[Physiotherapy of Eustachian tube dysfunction in adults--preliminary report].
The paper presents preliminary results of Eustachian tube dysfunction treatment with the use of vibroaerosols in adult patients. 21 patients aged 16-73 y.o. (mean age 49 y.o) have been included in the study. The treatment included inhalation of medicines individually selected for the patient, based on the results of the physical examination. The patients have been divided into 2 groups, depending on the type of tympanogram. Group I included patients with type A tympanogram and abnormal Eustachian tube patency test result. Group II comprised of patients with type B or C tympanogram and abnormal Eustachian tube patency test result. After treatment, subjective improvement has been observed in 88.9% of the ears, objective improvement in 61.5% of the ears. In group II, objective improvement observed by the change of tympanogram has been observed in 85% of ears. Lack of correlation between objective and subjective improvement have been observed in 26% of the ears. In 11.1% of the ears no benefit from treatment has been observed. The correlation between subjective and objective improvement has been observed in 74% of ears. It appears that treatment with the use of vibroaerosols is beneficial for patients with Eustachian tube dysfunction.


Siting criteria based on the prevention of deterministic effects from plutonium inhalation exposures.
Siting criteria are established by regulatory authorities to evaluate potential accident scenarios associated with proposed nuclear facilities. The 0.25 Sv (25 rem) siting criteria adopted in the United States has been historically based on the prevention of deterministic effects from acute, whole-body exposures. The Department of Energy has extended the applicability of this criterion to radionuclides that deliver chronic, organ-specific irradiation through the specification of a 0.25 Sv (25 rem) committed effective dose equivalent siting criterion. A methodology is developed to determine siting criteria based on the prevention of deterministic effects from inhalation intakes of radionuclides which deliver chronic, organ-specific irradiation. Revised siting criteria, expressed in terms of committed effective dose equivalent, are proposed for nuclear facilities that handle primarily plutonium compounds. The analysis determined that a siting criterion of 1.2 Sv (120 rem) committed effective dose equivalent for inhalation exposures to weapons-grade plutonium meets the historical goal of preventing deterministic effects during a facility accident scenario. The criterion also meets the Nuclear Regulatory Commission and Department of Energy Nuclear Safety Goals provided that the frequency of the accident is sufficiently low.


Combining fiber dissection, plastination, and tractography for neuroanatomical education: Revealing the cerebellar nuclei and their white matter connections.
In recent years, there has been a growing interest in white matter anatomy of the human brain. With advances in brain imaging techniques, the significance of white matter integrity for brain function has been demonstrated in various neurological and psychiatric disorders. As the demand for interpretation of clinical and imaging data on white matter increases, the needs for white matter anatomy education are changing. Because cross-sectional images and formalin-fixed brain specimens are often insufficient in visualizing the complexity of three-dimensional (3D) white matter anatomy, obtaining a comprehensible conception of fiber tract morphology can be difficult. Fiber dissection is a technique that allows isolation of whole fiber pathways, revealing 3D structural and functional relationships of white matter in the human brain. In this study, we describe the use of fiber dissection in combination with plastination to obtain durable and easy to use 3D white matter specimens that do not require special care or conditions. The specimens can be used as a tool in teaching white matter anatomy and structural connectivity. We included four human brains and show a series of white matter specimens of both cerebrum and cerebellum focusing on the cerebellar nuclei and associated white matter tracts, as these are especially difficult to visualize in two-dimensional specimens and demonstrate preservation of detailed human anatomy. Finally, we describe how the integration of white matter specimens with radiological information of new brain imaging techniques such as diffusion tensor imaging tractography can be used in teaching modern neuroanatomy with emphasis on structural connectivity.


The laboratory method as a variable in the diagnosis of hyperbilirubinemia.
Algorithms based on fractionation of bilirubin into direct-reacting and indirect-reacting fractions by diazo methods are frequently utilized for investigation of hyperbilirubinemia. Unfortunately, direct-reacting and indirect-reacting fractions do not correspond precisely with conjugated and unconjugated pigment. Advances in analytical methods allow accurate quantitation of the individual fractions of bilirubin in serum. Three cases of hyperbilirubinemia are presented in which bilirubin fractionation by diazo methods suggested an erroneous diagnosis. Analysis of the serum samples by high-performance liquid chromatography for bilirubin conjugates confirmed the correct clinical diagnosis. Diazo methods for bilirubin analysis are subject to marked discrepancies. While the new methodology utilizing high-performance liquid chromatography is not practical for routine bilirubin analysis, optimization of diazo methods utilizing rigid and meticulous protocol is suggested. Laboratories performing diazo bilirubin determinations should correlate their results with those of other laboratories and clinical data. Clinicians need to be aware of the reliability of a particular test result before embarking on a lengthy and expensive evaluation.


Venovenous extracorporeal membrane oxygenation in newborn infants using the umbilical vein as a reinfusion route.
The authors report on four neonates treated with venovenous (VV) extracorporeal membrane oxygenation (ECMO) using the umbilical vein as a reinfusion route. From 1994 to 1997, 26 instances VV-ECMO in neonates have been carried out at our neonatal center for the treatment of severe respiratory and cardiac failure. Among them, 22 patients could be treated with VV-ECMO mainly using 15F double-lumen catheter (DLC), adding the cephalic drainage using another catheter. In the remaining four cases, however, attempts to insert the DLC into the right internal jugular vein failed because the vein was too small or technical problems. For such instances, two catheters were cannulated into the right atrium and the cephalic portion of the right internal jugular vein, respectively. These two venous catheters were connected to the drainage route of ECMO circuit with a "Y" connector. Then, the umbilical vein was cannulated with 10F or 8F catheter, which was connected to the reinfusion route of ECMO to return the oxygenated blood to the infant. The median age at which ECMO was initiated was 18 hours, and the median ECMO course was 72 hours. The liver function tests were slightly and transiently worsened in two patients during VV perfusion, (in one patient serum glutamic-oxaloacetic transaminase [SGOT] elevated to 76 IU/L and serum glutamic-pyruvic transaminase [SGPT] to 49 IU/L, and in another patient SGOT elevated to 56 IU/L and SGPT remained in normal range). Preumbilical cannula pressures were measured in two patients. In a patient who used 10F umbilical cannula, the preumbilical maximum pressure was 43 mm Hg at 250 mL/min of ECMO flow. In another with an 8F catheter, it was 72 mm Hg at 180 mL/min of ECMO flow. All of the patients survived without any neurological complications. If the right internal jugular vein would not accommodate the DLC, VV-ECMO using the umbilical vein as a infusion route could be selected.


Engineered water-soluble two-dimensional magnetic nanocomposites: towards highly magnetic relaxometric properties.
Water dispersible two-dimensional magnetic nanocomposites are formed by phase-transferring hydrophobic manganese-doped ferrite nanoparticles (MFPs) into aqueous solvent using a one-step simple approach involving only graphene oxide (GO) as the phase transfer agent. The resultant hydrophilic magnetic nanocomposites (MFNs) are surprisingly stable in the aqueous phase despite its large hydrodynamic size (dhyd). Because of its unique construct that promotes water accessibility towards the MFP core, large MFNs loaded with an 18 nm MFP core (MFN-18; dhyd = 577.9 nm) exhibits transverse relaxivity (r2) up to ∼6.8 times (r2 = 800.8 mM [Mn + Fe](-1) s(-1)) higher than the typical individually coated MFP-18 with amphiphilic brush copolymers (r2 = 117.3 mM [Mn + Fe](-1) s(-1)). Meanwhile, the overall nanocomposites dhyd can be further reduced by employing a smaller pre-sonicated GO sheet phase transfer agent. As a result of using small GO sheets with enhanced hydrophilicity, the r2 of small MFN-18* nanocomposites (dhyd = 224.9 nm) increases by approximately 37% (r2 = 1097.4 mM [Mn + Fe](-1) s(-1)) as compared to larger MFN-18. From a simple comparative study among various magnetic nanocomposites involving a MFP-18 core, the high MFN-18 r2 relaxivity value can be attributed to enhanced water diffusion and exchange due to the GO sheet, allowing better interaction between magnetic the MFP core and water protons. The proposed method can be readily extended to convert other types of hydrophobic nanoparticles into water-dispersible nanocomposites.


Molybdenum Trihydride Complexes: Computational Determinations of Hydrogen Positions and Rearrangement Mechanisms.
In crystal structures of the molybdenum complexes [(1,2,4-C5H2(t)Bu3)Mo(PMe3)2H3] (Cp(t)Bu3) and [(C5H(i)Pr4)Mo(PMe3)2H3] (Cp(i)Pr4), the Mo-bound hydrogen positions were resolved for Cp(t)Bu3, but not for Cp(i)Pr4. NMR experiments revealed the existence of an unknown mechanism for hydrogen atom exchange in these molecules, which can be "frozen out" for Cp(t)Bu3 but not for Cp(i)Pr4. Density functional theory calculations of the most stable conformations for both complexes in the gas phase and in a continuum solvent model indicate that the H's of the Cp(i)Pr4 complex are unresloved because of their disorder, which does not occur for Cp(t)Bu3. A corresponding examination of alternative rearrangement pathways shows that the rearrangements of the H's could occur by two mechanisms: parallel to the cyclopentadienyl (Cp) ring in a single step and perpendicular to the Cp ring in two steps. The parallel pathway is preferred for both molecules, but it has a lower energy barrier for Cp(i)Pr4 than for Cp(t)Bu3.


The construction of a supramolecular polymeric rotaxane from bipyridine-ruthenium and cyclodextrin.
A luminescent supramolecular link is constructed by a very simple method using bipyridine-ruthenium and cyclodextrin, which displays not only a quasi-linear structure, but also a satisfactory fluorescence emission in both solution and the solid state.


Estrogenic regulation of gene and protein expression within the amygdala of female mice.
Estrogens exert important actions on fear and anxiety in both humans and non-humans. Currently, the mechanisms underlying estrogenic modulation of fear are not known. However, evidence suggests that estrogens may exert their influence on fear and anxiety within the amygdala. The purpose of the present study was to examine the genomic effects of estrogens within the amygdala of female mice using high-density oligonucleotide microarrays. We examined the effects of estrogens on gene expression at 2 and 24 h after an acute subcutaneous injection. Data from the microarrays revealed that 2 h following an acute injection of estradiol, 44 genes were significantly up- or downregulated, and at 24 h, 13 transcripts were significantly up- or downregulated. One interesting estrogen-regulated gene, (CaMKIIalpha), was downregulated ninefold 2 h following an acute estradiol injection but was not altered 24 h after injection. We further examined estrogen regulation of CaMKIIalpha, as well as CaMKIIbeta and CaMKIV within the amygdala using quantitative PCR and western blot analysis. The data indicate that estrogen decreases CaMKIIalpha and CaMKIV but not CaMKIIbeta gene expression within the amygdala. However, CaMKII protein levels were not different, and CaMKIV protein levels increased 2 h post-EB treatment. These results indicate that estrogen regulates CaMK gene expression and protein levels within the amygdala.


