Synthesis and evaluation of druglike parameters via in silico techniques for a series of heterocyclic monosquarate-amide derivatives as potential carboxylic acid bioisosteres.

Herein, we present a synthetic compound library comprising of 13 structurally diverse heterocyclic monosquarate-amide derivatives. The compounds featured in this library were designed as potential bioisosteric replacements carboxylic acid moiety's. A good selection of the compounds presented exhibit unique molecular architecture and have shown promising results following in silico evaluation of 'druglike properties' using Swiss ADME. The research presented in this work focuses on the preparation of derivatives of 3,4-dihydroxycyclobut-3-ene-1,2-dione, a known carboxylic acid bioisostere.

Electrokinetic Active Particles for Motion-Based Biomolecule Detection.

Detection of biomolecules is essential for patient diagnosis, disease management, and numerous other applications. Recently, nano- and microparticle-based detection has been explored for improving traditional assays by reducing required sample volumes and assay times as well as enhancing tunability. Among these approaches, active particle-based assays that couple particle motion to biomolecule concentration expand assay accessibility through simplified signal outputs. However, most of these approaches require secondary labeling, which complicates workflows and introduces additional points of error. Here, we show a proof-of-concept for a label-free, motion-based biomolecule detection system using electrokinetic active particles. We prepare induced-charge electrophoretic microsensors (ICEMs) for the capture of two model biomolecules, streptavidin and ovalbumin, and show that the specific capture of the biomolecules leads to direct signal transduction through ICEM speed suppression at concentrations as low as 0.1 nM. This work lays the foundation for a new paradigm of rapid, simple, and label-free biomolecule detection using active particles.

USA Department of Defense audit of surgical antibiotic prophylaxis prescribing patterns in inguinal hernia repair.

PURPOSE: Antibiotic prophylaxis in inguinal hernia repair (IHR) is contentious in literature and practice. In low-risk patients, for whom evidence suggests antibiotic prophylaxis is unnecessary, many surgeons still advocate for its routine use. This study surveys prescription patterns of Department of Defense (DoD) general surgeons. METHODS: An anonymous survey was sent electronically to approximately 350 DoD general surgeons. The survey asked multiple-choice and free text answers about prescribing patterns and knowledge of current evidence for low-risk patients undergoing elective open inguinal hernia repair without mesh (OIHRWOM), open inguinal hernia repair with mesh (OIHRWM), or laparoscopic inguinal hernia repair (LIHR). RESULTS: 110 DoD general surgeons consented to participate. 58.6, 95 and 84.2% of surgeons always administer antibiotic prophylaxis in OIHRWOM, OIHRWM, and LIHR, respectively. 37.9, 70.9, and 63.2% of surgeons believe that it reduces rates of surgical site infection in OIHRWOM, OIHRWM, and LIHR, respectively. The most common reasons for empirically prescribing antibiotic prophylaxis include "I think the evidence supports it" (27 of 72 responses), "I would rather be conservative and safe" (15 of 72 responses), and "I am following my hospital/department guidelines" (9 of 72 responses). 11.8, 40.8, and 32.9% of surgeons believe current evidence supports antibiotic prophylaxis use in OIHRWM, OIHRWOM, and LIHR, respectively. 50, 18.4, and 22.4% of surgeons believe current evidence refutes antibiotic prophylaxis use in OIHRWM, OIHRWOM, and LIHR, respectively. CONCLUSION: The survey results indicate that the majority of practicing DoD general surgeons still empirically prescribe surgical antibiotic prophylaxis in IHR despite more conflicting opinions that it has no meaningful effect or that current evidence does not supports its use.

Mechanistic understanding of the link between Sodium Starch Glycolate properties and the performance of tablets made by wet granulation.

The impact of varying Sodium Starch Glycolate (SSG) grade and wet granulation intensity on the mechanism of disintegration and dissolution of mannitol-based Immediate Release (IR) placebo tablets was investigated. MRI and 1H NMR provided mechanistic insight, and revealed a four-fold range in both tablet disintegration and dissolution rates. MRI was used to quantify the rates of change in tablet volumes and the data fitted to a hydration/erosion model. Reduced levels of cross-linking change SSG from a swelling to a gelling matrix. The tablet hydration and dissolution rates are related to the viscosity at the tablet-solution interface, with high viscosities limiting mass transport.

