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Results for “Deep generative model”

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PubMed2000

Photoaging of the skin from phenotype to mechanisms.

The skin is increasingly exposed to ambient UV-irradiation thus increasing its risk for photooxidative damage with longterm detrimental effects like photoaging, which is characterized by wrinkles, loss of skin tone, and resilience. Photoaged skin displays prominent alterations in the cellular component and the extracellular matrix of the connective tissue with an accumulation of disorganized elastin and its microfibrillar component fibrillin in the deep dermis and a severe loss of interstitial collagens, the major structural proteins of the dermal connective tissue. The unifying pathogenic agents for these changes are UV-generated reactive oxygen species (ROS) that deplete and damage non-enzymatic and enzymatic antioxidant defense systems of the skin. As well as causing permanent genetic changes, ROS activate cytoplasmic signal transduction pathways in resident fibroblasts that are related to growth, differentiation, senescence, and connective tissue degradation. This review focuses on the role of UV-induced ROS in the photodamage of the skin resulting in biochemical and clinical characteristics of photoaging. In addition, the relationship of photoaging to intrinsic aging of the skin will be discussed. A decrease in the overall ROS load by efficient sunscreens or other protective agents may represent promising strategies to prevent or at least minimize ROS induced photoaging.

Animals↗

PubMed2002

Neurostimulation systems for deep brain stimulation: in vitro evaluation of magnetic resonance imaging-related heating at 1.5 tesla.

PURPOSE: To assess magnetic resonance imaging (MRI)-related heating for a neurostimulation system (Activa Tremor Control System, Medtronic, Minneapolis, MN) used for chronic deep brain stimulation (DBS). MATERIALS AND METHODS: Different configurations were evaluated for bilateral neurostimulators (Soletra Model 7426), extensions, and leads to assess worst-case and clinically relevant positioning scenarios. In vitro testing was performed using a 1.5-T/64-MHz MR system and a gel-filled phantom designed to approximate the head and upper torso of a human subject. MRI was conducted using the transmit/receive body and transmit/receive head radio frequency (RF) coils. Various levels of RF energy were applied with the transmit/receive body (whole-body averaged specific absorption rate (SAR); range, 0.98-3.90 W/kg) and transmit/receive head (whole-body averaged SAR; range, 0.07-0.24 W/kg) coils. A fluoroptic thermometry system was used to record temperatures at multiple locations before (1 minute) and during (15 minutes) MRI. RESULTS: Using the body RF coil, the highest temperature changes ranged from 2.5 degrees-25.3 degrees C. Using the head RF coil, the highest temperature changes ranged from 2.3 degrees-7.1 degrees C.Thus, these findings indicated that substantial heating occurs under certain conditions, while others produce relatively minor, physiologically inconsequential temperature increases. CONCLUSION: The temperature increases were dependent on the type of RF coil, level of SAR used, and how the lead wires were positioned. Notably, the use of clinically relevant positioning techniques for the neurostimulation system and low SARs commonly used for imaging the brain generated little heating. Based on this information, MR safety guidelines are provided. These observations are restricted to the tested neurostimulation system.

Brain↗

PubMed2005

Efficacy of total ankle replacement with meniscal-bearing devices: a systematic review and meta-analysis.

INTRODUCTION: The reputation of total ankle arthroplasty for treating end-stage ankle arthritis of different origin is dubious. Newer generation meniscal-bearing prostheses may have overcome the known problems with earlier implants. There is, however, no systematic approach to the available scientific evidence allowing for a critical appraisal of their benefits and risks. MATERIALS AND METHODS: We conducted a systematic review meta-analysis of studies exploring the efficacy of three-component total ankle prostheses. We demanded a minimum sample size of 20 subjects, at least 1 year of follow-up, and a clinically relevant study endpoint (for example, results of ankle scoring, ranges of motion [ROM], complications, and survival rates). We identified citations by electronic medical databases and a manual search. We made no restrictions for language. We used an eight-point quality scale to appraise methodological standards, and modeled outcomes by random-effects meta-regression analysis. RESULTS: Eighteen of 1830 citations including 1086 patients fulfilled our eligibility criteria. Studies met a median of four quality items (interquartile range 2-5). Outcome estimates did not depend on methodological quality. There was no evidence of strong heterogeneity or publication bias. With standardized 100-point ankle and hindfoot scores, formal data pooling was possible for 10 trials (n =497), showing a mean improvement of 45.2 points (95% confidence interval [CI] 39.3-51.1). Overall ROM improved slightly (6.3 degrees, 95%CI 2.2-10.5 degrees ). Weighted complication rates ranged from 1.6% (deep infections) to 14.7% (impingement). Secondary surgery had to be performed in 12.5%, whereas secondary arthrodesis was necessary in 6.3%. The weighted 5-year prosthesis survival rate averaged 90.6%. CONCLUSIONS: Ankle arthroplasty improves pain and joint mobility in end-stage ankle arthritis. Its performance in comparison to the current reference standard (that is, ankle fusion) remains to be defined in a properly designed randomized trial.

