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T Meehan

Publications and source records attributed to T Meehan.

At least 37 records · Page 2Linked to original sources
PubMed1998

Synthesis and characterization of bay region halohydrins derived from Benzo[a]pyrene diol epoxide and their role as intermediates in halide-catalyzed cis adduct formation.

The bay region epoxide of benzo[a]pyrene (anti-BPDE) alkylates DNA to form adducts with >98% trans stereochemistry. Halide ions catalyze this reaction; however, this pathway is characterized by the formation of adducts with altered cis stereochemistry. Bay region halohydrins are possible intermediates in these reactions, but are too unstable to be isolated from aqueous solutions. However, we successfully synthesized halohydrins in tetrahydrofuran (THF) by treatment of anti-BPDE with the corresponding lithium halide salt in the presence of acetic acid. Absorbance and CD spectroscopy clearly indicated the formation of chloro-, bromo-, and iodohydrins. The structure and stereochemistry of the chlorohydrin was established by NMR. Chloride addition is exclusively at the benzylic position of the epoxide, and the stereochemistry of the C-9 and -10 positions is trans. The long-wavelength absorbance band in the chloro-, bromo-, and iodohydrin is red-shifted 7, 13, and 22 nm, respectively, relative to the hydrolysis product of anti-BPDE. The ellipticity of the same absorbance band in CD spectra of enantiomerically pure halohydrins is opposite in sign compared to that of the corresponding anti-BPDE enantiomer. The relative stability of these derivatives is chlorohydrin > bromohydrin > iodohydrin. The chloro- and bromohydrins were isolated, but the iodohydrin decomposed during this manipulation. The addition of 500 mM chloride decreased the hydrolysis rate of the chlorohydrin 4-fold in 50% THF/buffer. Direct evidence for the transient formation of the iodohydrin in aqueous buffer/acetone mixtures was obtained by absorbance spectroscopy. At 1 M chloride, bromide, and iodide, alkylation of deoxyadenosine by anti-BPDE in aqueous buffer yields 85, 91, and 92% cis adducts, respectively. In the absence of halide, alkylation of deoxyadenosine in buffer by anti-BPDE, the chlorohydrin, and the bromohydrin yields 32, 65, and 83% cis adducts, respectively.

7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide↗
PubMed1998

Arrests and incarceration of injection drug users for syringe possession in Massachusetts: implications for HIV prevention.

Multiperson use of syringes is a major risk behavior responsible for the spread of HIV-1 among injection drug users (IDUs). In Massachusetts, two laws regulate syringes: one is a prescription law prohibiting possession or purchase of syringes without a prescription, and the other makes it illegal to possess drug paraphernalia, including syringes. In 1993, Massachusetts amended the prescription law to permit the establishment of syringe exchange programs in two cities. Enrolled participants are allowed to possess syringes anywhere in the state, and about 5% of the estimated 40,000 IDUs in Massachusetts are program participants. To understand how HIV prevention efforts with active IDUs may be constrained by the enforcement of laws criminalizing possession of syringes after the amendment in the law, we reviewed data from multiple sources to assess the number of arrests for syringe possession in 10 large cities in Massachusetts to evaluate incarceration rates and lengths of sentences for those convicted of syringe possession and to estimate costs of incarceration for those convicted of syringe possession. At least 824 persons were arrested for syringe possession in 1995. In examining the data on convictions, we found that 417 persons were convicted in 1994 of syringe possession in the absence of other serious charges, and of these, 41.0% were sentenced to incarceration. The average sentence imposed was 5 months (range, 3 days-2 years). Assuming that those convicted serve about two thirds of their sentences, the cost of incarceration was estimated at $1,140,183 excluding costs for arrest, pretrial detention, prosecution, or other costs of enforcement. Costs for incarcerating persons convicted of both syringe and drug possession were not included; the total cost of incarceration of persons convicted of possession of a syringe, with or without other major charges, is probably considerably higher. Had these funds been allocated to pay for drug treatment, 1629 admissions to drug detoxification programs could have been purchased. Retaining drug paraphernalia and syringe prescription laws in Massachusetts may contribute to HIV transmission. These findings support the recommendation of the American Medical Association to modify drug paraphernalia laws so that IDUs can purchase and possess syringes without a prescription.

Boston↗
PubMed1998

Weight changes during clozapine treatment.

