Urothelial cell carcinoma of the bladder in pediatric patients: a systematic review and data analysis of the world literature.

BACKGROUND: Urothelial cell carcinoma (UCC) of the bladder is exceedingly rare in pediatric patients. Limited data are available to guide management in this population. METHODS: The authors systematically searched MEDLINE, Cochrane Library, and Google Scholar (through February 2019) for case reports and series to summarize data regarding presentation, evaluation, management, and follow-up for patients ≤ 18 years diagnosed with UCC of the bladder. Patient-level data were abstracted, and adjusted logistic regression was used to identify factors associated with a combined outcome of recurrence or death. RESULTS: One hundred two articles describing 243 patients from 26 countries met criteria. Average age was 12.5 years, 32.6% were female, 15.3% had medical comorbidities, and 13.2% had known risk factors for bladder cancer. Initial management was transurethral resection in 95.5% of patients, whereas 6.2% required secondary intervention. Tumor stage was TaN0M0 in 86.4% and low grade in 93.4%. Recurrence and death occurred in 8.6% and 3.7%, respectively. Mean time to recurrence or death was 8.6 months (standard deviation [SD] 7.6) for 10.7%. Mean disease free follow-up without recurrence or death was 56.9 months (SD 54.2) for 89.3%. Patients with comorbidities, risk factors, or family history (odds ratio [OR]: 2.4, 95% confidence interval [CI]: 1.02-5.6); ≥TaN0M0 disease (OR: 6.2, 95% CI: 2.5-15.6); and larger tumors at diagnosis (OR: 1.7, 95% CI: 1.2-2.4) had significantly greater adjusted odds of recurrence or death after initial treatment. CONCLUSION: Based on pooled results, disease recurrence or death occurred in 10.7% of pediatric patients and within 9 months for most and within 32 months for all patients. This may suggest that low-grade and stage UCC of the bladder in pediatric patients can be systematically monitored for at least 3 years. However, prospective evaluation of this clinical strategy is warranted.

Nutrient intake and contribution of home enteral nutrition to meeting nutritional requirements after oesophagectomy and total gastrectomy.

BACKGROUND/OBJECTIVES: This study evaluated nutrition after oesophago-gastric resection and the influence of home jejunostomy feeding in the six months after surgery. SUBJECTS/METHODS: Data on nutritional intake and physiologic measures were collected as part of a randomised trial with measurements taken before and up to six months after surgery. RESULTS: A total of 41 participants (32 oesophagectomy, 9 total gastrectomy) received home jejunostomy feeding (n=18) or usual care without feeding (n=23). At hospital discharge, oral intakes were adequate for energy and protein in 9% and 6%, respectively. By three and six months, these values had increased to 61% and 55%, 94% and 77% respectively. Six participants (26%) who received usual care required rescue feeding. Six weeks after hospital discharge, energy intakes were met in those who received jejunal feeding because of the contribution of enteral nutrition. Jejunal feeding did not affect oral intake, being similar in both groups (fed: 77% estimated need, usual care: 79%). At three months, inadequate micronutrient intakes were seen in over one third. Compared to baseline values, six weeks after surgery, weight loss exceeding 5% was seen in 5/18 (28%) who received feeding, 14/17 (82%) who received usual care and 5/6 (83%) of those who required rescue feeding, P=0.002. Weight loss averaged 4.1% (fed), 10.4% (usual care) and 9.2% (rescue fed), P=0.004. These trends persisted out to six months. CONCLUSIONS: Supplementary jejunostomy feeding made an important contribution to meeting nutrition after oesophago-gastric resection. Importantly, oral nutritional intake was not compromised dispelling the assertion that jejunal feeding deincentivises patients from eating.

Antiviral immune responses of bats: a review.