An estimate of hernia prevalence in Sierra Leone from a nationwide community survey.

PURPOSE: A large number of unrepaired inguinal hernias is expected in sub-Saharan Africa where late presentation often results in incarceration, strangulation, or giant scrotal hernias. However, no representative population-based data are available to quantify the prevalence of hernias. We present data on groin masses in Sierra Leone to estimate prevalence, barriers to care, and associated disability. METHODS: A cluster randomized, cross-sectional household survey of 75 clusters of 25 households with 2 respondents each was designed to calculate the prevalence of and disability caused by groin hernias in Sierra Leone using a verbal head-to-toe examination. Barriers to hernia repairs were assessed by asking participants the main reason for delay in surgical care. RESULTS: Information was obtained from 3,645 respondents in 1,843 households, of which 1,669 (46%) were male and included in the study. In total, 117 males or 7.01% (95% CI 5.64-8.38) reported a soft or reducible swelling likely representing a hernia with four men having two masses. Of the 93.2% who indicated the need for health care, only 22.2% underwent a procedure, citing limited funds (59.0%) as the major barrier to care. On disability assessment, 20.2% were not able to work secondary to the groin swelling. CONCLUSIONS: The results indicate groin masses represent a major burden for the male population in Sierra Leone. Improving access to surgical care for adult patients with hernias and early intervention for children will be vital to address the burden of disease and prevent complications or limitations of daily activity.

Predicting visual success in macular hole surgery.

AIM: Data on the outcome of surgery facilitate informed preoperative patient counselling. Most studies on the outcome of surgery for idiopathic full thickness macular hole surgery have concentrated on rates of anatomical closure. The aim of this study was to identify factors predicting visual success (better than 20/40; 6/12 Snellen) following macular hole surgery. METHODS: A retrospective study of 133 patients undergoing standardised macular hole surgery with at least 3 months of postoperative follow-up. All patients underwent preoperative measurement of the maximum macular hole diameter using optical coherence tomography. RESULTS: Multivariable regression analysis identified that age, preoperative visual acuity and macular hole size were significant predictors of visual success. The resulting model correctly classified the visual outcome of 80% of cases. Predicted rates of visual success varied from 93% in patients <60 years old with visual acuity better than 6/24 and a hole diameter of <350 mum, to 2% in patients those >79 years old with visual acuity of 6/60 or worse and hole diameter of >500 microm. CONCLUSION: The results provide a simple and clinically useful model to employ when counselling patients on macular hole surgery.

Cross-infection risk of felt-tipped marker pens in cataract surgery.

PURPOSE: To assess the potential of bacterial transmission using felt-tipped marker pens on forehead skin before cataract surgery. METHODS: A total of 64 marker pens taken from clinical stock were tested. Forty-eight new pens were cultured in the laboratory. They were first left to desiccate for 0, 4, and 16 h, then dipped into solutions of 0.5 Macfarlane's concentration of coagulase negative staphylococci (CNS), methicillin-resistant Staphylococcus aureus (MRSA) and coliforms, and transferred onto the culture medium after 5, 10, 30, and 120 min intervals of exposure to air. A further 16 pens were collected after routine clinical use for 5 working days and cultured. RESULTS: Positive cultures were observed in 100% of pens at 0 min, and 44.4% at 5 min after the organism was exposed to air. Escherichia coli showed least transmissibility with no growth in all plates after 5 min of exposure. Only MRSA showed heavy growth after 10 min of exposure. No pattern emerged with reference to the length of time; each pen was left to desiccate. No growth was observed in the cultures of all 16 marking pens after clinical use. CONCLUSIONS: The potential for transmission of bacteria through felt-tipped marker pens has not been explored in cataract surgery. This study demonstrated that a theoretical risk of transmission exists in a laboratory setting, and survival times of the bacteria decreased with time. This suggests that the interval in which patients are marked with the same pen may play a role in bacterial transmission.

Care within a veterans hospital: earlier detection of colon cancer.

