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Biomedical subjects

A Swann

Publications and source records attributed to A Swann.

At least 19 recordsLinked to original sources

An in vitro model to compare the antimicrobial activity of silver-coated versus rifampicin-soaked vascular grafts.

In situ replacement of infected vascular grafts is an accepted alternative to total graft excision and extraanatomic replacement. Its success relies upon the ability of the newly inserted graft to resist recurrent infection. This study compares the efficacy of two methods used to reduce the risk of graft reinfection: rifampicin soaking versus silver bonding of grafts. The grafts' resistance to infection was tested in vitro in two protocols, each using a panel of seven common bacteria, including methicillin-resistant Staphylococcus aureus (MRSA). The length of time the grafts remained free of organisms was compared between the groups. Both the silver graft and the rifampicin-soaked graft were significantly better than control graft at preventing bacterial growth on the graft surface. The rifampicin inhibited the growth of the gram-positive organisms, including MRSA, significantly better than the silver graft on days 2 and 3 (p < 0.001). Conversely, the silver graft was significantly more effective against the gram-negative organisms until day 4 (p < 0.0001). Both types of graft inhibit the in vitro growth of bacteria more effectively than controls, with rifampicin being most effective against gram-positive organisms and silver being best against the gram-negative organisms.

Acetates↗

Role of microbiological investigations in the management of non-perineal cutaneous abscesses.

BACKGROUND: Pus samples for microbiological examination are routinely sent after incision and drainage of abscesses. There is no evidence that microbiology reports influence treatment for non-perineal cutaneous abscesses. AIMS: This study assessed (1) how often the microbiology report is used to manage patients' treatment after incision and drainage of an abscess and (2) junior surgical trainees' opinions on sending pus for microbiological examination. METHOD: A retrospective analysis of the notes of all patients undergoing incision and drainage of abscesses from January 2001 to January 2002 was made. A telephone poll of junior surgical trainees was also undertaken. RESULTS: Most patients, 91%, had specimens referred for microbiology. Of these 43% yielded no growth. Staphylococcus aureus was the most common organism (55.9% of all positive cultures). Anaerobes were a frequent finding from axilla and groin abscesses. Mycobacterium tuberculosis was grown in two patients. Other less common organisms cultured were methicillin resistant S aureus (n=1) and Proteus sp (n=1). Follow up of microbiology reports was found to be inadequate. CONCLUSION: The bacteria present in non-perineal cutaneous abscesses are, for the most part, predictable. However, a significant number grow less common organisms. It is concluded that pus specimens should be sent routinely for culture and sensitivity and there should be further emphasis on following up microbiology reports by junior medical staff.

Abscess↗

Effects of lithium chloride on induction and expression of methylphenidate sensitization.

Repeated administration of psychomotor stimulants produces an enduring and progressively enhanced behavioral response known as behavioral sensitization, which has been implicated as a model for psychiatric disorders such as mania, schizophrenia, and drug addiction. The objective of the study was to determine whether lithium chloride (LiCl), an anti-manic agent, is effective in blocking the development and/or the expression of behavioral sensitization to methylphenidate. Male Sprague-Dawley rats (n=64) weighing 170-190 g were randomly divided into seven treatment groups. A computerized animal activity monitor system continuously recorded locomotor activity for 16 days. Effects of LiCl on induction of methylphenidate sensitization were studied by giving LiCl before or during six daily methylphenidate administrations. Effects of LiCl on the expression of methylphenidate sensitization were studied by injecting LiCl after sensitization to methylphenidate was induced. It was shown that LiCl treatment modulated the acute methylphenidate effects by transiently attenuating the locomotor response to methylphenidate during the six daily methylphenidate administrations but neither single nor multiple treatments with LiCl blocked the development or the expression of behavioral sensitization.

Animals↗

Methylphenidate sensitization is modulated by valproate.

Repeated administration of the stimulant methylphenidate (MPD) produces sensitization to its own effects. Glutamate, dopamine, and GABA have been implicated in the underlying mechanism of sensitization to stimulants such as amphetamine and cocaine. We have investigated effects of the GABAergic agent sodium valproate (VAL) on the locomotor response to MPD. Activities of male Sprague-Dawley rats were continuously recorded by a computerized activity monitoring system for 15 days. We studied the dose effect of valproate 1) at 50, 100, and 200 mg/kg (i.p.) on motor activities, 2) on the acute response of motor activities to 2.5 mg/kg MPD, and 3) on behavioral sensitization to subsequent repeated injections of MPD. Valproate alone did not significantly affect motor activities. All three doses of valproate attenuated the acute locomotor effects of MPD, while only the 50 mg/kg dose blocked the development of sensitization to subsequent administration. Possible mechanisms involving substrates for the effect of GABA agonists on sensitization are discussed.