Despite being the second most species-rich and abundant group of mammals, bats are also among the least studied, with a particular paucity of information in the area of bat immunology. Although bats have a long history of association with rabies, the emergence and re-emergence of a number of viruses from bats that impact human and animal health has resulted in a resurgence of interest in bat immunology. Understanding how bats coexist with viruses in the absence of disease is essential if we are to begin to develop therapeutics to target viruses in humans and susceptible livestock and companion animals. Here, we review the current status of knowledge in the field of bat antiviral immunology including both adaptive and innate mechanisms of immune defence and highlight the need for further investigations in this area. Because data in this field are so limited, our discussion is based on both scientific discoveries and theoretical predictions. It is hoped that by provoking original, speculative or even controversial ideas or theories, this review may stimulate further research in this important field. Efforts to understand the immune systems of bats have been greatly facilitated in recent years by the availability of partial genome sequences from two species of bats, a megabat, Pteropus vampyrus, and a microbat, Myotis lucifugus, allowing the rapid identification of immune genes. Although bats appear to share most features of the immune system with other mammals, several studies have reported qualitative and quantitative differences in the immune responses of bats. These observations warrant further investigation to determine whether such differences are associated with the asymptomatic nature of viral infections in bats.

Causes and management of a high-output stoma.

AIM: Patients with a high-output stoma (HOS) (> 2000 ml/day) suffer from dehydration, hypomagnesaemia and under-nutrition. This study aimed to determine the incidence, aetiology and outcome of HOS. METHOD: The number of stomas fashioned between 2002 and 2006 was determined. An early HOS was defined as occurring in hospital within 3 weeks of stoma formation and a late HOS was defined as occurring after discharge. RESULTS: Six-hundred and eighty seven stomas were fashioned (456 ileostomy/jejunostomy and 231 colostomy). An early HOS occurred in 75 (16%) ileostomies/jejunostomies. Formation of a jejunostomy (defined as having less than 200 cm remaining of proximal small bowel; n = 20) and intra-abdominal sepsis? obstruction (n = 14) were the commonest causes identified for early HOS. It was possible to stop parenteral infusions in 53 (71%) patients treated with oral hypotonic fluid restriction, glucose-saline solution and anti diarrhoeal medication. In 46 (61%) patients, the HOS resolved and no drug treatment was needed, 20 (27%) patients continued treatment, six (8%) of whom went home and continued to receive parenteral or subcutaneous saline, and nine died. Twenty-six patients had late HOS. Eleven were admitted with renal impairment and four had intermittent small-bowel obstruction. Eight patients were given long-term subcutaneous or parenteral saline and two also received parenteral nutrition. All had hypomagnesaemia. CONCLUSION: Early high output from an ileostomy is common and although 49% resolved spontaneously, 51% needed ongoing medical treatment, usually because of a short small-bowel remnant.

Semi-isometric registration of line features for flexible fitting of protein structures.

In this paper, we study a registration problem that is motivated by a practical biology problem - fitting protein structures to low-resolution density maps. We consider registration between two sets of lines features (e.g., helices in the proteins) that have undergone not a single, but multiple isometric transformations (e.g., hinge-motions). The problem is further complicated by the presence of symmetry in each set. We formulate the problem as a clique-finding problem in a product graph, and propose a heuristic solution that includes a fast clique-finding algorithm unique to the structure of this graph. When tested on a suite of real protein structures, the algorithm achieved high accuracy even for very large inputs containing hundreds of helices.

Electron cryomicroscopy and bioinformatics suggest protein fold models for rice dwarf virus.

The three-dimensional structure of rice dwarf virus was determined to 6.8 A resolution by single particle electron cryomicroscopy. By integrating the structural analysis with bioinformatics, the folds of the proteins in the double-shelled capsid were derived. In the outer shell protein, the uniquely orientated upper and lower domains are composed of similar secondary structure elements but have different relative orientations from that of bluetongue virus in the same Reoviridae family. Differences in both sequence and structure between these proteins may be important in defining virus-host interactions. The inner shell protein adopts a conformation similar to other members of Reoviridae, suggesting a common ancestor that has evolved to infect hosts ranging from plants to animals. Symmetry mismatch between the two shells results in nonequivalent, yet specific, interactions that contribute to the stability of this large macromolecular machine.

Further characterization of T cell receptor chains of marsupials.

cDNA clones encoding T cell receptor alpha (TCRalpha) and beta (TCRbeta) from the South American opossum, Monodelphis domestica were isolated and characterized. A single clone isolated encoding a TCRalpha chain was full length, containing the complete V (variable), J (joining) and C (constant) regions. Three partial cDNA clones were isolated for TCRbeta which contained complete C sequences. Phylogenetic analysis of the TCR Valpha revealed that the M. domestica sequence and a sequence from the Australian brushtail possum, Trichosurus vulpecula, belong to separate Valpha families and intersperse with sequences from eutherian mammals. Similar to results described for marsupial and eutherian light chains, diversity at the V region of the TCR is ancient and maintained. In contrast phylogenetic analysis of the TCR Calpha and Cbeta sequences from M. domestica, T. vulpecula, and other vertebrates revealed that the marsupial TCR C grouped together forming a sister group to eutherian mammals.

