecoxib, a long-acting (approximately 17-hour half-life) selective cyclo-oxygenase-2 inhibitor, for the acute treatment of migraine. METHODS: A randomized, double-blind, placebo-controlled, parallel-group study was conducted. Patients age > or =18 treated a moderate or severe migraine headache with placebo (n = 182), rofecoxib 25 mg (n = 183), or rofecoxib 50 mg (n = 192). The primary efficacy measure was headache relief (mild or no pain) 2 hours after dose. RESULTS: The proportions of patients with migraine headache relief at 2 hours after dose were 34.3% for placebo, 54.0% for rofecoxib 25 mg (p < 0.001 vs placebo), and 56.7% for rofecoxib 50 mg (p < 0.001 vs placebo). Rofecoxib 25 and 50 mg were superior to placebo in providing pain freedom at 2 hours, 24-hour sustained headache relief, and 24-hour sustained pain freedom; in reducing photophobia, phonophobia, nausea (50 mg only), and functional disability at 2 hours after dose; and in improving some quality-of-life scores over 24 hours. More patients on rofecoxib 50 mg reported adverse events (39.6%) than patients on rofecoxib 25 mg (26.8%) or placebo (23.6%) regardless of drug relatedness; however, the incidences of drug-related adverse events were similar between treatment groups. These adverse events were generally mild or moderate in severity. The most commonly reported adverse events were dry mouth, dizziness, somnolence, nausea, dyspepsia, paresthesia, and asthenia, with similar incidences between treatment groups. CONCLUSION: Rofecoxib 25 and 50 mg were effective and generally well tolerated for the acute treatment of migraine attacks.

Acute Disease↗

Prostaglandin D2 is a potent chemoattractant for human eosinophils that acts via a novel DP receptor.

Prostaglandin D2 (PGD2) is released following exposure of asthmatics to allergen and acts via the adenylyl cyclase-coupled receptor for PGD2 (DP receptor). In this study, it is reported that human eosinophils possess this receptor, which would be expected to inhibit their activation. In contrast, it was found that prostaglandin D2 is a potent stimulator of eosinophil chemotaxis, actin polymerization, CD11b expression, and L-selectin shedding. These responses are specific for eosinophils, as neutrophils display little or no response to prostaglandin D2. They were not due to interaction with receptors for other prostanoids, as prostaglandins E2 and F(2alpha), U46619 (a thromboxane A2 analogue), and carbaprostacyclin (a prostacyclin analogue) displayed little or no activity. Furthermore, they were not shared by the selective DP receptor agonist BW245C and were not prevented by the selective DP receptor antagonist BWA868C, indicating that they were not mediated by DP receptors. In contrast, the prostaglandin D2 metabolite 13,14-dihydro-15-oxoprostaglandin D2 induced eosinophil activation but did not stimulate DP receptor-mediated adenosine 3',5'-cyclic monophosphate (cAMP) formation. These results indicate that in addition to the classic inhibitory DP1 receptor, eosinophils possess a second, novel DP2 receptor that is associated with PGD2-induced cell activation. These 2 receptors appear to interact to regulate eosinophil responses to PGD2, as blockade of DP1 receptor-mediated cAMP production by BWA868C resulted in enhanced DP2 receptor-mediated stimulation of CD11b expression. The balance between DP1 and DP2 receptors could determine the degree to which prostaglandin D2 can activate eosinophils and may play a role in eosinophil recruitment in asthma.

Actins↗

The paper monster. Corporate compliance and the board.

Fraud and abuse lawsuits and settlements are getting bigger, and the DOJ shows no signs of letting up on its scrutiny of health care organizations. That's why a strong compliance program is your best defense, and it all starts with the board.

Confidentiality↗

Prevention of migraine during prodrome with naratriptan.

OBJECTIVE: To determine the role of naratriptan in preventing migraine headache when administered during prodrome. PROCEDURES: Baseline phase: patients recorded prodrome symptoms and time of onset, time when patient knew that headache was inevitable, time of onset and severity of headache. Treatment phase: patients given naratriptan 2.5 mg to take at the time they knew headache was inevitable. Patients recorded prodrome symptoms and time of onset, time they knew headache was inevitable, time naratriptan administered, time of onset and severity of any headache. Patients treated three prodromes separated by at least 48 h. FINDINGS: Twenty patients completed both phases. During baseline phase, 59 prodromes were reported and all were followed by headache. Severity of headache: 5% mild, 51% moderate, 44% severe. During treatment phase, 63 prodromes were reported. Of these, 38/63 (60%) were not followed by headache. Among headaches that occurred, the majority occurred within 2 h of naratriptan administration, suggesting that naratriptan is more effective in preventing headache if taken early in prodrome. Severity of 25 headaches: 44% mild, 24% moderate, 32% severe. CONCLUSIONS: Naratriptan 2.5 mg appears to prevent migraine headache when given early in prodrome. If headache occurs, severity appears to be reduced.

Adult↗

Neural coding: higher-order temporal patterns in the neurostatistics of cell assemblies.

