Measurement of the refractive index of highly turbid media: reply to comment.

Peiponen et al. [Opt. Lett.35, 4108 (2010)] have expressed concern that a theoretical model we proposed in Calhoun et al. [Opt. Lett.35, 1224 (2010)] for total internal reflection from a turbid medium may be inconsistent with the experimental data, in the sense that the model fails to take into account unexplained oscillations in our data. We show that their concern arises from misinterpretation of our data and theory, and is, therefore, unfounded. NOTE: Optics Letters apologizes to the authors for the delay in the publication of this Reply.

Diagnostic evaluation of children with daytime incontinence.

PURPOSE: This article is one of the standardization documents of the International Children's Continence Society, and discusses how anatomical/iatrogenic and functional/urodynamic causes of daytime incontinence in children of all ages are to be diagnosed, how neurogenic bladder dysfunction or urinary tract infection is excluded as a cause of the wetting, and how further diagnostic evaluation of children with disturbances such as overactive bladder, voiding postponement and dysfunctional voiding is performed. The roles of history taking (including prenatal and perinatal issues and family history), physical examination, diagnostic bladder diaries, noninvasive urodynamic investigations and radiological imaging are delineated but therapy is not within the scope of this document. MATERIALS AND METHODS: This document was designed and written by an international panel of authors with a large experience in assessment of children with incontinence. RESULTS: The best evidence was retrieved from the literature and assembled in a standardization document. CONCLUSIONS: Assessment of children with daytime symptoms is discussed. A noninvasive approach in these children allows us to select patients who will need a more invasive assessment.

Measurement of the refractive index of highly turbid media.

We demonstrate a first simultaneous measurement of the real and imaginary parts of the refractive index of a highly turbid medium by observing the real-time reflectance profile of a divergent laser beam made incident on the surface of the turbid medium. We find that the reflectance data are well described by Fresnel theory that correctly includes the effect on total internal reflection of angle-dependent penetration into the turbid medium.

Molecular basis for the binding of SH3 ligands with non-peptide elements identified by combinatorial synthesis.

BACKGROUND: Protein-structure-based combinatorial chemistry has recently been used to discover several ligands containing non-peptide binding elements to the Src SH3 domain. The encoded library used has the form Cap-M1-M2-M3-PLPPLP, in which the Cap and Mi's are composed of a diverse set of organic monomers. The PLPPLP portion provided a structural bias directing the non-peptide fragment Cap-M1-M2-M3 to the SH3 specificity pocket. Fifteen ligands were selected from > 1.1 million distinct compounds. The structural basis for selection was unknown. RESULTS: The solution structures of the Src SH3 domain complexed with two ligands containing non-peptide elements selected from the library were determined by multidimensional NMR spectroscopy. The non-peptide moieties of the ligands interact with the specificity pocket of Src SH3 domain differently from peptides complexed with SH3 domains. Structural information about the ligands was used to design various homologs, whose affinities for the SH3 domain were measured. The results provide a structural basis for understanding the selection of a few optimal ligands from a large library. CONCLUSIONS: The cycle of protein-structure-based combinatorial chemistry followed by structure determination of the few highest affinity ligands provides a powerful new tool for the field of molecular recognition.

The lithium librarian. An international index.

Lithium salts are being widely used for treatment and prophylaxis of bipolar affective disorder (manic-depressive psychosis) and are under investigation in more than 30 other illnesses. The relevant literature has grown from 43 articles published between 1949 and 1964 to nearly 4,000 today. A computer-based lithium librarian program has been developed that provides an up-to-date registry of all lithium references, rapid search capability, constant availability, and easy transferability to identical computer systems located on three continents. References provided by the system are more complete, more rapidly available, and less costly than references obtained from other bibliographic services. This specific response to the rapidly expanding lithium literature provides a model for comprehensive aquisition and searching of other specialized subjects areas needed by clinicians and researchers.

Role of calcium in isoproterenol cytotoxicity to cultured myocardial cells.

