The Impact of SARS-COV-2 on two Colorectal Cancer screening centres.

BowelScreen paused activity in March 2020 to prioritise the response to the COVID-19 pandemic. The aim of this study was to examine the impact of this delay. Cases affected by the pause and subsequently completed were compared to the same period in 2019. Endoscopy and histology data were obtained from the BowelScreen database and patient records. One-hundred and seven colonoscopies were performed during the study period. This compared with 224 colonoscopies during the same period in 2019. Median lead time to colonoscopy in 2020 was 74 days compared to 34 days in 2019. Adenoma detection rate was 59% for both periods. Advanced adenoma and cancer detection rates were similar in both periods. While there was a marked reduction in activity and significant delays for BowelScreen patients during the first wave of the COVID-19 pandemic, this does not appear to have impacted on clinical outcomes for patients who attended for screening colonoscopy.

Colistin causes profound morphological alteration but minimal cytoplasmic membrane perforation in populations of Escherichia coli and Pseudomonas aeruginosa.

Whilst colistin (polymyxin E) represents the last mainstream treatment option for multidrug-resistant Gram-negative pathogens, details of its mechanism of action remain to be fully resolved. In this study, the effects of sub-inhibitory, inhibitory-bactericidal, and supra-bactericidal levels of colistin on the membrane integrity and morphology of Escherichia coli and Pseudomonas aeruginosa were investigated using potassium loss, flow cytometry, and scanning electron microscopy (SEM). Supra-bactericidal colistin concentrations induced just 4-12% intracellular potassium loss from bacteria after 24 h. Flow cytometry data suggested colistin might alter cell arrangement, and SEM confirmed the antibiotic causes bacterial aggregation. Filamentation was not detected in either species at any concentration or time-point up to 24 h. These results argue against the hypotheses that colistin kills bacteria by puncturing the cytoplasmic membrane or disrupting DNA synthesis. The colistin-induced bacterial aggregation detected has implications for the interpretation of MBC, time-kill, and other test results obtained with this antibiotic.

Fibrin Glue Injections: A Minimally Invasive and Cost-Effective Treatment for Post-Renal Transplant Lymphoceles and Lymph Fistulas.

Pelvic lymphoceles/lymph fistulas are commonly observed after kidney allotransplantation, especially when the kidney is placed in a retroperitoneal position. While the majority are <5 cm in diameter and resolve without intervention, some may continue to enlarge, and cause local or systemic symptoms or graft dysfunction. Among 1662 recipients of both living and deceased donor kidney transplants between January 2003 and July 2014, we found 46 (2.7%) patients with symptomatic lymphoceles requiring intervention. We studied the clinical outcomes and charges for three treatment modalities including open surgical drainage (22), laparoscopic surgical drainage (11), and percutaneous fibrin glue injections into the drained lymphocele cavity (13). The patient demographics and clinical characteristics were comparable for each treatment group, although maintenance immunosuppressive drugs differed by era. We found fibrin glue injections resulted in significantly lower (p = 0.04) rates of recurrence (1; 7.7%) than either laparoscopic (6; 54%) or open surgical drainage (6; 27.3%). In addition, fibrin glue injections generated significantly (p < 0.001) lower median ($4559) charges compared to either laparoscopic ($26,330) or open surgical drainage ($23,758). Fibrin glue treatment has the advantage of being an outpatient procedure, performed with the patient under local anesthesia, and does not incur the expense of an operative procedure or hospital admission associated with laparoscopic or open surgery.

Potassium loss from chlorhexidine-treated bacterial pathogens is time- and concentration-dependent and variable between species.

