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The orientation of the magnetic field (B-field) in the filamentary dark cloud GF 9 was traced from the periphery of the cloud into the L1082C dense core that contains the low-mass, low-luminosity Class 0 young stellar object (YSO) GF 9-2 (IRAS 20503+6006). This was done using SOFIA HAWC+ dust thermal emission polarimetry (TEP) at 216 um in combination with Mimir near-infrared background starlight polarimetry (BSP) conducted at H-band (1.6 um) and K-band (2.2 um). These observations were augmented with published I-band (0.77 um) BSP and Planck 850 um TEP to probe B-field orientations with offset from the YSO in a range spanning 6000 AU to 3 pc. No strong B-field orientation change with offset was found, indicating remarkable uniformity of the B-field from the cloud edge to the YSO environs. This finding disagrees with weak-field models of cloud core and YSO formation. The continuity of inferred B-field orientations for both TEP and BSP probes is strong evidence that both are sampling a common B-field that uniformly threads the cloud, core, and YSO region. Bayesian analysis of Gaia DR2 stars matched to the Mimir BSP stars finds a distance to GF 9 of 270 +/- 10 pc. No strong wavelength dependence of B-field orientation angle was found, contrary to previous claims., 18 pages, 6 figures ApJ, accepted

Resume La genetique somatique et constitutionnelle prend une place grandissante dans la pratique de l’onco-hematologie pediatrique. Cette acceleration tient d’abord aux avancees technologiques et aux forces de poussees qu’exerce la recherche sur des maladies menacantes, de ce fait consideree comme imperieuse. Les demandes des familles elles-memes sont susceptibles d’etre influencees par la comprehension qu’elles auront de « la genetique » et l’explicitation qu’on leur donne des enjeux reels, ni minimises, ni fantasmes. Le groupe « Parents et soignants face a l’ethique en pediatrie » a reuni parents, soignants et un philosophe pour travailler sur les enjeux ethiques des investigations genetiques dans notre contexte professionnel. Un livret d’information destine aux parents a concretise ce travail. Cet article propose de concentrer l’essentiel des questions ethiques abordees dans ce groupe par une dialectique resumee par la formule « droit de savoir, droit a l’ignorance ». Sans amener a des solutions definitives, l’article conclut en donnant des reperes philosophiques pour orienter les decisions.

Bile acids (BAs) and BA receptors, including G protein-coupled bile acid receptor 1 (GPBAR1), represent novel targets for the treatment of metabolic and inflammatory disorders. However, BAs elicit myriad effects on cardiovascular function, although this has not been specifically ascribed to GPBAR1. This study was designed to test whether stimulation of GPBAR1 elicits effects on cardiovascular function that are mechanism based that can be identified in acute ex vivo and in vivo cardiovascular models, to delineate whether effects were due to pathways known to be modulated by BAs, and to establish whether a therapeutic window between in vivo cardiovascular liabilities and on-target efficacy could be defined. The results demonstrated that the infusion of three structurally diverse and selective GPBAR1 agonists produced marked reductions in vascular tone and blood pressure in dog, but not in rat, as well as reflex tachycardia and a positive inotropic response, effects that manifested in an enhanced cardiac output. Changes in cardiovascular function were unrelated to modulation of the levothyroxine/thyroxine axis and were nitric oxide independent. A direct effect on vascular tone was confirmed in dog isolated vascular rings, whereby concentration-dependent decreases in tension that were tightly correlated with reductions in vascular tone observed in vivo and were blocked by iberiotoxin. Compound concentrations in which cardiovascular effects occurred, both ex vivo and in vivo, could not be separated from those necessary for modulation of GPBAR1-mediated efficacy, resulting in project termination. These results are the first to clearly demonstrate direct and potent peripheral arterial vasodilation due to GPBAR1 stimulation in vivo through activation of large conductance Ca(2+) activated potassium channel K(Ca)1.1.

The Drosophila phototransduction cascade terminates in the opening of the ion channel transient receptor potential (TRP) and TRP-like (TRPL). Contrary to TRP, TRPL undergoes light-dependent subcellular trafficking between rhabdomeric photoreceptor membranes and an intracellular storage compartment, resulting in long term light adaptation. Here, we identified in vivo phosphorylation sites of TRPL that affect TRPL stability and localization. Quantitative mass spectrometry revealed a light-dependent change in the TRPL phosphorylation pattern. Mutation of eight C-terminal phosphorylation sites neither affected multimerization of the channels nor the electrophysiological response of flies expressing the mutated channels. However, these mutations resulted in mislocalization and enhanced degradation of TRPL after prolonged dark-adaptation. Mutation of subsets of the eight C-terminal phosphorylation sites also led to a reduction of TRPL content and partial mislocalization in the dark. This suggests that a light-dependent switch in the phosphorylation pattern of the TRPL channel mediates stable expression of TRPL in the rhabdomeres upon prolonged dark-adaptation. Background: Drosophila TRPL is a cation channel of the phototransduction cascade that undergoes light-dependent subcellular translocation between cell compartments. Results: Drosophila TRPL exhibits a light-dependent phosphorylation pattern required for its stable localization in the rhabdomere of photoreceptor cells. Conclusion: Multiple phosphorylation sites control localization and stability of TRPL. Significance: A member of the TRP ion channel family displays a complex phosphorylation pattern with functional relevance.