Primary cultures of rat myocardial cells were used to evaluate the cellular dynamics of calcium accumulation after exposure to isoproterenol (ISO). Non-toxic concentrations of ISO (2.4 X 10(-7) M) caused a gradual increase in myocyte calcium uptake. These effects peaked 3 min after exposure and returned to control levels within 2 min. Toxic concentrations of ISO caused a biphasic increase in calcium uptake. The initial phase peaked 1 min after exposure and returned to control levels by 3 min. A second phase was characterized by a progressive increase in calcium uptake that plateaued 10 min after exposure. Ascorbic acid (AA, 5 X 10(-3) M) and sodium bisulfite (SB, 9.6 X 10(-4) M) did not modify the calcium uptake of the initial phase, whereas propranolol (1 X 10(-6) M) and verapamil (1 X 10(-5) M) prevented the initial rise in calcium uptake. In contrast, the antioxidants prevented the the second phase of ISO-induced calcium uptake, whereas verapamil and propranolol did not. The toxic accumulation of calcium induced by ISO may be due to oxidative damage of the sarcolemma. Antioxidants may prevent the formation of oxidative metabolites from ISO and the subsequent calcium overload. Our results show that agents which modify slow calcium-channel transport do not prevent ISO-induced calcium overload in our cell culture system.

Cellular localization of a Hsp90 homologue in Porphyromonas gingivalis.

We previously reported an association between elevated serum antibody titers to the 90-kDa human heat shock protein (Hsp90), periodontal health and colonization by Porphyromonas gingivalis. In this study, we examined the cellular localization of the Hsp90 homologue of P. gingivalis. Cultures of P. gingivalis were heat-stressed (45 degrees C) and examined for localization of the Hsp90 homologue. Heat stress induced a 4-5-fold increase in anti-Hsp90 antibody reactivity over that of the unstressed controls. Western blot analysis revealed two bands (44 and 68 kDa) that reacted with anti-Hsp90 antibodies. The 68-kDa band was heat-inducible, while the 44-kDa band was not. Immunogold staining revealed that the Hsp90 homologue localized principally to the membrane and extracellular vesicles. Subcellular fractionation confirmed that the Hsp90 homologue was primarily membrane-associated.

Biofeedback therapy for children with dysfunctional voiding.

OBJECTIVES: Biofeedback therapy has been recognized as a treatment option for children with classic dysfunctional voiding (DV) where there is inadequate pelvic floor relaxation during voiding. However, there are few articles that discuss methodology and limited sites where it is available. In the hope of making biofeedback a more practical and accessible option, we report our indications, easy to duplicate methodology, and results. METHODS: Twenty-one consecutive children diagnosed with DV refractory to standard therapy were enrolled in our biofeedback program. Therapy consisted of extensive age-appropriate explanations of DV and demonstrations of normal and abnormal voiding patterns. Cyclic uroflow studies with pelvic floor electromyography are performed, which the child monitors on analog chart and audio recorders. The child returns weekly until consistent relaxation of the pelvic floor during voiding is demonstrated. Timing between sessions is then increased to monitor progress and retention of concepts previously taught. RESULTS: An excellent clinical response was one in which there was consistent relaxation of the pelvic floor throughout voiding, normal flow pattern, and no residual urine volume (urodynamic response), coupled with profound resolution of voiding symptoms. Seventeen of 21 (81%) had an excellent response, 3 (14%) had a fair response, and 1 (5%) was too inconsistent to rate. The average number of sessions to achieve a consistent urodynamic response was 3.7 (range 2 to 14) and full clinical response somewhat longer. Average follow-up since beginning therapy has been 34 months (range 14 to 51). CONCLUSIONS: Biofeedback therapy is an effective method for treating DV with poor pelvic floor relaxation. Although initially labor intensive, it yields sustained positive results in most patients in a short time.

Effects of pharmacological interventions on emetine cardiotoxicity in isolated perfused rat hearts.