Bridging the information gap: computational tools for intermediate resolution structure interpretation.

Due to large sizes and complex nature, few large macromolecular complexes have been solved to atomic resolution. This has lead to an under-representation of these structures, which are composed of novel and/or homologous folds, in the library of known structures and folds. While it is often difficult to achieve a high-resolution model for these structures, X-ray crystallography and electron cryomicroscopy are capable of determining structures of large assemblies at low to intermediate resolutions. To aid in the interpretation and analysis of such structures, we have developed two programs: helixhunter and foldhunter. Helixhunter is capable of reliably identifying helix position, orientation and length using a five-dimensional cross-correlation search of a three-dimensional density map followed by feature extraction. Helixhunter's results can in turn be used to probe a library of secondary structure elements derived from the structures in the Protein Data Bank (PDB). From this analysis, it is then possible to identify potential homologous folds or suggest novel folds based on the arrangement of alpha helix elements, resulting in a structure-based recognition of folds containing alpha helices. Foldhunter uses a six-dimensional cross-correlation search allowing a probe structure to be fitted within a region or component of a target structure. The structural fitting therefore provides a quantitative means to further examine the architecture and organization of large, complex assemblies. These two methods have been successfully tested with simulated structures modeled from the PDB at resolutions between 6 and 12 A. With the integration of helixhunter and foldhunter into sequence and structural informatics techniques, we have the potential to deduce or confirm known or novel folds in domains or components within large complexes.

Semi-automated icosahedral particle reconstruction at sub-nanometer resolution.

Electron cryomicroscopy of large macromolecular complexes is becoming an increasingly powerful tool for revealing three-dimensional structures without the need for crystallization. The execution of image processing, however, requires experience and is error-prone due to the need for a human operator to carry out interactive and repetitive processes. We have designed an approach which is intended to make image processing simple and rapid, both for experts and for novice users. We demonstrate this approach using the well-established reconstruction scheme for icosahedral particles. Finally, we implement semi-automated virus reconstruction (SAVR), an expert system that integrates the most CPU intensive and iterative steps using the scripting language Python. SAVR is portable across platforms and has been parallelized to run on both shared and distributed memory platforms. SAVR also allows the incorporation of new algorithms and facilitates the management of the increasingly large data sets needed to achieve higher resolution reconstructions. The package has been successfully applied to several data sets and shown capable of generating icosahedral reconstructions to sub-nanometer resolutions (7-10 A ).

Ontogeny of the immune system of the brushtail possum, Trichosurus vulpecula.

The numbers and distribution of T and B cells in the thoracic thymus, spleen and intestinal tissue and the proliferation of T lymphocytes were examined during pouch life and in the adult to determine when the developing brushtail possum reaches immunological maturity. CD3-positive cells were observed in the thoracic thymus at day 2 post-partum indicating that the thymus produces T lymphocytes at or soon after birth. By day 25 the thymus was fully populated with CD3-positive T lymphocytes and they were observed in distinct regions of the cortex and medulla. By day 48 post-partum, B and T lymphocytes were identified in the follicles and parafollicular areas of the spleen. Although the numbers of T and B cells in the spleen increased significantly from day 25 to day 100 post-partum (P < 0.005), fewer cells were present at day 150 post-partum than in the adult (P < 0.05). Peyer's patches were not observed in the intestines up to day 73 post-partum. However, both T and B cells were observed in the intestinal lymph nodes. Although the T lymphocytes at weaning showed a proliferative response, the response was not as great as that observed in the adult possum. Thus, the immune system of the possum is not fully developed at weaning but continues its development after pouch life.

Physiological changes in the brushtail possum (Trichosurus vulpecula) following relocation from Armidale to Brisbane, Australia.