The membrane-active antimicrobial agent chlorhexidine is used extensively as an antiseptic during infection prophylaxis and treatment. Whilst known to induce membrane damage that results in loss of internal solutes from bacteria, the present study sought to determine the rate and extent of cytoplasmic potassium loss and whether any species-specific differences exist. Direct measurement of potassium was achieved using flame emission spectrophotometry. Exposure of selected species to minimum inhibitory (MIC) or minimum bactericidal concentration (MBC) resulted in solute loss that was both concentration and time dependent. Within 5-min treatment with MIC levels, losses of 3 % from P. aeruginosa, 9 % from E. coli, and 15 % from S. aureus were recorded, whilst at 5 % w/v chlorhexidine, elevated loss of 20, 28, and 41 % occurred, respectively. Nonlinear potassium release was evident from all species when treated with 5 % chlorhexidine over a 60-min period. After this contact time, potassium loss from E. coli and S. aureus rose to 93 or 90 %, respectively; in contrast, P. aeruginosa retained 62 % intracellular potassium. Results confirm lethal concentrations of chlorhexidine induce rapid and substantial loss of cytoplasmic potassium from common pathogens. However, bacterial responses vary between species and should be borne in mind when considering mechanism of action.

Role of HIF1α and PKCß in mediating the effect of oxygen and glucose in a novel wound assay.

Delayed wound healing is characteristic of those affected by both Type 1 and Type 2 diabetes. We have developed a novel assay to investigate endothelial cell migration using primary microvascular endothelial cells of dermal origin. Endothelial cell migration was determined using defined monolayers of cells. Net migration or migration at a wounded edge was recorded after 24 or 48 h following incubation in either 20% or 5% oxygen in combination with either 5 mmol/l or 20 mmol/l glucose. Specific intracellular inhibitors of p42/44 MAPK, Pi3 kinase and protein kinase CßII were used. Hypoxia inducible factor type 1 alpha protein was detected using immunocytochemical staining. Cell migration was increased in the presence of hypoxia and decreased with high glucose concentration (p<0.001). The newly developed wound healing assay revealed that re-endothelialisation occurred at a greater rate (p<0.001) than endothelialisation. Inhibition of p42/44MAPK significantly reduced endothelial cell migration at both the intact and the wounded edge in 20 mmol/l glucose but not 5 mmol/l glucose. Inhibition of Pi3 kinase significantly (p<0.001) reduced migration in all test conditions, while inhibition of PKCß restored glucose mediated impaired migration (p>0.05). HIF-1α protein levels did not significantly reduce in the presence of a PKCß inhibitor at the wounded edge of cells in 20 mmol/l glucose. In conclusion, we have established a novel assay to determine endothelial cell migration that is robust and reproducible. Impaired cell migration mediated by high glucose concentration was restored using an inhibitor of the PKCßII pathway which correlated with an increase in the level of HIF1α protein.

Production and evaluation of an antimicrobial peptide-containing wafer formulation for topical application.

A targeted approach for direct topical antimicrobial delivery involving the formulation of impregnated freeze-dried wafers prepared from a natural polymer has been assessed to consider potential for treatment of wounded skin. The synthetic cationic antimicrobial peptides (CAPs) NP101 and NP108 were found to have modest in vitro activity against bacterial species commonly associated with wound infections. Minimum inhibitory concentration/minimum bactericidal concentrations against Escherichia coli, Staphylococcus aureus and Pseudomonas aeruginosa were found to be 0.31 mg/ml for NP101 and 0.25-0.5 mg/ml for NP108. Rapid, substantial cytoplasmic potassium loss was induced by NP108 in E. coli, but not the other species. Through scanning electron microscopy, both CAPs were observed to alter cell morphology, prevent normal septation, promote cell aggregation and trigger release or formation of extracellular filaments. Wafers harbouring these agents displayed substantial antibacterial activity when assessed by standard diffusion assay. These data confirm that topical delivery of CAPs, through their incorporation within freeze-dried wafer formulations prepared from natural polymers, represents a potential viable approach for treating skin infection.

Cross-sectional study to investigate the health-related quality of life in children with severe lower limb trauma in Victoria.