Abdominal patterning in Drosophila requires the function of Nanos (nos) and Pumilio (pum) to repress posterior translation of hunchback mRNA. Here we provide the first functional analysis of nanos and pumilio genes during blastodermal patterning of a short-germ insect. We found that nos and pum in the red flour beetle Tribolium castaneum crucially contribute to posterior segmentation by preventing hunchback translation. While this function seems to be conserved among insects, we provide evidence that Nos and Pum may also act on giant expression, another gap gene. After depletion of nos and pum by parental RNAi, Hunchback and giant remain ectopically at the posterior blastoderm and the posterior Krüppel (Kr) domain is not being activated. giant may be a direct target of Nanos and Pumilio in Tribolium and presumably prevents early Kr expression. In the absence of Kr, the majority of secondary gap gene domains fail to be activated, and abdominal segmentation is terminated prematurely. Surprisingly, we found Nos and Pum also to be involved in early head patterning, as the loss of Nos and Pum results in deletions and transformations of gnathal and pre-gnathal anlagen. Since the targets of Nos and Pum in head development remain to be identified, we propose that anterior patterning in Tribolium may involve additional maternal factors.

The Drosophila visual transduction cascade is embedded in the rhabdomeres of photoreceptor cells and culminates in the opening of the two ion channels, TRP and TRPL. TRPL translocates from the rhabdomeres to the cell body upon illumination and vice versa when flies are kept in the dark. Here, we studied the mechanisms underlying the light-dependent internalization of TRPL. Co-localization of TRPL and rhodopsin in endocytic particles revealed that TRPL is internalized by a vesicular transport pathway that is also utilized, at least partially, for rhodopsin endocytosis. TRPL internalization is attenuated under light conditions that result in a high rate of rhodopsin internalization and is highest in orange light that result in very little rhodopsin internalization. In line with a canonical vesicular transport pathway, we found that rab proteins, Rab5 and RabX4, are required for the internalization of TRPL into the cell body. Our results provide insight into stimulus-dependent internalization of a prominent member of the TRP superfamily.

Resume Selon une approche qualitative basee sur le temoignage et la narration, un groupe de reflexion et de recherche au sein de l’Espace ethique Assistance publique–Hopitaux de Paris a explore la question de « l’erreur medicale », ses circonstances et ses enjeux dans la relation entre les soignants, les parents et l’enfant. Plusieurs points forts emergent de ce travail : certaines circonstances sont susceptibles d’augmenter le risque de survenue d’une erreur : contexte hospitalier et societal, manque d’ecoute, climat de defiance, defaut de procedures de controle, situations de souffrance extreme… L’erreur est souvent le resultat d’une accumulation de defaillances successives ; il est possible de traverser l’erreur ensemble : parents, enfant et soignants ; cela depend de la qualite de la relation de confiance etablie depuis le debut de la maladie, mais aussi de la facon dont l’erreur est reconnue, communiquee et geree et ce quelle qu’en soit la gravite ou les consequences pour l’enfant ; en effet les consequences seules ne determinent pas le vecu de l’erreur : meme sans consequence tragique, une erreur peut engendrer un traumatisme durable. A contrario, des consequences tragiques pouvant aller jusqu’a la mort n’entrainent pas necessairement la rupture de la confiance. Les maitres-mots sont vigilance et maintien en eveil permanent. C’est d’un questionnement ethique et collectif sans relâche au sein des equipes hospitalieres et de l’institution que depend la capacite des soignants a faire de l’erreur un moteur d’amelioration des pratiques de soins et a donner a l’enfant et a chacun des membres de sa famille la possibilite de poursuivre l’ecriture de leur histoire personnelle et familiale dans un contexte si exceptionnellement douloureux.

The present work examines the validity of the Donnan approximation as a model for polyelectrolytes. A semi-empirical theory is presented and tested with a polymer of potassium-para-vinylbenzene sulfonate. A viscosity study was made with this polyelectrolyte in the presence of added electrolytes. The theory appears valid for fully ionized polyelectrolytes.

