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Thesis (doctoral)--Freie Universität Berlin, 1983.

The abuse of heroin and opiates in the Northeast United States has grown to reach epidemic proportions over the past fifteen years. As this epidemic rages on, many victims of addiction are unable to find or afford treatment, and unfortunately, most insurance companies only fund 30 to 60 days of treatment although it can often take that long to clear the drugs from an addict's system. This can lead to a lifelong cycle of recovery and relapse. For a solution to this problem of recovery, many recovery therapists look to Abraham Maslow's Hierarchy of needs. At the peak of Maslow's Hierarchy of Needs pyramid is the need for self-actualization: the desire "to become everything that one is capable of becoming." This "need" aligns with the predominant goal of the mental health recovery paradigm, which is for people to "strive to reach their full potential" (Henwood et. all). It is typically understood how architecture provides for basic physiological needs and safety for people in need, but how might it provide for "upper-level" needs, such as Maslow's concept of self-actualization? This idea of self-actualization relies heavily on the notion of individuality, creativity, and inspiration, so providing a framework for a user to work and create within could be beneficial to their growth and betterment as an individual. According to Kenney Miller, cofounder of the Maine Harm Reduction Alliance, "Using the arts, particularly story telling, may help rehumanize people and empower them to feel they have a voice and they have something worth saying... The more we can empower people in the recovery process, the more successful it can be" (MacQuarrie). Because addiction affects not only individuals, but rather their entire community, providing opportunity for empowerment on a personal scale must be able to lead to empowerment and reconstruction on a community scale as well. In a city such as Lewiston, Maine, which has lost its former textile-making based identity, residents have lost hope for job opportunity and have turned t drug and alcohol abuse as a coping mechanism. A new movement towards arts and skilled crafts has recently erupted in the downtown area, which is starting to bring back Lewiston's Identity as a maker-based community. This thesis will contribute to and solidify Lewiston's maker-based movement forward, while simultaneously looking backward, learning and growing from the scars that history has embedded in the city. It will also focus on the ways in which the physical environment affects not only creativity and self improvement, but the restoration of the human mind from an unhealthy state through internally-focused spaces as well as peripheral links to context and community. / 0 / SPK / specialcollections@tulane.edu

Intracellular recordings were made from neurones of the rat locus coeruleus (lc) contained within a brain slice maintained <i>in vitro</i>. When applied to the slice in known concentrations, K opioid receptor agonists produced a concentration-dependent, naloxone-reversible depression of the electrically evoked excitatory post-synaptic potential (epsp). This effect of K agonists was observed in the absence of changes in the membrane potential or input resistance of the post-synaptic cell. Similarly, the K agonists had no effect on the tetrodotoxin-resistant action potential waveform. Naloxone antagonised the response to U50488 with an apparent dissociation equilibrium constant (K<SUB>d)</SUB> of 28 nM, consistent with the response being mediated via K opioid receptors. In contrast, u opioid receptor agonists caused a membrane hyperpolarisation concomitant with a fall in neuronal input resistance, and depressed the tetrodotoxin-resistant action potential. These effects were concentration-dependent and antagonised by naloxone; the hyperpolarising action of [D-Ala<SUP>2</SUP> , NMePhe<SUP>4</SUP> , Gly-ol<SUP>5</SUP> ] enkephalin (DAGO) was antagonised by naloxone with a K<SUB>d</SUB> of 1.5 nM. These findings are in agreement with previous reports that u receptor activation increases a potassium conductance in lc neurones. The epsp was depressed, but not abolished, by the excitatory amino acid antagonists, 2-amino-5-phosphonovaleric acid (2APV) and kynurenic acid, suggesting that the epsp was at least partly mediated by an excitatory amino acid. U50488 did not depress the depolarisation produced by local application of L-glutamic acid. In addition to the epsp, a noradrenergic inhibitory post-synaptic potential (ipsp) could be evoked in lc neurones. U50488 depressed the ipsp, but this effect was not reversed by naloxone and therefore not mediated via opioid receptors. U50488 had no effect on the all or nothing depolarising potential which could be evoked in a proportion of lc neurones. The effect of U50488 on the epsp was reduced when experiments were performed in the presence of agents - either barium, quinine or 4-aminopyridine - which block potassium conductances. An <i>in vitro</i> autoradiographic study of <SUP>3</SUP> H bremazocine binding within the lc revealed that the majority of binding was displaced by a combination of unlabelled DAGO and [D-Ser<SUP>2</SUP> ] Leu enkephalin Threonine (DLSET) and so represented u sites. A significant proportion however, was displaceable by unlabelled U50488 and thus represented K binding sites. It is concluded that K opioid receptors are situated pre-synaptically within the lc and when activated depress excitatory synaptic transmission.