Ankle Joint↗

PubMed2001

Solar UV irradiation and dermal photoaging.

The skin is increasingly exposed to ambient UV-irradiation thus increasing risks for photooxidative damage with long-term detrimental effects like photoaging, characterized by wrinkles, loss of skin tone and resilience. Photoaged skin displays alterations in the cellular component and extracellular matrix with accumulation of disorganized elastin and its microfibrillar component fibrillin in the deep dermis and a severe loss of interstitial collagens, the major structural proteins of the dermal connective tissue. The unifying pathogenic agents for these changes are UV-generated reactive oxygen species (ROS) which deplete and damage non-enzymatic and enzymatic antioxidant defense systems of the skin. As well as causing permanent genetic changes, ROS activate cytoplasmic signal transduction pathways in resident fibroblasts that are related to growth, differentiation, senescence and connective tissue degradation. This review focuses on the role of UV-induced ROS in the photodamage of the skin resulting in clinical and biochemical characteristics of photoaging. In addition, the relationship of photoaging to intrinsic aging of the skin will be briefly discussed. A decrease in the overall ROS load by efficient sunscreens or other protective agents may represent promising strategies to prevent or at least minimize ROS-induced photoaging.

Aging↗

PubMed2003

Stimulation of the nervous system for the management of seizures: current and future developments.

Vagal nerve stimulation (VNS) for the treatment of refractory epilepsy appears to have started from the theory that since VNS can alter the EEG, it may influence epilepsy. It proved effective in several models of epilepsy and was then tried in short-term, open-label and double-blind trials, leading to approval in Canada, Europe and the US. Follow-up observations in these patients demonstrated continued improvement in seizure control for up to 2 years. Close to 50% of treated patients have achieved at least a 50% reduction in seizure frequency. This therapy was also useful as rescue therapy for ongoing seizures in some patients; many patients are more alert. The initial trials were completed in patients >/=12 years of age with refractory partial seizures. Subsequently, similar benefits were shown in patients with tuberous sclerosis complex, Lennox-Gastaut syndrome, hypothalamic hamartomas and primary generalised seizures. Implanting the generator and leads is technically easy, and complications are few. The method of action is largely unknown, although VNS appears to alter metabolic activity in specific brain nuclei. Considering that improvement in mood is frequently found in patients using VNS, it has undergone trials in patients with depression. Other illnesses deserving exploration with this unusual therapy are Alzheimer's disease and autism. Some aspects of VNS have proven disappointing. Although patients have fewer seizures, the number of antiepileptic drugs they take is not significantly reduced. In addition, there is no way to accurately predict the end of life of the generator. Optimal stimulation parameters, if they exist, are unknown. Deep brain stimulation is a new method for controlling medically refractory seizures. It is based on the observation that thalamic stimulation can influence the EEG over a wide area. Several thalamic nuclei have been the object of stimulation in different groups of patients. Intraoperative brain imaging is essential for electrode placement. The procedure is done under local anaesthesia. Experience with this therapy is currently limited, but growing.

Brain↗

PubMed2006

Ghrelin receptor inverse agonists: identification of an active peptide core and its interaction epitopes on the receptor.

