Moisture-insensitive adhesives: reactivity with water and bond strength to wet and saliva-contaminated enamel.
The purpose of this study was to investigate the reactivity with water of a moisture-insensitive orthodontic primer (Transbond MIP), in conjunction with a no-mix orthodontic adhesive (Unite), and a moisture-insensitive adhesive (Smartbond), and to assess their bond strength to wet and saliva-contaminated enamel relative to the conventional application of the no-mix adhesive. The reactivity of the moisture-insensitive products with water was investigated by micro-multiple internal reflectance Fourier transform infrared spectroscopy (micro-MIR FTIR). Sixty premolars were divided into two groups of 30 teeth each and, on the buccal enamel surfaces, a standardized volume (0.1 ml) of water or fresh whole saliva was applied. Standard edgewise stainless steel brackets were then bonded to enamel surfaces as follows: (a) Unite, (b) Unite with the Transbond MIP, and (c) Smartbond. The brackets were debonded under shear force at a speed of 2 mm/min and the debonded enamel surfaces were subjected to fractographic analysis. The statistical analysis of the bond strength values was performed by two-way ANOVA with condition (water, saliva) and adhesive type serving as discriminating variables (n = 10, alpha = 0.05). The results of the fractographic analysis were evaluated by chi 2 test (alpha = 0.05). FTIR analysis showed that only Smartbond set in the presence of water. Application of water in Transbond MIP increased the extent of carboxyl ionization without inducing any setting reaction. Transbond MIP did not improve bond strength values when combined with the no-mix adhesive. Most adhesive-enamel condition combinations showed a trend to present lower bond strength in the presence of saliva; however, this was not confirmed statistically. Fractography of enamel and bracket base surfaces showed that Unite + Transbond MIP resulted in the most adhesive fractures (leaving no resin on enamel surface), whereas Smartbond presented the highest frequency of cohesive fractures (adhesive left on bracket and enamel surfaces).


A mobilizable pool of d-amphetamine in adipose after daily administration to rats.
Six daily injections (subacute) of 2.5 mg d-amphetamine/kg resulted in a 60% higher concentration of unchanged drug in adipose compared with adipose from rats injected once. Subacute treatment also resulted in 30% less amphetamine in brain one hour after injection, when the animals were killed for tissue analysis. Moderate stress, in the form of foot shock for fifteen minutes, terminating fifteen minutes prior to sacrifice, mobilized the drug from adipose and doubled brain levels of amphetamine in the subacute group. Brain levels in the group given a single dose of drug were unaltered by shock, but heart content of amphetamine was increased 30% as a result of shock. It is concluded that enhanced reactivity to some of the behavioral effects of amphetamine, upon repeated administration, may be due to cumulation of the drug in mobilizable pools.


In vivo competitive studies between normal and common gamma chain-defective bone marrow cells: implications for gene therapy.
Corrective gene transfer into hematopoietic stem cells (HSCs) is being investigated as therapy for X-linked severe combined immunodeficiency (XSCID) and it is hoped that selective advantage of gene-corrected HSCs will help in achieving full immune reconstitution after treatment. Lines of evidence from the results of allogeneic bone marrow transplantation in patients with XSCID support this hypothesis that, however, has not been rigorously tested in an experimental system. We studied the competition kinetics between normal and XSCID bone marrow (BM) cells using a murine bone marrow transplantation (BMT) model. For easy chimerism determination, we used genetic marking with retrovirus-mediated expression of the enhanced green fluorescent protein (EGFP). We found that XSCID BM cells were able to compete with normal BM cells for engraftment of myeloid lineages in a dose-dependent manner, whereas we observed selective repopulation of T, B, and NK cells deriving from normal BM cells. This was true despite the evidence of competitive engraftment of XSCID lineage marker-negative/c-Kit-positive (Lin-/c-Kit+) cells in the bone marrow of treated animals. From these results we extrapolate that genetic correction of XSCID HSCs will result in selective advantage of gene-corrected lymphoid lineages with consequent restoration of lymphocyte populations and high probability of clinical benefit.


Effect of polyunsaturated fatty acids and some conventional penetration enhancers on transdermal delivery of atenolol.
The aim of our present study was to evaluate the in vitro percutaneous absorption of atenolol, a well-known antihypertensive, from a series of formulations containing various penetration enhancers. Particularly the promoting effect of EPA and DHA, two polyunsaturated fatty acids (PUFAs), has been studied, and drug permeation data have been compared with those obtained with the other formulations containing "classic" penetration enhancers such as transcutol, d-limonene, and PG. Not all the penetration enhancers tested were effective in increasing atenolol percutaneous flux and the best permeation profile for atenolol was obtained with the formulation containing transcutol (B) and PUFA (E). To explain the enhancer mechanism, the atenolol diffusion and partitioning coefficients from the different formulations were calculated. The results indicated that PUFAs increased the apparent diffusion coefficient of the drugs but did not affect their apparent stratum corneum (SC)/vehicle partition coefficient (K(m)). At this same time transcutol exerted its enhancer effect increasing significantly the apparent SC/vehicle partition coefficient (K(m)) and in a minor amount the apparent diffusion coefficient of skin permeation process (D(m)). The potential application of formulations B and E in atenolol percutaneous absorption was determined from the calculation of the steady-state plasma concentrations (C(ss)). These values resulted within the drug therapeutic range and suggest that atenolol transdermal delivery could be feasible.


Dielectric concentrator for Cherenkov radiation.
We report on a dielectric target that concentrates Cherenkov radiation into a small spatial area. In contrast to traditional devices, this target can focus almost all of the radiation without using additional lenses or mirrors. We consider the case where radiation is produced by a point charge moving along the axis of a cylindrical channel inside an axially symmetrical target. The specific form of the target is determined using the laws of ray optics. The field is calculated using an aperture integration method that can determine the field near the focus. Typical field plots and the spatial distribution of the field outside the target are presented. We demonstrate that at terahertz frequencies, this concentrator can increase the field magnitude by up to at least 2 orders of magnitude relative to that on the surface of the target.


[A KABP (knowledge, attitude, belief and behavior) study about AIDS among taxi drivers and hotel attendants in Beijing].
This article reports the KABP study on 448 taxi drivers and 556 hotel attendants in Beijing for the first time in China. A self-administered questionnaire was used to investigate knowledge, attitude, belief and practice (KABP) about AIDS. In terms of knowledge, 23.8% of hotel attendants and 36.8% of taxi drivers did not know that contact with blood could transmit HIV. Thirtyfive percent of hotel attendants and 42.2% of taxi drivers did not believe that intravenous drug users were at high risk. Some drivers (13.6%) and hotel attendants (3.4%) reported having multiple sexual partners. Forty-one point nine percent of taxi drivers and 16.6% of hotel attendants preferred the idea of multiple sexual partners. Among hotel attendants, a negative association was found between knowledge about AIDS and multiple sexual behavior (P < 0.01). Regarding attitude toward condom use, 56.2% of taxi drivers and 47.8% of hotel attendants who have had a sexual experience thought that condom use interfered with sexual pleasure. Seventy-six point eight percent of taxi drivers and 79.8% of hotel attendants believed that they could change their behaviors in order to minimize the chances of getting HIV. This study indicates that HIV education is important in reducing the number of sexual partners and promoting the use of safe sex practices like condom use. Furthermore, as reported by the study population, education can change behavior.


Freshwater fish parasites and environmental quality: an overview and caution.
The use of free-living invertebrates as indicators of freshwater quality is long established and well documented. The basic approaches employed are 1) recognition of indicator species, 2) recognition of changes, usually reduction, in community diversity and 3) construction of biological indices, combining knowledge of 1) and/or 2) and taking into account changes in species abundance. These approaches employ invertebrates because of their immobility and longevity, and rely on a detailed body of ecological knowledge so that biotic changes can be related clearly to particular environmental changes. If we are to use parasites in the same way, we must show that pollution does affect parasites and then ask whether they can serve as indicator species, and whether changes in parasite communities can serve as indicators of specific changes in environmental conditions. We must also ask if parasites are better indicators than free living organisms. Parasites also pose additional difficulties: they are mobile because their fish hosts are, and the effects of pollution may be direct on the parasite or indirect on any of its hosts or act via host immune systems. No species has evolved and adapted to pollution, and presence or absence of a parasite species or changes in community may have many causes. Both presence and community structure vary considerably between localities and over time within localities and we cannot yet relate these changes to particular causes. We can record changes and differences, but with present lack of knowledge cannot relate them unequivocally to specific causal factors or environmental changes. Use of parasites as bio-accumulators shows promise, as does monitoring of a locality over time, but one-off surveys are of no use. Until we are prepared to stand up in a court of law and be cross-examined on our statement that these parasites clearly show a particular change in the environment, the answer to both questions above must be no.


Induction of lymphokine-activated killer (LAK) activity in canine lymphocytes with low dose human recombinant interleukin-2 in vitro.
Interleukin-2 (IL-2) is an immunostimulatory cytokine that induces activation of peripheral blood lymphocytes (PBL) which can mediate augmented tumor cytotoxicity. Several regimens using IL-2 as treatment for metastatic melanoma and renal carcinoma have shown measurable tumor responses in 10-20% of human patients. Our overall goals are to determine the efficacy of IL-2 as an adjuvant treatment for canine tumors. In order to evaluate the possibility to extend the use of IL-2 in vivo in the dog, we examined the ability of a clinically relevant (low) dose of human recombinant IL-2 (100 units/ml) to enhance the tumoricidal properties of canine PBL in vitro. This was particularly important considering the need to establish the effects on canine PBL by IL-2 at a dose that is potentially achievable in vivo with acceptable side effects. Our data show, for the first time, the ability to separate canine natural killer (NK) cell activity from lymphokine-activated killer (LAK) cell activity (induced with a low IL-2 dose) mediated by canine PBL against two canine cell lines (CTAC and CML-10) used as targets in 4 vs. 16 hour killing assays. LAK cells generated by stimulation of canine PBL with 100 units/ml of IL-2 for 72 hours, could kill CTAC or CML-10 targets up to 11 or 18 times more efficiently, respectively, than fresh PBL in a 4 hour assay. However, the killing of efficiency of the LAK cells was only 2- to 3-fold greater than that of the fresh PBL in a 16 hour assay. This apparent reduction in the killing efficiency of the LAK cells was mostly due to increased spontaneous NK activity by the fresh PBL after 16 hours in culture; both the LAK cells and the fresh PBL (NK cells) mediated a greater overall cytotoxicity after 16 hours than they did in the 4 hour assays. These results indicate that a low dose of human recombinant IL-2 can augment tumor killing by canine PBL in vitro, and suggest that it may be feasible to examine the potential use of IL-2 as an immunotherapeutic agent in tumor-bearing dogs.


