Pain in alcohol use disorder: Evaluating effects of childhood trauma, perceived stress, and psychological comorbidity.

The relationship between pain and alcohol use disorder (AUD) is complex and bidirectional. The current study examines risk factors for pain in a large comprehensively phenotyped sample including individuals from across the spectrum of alcohol use and misuse. Participants (n = 1101) were drawn from the National Institute on Alcohol Abuse and Alcoholism Natural History Protocol and included treatment-seeking AUD inpatients (AUD+Tx, n = 369), individuals with AUD not seeking treatment (AUD+, n = 161), and individuals without AUD (AUD-, n = 571). General linear models were utilized to test the effects of AUD status, history of childhood trauma exposure, perceived stress, and psychological comorbidity on daily percent time in pain, as well as change in daily percent time in pain across the inpatient stay in AUD+Tx individuals. Overall, 60.2% individuals reported any pain, with a significantly higher prevalence in the AUD+Tx group (82.1%) compared to the AUD+ (56.5%) and AUD- (47.1%) groups. Daily percent time in pain was also highest in the AUD+Tx group (30.2%) and was further increased in those with a history of childhood abuse and comorbid posttraumatic stress disorder (PTSD). Years of heavy drinking and craving were also associated with increased percent time in pain in the AUD+Tx group. Percent time in pain decreased following acute withdrawal in the AUD+Tx group but plateaued around 25% just prior to discharge. Individuals seeking inpatient treatment for AUD, especially those with a history of childhood trauma and/or comorbid PTSD, report greater percent time in pain compared to those not seeking treatment and those without AUD. The prolonged experience of pain in abstinent AUD inpatients after the resolution of acute withdrawal may signal the early stages of protracted withdrawal. Integrative treatments targeting pain and other symptoms of protracted withdrawal may be effective in improving overall function in people with severe AUD.

Investigation of physical and biological properties of polypyrrole nanotubes-chitosan nanocomposites.

Polypyrrole nanotubes-chitosan (PPy-NTs:chitosan) nanocomposite films have been synthesized with varying concentration of polypyrrole nanotubes (PPy-NTs) and their physical and biological properties have been investigated. Scanning electron microscopy (SEM) micrographs exhibit the increase in surface roughness of the nanocomposite films with increasing concentration of PPy-NTs. Enhancement in hydrophilicity of the nanocomposite films has been observed after surface functionalization with glutaraldehyde which is attributed to increase in surface energy due to the incorporation of polar groups on the films surface. The increasing amount of PPy-NTs in the nanocomposite leads to an increase in haemolysis activity, while the treatment with glutaraldehyde results in the decrease in haemolysis activity giving rise to higher biocompatibility. Urease immobilization in glutaraldehyde treated films exhibits higher enzymatic activity as compared to that of the untreated films, which is attributed to the enhancement in hydrophilicity and biocompatibility of the PPy-NTs:chitosan nanocomposites after functionalization with glutaraldehyde.

Antibacterial and hemolysis activity of polypyrrole nanotubes decorated with silver nanoparticles by an in-situ reduction process.

Polypyrrole nanotube-silver nanoparticle nanocomposites (PPy-NTs:Ag-NPs) have been synthesized by in-situ reduction of silver nitrate (AgNO3) to suppress the agglomeration of Ag-NPs. The morphology and chemical structure of the nanocomposites have been studied by HRTEM, SEM, XRD, FTIR and UV-vis spectroscopy. The average diameter of the polypyrrole nanotubes (PPy-NTs) is measured to be 130.59±5.5 nm with their length in the micrometer range, while the silver nanoparticles (Ag-NPs) exhibit spherical shape with an average diameter of 23.12±3.23 nm. In-vitro blood compatibility of the nanocomposites has been carried out via hemolysis assay. Antimicrobial activity of the nanocomposites has been investigated with Escherichia coli (E. coli) and Staphylococcus aureus (S. aureus) bacteria. The results depict that the hemolysis and antimicrobial activities of the nanocomposites increase with increasing Ag-NP concentration that can be controlled by the AgNO3 precursor concentration in the in-situ process.

Modeling of particulate matter dispersion from a poultry facility using AERMOD.