[D-Arg1,D-Phe5,D-Trp7,9,Leu11]Substance P functions as a low-potency antagonist but a high-potency full inverse agonist on the ghrelin receptor. Through a systematic deletion and substitution analysis of this peptide, the C-terminal carboxyamidated pentapeptide wFwLX was identified as the core structure, which itself displayed relatively low inverse agonist potency. Mutational analysis at 17 selected positions in the main ligand-binding crevice of the ghrelin receptor demonstrated that ghrelin apparently interacts only with residues in the middle part of the pocket [i.e., between transmembrane (TM)-III, TM-VI and TM-VII]. In contrast, the inverse agonist peptides bind in a pocket that extends all the way from the extracellular end of TM-II (AspII:20) across between TM-III and TM-VI/VII to TM-V and TM-IV. The potency of the main inverse agonist could be improved up to 20-fold by a number of space-generating mutants located relatively deep in the binding pocket at key positions in TM-III, TM-IV and TM-V. It is proposed that the inverse agonists prevent the spontaneous receptor activation by inserting relatively deeply across the main ligand-binding pocket and sterically blocking the movement of TM-VI and TM-VII into their inward-bend, active conformation. The combined structure-functional analysis of both the ligand and the receptor allowed for the design of a novel, N-terminally Lys-extended analog of wFwLL, which rescued the high-potency, selective inverse agonism that was dependent upon both AspII:20 and GluIII:09. The identified pharmacophore can possibly serve as the basis for targeted discovery of also nonpeptide inverse agonists for the ghrelin receptor.

Amino Acid Sequence↗

PubMed2003

Pilot study of topical delivery of mono-L-aspartyl chlorin e6 (NPe6): implication of topical NPe6-photodynamic therapy.

Photodynamic therapy (PDT) is an evolving cancer treatment with promising results in treating malignant tumors by photoactivation of a photosensitizer with a specific wavelength. The second generation photosensitizer mono-L-aspartyl chlorin e6 (NPe6) was reported to have significant efficacy in killing cancer cells in vitro and in vivo. Though topical application might yield a higher local concentration and less systemic side effect, no data concerning topical absorption of NPe6 is available even though the drug has already been used in clinical trial for several years. To evaluate the possibility of topical delivery of NPe6 via an animal model, escalated concentrations of NPe6 were applied to BALB/c mouse skin for a different time periods after barrier disruption with tape stripping. Since NPe6 fluorescence intensity and drug concentration in tissue was well correlated, we evaluated drug penetration depth with frozen sections of treated and non-treated skin under a fluorescence microscope. An on-line fluorescence imaging system was used to monitor the NPe6 fluorescence kinetics in the skin. The fluorescence microscope confirmed successful topical delivery of NPe6 in mouse skin with or even without barrier disruption. Orange to red NPe6 fluorescence appeared at the epidermis, dermis, and even the muscular layer when using 10 mg/ml NPe6 application. The fluorescence intensity peaked at 1 h and revealed a dose-dependent response pattern. NPe6 treated versus non-treated skin showed a statistically significant difference by Student's t-test (P<0.05). The results described here suggest that topical delivery of NPe6 is possible. It showed fast and deep penetration into mouse skin. This implies that NPe6 might be useful as a topical photosensitizer for PDT in treating skin cancers.

Administration, Topical↗

PubMed2004

Noninvasive bladder volume measurements based on nonlinear wave distortion.

The purpose of this study is to suggest a new approach to measure noninvasively the fluid content of a human cavity; in particular, the bladder volume. Determination of bladder volume is important clinically for patients suffering from bladder dysfunction. Several ultrasonic methods were proposed in the past for such a purpose. Most of these methods are based on multiple cross-sectional images and detection of echoes from the bladder wall. We propose here, in a first step, a simple approach that is able to provide an indication of whether or not the bladder volume has exceeded a certain threshold volume. Second, the possibility of accurate volume assessment will be discussed. The approach takes advantage of the difference in harmonic generation of liquids (urine) and tissues. We know that nonlinear effects occur most strongly when ultrasound (US) propagates through liquids with relatively low acoustic attenuation, such as water or urine. However, within soft tissues, the tendency for wave distortion to occur is limited as a result of different acoustic characteristics, most notably the attenuation. Our method is based on measuring the presence of harmonics in an echo from a region-of-interest (ROI) at fixed depth beyond the bladder. The harmonic content in the echo will increase with increase of fluid in the echo path. Phantom measurements were carried out with a single-element transducer and a phased-array transducer. Phantoms containing different volumes were used. Furthermore, measurements on volunteers were performed. The results confirmed that the harmonic content of an echo measured at a deep ROI increases for a full bladder and decays strongly after the volunteer has voided. These preliminary results demonstrate the feasibility of the approach.

