Altered cellular distribution of iron in rat cerebral cortex during the oestrous cycle

Summary. Iron levels in blood, liver and the substantia nigra fluctuate during the oestrous cycle but it is not known whether the cellular distribution also changes. This study shows that during dioestrus, when serum levels of oestradiol are low, the amount of histochemically detectable iron in the cerebral cortex is significantly lower than in proestrus when oestradiol levels are highest. During dioestrus iron is concentrated within neurones, and the transition to proestrus is associated with a shift in iron localisation from neurones to vascular endothelial cells and oligodendrocytes. These data raise the possibility that changes in the concentration of serum oestrogen (or other reproductive hormones) during the oestrous cycle can influence the intercellular transport of iron in the brain.Current address: Neuroplasticity Department, European Neuroscience Institute, Göttingen, Germany     

Regulation of attention and response to therapy in dementia by butyrylcholinesterase

OBJECTIVES: To determine the response of patients with different butyrylcholinesterase genotypes to therapy, and the influence of butyrylcholinesterase on cognition. Acetylcholine plays a key role in attention and memory and reduced cortical acetylcholine is associated with the severity of dementia. Inhibitors of the enzyme acetylcholinesterase are an effective dementia treatment, though the role of the related enzyme butyrylcholinesterase is less well understood. METHODS: We examined the response of a cohort of dementia patients enrolled in a trial of a cholinesterase inhibitor who had been genotyped at the butyrylcholinesterase locus. Additionally a prospectively assessed cohort of dementia patients was genotyped and rate of cognitive decline examined, along with baseline cognitive performance in a group of elderly non-demented individuals. We identified that the presence of reduced-activity butyrylcholinesterase variants correlates with preserved attentional performance and reduced rate of cognitive decline. During cholinesterase inhibitor therapy, patients with normal butyrylcholinesterase show improved attention, though patients carrying reduced-activity enzyme do not, possibly due to being at ceiling performance. Butyrylcholinesterase did not however affect attentional performance in non-demented individuals with mild cognitive impairment. CONCLUSIONS: These findings indicate that the butyrylcholinesterase enzyme is a major regulator of attention especially in cholinergic deficiency states through its ability to hydrolyse acetylcholine. Pharmacologic manipulation of this enzyme may be a viable strategy in dementia treatment and, with butyrylcholinesterase genotyping, may provide pharmacogenomic treatment of dementia.     

Tegaserod pharmacokinetics are similar in patients with severe renal insufficiency and in healthy subjects

Tegaserod (HTF 919), a selective 5-HT4 receptor partial agonist with promotile activity throughout the gastrointestinal tract, is in development for the treatment of irritable bowel syndrome. In an open-label, parallel-group study, the pharmacokinetics of a single 12-mg oral dose of tegaserod in patients with severe renal insufficiency requiring hemodialysis were compared with data obtained from healthy subjects matched for age, weight, height, and gender (n = 10, both). The pharmacokinetics of tegaserod were similar in both groups (AUC(0h-tz), ng.h/ml: 14.6 +/- 8.5 vs. 14.3 +/- 7.1; Cmax, ng/ml: 4.6 +/- 2.3 vs. 5.1 +/- 2.2; tmax, h: 1.0, for both). Tegaserod had similar tolerability in renally impaired patients and healthy volunteers, with adverse events largely related to the gastrointestinal pharmacological actions of the drug. Therefore, no dose adjustment of tegaserod is necessary for patients with renal insufficiency.     

The role of cardiac morbidity in short- and long-term mortality in injured older patients who survive initial resuscitation

BACKGROUND: Elderly patients are an increasingly larger group of injured trauma care patients. Comorbidities influence outcome. Little is known of short- and long-term mortality in the elderly who survive initial resuscitation. METHODS: Short- and long-term mortality was retrospectively analyzed in 363 consecutively injured patients (Injury severity score >15) surviving more than 3 days after admission to a level 1 trauma center (including 197 patients >60 years). Cardiac morbidity was the focus. RESULTS: Survival to hospital discharge was similar comparing older patients with the entire group. Mortality increased incrementally with age. In older patients, cardiac morbidity was observed in 28% (fatal in 7); 2-year mortality was 36% (older group) and 60% (patients sustaining cardiac complications). Most elderly (80%) were discharged to long-term care. CONCLUSIONS: Elderly who survive initial resuscitation are as likely to survive to discharge as younger patients, but long-term survival is significantly lower as age increases. Cardiac morbidity is associated with higher long-term mortality. Most elderly are discharged to long-term care.     