The activity of the potassium ion was determined potentiometrically in concentrated solutions of potassium-p-polystyrene sulfonate. The results indicate that the magnitude of the activity coefficients are similar to the degree of dissociation found by diffusion and transference measurements.

The method of Flory and a modification of the method proposed by Elias and Cornet and van Ballegooijen were used to determine theta conditions for samples of dextran and poly(vinyl pyrolidone). Light scattering and viscosity measurements made at the theta condition for dextrans of widely ranging molecular weights showed the second virial coefficient to be zero and were in agreement with the theory of Zimm and Kilb for branched polymers. Viscosity and osmotic pressure measurements were made on various mixtures of dextran and poly(vinyl pyrolidone) in water and the theta solvents determined by the above methods. Osmotic pressure measurements for various mixtures of high-molecular-weight dextrans and poly(vinyl pyrolidone) made in water showed a minimum in the number-average molecular weight and osmotic second virial coefficient at all three temperatures. This minimum did not occur in blends of a lower molecular weight dextran and poly(vinyl pyrolidone).

Sulfur aroma compounds play a key role in the aroma of many thermally processed foods conferring mainly roasted, sulfury and meaty notes. This chapter describes the principle chemical reactions underlying their formation from the main precursors cysteine, thiamine, methionine and others. The Maillard reaction and its interaction with lipid oxidation are particularly important formation pathways for sulfur odourants in food – cysteine being its most relevant sulfur precursor. Other important thermal reactions include Strecker degradation, the conversion of S-alk(en)yl- l -cysteine derivatives and their sulfoxides during cooking of Allium bulbs (onion, garlic) and the formation of various thiols in roasted sesame seeds.

A resuscitative compound in freeze-dried form has been synthesized between a modified starch and a tetremerically stabilized hemoglobin. In order to complex the hemoglobin, the starch has been prepared in mono-, di-, tri-, and tetra-aldehyde moieties. The hemoglobin was stabilized with low molecular weight diacids. Electrophoretic densitometric patterns indicate compound formation. The resulting polymers were characterized with respect to oxygen transport (biotonometry), Hill constant and P50. The in vivo evaluation indicates that these compounds are effective in exchange-transfusion experiments with rats to a level of about 85% replacement of whole blood. The final product is a cost-effective acellular resuscitative compound which can be stored in freeze-dried form at room temperature for extended periods of time. This artificial blood substitute can be reconstituted upon the addition of water.

The TRP (transient receptor potential) family of ion channels is a heterogeneous family of calcium permeable cation channels that is subdivided into seven subfamilies: TRPC ("Canonical"), TRPV ("Vanilloid"), TRPM ("Melastatin"), TRPA ("Ankyrin"), TRPN ("NOMPC"), TRPP ("Polycystin"), and TRPML ("Mucolipin"). TRP-mediated ion currents across the cell membrane are determined by the single channel conductance, by the fraction of activated channels, and by the total amount of TRP channels present at the plasma membrane. In many cases, the amount of TRP channels at the plasma membrane is altered in response to physiological stimuli by translocation of channels to and from the plasma membrane. Regulated translocation has been described for channels of the TRPC, TRPV, TRPM, and TRPA family and is achieved by vesicular transport of these channels along cellular exocytosis and endocytosis pathways. This review summarizes the stimuli and signalling cascades involved in the translocation of TRP channels and highlights interactions of TRP channels with proteins of the endocytosis and exocytosis machineries.

The TRP (transient receptor potential) family of ion channels is a heterogeneous family of calcium permeable cation channels that is subdivided into seven subfamilies: TRPC ("Canonical"), TRPV ("Vanilloid"), TRPM ("Melastatin"), TRPA ("Ankyrin"), TRPN ("NOMPC"), TRPP ("Polycystin"), and TRPML ("Mucolipin"). TRP-mediated ion currents across the cell membrane are determined by the single channel conductance, by the fraction of activated channels, and by the total amount of TRP channels present at the plasma membrane. In many cases, the amount of TRP channels at the plasma membrane is altered in response to physiological stimuli by translocation of channels to and from the plasma membrane. Regulated translocation has been described for channels of the TRPC, TRPV, TRPM, and TRPA family and is achieved by vesicular transport of these channels along cellular exocytosis and endocytosis pathways. This review summarizes the stimuli and signalling cascades involved in the translocation of TRP channels and highlights interactions of TRP channels with proteins of the endocytosis and exocytosis machineries.

Background. A characteristic feature of prostatic adenocarcinoma is its great variation in biologic behavior. This variation and the observation that most carcinomas are of intermediate grade make standard histologic grading of limited value in determining the prognosis of a patient. DNA quantitation with the use of computer-assisted image analysis on Feulgen-stained nuclei was performed on the metastatic lymph nodes from patients with Stage D1 prostate carcinoma to determine whether ploidy was a useful predictor of survival or progression. The Gleason histologic score of the primary tumor, the number and extent of lymph node metastases, and the progression and survival intervals were documented. Treatment modalities included pelvic lymph node dissection, radical prostatectomy, external beam radiation therapy, and iodine 125 implantation.