Biophysical Phenomena↗

PubMed2004

Acoustic remote sensing of swimbladder orientation and species mix in the oreo population on the Chatham Rise.

A method for combining in situ measurements and theoretical swimbladder-derived estimates of target strength of the deep-water fish, black and smooth oreos, is described. The technique uses Monte Carlo simulation and yields fish length-target strength relationships suitable for use in estimating biomass from echo integration acoustic surveys. The relationships are derived from estimates of the mean and standard deviation of the tilt angle distributions of the wild fish generated by the method. The relationships may also be used to estimate proportions of the two oreo species in the wild. The mean tilt angle of black oreos in the wild was about 10 degrees with a standard deviation of 8 degrees. For smooth oreos it was close to zero with a standard deviation of about 4 degrees. The target strength relationships derived for biomass estimation purposes were TSB= -78.05+25.3 log10(L)+1.62 sin(0.0815L+0.238) and TSS = -82.16+24.6 log10(L)+1.03 sin(0.1165L-1.765), where L is the fish length and TSB and TSS are the target strengths of black and smooth oreos respectively.

Acoustics↗

PubMed1992

A comparison of stone damage caused by different modes of shock wave generation.

A standard stone phantom was used to compare stone damage after extracorporeal shock wave administration from electrohydraulic, electromagnetic and piezoelectric lithotripters. For each machine, a low and high shock wave intensity setting was chosen: 18 & 24 kV for electrohydraulic; 16 & 19 kV for electromagnetic; power levels 1 and 4 for piezoelectric. The shock wave was focused either at the front (surface facing the wave source) or back surface of the stone and 50, 100, 200 or 400 shocks were delivered to different stone groups. Effects of varying physical properties in the stone phantom were also investigated. Stone damage was described in terms of volume loss and both depth and width of the resulting damage crater. At the lower intensity settings, all three machines produced stone volume loss which was linearly related to the number of shock delivered. At higher intensity settings, volume loss increased rapidly as the number of shocks increased. With the same number of shocks, stone volume loss was greatest with the electrohydraulic machine, followed by electromagnetic and piezoelectric lithotripters for both low and high intensity settings. Damage craters from the piezoelectric device were narrow and deep; those from the electromagnetic machine were of the shape of a right angle circular cone; whereas those from the electrohydraulic lithotripter were shallow and wide. At the high intensity settings, damage from the piezoelectric and electrohydraulic lithotripters appeared to depend upon the position of the focal point with a higher volume loss when the shock waves were targeted at the front surface of the stone. For the electromagnetic device, a higher volume loss was found when we positioned the focal point at the back surface of the stone phantom. Stone phantoms with lower mechanical strength and acoustic impedance were more easily damaged than those with higher values. Finally, a computer regression model was developed to express volume loss in terms of the intensity setting, focal position and number of shocks for each lithotripter.

Calculi↗

PubMed1995

Crystal structure and site-directed mutagenesis of Bacillus macerans endo-1,3-1,4-beta-glucanase.

In beta-glucans those beta-1,4 glycosidic bonds which are adjacent to beta-1,3 bonds are cleaved by endo-1,3-1,4-beta-glucanases (beta-glucanases). Here, the relationship between structure and activity of the beta-glucanase of Bacillus macerans is studied by x-ray crystallography and site-directed mutagenesis of active site residues. Crystal structure analysis at 2.3-A resolution reveals a jelly-roll protein structure with a deep active site channel harboring the amino acid residues Trp101, Glu103, Asp105, and Glu107 as in the hybrid Bacillus beta-glucanase H(A16-M) (Keitel, T., Simon, O., Borriss, R., and Heinemann, U. (1993) Proc. Natl. Acad. Sci. U.S.A. 90, 5287-5291). Different mutant proteins with substitutions in these residues are generated by site-directed mutagenesis, isolated, and characterized. Compared with the wild-type enzyme their activity is reduced to less than 1%. Several mutants with isosteric substitutions in Glu103 and Glu107 are completely inactive, suggesting a direct role of these residues in glycosyl bond hydrolysis. The kinetic properties of mutant beta-glucanases and the crystal structure of the wild-type enzyme are consistent with a mechanism where Glu103 and Glu107 are the catalytic amino acid residues responsible for cleavage of the beta-1,4 glycosidic bond within the substrate molecule.