BACKGROUND: In 1998 the Veterans Administration mandated an externally monitored targeted colon cancer screening rate that was expected to result in earlier cancer detection and improved patient survival. The effectiveness of the protocol was evaluated in a retrospective case series at a tertiary care Veterans Administration Hospital that included all patients with the diagnosis of colon cancer between 1991 and 2003. METHODS: Tumor stage, tumor location, and patient survival data were recorded and compared to National Cancer Data Base (NCDB) benchmarks. RESULTS: The study facility had a greater percentage of early cancers and fewer later stage cancers than the NCDB benchmark. Overall survival was better for the VA cohort compared to NCDB (all-cause 5-year survival: VA, 0.72; NCDB, 0.47. p < or = .001). CONCLUSIONS: The VA facility had a significantly greater percentage of early cancers and fewer stage III or IV cancers compared to a national benchmark and significantly improved survival compared to the national benchmark.

Transnasal small-caliber esophagogastroduodenoscopy for preoperative evaluation of the high-risk morbidly obese patient.

BACKGROUND: Esophagogastroduodenoscopy (EGD) is an important facet of the preoperative evaluation for bariatric surgery. Morbidly obese patients are at high risk for airway complications during this procedure, and an attractive alternative is transnasal EGD. This report describes a series of patients evaluated successfully using this technique. METHODS: All patients undergoing preoperative transnasal small-caliber EGD for morbid obesity surgery between September 2004 and June 2005 at a Veterans Affairs Hospital were included in the analysis. The variables assessed were the adequacy of the examination, patient tolerance, the need for sedation, and the ability to perform interventions. RESULTS: The study enrolled 25 patients (17 men and 8 women) with an average age of 55 years (range, 44-63 years) and an average body mass index (BMI) of 47 kg/m2 (range, 38-69 kg/m2). All the patients met the 1991 National Institutes of Health (NIH) Consensus Conference Criteria for bariatric surgery and were undergoing preoperative evaluation. The most common comorbidities were hypertension (82%), diabetes mellitus (80%), and obstructive sleep apnea (68%). All 25 patients had successful cannulation of the duodenum's second portion with excellent tolerance. There were no sedation requirements for 23 (92%) of the 25 patients. Significant pathology was found in 14 (56%) of the 25 patients, including hiatal hernia (28%), gastritis (16%), esophageal intestinal metaplasia (16%), esophagitis (12%), gastric polyps (8%), gastric ulcer (4%) and esophageal varices (4%). Biopsies were indicated for 12 patients and successful for all 12 (100%). CONCLUSION: Transnasal small-caliber EGD is a feasible and safe alternative to conventional EGD for the preoperative evaluation of patients undergoing bariatric surgery. It requires minimal to no sedation in a population at high risk for complications in this setting. In addition, this technique is effective in identifying pathology that requires preoperative treatment and offers a complete examination with biopsy capabilities. This technique should be considered for all morbidly obese patients at high risk for airway compromise during EGD.

Cytomegalovirus Retinitis in infancy.

PURPOSE: To describe the presentation of cytomegalovirus retinitis (CMVR) in a series of infants. METHODS: Immunocompromised infants with either HIV or systemic cytomegalovirus (CMV) were examined for CMVR. Ocular involvement was recorded and monitored by digital imaging. RESULTS: Five infants were detected to have CMVR. All the infants demonstrated changes within the macula. One infant progressed from a fine granular pattern to fulminant CMVR. CONCLUSION: Infants under a year with CMVR have a predilection for the disease to present at the macula, in contrast to the presentation in adults, which tends to involve more peripheral parts of the retina.

Prediction of isotope patterns for partially deuterated analytes in HPLC/MS.

A probability model is given which accurately predicts the electrospray mass patterns of substance P arising from full or incomplete deuterium exchange in solution. For accurate determination of the number of exchangeable protons the solvent should have a deuterium purity of at least 98%. At 25 degrees C several minutes are required before the degree of exchange reaches the equilibrium value.

Effect of ionic strength on perfusive flow in capillary electrochromatography columns packed with wide-pore stationary phases.