OBJECTIVE: The aim of this study was to assess the prevalence and magnitude of weight changes pre- and post-clozapine and to explore the ability of demographic and clinical factors to predict weight gain at 12 months post-clozapine. METHOD: Weight changes in a sample of 51 patients were assessed at 3 months pre-clozapine, at baseline, and at 3 and 12 months post-clozapine. In addition, demographic data and information concerning changes in appetite and activity level at 3 months was gathered and used to predict weight gain at 12 months. RESULTS: Seventy percent of patients gained an average of 7.5 kg (10.6% increase in baseline body weight) over the 12-month period. Although post-clozapine weight gain for the total group was significant at 12 months, weight gain for the female subsample (n = 16) did not reach significance at either the 3 or 12 month assessments. The only factors associated with marked weight gain (> 15% increase) at 12 months were increased food intake early in treatment and having gained weight at 3 months. CONCLUSION: Clozapine treatment was found to be associated with significant weight gain in patients prescribed clozapine, especially male patients. Considering the long-term health risks associated with excess weight gain, health professionals can play an important role in educating clients about the potential for weight gain with clozapine treatment.

Adult↗
PubMed1998

Ultrasonographic monitoring of artificially stimulated ejaculation in three rhinoceros species (Ceratotherium simum, Diceros bicornis, Rhinoceros unicornus).

Manual massage of the penis and rectal electroejaculation methods have been minimally effective for collecting semen from the rhinoceros. These two methods for stimulating ejaculation were evaluated by rectal ultrasonography. One individual each of three rhinoceros species (Ceratotherium simum simum, Rhinoceros unicornis and Diceros bicornis) was stimulated by manual massage of the penis and two black rhinoceroses (Diceros bicornis) were electroejaculated. On ultrasonography, neither manual massage nor rectal electroejaculation affected the accessory glands. The pelvic urethra remained empty during manual massage of unconditioned animals; however, this area was filled before commencement of massage of conditioned animals. The pelvic urethra also filled during electroejaculation. Semen accumulated in the pelvic urethra during pauses between electrical stimulations and was moved distally into the penile urethra by rectal and penile massage. The volumes of seminal fluid recovered from electroejaculation in this study exceeded previously reported attempts. This study demonstrated the potential of transrectal imaging for improving the recovery of semen by these methods.

Animals↗
PubMed1998

Boarding house life for people with mental illness: an exploratory study.

The present study explored residents' perceptions of life in boarding houses within the Central Sydney Area Health Service. A purposeful sample of 14 people with a mental illness participated in semistructured interviews. The transcribed interviews were analysed for lifestyle issues to increase understanding of the factors that impact on quality of life from the consumers' perspective. It was encouraging to find that basic needs were being met, but it would appear that there is considerable room for improvement in quality of life for this vulnerable group of people. The findings of the present study should prove valuable for policy makers and health professionals who provide services to people with mental illness resident in boarding houses.

Adult↗
PubMed1997

Benzo[a]pyrene diol epoxide-DNA cis adduct formation through a trans chlorohydrin intermediate.

Alkylation of DNA by 7r,8t-dihydroxy,9t,10t-epoxy-7,8,9,10-tetrahydrobenzo[a]pyrene (anti-BPDE) forms mainly trans adducts (with respect to the C-9/10 positions). We recently described a halide-catalyzed pathway that preferentially generates cis adducts and now report that the trans chlorohydrin of anti-BPDE (trans-BPDCH) is an intermediate in the chloride-catalyzed reaction. trans-BPDCH was synthesized, and both it and anti-BPDE were reacted with deoxyadenosine as a model DNA nucleophile. The stereochemistry and yields of deoxyadenosine adducts were determined as a function of chloride concentration. In the absence of salt, the fraction of cis adducts obtained from anti-BPDE and trans-BPDCH are 0.33 and 0.67, respectively. Adding sodium chloride increases the fraction of cis adducts (and consequently decreases the fraction of trans adducts), with the midpoint of the increase for both substrates at approximately 35-40 mM chloride. The chloride-dependent curves for BPDE and BPDCH converge at 1 M chloride, where the fraction of cis adducts is 0.88. Chloride also increases the total yield of cis adducts with either substrate, whereas the yield of trans adducts from the chlorohydrin is not significantly changed. These results support a mechanism by which chloride ion undergoes nucleophilic addition to the benzylic C-10 position of anti-BPDE. This generates a trans halohydrin that alkylates DNA with inversion of configuration to form a cis adduct. This pathway may have biological significance because chlorohydrins could form in serum or in cells with relatively high intracellular concentrations of chloride.

