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Biomedical subjects

A McLean

Publications and source records attributed to A McLean.

At least 19 recordsLinked to original sources

Mycophenolic acid 12-h trough level monitoring in renal transplantation: association with acute rejection and toxicity.

Studies of renal transplantation utilizing trough plasma level monitoring of mycophenolic acid (MPA) have shown inconsistent associations with toxicity and rejection. In this study, 5600 12-h trough MPA samples from 121 renal transplant recipients immunosuppressed with mycophenolate mofetil (MMF) and tacrolimus in a steroid sparing protocol (steroids for 7 days only) were sequentially analyzed. Higher MPA levels were associated with lower hemoglobin concentrations and anemia (hemoglobin <10 g/dL). Similarly, higher MPA levels were associated with lower total white cell counts and an increased incidence of leucopenia (total white cell count <4.0 x 10(9)/L). Hypoalbuminemia and renal impairment were also associated with hemotoxicity. MMF-associated diarrhea and viral infection were associated with higher MPA levels. Conversely, biopsy-proven acute rejection within the first month post-transplantation was associated with lower MPA levels. Anti-CD25 antibody induction was also associated with reduced rejection rates. No association was seen between MPA levels and platelet count, thrombocytopenia or bacterial infection. An MPA level of 1.60 mg/L early post-transplantation best discriminated patients with and without rejection, and an MPA level of 2.75 mg/L best discriminated patients with and without toxicity later post-transplantation.

Adult↗

Steroid sparing in renal transplantation with tacrolimus and mycophenolate mofetil: three-year results.

Although renal transplantation with a 7-day steroid-sparing regimen, tacrolimus and mycophenolate, is associated with good short-term outcomes, late allograft dysfunction and failure remain concerns. In this study 101 consecutive patients underwent renal transplantation using this immunosuppressive regimen. In addition, anti-CD25 monoclonal antibody was used in 25 high-risk patients (regrafts, two-antigen human leukocyte antigen (HLA)-DR mismatch or sensitized with anti-HLA panel reactivity >30%). After a median follow-up of 39 months (range 29 to 49), overall patient survival is 98%, with two cardiac deaths. Three other graft losses occurred, one each to early venous thrombosis, polyoma viral nephropathy, and late rejection due to noncompliance. Therefore, overall graft survival is 95%. The acute rejection rate at 6 and 12 months was 19% (no rejection occurred between months 6 and 12). Late rejection was uncommon, with only two further episodes beyond 12 months. Mean creatinine at 12 months was 144 micromol/L and mean estimated glomerular filtration rate (GFR) of 55 mL/min. Graft function was stable at 3 years with a mean creatinine of 142 micromol/L and mean estimated GFR 56 mL/min. During the study, five patients developed posttransplant diabetes mellitus (two cases beyond 12 months). Tissue-invasive cytomegalovirus disease and BK viral nephropathy each occurred in three patients, with all episodes in the first 12 months. Mean weight gain is 3.3 kg and mean blood pressure is 135/81 on an average of 1.5 antihypertensive agents. This steroid-avoidance regimen is associated with excellent medium-term patient and graft outcomes and a low incidence of side effects.

Antibodies, Monoclonal↗

Tacrolimus monitoring in renal transplantation: a comparison between high-performance liquid chromatography and immunoassay.