The cardiotoxicity of emetine continues to be a significant clinical problem. The purpose of this study was to investigate the effect of several mechanistic interventions, including ICRF-187, an iron-chelating agent which protects against doxorubicin toxicity, atropine, and fructose-1,6-bisphosphate (FBP) on the toxicity of emetine in our isolated, perfused rat heart model. The model includes functional, electrocardiographic, and biochemical determinations in the same preparation. Atropine and ICRF-187 had no effect on the time needed for emetine to induce ventricular asystole, while FBP significantly increased this time. Administration of 47 microM atropine, 300 microM FBP, or 1 mM FBP decreased the release of lactate dehydrogenase (LDH) into the coronary effluent, while ICRF-187 had no effect. These pharmacological interventions variably changed the amplitude of the biphasic response of the coronary flow to emetine. Finally, FBP was very effective in slowing the rate of QRS-waveform degeneration in the perfused hearts. Emetine caused PR- and QRS-prolongation which was not altered by FBP.

In vivo effects of 1,3-bis(2-chloroethyl)-1-nitrosourea and doxorubicin on the cardiac and hepatic glutathione systems.

Doxorubicin and 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU) are anti-cancer drugs which have been used together in combination therapy of certain cancers. Each drug has been reported to affect intracellular glutathione stores and together, doxorubicin and BCNU have been shown to exert synergistic toxicity and to deplete completely the glutathione content of isolated hepatocytes. Cardiac and hepatic glutathione reductase activity was significantly inhibited following treatment in vivo with BCNU. Treatment of mice with both doxorubicin and BCNU resulted in increased mortality compared to either drug alone. There was, however, no depletion of hepatic or cardiac glutathione levels in vivo beyond that seen with either BCNU or doxorubicin alone. Diethyl maleate, a known glutathione depletor whose effects are enhanced by BCNU in vitro, also was unable to increase GSH depletion after BCNU in vivo. These discrepancies between in vivo and in vitro studies may be due to the presence of more effective compensatory mechanisms in the whole animal, or to differences in the metabolism and inactivation of these drugs.

The toxicity of tetrahydrobiopterin: acute and subchronic studies in mice.

Tetrahydrobiopterin (BH4) is presently being employed in clinical trials for the therapy of various neurological disorders. The toxicity of BH4 in mice was analyzed by acute and subchronic intraperitoneal and acute oral survival studies. Organ weight analysis and histopathology were performed after acute and subchronic i.p. administration. The effect of probenecid on BH4 toxicity was also tested. An LD50 of approximately 260 mg/kg was obtained from acute (14-day) intraperitoneal survival studies. A dose-dependent increase in kidney weights and histopathologic evidence of acute toxic tubular necrosis were noted in acute i.p. studies. Acute oral administration of up to 1318 mg/kg BH4 did not cause any significant morbidity or mortality, nor did subchronic (92-day) i.p. administration of 10 or 50 mg/kg BH4. Probenecid pretreatment did not decrease the toxicity of BH4. The importance of further evaluation of the potential toxicity of tetrahydrobiopterin in clinical utilization is emphasized.

Prevention of acetaminophen-induced hepatotoxicity by dimethyl sulfoxide.

Dimethyl sulfoxide (DMSO) has previously been shown to protect against acetaminophen (APAP)-induced hepatotoxicity, but the mechanism of this effect was not clear. Treatment of mice with 1 mg/kg DMSO 4 h before 250 mg/kg APAP resulted in significantly less hepatotoxicity than with APAP alone, as measured by serum glutamic pyruvic transaminase (SGPT) content 24 h after APAP. Protection was also evident when 1 ml/kg DMSO was given 4, but not 8 h after 250 mg/kg APAP. The APAP-induced depletion of liver glutathione was prevented in mice pretreated with DMSO, although DMSO alone had no effect on liver glutathione levels. The hepatic concentration of cytochrome P-450 (P450) 4 h after treatment of mice with 1 ml/kg DMSO, was significantly decreased compared to saline-treated animals. However, while this DMSO pretreatment significantly decreased the activity of cytochrome P-450-linked aminopyrine-N-demethylase, it increased the activity of aniline hydroxylase. Covalent binding of [14C]APAP to hepatic protein in vivo was significantly decreased in mice pretreated with DMSO. Covalent binding of [14C]APAP to hepatic microsomal protein in vitro was not significantly altered after in vivo treatment with DMSO. However, the presence of DMSO in the in vitro incubation mixture significantly decreased covalent binding of [14C]APAP in a dose-dependent manner compared to microsomal fractions from untreated, saline-treated or DMSO pretreated animals. These data suggest that the DMSO-induced alterations in cytochrome P-450 content and activity may not be the cause of the observed protective action of this chemical. The ability to competitively inhibit APAP bioactivation or to directly scavenge free radicals produced during APAP metabolism, including the activated species which covalently binds to protein, may account for the hepatoprotection afforded by DMSO.

