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The pharmacokinetics of L-carnitine and its metabolites were investigated in 7 healthy subjects following the oral administration of 0, 0.5, 1, and 2 g 3 times a day for 7 days. Mean plasma concentrations of L-carnitine across an 8-hour dose interval increased significantly (P < .05) from a baseline of 54.2 +/- 9.3 muM to 80.5 +/- 12.5 muM following the 0.5-g dose; there was no further increase at higher doses. There was a significant increase (P < .001) in the renal clearance of L-carnitine indicating saturation of tubular reabsorption. Trimethylamine plasma levels increased proportionately with L-carnitine dose, but there was no change in renal clearance. A significant increase in the plasma concentrations of trimethylamine-N-oxide from baseline was evident only for the 2-g dose of L-carnitine (from 34.5 +/- 2.0 to 149 +/- 145 muM), and its renal clearance decreased with increasing dose (P < .05). There was no evidence for nonlinearity in the metabolism of trimethylamine to trimethylamine-N-oxide. In conclusion, the pharmacokinetics of oral L-carnitine display nonlinearity above a dose of 0.5 g 3 times a day. [ABSTRACT FROM AUTHOR]

Abstract Background Egg white must provide nutrients and protection to the developing avian embryo. One way in which this is achieved is an arsenal of antimicrobial proteins and peptides which are essentially extensions of the innate immune system. Gallin is a recently identified member of a family of peptides that are found in egg white. The function of this peptide family has not been identified and they are potentially antimicrobial. Results We have confirmed that there are at least 3 forms of the gallin gene in the chicken genome in 3 separate lines of chicken, all the forms are expressed in the tubular cells of the magnum region of the oviduct, consistent with its presence in egg white. mRNA expression levels are in the order 10,000 times greater in the magnum than the shell gland. The conservation between the multiple forms of gallin in the chicken genome compared with the conservation between gallin and other avian gallin like peptides, suggests that the gene duplication has occurred relatively recently in the chicken lineage. The gallin peptide family contains a six cysteine motif (C-X5-C-X3-C-X11-C-X3-C-C) found in all defensins, and is most closely related to avian beta-defensins, although the cysteine spacing differs. Further support for the classification comes from the presence of a glycine at position 10 in the 41 amino acid peptide. Recombinant gallin inhibited the growth of Escherischia coli (E. coli) at a concentration of 0.25 μM confirming it as part of the antimicrobial innate immune system in avian species. Conclusions The relatively recent evolution of multiple forms of a member of a new defensin related group of peptides that we have termed ovodefensins, may be an adaptation to increase expression or the first steps in divergent evolution of the gene in chickens. The potent antimicrobial activity of the peptide against E. coli increases our understanding of the antimicrobial strategies of the avian innate immune system particularly those of the egg white and the evolution of the defensin family. The potential of this peptide and others in the family can now be investigated in a number of novel antimicrobial roles.

Abstract Background We explored how embayment watershed inputs, morphometry, and hydrology influence fish community structure among eight embayments located along the southeastern shoreline of Lake Ontario, New York, USA. Embayments differed in surface area and depth, varied in their connections to Lake Ontario and their watersheds, and drained watersheds representing a gradient of agricultural to forested land use. Results We related various physicochemical factors, including total phosphorus load, embayment area, and submerged vegetation, to differences in fish species diversity and community relative abundance, biomass, and size structure both among and within embayments. Yellow perch (Perca flavescens) and centrarchids numerically dominated most embayment fish communities. Biomass was dominated by piscivorous fishes including brown bullhead (Ameiurus nebulosus), bowfin (Amia calva), and northern pike (Esox lucius). Phosphorus loading influenced relative biomass, but not species diversity or relative abundance. Fish relative abundance differed among embayments; within embayments, fish abundance at individual sampling stations increased significantly with submerged vegetative cover. Relative biomass differed among embayments and was positively related to total phophorus loading and embayment area. Fish community size structure, based on size spectra analysis, differed among embayments, with the frequency of smaller-bodied fishes positively related to percent vegetation. Conclusion The importance of total phosphorus loading and vegetation in structuring fish communities has implications for anthropogenic impacts to embayment fish communities through activities such as farming and residential development, reduction of cultural eutrophication, and shoreline development and maintenance.

