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Biomedical subjects

M Farrell

Publications and source records attributed to M Farrell.

At least 37 records · Page 2Linked to original sources

Schwann cell invasion of the conus medullaris: case report.

As Schwann cells possess regenerative capabilities there is intense interest concerning their role in central nervous system (CNS) regeneration. We report on a case of an intramedullary schwannoma involving the conus medullaris and spinal cord above it. We discuss the possible origin of these cells and the mechanisms by which these cells may invade the CNS. We offer imaging and discuss experimental studies to support our hypothesis. This case concerns a 48-year-old man, who presented with a 6-month history of bilateral lower extremity weakness. Magnetic resonance imaging (MRI) revealed an intramedullary tumour extending from the conus to T11. At operation, following laminectomy and durotomy, a schwannoma was dissected free from the conus. Total gross resection of tumour was achieved. The patient made an uneventful and full recovery. This case shows that Schwann cells can invade the CNS. Manipulation of the transitional zone astrocytic barrier may offer a potential avenue for Schwann cells to enter the CNS in pathological states.

Humans↗

Presenilin-1 mutation (E280G), spastic paraparesis, and cranial MRI white-matter abnormalities.

The authors report unusual presentations of members of an Irish family with familial AD due to an E280G mutation in exon 8 of presenilin-1. One had spastic paraparesis and white matter abnormalities on cranial MRI. A sibling had an internuclear ophthalmoplegia, spastic-ataxic quadriparesis, and "cotton-wool plaques" with amyloid angiopathy on brain biopsy. Another affected sibling also had MRI white matter abnormalities. The MRI findings may reflect an ischemic leukoencephalopathy due to amyloid angiopathy affecting meningocortical vessels.

Adult↗

Drug use and initiation in prison: results from a national prison survey in England and Wales.

AIMS: To investigate heroin and cocaine use in a sample of British prisoners, and to explore the characteristics of inmates who use these drugs for the first time while in prison. DESIGN, PARTICIPANTS: A cross-sectional survey of all prisons in England and Wales conducted as part of a major national study of psychiatric morbidity. A total of 3142 prisoners (88.2% of those selected) completed a structured interviewer-administered questionnaire. MEASUREMENTS: Interview measures of personal demographics, social history, psychiatric morbidity and drug use. Personality disorders were diagnosed via the Structured Clinical Interview for DSM-IV (SCID-II) and neurotic symptoms were assessed using the revised Clinical Interview Schedule (CIS-R). FINDINGS: More than 60% of the heroin users and cannabis users reported that they had used these drugs in prison compared with less than a quarter of the life-time cocaine users. More than a quarter of the heroin users reported that they had initiated use of this drug in prison. The extent of an individual's experience of prison was related more consistently to heroin and/or cocaine use in and out of prison than other personal background, social history or psychiatric variables assessed. CONCLUSIONS: The findings indicate that prisons are a high-risk environment for heroin and other drug initiation and use. Although related to drug use, psychiatric variables were not generally associated with initiation in prison, which was dominated by prison exposure. There is a need to explore ways of reducing heroin initiation in prison as part of a broader risk-prevention strategy.

Adolescent↗

Psychosis and drug dependence: results from a national survey of prisoners.

BACKGROUND: The links between drug use and psychosis are of major aetiological and prognostic significance. Psychosis and drug dependence frequently co-occur within the prison population, providing the opportunity to study this link more closely. AIMS: To explore the relationship between psychosis and drug dependence in a sample of prisoners. METHOD: A total of 3142 prisoners were surveyed nationally, and structured clinical data were obtained from a subsample of 503 respondents. Psychiatric assessment was based on the Schedules for Clinical Assessment in Neuropsychiatry (version 1.0). Measures of amphetamine, cannabis, cocaine and heroin use and dependence were obtained through self-report. RESULTS: Logistic regression analyses indicated that first use of amphetamines or cocaine before the age of 16 years and severe cannabis or cocaine dependence were related to an increased risk of psychosis. In contrast, severe dependence on heroin was associated with a reduced risk of this classification. CONCLUSIONS: Severe dependence on cannabis and psychostimulants is associated with a higher risk of psychosis and is in contrast to severe dependence on heroin, which has a negative relationship with psychosis.

Adolescent↗

Neuronal hypertrophy in the neocortex of patients with temporal lobe epilepsy.

