PET network abnormalities and cognitive decline in patients with mild cognitive impairment.

Temporoparietal and posterior cingulate metabolism deficits characterize patients with Alzheimer's disease (AD). A H(2)(15)O resting PET scan covariance pattern, derived by using multivariate techniques, was previously shown to discriminate 17 mild AD patients from 16 healthy controls. This AD covariance pattern revealed hypoperfusion in bilateral inferior parietal lobule and cingulate; and left middle frontal, inferior frontal, precentral, and supramarginal gyri. The AD pattern also revealed hyperperfusion in bilateral insula, lingual gyri, and cuneus; left fusiform and superior occipital gyri; and right parahippocampal gyrus and pulvinar. In an independent sample of 23 outpatients with mild cognitive impairment (MCI) followed at 6-month intervals, the AD pattern score was evaluated as a predictor of cognitive decline. In this MCI sample, an H2(15)O resting PET scan was carried out at baseline. Mean duration of follow-up was 48.8 (SD 15.5) months, during which time six of 23 MCI patients converted to AD. In generalized estimating equations (GEE) analyses, controlling for age, sex, education, and baseline neuropsychological scores, increased AD pattern score was associated with greater decline in each neuropsychological test score over time (Mini Mental State Exam, Selective Reminding Test delayed recall, Animal Naming, WAIS-R digit symbol; Ps<0.01-0.001). In summary, a resting PET covariance pattern previously reported to discriminate AD patients from control subjects was applied prospectively to an independent sample of MCI patients and found to predict cognitive decline. Independent replication in larger samples is needed before clinical application can be considered.     

It's all about sex: gender, lung development and lung disease.

Accumulating evidence suggests that gender affects the incidence, susceptibility and severity of several lung diseases. Gender also influences lung development and physiology. Data from both human and animal studies indicate that sex hormones might contribute to disease pathogenesis or serve as protective factors, depending on the disease involved. In this review, the influence of gender and sex hormones on lung development and pathology will be discussed, with specific emphasis on pulmonary fibrosis, asthma and cancer.     

A PC-based free text retrieval system for health care providers

The purpose of this paper is to describe the design and development of the Clinical Practice Library of Medicine (CPLM). CPLM is an investigational project aimed at providing health care practitioners with critical in-depth information similar to that obtained from a medical reference library or consultant. When used in conjunction with the physician's knowledge, CPLM can provide valuable diagnostic prompting information to assist in rapidly reaching a suitable diagnosis for timely administration of appropriate treatment. This system may also be used to assist paramedical professionals working in remote areas where other expert medical assistance may not be available.     

Comparative genomic hybridization (CGH) of augmentation cystoplasties

OBJECTIVE: Tumors arising within augmentation cystoplasties are aggressive, have poor prognosis and the majority are not detected at follow-up cystoscopy. Genetic changes in tumors precede morphological abnormalities. Therefore, the aim of this study was to investigate whether genetic abnormalities detected by comparative genomic hybridization (CGH) could be used to identify those patients with augmentation cystoplasties at increased risk of tumorigenesis. METHODS: Bladder biopsy samples were obtained from 16 augmentation cystoplasty patients both distant from and near to the enterovesical anastomosis. CGH was used to detect genetic abnormalities in DNA extracted from the biopsies, archival specimens of two augmentation cystoplasties and two de novo bladder adenocarcinomas. RESULTS: A greater number of amplifications on 2p, 3q, 8q, 9p, 17p, 18pq and 20pq, were observed in bladder biopsies obtained near to the enterovesical anastomosis compared to those taken distant to the suture line. CGH of archival augmentation cystoplasty tumor DNA indicated abnormalities at several loci with amplifications at 2q, 5q, 10p and 21pq, while deletions occurred at 5p and 16p. CONCLUSIONS: The results of this study suggest that the urothelium adjacent to the bladder and/or bowel anastomosis in augmentation cystoplasties is genetically unstable. Furthermore, longitudinal studies are required to establish whether or not patients exhibiting genetic instability following augmentation cystoplasty are at greater risk of developing tumors than those with genetically stable epithelia.     

Evaluation of clinical outcomes in anterior cruciate ligament surgery

Clinical outcomes data can be used to facilitate patient management decisions, assess clinician and organizational performance, and to provide evidence for the effectiveness of surgery and rehabilitation. The validity of the inferences made from outcomes data are dependent on the validity of the outcomes measures themselves and the circumstances under which the data were collected, analyzed, and interpreted. Clinical outcomes may include measures of impairment of body structure and function, activity limitation, and participation restriction. However, because the relationship between impairment and the resulting activity limitation and participation restriction is not direct, and because activity limitations and participation restrictions are of the utmost concern to the athlete, the primary clinical outcome should be measures of activity limitation and participation restriction. Activity limitation and participation restriction may be measured either through direct observation of performance or by general or specific measures of health related quality of life. Clinical outcomes data must be collected systematically to ensure valid inferences from the data.     

