In vivo measurement of 5-aminolaevulinic acid-induced protoporphyrin IX photobleaching: a comparison of red and blue light of various intensities

BACKGROUND: In recent years, 5-aminolaevulinic acid (ALA) has become an increasingly popular photosensitizing drug for use in both photodynamic therapy (PDT) and photodetection (PD) of cancers. ALA metabolizes within tissue to form the photosensitizer protoporphyrin IX (PpIX). Like most photosensitizers, PpIX is fluorescent, and this fluorescence progressively decreases during PDT. This phenomenon is referred to as photobleaching. AIM: Our aim in carrying out this experiment was twofold: firstly, to compare the relative capacity of red and blue light to cause photobleaching; and secondly, to compare the capacity of a fixed light dose to cause photobleaching, when delivered at different intensities. METHOD: In this paper, we describe the implementation of a compact fluorescence spectrometer in monitoring the photobleaching of ALA-induced PpIX in vivo on the skin of healthy volunteers. RESULTS: We have been able to show that blue light causes more rapid photobleaching than red light, and that under illumination with red or blue light, delivery of a fixed light dose at a lower intensity results in more photobleaching. CONCLUSION: Comparison of the photobleaching rates suggests that a blue light intensity of 5 mW/cm(2) gives the same rate of photobleaching as the typical red light PDT intensity of 100 mW/cm(2). Further investigation of the correlation between PpIX photobleaching and PDT effect would be beneficial in interpreting the clinical significance of our findings.     

Animal model: The mode of inheritance of craniomandibular osteopathy in west highland white terrier dogs

Craniomandibular osteopathy is a disease of several breeds of dogs, principally West Highland White and Scottish terriers. It is characterized by a non-neoplastic proliferation of bone on the ramus of the mandible and/or the tympanic bulla. The disease in various respects resembles Paget's disease and infantile cortical hyperrostosis of humans. A retrospective pedigree analysis of a kindred of West Highland White terriers was performed to determine if the trait was inherited and to determine mode of inheritance. This study indicated that in West Highland White terriers, the condition is an autosomal recessive trait.     

Bioluminescence screening for bacteriuria.

A rapid screening test (45 min) for bacteriuria was evaluated in 1,000 clinical urine specimens. The test procedure is based upon firefly luciferase analysis of bacterial ATP and uses the Lumac kit and Lumac M2010 Biocounter (3M Co., St. Paul, Minn.). The procedure allows for removal and destruction of nonbacterial ATP and subsequent analysis of bacterial ATP by firefly luciferase with a single photon counter. Results, expressed in relative light units, were compared with actual CFU by the calibrated loop technique. Sensitivities and specificities were calculated separately for clean-catch midstream specimens and for urines obtained by catheterization. The sensitivity for 719 clean-catch specimens with a Lumac cutoff of greater than or equal to 500 relative light units, representing greater than or equal to 10(5) CFU/ml, was 93%. The sensitivity for 281 catheterized specimens with a Lumac cutoff of greater than or equal to 200 relative light units, representing greater than or equal to 10(4) CFU/ml, was 95%. There were 19 false-negative results in the 1,000 specimens tested; more than 50% of these were contaminated cultures and were not considered significant in determining bacteriuria. In conclusion, the Lumac bioluminescence assay is a reliable, rapid bacteriuria screening technique with the potential of reducing the laboratory cost and for reducing the turnaround time in processing negative urine cultures.     

Effect of adrenalectomy on ethanol-associated changes in lymphocyte cell numbers and subpopulations in thymus, spleen, and gut-associated lymphoid tissues

Consumption of ethanol (ETOH) by experimental animals and human beings is associated with elevated serum levels of corticosteroids. One of the most robust findings associated with ETOH consumption is a loss of lymphocytes from thymus and spleen, as well as from peripheral lymphoid organs to include mesenteric lymph nodes and Peyer's patches, which are lymphoid organs associated with the gastrointestinal tract. To study the role of corticosteroids in loss of cells from thymus, spleen, and gut-associated lymphoid organs, adrenalectomized (ADX) or intact C57Bl/6 mice were fed a liquid diet containing ETOH (to supply 36% of calories as ETOH) or an isocaloric control diet with a pair-feeding protocol. Loss of lymphocytes from all lymphoid organs was associated closely with serum corticosterone levels in both ETOH-fed and pair-fed groups. ETOH-fed ADX animals showed much less cell loss than did ETOH-fed intact animals. However, there was still an association between ETOH consumption and cell loss when cell loss in ETOH-fed ADX animals was compared with that in ADX pair-fed and ADX chow-fed groups. In both intact and ADX animals ETOH consumption was associated with a loss of immature (CD4(+) and CD8(+)) cells from the thymus. These data lead to the suggestion that corticosteroids are responsible for most of the cell loss from thymus, spleen, mesenteric lymph nodes, and Peyer's patches in association with ETOH consumption. Some cell loss, however, is independent of corticosteroids. The data presented here also support the suggestion that cell loss from lymphoid organs could be the result of nutritional factors.     