To determine the effect of relocation on the health of possums the body weights and hormone and immune responses of six male and nine female brushtail possums were monitored for 20 weeks following transfer from the environs of Armidale into enclosures in Brisbane. Over the first 6 weeks of captivity, male possums lost 11.0% of their original body weight and females lost 16.8%. The mean concentrations of plasma cortisol in the male and female possums were 14.5 and 29.4 ng/mL, respectively, and did not change over the 20-week period. Male and female possums displayed a similar pattern of thyroxine secretion over the 20 weeks, with low concentrations up to week seven (2.1 and 2.7 ng/mL, respectively) increasing to 6.9 and 5.8 ng/mL in weeks 7-12 (P < 0.005). This increase in the concentration of thyroxine corresponded with the increase in body weight. The number of white blood cells (WBCs) and the percentage of neutrophils increased from the capture to week 6-10. However, during the last 10 weeks of captivity the number of WBCs and the percentage of neutrophils decreased, indicating recovery of the immune system. This was in accord with the proliferative response of lymphocytes to the T cell mitogen PHA that increased from weeks 11-15 to weeks 16-20 in both male and female possums. The results above suggest that the Armidale possums, like the Brisbane possums, were stressed following their relocation; however, their immune systems were able to gradually recover as they adjusted to their new environment in Brisbane. The death rate of pouch young and of adult female possums after relocation was considerably higher in the Armidale possums compared to Brisbane possums. The mortality rate of Brisbane possums over the first 20 weeks of captivity was 8.3% and 19.6% for male and female possums, respectively, and for Armidale possums 16.6% and 47.1%, respectively. The possums transferred from the environs of Armidale into captivity in Brisbane were under greater stress than possums captured in Brisbane and placed in captivity in Brisbane.

Structure of double-shelled rice dwarf virus.

Rice dwarf virus (RDV), a member of the Reoviridae family, is a double-stranded RNA virus. Infection of rice plants with RDV reduces crop production significantly and can pose a major economic threat to Southeast Asia. A 25-A three-dimensional structure of the 700-A-diameter RDV capsid has been determined by 400-kV electron cryomicroscopy and computer reconstruction. The structure revealed two distinctive icosahedral shells: a T=13l outer icosahedral shell composed of 260 trimeric clusters of P8 (46 kDa) and an inner T=1 icosahedral shell of 60 dimers of P3 (114 kDa). Sequence and structural comparisons were made between the RDV outer shell trimer and the two crystal conformations (REF and HEX) of the VP7 trimer of bluetongue virus, an animal analog of RDV. The low-resolution structural match of the RDV outer shell trimer to the HEX conformation of VP7 trimer has led to the proposal that P8 consists of an upper domain of beta-sandwich motif and a lower domain of alpha helices. The less well fit REF conformation of VP7 to the RDV trimer may be due to the differences between VP7 and P8 in the sequence of the hinge region that connects the two domains. The additional mass density and the absence of a known signaling peptide on the surface of the RDV outer shell trimer may be responsible for the different interactions between plants and animal reoviruses.

Physiological changes in brushtail possums, Trichosurus vulpecula, transferred from the wild to captivity.