It is recommended that specific methods of tacrolimus monitoring rather than immunoassays, which overestimate tacrolimus levels, should be used in transplant recipients. Direct comparison of these techniques, however, has not been conducted in renal transplantation. In this study, 40 renal transplant recipients with tacrolimus monitoring by microparticle enzyme immunoassay (MEIA; target trough level 10 to 15 ng/mL) were compared with 40 patients monitored by high-performance liquid chromatography with tandem mass spectrometry (HPLC-MS; target trough level 8 to 13 ng/mL). All patients received anti CD25 antibody induction and mycophenolate mofetil in a steroid-sparing protocol. No differences were seen between MEIA and HPLC-MS groups in patient demographics. All patients were followed for 6 months. Patient survival was 100% in both groups; graft survival was 100% in the MEIA group and 97.5% in the HPLC-MS group. The groups did not differ in the number of dose changes required in the first 6 months or in the number of patients displaying tacrolimus levels within target range at 3 and 6 months. Delayed graft function occurred in 14 patients in the MEIA group and 12 patients in the HPLC-MS group (P = NS). Biopsy-proven acute rejection occurred in four patients in the MEIA group and one patient in the HPLC-MS group (P < .2). No differences were seen for the following parameters at 3 or 6 months: biopsy-proven tacrolimus nephrotoxicity, serum creatinine or estimated creatinine clearance, systolic or diastolic blood pressure, cholesterol, cytomegalovirus disease, posttransplant diabetes, or tremor. This study suggests that renal transplantation with HPLC-MS monitoring of tacrolimus is safe and effective.

Blood Pressure↗

The specificity of clinical characteristics in adults with attention-deficit/hyperactivity disorder: a comparison with patients with borderline personality disorder.

Characteristics of DSM-IV attention-deficit/hyperactivity disorder (ADHD) in adults can also be found as part of other psychiatric disorders. This study investigated the specificity of adult ADHD features in relation to patients with borderline personality disorder (BPD), a syndrome which shares some of its intrinsic features with ADHD and often co-occurs with ADHD. A group of 20 adult patients selected on the basis of a diagnosis of ADHD and 20 patients selected on the basis of a diagnosis of BPD were assessed by the self-report Attention Deficit Scales for Adults (ADSA). The two groups were matched for age, verbal IQ and gender. Of the nine ADSA scales, seven showed significant inter-group differences, in particular involving attention, organisation and persistence. The 'Consistency/Long-Term' scale, which mainly reflects impaired task and goal persistence, was the best discriminator between the groups. Furthermore, ratings on this scale correlated significantly with the error score of a computer-administered task of spatial working memory, the performance of which has been reported to be impaired in patients with ADHD. The results provide further validation for the ADSA scales and support a previous claim that 'long-term consistencies', i.e., related to task and goal persistence, is 'the centrepiece behavioural issue' for adults with ADHD.

Adult↗

Characteristic neurocognitive profile associated with adult attention-deficit/hyperactivity disorder.

BACKGROUND: It is now accepted that attention-deficit/hyperactivity disorder (ADHD) often persists into adulthood. However, relative to the considerable literature concerning the profile of neurocognitive deficits associated with this disorder in childhood, equivalent investigations in adult populations have been less common. The current study examined cognitive function in adults diagnosed with ADHD employing well-validated neuropsychological tasks. METHOD: Nineteen adult patients who satisfied DSM-IV criteria for ADHD and 19 matched (gender, age and verbal IQ), non-clinical control subjects were recruited. Patients were either unmedicated or had abstained from a psychostimulant medication regime for at least 24 h prior to neurocognitive assessment. A functionally wide-ranging test battery was administered. RESULTS: Relative to controls, ADHD adults performed significantly worse on spatial working memory, planning, and attentional-set shifting tests and were significantly slower to respond to target stimuli on the go/no-go task. In contrast, the two subject groups performed equivalently on decision-making and pattern/spatial recognition memory assessments. CONCLUSIONS: The demonstration of neuropsychological dysfunction in the adult ADHD cohort provides some support for the validity of this diagnosis in adulthood. In particular, there is broad consistency between the cognitive profile revealed in the current investigation and that previously demonstrated in a study of medication-naïve ADHD children. There is evidence that frontostriatal function is especially disrupted.

Adult↗

Impaired spatial working memory in adults with attention-deficit/hyperactivity disorder: comparisons with performance in adults with borderline personality disorder and in control subjects.