Introduction: Chronic wounds represent a significant burden to the health care system and patients., Objective: This study determined the effectiveness of a wound scaffold comprised of PCMP for use in nonhealing, cutaneous wounds; this study analyzes pooled data from the population of 3 combined registries., Materials and Methods: A total of 3 combined registry populations were pooled from a single-center study of 41 patients, a single-center study of 86 patients, and the RESPOND Registry of 307 patients treated at 28 centers. All 434 patients received PCMP and were followed for up to 48 weeks. Male and female patients 18 years or older with wounds between 0.2 cm2 and 200 cm2 were included., Results: In total, there were 95 VLUs, 78 DFUs, 90 PIs, 73 PSWs, and 98 wounds of other etiologies analyzed. The mean baseline area, depth, and volume of all 434 wounds was 15.1 cm2, 4.9 mm, and 7.2 cm3, respectively. K-M median time to wound closure for all wounds was 19 weeks. At weeks 20, 24, 28, and 48, the frequency of wound closure for all wounds was 51%, 56%, 62%, and 72%, respectively. The median time to closure by wound type was 22 weeks for VLUs, 24 weeks for DFUs, 23 weeks for PIs, 12 weeks for PSWs, and 14 weeks for other wounds. The proportion of wounds closed were 72% (VLUs), 52% (DFUs), 63% (PIs), 95% (PSWs), and 67% (other etiologies)., Conclusions: This 434-patient PCMP cohort analysis showed 72% wound closure and median time to wound closure of 19 weeks. PCMP demonstrated effectiveness for use in multiple wound types.

Background: The RESPOND registry study was the first prospective noninterventional study evaluating the real-world effectiveness of a native type 1 collagen matrix plus polyhexamethylene biguanide antimicrobial (PCMP) barrier in nonhealing wounds., Purpose: The objective of this secondary analysis was to describe the effects of PCMP in the subgroup of patients with venous leg ulcers (VLUs) in the RESPOND registry., Methods: RESPOND was a 28-site, prospective, noninterventional study for up to 32 weeks. All patients (N = 307) in RESPOND received PCMP. Eligibility criteria included patients being 18 years of age and older and having cutaneous wounds, not including third-degree burns. Kaplan-Meier methods analyzed the frequency and median time to wound closure., Results: For the cohort of PCMP-treated VLUs (n = 67), the mean baseline wound area was 20.07 cm2 and mean wound duration was 89 days. Wound closure frequencies were 33%, 42%, 45%, 53%, and 73% at weeks 8, 12, 16, 24, and 32, respectively. The median time to closure was 22 weeks. Incidences of achieving >60% reduction in baseline area and depth were 78% and 70%, respectively, with 87% showing a reduction of >75% in volume., Conclusion: PCMP appears to be a valuable adjunct for treating venous leg ulcers.

Aim: Determine the effectiveness of purified native type I collagen matrix plus polyhexamethylene biguanide antimicrobial (PCMP) on cutaneous wounds. Materials & methods: A prospective cohort study of 307 patients (67 venous leg ulcers, 62 diabetic foot ulcers, 45 pressure ulcers, 54 post-surgical wounds and 79 other wounds) was conducted. Results: Cox wound closure for PCMP was 73% at week 32. The median time to wound closure was 17 weeks (Kaplan-Meier). The incidence of PCMP-treated wounds showing >60% reductions in areas, depths and volumes were 81, 71 and 85%, respectively. Conclusion: PCMP demonstrated clinically meaningful benefits to patients with various types of cutaneous wounds. Clinical Trial registration number: NCT03286452.

Evidence indicates that a common problem for the person with an ostomy is pouch leakage and the development of peristomal skin irritation, which can negatively affect quality of life. While it is clear that the pouching system seal leakage can cause profound problems for the person with an ostomy, little information is available on interventions that focus on leakage. To address this gap, an international group of ostomy nurse experts was convened to develop consensus-based practice guidelines to assist ostomy nurses in determining the best pouching system for the patient. The outcomes of these guidelines for the person with a stoma are to decrease leakage and increase security and confidence leading to an increased quality of life. A large-scale Modified Delphi Consensus-Building Process was used to identify key factors in assessing body and stoma profiles to determine the best pouching system. The resulting consensus provides practice guidelines on how to assess body and stoma profiles, engage and educate patients, and when to follow up with patients after hospital discharge or product change.