7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide↗
PubMed1997

Council playgrounds in New South Wales: compliance with safety guidelines.

Despite initiatives to improve the safety of play environments, playground-related injuries continue to be a major public health problem. Efforts to address playground safety in New South Wales were consolidated during 1994 through the Kidsafe Playground Safety Project. In stage 1 of the project (described here), 240 council playgrounds were assessed to determine the extent to which playground equipment complied with safety guidelines. On-site inspection of the selected playgrounds provided data on 862 separate pieces of playground equipment. Of the 723 pieces requiring undersurfacing, less than half (45.4 per cent) had the recommended type of undersurfacing while only 42 of those pieces had undersurfacing to the recommended depth. However, when the fall height of equipment was considered in addition to the undersurfacing guidelines, only 13 (1.8 per cent) of the 723 pieces of equipment simultaneously satisfied all of the safety guidelines. Regrettably, none of the 240 council playgrounds assessed complied fully with the key safety guidelines. The results underscore the need for a collaborative effort on the part of local government, Kidsafe and health promotion and regional public health units to ensure that council playgrounds in New South Wales comply with recommended safety guidelines.

Child↗
PubMed1997

The use of behavioural mapping in a study of seclusion.

As part of a larger study into the use of seclusion we set out to examine some of the antecedents that led to patients being secluded in one locked psychiatric ward. Behavioural mapping was used to chart the location of incidents that resulted in seclusion. Incidents were observed in several ward areas but most of these occurred in the day room and the dining room. This finding enabled us to question the ward policy of confining patients to these areas to facilitate nursing observation and management. The policy may have contributed to the number of disturbances by limiting personal space for patients. Literature on body buffer zones, crowding and territoriality is used to clarify and interpret the findings.

Female↗
PubMed1997

Crisis intervention workers in New South Wales: knowledge, skills, qualities and preparation.

Ninety-five mental health workers employed by 13 randomly selected crisis intervention and extended hours teams in NSW responded to a questionnaire designed to elicit information concerning the perceived competencies required for crisis intervention. The findings reported and underscore the need for specialized knowledge and skills to address the problems presented by mentally ill clients in crisis. Assessment of suicide risk, being able to work as part of a team, and knowledge of crisis intervention strategies were perceived as the most important competencies required. It is suggested that these competencies are gained through initial induction programmes, 'on-the-job' experience, and clinical supervision rather than previous experience in the mental health field. The lists of competencies provided will be of interest to those involved in the development of induction and continuing education programmes for crisis intervention workers and in the selection of staff for positions in crisis intervention.

Clinical Competence↗
PubMed1997

Neuroleptic malignant syndrome: an assessment of registered psychiatric nurses' knowledge.

Neuroleptic Malignant Syndrome (NMS) is a potentially fatal complication of neuroleptic use and is frequently underdiagnosed by medical and nursing staff. The current project was undertaken to assess the knowledge registered psychiatric nurses (RPN) have of the signs, symptoms and interventions to be initiated in cases of NMS. A total of 126 RPN employed in a large tertiary inpatient facility and community mental health centre responded to a self-completed questionnaire. The results indicate that while the RPN in the study's sample demonstrated adequate knowledge of NMS, there was evidence to suggest that these RPN may actually lack confidence in their ability to identify and initiate appropriate interventions in suspected cases of NMS. Although RPN employed in the rehabilitation and psychogeriatric areas of the hospital had more years of experience in the mental health field, their overall knowledge of NMS was significantly lower than that of RPN employed in other clinical settings (F = 3.35; d.f. = 5119; P = 0.007). The findings underscore the importance of ongoing education for RPN employed within clinical mental health settings.

Clinical Competence↗
PubMed1994

The effect of sodium ion concentration on intrastrand base-pairing in single-stranded DNA.

The salt-induced formation of duplex structure (primarily hairpin loops) in denatured calf thymus DNA was monitored by measuring the decrease in absorbance at 260 nm as a function of increasing sodium ion concentration. It was found that this process was noncooperative and could be accurately described by the mass-action expression for the reversible formation of a binary complex: single strand (coil) + free sodium ion <==> hairpin (with associated sodium ion). The equilibrium constant for the transition was found to be 6 (M Na+)-1. The extrapolated absorbance at infinite salt concentration represents 11% hyperchromicity, which is one third of the hyperchromicity of denatured DNA in the absence of salt (36%).