MRI,Retrieval Analysis,and Histologic Evaluation of Adverse Local Tissue Reaction in Metal-on-Polyethylene Total Hip Arthroplasty

Background

The severity and location of adverse local tissue reaction (ALTR) seen in metal-on-polyethylene total hip arthroplasty (THA) is not well described.

Drosophila dSmad2 and Atr-I transmit activin/TGFβ signals

BACKGROUND: Much is known about the three subfamilies of the TGFbeta superfamily in vertebrates-the TGFbetas, dpp/BMPs, and activins. Signalling in each subfamily is dependent on both shared and unique cell surface receptors and Smads. In invertebrates, mutants for BMP pathway components have been extensively characterized, but thus far, evidence for an activin- or TGFbeta-like pathway has been lacking, preventing the use of the extensive genetic tools available for studying several key issues of TGFbeta signalling. RESULTS: Here we report the identification of dSmad2, a new Drosophila Smad which is most related to the activin/TGFbeta-pathway Smads, Smad2 and Smad3. We show that dSmad2 induces activin responsive genes in Xenopus animal cap assays. dSMAD2 is phosphorylated by ATR-I and PUNT, but not by activated THICK VEINS, and translocates to the nucleus upon activation. Furthermore, we show that dSMAD2 complexes with MEDEA only in the presence of ATR-I and PUNT. dSmad2 is expressed in the imaginal disks and in the outer proliferation centre of the larval brain, suggesting that it may have important proliferative and patterning roles during Drosophila development. CONCLUSION: Our data provide evidence for the existence of an activin/TGFbeta pathway in Drosophila. We show that dSmad2 participates in this pathway, and that it functions with Atr-I and punt. We show that Medea also participates in this pathway, indicating the conservation of roles for Co-Smads in diverse phyla. Expression patterns of dSmad2 suggest that it functions in imaginal disks and in the brain, in tissues that undergo extensive patterning and proliferation.     

Antidepressant drug use in an ambulatory elderly population: A 14-year overview

The objective of the work was to identify changes in antidepressant drug use and determine if the prevalence of antidepressant use has changed over 14 years. A longitudinal analysis comparing antidepressant drug use at 14 yearly intervals from 1978–79 to 1991–92 was undertaken using the longitudinal health screening program of ambulatory elderly participants (Florida Geriatric Research Program). Participants included all subjects screened in the Florida Geriatric Research Program from 1 August 1978 to 31 July 1992. The outcome measures were self-reported antidepressant drug use. Approximately 3.0 per cent (range of 2.3 to 3.2 per cent over 14 yearly intervals) of participants in this program reported the use of an antidepressant drug. There was no statistically significant change in antidepressant use between 1978–79 and 1991–92 (p > 0.6630). Across all study intervals women reported more frequent use of antidepressant drugs than men. In 1991–92, amitriptyline and imipramine represented over 50 per cent of all antidepressant drug use in this elderly population. Less than 6 per cent of all antidepressant drug use was for fluoxetine, the newest selective serotonin uptake inhibitor. The majority of elderly patients are receiving older tertiary amine tricyclic antidepressants such as amitriptyline, imipramine and doxepin that are not the preferred drugs for the elderly. Educational programs are needed to improve antidepressant prescribing for geriatric patients.     

Precision and accuracy of an ankle-worn accelerometer-based pedometer in step counting and energy expenditure

BACKGROUND: Walking is a widely used approach to increase physical activity levels in obese patients. In this paper, we investigate the precision and accuracy of an ankle-worn dual-axis accelerometer (Stepwatch) and investigate its potential application as a predictor of energy expenditure. METHODS: Twenty healthy subjects (10 lean, 10 obese) wore spring-levered (Accusplit), piezoelectric (Omron HF-100), and Stepwatch pedometers. Subjects walked on a treadmill at 1, 2, and 3 mph and in a hallway at 1 and 1.85 mph, during which energy expenditure was measured. RESULTS: The Stepwatch counted 99.7 +/- 0.67% (mean +/- SEM) of the manual counts. In comparison, the Omron pedometer counted 61 +/- 3.3% and the Accusplit counted 26 +/- 2.8% of the manual counts at 1 mph although all pedometers were accurate (> 98% of counts) at 3 mph. In repeated measures, the Stepwatch produced negligible variance (SD = 0.36) over all speed whereas the other pedometers showed a large amount of variance at all speed (SD = 4-13). Stepwatch counts were predictive of walking energy expenditure corrected by weight (r2 > 0.8). CONCLUSION: The counts from the Stepwatch were virtually identical to the manual counts from a trained investigator and provided a reliable predictor of walking energy expenditure.