This study evaluates the performance of AERMOD, the current U.S. Environmental Protection Agency (EPA) regulatory model, in simulating particulate matter (PM10 and PM2.5) dispersion from a poultry pullet facility. At the source, the daily mean PM10 and PM2.5 concentrations with strong diurnal patterns were estimated to be 436.01 ± 166.77 µg m⁻³ and 291.09 ± 105.81 µg m⁻³, respectively. This corresponded to daily mean emission rates of PM10 and PM2.5 as 0.067-0.073 g sec⁻¹ and 0.044-0.047 g sec⁻¹,respectively. The modeled hourly PM concentration showed acceptable accuracy relative to the measured PM concentrations downwind of the source. Increasing the averaging period from hourly to daily resulted in improved prediction. The simulations revealed that PM concentrations at and beyond the property line of the poultry facility were within the National Ambient Air Quality Standards. This study suggested that AERMOD is effective in predicting and assessing the impacts of PM downwind of poultry facilities.

Development of high-voltage pulse generator with variable amplitude and duration.

A high voltage pulse generator with variable amplitude (100-3000 V) and duration (100-2000 µs) has been designed and developed. The variable duration pulse has been generated by adopting a simple and novel technique of varying the turn off delay time of a high voltage Metal Oxide Semiconductor Field Effect Transistor (MOSFET) based switch by varying external gate resistance. The pulse amplitude is made variable by adjusting biasing supply of the high voltage switch. The high voltage switch has been developed using a MOSFET based stack of 3 kV rating with switching time of 7 ns.

Gabapentin-induced pharmacodynamic effects in the spinal nerve ligation model of neuropathic pain.

BACKGROUND: The function of brain networks can be changed in a maladaptive manner in response to chronic neuropathic pain. Analgesics can reduce pain by acting on such networks via direct or indirect (peripheral or spinal) mechanisms. This investigation aimed to map gabapentin's pharmacodynamics (PD) in the rodent brain following induction of neuropathic pain in order to further understand its PD profile. METHODS: Pharmacological magnetic resonance imaging (phMRI) and a novel functional connectivity analysis procedure were performed following vehicle or gabapentin treatment in the rat spinal nerve ligation (SNL) model of neuropathic pain as well as sham animals. RESULTS: phMRI performed in SNL animals revealed robust gabapentin-induced responses throughout the hippocampal formation, yet significant (p < 0.05, corrected for multiple comparisons) responses were also measured in other limbic structures and the sensorimotor system. In comparison, sham animals displayed weaker and less widespread phMRI signal changes subsequent to gabapentin treatment. Next, communities of networks possessing strong functional connectivity were elucidated in vehicle-treated SNL and sham animals. We observed that SNL and sham animals possessed distinct functional connectivity signatures. When measuring how gabapentin altered the behaviour of the discovered networks, a decrease in functional connectivity driven by gabapentin was not only observed, but the magnitude of this PD effect was greater in SNL animals. CONCLUSIONS: Using phMRI and functional connectivity analysis approaches, the PD effects of gabapentin in a preclinical neuropathic pain state were characterized. Furthermore, the current results offer insights on which brain systems gabapentin directly or indirectly acts upon.

Engineering polypyrrole nanotubes by 100 MeV Si9+ ion beam irradiation: enhancement of antioxidant activity.

In this work, the effect of 100 MeV Si(9+) ion beam with four different fluences on antioxidant and structural properties of polypyrrole nanotubes has been investigated. Polypyrrole nanotubes have been synthesized by reactive self degrade template method. Fragmentation of the polypyrrole nanotubes at higher fluence is revealed from the high resolution transmission electron micrograph (HRTEM) and X-ray diffraction (XRD) results. The decrease in characteristics band of polypyrrole in Fourier transmission of infrared spectra (FTIR) spectra suggests the main chain scission of polypyrrole during irradiation. The free radical scavenging activity of pristine and irradiated samples are evaluated by using α, α-diphenyl-ß-picrylhydrazyl (DPPH) assay. The decline of the UV-visible absorbance at 516 nm suggests the neutralization of DPPH free radicals through the reaction with polypyrrole. Significant increase in antioxidant activity of polypyrrole nanotubes is observed with increase in ion fluence.

Development of high-voltage pulse-slicer unit with variable pulse duration for pulse radiolysis system.

A high-voltage pulse-slicer unit with variable pulse duration has been developed and integrated with a 7 MeV linear electron accelerator (LINAC) for pulse radiolysis investigation. The pulse-slicer unit provides switching voltage from 1 kV to 10 kV with rise time better than 5 ns. Two MOSFET based 10 kV switches were configured in differential mode to get variable duration pulses. The high-voltage pulse has been applied to the deflecting plates of the LINAC for slicing of electron beam of 2 µs duration. The duration of the electron beam has been varied from 30 ns to 2 µs with the optimized pulse amplitude of 7 kV to get corresponding radiation doses from 6 Gy to 167 Gy.