Malignant melanoma in South Africans of mixed ancestry: a retrospective analysis

Little is known about the behaviour of melanoma in patients of mixed ancestry. A retrospective analysis of 844 consecutive patients presenting with melanoma over a 12-year period was performed. Forty patients (4.8%) were of mixed ancestry. The data evaluated included patient age, gender, delay in presentation, presenting stage, anatomical distribution, histology, management and outcome. The mean age at presentation was 52.8 years. Twenty-seven patients were female. The mean delay in presentation was 1.54 years. Seventy per cent of melanomas were confined to the extremities, of which one-third were plantar in origin. The most common histological variant, affecting 13 patients (32.5%), was acral lentiginous melanoma; 12.5% of patients presented with in situ (Stage 0) disease, 17.5% with Stage I disease, 22.5% with Stage II disease, 27.5% with Stage III disease and 7.5% with Stage IV disease. Twenty-seven patients (67.5%) remained alive at the end of the study after a median follow-up of 5.58 years, whilst 11 (27.5%) died after a median of 2.42 years. The median survival was 3.92 years. Although the histological type and anatomical distribution reflect the disease pattern of black populations, the overall 5-year survival of 74% is similar to that seen in white populations. An education programme is needed to improve melanoma awareness in mixed race populations.     

A review of 165 cases of transvaginal sacrospinous colpopexy performed by the Endo Stitch technique

The Endo Stitch technique has been in use in Geelong since 1994 as the method of performing transvaginal sacrospinous colpopexy (TSC). This article looks at the outcome of 165 of these procedures as assessed by a questionnaire. As the operation is technically easy, has a low complication rate and a high level of patient satisfaction we suggest that the Endo Stitch technique may be the method of choice for TSC.     

Prevention of orthopaedic wound infections: a quality improvement project

Using clinical practice improvement methodology, a project was undertaken to reduce the incidence of surgical wound infections following elective hip and knee replacement surgery. A team was established, key measures for improvement were identified, strategies for change were developed and an action plan was implemented. Outcomes for this project included a reduction in the rate of clean surgical wound infection for joint replacement surgery from 28% to zero. Average length of stay for total hip replacement surgery was reduced from 13.9 to 9.3 days and from 14.6 to 10.4 days for total knee replacement surgery. Guidelines for patient selection were developed along with a protocol for the management of preparation to prevent urinary tract infections. Post-discharge surveillance and a preoperative rehabilitation and exercise programme have been implemented. There is potential for wider uptake and implementation of the quality principles described herein.     

Changes in Mini-Mental State Exam in community-dwelling older persons over 6 years: relationship to health and neuropsychological measures

Although cognitive screening test scores change with advanced age, the significance of these changes (particularly decline in score) needs to be defined in terms of general health and neuropsychological functioning. Such analysis was undertaken in a subgroup of 287 healthy older men (mean age at baseline = 70.7 years) from the Western Collaborative Group Study, an ongoing cardiovascular and aging research project. Time from baseline to follow-up study averaged 6.0 years (SD = 0.5 years). Mini-Mental State Examination (MMSE) scores indicated that 15% of participants declined by three or more points (a 1+ standard deviation change among all change scores), 5% of participants improved by three or more points, and 80% of the sample remained within two points of their initial score. In health terms, decliners were significantly older, less active at follow-up, rated their health more poorly, and reported more depressive symptoms than non-decliners. Decliners also performed more poorly on several neuropsychological tests administered at follow-up. Results suggest that a decline of three or more points on the MMSE in community-dwelling, older persons without acute illness may signify important changes in health and cognition.