AIMS: The aim of this study is to investigate the health-related quality of life in children with severe lower limb trauma after at least 12 months post-injury and to assess patient and injury characteristics in association with the health-related quality of life scores. METHODS: All children in the state of Victoria, who were 18 years of age or younger, suffering from severe lower limb injury before 2006 were studied. Patient and injury characteristics were abstracted from medical records. The health-related quality of life (HRQOL) scores were obtained using the Paediatric Quality of Life Inventory. RESULTS: Thirty-two out of 64 eligible patients participated in this study. All aspects of health-related quality of life in children with severe lower limb trauma after at least 12 months post-injury were significantly poorer compared with non-affected children, particularly in the physical health domain (difference: -12.51 ± 7.43: P < 0.05). It was observed that bilateral limb involvement and the need for soft tissue management were related to poor physical functioning (P < 0.05). Other characteristics such as traumatic amputation, gender, growth plate injury, joint bony injury and accident mechanism did not affect the overall HRQOL scores (P > 0.05). CONCLUSIONS: The HRQOL in children with severe lower limb trauma was significantly impaired even after 12 months post-injury, notably in patient group with bilateral limb involvement and need for soft tissue management. Traumatic amputation, gender, growth plate injury, joint bony injury and accident mechanism did not have an impact on quality of life.

Comparison of the in vitro release characteristics of mucosal freeze-dried wafers and solvent-cast films containing an insoluble drug.

Drug release characteristics of freeze-dried wafers and solvent-cast films prepared from sodium carboxymethylcellulose have been investigated and compared. In vitro drug dissolution studies were performed using an exchange cell and drug release was measured by UV spectroscopy at 272 nm using distilled water. The dissolution profiles of hydrochlorothiazide from the wafers and films were compared by determining the rates of drug release, estimated from the % release versus time profiles and calculating their difference (f(1)) and similarity (f(2)) factors. The effects of drug loading, polymer content and amount of glycerol (GLY) (films) on the drug release characteristics of both formulations were investigated. Both the wafers and films showed sustained type release profiles that were best explained by the Korsmeyer-Peppas equation. Changes in the concentration of drug and GLY (films) did not significantly alter the release profiles whilst increasing polymer content significantly decreased the rate of drug release from both formulations. The rate of release was faster from the wafers than the corresponding films which could be attributed to differences in the physical microstructure. The results show the potential of employing both formulations in various mucosal drug delivery applications.

Characterization of the Sheep Round Window Membrane.

Intratympanic injection is a clinically used approach to locally deliver therapeutic molecules to the inner ear. Drug diffusion, at least in part, is presumed to occur through the round window membrane (RWM), one of the two openings to the inner ear. Previous studies in human temporal bones have identified a three-layered structure of the RWM with a thickness of 70-100 µm. This is considerably thicker than the RWM in rodents, which are mostly used to model RWM permeability and assess drug uptake. The sheep has been suggested as a large animal model for inner ear research given the similarities in structure and frequency range for hearing. Here, we report the structure of the sheep RWM. The RWM is anchored within the round window niche (average vertical diameter of 2.1 ± 0.3 mm and horizontal diameter of 2.3 ± 0.4 mm) and has a curvature that leans towards the scala tympani. The centre of the RWM is the thinnest (55-71 µm), with increasing thickness towards the edges (< 171 µm), where the RWM forms tight attachments to the surrounding bony niche. The layered RWM structure, including an outer epithelial layer, middle connective tissue and inner epithelial layer, was identified with cellular features such as wavy fibre bundles, melanocytes and blood vessels. An attached "meshwork structure" which extends over the cochlear aqueduct was seen, as in humans. The striking anatomical similarities between sheep and human RWM suggest that sheep may be evaluated as a more appropriate system to predict RWM permeability and drug delivery in humans than rodent models.

Development and mechanical characterization of solvent-cast polymeric films as potential drug delivery systems to mucosal surfaces.