OBJECTIVE: This study investigated a previous claim that working memory may be 'particularly impaired' in adult attention-deficit/hyperactivity disorder (ADHD), compared with other psychiatric disorders which affect frontal lobe-mediated executive functions. METHOD: Performance on spatial working memory (SWM) and two additional tasks were investigated for adult patients selected on the basis of DSM-IV ADHD (n = 19), adult patients selected on the basis of borderline personality disorder (BPD) (n = 19), and non-clinical control subjects (n = 19). Groups were matched for age, verbal IQ and gender. RESULTS: Analysis of variance showed that the ADHD group had significant impairment of SWM performance relative to the non-clinical controls. Although there was a trend towards impairment in the BPD group relative to non-clinical controls, this did not reach significance. CONCLUSION: The results are consistent with the claim that aspects of working memory are 'particularly impaired' in adult ADHD. Also, the BPD group had a longer deliberation time for one of the additional tasks, compared with the ADHD group, which indicated that the patient groups may have different patterns of neuropsychological impairments.

Adult↗

Outcome of halo immobilisation of 104 cases of cervical spine injury.

STUDY DESIGN: Retrospective review. OBJECTIVES: To present and discuss the outcome of halo jacket immobilisation of cervical spine injuries. SETTING: National Spinal Injuries Unit in a Scottish University teaching Hospital. METHODS: Retrospective review of case-notes and radiographs of all patients treated with halo jacket both as primary means of immobilisation or as adjunct to surgical stabilisation between 1992-1999 and followed up at a weekly halo clinic. RESULTS: Out of a total one hundred and four patients with cervical spine injury, eighty-six were treated with Halo jacket as primary means of cervical immobilisation. Halo was used as adjunct to surgical stabilisation for the rest. There were nine cases of true failure. This is a failure rate of 10% for primary halo immobilisation. Of the nine patients who had failure of bony healing, four had fibrous healing, three had surgery to stabilise spine, two were subsequently lost to follow-up. The highest incidence of recurrence of subluxation occurred in patients with fracture/subluxation with a healing rate of 85%. Patients with ankylosing spondylitis did well. Odontoid fractures had 18% failure rate. The commonest complication was loss of reduction, followed by pin-site infection. CONCLUSION: Halo is an effective non-surgical treatment for the injured cervical spine at both upper and lower levels.

Cervical Vertebrae↗

Neuropsychological evidence of a relatively selective profile of temporal dysfunction in drug-free MDMA ("ecstasy") polydrug users.

RATIONALE: Experimental evidence has shown that 3,4-methylenedioxymethamphetamine (MDMA, "ecstasy") can act as a serotonergic neurotoxin in laboratory animals. The serotonin system predominantly innervates frontal and limbic regions of the brain and has been associated with consolidatory learning and mnemonic processes in humans. OBJECTIVES: The aim of the present study was to investigate the cognitive neuropsychological profile of drug-free ecstasy users by employing a selection of tasks previously associated with lesion or neurodegenerative damage to the temporal lobe or fronto-striatal regions. METHODS: The study comprised 40 participants: 20 ecstasy polydrug users and 20 polydrug users who had never taken ecstasy. RESULTS: Ecstasy users were significantly impaired on a recognition task for complex visual patterns and spatial working memory, as a function of task difficulty rather than systematic search strategy. They also showed a trend towards impairment on several learning paradigms. Ecstasy users remained relatively unimpaired on most measures associated with prefrontal functioning, with the exception of verbal fluency "letter" generation. CONCLUSIONS: Initial cognitive deficits in ecstasy polydrug users may be more apparent in tasks known to be sensitive to temporal functioning.

Adolescent↗

Vacuum-assisted closure in the paediatric patient with post-cardiotomy mediastinitis.

Mediastinitis has a high mortality and is a major cause for concern in the neonatal cardiac surgical population. Vacuum-Assisted Closure (V.A.C.) is a newly established technique for expediting healing in the management of wounds resistant to established treatments; this includes the treatment of post-cardiotomy mediastinitis in the adult cardiac surgical patient. We describe the previously unreported use of the V.A.C. device for the successful treatment of post-cardiotomy mediastinitis in an infant. The device also improved the mechanics of respiration. We discuss potential risks and benefits of V.A.C. and suggest guidelines for its use.