To determine the effect of relocation on the health of possums, the body weights and hormone and immune responses of 11 male and 9 female brushtail possums were monitored following transfer from the environs of Brisbane into an established breeding colony in Brisbane. The possums were monitored weekly for the first 20 weeks of captivity, and their immune responses assessed again 12 months after capture. Over the first 5 weeks of captivity, male possums lost a mean of 8.8% of their original body weight, and females lost 15.3% over the first 6 weeks. Variation between individual possums was evident, and the 11 male possums could be divided into two groups, those that gained weight (number of animals, N = 4) and those that lost weight (N = 7) in captivity. Four males gained weight following capture, and their body weight after 20 weeks of captivity was higher than at capture. The remaining seven males lost weight over the 20 weeks following introduction into captivity, resulting in a lower weight at week 20 than at capture. All of the nine female possums lost weight and were slower to regain weight compared to the males. Plasma cortisol concentrations did not vary greatly over the 20 weeks in male possums, and the mean plasma concentration of cortisol for the 11 male possums was 7.8 ng/ml (number of samples, n = 220). The female possums showed a different pattern. The concentration of cortisol for the nine female possums at week 1 was 34.0 ng/ml, which was significantly higher than 13.3 ng/ml at week 20 (P < 0.016). No significant variation in the mean concentration of plasma thyroxine of 5.7 ng/ml occurred in the 11 male possums over the 20-week period (n = 220). The plasma concentration of thyroxine for the nine female possums was 2.5 ng/ml (n = 54) for the first 6 weeks. At week 6, an increase in the concentration of thyroxine occurred, and a peak concentration of 6.9 ng/ml was reached at week 13. This increase correlated with the females regaining body weight. A low concentration of thyroxine is often associated with stress, thus an increase in the concentration of this hormone, combined with an increase in body weight, may indicate that these females had begun to adjust to their new environment. The seven male possums that lost weight following introduction into captivity displayed a significantly higher concentration of cortisol (9.1 compared with 5.3 ng/ml P < 0.01), and a lower concentration of thyroxine compared to the four males that gained weight following capture (4.7 compared with 7.3 ng/ml, P < 0.005). Over the 20-week period, the total number of white blood cells increased, and the number of neutrophils increased in both males and females. The proliferative response of lymphocytes from male possums to the T-cell mitogen, phytohaemagglutin (PHA) decreased significantly over the 20-week period (P < 0.002). In females an initial decrease in the reactivity of lymphocytes observed over the first 10 weeks was followed by an increase in this response over the remaining 10-week period. Twelve months following capture, the white blood cell parameters of both males and females had returned to similar levels to those of the first 1-5 weeks. The reactivity of lymphocytes from male possums that had been in captivity for 12 months was significantly higher than that of the first 20 weeks of captivity (P < 0.005). Females that had been in captivity for 12 months displayed lymphocyte responses similar to those observed at weeks 16-20. The body weight and hormonal results would suggest that possums undergo a more severe stress response than males immediately following their capture. In contrast, the immune response of males is lower than females and is depressed for a longer period following capture.

Relationships between bilayer structure and phospholipase A2 activity: interactions among temperature, diacylglycerol, lysolecithin, palmitic acid, and dipalmitoylphosphatidylcholine.

Bilayers composed of phosphatidylcholine initially resist catalysis by phospholipase A2. However, after a latency period, they become susceptible when sufficient reaction products (lysolecithin and fatty acid) accumulate in the membrane. Temperatures near the main bilayer phase transition and saturated long-chain diacylglycerol in the bilayer modulate the effectiveness of the reaction products. The purpose of this study was to identify possible mechanisms for these effects of temperature and diacylglycerol. Various fluorescent probes were used to asses changes in the ability of the reaction products to perturb the bilayer and promote enzyme binding to he membrane surface. Temperature appeared to cause three effects. First, the degree of binding of enzyme at the end of the latency period was greatest near the phase transition temperature where the latency was shortest. Second, the bilayer was more sensitive to perturbation by reaction products near the transition. Third, the disturbance provoked by the products was confined to the membrane surface below the transition but affected deeper regions at higher temperature where the latency period was greater. The latter two effects of temperature required the presence of calcium. Diacylglycerol promoted lateral segregation of reaction products in the bilayer. This effect corresponded with the tendency of diacylglycerol to reduce the length of the latency period at temperature below the phase transition. Therefore, it appeared that temperature affects the latency period by alternating the binding of the enzyme and the depth and magnitude of the bilayer perturbation caused by reaction products. Alternatively, diacylglycerol may enhance the effectiveness of reaction products by inducing them to segregate in the bilayer and thus create local regions of increased impact on the bilayer surface.

Fentanyl-related 4-heteroanilido piperidine OHM3295 augments splenic natural killer activity and induces analgesia through opioid receptor pathways.