Magnetic resonance imaging and histological evidence for the blockade of cuprizone-induced demyelination in C57BL/6 mice.

Several neuroimaging studies have revealed that the brains of schizophrenic patients exhibit abnormalities in white matter pathways. Using magnetic resonance imaging (MRI) methods, such as T2-weighted imaging and diffusion tensor imaging (DTI), it is possible to objectively quantify white matter structural properties in patients as well as the pharmacological effect on white matter. In the preclinical domain, these strategies, however, have been hindered by a lack of in vivo imaging assays. One preclinical approach that has been used to pharmacologically challenge the integrity of the white matter is the chronic administration of the copper chelator, cuprizone. In the present study, C57BL/6 mice were given 0.2% cuprizone in their diet for five weeks with or without the antipsychotic drug, quetiapine (10 mg/kg). In accordance with previous studies, myelin breakdown in cuprizone-exposed mice was measured by using T2-weighted MRI and DTI. Here, we demonstrate that cuprizone-induced white matter changes were attenuated by quetiapine treatment. These MRI-based results and trends were confirmed by histological and immunohistochemistry measures. This study suggests that the cuprizone-exposed C57BL/6 mouse is a potential animal model to investigate the impact of treatments on white matter abnormalities in schizophrenia.

Design of microcontroller based system for automation of streak camera.

A microcontroller based system has been developed for automation of the S-20 optical streak camera, which is used as a diagnostic tool to measure ultrafast light phenomenon. An 8 bit MCS family microcontroller is employed to generate all control signals for the streak camera. All biasing voltages required for various electrodes of the tubes are generated using dc-to-dc converters. A high voltage ramp signal is generated through a step generator unit followed by an integrator circuit and is applied to the camera's deflecting plates. The slope of the ramp can be changed by varying values of the capacitor and inductor. A programmable digital delay generator has been developed for synchronization of ramp signal with the optical signal. An independent hardwired interlock circuit has been developed for machine safety. A LABVIEW based graphical user interface has been developed which enables the user to program the settings of the camera and capture the image. The image is displayed with intensity profiles along horizontal and vertical axes. The streak camera was calibrated using nanosecond and femtosecond lasers.

A high voltage programmable ramp generator.

In this paper, a ramp generator with programmable slope is presented. It consists of a high voltage step generator, followed by integrator. The capacitor and inductor in the integrator are designed such that they can be varied by a microcontroller. This circuit generates two bipolar ramps with fastest speed <1 ns and provides continuous speed variation from 6 to 30 ns for a ramp of 500 V. This is being developed as a part of automated streak camera for deflection of electron beam.

Hyponatremic seizures after suprapubic catheter placement in 7-year-old child.

We report a case of hyponatremic seizures in a 7-year old boy with spina bifida following cystoscopy and suprapubic catheter placement. Immediate postoperative cystogram and pelvic computed tomogram (CT) after the development of seizures demonstrated a fluid collection from the suprapubic catheter site into the anterior abdominal wall. The subsequent reabsorption of free water from the fluid collection, with the contribution of postoperative hypotonic intravenous fluid administration and possible transient inappropriate antidiuretic hormone (ADH) secretion resulted in acute dilutional hyponatremia and consequent seizures. Strategies to prevent hyponatremia in children during urological procedures, with emphasis on the importance of reserving free water as the irrigation fluid are discussed.

The predictive value of diagnostic imaging for histological lesions of the upper poles in duplex systems with ureteroceles.

OBJECTIVE: To compare the diagnostic imaging findings with the histological lesions in upper pole nephrectomy (UPN) specimens of duplex system ureteroceles, using renal ultrasonography (US) and nuclear renal scintigraphy. PATIENTS AND METHODS: Between 1992 and 2000, 86 patients with a ureterocele in a duplex system underwent surgery. The results from US were reviewed in 84 patients by a radiologist, for echogenicity, parenchymal thinning and hydronephrosis; 77 nuclear renal scans describing the differential function of the upper poles were also reviewed. Fifty-five patients underwent UPN (25 antenatal, 30 postnatal; 18 intravesical, 37 extravesical) and the specimens were available for independent review by a pathologist, describing five histological categories, i.e. chronic interstitial inflammation, fibrosis, tubular atrophy, glomerulosclerosis and dysplasia. Histological lesions were categorized as severe (> 25%) or minimal (

The use of tolterodine in children after oxybutynin failure.