The underlying cause of neocortical involvement in temporal lobe epilepsy (TLE) remains a fundamental and unanswered question. Magnetic resonance imaging has shown a significant loss in temporal lobe volume, and it has been proposed that neocortical circuits are disturbed functionally because neurons are lost. The present study used design-based stereology to estimate the volume and cell number of Brodmann's area 38, a region commonly resected in anterior temporal lobectomy. Studies were conducted on the neocortex of patients with or without hippocampal sclerosis (HS). Results provide the surprising finding that TLE patients have significant atrophy of neocortical gray matter but no loss of neurons. Neurons are also significantly larger, dendritic trees appear sparser, and spine density is noticeably reduced in TLE specimens compared with controls. The increase in neuronal density we found in TLE patients is therefore attributable to large neurons occupying a much smaller volume than in normal brain. Neurons in the underlying white matter are also increased in size but, in contrast to other reports, are not significantly elevated in number or density. Neuronal hypertrophy affects HS and non-HS brains similarly. The reduction in neuropil and its associated elements therefore appears to be a primary feature of TLE, which is not secondary to cell loss. In both gray and white matter, neuronal hypertrophy means more perikaryal surface area is exposed for synaptic contacts and emerges as a hallmark of this disease.

Adolescent↗

Genetic counseling and risk communication services of newborn screening programs.

OBJECTIVES: Newborn screening test results labeled "positive" can have uncertain implications for parents, especially when false-positive results occur or when heterozygous infants are detected using molecular tests for sickle cell hemoglobinopathy or cystic fibrosis. This study surveyed communication services across state newborn screening programs. METHODS: We surveyed newborn screening programs to identify current communication practices and the methods used for quality assessment. Two successive survey instruments with fixed-answer and free-answer questions were distributed to screening program follow-up coordinators or similar designated officials associated with 52 states and territories. RESULTS: Replies from 46 respondents (89% response rate) revealed that regional newborn screening programs vary widely in their approaches to counseling. Of the 46 respondents, 35 (76%) answered that they "routinely" provide counseling services to families of affected infants. Depending on the disease, an average of approximately one-half that number provide counseling after false-positive results or for heterozygous infants. Most respondents advocate nondirective counseling more than direct advice. Most programs reported that counseling was usually done by subspecialist physicians or specially trained nurses and counselors. Respondents reported a perception that the "quality" of counseling by these professionals is better than counseling by primary care physicians. Few programs reported systems for assessing quality assurance of counseling. CONCLUSIONS: Newborn screening programs in the United States vary widely with regard to counseling practices, and no best practices are currently evident. Few programs provide counseling quality assurance. Further study and advocacy is needed to optimize communication services, preferably before implementation of molecular tests arising as a result of the Human Genome Project.

Communication↗

Alpha2 adrenergic agonists for the management of opioid withdrawal.

BACKGROUND: Withdrawal (detoxification) is necessary prior to drug-free treatment. It may also represent the end point of long-term treatment such as methadone maintenance. The availability of managed withdrawal is essential to an effective treatment system. OBJECTIVES: To assess the effectiveness of interventions involving the use of alpha2 adrenergic agonists (clonidine, lofexidine, guanfacine, guanabenz acetate) to manage the acute phase of opioid withdrawal. SEARCH STRATEGY: Multiple electronic databases were systematically searched. Reference lists of retrieved studies, reviews and conference abstracts were handsearched and relevant pharmaceutical companies contacted. SELECTION CRITERIA: Randomised or quasi-randomised controlled trials that compared alpha2 adrenergic agonists with another form of treatment (or placebo) to modify the signs and symptoms of withdrawal in participants who were primarily opioid dependent. DATA COLLECTION AND ANALYSIS: One reviewer assessed studies for inclusion and undertook data extraction. Inclusion decisions and the overall process were confirmed by consultation between all four reviewers. MAIN RESULTS: Twenty-four studies, involving 1956 participants, were included. Nineteen were randomised controlled trials; in two allocation was by participant choice, one used alternate allocation and in two the method of allocation was unclear. Ten studies compared a treatment regime based on an alpha2 adrenergic agonist with one based on reducing doses of methadone. Diversity in study design, assessment and reporting of outcomes limited the extent of quantitative analysis. From the comparison of alpha2 adrenergic agonist regimes with reducing doses of methadone, withdrawal intensity is similar to, or marginally greater with alpha2 adrenergic agonists, but signs and symptoms of withdrawal occur and resolve earlier in treatment. Participants stay in treatment longer with methadone. The likelihood of completing withdrawal is similar, or slightly less, with clonidine or lofexidine. Clonidine is associated with more adverse effects (low blood pressure, dizziness, dry mouth, lack of energy) than reducing doses of methadone. Lofexidine does not reduce blood pressure to the same extent as clonidine, but is otherwise similar to clonidine. REVIEWER'S CONCLUSIONS: Treatment regimes based on the alpha2 adrenergic agonists clonidine and lofexidine, and those based on reducing doses of methadone over a period of around 10 days, have similar efficacy in the management of withdrawal from heroin or methadone. Participants stay in treatment longer with methadone regimes and experience less adverse effects. The lower incidence of hypotension makes lofexidine more suited to use in outpatient settings than lofexidine. There are insufficient data available to support a conclusion on the efficacy of guanfacine.