Amino Acid Sequence↗

PubMed1997

Structure-based discovery of ligands targeted to the RNA double helix.

Ligands capable of specific recognition of RNA structures are of interest in terms of the principles of molecular recognition as well as potential chemotherapeutic applications. We have approached the problem of identifying small molecules with binding specificity for the RNA double helix through application of the DOCK program [Kuntz, I. D., Meng, E. C., and Shoichet, B. K. (1994) Acc. Chem. Res. 27, 117-123], a structure-based method for drug discovery. A series of lead compounds was generated through a database search for ligands with shape complementarity to the RNA deep major groove. Compounds were then evaluated with regard to their fit into the minor groove of B DNA. Those compounds predicted to have an optimal fit to the RNA groove and strong discrimination against DNA were examined experimentally. Of the 11 compounds tested, 3, all aminoglycosides, exhibited pronounced stabilization of RNA duplexes against thermal denaturation with only marginal effects on DNA duplexes. One compound, lividomycin, was examined further, and shown to facilitate the ethanol-induced B to A transition in calf thymus DNA. Fluorine NMR solvent isotope shift measurements on RNA duplexes containing 5-fluorouracil provided evidence that lividomycin binds in the RNA major groove. Taken together, these results indicate that lividomycin recognizes the general features of the A conformation of nucleic acids through deep groove binding, confirming the predictions of our DOCK analysis. This approach may be of general utility for identifying ligands possessing specificity for additional RNA structures as well as other nucleic acid structural motifs.

Aminoglycosides↗

PubMed2003

The effect of elevated intraocular oxygen on organelle degradation in the embryonic chicken lens.

In the vertebrate lens, nuclei and other cytoplasmic organelles are degraded in fiber cells situated in the center of the tissue. This is believed to ensure the transparency of the tissue. The mechanism that triggers this process is unknown. We hypothesized that standing gradients of oxygen generated within the tissue may serve as a spatial cue for organelle degradation. To examine this possibility, we incubated fertilized chicken eggs under hyperoxic (50% O(2)) or normoxic (21% O(2)) conditions. Hyperoxic treatment was initiated on the seventh day of embryonic development (E7), five days before organelle degradation normally commences in the lens core. Hyperoxia was maintained until E17. Under normoxic conditions, the partial pressure of oxygen (P(O)) within the vitreous compartment was low. Direct measurement of P(O) using an optode oxygen sensor indicated values of 1.3 kPa and 0.4 kPa for the mid- and anterior vitreous, respectively. Similarly, treatment with pimonidazole, a bio-reductive hypoxia marker, led to the formation of immuno-positive protein adducts within the lens, suggesting that the embryonic lens is chronically hypoxic in situ. Following hyperoxic treatment, vitreous P(O) significantly increased, although pimonidazole staining in the lens was not markedly affected. Confocal microscopy of slices prepared from hyperoxic lenses revealed a significant increase in the size of the lens relative to age-matched normoxic controls. By E13, an organelle-free zone (OFZ) was present in the center of normoxic and hyperoxic lenses. However, in hyperoxic lenses, the OFZ was consistently smaller, and the distance from the lens surface to the border of the OFZ significantly larger, than in normoxic controls. These observations suggest that hyperoxia delays organelle breakdown and are consistent with a model in which hypoxia in the deep cortical layers of the normal lens serves as a trigger for the organelle loss process.

Animals↗

PubMed2002

Arterial embolization hyperthermia in porcine renal tissue.