OBJECTIVE: To assess the safety and efficacy of tolterodine tartrate prescribed to children who previously failed to tolerate oxybutynin chloride. PATIENTS AND METHODS: We reviewed 34 children, followed for>1 year, who were prospectively crossed-over from oxybutynin to tolterodine because of side-effects. The initial diagnosis was dysfunctional voiding in 31 patients. All patients were placed on a behavioural modification protocol. When their symptoms did not improve after 6 months, treatment with an anticholinergic agent was considered. Urodynamic studies were conducted in 20 patients, confirming uninhibited contractions in 19. The remaining 14 patients were empirically started on antimuscarinic or anticholinergic agents. The 34 patients were treated with oxybutynin for a median (range) of 6 (2-84) months. When significant side-effects were reported, they were crossed over to tolterodine. The efficacy of tolterodine was assessed as defined by the International Children's Continence Society, with tolerability assessed and side-effects documented using a questionnaire. RESULTS: The mean age at the first dose of tolterodine was 8.9 years; the dose was 1 mg twice daily for 12 patients and 2 mg twice daily for 22. The median treatment with tolterodine was 11.5 months, with 20 (59%) patients reporting no side-effects; six described the same but tolerable side-effects as with oxybutynin. Eight patients discontinued tolterodine because of side-effects after a median (range) of 5 (1-11) months. The efficacy of tolterodine was comparable with that of oxybutynin, as reported by the questionnaire and voiding diaries. The reduction in wetting episodes at 1 year was> 90% in 23 (68%), more than half in five and less than half (or failure) in six patients. CONCLUSION: Tolterodine is tolerated well in children. In this subgroup of patients who could not tolerate oxybutynin, 77% were able to continue tolterodine treatment with no significant side-effects.

Salvage radical prostatectomy.

Although technically challenging, salvage prostatectomy for radiorecurrent prostate cancer is an effective option in carefully selected patients and offers the best chance for cure and long-term survival. Alternatively, cystoprostatectomy may be indicated in some patients who have a small capacity fibrotic bladder or intractable voiding symptoms related to radiation cystitis. Good long-term results can be expected in this patient group; however, exenterative surgery in patients with locally advanced disease is associated with comparably inferior results and should not be advocated. If cystectomy is necessary, orthotopic urinary diversion can be performed safely in young motivated patients who wish to maintain a better quality of life with associated morbidity. Although the higher rate of incontinence and impotence after salvage procedures may detract from the quality of life, the impact of these long-term complications on the patient's overall well-being is less than previously believed, and most patients are satisfied with their treatment outcome and adjust well to the circumstances, accepting some increased degree of morbidity. This observation emphasizes the value of careful preoperative counseling and the discussion of treatment options and outcomes, which also should incorporate quality of life issues.

Intraoperative, perioperative, and long-term complications of radical prostatectomy.

With improved surgical technique and perioperative care, the intraoperative and early postoperative complications of radical prostatectomy have decreased over the last 2 decades. Incontinence and impotence are two of the most significant long-term complications related to this procedure. Although the wide range of incontinence and impotence rates reported has been attributed to multiple factors, including the method of data collection and patient selection, it is apparent that the surgeon's experience is a significant factor, and that lower long-term morbidity can be expected from centers with more experience with radical prostatectomies. The impact of long-term complications, including urinary and sexual dysfunction, on the quality of life may be less than previously reported and should be discussed with patients.

Impact of preoperative serum PSA level from 0 to 10 ng/ml on pathological findings and disease-free survival after radical prostatectomy.