In many multicomponent systems, a transition from a single phase of uniform composition to a multiphase state with separated regions of different composition can be induced by changes in temperature and shear. The density difference between the phase and thermal and/or shear gradients within the system results in buoyancy driven convection. These differences affect kinetics of the phase separation if the system has a sufficiently low viscosity. This investigation presents more preliminary developments of a theoretical model in order to describe effects of the buoyancy‐driven convection in phase separation kinetics. Polymer solutions were employed as model systems because of the ease with which density differences can be systematically varied and because of the importance of phase separation in the processing and properties of polymeric materials. Isopycnic polymer solutions were used to determine the viscosity and density difference limits for polymer phase separation. From these methods, it was possible ...

We cytogenetically studied four cases of adenocarcinoma of the prostate. All tumors were moderately differentiated or well-differentiated, with different degrees of invasion. One tumor with microscopic seminal vesicle invasion and lymph node metastasis (tumor 4) had trisomy 7 as a sole clonal abnormality, suggesting that this is a primary change in some prostatic tumors. Although only normal karyotypes were observed in the other three tumors, several nonclonal changes were evident. Monosomy 9 or deletion of the long arm of 9 was observed in at least one cell in the three tumors without trisomy 7. Furthermore, in one of these tumors (tumor 3, moderately differentiated), several rearrangements (five of 26 cells) were observed, two of which had a common breakpoint at 15q11. Although complex chromosome changes including del(10q) and del(7q) have been described in prostatic tumors, they were not observed in the four tumors studied. This is the first report of a prostate tumor with trisomy 7 as a single clonal chromosome abnormality.

Recycling of signaling proteins is a common phenomenon in diverse signaling pathways. In photoreceptors of Drosophila, light absorption by rhodopsin triggers a phospholipase Cβ-mediated opening of the ion channels transient receptor potential (TRP) and TRP-like (TRPL) and generates the visual response. The signaling proteins are located in a plasma membrane compartment called rhabdomere. The major rhodopsin (Rh1) and TRP are predominantly localized in the rhabdomere in light and darkness. In contrast, TRPL translocates between the rhabdomeral plasma membrane in the dark and a storage compartment in the cell body in the light, from where it can be recycled to the plasma membrane upon subsequent dark adaptation. Here, we identified the gene mutated in trpl translocation defective 14 (ttd14), which is required for both TRPL internalization from the rhabdomere in the light and recycling of TRPL back to the rhabdomere in the dark. TTD14 is highly conserved in invertebrates and binds GTP in vitro. The ttd14 mutation alters a conserved proline residue (P75L) in the GTP-binding domain and abolishes binding to GTP. This indicates that GTP binding is essential for TTD14 function. TTD14 is a cytosolic protein and binds to PtdIns(3)P, a lipid enriched in early endosome membranes, and to phosphatidic acid. In contrast to TRPL, rhabdomeral localization of the membrane proteins Rh1 and TRP is not affected in the ttd14 P75L mutant. The ttd14 P75L mutation results in Rh1-independent photoreceptor degeneration and larval lethality suggesting that other processes are also affected by the ttd14 P75L mutation. In conclusion, TTD14 is a novel regulator of TRPL trafficking, involved in internalization and subsequent sorting of TRPL into the recycling pathway that enables this ion channel to return to the plasma membrane., Author Summary Protein trafficking in neurons occurs throughout the lifetime of a cell and includes the internalization and redistribution of plasma membrane proteins. Regulated protein trafficking controls the equipment of the plasma membrane with receptors and ion channels and thereby attenuates or enhances neuronal function. Defects in recycling of plasma membrane proteins can cause detrimental neurodegenerative diseases such as Alzheimer’s disease, Parkinson’s disease and Down´s syndrome. In Drosophila photoreceptors, the TRPL ion channel, together with the TRP channel, mediates vision and light-dependently shuttles between an endomembrane storage compartment and the apical plasma membrane. Here, we report the identification of a mutation in the ttd14 gene that inhibits TRPL-trafficking in both directions and also results in photoreceptor degeneration. The TTD14 protein contains a region with weak homology to a PX-domain, which is also found in proteins that sort cargo in the endosome and enable protein recycling. We characterize TTD14 as a new regulator of photoreceptor maintenance and ion channel trafficking that binds to GTP and PtdIns(3)P, a phospholipid enriched in early endosomes.