Lead identification of 2-iminobenzimidazole antagonists of the chemokine receptor CXCR3.
Modification of a 2-iminobenzimidazole series derived from an HTS hit resulted in compounds with improved in-vitro species selectivity. Incorporation of an 8-quinoline amide and conformational rigidification of an aliphatic tether furnished potent compounds suitable for further lead optimization.


Health research, fair benefits and access to medicines.
Access to medicines within the context of health research is viewed as a negotiation for 'fair benefits" where it is judged by the host country that access to medicines is the most important and desirable benefit. Research ethics committees in the host country, both local and central, are set to be key players in that determination. However, access to medicines, or "reasonable availability" of medicines in research ethics guidelines, may be difficult to achieve in practice. In extreme cases, the problem of access to medicines may need to be viewed as a global problem, beyond the negotiations within the fair benefits framework.


Enhancing thermostability of maltogenic amylase from Bacillus thermoalkalophilus ET2 by DNA shuffling.
DNA shuffling was used to improve the thermostability of maltogenic amylase from Bacillus thermoalkalophilus ET2. Two highly thermostable mutants, III-1 and III-2, were generated after three rounds of shuffling and recombination of mutations. Their optimal reaction temperatures were all 80 degrees C, which was 10 degrees C higher than that of the wild-type. The mutant enzyme III-1 carried seven mutations: N147D, F195L, N263S, D311G, A344V, F397S, and N508D. The half-life of III-1 was about 20 times greater than that of the wild-type at 78 degrees C. The mutant enzyme III-2 carried M375T in addition to the mutations in III-1, which was responsible for the decrease in specific activity. The half-life of III-2 was 568 min while that of the wild-type was < 1 min at 80 degrees C. The melting temperatures of III-1 and III-2, as determined by differential scanning calorimetry, increased by 6.1 degrees C and 11.4 degrees C, respectively. Hydrogen bonding, hydrophobic interaction, electrostatic interaction, proper packing, and deamidation were predicted as the mechanisms for the enhancement of thermostability in the enzymes with the mutations.


Functional Anatomic Computer Engineered Surgery Protocol for the Management of Self-Inflicted Gunshot Wounds to the Maxillofacial Skeleton.
Virtual surgical planning (VSP) is an indispensable aid in craniomaxillofacial reconstruction, yet no protocol is established in facial gunshot wounds. We review our experience with computer-aided reconstruction of self-inflicted facial gunshot wounds (SIGSW'S) and propose a protocol for the staged repair. A retrospective case series enrolling patients with SIGSW's managed with the Functional Anatomic Computer Engineered Surgical protocol (FACES) was implemented. Subjects were evaluated at least one month postoperatively. Outcome variables were jaw position, facial projection, oro-nasal communication, lip competence, feeding tube and tracheostomy dependence, descriptive statistics were computed. The FACES protocol implemented during the initial hospitalization is as follows 1) damage control; 2) selective debridement; 3) VSP reconstruction back converted into navigation software 4) navigation assisted midfacial skeletal reconstruction; 5) computer aided oro-mandibular reconstruction with or without microvascular free flaps using custom cutting guides/hardware; 6) navigation assisted, computer aided palatomaxillary reconstruction with or without microvascular free flaps using cutting guides/hardware; 7) navigation assisted reconstruction of the internal orbit; 8) and confirmation of accurate reconstruction using intraoperative CT. The sample was composed of 10 patients, mean age of 43 years (range, 28 - 62 years, 70% M), 100% with SIGSW's to the submental/submandibular region. All had satisfactory facial projection (n=10), nine had satisfactory jaw position, were decannulated by one month's follow up and were feeding tube independent (90%). All traumatic oro-antral communications were closed (n=8, 7 surgical, 1 obturator), seven had adequate lip competence (70%). Complications included fibula malunion (n=1), plate exposure (n=2) infection (n=2), intracranial abscess (n=1) and microstomia (n=2). Computer-aided surgery is an indispensable tool in the reconstruction of SIGSW's. Successfully implemented, it proved to be a useful adjunct for: the restoration of orbital volume, facial projection and symmetry; the inset of composite tissue, and the facilitation of dental implant supported prosthetic rehabilitation.


Exploring the correlates of intermediate CAG repeats in Huntington disease.
To explore the clinical phenotype in individuals with huntingtin gene CAG repeat lengths between 27 and 35, a range that is termed "intermediate" and below one traditionally considered diagnostic of Huntington disease (HD). The Prospective Huntington Disease At-Risk Observational Study (PHAROS) found that patients with intermediate CAG lengths overlapped with those diagnosed as HD (≥ 37 CAG repeats) on the Unified Huntington's Disease Rating Scale (UHDRS) behavioral measures. Furthermore, several patients with intermediate CAG repeats demonstrating clinical (and pathological) evidence of HD have been reported. We reviewed all cases with intermediate CAG repeats who have presented to our clinic, as well as those reported in the literature. We describe 4 patients with intermediate repeats evaluated at our center whose clinical features were highly suggestive of HD. Investigations for HD phenocopies were negative. Anticipation was demonstrated in 1 case with supportive neuropathological evidence of HD. Additionally, we describe the clinical features of 5 other patients reported in the literature. Individuals with huntingtin gene CAG repeats in the intermediate (27-35) range should be considered at risk for the development of HD, particularly if they have a family history of HD, whether they exhibit clinical features of the disease.


An unusual complication associated with blepharoplasty.
The usual complications associated with blepharoplasty are well known. This report presents a case of second-degree burns of the face which occurred while oxygen was being administered to a patient undergoing blepharoplasty and a heat-producing cautery was being used for hemostasis. A possible cause for the complication is suggested. Surgeons are warned of the potential problem that may occur when this combination of factors are present.


Expression profile of the GA733 gene family in colorectal cancer: correlation with clinicopathological parameters.
GA733-1/-2/-3 genes have been detected in various types of cancer, although their role has not been fully clarified. GA733-2 and GA733-1 have been correlated with lymph node metastases in laryngeal cancer and liver metastases, respectively. Only a few studies have elucidated the mechanisms regulating GA733-1/-2 expression and their effect on colorectal cancer. Therefore, the expression pattern and the role of the aforementioned molecules in colorectal carcinogenesis were evaluated in this study. Tissue samples were obtained from 40 patients with colorectal cancer with no liver metastases. GA733-1/-2 mRNA levels were evaluated by quantitative real-time polymerase chain reaction. GA733-1/-2 gene expression in noncancerous/cancerous tissues was also correlated with clinicopathological parameters. The GA733-1 mRNA levels were very low; however, the GA733-1 mRNA transcripts were higher in cancerous tissues than in normal tissues (median ratio, 0.004391/0.00093; range, 0.000001- 0.025139/0.000001-0.007761), respectively (P = 0.012). GA733-2 gene expression was higher in noncancerous tissues than in cancerous tissues (median ratio 273.31/115.64; range, 65.24-1,486.41/11.58-1,189.14; P = 0.0000195). Lower GA733-2 expression in cancer tissues appeared to correlate with lymph node metastases (P < 0.05). GA733-1 gene expression was significantly higher in cancerous samples; conversely, the GA733-2 mRNA levels were higher in noncancerous tissues, and were significantly correlated with lymph node perforation in colorectal cancer (P < 0.05). Therefore, GA733-1/-2 mRNA expression levels appear to be a potential predictive marker of tumorigenesis.


[Minimally Invasive Coronary Artery Bypass Grafting Using Proximal Anastomoses Device;Report of a Case].
A 68-years-old male with diabetes mellitius (HbA1c 6.5%) was referred for coronary artery bypass grafting(CABG). Preoperative coronary angiography (CAG) signed 3-vessels coronary disease[#2 75 %,#4 posterior descending (PD) 75%,#6 90%,#14 90%]. Minimally invasive coronary artery grafting (MICS CABG) was selected because of faster postoperative recovery than off-pump CABG via a 10 cm left 5th thoracotomy approach. In situ bilateral internal thoracic artery(BITA) and saphenous vein (SVG) was harvested by special manner using long type Harmonic. Bypass graft design was in situ right internal thoracic artery-LAD, in situ left internal thoracic artery-left circumtlex#14, and aorta-SVG-#4PD-#4atrio-ventricular. BITA, the ascending aorta for proximal anastomoses, and all coronary targets were directly accessed with off-pump technique. Heartstring III Proximal Seal System was used to anastomose SVG to the ascending aorta. There were no major postoperative complications. Postoperative CAG revealed all grafts patent and postoperative hospital stay was 14 days. This case was the 1st usage of Heartstring III Proximal Seal System in our clinic. We believe that the usage of Heartstring III Proximal Seal System in MICS CABG is realistically possible, and providing good quality;however, further research will be needed.


Plasmapheresis in the treatment of steroid-resistant focal segmental glomerulosclerosis in native kidneys.
A circulating glomerular capillary albumin permeability factor (P(alb)) has been implicated in the pathogenesis of focal segmental glomerulosclerosis (FSGS), which recurs in transplanted kidneys. Plasmapheresis for recurrent FSGS may reduce proteinuria and stabilize renal function if instituted early. We performed six plasmapheresis treatments over 2 weeks in eight patients with a history of steroid-resistant idiopathic FSGS in native kidneys for an average of 12 +/- 2.3 months to determine whether treatment would decrease proteinuria or stabilize renal function. P(alb) was measured before and after plasmapheresis, and patients were followed-up for a mean of 29 +/- 4 months after the development of clinical symptoms. Proteinuria decreased in two of eight treated patients, although only transiently in one of the two. P(alb) improved in one of the two responding patients. Both patients with an improvement in proteinuria had stable renal function at last follow-up. In six of eight patients, there was no improvement in proteinuria despite an improvement in P(alb) (P < 0.0001) after plasmapheresis. At last follow-up, renal function was stable in two of the six nonresponding patients, and four of the six had significant progression of renal disease or were receiving dialysis treatments. These studies suggest that plasmapheresis may diminish proteinuria and stabilize renal function in a small minority of patients with steroid-resistant idiopathic FSGS. However, the lack of a relationship between the removal of the circulating permeability factor and the development of remission in these patients suggests that local factors associated with advanced renal injury or systemic factors unrelated to glomerular permeability play a significant role in determining proteinuria at this late stage of the disease.