Acute Disease↗

Antidepressants for cocaine dependence.

BACKGROUND: Cocaine dependence is a common and serious condition, which has become nowadays a substantial public health problem. The past decade has witnessed a sustained search for an effective pharmacotherapeutic agent for the treatment of cocaine dependence. While administration of cocaine acutely increases intercellular dopamine, serotonin, and norepinephrine levels by blocking their presynaptic reuptake, chronic cocaine abuse leads to down-regulation of monoamine systems. Post-cocaine use depression and cocaine craving may be linked to this down-regulation. Antidepressant pharmacotherapy, by augmenting monoamine levels, may alleviate cocaine abstinence symptomatology, as well as relieving dysphoria and associated craving by general antidepressant action. OBJECTIVES: To conduct a systematic review of all RCTs on the use of antidepressants for treating cocaine dependence. SEARCH STRATEGY: We searched the Cochrane Controlled Trials Register (Cochrane Library, issue 4, 2000), MEDLINE (from 1966 - 2000), EMBASE (from 1980 - 2000), LILACS (from 1982 - 2000), PsycLIT (from 1974 - 2000), Biological Abstracts (1982 to 2000). Other searches:reference searching; personal communication; conference abstracts; unpublished trials from pharmaceutical industry; book chapters on treatment of cocaine dependence. SELECTION CRITERIA: The inclusion criteria for all randomised controlled trials were that they should focus on the use of antidepressants on the treatment of cocaine dependence. Trials including patients with additional diagnosis such as opiate dependence were also eligible. DATA COLLECTION AND ANALYSIS: The reviewers extracted the data independently and Relative Risks, weighted mean difference and number needed to treat were estimated. The reviewers assumed that people who died or dropped out had no improvement and tested the sensitivity of the final results to this assumption. MAIN RESULTS: 18 studies were included in the review, with 1177 people randomised. Positive urine sample for cocaine metabolites was the main efficacy outcome, with no significant results obtained regardless the type of antidepressant. Compared to other drugs, desipramine performed better but showing just a non significant trend with heterogeneity present as revealed by the chi-square test (8.6, df=3; p=0.04). One single trial showed imipramine performed better than placebo in terms of clinical response according to patient's self-report. A similar rate of patients remaining in treatment was found for both patients taking desipramine or placebo. Results from one single trial suggest fluoxetine patients on SSRIs are less likely to dropout. Similar results were obtained for trials where patients had additional diagnosis of opioid dependence and/or were in methadone maintenance treatment. REVIEWER'S CONCLUSIONS: There is no current evidence supporting the clinical use of antidepressants in the treatment of cocaine dependence. Given the high rate of dropouts in this population, clinicians may consider adding psychotherapeutic supportive measures aiming to keep patients in treatment.

Antidepressive Agents↗

Dopamine agonists for cocaine dependence.