This paper presents two integrated non-reflective bandpass filters. The filters are implemented in a silicon germanium (SiGe) BiCMOS technology and fully depleted silicon on insulator (FDSOI) CMOS technology. The purpose of these circuits is to explore the feasibility of passive filter applications on silicon substrates while maintaining low insertion loss and 50 Ohm impedance matching. The SiGe-based filter achieved 3.3-4.2 dB insertion loss across 3.5-4.5 GHz with input return loss better than -10 dB from 1-10 GHz. The FDSOI filter simulation yielded an insertion loss of 4.5 dB across the design frequency of 3.7-4.3 GHz.

During Drosophila segmentation, gap genes function as short-range gradients that determine the boundaries of pair-rule stripes. A classical example is Drosophila Krüppel (Dm'Kr) which is expressed in the middle of the syncytial blastoderm embryo. Patterning defects in Dm'Kr mutants are centred symmetrically around its bell-shaped expression profile. We have analysed the role of Krüppel in the short-germ beetle Tribolium castaneum where the pair-rule stripes corresponding to the 10 abdominal segments arise during growth stages subsequent to the blastoderm. We show that the previously described mutation jaws is an amorphic Tc'Kr allele. Pair-rule gene expression in the blastoderm is affected neither in the amorphic mutant nor in Tc'Kr RNAi embryos. Only during subsequent growth of the germ band does pair-rule patterning become disrupted. However, only segments arising posterior to the Tc'Kr expression domain are affected, i.e. the deletion profile is asymmetric relative to the expression domain. Moreover,stripe formation does not recover in posterior abdominal segments, i.e. the Tc'Krjaws phenotype does not constitute a gap in segment formation but results from a breakdown of segmentation past the 5th eve stripe. Alteration of pair-rule gene expression in Tc'Krjaws mutants does not suggest a direct role of Tc'Kr in defining specific stripe boundaries as in Drosophila. Together, these findings show that the segmentation function of Krüppel in this short-germ insect is fundamentally different from its role in the long-germ embryo of Drosophila. The role of Tc'Kr in Hox gene regulation, however, is in better accordance to the Drosophila paradigm.

An X-band (8-12 GHz) low-noise amplifier (LNA) for receiver systems is presented. The microwave monolithic integrated circuit (MMIC) with no external matching components has been demonstrated using a 0.18 /spl mu/m silicon germanium (SiGe) bipolar CMOS (BiCMOS) technology. The amplifier employs a two-stage topology to achieve low noise figure and high linearity across 8-12 GHz. At 10 GHz the LNA yielded a gain of 24.2 dB, a noise figure of 1.68 dB, and a third-order intercept point of 17.5 dBm. The power dissipation of the circuit is 33.6 mW using a 1.8 V supply voltage. To the best of our knowledge, the circuit achieves the lowest noise figure for a wide bandwidth LNA realized in a SiGe technology.

Purpose: To determine whether autocrine motility factor receptor (AMFR) is detectable in the urine of patients with transitional cell carcinoma (TCC) of the bladder.Materials and Methods: We assayed the urine of 89 patients with bladder pathology and 28 normal controls for AMFR. A monoclonal antibody to AMFR was used.Results: All patients with muscle-invasive TCC tested positive for AMFR. Autocrine motility factor receptor was detectable for 80 percent of superficial tumors, with a correlation between AMFR and tumor grade. Seventy-five percent of control urines tested negative.Conclusions: Autocrine motility factor receptor is detectable in the urine of patients with TCC. Long-term follow-up and refinements in the assay should define the marker's utility for detection and prognosis.

Photodynamic therapy (PDT) principles were evaluated in management of benign prostatic hyperplasia (BPH) in a canine model. Five dogs were injected with benzoporphyrin derivative (BPD) and samples of prostate, bladder, urethra and rectum were taken at 1, 2, 3 and 4 hours and analyzed for BPD. Next, 16 dogs were treated with 100 Joules at 690 nm light form argon dye laser 1 hour after administration of BPD at 0.5 mg/kg using cylindrical diffuser tip fiber passed transurethrally. The prostates were harvested weekly up to 4 weeks and the size of the lesion was measured and the prostates were examined. Prostate had the highest BPD levels. Hemorrhagic lesion of 2.5 cm in diameter was noted at 1 week after PDT. At 3 and 4 weeks there were changes of glandular atrophy in the periurethral region. Minimally invasive technique of transurethral PDT causes glandular and stromal changes in the periurethral zone and has potential in the treatment of BPH.