Solvent-cast films from three polymers, carboxymethylcellulose (CMC), sodium alginate (SA), and xanthan gum, were prepared by drying the polymeric gels in air. Three methods, (a) passive hydration, (b) vortex hydration with heating, and (c) cold hydration, were investigated to determine the most effective means of preparing gels for each of the three polymers. Different drying conditions [relative humidity - RH (6-52%) and temperature (3-45 degrees C)] were investigated to determine the effect of drying rate on the films prepared by drying the polymeric gels. The tensile properties of the CMC films were determined by stretching dumbbell-shaped films to breaking point, using a Texture Analyser. Glycerol was used as a plasticizer, and its effects on the drying rate, physical appearance, and tensile properties of the resulting films were investigated. Vortex hydration with heating was the method of choice for preparing gels of SA and CMC, and cold hydration for xanthan gels. Drying rates increased with low glycerol content, high temperature, and low relative humidity. The residual water content of the films increased with increasing glycerol content and high relative humidity and decreased at higher temperatures. Generally, temperature affected the drying rate to a greater extent than relative humidity. Glycerol significantly affected the toughness (increased) and rigidity (decreased) of CMC films. CMC films prepared at 45 degrees C and 6% RH produced suitable films at the fastest rate while films containing equal quantities of glycerol and CMC possessed an ideal balance between flexibility and rigidity.

Decontamination of fluid milk containing Bacillus spores using commercial household products.

Although commercial sanitizers can inactivate bacterial spores in food processing environments, relatively little data exist as to the decontamination of products and surfaces by consumers using commercial household products. Should a large scale bioterrorism incident occur in which consumer food products were contaminated with a pathogenic sporeformer such as Bacillus anthracis, there may be a need to decontaminate these products before disposal as liquid or solid waste. Studies were conducted to test the efficacy of commercial household products for inactivating spores of Bacillus cereus (used as a surrogate for B. anthracis) in vitro and in fluid milk. Validation of the resistance of the B. cereus spores was confirmed with B. anthracis spores. Fifteen commercial products, designed as either disinfectants or sanitizers or as potential sanitizers, were purchased from retail markets. Products selected had one of the following active compounds: NaOCl, HCl, H2O2, acetic acid, quaternary ammonium compounds, ammonium hydroxide, citric acid, isopropanol, NaOH, or pine oil. Compounds were diluted in water (in vitro) or in 2% fat fluid milk, and spores were exposed for up to 6 h. Products containing hypochlorite were most effective against B. cereus spores. Products containing HCl or H2O2 also reduced significant numbers of spores but at a slower rate. The resistance of spores of surrogate B. cereus strains to chlorine-containing compounds was similar to that of B. anthracis spores. Therefore, several household products on the market may be used to decontaminate fluid milk or similar food products contaminated by spores of B. anthracis.

Collegiate rugby union injury patterns in New England: a prospective cohort study.

OBJECTIVE: To establish injury profile of collegiate rugby union in the USA. DESIGN/ SETTING: 31 men's and 38 women's collegiate rugby union teams prospectively recorded injuries during games and practice during the 2005-06 season. Three teams withdrew before data collection. An injury was defined as one: (1) occurring in an organised intercollegiate game or practice; and (2) requiring medical attention during or after the game or practice, or (3) resulting in any restriction of the athletes' participation for >or=1 day(s) beyond the day of injury, or in a dental injury. MAIN OUTCOME MEASURES: In total, 847 injuries (447 in men; 400 in women) during 48,026 practice (24,280 in men; 23,746 in women) and 25,808 game (13,943 in men; 11,865 in women) exposures were recorded. RESULTS: During games, injury rates of 22.5 (95% CI 20.2 to 25.0) and 22.7 (20.2 to 25.5) per 1000 game athletic exposures or 16.9 (15.1 to 18.9) and 17.1 (15.1 to 19.1) per 1000 player game hours were recorded for men and women, respectively. Over half of all match injuries were of major severity (>7 days' absence) (men 56%; women 51%) and the tackle was the game event most often associated with injury (men 48%; women 53%). CONCLUSIONS: Collegiate game injury rates for rugby were lower than rates recorded previously in men's professional club and international rugby and lower than reported by the National Collegiate Athletic Association Injury Surveillance System for American football, but similar to rates reported for men's and women's soccer in 2005-06.

Implementation of a psychodermatology clinic at a major health system in Detroit.