Animals↗

Occipital hypoperfusion on SPECT in dementia with Lewy bodies but not AD.

OBJECTIVE: To compare regional cerebral blood flow (rCBF) changes using 99mTc-hexamethylpropyleneamine oxime (99mTc-HMPAO) SPECT in subjects with dementia with Lewy bodies (DLB) and AD and in normal age-matched control subjects; to examine the utility of SPECT changes in the differential diagnosis of AD and DLB. METHOD: Whole-brain SPECT scans were acquired using a single-headed rotating gamma camera (IGE CamStar XR/T) in elderly subjects with consensus criteria DLB (n = 23; mean age = 79.4 years), National Institute of Neurological and Communicative Disorders and Stroke-Alzheimer's Disease and Related Disorders Association AD (n = 50; 81.9 years), and normal control subjects (n = 20; 78.1 years) after injection with 500 MBq of 99mTc-HMPAO. Region-of-interest analysis was performed using a SPECT template registered in Talairach space, with rCBF normalized to cerebellum. RESULTS: Both DLB and AD subjects had significantly reduced rCBF in parietal and temporal regions compared with the control subjects. The AD group also showed a significant reduction in rCBF in the frontal and medial temporal regions and the DLB in the occipital areas compared with control subjects. AD and DLB groups differed only in occipital perfusion (p < 0.01). SPECT measures (occipital and medial temporal) correctly classified 69% of all subjects, with a 65% sensitivity and 87% specificity for DLB against AD and control subjects. CONCLUSION: Temporoparietal hypoperfusion on SPECT is common to both AD and DLB. Occipital hypoperfusion is more frequently seen in DLB. Although not diagnostically specific in individual cases, occipital hypoperfusion on SPECT should raise suspicion that DLB may be the cause of dementia, prompting careful search for other features of the disorder.

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Prevalence and pharmacological management of behavioural and psychological symptoms amongst dementia sufferers living in care environments.

BACKGROUND: Behavioural and psychological symptoms in dementia (BPSD) are a common reason for placement in long term care and are often associated with indiscriminate prescription of psychotropic medication. AIMS: To determine the prevalence of BPSD in care environments, their relationship with severity of dementia and the pattern of psychotropic medication. METHODS: Two hundred and thirty-one elderly residents (39% living in social care facilities and 61% in nursing home care) were assessed using a range of standardised psychiatric schedules. Additional information about the residents and medication was obtained from professional carers. RESULTS: Overall 90% of residents had dementia, 79% of whom had clinically significant BPSD with 58% receiving psychotropic medication. There was no difference in the prevalence of BPSD between social and nursing care. Depression was most common in people with mild dementia, whilst delusions arose most frequently in those with moderate dementia and aberrant motor behaviour had a high prevalence in people with severe dementia. CONCLUSION: BPSD are common in elderly people with dementia living in care environments. More rigorous guidelines are needed pertaining to the prescription and monitoring of medication and the need to disseminate skills regarding psychosocial management approaches to care staff.

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The progression of cognitive impairment in dementia with Lewy bodies, vascular dementia and Alzheimer's disease.

BACKGROUND: Little is known about the rate of progression or associations of cognitive impairment in dementia with Lewy bodies (DLB), or the associations of accelerated decline. METHOD: Dementia patients from a case register were evaluated at baseline and 1 year follow-up using the Cambridge Assessment for Mental Disorders in the Elderly, section B (CAMCOG) and the Mini-Mental State Examination (MMSE) to determine the rate of cognitive decline. Operationalized clinical diagnoses were applied (NINCDS ADRDA for Alzheimer's disease (AD), NINCDS AIRENS for vascular dementia (VaD) and consensus criteria for DLB). RESULTS: One hundred and ninety-three patients completed annual MMSE schedules (AD, 101; DLB, 64; VaD, 38), of whom 154 completed the CAMCOG. The magnitude of cognitive decline (MMSE, 4-5 points; CAMCOG, 12-14 points) was similar in each of the dementias. The strongest predictor of accelerated cognitive decline in DLB was the apolipoprotein E4 allele (17.5 vs 8.3 points decline on the CAMCOG). CONCLUSION: Over 1 year, DLB, VaD and AD patients had similar rates of cognitive decline overall. Apolipoprotein E4 may be an important predictor of more rapid decline in DLB.