First Report of Impatiens Downy Mildew Outbreaks Caused by Plasmopara obducens Throughout the Hawai'ian Islands.
Downy mildew of impatiens (Impatiens walleriana Hook.f.) was first reported from the continental United States in 2004. In 2011 to 2012, severe and widespread outbreaks were documented across the United States mainland, resulting in considerable economic losses. On May 5, 2013, downy mildew disease symptoms were observed from I. walleriana 'Super Elfin' at a retail nursery in Mililani, on the Hawai'ian island of Oahu. Throughout May and June 2013, additional sightings of the disease were documented from the islands of Oahu, Kauai, Maui, and Hawai'i from nurseries, home gardens, and botanical park and landscape plantings. Symptoms of infected plants initially showed downward leaf curl, followed by a stippled chlorotic appearance on the adaxial leaf surfaces. Abaxial leaf surfaces were covered with a layer of white mycelia. Affected plants exhibited defoliation, flower drop, and stem rot as the disease progressed. Based on morphological and molecular data, the organism was identified as Plasmopara obducens (J. Schröt.) J. Schröt. Microscopic observation disclosed coenocytic mycelium and hyaline, thin-walled, tree-like (monopodial branches), straight, 94.0 to 300.0 × 3.2 to 10.8 μm sporangiophores. Ovoid, hyaline sporangia measuring 11.0 to 14.6 × 12.2 to 16.2 (average 13.2 × 14.7) μm were borne on sterigma tips of rigid branchlets (8.0 to 15.0 μm) at right angle to the main axis of the sporangiophores (1,3). Molecular identification of the pathogen was conducted by removing hyphae from the surface of three heavily infected leaves using sterile tweezers, then extracting DNA using the QIAGEN Plant DNA kit (QIAGEN, Gaithersburg, MD). The nuclear rDNA internal transcribed spacer was sequenced from each of the three samples bidirectionally from Illustra EXOStar (GE Healthcare, Piscataway, NJ) purified amplicon generated from primers ITS1-O and LR-0R (4). Resultant sequences (GenBank KF366378 to 80) shared 99 to 100% nucleotide identity with P. obducens accession DQ665666 (4). A voucher specimen (BPI892676) was deposited in the U.S. National Fungus Collections, Beltsville, MD. Pathogenicity tests were performed by spraying 6-week-old impatiens plants (I. walleriana var. Super Elfin) grown singly in 4-inch pots with a suspension of 1 × 104 P. obducens sporangia/ml until runoff using a handheld atomizer. Control plants were sprayed with distilled water. The plants were kept in high humidity by covering with black plastic bags for 48 h at 20°C, and then maintained in the greenhouse (night/day temperature of 20/24°C). The first symptoms (downward curling and chlorotic stippling of leaves) and sporulation of the pathogen on under-leaf surfaces of the inoculated plants appeared at 10 days and 21 days after inoculation, respectively. Control plants remained healthy. Morphological features and measurements matched those of the original inoculum, thus fulfilling Koch's postulates. To our knowledge, this is the first report of downy mildew on I. walleriana in Hawai'i (2). The disease appears to be widespread throughout the islands and is likely to cause considerable losses in Hawai'ian landscapes and production settings. References: (1) O. Constantinescu. Mycologia 83:473, 1991. (2) D. F. Farr and A. Y. Rossman. Systematic Mycology and Microbiology Laboratory, ARS, USDA. Retrieved from http://nt.ars-grin.gov/fungaldatabases/ July 16, 2013. (3) P. A. Saccardo. Syllogue Fungorum 7:242, 1888. (4) M. Thines. Fungal Genet Biol 44:199, 2007.


Decreased GABA-A Receptor Binding in Association With β-Lactam Antibiotic Use.
β-Lactam antibiotics are proconvulsive. In laboratory animals, this effect seems to be predominantly mediated through inhibition of GABA-A receptors, but it has not been demonstrated in humans in vivo. We report images of a [C]Ro15-4513 PET from a 40-year-old man who had completed a 1-week course of flucloxacillin before it. Relative to healthy controls, the participant had significantly lower mean gray matter binding. These novel data suggest that, in humans, the proconvulsive effect of β-lactam antibiotics is mediated via either competition for the same benzodiazepine-binding site as [C]Ro15-4513 or downregulation of GABA-A receptor expression.


Design, synthesis, and conformational analysis of a novel macrocyclic HIV-protease inhibitor.
Design modifications to the lead HIV-PR inhibitor 1 (MDL 73,669, Ki = 5 nM) have been postulated based on a computational model of the 1/HIV-PR complex. A novel macrocyclic inhibitor 8 (MDL 104,168) wherein the P1 and P3 side chains of the original acyclic inhibitor have been joined retains good biological activity (Ki = 20 nM). NMR analysis of the precursor alcohol (S)-7 shows the conformation of the cyclic region to be very similar to that observed in the enzyme-bound 8 as determined by the computational model. Consistency of the computational model with NMR data and in vacuo molecular dynamics simulations provide the basis for postulating further modifications of the cyclic inhibitor expected to optimize its interactions with HIV-PR.


Sensitivity of camptothecin-resistant human leukemia cells and tumors to anticancer drugs with diverse mechanisms of action.
Human leukemia U-937 cell clones resistant to 9-nitrocamptothecin (9NC) appear after exposure to increase 9NC-concentrations. Drug resistance is irreversible, regardless of whether the 9NC-resistant (U-937/CR150) cells grow in media with or without 9NC. U-937/CR150 cells are more sensitive than wild type U-937 (U-937/wt) cells to topoisomerase II-directed drugs, amsacrine, daunorubicin, and etoposide. The mitotic inhibitor, vincristine, induces hyperdiploidy in U-937/wt, but not in U-937/CR150 cells, whereas the antimetabolites, cytarabine and methotrexate, and the nitrosourea, carmustine, elicit similar responses in both U-937/wt and U-937/CR150 cells. U-937/CR150-generated tumors in nude mice are sensitive to etoposide. The clinical implications of increased sensitivity of 9NC-resistant tumors to some anticancer drugs are discussed.


Temperature regulation during rest and exercise in the cold in premenarcheal and menarcheal girls.
Temperature regulation during exercise in the cold was examined in 13 adolescent female individuals, aged 13-18 yr. Six girls with established menstrual cycles comprised the eumenorrheic menarcheal (EM) group, and seven nonmenstruating girls comprised the premenarcheal (PM) group. During the first visit, maximal oxygen consumption (Vo(2 max)), height, weight, and percent body fat were measured. The second visit included a determination of metabolic rate in thermoneutrality (21 degrees C), consisting of a 10-min rest period and 20 min of cycling (30% of Vo(2 max)), and a cold test (5 degrees C, 40% humidity, <0.3 m/s air velocity) involving a 20-min rest period and 40 min of cycling (30% of Vo(2 max)). Subjects in the EM group were tested twice in the chamber: once during the follicular and once during the luteal phase. Heat production per kilogram in thermoneutrality and in the cold was significantly (P < 0.05) higher in the PM compared with the EM girls. However, the PM girls had a significantly (P < 0.05) lower core temperature in the cold than the EM group. PM girls also had a significantly higher body surface area-to-mass ratio compared with the EM girls. Although percent body fat between groups was not significantly different, within the PM group percent body fat explained 79% (P < 0.01) of the variance in the decrease of core temperature. There were no menstrual phase-related differences in temperature regulation in either the thermoneutral or cold environment. In conclusion, menstrual phase does not influence temperature regulation in female individuals during adolescence. EM girls had lower metabolic heat production but maintained their core temperature more effectively in the cold than did the PM girls. This thermoregulatory difference between PM and EM girls is mainly a function of geometric differences with maturation-related peripheral vasoconstrictive differences maybe limiting the effectiveness of the mechanism of increased heat storage in younger female individuals.


Multimodal treatments for childhood attention-deficit/hyperactivity disorder: interpreting outcomes in the context of study designs.
The goal of this article was to outline issues critical to evaluating the literature on incremental benefit of multiple effective treatments used together, vs. a single effective treatment, for childhood ADHD. These issues include: (1) sequencing and dosage of treatments being combined and compared; (2) difficulty drawing valid conclusions about individual components of treatment when treatment packages are employed; (3) differing results emerging from measurement tools that purportedly measure the same domain; and (4) the resultant difficulty in reaching a summary conclusion when multiple outcome measures yielding conflicting results are used. The implications of these issues for the design and conduct of future studies are discussed, and recommendations are made for future research.


Fractional exhaled nitric oxide in children with acute exacerbation of asthma.
To determine whether fractional exhaled nitric oxide (FENO) has a utility as a diagnostic or predictive maker in acute exacerbations of asthma in children. Analysis of data collected in a pediatric asthma cohort. Pediatric Chest Clinic of a tertiary care hospital. A cohort of children with asthma was followed up every 3 months in addition to any acute exacerbation visits. Pulmonary function tests (PFT) and FENO were obtained at all visits. We compared the FENO values during acute exacerbations with those at baseline and those during the follow up. 243 asthmatic children were enrolled from August 2009 to December 2011 [mean (SD) follow up - 434 (227) days]. FENO during acute exacerbations was not different from FENO during follow up; however, FENO was significantly higher than personal best FENO during follow up (P < 0.0001). FENO during acute exacerbation did not correlate with the severity of acute exacerbation (P=0.29). The receiver operating characteristics curve for FENO as a marker for acute exacerbation had an area under the curve of 0.59. Cut-off of 20 ppb had a poor sensitivity (44%) and specificity (68.7%) for acute exacerbation. FENO levels during acute exacerbation increase from their personal best levels. However, no particular cut off could be identified that could help in either diagnosing acute exacerbation or predicting its severity.