The association between psychiatric and dermatologic disorders has been well characterized in the present literature with estimates of up to 40% of dermatology patients having concomitant psychiatric problems that are often related to their skin condition. Here, we present our experience regarding the implementation of a psychodermatology clinic in Detroit, Michigan. The most commonly referred conditions were delusions of parasitosis, neurotic excoriations, and isotretinoin initiation for patients with a history of psychiatric conditions. Seventy-three percent of referred patients were female. By creating a monthly clinic for patients who are diagnosed with skin conditions and associated psychiatric disorders or psychological symptoms, we are able to meet the needs of these patients with a synergistic relationship between health care providers.

Effects of poor glucose handling on arterial stiffness and left ventricular mass in normal children.

AIM: Cardiovascular risk factors can be present in children and young adults. We previously found abnormal microvascular function in children who had glucose intolerance and insulin resistance. The aim of the present study was to investigate whether they also have abnormalities in left ventricular mass (LVM) and arterial stiffness. METHODS: We measured heart dimensions and LVM using echocardiography, and arterial stiffness using pulse wave analysis in 23 children with good glucose handling (postfeeding glucose: 3.9 to 5 mmol/L) and 21 with poor glucose handling (7.7 to 11.4 mmol/L). RESULTS: The time to pulse reflection was slightly shorter in the poorer glucose handlers (mean+/-SD: 143+/-10 vs 153+/-20 ms, P=0.04), suggestive of increased arterial stiffness. Also in this group, there were significant relationships between intraventricular septal thickness, blood pressure and body mass index, but not in the normal glucose handlers. CONCLUSIONS: We have found that normal children who are in the lowest quintile of glucose tolerance in comparison with their peers are exhibiting the first signs of arterial stiffening. In addition, we have seen the beginnings of a relationship between blood pressure, body mass index and left ventricular enlargement in this group. While these changes may not yet be clinically significant, their emergence might be further evidence of early predisposition to cardiovascular disease.

Preformulation of cysteamine gels for treatment of the ophthalmic complications in cystinosis.

Nephropathic cystinosis is a rare autosomal recessive disease characterised by raised lysosomal levels of cystine in the cells of all organs. It is treated by regular administration of the aminothiol, cysteamine. Corneal crystal deposition is one of the most troublesome complications affecting patients and requires the hourly administration of cysteamine eye drops. In an attempt to reduce this frequency and improve the treatment, the preformulation and evaluation of cysteamine containing gels is reported. Suitability for ophthalmic delivery was determined by analysis of rheology, bioadhesion, dissolution and stability. The results demonstrated that three polymers were suitable for ophthalmic delivery of cysteamine; namely sodium hyaluronate, hydroxyethyl cellulose and carbomer 934. Sodium hyaluronate displayed optimum performance in the preformulation tests, being pseudoplastic (reduction in apparent viscosity under increasing shear rate), bioadhesive, releasing cysteamine over 40min and displaying stability over time. In conclusion these results offer the possibility to formulate cysteamine in an ocular applicable gel formulation.

Advanced breast cancer: a phase II trial with gemcitabine.

PURPOSE: In this phase II study, the efficacy and tolerability of gemcitabine were studied in 44 patients with locally advanced or metastatic breast cancer. PATIENTS AND METHODS: Of 40 patients assessable for response, 14 were chemotherapy-naive, seven had received adjuvant chemotherapy, and 19 had received one prior chemotherapy regimen for metastatic disease. Gemcitabine was administered as a 30-minute intravenous infusion once a week for 3 weeks followed by a 1-week rest every 4 weeks. The mean number of completed cycles administered was 2.7 and the mean dosage delivered was 725 mg/m2 per injection. Eighty-one percent of doses were delivered as scheduled. RESULTS: There were three complete responses and seven partial responses, for an overall response rate of 25.0% (95% confidence interval [CI], 12.7% to 41.2%). Four patients were not assessable for efficacy (one had insufficient therapy, two had no bidimensionally measurable disease, and one had neither). All responses were independently validated by an external oncology review board. Responses were observed early in treatment, with a median time to response of 1.9 months. The median survival duration for all 40 assessable patients was 11.5 months. Hematologic toxicity was generally mild, with World Health Organization (WHO) grade 3 and 4 leukopenia occurring in 6.8% and 2.3% of patients and neutropenia in 23.3% and 7.0%, of patients, respectively. The only other grade 4 toxicities were infection and nausea and vomiting in one patient each. One patient was withdrawn due to shortness of breath, possibly drug-related. Flu-like symptoms, which were mild, transient, and treatable with acetominophen, were reported in 6.8% of patients. Only one patient developed alopecia of severity greater than WHO grade 2. CONCLUSION: In view of the single-agent activity seen in advanced breast cancer, modest toxicity profile, and novel mechanism of action, gemcitabine deserves evaluation in breast cancer and is an ideal candidate for combination therapy.