Application of indirect calorimetry has aided nutritional support and management in critically ill populations. However, knowledge of resting energy expenditure is only one-half of the nutritional profile. Knowledge of protein losses and requirements are also important. Attainment of positive protein balance is believed to play an important role in wound healing, host defenses, morbidity, and mortality. Previous limitations of the measurement of protein losses (time and cost) have limited its application to the ICU patient. This report describes a relatively new technology which measures elemental nitrogen in biologic samples. We have found this instrument to be fast, accurate, easy to calibrate and use. Its application in the critically ill patient allows us to monitor daily changes in protein losses and balance.

The aim of the study was to determine the sensitivity and specificity of the lactate stress test in the detection of mitochondrial myopathies. Thirty one healthy subjects, 10 patients with non-mitochondrial myopathy and 26 patients with mitochondrial myopathy underwent lactate stress testing at a standardized workload of 30 W during 15 min on a bicycle ergometer. Lactate was determined before the exercise (R1), 5, 10, 15 min after starting the exercise (S5, S10, S15) and 15 min after finishing the exercise (R2). A result was interpreted as pathologic if more than two of the five lactate values were above the corresponding upper reference limits. The upper reference limits for the venous lactate at R1, S5, S10, S15 and R2 were 1.9, 2.0, 2.1, 2.0 and 1.7 mmol/l respectively. The lactate stress test was pathologic in 1/10 of the non-mitochondrial myopathies and in 18/26 of the mitochondrial myopathies. The sensitivity of the lactate stress test was 69%. The specificity of the test was 90%. In conclusion, the lactate stress test proved to be helpful for evaluating the integrity of the oxidative metabolism in the majority of patients with mitochondrial myopathy.

In this reported case, a variant petrotympanic fissure--opening at the height of the orifice of the Eustachian tube into the hypotympanon--was identified by high resolution computed tomography (CT) as the possible cause of a tympanic membrane perforation. Inner ear function was preserved by an otosclerotic stapes which prevented destruction of the labyrinth. The perforation was closed by a myringoplasty and was to be followed by a stapedectomy after six months to restore normal hearing. Surgeons performing temporomandibular joint arthroscopy should be aware that in a small percentage of patients a variant anatomy of the tympanic plate exists and, therefore, great care must be exercised in the manipulation of instruments near this structure. A preoperative high resolution CT with thin slices of the temporal bone might allow identification of these high risk patients.

A prospective phase II study was carried out to determine whether estramustine phosphate (EMP) plus vinblastine (VBL) in combination with radiotherapy (RT) would improve the control of locally advanced prostate cancer. The rationale for combining EMP plus VBL with RT was based on the clinical and radiobiological data that EMP plus VBL acted as an excellent radiation sensitizer in cultured human prostatic carcinoma cells with the property of tissue selectivity. The combined EMP and VBL were well tolerated in the phase II clinical study of patients with advanced prostate cancer.Between January 1991 and July 1996, 65 patients, stage T2 (B2) through stage T4 (D1), were entered into the study. Gleason pattern scores ranged from 4 to 10. Pretreatment prostate-specific antigen (PSA) was as follows:20 in 21 patients (32%), 20 to 50 in 23 patients (35%), and50 in 21 patients (32%). The median age was 70 years (55-83). All patients were treated with megavoltage beam radiation with a total tumor dose of 65 to 70 Gy. Oral EMP 450 mg/m2 daily and VBL 3 mg/m2 weekly were given concomitantly in 46 patients during the 7- to 7 1/2-week course of radiotherapy.All patients showed prompt and complete tumor regression on digital rectal examination at 6 weeks following the completion of treatment. Median follow-up time is 43 months (3-65). PSA fell to an undetectable level by 6 weeks in 56 of 65 patients (86%). For the whole group at 5 years clinical control was 81%, but biochemical control (PSA4 ng/mL) was 48%. The likelihood of being free of biochemical relapse at 5 years was a function of initial PSA value (PSA20 in 64% of the cases, 21-50 in 60%, and50 in 0%). The biochemical-relapse-free survival at 5 years for each stage was T2, 49%; T3, 38%; and T4, 17%. In particular, a group of patients with pretreatment PSA levels of 20 to 50 ng/mL responded quite favorably to the present combined regimen in that only 40% of the patients showed a biochemical failure at 5 years, considering the high level of initial PSA.The present combined approach is effective in achieving a high rate of tumor control with no disproportionately enhanced side effects. The rapid regression of the tumor nodules and sustained freedom from biochemical relapse suggest excellent long-term tumor control, especially in the group of patients with pretreatment PSA levels of 20 to 50 ng/mL.

A useful decontaminant for mustard would be one which is readily available in large quantities, inexpensive and potentially biodegradable. Currently one that is being investigated consists of a mixture containing bovine hemoglobin, gelatin and poi. Two of them, gelatin and poi, are common foodstuffs in the diet on the mainland of the United States and in the Hawaiian culture, respectively. Various combinations of these substances have unusual flow properties since the physical states change from a liquid to a gel form. The hydrolytic kinetics of the mustard simulants, 2-chloroethyl ethyl, 2-chloroethyl methyl and 2-bromoethyl phenyl sulfide are reported. The kinetic mechanisms and rate constants are dependent upon the mixtures' concentration and viscosity.