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How do memory clinics compare with traditional old age psychiatry services?

METHODS: 100 consecutive referrals to the Northern Memory Clinic (NMC) were compared with 100 referrals to a traditional Old Age Psychiatry (OAPsych) service in the same city in terms of demographic variables, cognitive function (assessed by the Mini-Mental State Examination), and diagnosis. The study also examined the ability of psychometric assessments (CAMCOG, MMSE, Trail-Making Tests A & B, Word Fluency) and CT scans included in the NMC assessment to differentiate between those with and without DSM-IV dementia. RESULTS: NMC patients were significantly younger than OAPsych patients, had lower levels of cognitive impairment, and had a wider range of diagnoses. The NMC patients who were diagnosed as having dementia were found to be at least 2 years earlier in the course of the disease than those seen by the OAPsych team. The CAMCOG and MMSE were proved to be effective at distinguishing between patients diagnosed as dementing versus non-dementing with cut-offs of 82/83 and 23/24 respectively, confirming previous findings. The Memory subscale of the CAMCOG, though much shorter, was equally as effective using a cut-off of 20/21. Trail-Making Tests, Word Fluency (FAS), and measurement of the minimum width of the medial temporal lobe (MTL) on angled CT scans were poor indicators of dementia in this sample. CONCLUSIONS: This study confirms that the memory clinic is targeting a distinct patient group compared to traditional old age psychiatry services, is identifying cases of dementia much earlier, and as such has potential to make valuable contributions to patient care.

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Blockade of sensitization to methylphenidate by MK-801: partial dissociation from motor effects.

The role of MK-801's locomotor effect in blocking the development of sensitization to methylphenidate was investigated utilizing a computerized locomotor activity monitoring system. After 7 days of acclimation to a 12:12 light-dark cycle (lights on at 07:00), male Sprague-Dawley rats (n=62) were housed in test cages and motor activity was recorded continuously for 16 days. The first 2 days of recording served as a baseline for each rat, and on day 3 each rat received a saline injection. On days 4 to 9 rats were randomly divided into seven groups: Rats received either six daily s.c. injections of methylphenidate (2.5 mg/kg; Group 1), or six daily i.p. injections of 0.30 mg/kg, 0.05 mg/kg MK-801 (Groups 2 and 3, respectively); two MK-801 pre-treatment groups received a single i.p. injection of 0.05, or 0.30 mg/kg MK-801 one hour prior to 2.5 mg/kg methylphenidate (n=8 each) on day 4 followed by five daily injections of 2.5 mg/kg methylphenidate; and finally, two cotreatment groups received a challenge dose of 2.5 mg/kg methylphenidate on day 4 followed by either 0.05 or 0.30 mg/kg MK-801 i.p. one hour prior to 2.5 mg/kg methylphenidate from days 5 to 9. All groups were allowed five days of no treatment before being re-challenged on day 15 with the same treatment they received on day 4. Methylphenidate and 0.30 mg/kg MK-801 sensitized to their own locomotor effects, but 0.05 mg/kg MK-801, which had no acute motor effects, did not. The administration of MK-801 (0.30 mg/kg) prior to methylphenidate either singly on day 4, or coadministered throughout the repeated methylphenidate treatment phase, blocked the development of sensitization to methylphenidate. However, MK-801 at 0.05 mg/kg delayed the development of sensitization when co-administered on days 5 to 9, but a single injection 1 h prior to methylphenidate on day 4 did not prevent sensitization to subsequent methylphenidate administration. In conclusion, MK-801 prevents sensitization to methylphenidate; motor stimulation by MK-801 is not necessary for short-term prevention or delay of sensitization to methylphenidate but may be necessary for a persistent blockade of sensitization.

Animals↗

The role of MK-801 in sensitization to stimulants.

Behavioral responses to stimulants can be progressively and persistently enhanced by their repeated administration. This phenomenon, called behavioral sensitization, may underlie substance abuse, psychosis, recurrence in bipolar disorder, or other psychiatric problems. A growing body of work has implicated excitatory amino acid systems in behavioral sensitization. Most of the evidence for a role of excitatory amino acids has come from experiments demonstrating prevention of sensitization by excitatory amino acid antagonists, especially the noncompetitive NMDA receptor antagonist MK-801. Results of studies with MK-801 have varied, however, leading to conflicting interpretations of its relationship to behavioral sensitization. This paper critically discusses the design of experiments that have used MK-801, and interprets data from these experiments in terms of the two leading explanations for the role of MK-801: 1) that sensitization is an example of the family of plastic events that require excitatory amino acid transmission or 2) that interoceptive cues associated with MK-801 lead to state-dependent learning that modifies sensitization because, in essence, the animal does not recognize the stimulant as the same drug if it is given in close association with MK-801. Based on conflicting reports on effects of MK-801, we propose 1) strategies for distinguishing components of MK-801's effects on responses to stimulants, 2) a model that is a hybrid of the two interpretations of its effects on sensitization, and 3) experimental strategies for testing this model.