BACKGROUND: Cocaine is a major drug of abuse. Cocaine dependence is a common and serious condition, which has become nowadays a substantial public health problem. There is a wide and well documented range of consequences associated to chronic use of this drug, such as medical, psychological and social problems, including the spread of infectious diseases (e.g. AIDS, hepatitis and tuberculosis), crime, violence and neonatal drug exposure. Therapeutic management of the cocaine addicts includes an initial period of abstinence from the drug. During this phase the subjects may experience, besides the intense craving for cocaine, symptoms such as depression, fatigue, irritability, anorexia, and sleep disturbances. It was demonstrated that the acute use of cocaine may enhance dopamine transmission and chronically it decreases dopamine concentrations in the brain. Pharmacological treatment that affects dopamine could theoretically reduce these symptoms and contribute to a more successful therapeutic approach. OBJECTIVES: To evaluate the efficacy and acceptability of dopamine agonists for treating cocaine dependence. SEARCH STRATEGY: We searched: The Cochrane Controlled Trials Register (Cochrane Library, issue 4, 2000), MEDLINE (from 1966 - 2000), EMBASE (from 1980 - 2000), LILACS (from 1982 - 2000), PsycLIT (from 1974 - 2000), Biological Abstracts (1982 to 2000). Reference searching; personal communication; conference abstracts; unpublished trials from pharmaceutical industry; book chapters on treatment of cocaine dependence. SELECTION CRITERIA: The inclusion criteria for all randomised controlled trials were that they should focus on the use of dopamine agonists on the treatment of cocaine dependence. Trials including patients with additional diagnosis such as opiate dependence were also eligible. DATA COLLECTION AND ANALYSIS: The reviewers extracted the data independently and Relative Risks, weighted mean difference and number needed to treat were estimated. The reviewers assumed that people who died or dropped out had no improvement and tested the sensitivity of the final results to this assumption. MAIN RESULTS: Twelve studies were included, with 587 participants randomised. Amantadine and Bromocriptine were compared to placebo in most of trials. In two studies amantadine was directly compared to bromocriptine, while amantadine was compared to desipramine, an antidepressant in three. The main efficacy outcome presented was positive urine sample for cocaine metabolites, with no significant differences between interventions. When retention in treatment was assessed as an acceptability measure, it was found a similar rate of patients remaining in treatment in both placebo and active drugs. There were no significant differences in trials where participants had primary cocaine dependence or had additional diagnosis of opioid dependence and/or were in methadone maintenance treatment. REVIEWER'S CONCLUSIONS: Current evidence does not support the clinical use of dopamine agonists in the treatment of cocaine dependence. Given the high rate of dropouts in this population, clinicians may consider adding psychotherapeutic supportive measures aiming to keep patients in treatment.

Amantadine↗

Factors predicting subcutaneous implanted central venous port function: the relationship between catheter tip location and port failure in patients with gynecologic malignancies.

OBJECTIVE: We set out to determine the factors that predict subcutaneous implanted central venous port function. Specifically, we sought to determine whether the location of the catheter tip is correlated with port failure. METHODS: A review of all gynecologic oncology patients who underwent initial port placement between 1993 and 1998 was undertaken. The initial chest radiograph following port placement was reviewed, and the venous location of the catheter tip was recorded. Patients were followed until port removal, death, or the last documentation of port function. RESULTS: Two hundred thirty-six patients underwent port placement during the study period. The majority of patients (97%) had their port placed for intravenous chemotherapy. The median time of port duration in patients with a functional port was 21.6 months. Forty of the 236 ports (17%) were removed because of device malfunction. Catheter tips were located in the central venous system in 164 (69%) cases and outside of the central venous system in 72 (31%) cases. Removal secondary to malfunction was significantly higher when the catheter tip was located outside of the central venous system (30/72 (42%) versus 10/164 (6%), P = 0.001). By life-table analysis, ports removed for malfunction with their tips located centrally had a significantly longer median duration of functional use than those whose tips were located peripherally (78 versus 44 months, P = 0.0001). CONCLUSIONS: The rate of port removal secondary to malfunction is significantly less if the catheter tip is located in the central venous system. Confirmation of the location of the catheter tip is imperative for the long-term function of a subcutaneous implanted central venous port.

Adult↗

'Breaking bad news' within a paediatric setting: an evaluation report of a collaborative education workshop to support health professionals.

UNLABELLED: AIMS OF PROJECT: To evaluate a workshop to prepare health professionals for breaking bad news in the paediatric setting. BACKGROUND: Breaking bad news can be difficult for health professionals, and it seems that few receive specific training for undertaking this challenging task. Latterly, however, there have been reports of training programmes being developed to prepare health professionals for breaking bad news, although most focus upon meeting needs of medical staff only. While doctors have a uniquely important role in breaking bad news it is evident that other health professionals, most frequently nurses, can be equally involved in this encounter. Accordingly, nurses and other professionals need training to recognize the contribution that they can make in ensuring sensitive and effective bad news disclosure. DESIGN: A one-day, multi-professional, experiential training workshop. METHOD: Forty-five participants, mainly nurses (34, 76%) and doctors (10, 22%), attended one of five breaking bad news workshops set up for staff working in a range of paediatric settings including Accident and Emergency and Intensive Care. Each of the workshops was facilitated by three facilitators from varied backgrounds. Using an experiential design, participants were supported to explore and reflect upon breaking bad news issues, which also included engagement with actors to act out realistic bad news scenarios. Debriefing, using a positive learner-centred model of feedback, provided the main platform for promoting learning. Following the workshop, participants completed an evaluation questionnaire, seeking their perceptions of the effectiveness of the workshop in enhancing knowledge and communication skills. DATA ANALYSIS: Atlas.ti, a qualitative computer data analysis software program was used to explore the evaluation comments made by participants, resulting in the generation of common themes. FINDINGS: Seven themes, including development of practice, the value of sharing, benefit of feedback, and team work, emerged from responses. All responses indicated that the workshop had been beneficial and an effective training method, with most participants (40 of 89%) indicating that they would strongly recommend their colleagues to attend a similar workshop. CONCLUSION: The educational approach reported is considered by participants to be beneficial in preparing health professionals for breaking bad news in a collaborative way.