The hen's egg chorioallantoic membrane (HET-CAM) test to predict the ophthalmic irritation potential of a cysteamine-containing gel: Quantification using Photoshop® and ImageJ.

A modified hen's egg chorioallantoic membrane (HET-CAM) test has been developed, combining ImageJ analysis with Adobe(®) Photoshop(®). The irritation potential of an ophthalmic medicine can be quantified using this method, by monitoring damage to blood vessels. The evaluation of cysteamine containing hyaluronate gel is reported. The results demonstrated that the novel gel formulation is non-irritant to the ocular tissues, in line with saline solution (negative control). In conclusion, the modification of the established HET-CAM test can quantify the damage to minute blood vessels. These results offer the possibility to formulate cysteamine in an ocular applicable gel formulation.

Nursing home patients transferred by ambulance to a VA emergency department.

Nursing home residents are frequently transferred to hospital emergency departments. Delayed transfer may lead to poor outcomes. However, inappropriate transfer of the frail elderly may cause social and financial problems. We prospectively evaluated 221 consecutive ambulance transfers from community nursing homes to a VA emergency department. The objectives of the study were to describe the process and outcomes of transferred patients and to determine if alternative interventions were feasible. The results indicate that the problems of nearly half the study group could have been treated at the nursing home by a visiting physician with minimal medical equipment. Those admitted to the hospital (52%) were seriously ill, had prolonged lengths of stay (23.6 days), and had a high mortality rate (11%). Complex issues of physician reimbursement, proprietary nursing home budgeting, and day-to-day expediency appear to be involved in decisions to transport patients by ambulance to VA emergency departments.

Hearing loss in former prisoners of war of the Japanese.

OBJECTIVE: To describe the prevalence, degree, and types of hearing loss present in a group of older American veterans who had been prisoners of war of the Japanese. DESIGN: A descriptive study. SETTING: A Veterans Affairs university hospital. PARTICIPANTS: Seventy-five male veterans, mean age 68 (+/- 3.6) years. INTERVENTIONS: Hearing aids were prescribed for eight veterans. MEASUREMENTS: Subjects were examined, and pure tone air and bone conduction, speech reception threshold, and speech discrimination were determined. Results were compared with age- and sex-matched controls from the largest recent American population study of hearing loss. RESULTS: 95% of subjects had been imprisoned longer than 33 months. Starvation conditions (100%), head trauma (85%), and trauma-related loss of consciousness (23%) were commonly reported. A total of 73% complained of hearing loss, and 29% (22/75) dated its onset to captivity. Most of those with the worst losses in hearing and speech discrimination were found in this subgroup. When the entire group was compared with published age- and sex-matched controls from the Framingham Study, no significant differences were found. CONCLUSIONS: We advocate screening examinations and long-term follow-up of populations with similar histories of starvation, head trauma, and torture.

Urinary infection caused by Micrococcus subgroup 3.

The laboratory findings and clinical presentations in urinary infections in 23 nurses, 10 caused by Micrococcus subgroup 3 and 13 by Escherichia coli, were studied, and the symptoms and possible predisposing factors compared. There were no important differences between the two groups. The infections caused by Micrococcus subgroup 3 were symptomatically severe, as were those caused by Escherichia coli.