The use of wide-pore stationary phases in capillary electrochromatography has shown exceptional increases in separation efficiency in conjunction with high electroosmotic flow. These effects are due to the perfusive flow mechanism which is primarily controlled by the ionic strength of the mobile phase. Good correlation between calculated values of electrochemical double-layer thickness and efficiency data have also been obtained. Reduced plate height values of <0.5 have been observed with pore sizes of 4000 A. In addition, electroosmotic flow mobility twice that of 3 microm Spherisorb ODS-1 has been obtained.

Decompressive colonoscopy with intracolonic vancomycin administration for the treatment of severe pseudomembranous colitis.

BACKGROUND: We explored the potential of early decompressive colonoscopy with intracolonic vancomycin administration as an adjunctive therapy for severe pseudomembranous Clostridium difficile colitis with ileus and toxic megacolon. METHODS: We reviewed the symptoms, signs, laboratory tests, radiographic findings, and outcomes from the medical records of seven patients who experienced eight episodes of severe pseudomembranous colitis with ileus and toxic megacolon. All seven patients underwent decompressive colonoscopy with intracolonic perfusion of vancomycin. RESULTS: Fever, abdominal pain, diarrhea, abdominal distention, and tenderness were present in all patients. Five of seven patients were comatose, obtunded, or confused, and six of the seven required ventilatory support. The white blood cell count was greater than 16,000 in seven cases (six patients). Colonoscopy showed left-side pseudomembranous colitis in one patient, right-side colitis in one patient, and diffuse pseudomembranous pancolitis in five patients. Two patients were discharged with improvement. Five patients had numerous medical problems leading to their death. Complete resolution of pseudomembranous colitis occurred in four patients. One patient had a partial response, and two patients failed therapy. CONCLUSION: Colonoscopic decompression and intracolonic vancomycin administration in the management of severe, acute, pseudomembranous colitis associated with ileus and toxic megacolon is feasible, safe, and effective in approximately 57% to 71% of cases.

Characterisation of electroosmotic flow in capillary electrochromatography columns.

Currently available capillary electrochromatography (CEC) instrumentation using UV-Vis detection dictates the use of duplex columns. Due to discontinuities (electric field strength and conductivity) that arise at the boundary between the packed and open sections in these columns, the determination of the electroosmotic flow (EOF) is complicated. Thiourea has been found to be an accurate EOF marker under the conditions employed in this study. By injecting this compound onto a fully packed column and comparing the obtained mobilities with those calculated from measured zeta potential values a value for tortuosity has been obtained. The use of laser Doppler velocimetry (LDV) for the measurement of zeta potential has been found to be the most direct and rapid method of characterising silica support materials in terms of electroosmotic mobility. The open section in duplex CEC columns has been shown to influence the actual column flow-rate. The EOF measured using duplex columns of varying packed and open section lengths have been compared with those obtained for a fully packed column.

Influence of the unpacked section on the chromatographic performance of duplex strong anion-exchange columns in capillary electrochromatography.

This work describes initial investigations of strong anion-exchange (SAX) packing materials for capillary electrochromatography (CEC). The use of SAX phases in CEC is theoretically appealing for the analysis of negatively charged species. The reversed direction of the electroosmotic flow (EOF) generated by SAX phases (in comparison to reversed phases and strong cation-exchange phases) means that negative species can migrate with the EOF, not against it, hence the analysis times, of such species should be decreased and efficiencies improved. Duplex CEC columns (the standard for instruments using UV detection) consist of a packed and an unpacked section. Using common reversed-phase packing materials the direction of the EOF in both sections is co-linear, however when normal fused-silica capillaries are packed with SAX material the direction of the EOF in the two sections oppose one another. It has been shown, using conventional duplex CEC columns and fully packed CEC-MS columns that the opposing direction of EOF causes a massive degradation in column performance. Consequentially, it is demonstrated that if the EOF in the open section of the duplex SAX column can be controlled via pH or capillary derivatisation then good, reproducible CEC can be performed on anionic species using SAX packed CEC columns.

Results of a screening program for prostate cancer in patients scheduled for abdominoperineal resection for colorectal pathologic findings.