BACKGROUND: Arterial embolization hyperthermia (AEH) consists of arterially embolizing tumors with ferromagnetic particles that generate hysteretic heating on exposure to an alternating magnetic field. It was the objective of this study to evaluate AEH using the kidney of a large animal as a tumor model. METHODS: Between 50 and 400 mg of ferromagnetic microspheres (32 microm in diameter) was arterially infused into the kidneys of three pigs. Temperature probes were inserted into renal tissue, skin, and subcutaneous fat. Each subject was then exposed to an alternating magnetic field for 5 min, while under a general anesthetic. A femoral artery catheter was used to monitor the cardiac pulse. Three days after treatment the renal tissue was chemically analyzed for iron content, which was then correlated with tissue heating rates. RESULTS: There was a linear relationship between heating rate and iron concentration (N = 18, correlation = 0.72, P < 0.001) that suggested tissue iron concentrations in the range of 1.55 to 4.05 mg/g would yield tissue heating rates of 0.5 to 1.0 degrees C/min. No temperature increases were detected in control renal tissue (N = 6). The median increase in skin temperature after 5 min of heating was 0.8 degrees C (N = 6, min = 0.7 degrees C, max = 1.3 degrees C), and that in subcutaneous fat was 1.1 degrees C (N = 6, min = 0.8 degrees C, max = 1.2 degrees C). There was no detectable stimulation of cardiac or skeletal muscle or peripheral nerves during treatment. All subjects had uneventful 3-day posttreatment survivals. CONCLUSION: This study has shown that AEH can target deep-seated, vascularized tissue in a large animal with therapeutic temperatures (> 42 degrees C), and that the treatment is safe and well tolerated. Further assessment of treatment schedules should allow for a human trial in the near future.

Adipose Tissue↗

PubMed1995

Active site topology and reaction mechanism of GTP cyclohydrolase I.

GTP cyclohydrolase I of Escherichia coli is a torus-shaped homodecamer with D5 symmetry and catalyzes a complex ring expansion reaction conducive to the formation of dihydroneopterin triphosphate from GTP. The x-ray structure of a complex of the enzyme with the substrate analog, dGTP, bound at the active site was determined at a resolution of 3 A. In the decamer, 10 equivalent active sites are present, each of which contains a 10-A deep pocket formed by surface areas of 3 adjacent subunits. The substrate forms a complex hydrogen bond network with the protein. Active site residues were modified by site-directed mutagenesis, and enzyme activities of the mutant proteins were measured. On this basis, a mechanism of the enzyme-catalyzed reaction is proposed. Cleavage of the imidazole ring is initiated by protonation of N7 by His-179 followed by the attack of water at C8 of the purine system. Cystine Cys-110 Cys-181 may be involved in this reaction step. Opening of the imidazole ring may be in concert with cleavage of the furanose ring to generate a Schiff's base from the glycoside. The gamma-phosphate of GTP may be involved in the subsequent Amadori rearrangement of the carbohydrate side chain by activating the hydroxyl group of Ser-135.

Amino Acid Sequence↗

PubMed2000

Field studies of the leachability of aged brown coal ash.

The environmental management of ash produced from the brown coal power stations of the Latrobe Valley region of Australia has been studied. Current practice consists of slurrying fly and bottom ash, a short distance to an ash disposal pond. However, storage facilities are approaching capacity and alternative ash management strategies are required in the near future. Initially, the ash produced within the power stations is known to possess a large soluble mass, which can leach rapidly to generate a saline leachate with minor trace metal content. After slurrying and deposition within the ash pond, it has been demonstrated that the soluble mass is significantly lower and the ash can be considered as aged or "leached" ash - a more benign waste that meets the criteria for fill material. In order to assess the long-term behaviour of the leached ash and its suitability for co-disposal in engineered sites within overburden dumps, two field cells were constructed and monitored over a period of 1 year. Each cell was 5 x 5 m in area, 3-m deep and HDPE lined with a coarse drainage layer and leachate collection pipe. The first cell only collected natural rainfall and was known as the Dry Cell. The second cell had an external tank of 5000 l installed (200-mm rainfall equivalent) and water was spray-irrigated regularly to simulate higher rainfall and accelerate the leaching process. The cumulative inflow and outflow for each cell has been calculated using a linear relationship and the leachate quality was monitored over time. The results demonstrate that the ash behaves as an unsaturated porous material, with the effect of evaporation through the profile being dominant and controlling the production of leachate. The leachate quality was initially moderately saline in both cells, with the concentration dropping by nearly 95% in the Wet Cell by the end of the field study. The leachate chemistry has been analysed using the PHREEQC geochemical model. The log activity plots of various species suggest the mineralogical controls on these species in leachate. The full results from this study are presented.