Bandages↗

Encouraging prospects for immunisation against primary cytomegalovirus infection.

Congenital cytomegalovirus (CMV) infection is the leading infectious cause of mental retardation in children. Using seroprevalence data from two large antenatal populations (in excess of 14000 women) coupled with a mathematical modelling approach, we have shown that CMV has a low force of infection (ca. 0.03 per seronegative per annum) and its basic reproductive number R0 is relatively modest at 2.4. On the basis of these results, the critical vaccination proportion required for eradication of CMV is between 59-62%. In contrast to the predicted and observed effects of rubella vaccination on the incidence of congenital rubella, the increase in the average age of infection following instigation of a CMV vaccine programme will not increase the number of congenital infections. In conclusion, CMV is a prime candidate for eradication from the human population through vaccination.

Adult↗

Determination of amphetamine in dog plasma by gas chromatography with mass selective detection.

This paper describes the validation of an analytical method for the determination of amphetamine in beagle dog plasma by gas chromatography coupled to mass spectrometry (GC-MS). d-Amphetamine-d(6) was used as the internal standard. The method consisted of a rapid single-step liquid-liquid extraction and derivatization of amphetamine with 2,2,2-trichloroethyl chloroformate, followed by sensitive GC-MS detection. This is the first report utilizing the combination of trichloroethyl chloroformate as a derivatization reagent and a deuterated amphetamine analog as an IS for the quantification of amphetamine in plasma. The method was validated in terms of specificity, curve fit, precision, accuracy, recovery and stability, and was acceptable according to FDA draft guidelines for validation of bioanalytical methods. The limit of detection was 0.65 ng/mL. The calibration range was 5-150 ng/mL. The validated method was successfully employed for the quantitation of amphetamine in dog plasma samples for pharmacokinetic profiling.

Amphetamines↗

Power in the nursing home: the case of a special care unit.

This article examines the effects and nature of power in a special care unit of a nursing home devoted to elders with dementia and/or disturbed behaviors. Drawing from two case studies and contemporary theories on power, I illustrate how the hierarchical structure of the clinic, together with the diffuseness and pervasiveness of disciplinary power, serves to shape the lives of--and to constrain the resistance opportunities open to--elders within the clinic. I also discuss the dilemma facing ethnographers of the clinic who may witness the sometimes disastrous effects of power but feel incapable, in their positions as researchers, of challenging the actions of clinical staff. At the same time, I observe how the contradictions of disciplinary power are often experienced by clinical staff who themselves struggle between taking actions they feel they must and those they would prefer. Far from acceding to the impotency that clinical anthropologists too often feel within a research setting, I argue that they can help to incite in their clinical colleagues the urgency of carrying out more productive alternatives to conventional "disciplinary" practices.

Aged↗

The influence of food on the bioavailability of a twice-daily controlled release carbamazepine formulation.

Carbatrol, a new dosage form of carbamazepine (CBZ), was developed consisting of three different types of pellets (immediate release, controlled release, and enteric release). The objective of this study was to explore the influence of food on absorption of CBZ. This was a randomized, open-label, single-dose crossover study conducted in 12 healthy volunteers. Treatments were 2 x 200 mg Carbatrol with a high-fat meal, fasted, or sprinkled over applesauce (but otherwise fasted). Each subject received one dose of each treatment separated by a washout period of at least 2 weeks. CBZ bioequivalence was established based on the equivalence of AUC (extent of absorption) in all three conditions. Carbatrol may be taken with or without food or the capsule opened and sprinkled on food.

Adolescent↗

Interhemispheric comparisons in a man with complete forebrain commissurotomy.

