When euthymia is just not good enough: the neuropsychology of bipolar disorder

Bipolar disorder (BD) is a debilitating psychiatric illness that is uniquely characterized by switching between psychopathologically contrasting phases of mania and depression, often with intervening periods of euthymia. However, these periods of apparent clinical recovery (euthymia) are marked by subtle social, occupational, and cognitive impairments, profiled by recent neuropsychological investigations. Determining the cognitive changes across these three phases may help differentiate the disruptions that are mood state-dependent from those associated with underlying pathology. This article therefore critically reviews the reported neuropsychological impairments in BD and the methodological limitations facing such research. Integration of the available evidence, principally from the field of neuropsychology, when synthesized, implicates the prefrontal cortex in the etiopathogenesis of BD and posits cortical-subcortical-limbic disruption in recovered euthymic patients that manifests as cognitive dysfunction.     

Central penetration and stability of N-terminal tripeptide of insulin-like growth factor-I, glycine-proline-glutamate in adult rat

Insulin-like growth factor-I is a neurotrophic factor and can prevent neurons from ischemic brain injury. However, the large molecular weight and metabolic effects can be problematic in its central delivery. Glycine-proline-glutamate (GPE) is the N-terminal tripeptide of insulin-like growth factor-I, which is naturally cleaved in the plasma and brain tissues. GPE reduces neuronal loss from hypoxic-ischemic brain injury following central administration. Central penetration and the stability of GPE in the plasma and central nervous system were examined in rats using radioimmunoassay and HPLC. GPE was rapidly metabolised in the plasma (8 min) after intraperitoneal administration. Despite having a short half-life in plasma, GPE was detected in the cerebrospinal fluid up to 40 min after intraperitoneal administration. With present of peptidase inhibitors, GPE existed in the brain tissue up to 3 h after intracerebroventricular administration, suggesting a role for peptolysis in its stability. The endopeptidase inhibitors 4- (2-aminoethyl) benzenesulfonyl fluoride hydrochloride (AEBSF) reduced GPE metabolism in the brain tissue while acid peptidase inhibitor pepstatin-A decreased GPE metabolism in the plasma. GPE reduced neuronal loss in the CA1-2 sub-region of the hippocampus given (intraperitoneally) after 30 min of hypoxic-ischemic injury in adult rats, further suggested the effectiveness of GPE central uptake. These results indicated that GPE crosses the blood-CSF and the functional CSF-brain barriers. The longer half-life of GPE in the CNS may be due to its unique enzymatic stability.     

Chemotherapy-induced alopecia: psychosocial impact and therapeutic approaches

Despite advances in the treatment of many side effects associated with chemotherapy, alopecia remains an issue that is difficult to resolve. Chemotherapy-induced alopecia (CIA) is a condition that can have profound psychosocial and quality-of-life consequences, resulting in anxiety, depression, a negative body image, lowered self-esteem, and a reduced sense of well-being. Patients who fear CIA may sometimes select regimens with less favorable outcomes or may refuse treatment. When supporting patients with CIA, health care providers should use an individualized approach with a focus placed on the actual moment of hair loss. Education, support groups, and self-care strategies are important components of any management approach. No treatment modality for preventing CIA has been clearly shown to be effective. Recent evidence suggests that new scalp hypothermic regimens may be safe and effective. There remains a critical need for effective new approaches to this problem.     

Clinical experience with perindopril in patients nonresponsive to previous antihypertensive therapy: a large US community trial

A subgroup analysis of a large US community trial was conducted to evaluate the antihypertensive efficacy and safety of perindopril, an angiotensin-converting enzyme inhibitor (ACEI), in 3159 patients who lacked blood pressure (BP) control at entry with previous antihypertensive therapy. Patients received 4 mg perindopril daily for 6 weeks. Based on physicians' assessment of BP response, the patients were then either maintained on 4 mg daily (group 1) or the dose was increased to 8 mg daily (group 2) for an additional 6 weeks. The mean baseline sitting BP was 158.2/92.9 mm Hg. Perindopril monotherapy produced a significant BP decrease from baseline of 11.6/6.5 mm Hg and 14.9/8.4 mm Hg at weeks 6 and 12, respectively. In group 1 patients, the majority of BP decrease occurred at week 6 (17.3/9.5 mm Hg) and was maintained until the end of week 12 (18.2/10.1 mm Hg). In group 2 patients, the BP decrease on the 4-mg dose was modest at week 6 by 5.2/3.1 mm Hg. However, further dose up-titration of perindopril to 8 mg resulted in a clinically significant BP decrease of 11.9/6.8 mm Hg from baseline to week 12. Significant antihypertensive effects of perindopril were also demonstrated in the special patient populations of elderly (>or=65 years), black, isolated systolic hypertension, patients with concomitant cardiovascular diseases, and patients nonresponsive to other ACEI therapy. Overall, BP control (<140/<90 mm Hg) was achieved in 40.0% of patients at week 12. Perindopril was well tolerated with cough and angioedema reported in 8.5% and 0.4% patients, respectively. Physicians assessed therapeutic response to perindopril as satisfactory in 73.8% patients who were nonresponsive to previous antihypertensive therapy. These results suggest that, in a community-based practice, perindopril monotherapy (4-8 mg/d) is an effective and safe therapeutic option in patients nonresponsive to previous antihypertensive therapy.     