A thermodynamic "vocabulary" for metal ion interactions in biological systems.
This Account focuses on metal ion-ligand complexes of biological relevance and measurements of the bond dissociation energies (BDEs) of such species. These complexes yield thermochemistry that begins to provide a thermodynamic "vocabulary" for thinking quantitatively about the strength of interactions in biological systems. The method utilized is threshold collision-induced dissociation in a guided ion beam tandem mass spectrometer. Accurate determination of BDEs requires attention to many details of the experiments and data analysis, as outlined here. Trends in metal ion-ligand BDEs are examined as a function of the metal ion, ligand, and extent of ligation. We elucidate the importance of ion-dipole and ion-induced dipole interactions, chelation, conformation, tautomeric form, steric interactions, and electronic effects such as hybridization and promotion. Interactions of metal ions with nucleobases and amino acids are quantified and the effects of hydration on these values are explored for the amino acid systems. Although data limitations restrict the present discussion to monocations, the trends elucidated here should be relevant to multiply charged metal ions, for which data is forthcoming.


Stability of the glutamate content of synaptosomes during their preparation.
The glutamate content of synaptosomal-enriched fractions is stable during the preparation and isolation of the organelles provided that the temperature of the preparation is maintained at 0--2 degrees C and that inorganic ions are not added to the homogenizing and centrifugation media. Consequently, drug-induced in vivo changes in the glutamate content of nerve endings should be reflected by the corresponding changes in glutamate levels of synaptosomes prepared from the brain tissue.


A novel design of a polynuclear co-delivery system for safe and efficient cancer therapy.
We report a novel and easy-to-fabricate polynuclear nanoparticle based on the collaborative re-assembly of nanoparticles as a robust chemogene co-delivery platform. Specifically, the polynuclear nanoparticle carrying DOX and siBcl-2 exerts remarkable co-delivery efficiency, increases tumour cell apoptosis and inhibits tumour cell proliferation in vitro and in vivo.


Dorsal unpaired median (DUM) neurones with neurohaemal functions in the locust, Locusta migratoria.
Certain members of the class of dorsal unpaired median (DUM) neurones do not only innervate skeletal muscles, but they also establish neurohaemal release sites on the surface of peripheral nerves. These release sites may be associated with well-known neurohaemal organs, but they also occur in other parts of the peripheral nervous system. These DUM neurones are most likely responsible for the release of octopamine into the haemolymph as has been observed in certain behavioural contexts.


Faster determination of clottable fibrinogen in human plasma: an improved method and kinetic study.
Clottable fibrinogen in human plasma was determined by measuring spectrophotometrically the increase in turbidity with time due to the fibrinogen-fibrin conversion with thrombin. From the maximal absorbance, Amax, at 450 nm obtained 2 min or less after thrombin as added to plasma, we estimated the fibrinogen concentration in plasma of normal subjects and patients. Analysis of the rate of the absorbance increase yielded the Km value, 1.6 X 10(-5) mol/liter, which closely agrees with the Km of 1.2 X 10(-5) mol/liter obtained by analysis of the fibrinopeptides released from fibrinogen.


Opsoclonus myoclonus ataxia associated with West Nile virus infection: A dramatic presentation with benign prognosis?
Opsoclonus myoclonus and ataxia is a combination of severe neurological signs associated with several pathologic agents and conditions. Only few cases of opsoclonus have been related to West Nile virus infection. We report on a 61-year-old woman and on a 55-year-old man who had history of recent fever, who were hospitalized because of acute severe truncal ataxia, opsoclonus and tremor with minimal myoclonic jerks. A through work-up revealed the presence of both IgM and IgG antibodies against West Nile virus both in the serum and Cerebrospinal Fluid and excluded other causes known to be associated with this combination of neurological signs. The first case was treated with corticosteroids, followed by significant improvement, and the second recovered spontaneously. The acute combination of opsoclonus, severe truncal ataxia and tremor with a history of recent fever requires, during the relevant season and in the relevant geographic area, a search for a recent infection with West Nile virus. Though initially suffering from a devastating sickness, our patients eventually recovered.


The mediating role of catastrophizing in the relationship between pain intensity and depressed mood in older adults with persistent pain: A longitudinal analysis.
Depression is common in older adults with persistent pain. Cognitive-behavioural models of pain propose that the relationship between pain and depression is influenced or mediated by interpretations of events (cognitions), rather than by the event itself. Almost exclusively, the evidence for this position has come from studies of people aged less than 65 years. The role of cognitions in the pain experience of older adults has been unclear due to the limited and conflicting evidence available. The aim of our study was to examine the role of catastrophizing in mediating the relationship between pain intensity and depressed mood in older adults with persistent pain using reliable and valid measures for this population. In a two-wave longitudinal design, a sample of 141 patients (89 women, 52 men) 65 years and over with persistent pain participating in an evaluation of a pain self-management programme completed questionnaires measuring usual level of pain intensity (NRS), depressed mood (DASS-21) and the catastrophizing factors of magnification and helplessness (PRSS) at the beginning of the programme and 6 months later. Demographic data and pain history were collected by self-completion questionnaires, which were mailed to patients prior to participating in the programme and returned by post. Change scores for usual level of pain intensity (NRS), depressed mood (DASS-21) and the magnification and helplessness factors on the PRSS-Catastrophizing were calculated by subtracting the scores at 6 months after completion of the study (Time 2) from the scores at the beginning of the study (Time 1). In the longitudinal analyses of mediation, using a series of regression analyses, change scores for both factors (magnification, helplessness) of the measure of catastrophizing (PRSS) totally and significantly mediated the relationship between change scores for pain intensity and depressed mood. The significant relative magnitude of beta between pain intensity and depression reduced from 0.22 to 0.13 and became non-significant after introducing magnification as a mediating variable, whilst the significant relative magnitude of beta reduced from 0.22 to 0.12 and also became non-significant after introducing helplessness as a mediating variable. These results support a cognitive-behavioural model and highlight the importance of cognitive factors, in this case catastrophizing, in the relationship between pain intensity and depressed mood in older adults with persistent pain. These findings also have important clinical implications for the treatment of older adults with persistent pain. They highlight the importance of targeting interventions to reduce the influence of catastrophizing as a prerequisite for reducing depressive symptoms in this growing population.


Glutathionyl- and hydroxyl radical formation coupled to the redox transitions of 1,4-naphthoquinone bioreductive alkylating agents during glutathione two-electron reductive addition.
The kinetic parameters of the redox transitions subsequent to the two-electron transfer implied in the glutathione (GSH) reductive addition to 2- and 6-hydroxymethyl-1,4-naphthoquinone bioalkylating agents were examined in terms of autoxidation, GSH consumption in the arylation reaction, oxidation of the thiol to glutathione disulfide (GSSG), and free radical formation detected by the spin-trapping electron spin resonance method. The position of the hydroxymethyl substituent in either the benzenoid or the quinonoid ring differentially influenced the initial rates of hydroquinone autoxidation as well as thiol oxidation. Thus, GSSG- and hydrogen peroxide formation during the GSH reductive addition to 6-hydroxymethyl-1,4-naphthoquinone proceeded at rates substantially higher than those observed with the 2-hydroxymethyl derivative. The distribution and concentration of molecular end products, however, was the same for both quinones, regardless of the position of the hydroxymethyl substituent. The [O2]consumed/[GSSG]formed ratio was above unity in both cases, thus indicating the occurrence of autoxidation reactions other than those involved during GSSG formation. EPR studies using the spin probe 5,5'-dimethyl-1-pyrroline-N-oxide (DMPO) suggested that the oxidation of GSH coupled to the above redox transitions involved the formation of radicals of differing structure, such as hydroxyl and thiyl radicals. These were identified as the corresponding DMPO adducts. The detection of either DMPO adduct depended on the concentration of GSH in the reaction mixture: the hydroxyl radical adduct of DMPO prevailed at low GSH concentrations, whereas the thiyl radical adduct of DMPO prevailed at high GSH concentrations. The production of the former adduct was sensitive to catalase, whereas that of the latter was sensitive to superoxide dismutase as well as to catalase. The relevance of free radical formation coupled to thiol oxidation is discussed in terms of the thermodynamic and kinetic properties of the reactions involved as well as in terms of potential implications in quinone cytotoxicity.


Comparison of the efficacy of topical 1% lindane vs 5% permethrin in scabies: a randomized, double-blind study.
Permethrin, a pyrethroid insecticide, is not yet available in Iran and may be a useful substitute for the control of scabies in Iran. To compare the efficacy of topical lindane with topical permethrin in the treatment of scabies in a population in Iran. In a double-blind, randomized study, all consecutive patients with scabies were randomized into two groups. One group and their family contacts received 1% lindane cream, and the other group and their family contacts were treated with topical 5% permethrin cream. Subsequently, patients were followed up at 2- and 4-week post-treatment. Of the 99 patients enrolled in the study, 47 patients received 1% lindane cream, and 52 patients were treated topically with 5% permethrin cream. Permethrin provided an improvement rate of 84.6% after two weeks, whereas lindane was effective only in 48.9% of patients. Permethrin (5%) cream was found to be significantly more effective in the treatment of scabies in comparison with lindane in this study, and it seems that it could be an alternative treatment.


Developments in the diagnosis and treatment of primary CNS lymphoma. A prospective series.
Current experience with 12 patients studied prospectively suggests a new approach in the diagnosis and treatment of primary central nervous system (CNS) lymphoma, integrating the techniques of needle brain biopsy, immunohistochemical staining for monoclonal antibody and chemotherapeutic drug delivery in association with blood-brain barrier modification. Computed tomography (CT)-guided needle biopsy of deep parenchymal lesions contributed to the diagnosis in six patients. Immunohistochemical staining methods detected monoclonal immunoglobulins in those patients so tested. Following diagnosis, the patients have been treated with multi-agent chemotherapy in conjunction with osmotic blood-brain barrier modification (five without antecedent cranial irradiation) with an initial complete response rate by CT scan in nine patients, a median follow-up of 19 months from diagnosis, and a 1-year survival of 75%. This experience emphasizes the value of CT-guided stereotaxic or CT-guided needle biopsy, which limits the need for therapy without a diagnosis or the need for a major craniotomy in what are commonly deep, paraventricular lesions. Immunoperoxidase cytochemical stains can detect monoclonal immunoglobulin characteristic of CNS B-cell malignant lymphomas and provide an important diagnostic aid when only modest quantities of tissue or cells are obtained. Finally, chemotherapy administered in conjunction with osmotic blood-brain barrier modification results in a clinical response rate and survival that are at least as effective as radiotherapy as a primary therapeutic modality.