No description available.

Aims and objectives Substance misuse is a chronic relapsing condition associated with high morbidity and mortality. Treatment attempts to reduce harms associated with drug use and to promote recovery and has developed considerably in the last 30 years. Opioid substitution therapy using methadone (OST-M) is an effective treatment for opioid dependency. Though the effectiveness of OST-M in delivering harm-reduction is well evidenced, evidence demonstrating recovery is limited as is understanding of those factors influencing progress. In this context, national policy makers and stakeholders have repeatedly questioned the value of OST-M as a substance misuse treatment and, at times, have sought to limit its use. Rigorous, long term outcome studies of UK subjects are required to improve clinical outcomes in OST-M subjects and to ensure ongoing availability of evidence-based treatments. In this context, the study had two main objectives: to demonstrate that standard clinical information systems can deliver rich, valid datasets to support outcome research; to use these data to explore the relationships between a selection of baseline variables (patient characteristics, comorbid conditions, the nature of substance misuse and the treatment received), the clinical process and long term outcomes achieved in a large cohort of OST-M patients in a standard NHS treatment setting. Methods and materials Standard clinical information, collected over 7 years, was linked with validated data from a range of databases. A large representative sample (76% of the OST-M treatment population in a region) was described in detail. Follow-up data were retrieved from clinical casenotes (4 years) and linked datasets (4-7 years) and collated to create a database for analysis. Variables for analysis were selected following a review of the published literature. Univariate analyses were undertaken to demonstrate statistically significant associations between baseline and follow-up variables. Significant variables were then entered into multiple regression analyses to develop predictive models for selected outcomes. Any predictive models were then subjected to cross-validation to determine their predictive power in novel datasets. Key results Many highly significant associations were shown. Significant personal (demographic) factors included: age, gender, having children, having conflict in personal relationships, educational level achieved and being in employment. It was notable that the area lived in (of three districts) was strongly associated with a wide variation in clinical process and outcomes achieved. Whether treated in primary care or specialist services, the medical treatments received, the level of non-NHS support and patient satisfaction showed strong associations with outcome. Baseline illicit drug use was also strongly associated with outcome. Multiple regression analyses found that despite these highly significant associations, strong predictive models of long terms outcome could not be demonstrated. Where weak models were created - predicting drug use (by self - report); drug use (positive tests); family stability - cross validation showed these had no predictive value in novel datasets. Conclusions Standard clinical information, linked with relevant NHS datasets can give rich and comprehensive data suitable for research of large representative samples over long time periods. This study represents one of the largest OST-M populations ever described in the UK with longer follow-up periods than most of the published literature. In this study strong associations were found between a range of independent and dependent variables over 4-7 years. These findings broadly reflected the evidence base. However, the associated variables could not generate strong useful predictive models of long term outcome. This could reflect issues of study design or data quality. This type of approach should be further developed in the field of substance misuse research. Issues of data quality would require to be addressed to maximize the value of these datasets. Further research is required to develop better understanding into key factors influencing long term outcomes of treatment in substance misuse.

Identification of maternal opioid abuse in pregnancy is often difficult to ascertain in the absence of reliable self report. For this reason, physicians and child protection workers often turn to maternal and neonatal hair analysis for the detection of in utero opioid exposures. Since neonatal opiate hair analysis continues to prove difficult due to the scarcity of the hair sample and low drug concentrations, I developed a sensitive method utilizing headspace solid-phase microextraction (HS-SPME) coupled with gas chromatography-mass spectrometry (GC-MS) for the detection of three principal opiates (morphine, codeine, and 6-monoacetylmorphine) in human hair. Moreover, I characterized an at-risk neonatal population for in utero opiate exposures as well as for other drugs of abuse and alcohol. Equipped with a sensitive and specific method for the detection of opiate exposures and understanding the addiction profiles of pregnant women may lead to better clinical and social management and may benefit an at-risk population.