Ultrastructures of mechanoreceptors in the oral mucosa.
The present review describes the fine structures of lamellated mechanoreceptive corpuscles, Merkel cell-neurite complexes and free nerve endings in the oral mucosae of mammals, with special attention to axon terminals and lamellar cells. The mechanoreceptive nerve endings of the oral mucosa were studied using histochemistry, immunohistochemistry and transmission electron microscopy techniques. The organized mechanoreceptive corpuscles are present in the mucosae of gingiva, cheek, tongue and soft and hard palate. They are elongated or globular in shape, being located in the connective tissue papillae. The capsule is composed of several layers of cytoplasmic extensions of perineural cells. Numerous bundles of collagen fibers are noted at the periphery of the corpuscle. The lamellated corpuscles are surrounded by several layers of superimposed flattened capsular cell processes. The interlamellar spaces are 0.2-0.4 micron in width and filled with thin fibrillar collagen fibers embedded in the amorphous substance. The lamellar cells contain rich microtubules and are characterized by the presence of caveolae on the surface plasma membrane. The terminal axon contains an abundance of mitochondria and small clear vesicles (20-50 nm in diameter). There are neurofilaments in the center of the axon terminal. Intermediate-type junctions are seen between the adjacent lamellar cells and between the axon and adjacent lamellae. The free nerve endings are found in the subepithelial regions, very close to the basal laminae of mucosal epithelium. They are surrounded by a thin cytoplasm of Schwann cells. Sometimes Schwann cell basal larinae become multilayered. Merkel cells are present within the basal layer of mucosal epithelium and contain characteristic electron-dense granules that are located almost exclusively at the side of cytoplasm in contact with axon terminals. Intermediate-type junctions are noted between axon terminals and Merkel cells.


Identification of glyburide metabolites formed by hepatic and placental microsomes of humans and baboons.
Glyburide (glibenclamide) is a second-generation sulfonylurea used for treatment of type-2 and gestational diabetes mellitus. To date, two glyburide metabolites have been identified in maternal urine: namely, 4-trans-hydroxycyclohexyl glyburide and 3-cis-hydroxycyclohexyl glyburide. The use of glyburide to treat gestational diabetes prompted us to investigate its metabolism by the placenta. The metabolism of glyburide by microsomal preparations from human and baboon placenta was compared with metabolism by their livers. The metabolites formed by the microsomes of the four tissues were identified by high-performance liquid chromatography-mass spectrometry using retention times, ion current (extracted at m/z 510), and selected-ion monitoring. The data obtained revealed the formation of six distinct hydroxylated derivatives of glyburide by each of the four microsomal preparations. However, the amounts of the six metabolites formed by the placentas were a fraction of that formed by the livers. Moreover, the relative quantities of each metabolite formed differed between species as well as between the two tissues. Also, the structure of the unidentified metabolites was determined by comparison with synthesized standards. These metabolites were identified as the 4-cis-hydroxycyclohexyl glyburide, 3-trans-hydroxycyclohexyl glyburide, and 2-trans-hydroxycyclohexyl glyburide. Therefore, one glyburide metabolite remains to be identified, but the data we obtained allowed us to suggest its structure.


Comparison of fatty acid profile in the chicken meat after feeding with narasin, nicarbazin and salinomycin sodium and phyto-additive substances.
The purpose of this study was an experimental investigation and a statistical evaluation of the influence of various additives in feed mixtures of broiler chickens on fatty acids content and their ratio in breast and thigh muscles. First feed additive consisted of narasin, nicarbasin and salinomycin sodium, and other five additives were of phytogenic origin. In vivo experiment was realized on the poultry experimental station with deep litter breeding system. A total of 300 one-day-old hybrid chickens Cobb 500 divided into six groups were used for the experiment. The experimental period was divided into four phases, i.e. Starter, Grower 1, Grower 2 and Final, according to the application of commercial feed mixture of soy cereal type. Additive substances used in feed mixtures were different for each group. Basic feed mixtures were equal for all groups. Fatty acid profile of breast and thigh muscles was measured by the method of FT IR Nicolet 6700. Investigated additive substances in the feed mixtures did not have statistically significant effect on fatty acid content and omega-6/omega-3 polyunsaturated fatty acid (PUFA) ratio in breast and thigh muscles. Strong statistically significant relation between omega-6 PUFAs and total PUFAs were proved by experiment. A relation between omega-3 PUFAs and total PUFAs was found only in the group with Biocitro additive.


Effect of Alcohol Consumption on Recovery From Eccentric Exercise Induced Muscle Damage in Females.
This study was designed to investigate the effects of alcohol consumption on recovery of muscle force when consumed immediately postexercise in young females. Eight young women completed 300 maximal eccentric actions of the quadriceps femoris muscle on an isokinetic dynamometer on two occasions in a randomized, cross-over design after which an alcoholic beverage (0.88g ethanol/kg body weight) or an iso-caloric placebo was consumed. Maximal isokinetic (concentric and eccentric) torque and isometric tension produced across the knee were measured in both the exercised and control leg predamage, 36 hr post, and 60 hr post damage. Venous blood creatine kinase (CK) activity and muscle soreness ratings were taken before damage and once per day to 60 hr post damage. Significant differences were observed between the exercised and control leg for maximal concentric, and eccentric torque and isometric tension (p < .05). A near significant Treatment × Time interaction was observed for isometric tension (p = .077), but not for concentric or eccentric torque. No main effects of treatment (alcohol) or interactions with Time × Leg or Leg × Treatment were observed. Perceived muscle soreness during box stepping and squatting showed significant time effects (p < .05), and CK activity did not significantly change. Our results indicate that the consumption of 0.88g ethanol/kg body weight following eccentric exercise-induced muscle damage does not affect recovery in the days following damage in females.


[Bladder leiomyoma: review of the literature and report of 3 clinical cases].
Presentation of three cases of bladder leiomyoma in women. All cases were characterized for the unspecific clinical presentation and a difficult pre-operative diagnosis, where ultrasound, cystoscopies, CAT and PAAF were used as complementary methods. The certainty diagnosis was only obtained after the histological study of the surgical piece. Treatment was in all three cases surgical, and the pathoanatomical diagnosis was bladder leiomyoma.


Oviduct: roles in fertilization and early embryo development.
Animal oviducts and human Fallopian tubes are a part of the female reproductive tract that hosts fertilization and pre-implantation development of the embryo. With an increasing understanding of roles of the oviduct at the cellular and molecular levels, current research signifies the importance of the oviduct on naturally conceived fertilization and pre-implantation embryo development. This review highlights the physiological conditions within the oviduct during fertilization, environmental regulation, oviductal fluid composition and its role in protecting embryos and supplying nutrients. Finally, the review compares different aspects of naturally occurring fertilization and assisted reproductive technology (ART)-achieved fertilization and embryo development, giving insight into potential areas for improvement in this technology.


[A new LH-RIA rapid test for determining peak levels of serum LH--a methodological contribution to in-vitro fertilization].
A highly sensitive, easy to operate LH-RIA rapid test was developed by changing the incubation period and temperature and by reducing the standard curve to three measurement data, using commercially available reagents. The results obtained by means of the LH-RIA rapid test correlate most loosely with those of a conventional 5-hour LH-RIA. The new LH-RIA rapid test is ideally suited for LH peak search at short intervals for exact determination of the time of ovulation as part of in-vitro fertilisation or insemination.


[Whipple disease: a differential diagnosis of polyarthritis to keep in mind].
Whipple disease is a rare and potentially fatal bacterial infection induced by a Gram-positive bacillus, Tropheryma whipplei. It is responsible for articular, digestive, neurological, ophthalmological and cardiological symptoms that occur either concomitant or isolated. Thus, the diagnosis is difficult to make and therefore often delayed. A paradoxal exacerbation of the symptoms under immunosuppressive drugs such as glucocorticoids and anti-TNF mAb, or inexpected improvements under antibiotic treatment applied for other reasons should raise a clinicial suspicion of Whipple's disease. Detection of the germ on stool and saliva samples by molecular biology methods has become straightforward with very good positive and negative predictive values. Long-term antibiotic treatment close follow-up are required for the induction of remission and to recognize relapse.


Synthesis and structure-activity relationships of an orally available and long-acting analgesic peptide, N(alpha)-amidino-Tyr-D-Arg-Phe-MebetaAla-OH (ADAMB).
A novel dermorphin tetrapeptide N(alpha)-amidino-Tyr-D-Arg-Phe-MebetaAla-OH (ADAMB) was designed based on the structures of several dermorphin tetrapeptide analogues, including N(alpha)-amidino-Tyr-D-Arg-Phe-Gly-OH (ADA-DER), H-Tyr-D-Arg-Phe-betaAla-OH (TAPA), and H-Tyr-D-Arg-Phe-Sar-OH (DAS-DER). These parent compounds were known to show a weak oral analgesic activity in animals and/or to possess a different mechanism of analgesia from other mu-opioid peptides. Six analogues of ADAMB were also synthesized to investigate the effect on potency of N-terminal amidination and N-methyl-beta-alanine (MebetaAla) substitution at position 4. Compounds were assessed using the tail pressure test in mice after subcutaneous and oral administration. Among the peptides tested, ADAMB showed the strongest oral antinociceptive activity, with an ED(50) of 5.8 vs 22.2 mg/kg for morphine, as well as a 38-fold stronger activity after subcutaneous administration. ADAMB also showed long-lasting antinociceptive activity, with 50% of the maximum effect persisting in the tail pressure test at 10 h after oral administration (10 mg/kg). In contrast, orally administered morphine (80 mg/kg) showed a rapid decrease of activity in the same test and its antinociceptive effect disappeared within 4 h. When the antinociceptive effect of ADAMB was compared with that of analogues possessing betaAla(4) (1) or Sar(4) (2), as well as analogues with N-substitution (3-6), it was found that both the N(alpha)-amidino substitution and the MebetaAla(4) were synergistically involved in creating ADAMB's exceptionally high antinociceptive activity.


Transaortic transcatheter aortic valve implantation using the Lotus valve: first-in-man experience.
To demonstrate the feasibility of implanting the Lotus second-generation transcatheter heart valve (THV) (designed for a transfemoral procedure) via a transaortic approach. We describe a case with severe aortic stenosis in the presence of small calibre and calcified femoral access and severe chronic obstructive pulmonary disease. The transaortic approach was the ideal approach for this patient and we successfully implanted a 25 mm Lotus valve without any complication. The transaortic access is a feasible and safe alternative in patients who have suboptimal iliofemoral conduits and who will benefit from the unique features of the Lotus THV.


[Information systems for clinicians I. How to know what type of patients are attended in our hospitals].
We describe a series of tools to study the types of patients treated in hospitals: the Minimum Basic Data Set (MBDS), International Classification of Diseases (ICD) and the more used patient classification system: Diagnosis Related Groups (DRG) and suggest their possible applications in the fields of management and clinical research.