Should patients with benign positional vertigo be imaged?
Unexpected intra-cranial pathology is unusually encountered in patients with BPV in the presence of a classically positive Hallpike's response and in the absence of any other neurological signs or symptoms. We carried out a retrospective review to assess the incidence of unexpected intra-cranial pathology in patients with a clinical diagnosis of benign positional vertigo (BPV) and to review the role of radiological imaging in these patients. 145 consecutive patients seen by the senior author with a diagnosis of posterior semi-circular canal BPV over a five-year period were reviewed. In the series of 63 patients who underwent MRI, two cases (3.2%) had cerebral aneurysms, one patient had an epidermoid cyst (1.58%) and one patient had a large right parietal arterio-venous malformation. We would conclude that possible warning signs exist that may alert the clinician to the possibility of unexpected intracranial pathology including failed response to the initial Epley manoeuvre or any asymmetry in hearing. Thus, we would advocate imaging be performed on this sub-group of patients with BPV.


Novel rhythms of N1-acetyl-N2-formyl-5-methoxykynuramine and its precursor melatonin in water hyacinth: importance for phytoremediation.
N1-acetyl-N2-formyl-5-methoxykynuramine (AMFK) is a major metabolite of melatonin in mammals. To investigate whether AFMK exists in plants, an aquatic plant, water hyacinth, was used. To achieve this, LC/MS/MS with a deuterated standard was employed. AFMK was identified in any plant for the first time. Both it and its precursor, melatonin, were rhythmic with peaks during the late light phase. These novel rhythms indicate that these molecules do not serve as the chemical signal of darkness as in animals but may relate to processes of photosynthesis or photoprotection. These possibilities are supported by higher production of melatonin and AFMK in plants grown in sunlight (10,000-15,000 microW/cm2) compared to those grown under artificial light (400-450 microW/cm2). Melatonin and AFMK, as potent free radical scavengers, may assist plants in coping with harsh environmental insults, including soil and water pollutants. High levels of melatonin and AFMK in water hyacinth may explain why this plant more easily tolerates environmental pollutants, including toxic chemicals and heavy metals and is successfully used in phytoremediation. These novel findings could lead to improvements in the phytoremediative capacity of plants by either stimulating endogenous melatonin synthesis or by adding melatonin to water/soil in which they are grown.


Calcium regulation of tissue plasminogen activator and prostaglandin biosynthesis in HeLa cells.
Phorbol 12-myristate 13-acetate, 1-20 nM, induced the synthesis in HeLa cells of a 65 200 Mr tissue-type plasminogen activator, and of prostaglandin E2. Omission of Ca2+ from the incubation medium inhibited the induction of plasminogen activator synthesis by 40-60% and abolished the induction of prostaglandin E2 synthesis. Maximal plasminogen activator synthesis could be maintained at extracellular Ca2+ concentrations of approx. 0.1 mM, while maximal prostaglandin synthesis required at least 0.45-0.9 mM Ca2+. The induction of each factor was inhibited by 10-100 microM 8-(N,N-diethylamino)octyl-3,4,5-trimethoxybenzoate (TMB-8), an inhibitor of intracellular C2+ mobilization. Prostaglandin synthesis, but not plasminogen activator synthesis, was also inhibited by 10-100 microM verapamil and nifedipine, which inhibit intracellular Ca2+ uptake via the so-called 'slow-channels' and by 0.5-10 microM trifluoperazine, an inhibitor of calmodulin. Neither plasminogen activator synthesis nor prostaglandin synthesis were stimulated by 5-50 microM 1-oleoyl-2-acetylglycerol or 1-250 microM 1,2-dioctanoylglycerol, alone and in combination with 50 nM-1 microM ionophore A23187. These results indicate that the synthesis of plasminogen activator and prostaglandins in HeLa cells is Ca2+-dependent, and that the Ca2+ requirements for each process are not identical. Thus, Ca2+ regulation of the production of tissue plasminogen activator and prostaglandin E2 occurs at multiple points in their biosynthetic pathways.


Purification and characterization of human liver beta-galactosidase from a patient with the adult form of GM1 gangliosidosis and a normal control.
beta-Galactosidases were purified to homogeneity from livers of a normal control and a patient with the adult form of GM1 gangliosidosis. The purification was achieved by chromatography on DEAE-Sepharose fast flow, Con A-Sepharose, p-aminophenyl-1-thio-beta-D-galactopyranoside-Sepharose, and QAE-Mono Q. The normal and mutant enzymes were purified about 5000-fold with a yield of 10% and 1800-fold with a yield of 34%, respectively, and could hydrolyze 4-methylumbelliferyl-beta-D-galactoside, GM1 ganglioside, and asialofetuin. The purified normal enzyme was eluted from a TSK gel G-4000SW column as three symmetrical peaks of protein which were coincident with the three peaks of enzyme activity. The enzyme in these three peaks had apparent molecular weights of 800,000 (polymer), 140,000 (dimer), and 65,000 (monomer), whereas the mutant enzyme was eluted as two symmetrical peaks of protein and enzyme activity. The apparent molecular weight of a major monomeric form of the enzyme (beta-galactosidase A) was 60,000, and no dimeric form of the enzyme existed. Normal and mutant purified enzyme preparations migrated as a single major protein band with apparent molecular weights of 65,000 or 60,000, respectively, by SDS-polyacrylamide gel electrophoresis after treatment with mercaptoethanol. On isoelectric focussing, the mutant enzyme migrated more anodally than the normal enzyme. The mutant enzyme also had altered enzyme properties, such as pH optimum, Km values, substrate specificity and heat-stability. These data on the characteristics of the purified enzyme preparations provide the first direct evidence that patients with the adult form of GM1 gangliosidosis have a structurally altered beta-galactosidase.


Insight and frontal cortical function in schizophrenia: a review.
Insight into illness has been identified as a clinically important phenomenon, in no small part due to an association with treatment-adherence. An increasing number of studies, but not all, have observed poor insight to be a reflection of cognitive dysfunction in schizophrenia. A review of 34 published English-language studies found a significant number (i.e., 21) reporting a relationship between insight deficits and impaired performance on cognitive tasks primarily mediated by frontal cortex. A significant number of reviewed studies examined insight function in more than one psychiatric population, including bipolar and schizoaffective disorder. The most replicated findings from these studies were the correlations between insight deficits and impaired performance on the Wisconsin Card Sorting Test (WCST). More specifically, WCST perseverative errors correlated positively and the number of categories completed correlated negatively with poor insight, suggesting that impaired insight may be mediated by deficiencies in conceptual organization and flexibility in abstract thinking. Since the WCST requires the ability to demonstrate conceptual flexibility through the generation, maintenance and switching of mental sets along with the capacity to use verbal feedback to correct errors, it would appear that such 'executive' functions are most related to insight. In addition, recently identified structural correlates of poor insight in schizophrenia show some association with anosognosia in neurological patients. This review will discuss the implications of these findings and directions for future research.


Poly(ADP-ribose) biosynthesis and suicidal NAD+ depletion following carcinogen exposure of mammalian cells.
Hepatocytes were found to be remarkably resistant to suicidal NAD+ depletion due to consumption for chromatin-associated poly(ADP-ribose) biosynthesis, which normally follows infliction of DNA damage in mammalian cells. N-methyl-N'-nitro-N-nitrosoguanidine treatment, which depleted NAD+ levels of confluent fibroblasts to about 40% of controls, did not reduce hepatocellular NAD+ pools, although poly(ADP-ribose) concentrations were concomitantly elevated by 21-fold. This differential behavior, demonstrable also with other carcinogens, can be attributed to the different NAD+ biosynthetic capacities of these cells.


DNA ploidy in breast lesions. A comparative study using two commercial image analysis systems and flow cytometry.
DNA ploidy determinations on a series of 24 breast specimens were performed independently utilizing flow cytometry (FCM) and two separate commercially available computerized image analysis systems for image cytometry (ICM). The tissues analyzed were obtained from 20 carcinomas, 2 benign neoplasms and 2 benign reductive procedures. The results showed a close correlation between the DNA indices (DIs) obtained by all methods in 14 of the 24 cases. In four cases, all methods showed aneuploid peaks, but with differing DIs. In six cases (two benign and four malignant) FCM showed diploidy while ICM showed peridiploid cell populations. The results obtained with the two image analysis systems were in agreement for 20 of the 24 cases. ICM is an acceptable alternative to FCM for reproducible ploidy analysis. ICM-based measurements have the advantage of the visual discrimination of abnormal cells and therefore may have a greater sensitivity in identifying small aneuploid populations. Populations with DIs in the range of 1.0 to 1.3 need to be assessed carefully in ICM-based determinations due to the potential that these "aneuploid" peaks may represent shifted diploid populations.


An intraoperative localization technique for a postexcision specimen of nonpalpable breast calcifications: a pilot study.
The specimens obtained through excisional biopsy (EB) are commonly large in size and it is difficult to remove the tissues containing nonpalpable calcifications accurately from them for pathologic examination. Therefore, the aim of the study is to develop a novel method of subarea localization technique (SLT) for sampling from the postexcisional specimens. A retrospective clinical study of 48 consecutive patients with breast microcalcifications were divided into a study group (n = 24 patients, 25 breasts) and a control group (n = 24 patients, 24 breasts) in time sequence. The specimens of study group were localized by SLT performed by cutting lines and/or metallic markers. The main study end points were the duration of intraoperative pathologic diagnosis (DIPD) and duration of conclusive pathology diagnosis (DCPD). The number of frozen blocks, number of paraffin blocks, number of sections, and other parameters correlated with pathologic diagnosis were compared between the two groups. SLT was succeeded in 48 of 48 (100%) patients, which shortened DIPD (29.3 vs 45.5 minutes, P < 0.01) significantly with less frozen blocks (6.2 vs 12.6, P < 0.01) and less frozen sections (8.5 vs 13.7, P = 0.01) than that of the control group. Moreover, SLT shortened DCPD (4.1 vs 5.1 days, P = 0.02) with less paraffin blocks (12.2 vs 21.7, P < 0.01) and less paraffin sections (20.0 vs 39.9, P < 0.01) than that of the control group. SLT decreased workload of the specimens sampling procedure and SLT may be recommended as a reliable specimens sampling method to guide pathology test for EB specimens containing calcifications.