Clinical review: Vasculitis on the intensive care unit – part 2: treatment and prognosis

The second part of this review addresses the treatment and prognosis of the vasculitides Wegener's granulomatosis, microscopic polyangiitis, Churg–Strauss syndrome and polyarteritis nodosa. Treatment regimens consist of an initial remission phase with aggressive immunosuppression, followed by a more prolonged maintenance phase using less toxic agents and doses. This review focuses on the initial treatment of fulminant vasculitis, the mainstay of which remains immunosuppression with steroids and cyclophosphamide. For Wegener's granulomatosis and microscopic polyangiitis plasma exchange can be considered for first-line therapy in patients with acute renal failure and/or pulmonary haemorrhage. Refractory disease is rare and is usually due to inadequate treatment. The vasculitides provide a particular challenge for the critical care team. Particular aspects of major organ support related to these conditions are discussed. Effective treatment has revolutionized the prognosis of these conditions. However, mortality is still approximately 50% for those requiring admission to intensive care unit. Furthermore, there is a high morbidity associated with both the diseases themselves and the treatment.     

High-resolution immunophenotyping of subcellular compartments in tissue microarrays by enzyme metallography.

Ultrasensitive bright field in situ hybridization assays using enzyme metallography (EnzMet) have been developed and validated, but little is known regarding the applicability of EnzMet for immunophenotypic detection of protein via IHC. Superior resolution via discrete metallographic deposits offers the potential for enhancing high-resolution immunophenotyping. Using high-complexity tissue microarrays (TMAs), 88 common solid tumors were evaluated by automated EnzMet (Nanoprobes and Ventana). Targets were chosen to assess the ability of EnzMet to specifically localize encoded antigens in the nucleus (estrogen receptor), cytoplasm (cytokeratins), and cytoplasmic membrane (HER2) in TMAs. Results were compared with conventional IHC diaminobenzidine (DAB) immunostaining. There was full concordance between the EnzMet and conventional IHC results. Furthermore, the EnzMet reaction products did not appreciably diffuse, were dense and sharply defined, and provided excellent high-resolution differentiation of cellular compartments in paraffin sections for the nuclear, cytoplasmic, and cell membrane-localized antigens evaluated. The higher density of elemental silver deposited during enzyme metallography permitted evaluation of core immunophenotypes at a relatively low magnification, allowing more tissue to be screened in an efficient manner. This preliminary study shows the utility of using enzyme metallography for high-resolution immunophenotyping in TMAs.     

A simple and reliable method for rapidly harvesting split skin grafts in rats

A technique is presented which allows the rapid precise harvesting of split-skin grafts in rats. This technique uses the skin which would have been discarded in the formation of an open wound as a donor site thus reducing the overall assault on the animal.     

Adding Bupivacaine to High-potassium Cardioplegia Improves Function and Reduces Cellular Damage of Rat Isolated Hearts after Prolonged, Cold Storage

Background: Bupivacaine retards myocardial acidosis during ischemia. The authors measured function of rat isolated hearts after prolonged storage to determine whether bupivacaine improves cardiac protection compared with standard cardioplegia alone.

Methods: After measuring cardiac function on a Langendorff apparatus, hearts were perfused with cardioplegia alone (controls), cardioplegia containing 500 [mu]m bupivacaine, or cardioplegia containing 2 mm lidocaine; were stored at 4[degrees]C for 12 h; and were then reperfused. Heart rate and left ventricular developed pressures were measured for 60 min. Maximum positive rate of change in ventricular pressure, oxygen consumption, and lactate dehydrogenase release were also measured.

Results: All bupivacaine-treated, four of five lidocaine-treated, and no control hearts beat throughout the 60-min recovery period. Mean values of heart rate, left ventricular developed pressure, maximum positive rate of change in ventricular pressure, rate-pressure product, and efficiency in bupivacaine-treated hearts exceeded those of the control group (P < 0.001 at 60 min for all). Mean values of the lidocaine group were intermediate. Oxygen consumption of the control group exceeded the other groups early in recovery, but not at later times. Lactate dehydrogenase release from the bupivacaine group was less than that from the control group (P < 0.001) but did not differ from baseline.