Transthyretin distribution in the developing choroid plexus of the South American opossum (Monodelphis domestica).
The distributions of transthyretin and albumin in the choroid plexus during brain development have been compared. The South American opossum was chosen because the young are born around the time of choroid plexus formation. Previous work showed that in the adult opossum, transthyretin is expressed in the choroid plexus cells. However, systematic studies of transthyretin in the choroid plexus during development have not been carried out before. Transthyretin was present in 90-95% of the choroidal cells form birth to adulthood. In most cells, transthyretin immunoreactivity was concentrated in the apical region of the cytoplasm. Double labelling of choroid plexus sections with antibodies to albumin and transthyretin showed that 1-2% of cells were positive for both proteins. These findings suggest that from the very earliest stage of choroid plexus formation most epithelial cells both synthesize and contain transthyretin, and a few of these transthyretin-synthesizing cells also contain albumin that is probably being transferred form blood to the cerebrospinal fluid.


Development of useful reactions based on the novel reactivities of allenic compounds and their application to tandem cyclizations.
This review highlights a recent study on allenic compounds by the author's group. In the first section, the organocopper-mediated ring-opening reaction of ethynylaziridines and palladium-catalyzed reductive synthesis of allenes are described. In the second section, palladium-catalyzed stereoselective cyclization of allenes, including the tandem reaction, leading to aziridines, pyrrolidines, benzoisoindoles, and cyclopropanes is presented. The final section reviews aziridination and medium-ring formation due to the intramolecular reaction of bromoallenes. The latter reaction is based on the author's recent discovery that bromoallenes can act as allylic dication equivalents in the presence of a palladium catalyst and alcohol.


Does experience in colposcopy improve identification of high grade abnormalities?
This study investigates whether experience in colposcopy improves identification of high grade abnormalities. The sensitivity and positive predictive value (PPV) of colposcopy in identifying high grade intra-epithelial lesions (HSIL) performed by relatively inexperienced as compared to experienced colposcopists are evaluated. Of 18,421 colposcopies performed at the Royal Women's Hospital, Melbourne, Australia, between 1999 and 2004 by 5 senior and 11 junior colposcopists, the colposcopic impression was correlated with the histopathology result of the biopsy taken at 6020 colposcopies, with respect to the experience of the colposcopist. Colposcopy had a 60% sensitivity and 60% PPV in identifying HSIL in this study. In case of a high-grade referral smear the sensitivity and PPV in identifying HSIL were, respectively 76% and 73%, compared with 26% and 48% in case of a low-grade referral smear, no difference in overall colposcopic performance between experienced and inexperienced colposcopists was observed. However, the sensitivity of identifying HSIL was significantly higher with inexperienced colposcopists, and the PPV was significantly higher with experienced colposcopists. In this study experience did not improve colposcopic performance, but differences in colposcopic strategy between the two groups were noted. The rather low overall sensitivity and PPV of colposcopy in identifying HSIL, especially in case of a low-grade referral smear, indicate that the role of colposcopy in the detection and treatment of cervical abnormalities is to assess size, site, and extent of an abnormality, rather than to assess the severity of this abnormality. Histology must remain the gold standard for treatment.


Biocompatibility studies of titanium-based alloy pedicle screw and rod system: histological aspects.
Few histological studies of pedicle screw and rod systems have been done, and spinal surgery with pedicle screw and rod system is increasing. To know the biocompatibility of pedicle screw and rod systems histologically. Titanium-based alloy pedicle screws were removed from 20 patients. Histological studies of the tissue response to the screws were performed by light microscopy. Twenty patients, who were diagnosed with burst type spinal fracture, spondylolysis, spondylolisthesis, and lumbar disc herniation. All slides were observed by light microscopy, and inflammation, fibrous tissue formation, and wear debris were evaluated using a subjective scale. Before the surgery, plain radiographs were taken to confirm the solid arthrodesis. Histological analysis was divided into four areas and studied using light microscopy. Inflammation and fibrous tissue formation were the main tissue reactions to the implants. No tissue surrounding the implants showed irreversible changes. Fibrous tissue was often observed at the bone-screw interface without direct contact of screw and bone at the muscle-screw interface histologically. Although some titanium debris was observed in both interfaces, no debris of inflammatory cells were seen at 1 cm distance from the screws. The inflammatory response to the screw debris was localized. Titanium-based alloy pedicle screws produced some metal debris and caused localized inflammation. No adverse tissue reaction was observed around the screws and rods. Direct contact without any fibrous tissue formation at the bone-screw interface was observed in some patients. A titanium-based alloy pedicle screw and rod system is considered biocompatible histologically.


Postoperative adjuvant arterial infusion chemotherapy for patients with hepatocellular carcinoma.
The efficacy of postoperative hepatic arterial infusion chemotherapy (PAI) in the prevention of the recurrence of hepatocellular carcinoma (HCC) following hepatic resections was examined. Between November 1982 and February 1994, hepatic resections were carried out in 74 consecutive HCC patients with stage III and IV at Oita Medical University Hospital. They were divided into two groups. In PAI group patients (n = 26), cis-diamminedichloroplatinum or a combination of 5-fluorouracil, adriamycin and mitomycin was alternately infused every 3 months. The remaining patients who did not receive PAI therapy served as the control (n = 48). The patient survival and disease-free survival of the two groups were compared. The cumulative survival rates in the PAI group (90.3%, 71.3%, and 71.3% at 1, 2, and 3 years after hepatectomy, respectively) were significantly higher than those in the control (67.2, 41.7%, and 32.0%, respectively, p < 0.05). The disease-free survival rate in the PAI group (62.9%, 50.3%, and 26.8% at 1, 2, and 3 years after hepatectomy, respectively) was also significantly higher relative to the control (38.6%, 21.7%, and 12.1%, respectively, p < 0.01). Our data indicate that PAI can be efficacious in preventing postoperative recurrence of carcinoma and may lead to a prolonged survival of advanced HCC patients following hepatic resection.


Cardiovascular disease in postmenopausal women.
Cardiovascular disease is a major cause of death in both sexes. Women suffer almost as many myocardial infarctions as men, although they tend to occur at a greater age. Prevention programs for heart disease have impacted more positively on men than women and relatively young women aged 35-54 years may have fared worse. Hypertension is more prevalent amongst younger men than women, but above 65 years of age it becomes more common in women. Adequate treatment of hypertension has many rewards, but is only received by a minority of hypertensives. Heart failure, too, is a major burden of cardiovascular disease, particularly in older women. Approximately 30% of all cardiac surgery is performed on women, who have a worse short-term postoperative prognosis than men, although the two sexes fare equally in long-term survival. Hypertension, heart failure and diabetes have been identified as key preoperative factors determining a poorer prognosis for cardiac surgery amongst women. The renin-angiotensin-aldosterone system is thought to be central to the development of cardiovascular disease, with elevated levels of angiotensin II hypothesized as the factor which stimulates the formation of large insulin-resistant adipocytes, en route to diabetes. At the cellular level, estrogens have many effects on cardiovascular cells capable of being interpreted as beneficial in terms of cardiovascular disease. New studies demonstrate that approximately 5% of proteins produced by human myocardial cells are modulated by estrogens, estrogens receptors are modulated by age and disease, and estrogens modulate expression of receptors for endothelin-1, a neurohormone implicated in cardiovascular disease.


Alpha 2-adrenoceptor antisecretory responses in the rat jejunum.
1. Addition of noradrenaline (5 microM), UK-14,304 (0.1 microM) or phenylephrine (100 microM) to the serosal surface of sheets of rat jejunum mounted in Ussing type chambers decreased resting transepithelial short circuit current (SSC). These responses were inhibited by the selective alpha 2-adrenoceptor antagonist idazoxan (0.5-5.0 microM) but were not significantly affected by the alpha 1-adrenoceptor antagonist corynanthine (100 microM). 2. All three agonists caused a dose-related reduction of SSC which had been elevated by prior addition of theophylline (4 mM). UK-14,304 was 8.1 times more potent than noradrenaline and 76.2 times more potent than phenylephrine. Idazoxan (10 nM-1 microM) caused rightward, parallel displacements of the concentration-response curves for noradrenaline and UK-14,304; PA2 values were 7.87 and 8.02 respectively. Dose-response curves to noradrenaline were unaffected by prazosin (1 microM). 3. The reduction by noradrenaline (10 microM) of SCC which had been elevated by theophylline (4 mM) was not significantly affected by tetrodotoxin (5 microM), suggesting that noradrenaline reduces SCC in rat jejunum via a direct mucosal mechanism. 4. The resting SCC was markedly reduced in chloride-free PSS and under these conditions, noradrenaline did not elicit any further fall in SCC. In bicarbonate-free physiological salt solution (PSS) the resting SCC and the noradrenaline-induced fall in SCC were not significantly different from those in normal PSS. It is concluded that the decrease in SCC observed with noradrenaline, UK-14,304 and phenylephrine is mediated via stimulation of postjunctional alpha 2-adrenoceptors.


The influence of incubation pH on the activity of rat and human gut flora enzymes.
The activities of three bacterial biotransformation enzymes (beta-glucuronidase, beta-glucosidase, nitrate reductase) were determined in suspensions of rat caecal contents or human faeces over the pH range 6-8. All three enzymes were influenced by pH, as exemplified by beta-glucosidase activity which diminished as pH increased. In other instances the rat and human flora showed distinct profiles, with nitrate reductase activity undetectable in human faeces below pH 6.6, whereas the rat caecal flora displayed optimal reduction of nitrate around neutrality. The most pronounced host-species difference was found with beta-glucuronidase, which showed maximal activity at pH 6.0 in human faecal bacteria, while the rat caecal flora expressed greatest activity at pH 8.0. All three enzyme activities were associated with that fraction of rat caecal or human faecal material sedimented by centrifugation at 5000 g for 15 min, with little or no metabolism occurring in the 11,000 g supernatant fluid. The results demonstrate that pH has a pronounced effect on the enzymic activity of bacterial preparations from rat and human sources.


The dopamine D1 receptor agonist SKF 38393 suppresses detrusor hyperreflexia in the monkey with parkinsonism induced by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP).
A pharmacological study using monkeys, in which parkinsonism was induced by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), was undertaken to elucidate the mechanism underlying urinary bladder dysfunctions in Parkinson's disease. Under ketamine anesthesia, cystometrograms showed that, in MPTP-treated monkeys, a contraction of the urinary bladder was induced with smaller bladder volume than that in normal monkeys. In MPTP-treated monkeys, subcutaneously injected SKF 38393, a dopamine D1 receptor agonist, significantly increased the bladder volume and pressure thresholds for inducing the micturition reflex without affecting those in normal monkeys. In contrast, subcutaneous injections of quinpirole, a dopamine D2 receptor agonist, and apomorphine, a dopamine D1 and D2 receptor agonist, slightly, but significantly reduced the volume threshold of the bladder for the micturition reflex in both normal and MPTP-treated groups. These results indicate that, in parkinsonism, the degeneration of dopaminergic neurons in the substantia nigra leads to the detrusor hyperreflexia, probably due to a failure of activation of dopamine D1 receptors.