Recently, the fentanyl-related compound OHM3295 has been shown to induce a naltrexone-sensitive, dose-related analgesia in CD1 mice. However, unlike morphine or fentanyl, which are potent immunosuppressive drugs, OHM3295 has been found to augment splenic natural killer (NK) activity in a dose-related and naltrexone-reversible manner. The present study investigated the type (delta, kappa or mu) of opioid receptor involved in analgesia and immunomodulation after acute administration of OHM3295. CD1 mice pretreated with beta-funaltrexamine (beta-FNA, 40.0 mg/kg) showed an insignificant induction of analgesia (8.4 +/- 3.7%) after 3.2 mg/kg OHM3295, whereas mice pretreated with vehicle, norbinaltorphimine (10.0 mg/kg) or naltrindole (20.0 mg/kg) exhibited 43.6 +/- 12.6% of maximal analgesia, as determined by the tail-flick latency test. Consistent with previous results, acute administration of OHM3295 (3.2 mg/kg) augmented splenic NK activity (20.7 +/- 3.4 lytic units [LU]) relative to vehicle-treated mice (8.2 +/- 0.7 LU). Pretreatment with beta-FNA (40.0 mg/kg) completely blocked (9.0 +/- 1.9 LU) OHM3295-mediated augmentation of NK activity, whereas pretreatment with norbinaltorphimine (10.0 mg/kg) partially blocked (15.8 +/- 2.2 LU) the drug-induced effect. However, pretreatment with naltrindole (20.0 mg/kg) did not antagonize OHM3295-induced increases in splenic NK activity but rather further enhanced (32.3 +/- 4.2 LU) the effect. NK-enriched effector cells from OHM3295-treated mice displayed an increase in conjugation with YAC-1 target cells, an increase in the percent killing of target cells and a significant increase in the number of active killer cells compared with NK-enriched effector cells from vehicle-treated mice.(ABSTRACT TRUNCATED AT 250 WORDS)

Effects of temperature and glycerides on the enhancement of Agkistrodon piscivorus piscivorus phospholipase A2 activity by lysolecithin and palmitic acid.

The effect of temperature and various glycerides to modulate the ability of lysolecithin and fatty acid to promote high phospholipase A2 activity was studied using dipalmitoylphosphatidylcholine large unilamellar vesicles as substrate. The length of the lag phase prior to the accumulation of sufficient hydrolysis products (lysolecithin and fatty acid) to support high phospholipase activity was shortest at temperatures near the thermotropic phase transition of the phospholipid substrate. A reduction in the lag phase correlated with a reduction in the requirement for hydrolysis products at the phase transition temperature, where the bilayer exists in a state of fluctuating domains of gel and liquid crystal. Dipalmitoylglycerol and tripalmitoylglycerol also reduced the length of the lag phase. This reduction was both concentration-dependent and temperature-dependent relative to the phase transition in the presence of the glycerides. As with the effect of temperature, the ability of di- and triglycerides to decrease the lag time correlated with a decrease in the amount of reaction products necessary to promote high phospholipase activity. This effect coincided with the tendency of the glycerides to form domains in the bilayer. Glycerides that did not form domains either had no effect (monopalmitoylglycerol) or increased the length of the lag phase (dicaprylglycerol). These data suggest that the effect of the reaction products to increase phospholipase A2 activity is aided by the presence of fluctuations in lipid domains within the bilayer.

Enhancement of Agkistrodon piscivorus piscivorus venom phospholipase A2 activity toward phosphatidylcholine vesicles by lysolecithin and palmitic acid: studies with fluorescent probes of membrane structure.

The activity of phospholipase A2 from snake venom to hydrolyze bilayers of phosphatidylcholines is greatly enhanced by the presence of the hydrolysis products, lysolecithin and fatty acid, in the bilayer. The fluorescence of several probes of membrane structure was used to monitor changes in bilayer physical properties during vesicle hydrolysis. These changes were compared to emission spectra and fluorescence polarization results occurring upon direct addition of lysolecithin and/or fatty acid to the bilayer. The excimer to monomer ratio of 1,3-bis(1-pyrene)propane was insensitive to vesicle hydrolysis, suggesting that changes in the order of the phospholipid chains were not relevant to the effect of the hydrolysis products on phospholipase activity. The fluorescence of 6-propionyl-2-(dimethylamino)-naphthalene (Prodan) suggested that the polarity of the bilayer in the region of the phospholipid head groups increases as the hydrolysis products accumulate in the bilayer. The fluorescence of 6-dodecanoyl-2-(dimethylamino)naphthalene (Laurdan) confirmed that such effects were restricted to the bilayer surface. Furthermore, the lysolecithin appeared to be the product most responsible for these changes. These results suggested that lysolecithin increases the activity of phospholipase A2 during vesicle hydrolysis by disrupting the bilayer surface, making the phospholipid molecules more accessible to the enzyme active site.