The optical absorption and transport scattering coefficients of normal prostate tissue have been measured in vivo in dogs. The measurements were made at 630 nm before and during treatment by Photofin® photodynamic therapy using interstitial optical fiber fluence-rate detectors. Corresponding measurements were made ex vivo, at 1 week after treatment, in the contralateral lobe. The optical properties were derived by applying a diffusion theory model to the fluence rates measured at two different source-detector fiber distances. While the in vivo pretreatment and in vivo contralateral post-treatment absorption and scattering values are self-consistent and in agreement with published data, significant changes were observed in the light fluence rates, and hence in the derived optical properties, during light irradiation. The possible causes of such changes are considered, and the implications for light dosimetry in photodynamic therapy are discussed.

Prior to a possible clinical application of photodynamic therapy (PDT) for prostatic diseases such as benign prostatic hyperplasia and prostate cancer, optical properties of the prostate gland need to be studied. The specific objectives of this study were (1) to determine the light penetration depth, (2) to document the photosensitizer levels in the prostate, and (3) to document the lesion size after PDT. Sixteen dogs were injected with Photofrin II (1, 3 and 5 mg/kg) 24 hrs prior to laser application. After laparotomy and exposure of prostate, monochromatic light (630 nm, via an argon pumped dye laser) was applied through an isotropic fiber at 100 mw for a total dose of 400 joules. Continuous light fluence and temperature were documented. Prostates were harvested at 1 week and examined histologically for the lesion size. Four sham dogs were treated without Photofrin II. At Photofrin doses of 1, 3 and 5 mg/kg the mean prostatic Photofrin levels were 1.78 plus or minus 0.33, 1.47 plus or minus 0.08 and 1.95 plus or minus 0.44 (mu) gm/ml. The mean light penetration depths were 2.08, 1.37 and 1.64 mm respectively. Photofrin dose escalation (1, 3 and 5 mg/kg) increased the lesion size to radius of 4.1 plus or minus 0.9 mm, 4.4 plus or minus 0.8 mm and 6.3 plus or minus 0.9 mm. There were no lesions seen in sham dogs. These results demonstrate that light penetration in prostate is consistent and therapeutic levels of photosensitizer are achieved in prostatic tissue. Moreover, increasing size of the lesions were documented with dose escalation.© (1996) COPYRIGHT SPIE--The International Society for Optical Engineering. Downloading of the abstract is permitted for personal use only.

To determine whether autocrine motility factor receptor (AMFR) is detectable in the urine of patients with transitional cell carcinoma (TCC) of the bladder.We assayed the urine of 89 patients with bladder pathology and 28 normal controls for AMFR. A monoclonal antibody to AMFR was used.All patients with muscle-invasive TCC tested positive for AMFR. Autocrine motility factor receptor was detectable for 80% of superficial tumors, with a correlation between AMFR and tumor grade. Seventy-five percent of control urines tested negative.Autocrine motility factor receptor is detectable in the urine of patients with TCC. Long-term follow-up and refinements in the assay should define the marker's utility for detection and prognosis.

To provide basic scientific information for utilizing photodynamic therapy to treat prostatic carcinoma, PDT dosimetry and effective treatment volume were investigated using canine prostate as an in vivo animal model. The prostate glands were surgically exposed. Isotropic tip fibers were inserted into the gland for either light irradiation or detection. PDT doses of 400 J and 1, 3 or 5 mg/kg Photofrin were used for single fiber irradiation treatments. All animals were terminated at 1 week and the prostates evaluated histopathologically. The results show that the lesion size was dependent on the treatment dose. The maximum lesion dimension was approximately 1.6 cm. The data acquired from the single fiber irradiation study were then used to plan for multi-fiber interstitial PDT treatments with a goal of achieving a larger treatment volume for practical purpose. The data indicate that the lesion size from the multiple fiber treatment could be predicted based on the single fiber treatment with the light pattern summed from all sources.© (1994) COPYRIGHT SPIE--The International Society for Optical Engineering. Downloading of the abstract is permitted for personal use only.

A new modality of interstitial therapy to treat prostate cancer using photodynamic principles has been studied in a canine model. The effect of interstitial application of monochromatic light from an argon pumped dye laser at 630 nm was studied in a canine model. No significant hyperthermia was seen during the treatment. A concentric zone around the treatment fiber was seen during the treatment. A concentric zone around the treatment fiber was seen in PDT treated dogs and the maximum size was 18 mm. The data suggests that PDT may be clinically applicable in achieving tissue necrosis using interstitial light application in a solid organ like prostate.© (1994) COPYRIGHT SPIE--The International Society for Optical Engineering. Downloading of the abstract is permitted for personal use only.