Resuscitation attitudes among medical personnel: how much do we really want to be done?

Cardiopulmonary resuscitation (CPR) is attempted every day. Whereas medical professionals and personnel perform these resuscitation attempts, no previous studies have reported the attitudes of medical personnel towards resuscitation for themselves. We have attempted to assess the prevalent attitudes among various physicians at various levels in training and nurses. An eleven item questionnaire was sent to medical students, house officers, attending physicians and registered nurses at university medical centers. Each questionnaire consisted of respondent's sociodemographic information, their attitudes about CPR for themselves and their beliefs about outcome after CPR with particular disease states. The results were analyzed using chi-square analysis. Four hundred questionnaires were mailed and 240 were returned (60% response rate). All groups favored resuscitation in a university hospital over other sites (P less than 0.05). More nurses requested to be 'no code' compared with other professionals (P less than 0.005). Attending physicians requested that CPR attempts be terminated after less time than any other group (P less than 0.005). Medical students requested resuscitation significantly more than any other group in the presence of terminal conditions such as metastatic cancer, acquired immunodeficiency syndrome and severe chronic obstructive pulmonary disease (P less than 0.005). Medical personnel's beliefs about CPR may be influenced by their experiences with particular patients and events. As trainees acquire more experience they appear less inclined to desire resuscitation efforts for themselves.

In vitro photodecomposition of uric acid in presence of riboflavin II.

In vitro studies on the photodecomposition of uric acid in the presence of the monosodium salt of riboflavin 5'-phosphate in buffers at various pH values, in methanol, and in human plasma are reported. The decomposition rate increased with increasing pH and was independent of solvent or buffer species. The mechanism appears to be an energy transfer process involving triplet riboflavin and single oxygen. Riboflavin-enhanced photodecomposition of uric acid occurred in vitro in hyperuricemic human plasma.

High steady-state levels of uric acid produced in rats by dietary training and potassium oxonate.

To reduce the inherent variability in serum uric acid levels of animals allowed ad libitum exposure to food containing potassium oxonate and uric acid, male Sprague-Dawley rats were trained to eat their daily food allotment in a 1.25-hr period each morning. After training the rats were fed a food mixture containing 5% potassium oxonate and 2% uric acid (w/w each). Serum blood levels of uric acid reached a steady state within 2 hr; these levels were maintained for an additional 4 hr. It is believed that the stomach emptying rate is a zero-order process under these experimental conditions.

Effect of water-soluble carriers on morphine sulfate release from a silicone polymer.

The influence of gelatin, sodium lauryl sulfate, lactose, and sodium alginate on morphine sulfate diffusion from cylindrical silicone polymer pellets was examined in isotonic pH 7.4 phosphate buffer. These water-soluble carriers caused the pellets to swell in aqueous media. Sodium alginate exerted the greatest influence on drug release. The morphine sulfate diffusion rate from the cylindrical pellets increased as the matrix alginate content increased up to 20%. Water-soluble carrier incorporation into silicone polymeric matrixes permits controlled release of water-soluble drugs that otherwise would be released extremely slowly from the polymer. Drug diffusion from the silicone matrix containing sodium alginate followed second-order kinetics. The release mechanism probably involves the creation of pores or pathways through the matrix secondary to the swelling.

Influences of matrixes on nylon-encapsulated pharmaceuticals.