Thoracic mycoses from opportunistic fungi: radiologic-pathologic correlation.
Fungi of the genera Aspergillus, Candida, and Cryptococcus and the class Zygomycetes are the most common causes of thoracic opportunistic mycoses in immunocompromised patients. Candidiasis and zygomycosis usually manifest as severe, often life-threatening, pneumonias. Aspergillus species are commonly implicated as the causative organisms in a broad spectrum of pulmonary disorders, ranging from hypersensitivity lung disease in atopic patients to invasive pneumonia in immunocompromised patients. Cryptococcus neoformans infects both immunologically normal and abnormal patients, with variable clinical and radiologic findings. The diagnosis of an opportunistic mycosis requires familiarity with the epidemiology of the disease, the various modes of clinical presentation, and the full spectrum of radiologic manifestations. Because many of these fungi may normally colonize in the upper respiratory tract, sputum cultures are considered diagnostically unreliable. Instead, definitive diagnosis hinges on either culture of the fungus from infected tissue or demonstration of the organism at microscopic examination.


Functional interactions within the newborn brain investigated by adaptive coherence analysis of EEG.
To assess functional cortical organization in newborns during quiet sleep we investigated instantaneous interhemispheric coherences in six healthy full-term subjects using linked ear reference and average reference. Tracé alternant was the most frequent EEG pattern during quiet sleep of these newborns and consists of burst and interburst periods. The calculation of coherence was performed by means of time-variant autoregressive models on the basis of Kalman filtering. Coherence changes simultaneously with the appearance of these burst and interburst periods. The highest level of coherence was observed during burst periods in comparison with interburst periods. The lowest level of coherence was observed just before the burst started. During burst, maximal coherence was reached at different moments--late in the low frequency band (0.5-1.5 Hz; about 3 s after the burst started) and earlier in higher frequency bands (> 2 Hz, about 2 s). Interhemispheric coherence depended on the region being investigated. A significant level of coherence could be observed over frontal, temporal and occipital regions. Our data demonstrate significant modification of interhemispheric coherence during quiet sleep of full-term newborns and, irrespective of the immaturity of the brain, these coherences differ significantly between cortical regions.


Exotic plant invasions under enhanced rainfall are constrained by soil nutrients and competition.
To predict the net impact of climate change on invasions, it is critical to understand how its effects interact with environmental and biotic context. In a factorial field experiment, we examined how increased late-season rainfall influences the growth and reproductive success of two widespread invasive species (Centaurea solstitialis and Aegilops triuncialis) in heterogeneous Californian grasslands, and, in particular, how its impact depends on habitat type, nutrient addition, and competition with resident species. Rainfall enhancement alone exhibited only weak effects, especially in naturally infertile and relatively uninvaded grasslands. In contrast, watering and fertilization together exhibited highly synergistic effects on both invasive species. However, the benefits of the combined treatment were greatly reduced or offset by the presence of surrounding competitors. Our results highlight the roles of nutrient limitation and biotic resistance by resident competitors in constraining the responses of invasive species to changes in rainfall. In systems with strong environmental control by precipitation, enhanced rainfall may promote invasions mainly under nutrient-rich and disturbed conditions, while having lesser effects on nutrient-poor, native "refuges".


What do families want from well-child care? Including parents in the rethinking discussion.
The content and systems surrounding well-child care have received increasing attention, and some propose that it is time to rethink both the delivery structure and central themes of well-child visits. A key, but largely missing perspective in these discussions has been that of parents, whose experiences and expectations are central to developing approaches responsive to family needs. In this study, we asked parents to address several core issues: why they attend well-child visits; aspects of well-child care that they find most valuable; and changes that could enhance the well-child care experience. Twenty focus groups with parents (n = 131 [91% mothers]) were conducted by using a semistructured interview guide. Verbatim transcripts were coded for key words, concepts, and recurrent themes. Primary reasons for visit attendance included reassurance (child and parent) and an opportunity to discuss parent priorities. Families valued an ongoing relationship with 1 clinician who was child-focused and respected parental expertise, but continuity of provider was not an option for all participants. Suggestions for enhancement included improved promotion of well-child care, greater emphasis on development and behavior, and expanded options for information exchange. As the consumers of care, it is critical to understand parents' needs and desires as changes to the content and process of well-child care are considered. Taking into account the multifaceted perspectives of families suggests both challenges and opportunities for the rethinking discussion.


Phase Separation and the Centrosome: A Fait Accompli?
There is currently intense interest in the idea that many membraneless organelles might assemble through phase separation of their constituent molecules into biomolecular 'condensates' that have liquid-like properties. This idea is intuitively appealing, especially for complex organelles such as centrosomes, where a liquid-like structure would allow the many constituent molecules to diffuse and interact with one another efficiently. I discuss here recent studies that either support the concept of a liquid-like centrosome or suggest that centrosomes are assembled upon a more solid, stable scaffold. I suggest that it may be difficult to distinguish between these possibilities. I argue that the concept of biomolecular condensates is an important advance in cell biology, with potentially wide-ranging implications, but it seems premature to conclude that centrosomes, and perhaps other membraneless organelles, are necessarily best described as liquid-like phase-separated condensates.


Predictive and prognostic effect of inflammatory lymphadenopathies in renal cell carcinoma.
A significant proportion of patients affected by renal cell carcinoma (RCC) shows a suspicious lymph node involvement (LNI) at preoperative imaging. We sought to evaluate the effect of lymphadenopathies (cN1) on survival in surgical RCC patients with no evidence of LNI at final pathology (pN0). 719 patients underwent either radical or partial nephrectomy and lymph node dissection at a single tertiary care referral centre between 1987 and 2015. All patients had pathologically no LNI (pN0). Outcomes of the study were cancer-specific mortality (CSM) and other-cause mortality. Multivariable competing-risks regression models assessed the impact of inflammatory lymphadenopathies (cN1pN0) on mortality rates, after adjustment for clinical and pathological confounders. 114 (16%) and 605 (84%) patients (16%) were cN1pN0 and cN0pN0, respectively. cN1pN0 patients were more frequently diagnosed with larger tumours (8.4 vs. 6.5 cm), higher pathological tumour stage (pT3-4 in 71 vs. 36%), higher Fuhrman grade (G3-G4 in 64 vs. 31%), more frequently with necrosis (75 vs. 44%), and distant metastases (33 vs. 10%) (all p < 0.0001). At univariable analysis, inflammatory lymphadenopathies resulted associated with worse CSM (HR 2.45; p < 0.0001). However, at multivariable analysis, inflammatory lymphadenopathies were not an independent predictor of CSM (HR 0.81; p = 0.4). The presence of metastases at diagnosis was the most important factor affecting CSM (HR 6.54; p < 0.0001). This study is limited by its retrospective nature. In RCC patients, inflammatory lymphadenopathies (cN1pN0) are associated with unfavourable clinical and pathological characteristics. However, the presence of inflammatory lymphadenopathies does not affect RCC-specific mortality.


Neonatal listeriosis.
In Western developed countries, Listeria monocytogenesis not an uncommon pathogen in neonates. However, neonatal listeriosis has rarely been reported in Taiwan. We describe two cases collected from a single medical institute between 1990 and 2005. Case 1 was a male premature baby weighing 1558 g with a gestational age of 31 weeks whose mother had fever with chills 3 days prior to delivery. Generalized maculopapular rash was found after delivery and subtle seizure developed. Both blood and cerebrospinal fluid culture collected on the 1st day yielded L. monocytogenes. In addition, he had ventriculitis complicated with hydrocephalus. Neurologic development was normal over 1 year of follow-up after ventriculoperitoneal shunt operation. Case 2 was a 28-weeks' gestation male premature baby weighing 1180 g. Endotracheal intubation and ventilator support were provided after delivery due to respiratory distress. Blood culture yielded L. monocytogenes. Cerebrospinal fluid showed pleocytosis but the culture was negative. Brain ultrasonography showed ventriculitis. Sudden deterioration with cyanosis and bradycardia developed on the 8th day and he died on the same day. Neonatal listeriosis is uncommon in Taiwan, but has significant mortality and morbidity. Early diagnosis of perinatal infection relies on high index of suspicion in perinatal health care professionals.


[Adjuvanticity of vitamin A in advanced irradiated cervical cancer (author's transl)].
For treatment of patients with inoperable cervical cancer (FIGO III) a randomized trial has been initiated. Patients were randomized to receive either conventional irradiation therapy together with vitamin A palmitate (1.5 mill. IU/day; total dose 30 mill. IU), applied orally, or irradiation alone. 42 patients have been included in this study. Patients were monitored by several immunological tests. Delayed cutaneous hypersensitivity reaction to a battery of recall antigens did not reveal any changes, neither within nor between the treatment groups. A challenge reaction to DNCB could be evoked after treatment in 50% of the patients in both treatment groups. No significant changes of immunoglobulin levels have been observed after termination of therapy in each treatment group. When lymphocyte reactivity to PHA (maximum response during therapy) was compared within the groups, it was found, that 66% of the patients who received an irradiation combined with vitamin A palmitate, showed an increase in their blastogenic response, while in irradiated patients without vitamin A palmitate a response was only in 33%. This difference being statistically significant in comparison to pretreatment values. From immunological data it can be concluded that vitamin A has an effect on functional response of T-cells. Concerning the clinical outcome, after an observation period of 12 months relapse rates were lower in the vitamin A group, but not significantly reduced. Therefore further follow up is warranted.


Hypochondriasis and obsessive-compulsive disorder in schizophrenic patients treated with clozapine vs other atypical antipsychotics.
The aim of the study was to investigate the prevalence rates of obsessive-compulsive disorder (OCD) and hypochondriasis in schizophrenic patients treated with atypical antipsychotics (AAPs) and to investigate the different comorbidity rates of OCD and hypochondriasis between clozapine-treated patients and patients treated with other AAPs. We therefore recruited 60 schizophrenic patients treated with clozapine or other AAPs. We assessed the prevalence rates of OCD or OC symptoms and hypochondriasis or hypochondriac symptoms in the whole group of patients and in clozapine-treated patients versus patients treated with other AAPs. Schizophrenic patients had a higher comorbidity rate of OCD (26.6% vs 1-3%) and hypochondriasis (20% vs 1%) than the general population. These comorbidities were more frequent in schizophrenic patients treated with clozapine versus patients treated with other AAPs (36.7% vs 16.7% and 33.3% vs 6.7%). Clozapine-treated patients showed a higher mean Y-BOCS and HY-BOCS score when compared to patients treated with other AAPs (10.90 vs 5.90, p = .099; 15.40 vs 8.93, p = .166). A statistical significant correlation was found between the Y-BOCS and HY-BOCS scores of the whole group (r = .378, p = 0.03). Furthermore, we found an inverse correlation between the global level of functioning and the diagnosis of hypochondriasis (p = .048) and the severity of hypochondriac symptoms (p = .047). Hypochondriasis could represent an important clinical feature of schizophrenic patients treated with atypical antipsychotics, and further research is needed in this field.