Animals↗
PubMed1994

Chloride ions catalyze the formation of cis adducts in the binding of anti-benzo[a]pyrene diol epoxide to nucleic acids.

The alkylation of DNA by racemic 7r,8t-dihydroxy-9t,10t-epoxy-7,8,9,10-tetrahydrobenzo[a]pyrene (anti-BPDE) exhibits a strong preference for formation of trans adducts between the N2 deoxyguanosine alkylation site and the (+)-enantiomer of anti-BPDE. In the presence of 10 mM buffer with no added salt, 98% of the adducts formed with native calf thymus DNA result from trans opening of the epoxide ring. The strong selectivity for trans adduct formation obtained with duplex DNA at low salt concentration is found to a lesser degree with poly(G) but is nearly absent with dAMP. When DNA adducts are formed in 10 mM MgCl2 or 1 M NaCl, the proportion of cis adducts increases to approximately 7 and approximately 26%, respectively. At low salt, 10 mM MgCl2, and 1 M NaCl, deoxyguanosine adducts are approximately 1%, 6%, and 24% cis, whereas deoxyadenosine adducts are approximately 11%, 14%, and 37% cis, respectively. NaCl also increases the proportion of cis adducts formed with poly(G) and dAMP. It is proposed that the increase in cis-adduct formation due to salt results from SN1 attack of chloride ion on the BPDE carbocation, forming a trans chlorohydrin, followed by SN2 attack of DNA.

7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide↗
PubMed1994

Alar cartilage haematoma.

We present a previously undescribed site of a subperichondrial haematoma--the alar cartilage. Two children presenting acutely, following trauma, with the clinical appearance of a 'blueberry' within the nasal vestibule are described. We recommend early surgical drainage of this lesion, as delay in definitive treatment may give rise to a cosmetic deformity.

Cartilage↗
PubMed1992

Use of binding site neighbor-effect parameters to evaluate the interactions between adjacent ligands on a linear lattice. Effects on ligand-lattice association.

A method using binding site "neighbor-effect" parameters (NEPs) is introduced to evaluate the effects of interaction between adjacent ligands on their binding to an infinite linear lattice. Binding site overlap is also taken into account. This enables the conditional probability approach of McGhee & von Hippel to be extended to more complex situations. The general equation for the isotherm is v/LF = SFKF, where v is the ratio of bound ligands to lattice residues, LF is the free ligand concentration, SF is the fraction of binding sites that are free, and KF is the average association constant of a free site. Solutions are derived for three cases: symmetric ligands, and asymmetric ligands on isotropic or anisotropic lattices. For symmetric ligands there is one NEP, E, which is the ratio of the average binding affinity of a free site if the status of the lattice residue neighboring one end of the site is unspecified (left to chance) to the affinity when this residue is free (holding the other neighbor constant). Thus KF is KE2, where K is the affinity of an isolated site. If a site is n residues long, SF is f ffn-1, where f = 1 - nv is the fraction of residues that are free and ff is the conditional probability that a free residue is bordered on a given side by another free residue. The expression for ff is 1/(1 + x/E), where x is v/f, E is (1 - x + [(1 - x)2 + 4x omega]1/2)/2, and omega is the co-operativity parameter. The binding of asymmetric ligands to an isotropic lattice is described by two NEPs; the last case involves four NEPs and a bound ligand orientation parameter. For each case, the expected length distribution of clusters of bound ligands can be calculated as a function of v. When Scatchard plots with the same intercepts and initial slope are compared, it is found that ligand asymmetry lowers the isotherm (relative to the corresponding symmetric ligand isotherm), whereas lattice anisotrophy raises it.

Binding Sites↗
PubMed1992

Haematopoietic malignancies in zoo animals.

Myelogenous leukaemia was found in a Russell's viper, a Honduran milk snake, a marine toad, a Byrne's marsupial mouse and an African hedgehog. Lymphocytic leukaemia was present in a broad banded copperhead and an Indian lion. Visceral lymphomatosis was observed in a snowy owl.

Animal Diseases↗
PubMed1992

An unusual pharyngeal pouch.

The third case of a double pharyngeal pouch is reported. It was excised and the patient made an uneventful recovery.

Humans↗