Age-related differences in the temporal and spatial regulation of matrix metalloproteinases (MMPs) in normal skin and acute cutaneous wounds of healthy humans

Despite the association of increasing age with chronic wound-healing disorders and an impaired rate of healing of acute cutaneous wounds, the role of matrix metalloproteinases (MMPs) is unknown. To determine the spatial and temporal patterns and activities of MMP-1, -2, -3 and -9, 132 healthy humans aged between 19 and 96 years underwent 4-mm punch biopsies followed by wound excision between day 1 and day 180 post-wounding. Wounds showed an age-related increase in MMP-2 and MMP-9 immunostaining from day 3; this was associated with degradation of gelatin as shown by zymograms and with increased proteinase activity as shown by azocoll assays. Distinct spatial localisations for each MMP were observed: MMP-2 was found in epidermal structures; MMP-9 was observed in inflammatory cells up to day 21; MMP-1 was localised to keratinocytes at the wound margin. Normal old skin showed pro-MMP-2 bands on zymography and increased MMP-2 immunostaining. These results indicate that: (1) intrinsic ageing is associated with the up-regulation of MMPs previously associated with chronic wound healing; (2) wound-tissue proteinases are essentially active up to day 21 postwounding; and (3) intrinsic ageing may predispose to tissue breakdown disorders because of MMP-2 up-regulation in normal skin.     

Postmortem distribution of nicotine and cotinine from a case involving the simultaneous administration of multiple nicotine transdermal systems

A 31-year-old female was found dead with 18 nicotine transdermal system patches taped to her upper body and a plastic bag taped over her nose and mouth (the cause of death was ruled asphyxiation). Nicotine concentrations in biological fluids and tissues were analyzed using a liquid-liquid extraction followed by injection onto and HP-5890 gas chromatograph (GC) equipped with a nitrogen-phosphorus detector. Cotinine was separated from the biological matrices using solid-phase extraction followed by analysis on an HP-5890 GC with flame ionization detection. A variety of specimens were analyzed, including blood, urine, vitreous, brain, liver, and gastric contents. Heart and femoral blood concentrations (1.4 and 0.46 micrograms/mL, respectively) were 175 and 57 times, respectively, the mean C(max) value reported following the proper administration of a single 7-mg/day patch.     

Paget bone disease involving young adults in 3 generations of a Korean family

Pancreatic cancer is an aggressive disease with a dismal prognosis. It has long been regarded as one of the most difficult cancers to accurately diagnose and stage preoperatively. The purpose of this review is to provide an update of the state-of-the-art for early detection, diagnosis, and staging of pancreatic cancer. These methods include spiral CT scans, magnetic resonance imaging, positron emission tomography (PET) imaging, laparoscopy, endoscopic ultrasound, CA 19-9 serology, fine needle aspiration cytology, ERCP brush cytology, and screening for p53 and ras oncogenes. These advanced techniques should help us to detect pancreatic cancers in high-risk populations at a curative stage and to decrease pancreaticoduodenectomies for benign disease which could otherwise be treated with less morbid procedures. In addition, these tests will help reliably diagnose pancreatic cancer preoperatively.     

Laser Doppler flowmetry during open reduction for developmental dysplasia of the hip

Laser Doppler flowmetry was used intraoperatively to monitor femoral head perfusion during open reduction of 13 congenital hip dislocations in 11 patients. Laser Doppler determinations ranged from 12 to 400 mV before reduction and 30 to 300 mV after reduction. Three patients had magnitude changes in excess of 50%. One had increased perfusion, and two had decreased blood flow. Avascular necrosis of the hip occurred in one patient that was not predicted by laser Doppler flowmetry. Femoral head perfusion measured 175 mV for the dislocated hip and 180 mV after reduction of the femoral head and completion of the pelvic osteotomy. The authors conclude that laser Doppler flowmetry is not a reliable method for monitoring femoral head perfusion during open reduction of the hip for developmental hip dysplasia.     

Relationships between Diabetes and the Intestinal Microbial Population

Diabetes is a metabolic disorder characterized by lower responsiveness of tissues to insulin and consequent large variations in circulating levels of glucose. This fluctuation has harmful effects as both hyperglycemia and hypoglycemia can be very injurious. The causes of diabetes are varied but the consequences are rather uniform. Dietary factors are important especially in adult onset type 2 diabetes (T2D) while type 1 diabetes (T1D) is characterized by having a stronger heritable component and involving autoimmune attach on pancreatic beta cells. This review is focused on the relation of the bacterial components found within the intestine, to the establishment and maintenance of diabetes. The precise composition of the gut microbiome is increasingly recognized as a factor in organismic health and its interaction with a variety of disease states has been described. This is especially marked in the case of diabetes since the nature of the diet is an important factor in establishing both the microbiome and the incidence of diabetes. The bidirectional nature of this relationship is discussed. The effects of disease that lead to altered microbiomal composition together with aberrant metabolic changes are also included. Emphasis is given to the important role of short chain fatty acids (SCFAs) as mediators of the microbiome-diabetes relation.     

Influence of timing on the dosimetric analysis of transperineal ultrasound-guided, prostatic conformal brachytherapy

Postoperative computed tomography (CT)-based dosimetric analysis of transperineal ultrasound-guided conformal prostate brachytherapy provides detailed information regarding the coverage and uniformity of the implant. However, there is no generally accepted standard for the optimal timing of the postoperative dosimetry. This report details dosimetric analysis and the effect of timing based upon CT and orthogonal film evaluation for ten unselected patients implanted with either iodine-125 (125I) or palladium-103 (103Pd). Within 2 hours after implantation, patients underwent a CT scan and the first of four sequential sets of orthogonal films. Subsequent orthogonal films were obtained on days 3, 14, and 28 postimplant. CT-based dosimetry revealed coverage of the prostate to the prescribed minimal peripheral dose (mPD) at 93.1 +/- 3.6% of the volume, the prostate volume receiving 150% of mPD was 38.2 +/- 8.7%, and the urethral and rectal doses were 114 +/- 12% and 78 +/- 19% of mPD, respectively. The implanted seeds seen on orthogonal films acted as markers for temporal changes in prostate dimensions, and the standard deviation of each dimension was used as input in an ellipsoidal volume calculation. Seed coordinates were self normalized to the center of gravity of each two-dimensional view and were measured relative to the linear regression line in the superior-inferior direction. The reproducibility of the anteroposterior (AP) film setup in terms of temporal variation in the angle of the regression line was markedly better than that of the lateral films, 1.8 degrees +/- 1.2 degrees vs. 4.3 degrees +/- 2.6 degrees, respectively. Dimensional contraction from day 0 to day 28 averaged 11.3% in the superior-inferior direction, 8.5% in the AP/PA (posteroanterior) direction, and 2.5% in the right-left lateral direction. This translated into a volume change of 20.9% (ranged 11.6-31.6%), which was determined by using the ellipsoid method. The half-life for edema resolution was 10.6 +/- 1.8 days (range 8.6-14.3 days). However, because of variability in the degree and extent of edema and its rate of resolution, we believe that it may be futile to define a single point in time as the most accurate indicator of the postoperative dose distribution. Rather, it may be preferable to accept universal standardization of timing and methodology for CT-based postoperative dosimetry, which would facilitate comparison of results between centers and maximize the information content of that single measurement. We conclude that day 0 represents the optimal time, because dosimetric evaluation at that time minimizes patient discomfort and inconvenience (a catheter is already in place), provides information about edema when it is near its maximum extent, and provides prompt closure of the learning loop and, as such, hopefully will result in improved implantation techniques and results.