Treatment of childhood renal cell carcinoma with lymph node metastasis: two cases and a review of literature.
Standard treatment for renal cell carcinoma (RCC) is radical nephrectomy with lymph node dissection. Stages I and II have encouraging prognoses, but Stage III with regional lymph node metastasis can be unfavorable. Adjuvant therapy for pediatric patients with advanced RCC with lymph node involvement or metastatic lesion has not been defined. Advanced pediatric RCC is reported in two patients (boys, aged 6 and 9 years: Stage IIIs, Robson; Stage III and IV, pTNM classification) treated by nephrectomy and lymph node dissection followed by postoperative interferon-alpha (IFN), that can be used as an adjuvant therapy with side effects such as fever, bone marrow suppression, or decreased liver function. One is doing well for 7 years, another is suffered from lung metastases at 3 years after surgery. Although immunotherapy is expected to improve survival in pediatric patients with advanced RCC, surgical resection of renal and metastatic tumors remains the standard treatment.


Prenatal oxazepam effects on cocaine conditioned place preference in developing mice.
The positively reinforcing and activity enhancing effects of IP cocaine (0, 5, or 25 mg/kg) were assessed at three ages (14-17, 21-24, and 28-31 days) in outbred CD-1 mouse pups treated prenatally by either oxazepam (OX, 15 mg/kg PO twice/day on days 12-16 of pregnancy) or vehicle (VEH). A 4-day unbiased conditioned place preference (CPP) procedure was used with combined visual and tactile cues (white walls and wide-mesh metal floor versus black walls and narrow-mesh floor). A single 25 mg/kg cocaine dose produced CPP in both prenatal groups of 28-31 day-old mice. At the two younger ages, a significant cocaine CPP was found in prenatal OX mice but not in vehicle animals; the latter apparently developed CPP less readily than the offspring of indisturbed dams in a previous experiment. On the other hand, prenatal OX did not produce substantial changes in the developmental profile of cocaine effects on locomotor activity, consisting of a dose-related response enhancement which is much more marked at 22 and 29 days than before weaning.


Flexible construction of hierarchical scale-free networks with general exponent.
Extensive studies have been done to understand the principles behind architectures of real networks. Recently, evidence for hierarchical organization in many real networks has also been reported. Here, we present a hierarchical model that reproduces the main experimental properties observed in real networks: scale-free of degree distribution P (k) [frequency of the nodes that are connected to k other nodes decays as a power law P (k) approximately k(-gamma) ] and power-law scaling of the clustering coefficient C (k) approximately k(-1) . The major points of our model can be summarized as follows. (a) The model generates networks with scale-free distribution for the degree of nodes with general exponent gamma>2 , and arbitrarily close to any specified value, being able to reproduce most of the observed hierarchical scale-free topologies. In contrast, previous models cannot obtain values of gamma>2.58 . (b) Our model has structural flexibility because (i) it can incorporate various types of basic building blocks (e.g., triangles, tetrahedrons, and, in general, fully connected clusters of n nodes) and (ii) it allows a large variety of configurations (i.e., the model can use more than n-1 copies of basic blocks of n nodes). The structural features of our proposed model might lead to a better understanding of architectures of biological and nonbiological networks.


Antianalgesic action of dynorphin A mediated by spinal cholecystokinin.
Previous work indicates that the antianalgesic action of pentobarbital and neurotensin administered intracerebroventricularly in mice arises from activation of a descending system to release cholecystokinin (CCK) in the spinal cord where CCK is known to antagonize morphine analgesia. Spinal dynorphin, like CCK, has an antianalgesic action against intrathecally administered morphine. This dynorphin action is indirect; even though it is initiated in the spinal cord, it requires the involvement of an ascending pathway to the brain and a descending pathway to the spinal cord where an antianalgesic mediator works. The aim of the present investigation was to determine if the antianalgesic action of intrathecal dynorphin A involved spinal CCK. All drugs were administered intrathecally to mice in the tail flick test. Morphine analgesia was inhibited by dynorphin as shown by a rightward shift of the morphine dose-response curve. The effect of dynorphin was eliminated by administration of the CCK receptor antagonists lorglumide and PD135 158. One hour pretreatment with CCK antiserum also eliminated the action of dynorphin. On the other hand, the antianalgesic action of CCK was not affected by dynorphin antiserum. Thus, CCK did not release dynorphin. Both CCK and dynorphin were antianalgesic against DSLET but not DPDPE, delta 2 and delta 1 opioid receptor peptide agonists, respectively. The results suggest that the antianalgesic action of dynorphin occurred through an indirect mechanism ultimately dependent on the action of spinal CCK.


Effects of oxygen supply on electrical and secretory responses of humorally stimulated acinar cells in isolated rat pancreas.
A technique is described for perfusing isolated rat pancreas with a modified Krebs-Henseleit solution. This preparation made feasible the simultaneous measurement of transmembrane potential, effective membrane resistance, rate of flow of pancreatic juice and amylase output. The hyperpolarizing effect of cholecystokinin-pancreozymin (CCK-PZ) was confirmed by perfusion with a solution containing 5 mU CCK-PZ/ml. The hyperpolarizing efffect of CCK-PZ was enhanced when the pancreas was perfused with an oxygenated solution containing dog erythrocytes. This effect was inhibited by ouabain and anaerobic conditions. It is suggested that the oxidative metabolism supplies energy for a mechanism which is responsible for the hyperpolarizing effect of CCK-PZ. The amylase output and the rate of flow of pancreatic juice were enhanced concurrently under conditions that augumented the hyperpolarizing effect, and they were inhibited under conditions that suppressed the effect. Cellular events in stimulus-secretion coupling in the pancreatic acinar cell are discussed by correlating the electrophysiological responses and the secretory responses under various conditions.


Effects of aerobic exercise conditioning at intensities corresponding to lactate threshold in the elderly.
In this study we attempted to determine the effects of exercise training at the intensity corresponding to lactate threshold (Thla-) on various health-related variables in sedentary but apparently healthy elderly subjects. Six men and five women volunteers [mean age 68.9 (SD 3.4) years] performed supervised endurance-type training on stationary cycle ergometers for 30 min and recreational activities for 30 min, 3 days a week for 12 weeks. Four men and four women served as the control group [68.8 (SD 4.4) years]. As a result of the training programme, statistically significant increases in maximal oxygen consumption (10%), oxygen consumption at Thla- (18%), distance covered in 12-min walk, side step, and leg extensor power were found in the training group, while no changes occurred in the control group. The changes in serum cholesterol and triglyceride concentrations from the pre- to post-training period were statistically significant. High-density lipoprotein cholesterol remained unchanged, and low-density lipoprotein cholesterol tended to decrease following the training programme. These data would indicate that exercise training at the intensity corresponding to Thla- may have favourable effects on overall physical fitness and some serum lipid variables in older individuals.


Adapting to psychiatric disability and needs for home- and community-based care.
The objective of the study was to describe adaptation strategies and use of formal and informal support by individuals with psychiatric disabilities, to delineate remaining needs, and to determine how home- and community-based services might address those needs. Using in-depth interviews and structured questionnaires, we examined functional status, adaptation, and needs for home- and community-based care among 33 severely mentally ill members of a large health maintenance organization. Despite success in community living, participants had significant functional deficits (physical and emotional), relied heavily on only one or two key informal caregivers, and often needed significant support from mental health professionals. Limited numbers of caregivers and social isolation placed participants at risk of negative outcomes if informal support resources were to be lost. Home- and community-based care interventions that attempt to increase informal support networks and provide instrumental help (cooking, cleaning, transport) on short notice during flare-ups could augment existing (but limited) informal caregiving, help severely mentally ill individuals remain independent, and reduce the likelihood that loss of an informal caregiver would result in unwanted outcomes.


[Human papillomavirus and cervical cancer].
Human papillomaviruses (HPVs) are double stranded DNA viruses. To date, over 100 genotypes have been identified. Oncogenic types of HPV, including types 16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, 59 and 68, are commonly associated with cervical cancer, with HPV16 being the most frequently detected genotype in women with cervical cancer worldwide. Genital HPV infections are common among young sexually active women and usually transient. Only a small fraction of infected women develop cervical cancer, implying the involvement of environmental and genetic cofactors in cervical carcinogenesis. The epidemiology of HPV infections and current advances on HPV vaccines will be reviewed here.


Reduced E-cadherin and alpha-catenin expressions have no prognostic role in bladder carcinoma.
In various human cancers, dysfunction of the E-cadherin-catenin complex is associated with a decrease in cellular and tissue differentiation, and with higher invasive and metastatic potentials. The objective of this study was to investigate E-cadherin and alpha-catenin expression in superficial noninvasive papillary TCC and invasive TCC, and correlate these results with pathological and clinical parameters. We have used immunohistochemistry to localize Ecadherin and alpha-catenin in 56 formalin-fixed, paraffin-embedded tissue blocks from 41 patients with superficial bladder cancer and 15 with invasive bladder cancer. The 46 male and 10 female patients had a mean age of 67 years, with range of 40 to 82 years. The mean follow-up time was 33.4 (range 5-120) months. Tumor grade 1:2:3 ratios were 5:32:19. In superficial bladder tumor, abnormal expression of E-cadherin and alpha-catenin was demonstrated in 37 and 71% of the tumors, respectively. In advanced bladder tumor, abnormal expression of E-cadherin and alpha-catenin was demonstrated in 80 and 100% of the tumors, respectively. Differences in expression of E-cadherin and alpha-catenin could be discerned between superficial and advanced bladder tumors (p=0.004, p=0.024, respectively). However, the association between E-cadherin and alpha-catenin expression and tumor grade was not statistically significant (p>0.05). In addition, the expression of E-cadherin and alpha-catenin did not correlate with tumor number and size (p>0.05). We have demonstrated that abnormal expression of E-cadherin and/or alpha-catenin occurs in more than 85% of bladder carcinomas and correlates significantly only with advanced stage. Nevertheless, these observations need to be confirmed in larger prospective clinical studies.