Transport of procainamide via H(+)/tertiary amine antiport system in rabbit intestinal brush-border membrane.
Transport characteristics of procainamide in the brush-border membrane isolated from rabbit small intestine were studied by a rapid-filtration technique. Procainamide uptake by brush-border membrane vesicles was stimulated by an outward H(+) gradient (pH(in) = 6.0, pH(out) = 7.5) against a concentration gradient (overshoot phenomenon), and this stimulation was reduced when the H(+) gradient was subjected to rapid dissipation by the presence of a protonophore, FCCP. An outward H(+) gradient-dependent procainamide uptake was not caused by H(+) diffusion potential. The initial uptake of procainamide was inhibited by other tertiary amines with N-dimethyl or N-diethyl moieties in their structures, such as triethylamine, dimethylaminoethyl chloride, and diphenhydramine, but not by tetraethylammonium and thiamine. Furthermore, procainamide uptake was stimulated by preloading the vesicles with these tertiary amines (trans-stimulation effect), indicating the existence of a specific transport system for tertiary amines. These findings indicate that procainamide transport in the intestinal brush-border membrane is mediated by the H(+)/tertiary amine antiport system that recognizes N-dimethyl or N-diethyl moieties in the structures of tertiary amines.


[The impact of a food service in the school milieu on the quality of nutrition in children].
The food service at the Le Tremplin school (QC), which is managed by a non-profit organization including parents and members of the community, was evaluated in terms of its impact on the nutritional quality of the meals consumed by the students from the point of view of the prevention of cardiovascular diseases (CVDs) in children. This was done by comparing it with a traditional food service operated by a concessionnaire. On the nutritional level, the menus offered in the two schools were comparable: in both cases, they fell far short of meeting nutritional recommendations related to the prevention of CVDs. In other respects, the nutritional value of the meals consumed by the children differed according to the school. It was closer to meeting recommendations in the case of the Le Tremplin school. The results obtained show that the organization of the food service at the Le Tremplin school appears to favour a more adequate consumption of lipids and carbohydrates, as well as a more appropriate distribution of the different fatty acids in the food.


Effect of government-community healthcare co-financing on maternal and child healthcare in Nigeria.
Effective maternal and child healthcare delivery requires a proper and adequate funding of the health sector. To determine the effect of government-community healthcare co-financing on maternal and child healthcare services' delivery. A descriptive, cross-sectional study with an intervention component, conducted amongst 240 women from Igboukwu (intervention area), and Ekwuluobia (control area), of Anambra State of Nigeria. The biosocial characteristics of the respondents were essentially similar. Better utilization of health services occurred in the intervention area post-intervention. Quality of service from intervention clients' perspective showed significant improvement post-intervention. Distance less than five km, transportation cost less than N40, and maternal education above secondary level impacted positively on utilization of maternal and child health services. Acceptability of the scheme was better for the intervention facility evident from the higher number of respondents showing "willingness to join", and "willingness to pay". Health sector funding partnership, positively impacts on maternal and child health services. Government's total commitment, backed with legislation, and community mobilization, will sustain the scheme.


What is known about the structure and function of the Escherichia coli protein FirA?
The firA gene is essential for growth of Escherichia coli growth and lies in the 4-minute region of the genome. firA encodes the FirA protein which contains 341 amino acids and has an apparent molecular mass of 36 kDa. Genetic evidence suggests that FirA plays a role in transcription since certain firA alleles confer temperature sensitivity for growth and RNA synthesis as well as reversing the rifampin resistance of rifampin-resistant rpoB mutants ('fir' effect). FirA co-immunoprecipitates with RNA polymerase holoenzyme, implying a physical association with the transcriptional machinery, possibly with the beta subunit of RNA polymerase. FirA contains a previously undescribed isoleucine/valine-rich six-amino-acid repeat occurring 14 times within the N-terminal and 12 more times within the C-terminal half of the protein. This repeat can be formulated as [HXXXhZ]n with 'H' representing a large non-polar residue (usually isoleucine), 'h' representing a smaller non-polar residue, 'Z' representing either charged/polar or aromatic residues, XXX representing residues typical of beta turns, and 'n' being equal to the repeat number. We refer to this repeat as an isoleucine patch. Proteins encoded by three E. coli acyltransferases also contain this motif which is roughly positioned in each case, within the amino- and carboxyl termini, as in FirA. When the sequences of these proteins are aligned, a region of poor similarity separates the isoleucine patches. The significance of these repeats remains unknown although we speculate that they play an important structural role in the organization and function of FirA (and other proteins containing isoleucine patches), possibly by acting as homo- or hetero-dimerization interfaces.(ABSTRACT TRUNCATED AT 250 WORDS)


Traumatic splenic injury: splenectomy vs. repair.
Splenectomy has been the standard treatment during this century for traumatic splenic injuries. Because of the association between asplenia and overwhelming sepsis, recent attempts have been made to repair injured spleens. Details of splenic anatomy and blood supply allow prediction of the usual type of splenic injury that can be repaired. By utilizing a topical hemostatic agent, capsular sutures, and arterial ligation, severely traumatized spleens have been repaired. Postoperative splenic scanning is available in assessing remaining splenic tissue. The present and future ramifications of reparative splenic surgery are presented.


Health, health care utilization and living conditions in foreign-born diabetic patients in southern Sweden.
To compare foreign- and Swedish-born diabetic subjects regarding health care utilization, complications, clinical and socio-economic characteristics. Cross-sectional study. All known diabetic patients living in six defined primary health care districts. Of 1861 identified subjects aged > 25 years 90.1%. 113 foreign- and 1564 Swedish-born subjects participated. Mean time of residence in Sweden was 32 +/- 1.2 years, 93% > 10 years. A standardized interview, a physical examination and an evaluation of medical records. No differences were found regarding living conditions or health care utilization, with the exception of higher use of home-care from public authorities in Swedish-born subjects (P < 0.05) despite no difference in dependency on help according to Katz's ADL index. There were no major differences in objective health (glycaemic control and complications related to diabetes) with the exception of lower frequency of sensory neuropathy (P < 0.01) and peripheral vascular disease (P < 0.05) in foreign-born subjects. The prevalence of diabetes was 2.1% (95% CI 1.7-2.5) in the foreign-born and 2.6% (95% CI 2.5-2.7) in Swedes. Foreign-born individuals were five years younger (P < 0.001), were more often diagnosed > or = 30 years (P < 0.05), had a two years' shorter duration of disease (P < 0.001) and were less often treated with insulin (P < 0.01). Treatment with insulin was related to the duration and presence of complications related to diabetes. There were no major differences in objective health or use of health care in European migrants with diabetes mellitus, mainly Scandinavians, with short cultural distance and long residence in Sweden compared to Swedish-born diabetic patients.


Does the DSM-IV clinical significance criterion for major depression reduce false positives? Evidence from the National Comorbidity Survey Replication.
To reduce false positive diagnoses, DSM-IV added a clinical significance criterion to many diagnostic criteria sets requiring that symptoms cause significant distress or impairment. The DSM-V Task Force is considering whether clinical significance should remain a diagnostic threshold or become a separate dimension, as it is in ICD. Yet, the criterion's effectiveness in validly reducing the prevalence of specific disorders remains unclear. Critics have argued that for some categories, notably major depression, the criterion is redundant with symptoms, which are inherently distressing or impairing. The authors empirically evaluated the criterion's effect on the prevalence of major depression in the community. This report also considers more broadly the relationship of symptoms to impairment in diagnosis. Subjects were respondents, aged 18 to 54 years, who participated in the National Comorbidity Survey Replication (N=6,707). The effect of the clinical significance criterion's distress and impairment components on major depression was assessed in this sample. Distress questions were administered to all respondents reporting persistent sadness (> or = 2 weeks) or the equivalent. Questions pertaining to role impairment were asked of all respondents satisfying major depression symptom-duration criteria. Of 2,071 individuals reporting persistent sadness or the equivalent, 97.2% (N=2,016) satisfied criteria for distress. Of 1,542 individuals satisfying depression symptom-duration criteria, 96.2% (N=1,487) satisfied criteria for impairment. These findings support the redundancy thesis. Distress is virtually redundant with symptoms of persistent sadness, even in the absence of major depression, and impairment is almost always entailed by major depression-level symptoms. Thus, the clinical significance criterion does not substantially reduce the prevalence of major depression in the community. The DSM-V Task Force should consider eliminating the criterion and explore alternative ways to identify false positives in the diagnosis of depression. The criterion's status for other disorders should be evaluated on a disorder-by-disorder basis because the diagnostic relationship between symptoms and impairment varies across categories.


The species concept and its application to tailed phages.
A recently proposed polythetic definition of virus species appears easily applicable to bacteriophages. Criteria for classification of tailed phages are evaluated. Morphology, DNA homology, and serology are the most important criteria for delineation of species, but no single criterion is satisfactory. Dot-blot hybridization and seroneutralization may suggest false relationships by detecting common sequences in the DNA of otherwise unrelated phages. Species of tailed phages can be defined by a combination of morphology and DNA homology or serology. A procedure for identification of novel phages is outlined. Phage names should include elements of host names.


Insights into defibrotide: an updated review.
Defibrotide is a polydisperse oligonucleotide with antiatherosclerotic, anti-inflammatory, anti-ischaemic, pro-fibrinolytic and antithrombotic actions without significant systemic anticoagulant effects. It has been used in the treatment of various cardiovascular disorders, and especially in endothelial complications of allogeneic stem-cell transplantation. We reviewed the published work for the mechanism of action and clinical use of defibrotide to consolidate data and to describe new applications of this drug. We reviewed the most relevant papers on defibrotide published from November 1982 to January 2008. (selected through PubMed), and used recent meeting abstracts as sources for this review. Reports have suggested that defibrotide has clinical efficacy for treatment and prophylaxis of hepatic sinusoidal obstruction syndrome occurring after stem-cell transplantation. Animal models have clearly shown the potential antineoplastic effect of this drug. Further clinical investigations are needed to clarify this new application.


Ruxolitinib treatment for myelofibrosis: Efficacy and tolerability in routine practice.
Ruxolitinib has been shown in two randomized clinical trials to be effective in alleviating systemic symptoms and reducing spleen size in patients with myelofibrosis (MF). We retrospectively evaluated efficacy and tolerability of ruxolitinib in a cohort of unselected MF patients treated in routine clinical practice. One hundred and two patients who began ruxolitinib therapy were identified in 13 participating centers. Ninety three of the patients receiving ruxolitinib for at least 3 months were evaluated for treatment efficacy and toxicity. Median age at ruxolitinib initiation was 67 years. Indications for treatment were constitutional symptoms (15%), symptomatic splenomegaly (6%) or both (76%). Two patients received ruxolitinib for other indications. The median initial ruxolitinib dose was 30mg/day. Median duration of therapy was 11 months. Eighty two patients (88.2%) responded to therapy, 76 (84.4%) patients had improvement in constitutional symptoms and 60 patients (70.6%) had reduction in spleen length. While on ruxolitinib, 30% of patients had grade 3-4 anemia and 12.9% of patients had grade 3-4 thrombocytopenia. Thirteen patients (14%) discontinued therapy. This analysis of a cohort of MF patients treated with ruxolitinib in routine clinical practice demonstrates the efficacy and tolerability of this drug outside of a highly monitored clinical trial setting.