The preparation and properties of nylon microcapsules containing three different matrixes (formalized gelatin, calcium alginate, and calcium sulfate) are described. Microcapsules containing each matrix were dense and free flowing and could be made of very small diameter by controlling the stirring speed during nylon formation. The preparation of microcapsules containing calcium alginate employed freeze-drying procedures. Lyophilization was not necessary with the formalized gelatin and calcium sulfate systems. Various representative drugs (anionic, cationic, nonionic, quaternary, and amphoteric compounds) were used in the formulation studies. The effects of pH, matrix, and encapsulated species on retention of drug in the microcapsules are described. In addition, the surface morphology of the microcapsules was examined using scanning electron microscopy.

Emetine-induced lactate dehydrogenase release, functional changes and electrocardiographic changes in the rat heart in vitro.

Emetine is an old drug which is used primarily as a emetic in ipecac syrup and as an alternative amoebicide. The major problem with emetine is that chronic use causes severe cardiotoxicity. In order to explore the mechanism of emetine cardiotoxicity, simultaneous recordings of mechanical activity and electrocardiograms, and biochemical assays were performed on male Sprague-Dawley rat hearts perfused by the Langendorff technique. Emetine was perfused constantly at concentrations of 19 or 37 mum for 10 min. All of the effects of emetine were concentration dependent. The most significant toxicological effect was the large amounts of LDH which appeared in the coronary effluent. A significant degree of injury to the cardiac plasma membrane is indicated by this observation, since LDH normally is an intracellular enzyme. Such damage to the membrane might accumulate and lead to the chronic, cumulative cardiotoxicity observed clinically with emetine. The pharmacological effects of emetine perfusion included decreased contractility which occurred concurrently with P-R interval prolongation, QRS duration prolongation, and degeneration of the QRS waveform. Coronary flow increased early during emetine perfusion, but then dropped to below control levels. The atria were more delayed in their response to emetine and in their recovery following emetine than were the ventricles. The simultaneous measurement of several parameters is a useful technique for the study of cardiac toxicity.

Arthroscopic acromioclavicular joint resection. An anatomical study.

Distal clavicle resection has been an effective procedure for treatment of acromioclavicular arthritis. The conventional open surgical technique involves deltoid detachment and reattachment, which may cause postoperative weakness and requires protection during the postoperative period to allow for healing. Arthroscopic acromioclavicular joint resection has the theoretical advantages of no deltoid disruption and a shorter rehabilitation period. The purpose of this study was to compare open versus arthroscopic acromioclavicular joint resection in a laboratory setting. The goals of acromioclavicular joint resection in this study were to remove 5 mm of the medial acromion and 10 mm of the distal clavicle. Acromioclavicular joint resections were performed on 10 cadaver shoulders (5 open resections and 5 arthroscopic resections). Open resection was successful at 10 of 15 distal clavicle locations and 14 of 15 medial acromial locations. Arthroscopic resection was successful at 14 of 15 distal clavicle locations and 10 of 15 medial acromial locations. The combined bone resection averaged 14.8 mm (+/- 1.99 mm) for the open technique and 14.8 mm (+/- 2.58 mm) for the arthroscopic technique. The combined bone resection was 1.5 cm or more in all of the measured locations for the open technique and in 14 of 15 measure locations for the arthroscopic technique. There was no statistically significant difference between the two groups. In the laboratory setting, acromioclavicular joint resection was performed effectively and predictably with arthroscopic instruments. Arthroscopic bone resection was comparable to open bone resection.

Consciousness as a self-organizing process: an ecological perspective.

The evolution of consciousness is seen in the context of energy-driven evolution in general, where energy and information are understood as two sides of the same coin. From this perspective consciousness is viewed as an ecological system in which streams of cognitive, perceptual, and emotional information form a rich complex of interactions, analogous to the interactive metabolism of a living cell. The result is an organic, self-generating, or 'autopoietic', system, continuously in the act of creating itself. Evidence suggests that this process is chaotic, or at least chaotic-like, and capable of assuming a number of distinct states best understood as chaotic attractors.