Cellular mechanisms involved in morphine-mediated suppression of CTL activity.

Based on a plethora of data from many laboratories, we have proposed the following mechanisms by which morphine alters immune homeostasis and immunocompetence in vivo (Fig. 2). Specifically, the administration of morphine subcutaneously via routing through blood interacts directly with opioid receptors on cells of the immune system or on receptors within the central nervous system. Although there is currently no evidence to support the direct involvement of morphine on lymphocyte opioid receptors, in vitro studies show the existence of functional, naloxone-sensitive opioid receptors (25). In addition, pharmacological and biochemical characterization of lymphocyte opioid receptors has been shown to be consistent in many instances, with the profile of neural-derived opioid receptors (25-27). Finally, recent molecular studies using oligonucleotide primers specific for the delta-class opioid receptor cloned from NG-108-15 cells (28) have been used in reverse transcription-polymerase chain reactions to generate a 400 bp product in SL which has 100% sequence homology with a published opioid receptor cloned from a brain library (35). However, future studies are necessary to establish the role of lymphocyte opioid receptors following the in vivo administration of opioids (e.g. fentanyl, methadone, and morphine). Since the administration of morphine subcutaneously appears to predominately interact with brain opioid receptors (3) located in the mesencephalon (5), other neuroendocrine systems become candidates for activation and subsequent direct modulation of immune function: (i) the HPA axis and (ii) the sympathetic nervous system (SNS).(ABSTRACT TRUNCATED AT 250 WORDS)

OHM3295: a fentanyl-related 4-heteroanilido piperidine with analgesic effects but not suppressive effects on splenic NK activity in mice.

The immunoregulatory effects of fentanyl and a fentanyl-related compound, OHM3295, were studied in mice. Male CD1 mice treated with a range of fentanyl doses (0.1-1.0 mg/kg, subcutaneously) showed suppression of splenic natural killer (NK) activity following 0.25-0.50 mg/kg fentanyl dose but not higher (0.75-1.0 mg/kg) or lower (0.1 mg/kg) doses. Fentanyl (0.01-32.0 mg/kg) also induced dose-related analgesia as measured by an increase in tail flick latency; these analgesic effects were antagonized by naltrexone (1.0-10.0 mg/kg). Pretreatment with naltrexone (1.0-3.2 mg/kg) resulted in significant suppression of splenic NK activity following fentanyl (10.0-32.0 mg/kg) administration. In comparison to fentanyl, OHM3295 (3.2-25.0 mg/kg) augmented splenic NK activity in a naltrexone-reversible manner. Similar to fentanyl, OHM3295 (1.0-32.0 mg/kg) also induced a naltrexone-sensitive, dose-related analgesia as measured by an increase in tail flick latency. These results with OHM3295 demonstrate a novel profile of effects which includes naltrexone-sensitive analgesic effects in the absence of immunosuppressive effects. In addition, this is the first reported case in which a compound with opioid analgesic effects has been shown to potentiate natural killer cytolytic activity following in vivo administration.

Effects of gallstone solvents on commonly used catheters.

PURPOSE: To determine what interaction and effect different cholesterol gallstone solvents have on catheters used for gallstone chemolysis. MATERIALS AND METHODS: Five types of catheters used for biliary procedures were chosen: polyethylene, Percuflex, silicon, Silitek, and polyurethane. The solvents chosen were methyl tert-butyl ether, ethyl propionate, isopropyl acetate, and N-propyl acetate. After incubation of the catheters in the solvents for 72 hours, they were air dried. Weight and area changes were determined for each catheter. Additionally, carbon-13 nuclear magnetic resonance (NMR) spectroscopy was performed for analysis of composition changes. RESULTS: Three catheters--silicone, Silitek, and polyurethane--showed changes in their physical characteristics that would make them less desirable for stone chemolysis. The silicone catheter showed changes in elastic texture as well as marked weight reduction. The Silitek and polyurethane catheters had similar, but less dramatic changes. C-13 NMR analysis of collected solvents showed that commonly used plasticizers were leached out of some catheters. CONCLUSION: These results suggest that all catheters are not suitable for use with all solvents. The choice of catheter should be made based on the solvent in use. The polyethylene catheter performed best under the conditions and endpoints used in this study.