Lobaric acid and pseudodepsidones inhibit NF-κB signaling pathway by activation of PPAR-γ.
Herein we report the anti-inflammatory activity of lobaric acid and pseudodepsidones isolated from the nordic lichen Stereocaulon paschale. Lobaric acid (1) and three compounds (2, 7 and 9) were found to inhibit the NF-κB activation and the secretion of pro-inflammatory cytokines (IL-1β and TNF-α) in LPS-stimulated macrophages. Inhibition and docking simulation experiments provided evidence that lobaric acid and pseudodepsidones bind to PPAR-γ between helix H3 and the beta sheet, similarly to partial PPAR-γ agonists. These findings suggest that lobaric acid and pseudodepsidones reduce the expression of pro-inflammatory cytokines by blocking the NF-κB pathway via the activation of PPAR-γ.


[Gated blood pool imaging in the diagnosis and management of arrhythmia].
The usefulness of multigated cardiac blood pool imaging in evaluating left ventricular function and ventricular activation was studied in patients with cardiac arrhythmias. Subjects consisted of 12 patients with the Wolff-Parkinson-White (WPW) syndrome; 20 with ventricular premature contractions (VPC); 21 with various modes of artificial pacemakers; and two normal controls. Phase analysis was useful in localizing the bypass tract in patients with the WPW syndrome. In four patients with the WPW syndrome and five with VVI pacing, the phase difference between the posterolateral wall of the left ventricle (LV) and the right ventricular apex correlated significantly with the activation time difference between these two regions as assessed by endocardial electrograms (r = 0.94, p less than 0.001). Images of VPC were obtained using the bad beat rejection program in an ADAC computer system. The origin of VPCs evaluated by phase image coincided with results of standard 12-lead electrograms. It was in the right ventricle in four patients, the LV in one, and probably in the interventricular septum in one. The LV ejection fraction (LVEF) decreased significantly (p less than 0.001) after the injection of lidocaine (-3.7%) or disopyramide (-6.2%). The percent reduction in LVEF was significantly greater with disopyramide than with lidocaine (-15.1 vs -11.2%). The plasma concentration of disopyramide was higher in four patients with organic heart diseases than in 11 without. There was a significant correlation between the percent reduction in LVEF and the disopyramide plasma concentrations (r = -0.62, p less than 0.001). The influence of the pacing mode and exercise on LV function was studied in 21 patients with artificial pacemakers. In the VDD and DDD modes, end-diastolic volume (EDV) and cardiac output (CO) decreased after converting to VVI mode. CO increased markedly to approximately 250% of the control value in the VDD and DDD, and moderately in the VVI and AAI modes during ergometer exercise. In conclusion, multigated cardiac pool imaging is considered useful in diagnosing and managing patients with cardiac arrhythmias.


Linking Global Youth Tobacco Survey (GYTS) data to the WHO Framework Convention on Tobacco Control: the case for Indonesia.
Indonesia has the fifth highest rate of annual cigarette consumption per person of all countries worldwide. The Global Youth Tobacco Survey (GYTS) was developed to provide data on youth tobacco use to countries for their development of youth-based tobacco control programs. Data in this report can be used as baseline measures for future evaluation of the tobacco control program implemented by Indonesia's Ministry of Health. The 2006 Indonesia GYTS is a school-based survey that included separate samples for Java and Sumatera, representing more than 84% of the population of Indonesia. Each sample used a two-stage cluster sample design that produced representative samples of students in secondary grades 1-3, which are associated with ages 13-15 years. This report shows that more than 1 in 10 students (12.6%) currently smoked cigarettes, with the prevalence among boys (24.5%) significantly higher than among girls (2.3%). Of the students who currently smoked, more than 7 in 10 (75.9%) reported that they desired to stop smoking now. Regarding secondhand smoke exposure, more than 6 in 10 students (64.2%) reported that they were exposed to smoke from other people in their home during the week before the survey. More than 9 in 10 students (92.9%) had seen a lot of advertisements for cigarettes on billboards during the past month and more than 8 in 10 (82.8%) had seen a lot of advertisements for cigarettes in newspapers or in magazines. Tobacco control in Indonesia will likely not move forward until the government evaluates and strengthens existing laws, considers passing new strong laws, and develops protocols for enforcing all laws. The Indonesian government also should strongly consider accession to the World Health Organization Framework Convention on Tobacco Control.


Homology modeling of the transmembrane domain of the human calcium sensing receptor and localization of an allosteric binding site.
A homology model for the human calcium sensing receptor (hCaR) transmembrane domain utilizing bovine rhodopsin (bRho) structural information was derived and tested by docking the allosteric antagonist, NPS 2143, followed by mutagenesis of predicted contact sites. Mutation of residues Phe-668 (helix II), Arg-680, or Phe-684 (helix III) to Ala (or Val or Leu) and Glu-837 (helix VII) to Ile (or Gln) reduced the inhibitory effects of NPS 2143 on [Ca2+]i responses. The calcimimetic NPS R-568 increases the potency of Ca2+ in functional assays of CaR. Mutations at Phe-668, Phe-684, or Glu-837 attenuated the effects of this compound, but mutations at Arg-680 had no effect. In all cases, mutant CaRs responded normally to Ca2+ or phenylalanine, which act at distinct site(s). Discrimination by the Arg-680 mutant is consistent with the structural differences between NPS 2143, which contains an alkyl bridge hydroxyl group, and NPS R-568, which does not. The homology model of the CaR transmembrane domain robustly accounts for binding of both an allosteric antagonist and agonist, which share a common site, and provides a basis for the development of more specific and/or potent allosteric modulators of CaR. These studies suggest that the bRho backbone can be used as a starting point for homology modeling of even distantly related G protein-coupled receptors and provide a rational framework for investigation of the contributions of the transmembrane domain to CaR function.


Osteogenic properties of a short BMP-2 chimera peptide.
Bone morphogenetic proteins (BMPs) play a key role in bone and cartilage formation. For these properties, BMPs are employed in the field of tissue engineering to induce bone regeneration in damaged tissues. To overcome drawbacks due to the use of entire proteins, synthetic peptides derived from their parent BMPs have come out as promising molecules for biomaterial design. On the structural ground of the experimental BMP-2 receptor complexes reported in the literature, we designed three peptides, reproducing the BMP-2 region responsible for the binding to the type II receptor, ActRIIB. These peptides were characterized by NMR, and the structural features of the peptide-receptor binding interface were highlighted by docking experiments. Peptide-receptor binding affinities were analyzed by means of ELISA and surface plasmon resonance techniques. Furthermore, cellular assays were performed to assess their osteoinductive properties. A chimera peptide, obtained by combining the sequence portions 73-92 and 30-34 of BMP-2, shows the best affinity for ActRIIB in the series and represents a good starting point for the design of new compounds able to reproduce osteogenic properties of the parent BMP-2.


Nontoxic Metal-Cyclam Complexes, a New Class of Compounds with Potency against Drug-Resistant Mycobacterium tuberculosis.
Tuberculosis (TB) accounted for 1.5 million deaths in 2014, and new classes of anti-TB drugs are required. We report a class of functionalized 1,8-disubstituted cyclam derivatives that display low micromolar activity against pathogenic mycobacteria. These compounds inhibit intracellular growth of Mycobacterium tuberculosis, are nontoxic to human cell lines, and are active against multidrug-resistant M. tuberculosis strains, indicating a distinct mode of action. These compounds warrant further appraisal as novel agents to control TB in humans.


[Pharmacologic aspects of sleep disorders].
Sleep disorders are becoming a major issue. Insomnia affects a substantial part of the population and may compromise individual quality of life. The principal existing hypnotic drugs, Barbiturates and Benzodiazepines are not safely. They have modes of action which results in the action of common mechanism: facilitating neurotransmission in GABAergic synapses. Stimulation of GABA receptors of the A type opens chloride ion channels which inhibits the ability of neurons to conduct nerve impulse. The clinical effects resulting which induce anticonvulsant, muscle relaxant, anxiolytic, sedative, hypnotic and amnesic effects are discussed.


Borna disease virus-specific antigens: two different proteins identified by monoclonal antibodies.
A variety of cells originating from different species, including man, can be infected with Borna disease (BD) virus. Two different virus infection-specific antigens with molecular weights of 24 kD and 35/38 kD (double band) could be demonstrated using antigen preparations from persistently infected cells and rat brains, and polyvalent antisera from naturally and experimentally infected animals. Three different monoclonal antibodies were selected. One was specific for the 24-kD protein and two others reacted with the 35/38-kD antigen. The 24- and 35/38-kD antigens could be monitored concomitantly with the appearance of newly synthesized infectious virus. Both antigens could be detected at the same time during the infection cycle, and showed identical distribution in the cell. Their relationship to one another and their possible function is discussed.


Elimination kinetics of L-alanyl-L-glutamine in ICU patients.
A randomised, double blind, placebo-controlled study was performed giving 0.5 g x kg(-1) x day(-1) of undiluted alanyl-glutamine (20%) or saline in a peripheral vein during 4 hours in ICU patients (n = 20). During the infusion period a steady state in plasma concentration was reached for alanyl-glutamine, but not for alanine, glutamine or glutamate. On the other hand there was no accumulation of any of the amino acids, as the pre-infusion concentrations were reached within 8 hours after the end of infusion. The half-life of the dipeptide was 0.26 hours (range, 0.15-0.63 h). The distribution volume of alanyl-glutamine was larger than the extracellular water volume, indicating a rapid hydrolysis of the dipeptide. There was no detectable alanyl-glutamine in the urine of any of the patients. All patients had excretion of small amounts of amino acids in urine, but the renal clearance of alanine, glutamine and glutamate were not different between the two groups.


Glutamate and aspartate measurements in individual planaria by rapid capillary electrophoresis.
Planaria present a unique model organism for studying primitive central nervous systems. The major mammalian excitatory neurotransmitters, glutamate and aspartate, have previously been measured in planaria via high pressure liquid chromatography (HPLC). A faster extraction and analysis procedure using capillary electrophoresis (CE) was developed which confirms the presence of these amino acids in single planaria homogenates. Following homogenization and centrifugation of individual planaria in hydrochloric acid/acetonitrile, glutamate and aspartate were derivatized with naphthalene-2, 3-dicarboxaldehyde (NDA). The labeled amino acids were measured using capillary electrophoresis with laser-induced fluorescence (CE-LIF). CE-LIF electropherograms were generated in less than 1 min. The mean ± S.D. amounts of glutamate and aspartate were 1200 ± 500 and 1900 ± 700 pmol/mg-planarian (n=22), respectively. Spiked average recoveries of glutamate and aspartate were 96% and 91%, respectively. The high-throughput method provides the ability to quantitate changes in excitatory neurotransmitters under developmental or stimulatory conditions. The capability to monitor multiple neurotransmitter levels offers the opportunity to correlate behavioral responses with biochemical changes in planaria.