Auto-PEEP: how to detect and how to prevent--a review.
Auto-positive end expiratory pressure (auto-PEEP) is a physiologic event that is common to mechanically ventilated patients. Auto-PEEP is commonly found in acute severe asthma, chronic obstructive pulmonary disease, or patients receiving inverse ratio ventilation. Factors predisposing to auto-PEEP include a reduction in expiratory time by increasing the respiratory rate, tidal volume or inspiratory time. Auto-PEEP predisposes the patient to increased work of breathing, barotrauma, hemodynamic instability and difficulty in triggering the ventilator. Failure to recognize the hemodynamic consequences of auto-PEEP may lead to inappropriate fluid restriction or unnecessary vasopressor therapy. Auto-PEEP can potentially interfere with weaning from mechanical ventilation. Many methods have been described to measure the Auto-PEEP. Although not apparent during normal ventilator operation, the auto-PEEP effect can be detected and quantified by a simple bedside maneuver: expiratory port occlusion at the end of the set exhalation period. The measurement of static and dynamic auto-PEEP differs and depends upon the heterogeneity of the airways. The work of breathing can be decreased by providing external PEEP to 75-80% of auto-PEEP in patients who are spontaneously breathing during mechanical ventilation but there is no evidence such external PEEP would be useful during controlled mechanical ventilation when there is no patient inspiratory effort. Ventilator setting should aim for a prolonged expiratory time by reducing the respiratory rate rather than increasing inspiratory flow. Routine monitoring for auto-PEEP in patients receiving controlled ventilation is recommended.


A significant linear association exists between nuchal translucency thickness and adverse perinatal outcome in euploid fetuses.
Evaluating the correlation between the nuchal translucency (NT) measurement throughout its range of values independent of gestational age, and adverse pregnancy outcome: in euploid structurally normal fetuses. A prospective observational study was conducted in which NT measurements were made in consecutive singleton euploid fetuses derived from an unselected pregnant population. Pregnancies terminated before the 22nd gestational week, and those with major malformations (diagnosed before or after delivery) were excluded from the analysis. We evaluated the linear association between NT thickness and selected obstetric outcomes. A total of 2205 euploid singleton fetuses were evaluated during the study period. Significant linear-by-linear association was documented between the NT measurement and perinatal mortality (p < 0.001). Thicker NT was significantly associated with diabetes (either gestational or pre-gestational) (p = 0.013). A linear association exists between NT thickness in chromosomally and structurally normal fetuses, and the risk for gestational diabetes and perinatal mortality.


Prevalence of Neuropathic Pain in Patients with Traumatic Brachial Plexus Injury: A Multicenter Prospective Hospital-Based Study.
Prevalence and clinical characteristics of neuropathic pain due to traumatic brachial plexus injury. Observational epidemiological study. Hospital-based multicenter study. One hundred seven prospectively enrolled patients with brachial plexus injury. All the patients underwent clinical examination and neurophysiological testing for a definitive diagnosis of the brachial plexus lesion. The DN4 questionnaire was used to identify neuropathic pain, and the Neuropathic Pain Symptom Inventory (NPSI) to evaluate the different symptoms of neuropathic pain. The SF36 questionnaire and the Beck Depression Inventory (BDI) were used to assess quality of life and mood disturbances in patients with neuropathic pain. Of the 107 enrolled patients, 74 had pain (69%); neuropathic pain, as assessed by means of the DN4, was identified in 60 (56%) of these patients. According to the NPSI, the most frequent and severe pain type was the spontaneous burning pain. Clinical and neurophysiological findings showed that pain is unrelated to age but is associated with the severity of peripheral nerve damage. The SF36 questionnaire and BDI showed that neuropathic pain impairs quality of life and causes depression. Our study provides information on the prevalence, characteristics, and variables associated with neuropathic pain due to traumatic brachial plexus injuries that might provide a basis for improving the clinical management of this condition.


Comparison of early renal dysfunction in type I and type II diabetes: differing associations with blood pressure and glycaemic control.
This study has investigated the relationship of glycaemic control, blood pressure and proteinuria to early renal dysfunction in a cohort of 50 type I and 65 type II diabetics, with renal function ranging from normal to mildly impaired (serum creatinine less than 0.2 mM). Repeated measurements were made over a mean interval of 7 years and mean data from each subject were analysed by stepwise multiple linear regression. This enabled associations to be determined independently of the confounding influence of age and duration of disease. In type I diabetics, mean creatinine clearance was inversely related to systolic blood pressure (P less than 0.001), glycosylated haemoglobin (P less than 0.05), fasting plasma glucose (P less than 0.05) and to the renal clearance of albumin (P less than 0.001), transferrin (P less than 0.01) and IgG (P less than 0.05). By contrast, in type II diabetics, none of these associations were significant. No significant relationships were found with the rate of decline of creatinine clearance in either type of diabetic. Further studies will be needed to determine whether the changes in blood pressure and glycaemic control precede or follow the development of renal disease. However, these findings raise the possibility of a difference in the pathogenesis of renal disease in type I and type II diabetes.


Collective behaviour, uncertainty and environmental change.
A central aspect of cultural evolutionary theory concerns how human groups respond to environmental change. Although we are painting with a broad brush, it is fair to say that prior to the twenty-first century, adaptation often happened gradually over multiple human generations, through a combination of individual and social learning, cumulative cultural evolution and demographic shifts. The result was a generally resilient and sustainable population. In the twenty-first century, however, considerable change happens within small portions of a human generation, on a vastly larger range of geographical and population scales and involving a greater degree of horizontal learning. As a way of gauging the complexity of societal response to environmental change in a globalized future, we discuss several theoretical tools for understanding how human groups adapt to uncertainty. We use our analysis to estimate the limits of predictability of future societal change, in the belief that knowing when to hedge bets is better than relying on a false sense of predictability.


Fibromuscular dysplasia of cervico-cephalic arteries with multiple dissections and a carotid-cavernous fistula. A pathological study.
A rare case of widespread fibromuscular dysplasia (F.M.D.) is reported, involving the cervico-cephalic arteries associated with multiple dissections, saccular aneurysms and a carotid-cavernous fistula. A detailed post-mortem examination revealed FMD involvement of the intracranial vessels, not demonstrated by arteriography.


The peculiar spectrum of beta-thalassemia genes in Tunisia.
We have determined the spectrum of mutations producing beta-thalassemia (beta-thal) in Tunisia by direct DNA analysis using hybridization with allele-specific oligonucleotide probes and restriction endonuclease assay. In all, 34 unrelated beta-thal patients originating from different parts of the country were available for study. The beta-globin gene cluster of each was subjected to haplotype analysis, and on the basis of this analysis, we tested each patient's DNA for one or more mutations previously shown to be linked to that haplotype. We identified four previously unreported haplotypes and found that this population differs from others in Mediterranean areas in the frequency of the beta-thal haplotypes, the unexpected observation being the high frequency of haplotype IX. Six different point mutations were found, accounting for 62% of beta-thal genes in this Tunisian population. The molecular defects known to be the most frequent in Mediterraneans (nonsense codon 39, IVS1 nt 110, IVS1 nt 6) only make up 37% of the mutant genes. One as yet undescribed mutation (IVS1 nt 2 T----G) was identified by molecular cloning and sequencing. Our results should help the implementation of a prenatal diagnosis program for beta-thal in Tunisia.


Genetic susceptibility to total hip arthroplasty failure--positive association with mannose-binding lectin.
Mannose-binding lectin (MBL) may be involved in the biologic cascade of events initiated by wear debris and bacterial infection around loosened total hip arthroplasties (THAs). Individual responses to such stimuli may be dictated by genetic variation caused by single nucleotide polymorphisms (SNPs). We performed a case-control study on 4 MBL SNPs using case patients (n = 91) with aseptic loosening or deep infection (n = 71). Control subjects (n = 150) had clinically and radiologically well-fixed THAs for more than 10 years. Frequency of the C allele (P = .001) and that of the genotype C/C (P = .004) for the -550 SNP were associated with aseptic failure. The codon 54 SNP G allele (P = .012) and G/G genotype (P = .027) frequencies were associated with aseptic failure as well. In the septic group, the frequency of the C allele (P = .01) and that of the genotype C/C (P = .05) for the -550 SNP were significant. Failure of THAs may be under genetic influence to candidate susceptibility genes such as MBL.


Orthodeoxia and platypnoea after acute organophosphorus poisoning reversed by CPAP: a newly described cause and review of the literature.
The case of a 60-year-old male patient, who survived severe organophosphorus poisoning, and subsequently developed platypnoea and orthodeoxia is described. The patient was mechanically ventilated for a long period of time in the intensive care unit. During the weaning trial, he developed platypnoea and orthodeoxia (PaO2 85 mmHg in recumbency, and 40 mmHg in upright position). Interestingly, the patient's orthodeoxia was alleviated on continuous positive airway pressure (CPAP) treatment. This is a newly described cause of the platypnoea-orthodeoxia syndrome. The possible pathophysiological mechanisms are discussed and a review of the reported abnormal states associated with this condition is presented.


Lipoprotein heterogeneity and its effect on apolipoprotein assays.
A number of techniques have been proposed for separating lipoproteins according to their physicochemical properties. However, more recent evidence has pointed out that the physicochemically defined lipoproteins such as VLDL, IDL, LDL or HDL are both chemically and metabolically heterogeneous. According to Alaupovic concept, the plasma lipoprotein system consists of a mixture of particles, each of which is characterized by unique apolipoprotein composition. Using enzyme linked differential antibody immunosorbent assay and differential electroimmunoassay, we have discovered that the determination of lipoprotein particle profiles is essential for further clarification of the diagnostic value of measuring apo B and apo A-I. The metabolism of apo B and apo A-I containing lipoprotein particles seems to be affected primarily by their corresponding apolipoprotein composition. Some particular subpopulations of apo B containing lipoprotein particles, such as LpB containing only apo B, LpB:E containing apo B and (a), have been identified as important risk factors for atherosclerosis. We have also recently demonstrated that the protective effect of HDL is due to particles containing apo A-I but not apo A-II (LpA-I), while those containing apo A-I and apo A-II (LpA-I:A-II) have little or no effect. Dyslipoproteinemias are characterized by distinct profiles of apo B containing particles. Abnormalities in apo A-I containing particles distribution are related to the family history of coronary artery disease in young children and could explain differences in age standardized mortality from ischaemic heart diseases in different populations. Moreover hypolipidemic drugs seem to affect discrete apo B and apo A-I particles in a specific manner.