The implications of NICE guidelines on the management of children presenting with head injury

Background: NICE guidelines for the management of head injury were published in June 2003. Their recommendations differ markedly from previous guidelines published by the Royal College of Surgeons (RCS). In place of skull radiography and admission, computed tomography (CT) is advocated. The impact of these guidelines on service provision in the UK is unknown. Methods: Data on all clinical correlates of children presenting with any severity of head injury was collected in three hospitals in the northwest of England. The current skull radiograph (SXR), CT scan, and admission rates were determined. The rates of SXR, CT scan, and admission that should have occurred when following either the RCS or NICE guidelines were then determined. Results: Data from 10 965 patients who attended three hospitals between February 2000 and August 2002 was studied. Twenty five per cent of patients received a SXR, 0.9% a CT scan, and 3.7% were admitted. Strict adherence to the RCS guidelines would have resulted in a 50% SXR rate, a 1.6% CT scan rate, and a 7.1% admission rate. Adherence to NICE guidelines would result in a 0.3% SXR rate, an 8.7% CT scan rate, and a 1.4% admission rate, although the CT rate would drop to 6.3% if vomiting three or more times in the under 12s was used instead of more than one vomit. Conclusions: The new NICE guidelines do not increase the workload caused by patients attending with head injury but they move their management from the observation ward to the radiology department.     

Antihypertensive utility of perindopril in a large, general practice-based clinical trial

The authors evaluated, in a community-based open-label trial, the effectiveness and safety of perindopril in 13,220 US hypertensive patients and studied how physicians adhere to hypertension treatment guidelines. Patients received perindopril 4 mg q.d. for 6 weeks. Based on physicians' perception of blood pressure response, the patient was either maintained on 4 mg or the dose was increased to 8 mg for an additional 6 weeks. From baseline to week 12, the mean sitting blood pressure significantly declined from 156.9/94.5 mm Hg to 139.2/84.0 mm Hg. Further dose titration resulted in a clinically significant reduction in blood pressure in all patients with inadequate response on 4 mg at week 6. Blood pressure control (<140/<90 mm Hg) was achieved at 12 weeks in 48.8% patients. The subpopulation analyses demonstrated that perindopril monotherapy was effective in both men and women, in patients of all ethnicities, and in patients <65 and ≤65 years of age. Perindopril was safe and well tolerated in all hypertensive subgroups including high-risk patients. Physicians were more attuned to controlling diastolic than systolic blood pressure, and their adherence to the treatment guidelines was found to be not optimal.     

Accumulation of tributyltin in Hyalella azteca as an indicator of chronic toxicity: survival, growth, and reproduction

The chronic toxicity of tributyltin (TBT) was examined by exposing two successive generations of the freshwater amphipod, Hyalella azteca, to sediments spiked with TBT. Survival was the most sensitive measure of effect, with lethal concentration resulting in 50% mortality (LC50) values on a water and body concentration basis ranging from 76 to 145 ng Sn/L and 2,790 to 4,300 ng Sn/g, respectively. Individual growth of amphipods was not negatively affected by TBT, and although reproduction might be more sensitive than survival, the data were too variable to use on a routine basis. There were no detectable TBT-induced differences in the response between first- and second-generation animals. The relationship between toxicity and bioaccumulation of TBT in H. azteca was determined and can be used as a tool to predict the toxicity of TBT in environmental samples. Body concentrations exceeding 2,000 ng Sn/g in H. azteca exposed to field-collected samples would indicate that chronic toxicity due to TBT is likely occurring in amphipod populations at those sites.     

Ethics roundtable debate: should a sedated dying patient be wakened to say goodbye to family?

Intensivists have the potential to maintain vital signs almost indefinitely, but not necessarily the potential to make moribund patients whole. Current ethical and legal mandates push patient autonomy to the forefront of care plans. When patients are incapable of expressing their preferences, surrogates are given proxy. It is unclear how these preferences extend to the very brink of inevitable death. Some say that patients should have the opportunity and authority to direct their death spiral. Others say it would be impossible for them to do so because an inevitable death spiral cannot be effectively palliated. Humane principles dictate they be spared the unrelenting discomfort surrounding death. The present case examines such a patient and the issues surrounding a unique end-of-life decision.     

Peri-operative risk factors for acute lung injury after elective oesophagectomy

Acute lung injury after oesophagectomy is well recognized butthe risk factors associated with its development are poorlydefined. We analysed retrospectively the effect of a numberof pre-, peri- and post-operative risk factors on the developmentof lung injury in 168 patients after elective oesophagectomyperformed at a single centre. The acute respiratory distresssyndrome (ARDS) developed in 14.5% of patients and acute lunginjury in 23.8%. Mortality in patients developing ARDS was 50%compared with 3.5% in the remainder. Features associated withthe development of ARDS included a low pre-operative body massindex, a history of cigarette smoking, the experience of thesurgeon, the duration of both the operation and of one-lungventilation, and the occurrence of a post-operative anastomoticleak. Peri-operative cardiorespiratory instability (measuredby peri-operative hypoxaemia, hypotension, fluid and blood requirementsand the need for inotropic support) was also associated withARDS. Acute lung injury after elective oesophagectomy is associatedwith intraoperative cardiorespiratory instability. Br J Anaesth 2001; 86: 633–8     

Critical evaluation of neurolaryngological disorders

Otolaryngological examinations, videostroboscopic image analysis, and laryngeal electromyography were used as a test battery for a critical evaluation in 80 patients. Vocal fold movements were categorized into mobility, restricted mobility, immobility with different positions, and overactive movement. Laryngeal electromyographic examinations were conducted in all patients, and the results were classified into normal, neuropathic, and myopathic patterns. The electromyographic data were integrated with videostroboscopic findings, interpreted with knowledge of biomechanical and electrophysiological mechanisms of the larynx, and correlated clinically with underlying diseases. It is suggested that neurolaryngological procedures are most clinically useful when dictated by a decision-making algorithm.