Amphetamine-Related Disorders↗

Quality of life for people with dementia living in residential and nursing home care: the impact of performance on activities of daily living, behavioral and psychological symptoms, language skills, and psychotropic drugs.

Many people with dementia reside in care facilities. Little is known about how key parameters impact upon their quality of life (QOL). All 209 people with dementia in six facilities received a standardized assessment (Neuropsychiatric Inventory [NPI], Barthel Scale, psychotropic drugs). One hundred twelve residents were assessed using Dementia Care Mapping, an observational method for QOL indices. Lower performance on activities of daily living (reduced well-being [WB] r = +0.39, p < .0001; social withdrawal [SW] r = +0.42, p < .0001; engagement in activities [EA] r = +0.31, p = .001) and taking psychotropics (WB 2.5 vs. 3.2, t = 2.3, p = .02; SW 11.4% vs. 2.7%, t = 3.0, p = .004; EA 56.5% vs. 71.9%; t = 3.5, p = .001) were associated with reduced QOL, but symptoms from the NPI were not. More focused prescribing of psychotropics and better staff training are essential.

Activities of Daily Living↗

Valproate prevents the induction of sensitization to methylphenidate (ritalin) in rats.

Repetitive exposure to methylphenidate (MPD) elicits sensitization to its locomotor effects. Drugs that affect the GABA system may modify adaptations to drug exposure. Therefore, we have examined the effect of sodium valproate, which enhances GABA function, on the development of sensitization to MPD using an automated, computerized animal activity monitoring system to record each rat's motor activities for 15 consecutive days. Rats were recorded before and after saline injection (Days 1-2) to provide baseline activity. Animals were then randomly assigned to the following three groups that received: (1) 2.5 mg/kg MPD (s.c.) for six consecutive days (Days 3-8), (2) a single dose of valproate (50 mg/kg; i.p.) 1 h prior to the first (Day 3) of six daily doses of MPD (2.5 mg/kg; s.c. ), or (3) five daily doses of valproate (50 mg/kg, i.p.) 1 h prior to MPD (2.5 mg/kg, s.c.) on Days 4-8. There was no drug treatment during the next 5 days (Days 9-13). All rats were then re-challenged with MPD (2.5 mg/kg, s.c.) on Day 14. Group 2 rats were also re-challenged with 50 mg/kg valproate followed by 2.5 mg/kg MPD 1 h later on Day 15. Administration of MPD alone produced a sensitized response. Multiple valproate injections prevented the induction of MPD-elicited sensitization in all four motor indices, while a single valproate injection prevented the induction of MPD-elicited sensitization in two of four motor indices studied. In conclusion, a single injection 50 mg/kg valproate given prior to any MPD treatment partially blocked the induction of MPD sensitization while repeated injections of valproate co-administered with MPD treatment completely prevented this effect.

Animals↗

Valproate modulates the expression of methylphenidate (ritalin) sensitization.

Repeated administration of amphetamine, cocaine, and methylphenidate (MPD) has been reported to elicit behavioral sensitization to their locomotor and stereotypic effects in rodents. GABAergic drugs have been shown to inhibit behavioral effects of stimulants. The objective of the present study was to determine whether single or multiple administration of sodium valproate, a GABA agonist, would prevent the expression of sensitization to the locomotor effect of MPD once it has developed. Twenty-eight male Sprague-Dawley rats were randomized into three treatment groups: a control group received only 2.5 mg/kg MPD during the 14-day cycle, a group received a single 50 mg/kg valproate injection on Day 9, and a group received multiple 50 mg/kg valproate injection on Days 9-13. Rats were housed in test cages and behavioral activities were recorded for 14 consecutive days. All injections were given between 12:00 h and 14:00 h. Multiple injection of MPD elicited sensitization to its locomotor and stereotypic effects. Single administration of valproate did not block the expression of sensitization in the four locomotor indices measured. However, multiple administration of valproate prevented MPD sensitization to horizontal activity, total distance and number of stereotypic movements.