To evaluate the biophysical properties of two acellular resuscitative fluids, experiments were performed using mixtures of these with suspensions of red blood cells. Two acellular resuscitative fluids were synthesized using a diacid to tetramerically stabilized hemoglobin and then complexing it with either a hydroxyethyl starch or a Tetronic Polyol. The new polymers were characterized with respect to the molecular weight, second virial coefficient and intrinsic viscosity. These fluids were then combined with red cells and the following measurements were made: non-Newtonian flow properties, malonamide induced hemolytic kinetics, sedimentation rates and oxygen transport. The in vitro evaluation indicates that these compounds are effective hemodiluents, offer protection to the red cell membrane and do not cause erythrocyte aggregation. The oxygen transport was satisfactory.

The present study explores the possibility of utilizing photodynamic therapy (PDT) in treating localized prostate carcinoma. Optical properties of ex vivo human prostatectomy specimens, and in vivo and ex vivo dog prostate glands were studied. The size of the PDT induced lesion in dog prostate was pathologically evaluated as a biological endpoint. The data indicate that the human normal and carcinoma prostate tissues have similar optical properties. The average effective attenuation depth is less in vivo than that of ex vivo. The PDT treatment generated a lesion size of up to 16 mm in diameter. The data suggest that PDT is a promising modality in prostate cancer treatment. Multiple fiber system may be required for clinical treatment.© (1993) COPYRIGHT SPIE--The International Society for Optical Engineering. Downloading of the abstract is permitted for personal use only.

This study reports some recent work dealing with the stabilization of the tetramers of hemoglobin. It is shown that by using a variety of diacids, it is possible to increase the P50 above that of stroma free hemoglobin. In order to lengthen the retention times in the circulatory system, the stabilized hemoglobins were complexed with both hydroxyethyl starch polymers and polyol tetronic polymers. The resulting hemoglobin-polymer compounds were then freeze-dried. It was possible to reconstitute the powder by the addition of physiological saline when needed. The methods presented here appear to be appear to be as effective as using pyridoxal phosphate but at a fraction of the cost.

Although PSA is considered to be the true serum marker of prostatic tissue and a valuable indicator for cancer in the gland, knowledge of its significance and limitations is essential to its use for screening, staging, and monitoring CAP. PSA may be used in conjunction with DRE for early detection of CAP. Men with abnormal DRE should have a TRUS with or without biopsy. In men older than 50 years and with negative DRE and PSA4 ng/mL, annual evaluations are prudent. In patients with a PSA range of 4.0 to 9.9 ng/mL, high-risk groups such as black males and those with a positive family history should have TRUS. Males with negative DRE in the PSA range of 4.0 to 9.9 ng/mL should have TRUS to evaluate prostate volume and PSAD. Biopsy should be considered in those with PSAD0.15. Men with PSA10 ng/mL, even in the presence of an enlarged benign prostate, should have multiple directed biopsies under TRUS guidance.

New methods of early detection combined with recent advances in surgical techniques have resulted in more patients undergoing radical surgery for treatment of localized carcinoma of the prostate. Over 350 radical prostatectomies have been performed by our group since January 1987. We review the role of radical prostatectomy in the treatment of prostate cancer and our experience with 100 patients undergoing radical retropubic prostatectomy since the advent of nerve-sparing techniques to preserve potency.

The use of Doppler ultrasound as a means of obtaining cardiac output (CO) measurements quickly, easily, and noninvasively has been made possible by recent technologic developments. We evaluated a new pulse Doppler ultrasonic unit (Velcom-100, Waters Instruments, Inc) in the Surgical Intensive Care Unit at the University of Michigan Medical Center. Accuracy of this device was determined by comparison of CO results obtained from the Velcom-100 (COV) against those of conventional thermal dilution cardiac output (COT) measurements. Twenty-six postoperative patients were used for this study, ranging in age from 20 to 82 years old. Initial studies prior to in vivo standardization demonstrated a significantly lower result (p = 0.039) for the Velcom-100 with a mean difference of 0.86 L/min (COT-COV). This comparison was significantly improved in subsequent studies following in vivo standardization (COT-COV = 0.02 L/min, p = 0.646). Linear regression analysis showed a significant, positive correlation between the two results (r = 0.82, p less than 0.05) indicating an excellent trending capability for the Velcom-100. Our evaluation found the Velcom-100 to be user friendly, allowing rapid training of ICU technicians and applicability for postoperative monitoring.