OBJECTIVES: Because of the difficulty of accessing the prostate for tissue sampling after surgical removal of the rectum and obliteration of the anus, we started an early detection program for prostate cancer in all men scheduled for abdominoperineal resection. METHODS: Twenty consecutive men were screened for prostatic adenocarcinoma before planned abdominoperineal resection for colorectal pathologic findings. Patients were 48 to 77 years old (mean 66.9). Screening included serum prostate-specific antigen determination and digital rectal examination. Those patients with suspicious findings underwent transrectal ultrasound-guided sextant biopsies of the prostate. RESULTS: One patient was excluded because of a prior history of prostate cancer. Six (31.6%) of the remaining 19 patients demonstrated elevated prostate-specific antigen levels (greater than 4.0 ng/mL); two of these patients also had an abnormal digital rectal examination. Transrectal ultrasound and prostate biopsies in these 6 patients revealed prostatic adenocarcinoma in 3 patients (50% of those undergoing biopsies or 15.8% of those screened). The 13 patients who did not undergo prostate biopsies had prostate-specific antigen levels from 0.4 to 2.4 ng/mL (mean 0.9) and normal prostate glands according to the digital rectal examinations. CONCLUSIONS: Screening for prostate cancer in men 50 years old or older with 10 years or longer life expectancy before they undergo abdominoperineal resection detects a significant number of prostatic malignancies and should be encouraged.

External beam radiotherapy for synchronous rectal and prostatic tumors.

Two patients were diagnosed with large rectal tumors and localized prostate cancer. The prostate-specific antigen level at diagnosis was 7.9 ng/mL and 9.0 ng/mL in the 2 patients. Knowledge of the presence of both tumors and their close proximity allowed creation of a modified three-dimensional conformal radiotherapy plan to treat both tumors. The patients had no evidence of rectal tumor recurrence and their prostate-specific antigen level was 0.5 ng/mL and 0.7 ng/mL at 1 and 2 years after therapy, respectively. We conclude that efficient, effective pelvic irradiation can be designed for synchronous rectal and prostate malignancies.

Use of telehealth for chronic wound care: a case study.

Use of telehealth in wound care continues to expand as technology is enhanced and clinicians become more familiar with use of the new technology as a supplement to usual care. This article describes the Telehealth Wound Care Program implemented at Mount Sinai Hospital Home Health Agency and Mount Sinai Hospital Wound Care Center. Results of the wound care provided for one patient are included in the case study described in this article. The authors note the many benefits of telehealth as an adjunct to usual therapy in wound care.

Does an infected peripancreatic fluid collection or abscess mandate operation?

OBJECTIVE: To assess the treatment of peripancreatic fluid collections or abscess with percutaneous catheter drainage (PCD). SUMMARY BACKGROUND DATA: Surgical intervention has been the mainstay of treatment for infected peripancreatic fluid collections and abscesses. Increasingly, PCD has been used, with mixed results reported in the literature. METHODS: A retrospective chart review of 1993 to 1997 was performed on 82 patients at a tertiary care public teaching hospital who had computed tomography-guided aspiration for suspected infected pancreatic fluid collection or abscess. Culture results, need for subsequent surgical intervention, length of stay, and death rate were assessed. RESULTS: One hundred thirty-five aspirations were performed in 82 patients (57 male patients, 25 female patients) with a mean age of 40 years (range 17-68). The etiologies were alcohol (41), gallstones (32), and other (9). The mean number of Ranson's criteria was four (range 0-9). All patients received antibiotics. Forty-eight patients had evidence of pancreatic necrosis on computed tomography scan. Cultures were negative in 40 patients and positive in 42. Twenty-five of the 42 culture-positive patients had PCD as primary therapy, and 6 required subsequent surgery. Eleven patients had primary surgical therapy, and five required subsequent surgery. Six patients were treated with only antibiotics. The death rates were 12% for culture-positive patients and 8% for the entire 82 patients. CONCLUSIONS: Historically, patients with positive peripancreatic aspirate culture have required operation. This series reports an evolving strategy of reliance on catheter drainage. PCD should be considered as the initial therapy for culture-positive patients, with surgical intervention reserved for patients in whom treatment fails.