Prevalence and significance of anaemia in patients receiving long-course neoadjuvant chemoradiotherapy for rectal carcinoma.
The study aimed to assess the prevalence and significance of anaemia during long-course neoadjuvant radiotherapy for rectal cancer at our centre. Hospital coding and a prospective oncology database were used to identify all patients undergoing long-course neoadjuvant radiotherapy for rectal cancer at our centre between 2004 and 2009. A retrospective review of computerized records was used to extract individual patient data. Anaemia was defined as a haemoglobin level of < 11.5 g/dl for women and of < 13 g/dl for men. Downstaging was assessed by comparing radiological stage (rTNM) with histological stage (ypTNM). Tumour regression after radiotherapy was assessed using the Rectal Cancer Regression Group (RCRG) scores of 1-3. The results were analysed using Gnu PSPP statistical software. There were 70 patients (51 men) of median age 66 (interquartile range 60-72.75) years. Of these, 24 were anaemic. Two (3%) had no haemoglobin level recorded and were excluded. Forty-two per cent of anaemic patients demonstrated mural (T) downstaging compared with 68% of nonanaemic patients (P = 0.03). There was no difference in nodal downstaging between the groups. The RCRG scores showed more tumour regression in nonanaemic patients than in anaemic patients, as follows: RCRG 1, 59%vs 30%; RCRG 2, 11%vs 17%; and RCRG 3, 38%vs 46% (P < 0.001). The prevalence of anaemia in patients undergoing long-course neoadjuvant radiotherapy was 35%. Anaemia during long-course neoadjuvant radiotherapy was associated with significant reductions in tumour downstaging and regression.


Modeling the Length of Stay of Respiratory Patients in Emergency Department Using Coxian Phase-Type Distributions With Covariates.
Variability and unpredictability are typical features of emergency departments (EDs) where patients randomly arrive with diverse conditions. Patient length of stay (LOS) represents the consumption level of hospital resources, and it is positively skewed and heterogeneous. Both accurate modeling of patient ED LOS and analysis of potential blocking causes are especially useful for patient scheduling and resource management. To tackle the uncertainty of ED LOS, this paper introduces two methods: statistical modeling and distribution fitting. The models are applied to 894 respiratory diseases patients data in the year 2014 from ED of a Chinese public tertiary hospital. Covariates recorded include patient region, gender, age, arrival time, arrival mode, triage category, and treatment area. A Coxian phase-type (PH) distribution model with covariates is proposed as an alternative method for modeling ED LOS. The expectation-maximization (EM) algorithm is used to implement parameter estimation. The results show that ED LOS data can be modeled well by the proposed models. Distributions of ED LOS differ significantly with respect to patients' gender, arrival mode, and treatment area. Using the fitted Coxian PH model will assist ED managers in identifying patients who are most likely to have an extreme ED LOS and in predicting the forthcoming workload for resources.


Levetiracetam prophylaxis ameliorates seizure epileptogenesis after fluid percussion injury.
To determine whether post-traumatic seizure severity would be affected by the interval between seizures and head injury, we measured seizures after various times with or without fluid percussion brain injury (2atm fluid percussion injury; FPI). To determine efficacy of anti-seizure medication, we also determined if levetiracetam (LEV) would alter the relationship between injury and subsequent seizures. Early post-traumatic seizures were induced by Kainic acid (KA) at one week after 2atm fluid percussion injury (FPI) in one group (FPI-ES). Seizures were induced at two weeks after FPI by KA in another group (FPI-LS). In addition, one group had induced seizures by KA without FPI, (sham-ES). Finally one group of animals received the antiepileptic agent (levetiracetam) infusion for one week after FPI and then had seizures induced by KA (FPI-LEV-ES). We measured seizure onset time, ictal duration and severity of seizures using a modified Racine's scale. Histopathological changes in the hippocampus CA1 region were also analyzed. Severity of seizures were increased in the FPI-ES group compared with sham-ES animals. Severity was also enhanced in early post-injury seizures induced by KA (FPI-ES vs. FPI-LS); this exacerbation of seizure severity could be ameliorated by levetiracetam infusion (FPI-ES vs. FPI-LEV-ES). Neuronal degeneration in CA1 was more severe in the FPI-ES group and this degeneration was also diminished by LEV. We conclude that early post injury seizures exacerbate susceptibility and severity of post traumatic seizures and increase neuronal degeneration in the CA1 layer of hippocampus. These changes are partially reversed by LEV infusion after FPI.


Going upstream: the implication and opportunities of early detection.
Chronic kidney disease (CKD) is common, harmful and treatable but has, until recently not been recognised in its early stages. The British National Health Service (NHS) provides a unique opportunity to study CKD because it is in effect a closed-managed care system. This single healthcare system for the United Kingdom is funded by the Government and paid for by general taxation. All UK citizens are registered with primary care physicians who control access to secondary care services. As a managed care system it should be able to offer integrated care across the whole patient pathway--allowing early identification of CKD, interventions to reduce risk and prompt management of complications. In reality, there are professional, organisational and institutional barriers to coordination and delivery of care in the NHS. The establishment of general-practice-based disease registers linked to a quality and outcomes framework in 2004 provides a basis for implementing the chronic disease model of care. The publication of the National Service Framework for renal services complemented by these changes in primary care has resulted in a paradigm shift from kidney disease being viewed as a secondary care condition to being a primary care priority as part of vascular control and management. In the first two years of the initiative, over 40% of the expected CKD stage 3 to 5 population has been registered in primary care. Kidney disease is now recognised as a public health problem in the United Kingdom, preventative strategies are being integrated into comprehensive vascular risk assessments and management programmes and kidney disease has become an NHS priority area.


Larval habitats of anopheline mosquitoes in the Upper Orinoco, Venezuela.
Survey of larval habitats of anopheline mosquitoes was conducted in Ocamo in the State of Amazonas, southern Venezuela. The sampled habitats belonged to three different hydrological types: lagoons (26 habitats), forest pools including flooded forest (16 habitats), and forest streams (4 habitats). Out of 46 habitats surveyed, 31 contained anopheline larvae. Six species were found: Anopheles darlingi, Anopheles triannulatus, Anopheles oswaldoi, Anopheles peryassui, Anopheles punctimacula, and Anopheles mediopunctatus. Anopheles triannulatus was the most abundant species. Significantly higher numbers of anopheline larvae, in general, and of An. triannulatus specifically were found in lagoons with submersed macrophytes and sparse emergent graminoids than in forest pools with detritus.


Apolipoprotein E polymorphism and renal function in German type 1 and type 2 diabetic patients.
To examine the association of renal function in diabetic patients with apolipoprotein (apo) E polymorphism. Apo E genotypes, lipid and lipoprotein serum levels, creatinine clearance (CCr), and excretion of marker proteins were determined in German type 1 (IDDM; n = 162) and type 2 (NIDDM; n = 124) diabetic patients. Albumin and immunoglobulin (Ig) G are considered to reflect charge-size permselectivity of the glomerular capillary basement membrane, and increased alpha 1-microglobulin (MG) excretion indicates compromised reabsorptive capacity of the renal tubules. Patients with NIDDM had higher lipid levels and lower CCrs than patients with IDDM. In patients with IDDM, age- and sex-adjusted analysis of variance showed an association between apo E genotypes and CCr, and the Jonckheere-Terpstra test demonstrated a decreasing glomerular filtration rate in the following order of genotypes: epsilon 4 epsilon 4/epsilon 4 epsilon 3 > epsilon 3 epsilon 3 > epsilon 2 epsilon 2/epsilon 2 epsilon 3. Multiple linear regression analyses revealed that in patients with IDDM, the epsilon 2 allele was a negative predictor of CCr and a positive predictor of urinary excretion of albumin, IgG and alpha 1-MG independent from HDL and LDL cholesterol, TG concentration, age, and sex. Apo E polymorphism influences serum lipoprotein levels in patients with IDDM and NIDDM. Apo E polymorphism may be a renal risk factor of clinical relevance in normolipidemic patients with IDDM.


Biotransformation patterns of 2,4,6-trinitrotoluene by aerobic bacteria.
2,4,6-Trinitrotoluene (TNT), a toxic nitroaromatic explosive, accumulates in the environment, making necessary the remediation of contaminated areas and unused materials. Although bioremediation has been utilized to detoxify TNT, the metabolic processes involved in the metabolism of TNT have proven to be complex. The three aerobic bacterial strains reported here (Pseudomonas aeruginosa, Bacillus sp. , and Staphylococcus sp.) differ in their ability to biotransform TNT and in their growth characteristics in the presence of TNT. In addition, enzymatic activities have been identified that differ in the reduction of nitro groups, cofactor preferences, and the ability to eliminate-NO2 from the ring. The Bacillus sp. has the most diverse bioremediation potential owing to its growth in the presence of TNT, high level of reductive ability, and capability of removing-NO2 from the nitroaromatic ring.


The excitatory and inhibitory effects of nitrous oxide on spinal neuronal responses to noxious stimulation.
Because of the logistical obstacles to measurement under hyperbaric conditions, the effect of nitrous oxide (N2O) alone on spinal neuronal responses has not been tested. We hypothesized that, like other inhaled anesthetics, N2O would depress spinal neuronal responses to noxious stimulation. The lumbar spinal cord was exposed in rats anesthetized with isoflurane. Mechanically ventilated rats were placed into a hyperbaric chamber and needle electrodes were inserted into the hindpaws. Isoflurane administration was discontinued and anesthesia converted to N2O by pressurizing the chamber with N2O. A microelectrode was inserted into the lumbar cord using computer-controlled motors and a hydraulic microdrive. Neuronal responses to electrical stimulation of the hindpaw were sought at 1.5, 2, and 2.5 atm N2O (0.8-1.3 minimum alveolar concentration). Increasing N2O partial pressures variably affected neuronal responses to a 2 s 100-Hz electrical stimulus. Neuronal depth and neuronal response were correlated, with superficial neurons tending to be facilitated, while deeper neurons were depressed; (overall responses were 1331 +/- 408, 1594 +/- 383, and 1578 +/- 500 impulses/min at 1.5, 2, and 2.5 atm N2O, respectively; mean, standard error). N2O did not affect neuronal responses to a repetitive "windup" stimulus. Infusion of the N-methyl-d-aspartate blocker MK-801 into separate rats increased the neuronal response to the 100-Hz stimulus (from 781 +/- 216 to 1352 +/- 269 impulses/min, P < 0.05). N2O facilitated superficial spinal neuronal responses to noxious stimulation while depressing deeper neurons. These results suggest that anesthetic partial pressures of N2O have divergent effects on spinal neuronal responses to noxious stimulation, the specific responses depending on the depth of the spinal neurons.