BACKGROUND: To determine the impact of various preoperative serum prostate specific antigen (PSA) levels in the range from 0.1 to 10 ng/ml on pathological stage and disease-free survival after radical prostatectomy. METHODS: We selected a cohort of 585 patients who underwent radical prostatectomy between 1991-1996 for clinically localized prostate cancer and presented with preoperative serum PSA levels from 0.1 to 10 ng/ml. RESULTS: Pathological organ-confined disease was present in 57.6% of patients. The rate of organ-confined disease decreased from an average of 85% for patients with a PSA value < 2 ng/ml, to 46.8% for patients with a PSA value > 7 ng/ml. We found statistically significant correlations between preoperative serum PSA level and overall pathological stage (P = 0.001), pathologically organ-confined disease (P = 0.001), margin positive rates (P = 0.001), extra prostatic extension (P = 0.001), and seminal vesicle invasion (P = 0.001). The overall disease-free survival rate was 87%, with a median follow up of 42.4 months. Disease free survival was significantly better for patients with PSA up to 4 ng/ml (P = 0.005). CONCLUSIONS: Our data suggests that PSA detection programs should strive to detect prostate cancer in men before the PSA level rises above 7 ng/ml. In addition, since patients with a PSA level < 4 ng/ml had better disease-free survival rates than those with a PSA level between 4.1-10 ng/ml, eliminating an arbitrary cutoff of 4 ng/ml, may lead to improved disease-free survival.

Testicular position in the androgen insensitivity syndrome: implications for the role of androgens in testicular descent.

PURPOSE: We compared testicular position with genital phenotype in a clinical series and a literature review of androgen receptor mutations to assess the role of androgens in testicular descent. MATERIALS AND METHODS: Our clinical reports, the androgen receptor mutations database and selected literature were reviewed. Subjects with a proved androgen receptor mutation were included in our study when a female or ambiguous phenotype was present (Quigley grade 3 to 7) and testicular position was documented. Comparison among groups was done by Fisher's exact or chi-square test. RESULTS: Of the 7 patients with detailed clinical records 5 had abdominal (bilateral in 4) and 2 had bilateral inguinal testes. Four patients with abdominal testes also had aberrant pelvic ligaments extending medially from the gonads. Including an additional 102 cases identified in the literature, abdominal testes were present in 52% and 3% of those with complete and partial androgen insensitivity, respectively. The incidence of abdominal testes was highest (86%) in patients with a complete female phenotype and no pubic hair (grade 7). It decreased significantly with increasing masculinization and was higher in phenotypic females diagnosed at or after (67%) than in those identified before (22%) puberty. Hernia was associated with inguinal and abdominal testes. CONCLUSIONS: Testicular position correlates with genital phenotype in patients with androgen receptor mutations, supporting a major role for androgens in testicular descent. Inguinal hernia and abnormal pelvic ligaments in these individuals may partially determine testicular position but to our knowledge the role of androgen receptors, if any, in their development is unknown.

Massive hematuria in adults with Klippel-Trenaunay syndrome associated with vascular malformation of the bladder.

Although hematuria has been reported in children with Klippel-Trenaunay syndrome, it is a rare presentation in the adult population. Two cases of massive hematuria in adults with Klippel-Trenaunay syndrome are reported here. A unique feature was venous malformations of the bladder which were responsible for massive recurrent bleeding in 1 patient. The clinical presentation and management are discussed. Conservative endoscopic and arteriographic control seems to be appropriate as initial management in these patients.

Impact of location and multifocality of positive surgical margins on disease-free survival following radical prostatectomy: a comparison between African-American and white men.

OBJECTIVES: Although the rate of positive surgical margins is higher in African-American men (AAM) than in white men (WM), the impact of this difference on survival is not clear. Furthermore, it is unknown whether there are racial differences in the distribution of the positive surgical margins after radical retropubic prostatectomy (RRP). We investigated the differences between AAM and WM in terms of the site and multifocality of the positive surgical margins and their effect on disease-free survival (DFS) following RRP. METHODS: Between January 1991 and December 1995, 493 patients (288 WM and 205 AAM) were treated with RRP as monotherapy. Positive surgical margins were observed in 179 patients (86 WM and 93 AAM). Patients were divided in two groups: group 1 = WM and group 2 = AAM. The incidence and location of the positive surgical margins and their correlation with DFS were determined and compared. RESULTS: Overall, AAM had a higher rate of positive surgical margins than WM (48% versus 33%, respectively, P = 0.001). There was no significant difference in the frequency of multifocality of the positive margins (P = 0.4). Positive surgical margins were located significantly more often at the base in AAM (P = 0.015); however, the location of the positive surgical margins did not impact on DFS between groups. In those with multifocal positive surgical margins, AAM had a worse DFS compared with WM (P = 0.03). CONCLUSIONS: Race is an independent prognostic factor for DFS in patients with positive surgical margins. There were no differences in DFS between WM and AAM based on the margin location. In WM, prognostic factors for DFS in those with positive surgical margins were preoperative serum prostate-specific antigen, Gleason score, and pathologic stage. Conversely, in AAM none of these parameters were significant predictors of failure.