Recent advances in the technology of multiunit recordings make it possible to test Hebb's hypothesis that neurons do not function in isolation but are organized in assemblies. This has created the need for statistical approaches to detecting the presence of spatiotemporal patterns of more than two neurons in neuron spike train data. We mention three possible measures for the presence of higher-order patterns of neural activation--coefficients of log-linear models, connected cumulants, and redundancies--and present arguments in favor of the coefficients of log-linear models. We present test statistics for detecting the presence of higher-order interactions in spike train data by parameterizing these interactions in terms of coefficients of log-linear models. We also present a Bayesian approach for inferring the existence or absence of interactions and estimating their strength. The two methods, the frequentist and the Bayesian one, are shown to be consistent in the sense that interactions that are detected by either method also tend to be detected by the other. A heuristic for the analysis of temporal patterns is also proposed. Finally, a Bayesian test is presented that establishes stochastic differences between recorded segments of data. The methods are applied to experimental data and synthetic data drawn from our statistical models. Our experimental data are drawn from multiunit recordings in the prefrontal cortex of behaving monkeys, the somatosensory cortex of anesthetized rats, and multiunit recordings in the visual cortex of behaving monkeys.

Action Potentials↗

Pediatric management of ambiguous and traumatized genitalia.

PURPOSE: The present standard of practice in the management of ambiguous and traumatized genitalia was evaluated. MATERIALS AND METHODS: Published cases of intersexuality and protocols for the management of traumatized genitalia were reviewed with consideration of the input of intersexual individuals. Independent research on different types of intersexuality is also presented. RESULTS: The present standard pediatric recommendations and precepts for the management of ambiguous or traumatized genitalia are wanting. Followup studies on which to base treatment decisions are needed. Evidence based principles of medical management are proposed. CONCLUSIONS: A moratorium on sex reassignment cosmetic surgery is recommended. Also recommended are that followup studies should be instituted on past cases, and honesty and counseling should be the core of initial and subsequent treatment.

Child↗

The impact of cellular fragmentation induced experimentally at different stages of mouse preimplantation development.

It has been demonstrated previously that removal of acellular debris from the preimplantation mouse embryo is beneficial for subsequent development to the hatched blastocyst stage. We have studied the impact of cellular fragmentation induced in the mouse embryo during the late pronuclei and 8-cell stages on the hatching frequency and total cell number at the blastocyst stage. At the late pronuclei stage about one-quarter of the cytoplasm was removed from embryos in the experimental group, in four to six steps, thus creating four to six cytoplasts that were subsequently returned as anucleated fragments under the zona pellucida. Embryos with one-quarter of the cytoplasm removed and with intact cytoplasm after partial zona dissection (PZD) served as controls. At the 8-cell stage, embryos with their nucleoplast removed from two blastomeres served as an experimental group. Groups of embryos with part of the cytoplast removed from two blastomeres (nucleated fragments), embryos with two blastomeres removed and embryos after PZD alone served as controls. After manipulation all embryos were left in culture and analysed at about 100 h after human chorionic gonadotrophin administration. Fragments induced at the late pronuclei stage did not participate in compaction and were often spontaneously expelled from the embryo during hatching. Neither embryo hatching rate nor total cell number was affected when compared with zygotes with reduced cytoplasm. Although both nucleated and anucleated fragments induced at the 8-cell stage participated in recompaction, hatching was not compromised and there was no interference in further development as assessed by the cell number or hatching rate at the blastocyst stage, as compared with embryos with blastomeres removed. We conclude that anucleated cellular fragments formed in an otherwise healthy embryo, both before and after acquisition of the ability for compaction, are benign and that their removal provides no benefit for embryo development, at least to the hatched blastocyst stage.

Animals↗

Sex reassignment at birth. Long-term review and clinical implications.

This article is a long-term follow-up to a classic case reported in pediatric, psychiatric, and sexological literature. The penis of an XY individual was accidentally ablated and he was subsequently raised as a female. Initially this individual was described as developing into a normally functioning female. The individual, however, was later found to reject this sex of rearing, switched at puberty to living as a male, and has successfully lived as such from that time to the present. The standard in instances of extensive penile damage to infants is to recommend rearing the male as a female. Subsequent cases should, however, be managed in light of this new evidence.

Adult↗

From fertilization to adult sexual behavior.

Research has established the broad mammalian developmental plan that genes on the sex chromosomes influence gonad development which determines gonadal hormone production (or its absence) leading to modification of the genitalia and simultaneously biasing the nervous system to organize adult sexual behavior. This might be considered the "gonad to hormones to behavior" model. It is clear, however, that although this model generally works well it is incomplete. The model does not account for behavioral influences attributed to the environment or to genetic but nongonadal or hormonal factors. In this essay we probe those areas of sexual development that are neither differentiated by hormones nor activated by them. The concept of the environment used for our discussion is very broad; it incorporates considerations of both the molar and the molecular levels. The general sense of the word "environment" as something exterior to the person is retained, even if that something influences intraperson processes. In addition, we focus directly on molecular events themselves. Here the "environment" involved can be that within a DNA segment. We also expand the notion of "biologically based sex differences." Although many, and perhaps most, important sex differences arise from gonadal and hormonal development, also important are sex differences which are neither gonadal nor hormonal. All these factors affect the internal workings of the individual and intervene in structuring how the social environment might or might not modify sexual behavior. This discourse calls attention to features that are central to the so-called nature-nurture discussion.

Fertilization↗

Prenatal predisposition and the clinical management of some pediatric conditions.

Theoretical understanding of psychosexual development, particularly in regard to sexual identity, has undergone several historical changes. Most notable has been the transition away from a learning paradigm, which held that individuals are psychosexually neutral at birth and that they develop their sexual identity due to rearing. This has shifted to contemporary acceptance that an interaction of both nature and nurture is responsible for psychosexual development. That there probably exists an inherent predisposition or bias toward a male or female identity, which is inferred by prenatal influences, is also current theory. However, while this shift has occurred in the theoretical understanding of the phenomenon, a comparable shift has not occurred in the clinical management of individuals where sex assignment or reassignment is a real issue. The theoretical change and real case management should be concordant.

Child Rearing↗