Ingested aggregates of ultrafine carbon particles and interferon-gamma impair rat alveolar macrophage function.
Alveolar macrophages (AM), obtained by lavage from the rat lung, were allowed to ingest aggregated ultrafine carbon particles, about 1 microgram/10(6) AM, which is a realistic result of long-term exposure to ambient air. The effects of the ingested carbon on the phagocytosis of test particles and oxidative metabolism of the AM were studied. In addition, the effects of short-term (40 min or 2 h) and long-term (28 or 44 h) incubation with interferon gamma (IFN-gamma) on AM loaded and unloaded with carbon were investigated. Phagocytic activity was studied using fluorescein-labeled 3.2-microgram silica particles. The attachment and ingestion processes were evaluated separately. The ingested carbon markedly impaired the phagocytosis of silica particles; the accumulated attachment (sum of attached and ingested particles per AM) decreased from 5.0 to 4.2 particles/AM and the ingested fraction (number of ingested particles per AM divided with accumulated attachment) from 0.42 to 0.27. The short-term incubation with IFN-gamma tended to increase the accumulated attachment (from 5.0 to 5.7 particles/AM) and decreased the ingested fraction (from 0.42 to 0.34) in unloaded AM. Long-term incubation with IFN-gamma markedly impaired both the accumulated attachment (to 3.8 particles/AM) and the ingested fraction (to 0.24) in unloaded AM and the carbon load further decreased the accumulated attachment to 2.8 particles/AM, and the ingested fraction to 0.21. The oxidative metabolism was not effected by the ingested carbon or the short-term incubation with IFN-gamma, but the long-term incubation with IFN-gamma increased it with a factor of almost 3. Our results suggest that ingested environmental particles in AM may markedly impair their phagocytic capacity, especially during long-term exposure to IFN-gamma as after infections, and there might be an increased risk for additional infections. Moreover, during an episode of high ambient particle concentration the inhaled particles will not be efficiently phagocytized and may thereby damage the Lung tissue.


Total intravenous anesthesia with midazolam, ketamine, and xylazine or detomidine following induction with tiletamine, zolazepam, and xylazine in red deer (Cervus elaphus hippelaphus) undergoing surgery.
Sixteen captive female red deer were successfully anesthetized to surgically implant a telemetry system. The deer were immobilized with (mean±SD) 1.79±0.29 mg/kg xylazine and 1.79±0.29 mg/kg tiletamine/zolazepam given intramuscularly with a dart gun. Anesthesia was maintained for 69±2 min using a total intravenous protocol with a catheter placed in the jugular vein. Group X received xylazine (0.5±0.055 mg/kg/hr) and group D, detomidine (2±0.22 μg/kg/hr), both in combination with ketamine (2±0.02 mg/kg/hr) and midazolam (0.03±0.0033 mg/kg/hr), as a constant rate infusion. Anesthesia was reversed with 0.09±0.01 mg/kg atipamezole and 8.7±1.21 μg/kg sarmazenil given intravenously in both groups. These drug combinations provided smooth induction, stable anesthesia for surgery, and rapid recovery. Respiratory depression and mild hypoxemia were seen, and we, therefore, recommend using supplemental intranasal oxygen.


Antibodies to insulin receptor followed by anti-idiotype. Antibodies to insulin in child with hypoglycemia.
A child presenting severe hypoglycemia despite low or normal secretion of insulin was found to have IgM antibodies to the insulin receptor. These antibodies stimulated lipogenesis in fat cells in vitro and competed with insulin for binding to insulin receptors. After treatment with glucocorticoids, the anti-receptor antibodies and the hypoglycemia both disappeared, and antibodies to insulin appeared in the patient's serum. The anti-insulin antibodies were isolated by affinity chromatography and were found to inhibit the anti-insulin-receptor antibodies that were present earlier. The interaction between the patient's anti-insulin antibodies and his anti-receptor antibodies suggests that these two species of antibodies are related as idiotypes and anti-idiotypes. We also studied the interaction of the hypoglycemic patient's anti-receptor antibodies with anti-insulin antibodies of a diabetic patient and with anti-insulin antibodies of mice immunized to insulin. The hypoglycemic patient's anti-receptor antibodies were neutralized by the diabetic patient's anti-insulin antibodies, indicating that anti-insulin antibodies with a common idiotype may arise in both diabetes and hypoglycemia. Moreover, mouse anti-insulin antibodies that interacted with mouse anti-receptor antibodies neutralized the hypoglycemic patient's anti-receptor antibodies. In contrast, mouse anti-insulin antibodies that did not interact with the mouse anti-receptor antibodies did not neutralize the hypoglycemic patient's anti-receptor antibodies. Thus, the human anti-insulin antibodies share an idiotype with a specific class of mouse anti-insulin antibodies.(ABSTRACT TRUNCATED AT 250 WORDS)


Randomized sequential trial of valproic acid in amyotrophic lateral sclerosis.
To determine whether valproic acid (VPA), a histone deacetylase inhibitor that showed antioxidative and antiapoptotic properties and reduced glutamate toxicity in preclinical studies, is safe and effective in amyotrophic lateral sclerosis (ALS) using a sequential trial design. Between April 2005 and January 2007, 163 ALS patients received VPA 1,500mg or placebo daily. Primary end point was survival. Secondary outcome measure was decline of functional status measured by the revised ALS Functional Rating Scale. Analysis was by intention to treat and according to a sequential trial design. This trial was registered with ClinicalTrials.gov (number NCT00136110). VPA did not affect survival (cumulative survival probability of 0.72 in the VPA group [standard error (SE), 0.06] vs 0.88 in the placebo group [SE, 0.04] at 12 months, and 0.59 in the VPA group [SE, 0.07] vs 0.68 in the placebo group [SE, 0.08] at 16 months) or the rate of decline of functional status. VPA intake did not cause serious adverse reactions. Our finding that VPA, at a dose used in epilepsy, does not show a beneficial effect on survival or disease progression in patients with ALS has implications for future trials with histone deacetylase inhibitors in ALS and other neurodegenerative diseases. The use of a sequential trial design allowed inclusion of only half the number of patients required for a classic trial design and prevented patients from unnecessarily continuing potentially harmful study medication.


Safety evaluation of an enzymatically-synthesized glycogen (ESG).
An enzymatically-synthesized glycogen (ESG), intended for use as a food ingredient, was investigated for potential toxicity. ESG is synthesized in vitro from short-chain amylose by the co-operative action of branching enzyme and amylomaltase. In an acute toxicity study, oral administration of ESG to Sprague-Dawley rats at a dose of 2000 mg/kg body weight did not result in any signs of toxicity. ESG did not exhibit mutagenic activity in an in vitro bacterial reverse mutation assay. In a subchronic toxicity study, increased cecal weights noted in the mid- (10%) and high-dose (30%) animals are common findings in rodents fed excess amounts of carbohydrates that increase osmotic value of the cecal contents, and thus were considered a physiological rather than toxicological response. The hematological and histopathological effects observed in the high-dose groups were of no toxicological concern as they were secondary to the physiological responses resulting from the high carbohydrate levels in the test diets. The no-observed-adverse-effect level for ESG in rats was therefore established to be 30% in the diet (equivalent to approximately 18 and 21 g/kg body weight/day for male and female rats, respectively). These results support the safety of ESG as a food ingredient for human consumption.


Learning Curves of Emergency Tourniquet Use Exploring for Utility in Training.
Emergency tourniquet use to control hemorrhage from limb wounds is associated with improved survival and control of shock. In 2013, we introduced a way to measure learning curves of tourniquet users. With a dataset from an unrelated study, we had an opportunity to explore learning in detail. The study aim was to generate hypotheses about measurement methods in the learning of tourniquet users. We gathered data from a previous experiment that yielded a convenient sample of repeated tourniquet applications used as a marker of learning. Data on consecutive applications on a manikin were used in the current report and were associated with two users, three models of tourniquet, and six metrics (i.e., effectiveness, pulse cessation, blood loss, time to effectiveness, windlass turn number, and pressure applied). There were 840 tests (140 tests per user, two users, three models). Unique characteristics of learning were associated with each user. Hypotheses generated included the following: trainee learning curves can vary in shape (e.g., flat, curved) by which metric of learning is chosen; some metrics may show much learning, whereas others show almost none; use of more than one metric may assess more comprehensively than using only one metric but may require more assessment time; number of uses required can vary by instructional goal (e.g., expertise, competence); awareness of the utility of specific metrics may vary by instructor; and some, but not all, increases in experience are associated with improved performance. This first-aid study generated hypotheses about caregiver learning for further study of tourniquet education and standards.


Effect of polydispersity on natural organic matter transport.
The mobility of humic-substance dominated natural organic matter (NOM) concentrated from a freshwater wetland by reverse osmosis was examined in sand columns at pH 5-8, in 0.001 M and 0.01 M NaClO4. Greater mobility was observed at higher pH and lower ionic strength, although breakthrough curves (BTCs) for bulk NOM exhibited extensive tailing under all conditions examined. Based on observations from previous batch experiments indicating preferential adsorption of intermediate to high molecular weight (MW) NOM, we postulate that 'adsorptive fractionation' of the NOM pool leads to the observed tailing behavior, and develop a novel approach to assess the effects of polydispersity on transport of NOM and associated contaminants. BTCs for different NOM fractions were constructed by separating column effluent MW distributions determined by high-pressure size exclusion chromatography into five discrete intervals or 'bins' and calculating the mass of NOM within each bin at four sampling times. Observed retardation factors (Ro), reflecting median arrival time relative to that of a nonreactive tracer, ranged from 1.4 to 7.9 for the various bins and generally increased with MW. NOM retarded transport of the contaminant metal Cd (2.5 ppm, in 0.01 M NaClO4) slightly at pH 5 and more substantially at pH 8. Although Cd had little or no effect on bulk NOM transport, retention of the more aromatic, IMW-HMW NOM appeared to be slightly enhanced by Cd. Study results demonstrate that heterogeneity in retardation as a function of MW is likely a major factor contributing to bulk NOM BTC tailing and may have important implications for contaminant transport.