Maternal exposure to delta9-tetrahydrocannabinol facilitates morphine self-administration behavior and changes regional binding to central mu opioid receptors in adult offspring female rats.
Opiates and cannabinoids are among the most widely consumed habit-forming drugs in humans. Several studies have demonstrated the existence of interactions between both kind of drugs in a variety of effects and experimental models. The present study has been focused to determine whether perinatal delta9-tetrahydrocannabinol (Delta9-THC) exposure affects the susceptibility to reinforcing effects of morphine in adulthood and whether these potential changes were accompanied by variations in mu opioid receptor binding in brain regions related to drug reinforcement. Adult female rats born from mothers that were daily treated with delta9-THC during gestation and lactation periods, exhibited a statistically significant increase in the rate of acquisition of intravenous morphine self-administration behavior when compared with females born from vehicle-exposed mothers, an effect that did not exist in delta9-THC-exposed male offspring. This increase was significantly greater on the last day of acquisition period. There were not significant differences when the subjects were lever pressing for food. In parallel, we have also examined the density of mu opioid receptors in the brain of adult male and female offspring that were exposed to Delta9-THC during the perinatal period. Collectively, perinatal exposure to delta9-THC produced changes in mu opioid receptor binding that differed regionally and that were mostly different as a function of sex. Thus, delta9-THC-exposed males exhibited a lower density for these receptors than their respective oil-exposed controls in the caudate-putamen area as well as in the amygdala (posteromedial cortical nucleus). On the contrary, delta9-THC-exposed females exhibited higher density of these receptors than their respective oil-exposed controls in the prefrontal cortex, the hippocampus (CA3 area), the amygdala (posteromedial cortical nucleus), the ventral tegmental area and the periaqueductal grey matter, whereas the binding was lower than control females only in the lateral amygdala. These results support the notion that perinatal delta9-THC exposure alters the susceptibility to morphine reinforcing effects in adult female offspring, in parallel with changes in mu opioid receptor binding in several brain regions.


[Radiation therapy for heterotopic ossification prophylaxis].
Heterotopic ossification (HO) is a well-known condition of bone formation in soft tissues due to trauma (e.g. surgery) or neurological injury, but the exact aetiology is unknown. In most cases, HO is asymptomatic, but it may cause pain, reduced mobility of joints, and loss of functioning. Various patient groups have a significant risk of developing HO after surgery and should be offered prophylactic treatment. Nonsteroidal anti-inflammatory drugs and radiotherapy are internationally accepted treatments. This review discusses the potential for radiotherapy as prophylaxis against HO.


A psychosocial analysis of women planning birth outside hospital.
Most of the women requesting out-of-hospital delivery considered delivery a natural process, not an illness requiring hospital care. The women cited freedom of choice concerning the delivery, less anxiety in the home than in the hospital environment, a more personal relationship with the midwife, and, as far as possible, making do without medical equipment. The interviewed women were a selected collective regarding age, parity, socioeconomic status and obstetric risk profile. Nonetheless, the results suggest ways that in-hospital obstetrics can be adapted to meet the requirements of pregnant women. Individualized, family-oriented obstetrics with judicious use of medical technology should be possible in the clinical setting.


Multiparametric tumor marker (CA 19-9, CEA, AFP, POA) analyses of pancreatic juices and sera in pancreatic diseases.
With respect to their diagnostic utility CA 19-9, CEA, AFP and POA were determined in pancreatic secretions and serum of patients suffering from pancreatic cancer (n = 76/55) or chronic pancreatitis (n = 79/45) and of controls (n = 81/42), respectively. While the determination of AFP and POA both in pancreatic secretions and serum does not permit a differential diagnosis, serum CEA (greater than 10 ng/ml) and CA 19-9 (greater than 50 U/ml) levels were indicative of pancreatic cancer in 30% and 83%, respectively, with a rate of false positive results of 5% and 8.5% confined to the chronic pancreatitis patients. A combination of tumor marker analyses, that is, serum CA 19-9 (greater than 50 U/ml) and pancreatic secretion CEA (greater than 70 ng/ml), proved to be positive in 92.9% of tumor patients with a maximum of 10.5% false positives. Likewise, values of serum CA 19-9 (greater than 50 U/ml) and serum CEA (greater than 10 ng/ml) were found in 85.8% of the pancreatic cancer patients with only 8.8% false positives, which were confined to the chronic pancreatitis patients. These results indicate the superiority of multiparametric tumor marker analyses for the diagnosis of pancreatic cancer, especially when including new monoclonal antibody defined tumor markers.


Regulation of 1 alpha, 25-dihydroxyvitamin D3 synthesis in macrophages from arthritic joints by phorbol ester, dibutyryl-cAMP and calcium ionophore (A23187).
Phorbol 12-myristate 13-acetate (100 nM), a potent protein kinase C and macrophage activator, has a biphasic affect on 25(OH)D3-1 alpha-hydroxylase activity in synovial fluid macrophages from arthritis patients. After 5 h, 1 alpha, 25(OH)D3 synthesis fell from 5.2 +/- 0.1 to 1.6 +/- 0.2 pmol/h per 10(6) cells, however, after 24 h and 48 h, synthesis increased to 17.4 +/- 0.3 and 22.3 +/- 1.4 pmol/h per 10(6) cells, respectively. Although an independent short-term mechanism is suggested, protein kinase C may promote macrophage activation, thus increasing long-term 25(OH)D3-1 alpha-hydroxylase expression. Intracellular calcium and cAMP are unlikely to activate the enzyme, since 0.1 microM of the calcium ionophore, A23187, and 1 mM dibutyryl-cAMP inhibited synthesis by 87% and 79%, respectively, after 24 h.


Paclitaxel-resistant cells have a mutation in the paclitaxel-binding region of beta-tubulin (Asp26Glu) and less stable microtubules.
Resistance to paclitaxel-based therapy is frequently encountered in the clinic. The mechanisms of intrinsic or acquired paclitaxel resistance are not well understood. We sought to characterize the resistance mechanisms that develop upon chronic exposure of a cancer cell line to paclitaxel in the presence of the P-glycoprotein reversal agent, CL-347099. The epidermoid tumor line KB-3-1 was exposed to increasing concentrations of paclitaxel and 5 micromol/L CL-347099 for up to 1 year. Cells grown in 15 nmol/L paclitaxel plus CL-347099 (KB-15-PTX/099) developed 18-fold resistance to paclitaxel and were dependent upon paclitaxel for maximal growth. They grew well and retained resistance to paclitaxel when grown in athymic mice. Cross-resistance (3- to 5-fold) was observed in tissue culture to docetaxel, the novel taxane MAC-321, and epothilone B. Collateral sensitivity (approximately 3-fold) was observed to the depolymerizing agents vinblastine, dolastatin-10, and HTI-286. KB-15-PTX/099-resistant cells did not overexpress P-glycoprotein nor did they have an alteration of [14C]paclitaxel accumulation compared with parental cells. However, a novel point mutation (T to A) resulting in Asp26 to glutamate substitution in class I (M40) beta-tubulin was found. Based on an electron crystallography structure of Zn-stabilized tubulin sheets, the phenyl ring of C-3' NHCO-C6H5 of paclitaxel makes contact with Asp26 of beta-tubulin, suggesting a ligand-induced mutation. Optimized model complexes of paclitaxel, docetaxel, and MAC-321 in beta-tubulin show a novel hydrogen bonding pattern for the glutamate mutant and rationalize the observed resistance profiles. However, a mutation in the paclitaxel binding pocket does not explain the phenotype completely. KB-15-PTX/099 cells have impaired microtubule stability as determined by a reduced percentage of tubulin in microtubules and reflected by less acetylated tubulin. These results suggest that a mutation in tubulin might affect microtubule stability as well as drug binding and contribute to the observed resistance profile.


MRI of the wrist in juvenile idiopathic arthritis: erosions or normal variants? A prospective case-control study.
Bony depressions at the wrist resembling erosions are frequently seen on MRI in healthy children. The accuracy of MRI in detecting early bony destruction is therefore questionable. We compared findings on MRI of the wrist in healthy children and those with juvenile idiopathic arthritis (JIA) to investigate markers for true disease. We compared the number and localisation of bony depressions at the wrist in 85 healthy children and 68 children with JIA, ages 5-15 years. The size of the wrist was assessed from a radiograph of the wrist performed on the same day as the MRI. No significant difference in the number of bony depressions in the carpal bones was seen between healthy children and children with JIA at any age. Depressions are found in similar locations in the two groups, except for a few sites, where bony depressions were seen exclusively in the JIA group, particularly at the CMC joints. The wrist was significantly smaller in children with JIA (P < 0.001). Using adult scoring systems and standard MR sequences in the assessment of bone destruction in children may lead to overstaging or understaging of disease. At present, standard MRI sequences cannot easily be used for assessment of early signs of erosions in children.


Forearm muscle oxygenation decreases with low levels of voluntary contraction.
The purpose of our investigation was to determine if the near infrared spectroscopy technique was sensitive to changes in tissue oxygenation at low levels of isometric contraction in the extensor carpi radialis brevis muscle. Nine subjects were seated with the right arm abducted to 45 degrees, elbow flexed to 85 degrees, forearm pronated 45 degrees, and wrist and forearm supported on an armrest throughout the protocol. Altered tissue oxygenation was measured noninvasively with near infrared spectroscopy. The near infrared spectroscopy probe was placed over the extensor carpi radialis brevis of the subject's right forearm and secured with an elastic wrap. After 1 minute of baseline measurements taken with the muscle relaxed, four different loads were applied just proximal to the metacarpophalangeal joint such that the subjects isometrically contracted the extensor carpi radialis brevis at 5, 10, 15, and 50% of the maximum voluntary contraction for 1 minute each. A 3-minute recovery period followed each level of contraction. At the end of the protocol, with the probe still in place, a value for ischemic tissue oxygenation was obtained for each subject. This value was considered the physiological zero and hence 0% tissue oxygenation. Mean tissue oxygenation (+/-SE) decreased from resting baseline (100% tissue oxygenation) to 89 +/- 4, 81 +/- 8, 78 +/- 8, and 47 +/- 8% at 5, 10, 15, and 50% of the maximum voluntary contraction, respectively. Tissue oxygenation levels at 10, 15, and 50% of the maximum voluntary contraction were significantly lower (p < 0.05) than the baseline value. Our results indicate that tissue oxygenation significantly decreases during brief, low levels of static muscle contraction and that near infrared spectroscopy is a sensitive technique for detecting deoxygenation noninvasively at low levels of forearm muscle contraction. Our findings have important implications in occupational medicine because oxygen depletion induced by low levels of muscle contraction may be directly linked to muscle fatigue.