Attitude of Health Personnel↗

The perceived learning needs of paediatric intensive care nurses caring for children requiring haemofiltration.

This paper reports on a small exploratory phenomenological study to describe the lived experiences of paediatric intensive care nurses, who extended their roles to care for critically ill children requiring continuous veno-venous haemofiltration. In describing and understanding this learning experience, an insight into the educational and support needs of these nurses is offered. From the insight shared, five main themes were identified. These included the overwhelming need to be a competent practitioner, which was perceived within the context of knowledge for effective practice and technical dexterity.While generalizability of findings is not intended, the findings could be of value to other intensive care settings to guide the identification and implementation of strategies to meet the needs of nurses undertaking similar roles.

Child↗

A prospective study of complications associated with cuffed, tunnelled haemodialysis catheters.

BACKGROUND: Despite the US Dialysis Outcome Quality Initiative )DOQI( guidelines, for various reasons, increasing numbers of end-stage renal disease patients are becoming dependent on cuffed haemodialysis catheters (HCs) for chronic haemodialysis access. Their use is complicated by frequent failure due to thrombosis and catheter-related sepsis. In our unit, all HCs are put in place by the radiology department. METHODS: In a prospective study we looked at the outcome of all HCs over a three-year period, during which time 573 consecutive HCs were placed in 336 patients. Each line was followed individually until it was removed or until the end of the study. RESULTS: In a survival analysis of those HCs removed following HC failure, HC half-life was 312 days and one-year HC survival was 47.5%. The most frequent indications for HC removal were non-function (36.6%), clinical suspicion of line sepsis (16.4%) and patient death (14.4%). Using a Cox proportional hazards model, catheter number in a given patient and the presence of diabetes mellitus were found to be independent predictors of HC failure. The total incidence of HC-related sepsis was 1.3 episodes/1000 catheter days. The probability of developing bacteraemic HC-related sepsis was 27.5% at one year. CONCLUSIONS: Less than half of the HCs were removed electively because of availability of a more permanent mode of renal replacement, thereby illustrating the level of dependence that has developed on them as permanent access. Consequently, their limitations (infection and malfunction) are placing an ever increasing burden on the healthcare services.

Catheters, Indwelling↗

Evaluating preceptorship arrangements in a paediatric setting.

Preceptorship can be a valuable support mechanism for newly qualified nurses. Both preceptors and preceptees need support to ensure effective preceptorship arrangements. Maintaining effective preceptorship arrangements can be challenging for preceptees, preceptors and the organisation. Further research is required to explore the full potential of preceptorship.

Humans↗

Nicotine, alcohol and drug dependence and psychiatric comorbidity. Results of a national household survey.

BACKGROUND: There is a well-recognised relationship between substance use disorders and other psychiatric disorders. This relationship has been well documented in a range of population-based studies. AIMS: This study aims to report on consumption patterns of and dependence on nicotine, alcohol and non-prescribed drugs and to report on the levels of psychiatric morbidity in these groups. METHOD: A national household study of psychiatric morbidity was conducted in England and Wales. Psychiatric assessment was based on the Clinical Interview Schedule-Revised (CIS-R). Measures of nicotine, alcohol and drug use and dependence were obtained. This paper compares the levels of psychiatric morbidity in the non-dependent and the nicotine-, alcohol- and drug-dependent cases. RESULTS: Twelve per cent of the non-dependent population were assessed as having any psychiatric disorder compared with 22% of the nicotine-dependent, 30% of the alcohol-dependent and 45% of the drug-dependent population. CONCLUSIONS: There is a clear relationship between dependence on nicotine, alcohol and drugs and other psychiatric morbidity.

Adolescent↗