Australia↗

PubMed2006

The treatment of hip fractures: variations in care.

UNLABELLED: The purpose of this descriptive study was to identify the ranges of operative treatment, perioperative management, and mortality rate of elderly patients with hip fractures. We retrospectively identified 1001 elderly patients who had operative treatment for a fractured hip in 49 medium- and high-volume California hospitals using a two-stage stratified cluster sample of hospitalizations for hip fractures. This sampling method allowed for generation of weighted estimates that described the overall care of all patients with hip fractures in California from 1995 to 1996. The in-hospital, 30-day, and 6-month mortality rates were 1.7%, 5%, and 12% respectively. Bipolar hemiarthroplasties were used more often than unipolar implants (73% versus 26%). There were some deviations from generally accepted guidelines for care of patients with hip fractures particularly related to administration of antibiotic and deep vein thrombosis prophylaxis. Fourteen percent of patients did not receive any antibiotic prophylaxis before and during surgery, and 24% did not receive prophylaxis within 4 hours of the beginning of the surgical procedure. Twenty-four percent of patients received no prophylaxis for deep vein thrombosis, and 81% of patients did not receive prophylaxis after hospital discharge. Surgeons need to continually evaluate the treatment regimens for patients with hip fractures to optimize care. LEVEL OF EVIDENCE: Descriptive Study, Level II (retrospective cohort study). See the Guidelines for Authors for a complete description of levels of evidence.

Aged↗

PubMed2003

Photodynamic therapy with Pd-Bacteriopheophorbide (TOOKAD): successful in vivo treatment of human prostatic small cell carcinoma xenografts.

Small cell carcinoma of the prostate (SCCP), although relatively rare, is the most aggressive variant of prostate cancer, currently with no successful treatment. It was therefore tempting to evaluate the response of this violent malignancy and its bone lesions to Pd-Bacteriopheophorbide (TOOKAD)-based photodynamic therapy (PDT), already proven by us to efficiently eradicate other aggressive non-epithelial solid tumors. TOOKAD is a novel bacteriochlorophyll-derived, second-generation photosensitizer recently, developed by us for the treatment of bulky tumors. This photosensitizer is endowed with strong light absorbance (epsilon(0) approximately 10(5) mol(-1) cm(-1)) in the near infrared region (lambda=763nm), allowing deep tissue penetration. The TOOKAD-PDT protocol targets the tumor vasculature leading to inflammation, hypoxia, necrosis and tumor eradication. The sensitizer clears rapidly from the circulation within a few hours and does not accumulate in tissues, which is compatible with the treatment of localized tumor and isolated metastases. Briefly, male CD1-nude mice were grafted with the human SCCP (WISH-PC2) in 3 relevant anatomic locations: subcutaneous (representing tumor mass), intraosseous (representing bone metastases) and orthotopically within the murine prostate microenvironment. The PDT protocol consisted of i.v. administration of TOOKAD (4 mg/kg), followed by immediate illumination (650-800 nm) from a xenon light source or a diode laser emitting at 770 nm. Controls included untreated animals or animals treated with light or TOOKAD alone. Tumor volume, human plasma chromogranin A levels, animal well being and survival were used as end points. In addition, histopathology and immunohistochemistry were used to define the tumor response. Subcutaneous tumors exhibited complete healing within 28-40 days, reaching an overall long-term cure rate of 69%, followed for 90 days after PDT. Intratibial WISH-PC2 lesions responded with complete tumor elimination in 50% of the treated mice at 70-90 days after PDT as documented histologically. The response of the orthotopic model was also analyzed histologically with similar results. The study with this model suggests that TOOKAD-based PDT can reach large tumors and is a feasible, efficient and well-tolerated approach for minimally invasive treatment of local and disseminated SCCP.

Animals↗