Animals↗

Diurnal differences in sensitization to methylphenidate.

Using a computerized monitoring system, we investigated the development of motor sensitization to methylphenidate (MPD) in the rat, and determined whether sensitization was dependent on the time of drug administration. Male Sprague-Dawley rats were housed in test cages and motor activity was recorded continuously for 16 days. The first 2 days served as baseline for each rat, and on day 3 each rat received a saline injection. The locomotor response to 0.6, 2.5, or 10 mg/kg of MPD was tested on day 4, followed by 5 days of single injections of 2.5 mg/kg MPD (days 5-9). After 5 days without injection (days 10-14) rats were re-challenged (day 15) with the same doses they received on day 4. There were three separate challenge doses and four different times of administration: 08:00, 14:00, 20:00, or 02:00 h. Horizontal activity, total distance, vertical activity, stereotypic activity, and number of stereotypic movements were recorded. Sensitization to MPD was dependent on the time of administration, the motor index studied, and the challenge dose used. It was more pronounced for forward ambulation than for rearing, with no augmented response to stereotypic effects. The expression of the sensitized response was dose-dependent and mainly observed with the 0.6 and 2.5 mg/kg challenge dose groups. The development of sensitization to MPD was also time-dependent with the most robust sensitization occurring during the light phase, while no sensitization was observed during the middle of the dark phase. In addition, repeated MPD administration caused a significant increase in the amount of nocturnal forward ambulation that persisted long after cessation of drug treatment.

Animals↗

Prospective validation of consensus criteria for the diagnosis of dementia with Lewy bodies.

OBJECTIVE: To determine the validity of a clinical diagnosis of probable or possible dementia with Lewy bodies (DLB) made using International Consensus criteria. BACKGROUND: Validation studies based on retrospective chart reviews of autopsy-confirmed cases have suggested that diagnostic specificity for DLB is acceptable but case detection rates as low as 0.22 have been suggested. METHODS: We evaluated the first 50 cases reaching neuropathologic autopsy in a cohort to which Consensus clinical diagnostic criteria for DLB, National Institute for Neurological and Communicative Disorders and Stroke-Alzheimer's Disease and Related Disorders Association criteria for AD, and National Institute of Neurological Disorders and Stroke-Association Internationale pour la Recherche et l'Enseignement en Neurosciences criteria for vascular dementia (VaD) had been prospectively applied. RESULTS: Twenty-six clinical diagnoses of DLB, 19 of AD, and 5 of VaD were made. At autopsy, 29 DLB cases, 15 AD, 5 VaD, and 1 progressive supranuclear palsy were identified. The sensitivity and specificity of a clinical diagnosis of probable DLB in this sample were 0.83 and 0.95. Of the five cases receiving a false-negative diagnosis of DLB, significant fluctuation was present in four but visual hallucinations and spontaneous motor features of parkinsonism were generally absent. Thirty-one percent of the DLB cases had additional vascular pathology and in two cases this contributed to a misdiagnosis of VaD. No correlations were found between the distribution of Lewy bodies and clinical features. CONCLUSION: The Consensus criteria for DLB performed as well in this prospective study as those for AD and VaD, with a diagnostic sensitivity substantially higher than that reported by previous retrospective studies. DLB occurs in the absence of extrapyramidal features and in the presence of comorbid cerebrovascular disease. Fluctuation is an important diagnostic indicator, reliable measures of which need to be developed further.

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End of life treatment decisions in people with dementia: carers' views and the factors which influence them.

OBJECTIVE: Treatment decisions in life threatening situations (TD) are poorly studied in people with dementia. METHOD: The carers of people with dementia were asked four TD questions, pertaining to cardiac resuscitation, intravenous fluids, oral antibiotics and intravenous antibiotics. The impact of key variables (age, dementia severity, psychiatric co-morbidity, physical illness, family relationship of carer) on TD were evaluated. RESULTS: Fifty carers participated, 46% wanted cardiac resuscitation, 60% wanted treatment with intravenous fluids, 52% wanted treatment with intravenous antibiotics and 60% wanted treatment with oral antibiotics. Agreement between questions was high (76 - 89%), suggesting that relatives were either for or against intervention. There was an association between more severe dementia and a reduced wish for intravenous antibiotics. None of the variables significantly influenced other TD. CONCLUSION: The 'global' view of carers, was not influenced greatly by key disease variables. There are potential implications for the way in which carers are used as proxy decision makers.

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