J. Sergent (1991) claimed that split-brained people are highly accurate in judging which is the larger of 2 circles in opposite visual hemifields but are relatively poor at judging whether circles in the 2 hemifields are of the same size. The discrepancy could be due, at least in part, to an artifact. A split-brained man, L.B., was markedly worse than normals at judging which was the larger of 2 circles or the longer of 2 horizontal lines in opposite hemifields, and his performance could be largely accounted for without assuming any interhemispheric transfer. L.B. also judged whether a single flashed line extended further into the left or right hemifield and, as in a previous study (M. C. Corballis, 1995), was strongly biased to respond "right longer." This bias was not observed in the judgments about the circles or the separated lines, suggesting that it is not due to a compression of perceived space in the left hemifield.

Adult↗

Response of naïve and memory CD8+ T cells to antigen stimulation in vivo.

We studied the influence of memory T cell properties on the efficiency of secondary immune responses by comparing the in vivo immune response of the same numbers of T cell receptor (TCR) transgenic (Tg) naïve and memory T cells. Compared to naïve Tg cells, memory cells divided after a shorter lag time; had an increased division rate; a lower loss rate; and showed more rapid and efficient differentiation to effector functions. We found that initial naïve T cell priming resulted in cells expressing mutually exclusive effector functions, whereas memory T cells were multifunctional after reactivation, with each individual cell expressing two to three different effector functions simultaneously. These special properties of memory T cells ensure the immediate control of reinfection.

Animals↗

Quality of life of mothers and families caring for preterm infants requiring home oxygen therapy: a brief report.

OBJECTIVE: To investigate the impact on mothers and families of caring for a premature infant receiving home oxygen therapy (HOT). METHODS: Standard questionnaires were used to compare the functioning of mothers and families of 10 premature infants receiving HOT, 10 premature infants who were discharged from hospital on HOT but who no longer required it and 20 premature infants who had never required treatment with HOT. RESULTS: After adjustment for gestational age, chronological age, birthweight and place of residence (urban/rural), the care required by premature infants receiving HOT had a significantly greater impact on their families than the care of infants not receiving HOT. Mothers of premature infants receiving HOT reported significantly less vitality and more mental health problems than mothers of infants not receiving HOT. CONCLUSIONS: The use of HOT for premature infants may have a significant adverse impact on their mothers and families.

Adult↗

Comparison of Pulmicort pMDI plus Nebuhaler and Pulmicort Turbuhaler in asthmatic patients with dysphonia.

BACKGROUND: Dysphonia is a known local adverse effect of inhaled corticosteroids. This symptom was investigated by laryngoscopy and assessment in a voice laboratory. The effects of changing the treatment of patients with dysphonia, reported whilst using the pMDI, to pMDI plus Nebuhaler or Tubuhaler was also assessed. METHODS: Seventy-two patients reporting dysphonia and taking inhaled steroids from a pMDI entered a 12-week, open, parallel group study. Fifty-one completed the study per protocol; 26 in the Nebuhaler group [21 female, mean age 57 years (22-77)] and 25 in the Turbuhaler group [18 female, mean age 58 years (21-81)]. A dysphonia diary card was completed weekly. Voice laboratory assessments and laryngoscopy were performed on entry and at 12 weeks. RESULTS: There were no differences in voice laboratory data, laryngoscopic evidence of disordered glottic closure and diary data between the two groups at 12 weeks. At study entry laryngoscopic appearances were normal in almost half the patients. Vocal cord bowing was rarely seen. Glottic closure changed in nine patients during the study period, but there was no correlation with voice symptoms. The trend of symptomatic improvement of voice status in the Turbuhaler group did not correlate with voice laboratory assessments and laryngoscopic evidence of disordered glottic closure. After 4 weeks, 40% of patients using Turbuhaler and 8% in the Nebuhaler group scored their voice status as better (P < 0.02) but there was no significant difference between the two groups at 12 weeks (Turbuhaler 52%, Nebuhaler 23%, P=0.08). CONCLUSION: This study does not support the view that dysphonia in asthmatics inhaling corticosteroids is usually caused by myopathic bowing of the vocal cord muscles.

Administration, Inhalation↗