Cutaneous disease can present with lesions of all colors of the visible spectrum. Lesions of the skin, nail, and mucous membranes with an orange color can be due to a variety of etiologies. The conditions may appear as purely orange, yellow-orange, red-orange, tan, or brown with an orange hue. The orange color may also present as a transient phase of a disease process. As with all dermatologic pathology, a key way to distinguish orange-colored lesions is by distribution and morphology. The sclera, palate, lips, gingiva, and nails may also be involved. A literature review using PubMed with keywords, including orange, skin, mucosa, cutaneous, xanthoderma, and granuloma, was conducted to gather all dermatologic conditions that can present with an orange color. The relevant diseases were categorized by etiology and include inflammatory, infectious, neoplastic, and exogenous causes., (Copyright © 2019. Published by Elsevier Inc.)

Background: Biofilm can impair wound healing by maintaining an elevated, but ineffective, inflammatory state. This article describes interim results from the prospective RESPOND postmarketing registry evaluating the use of a native type 1, porcine collagen matrix with the embedded antimicrobial polyhexamethylene biguanide (PCMP) in the management of chronic wounds., Methods: Adults ≥18 years of age with ≥1 appropriate wound were eligible for inclusion. Data that were final on January 26, 2018 were included in this analysis. At week 0, wounds were cleaned, debrided, and prepared as necessary and PCMP was applied, with a dressing to fix it in place. Patients received standard wound care plus PCMP weekly, up to 24 weeks, at the investigator's discretion. At each visit, wounds were assessed for area and quality of granulation tissue., Results: Most common wound types (N = 63) were venous ulcers (28.6%), trauma and lacerations (22.2%), postsurgical open wounds (15.9%), pressure injuries (12.7%), and diabetic ulcers (9.5%). Median baseline wound area was 6.5 cm 2 ; mean wound duration at baseline was 4 months. Of the 63 wounds, 43 (68.3%) achieved complete wound closure, 41 of 43 (95.3%) closed after PCMP treatment, and 2 of 43 (4.7%) after bridging to other modalities and surgical closure. Twelve out of 63 wounds were bridged to other modalities after PCMP treatment. Mean time to closure for PCMP wounds was 5.0 weeks., Conclusions: PCMP appears to be a useful adjunct for treating various wound types. PCMP use should be considered when managing chronic or acute wounds., (Copyright © 2019 The Authors. Published by Wolters Kluwer Health, Inc. on behalf of The American Society of Plastic Surgeons.)

Excoriation disorder (ED), also known as dermatotillomania, is a condition characterized by repeated "skin picking" that leads to the formation of skin lesions. Because of the similarity of its symptoms to obsessive compulsive disorder, ED is classified as a subcategory of obsessive compulsive disorder by Diagnostic and Statistical Manual of Mental Disorders Fifth Edition. Although the majority of the self-inflicted wounds are not clinically significant, many wounds lead to social and occupational dysfunction by becoming infected, chronic, and life threatening. This report describes the successful use of a viable intact cryopreserved human amniotic membrane in conjunction with selective serotonin re-uptake inhibitors in treating an ED patient who presented with a large calvarial wound of 3-year duration that had failed previous extensive medical and surgical interventions.

Objective: To determine whether the prevalence of depression, its associated quality of life, treatment and mental health literacy about depression varied according to accessibility to health services., Design: Face-to-face interviews with a random and representative sample of the South Australian population (aged >or= 15 years) were conducted between March and June 2004, with the respondents stratified using the Accessibility and Remoteness Index of Australia into categories of 'highly accessible', 'accessible', and 'moderately accessible and remote'., Results: From 4700 households selected, 3015 participants were interviewed (65.9% response rate). The prevalence of major depression and other depressions was not significantly different between each of the categories, although there was a trend for those from moderately accessible and remote areas to be less depressed overall. A significantly lower proportion of respondents from moderately accessible and remote locations reported that they had family or close friends who had suffered from symptoms consistent with depression, or that they had ever had treatment for those symptoms. However, there was no significant difference between the groups in those who had ever had or who were currently taking antidepressant medication. For those who were depressed, a significantly higher proportion from the accessible, and moderately accessible and remote regions had seen a community or district health service, social worker or other counsellor as compared with those from the highly accessible area., Conclusions: These findings indicate that depression is no more prevalent in less accessible regions of South Australia, and that when it is present, its treatment, in terms of antidepressants, which can be considered as a proxy marker for the overall management of depression, is similar to treatment in more accessible areas.

L-Carnitine has important roles in intermediary metabolism and patients with end-stage renal disease who are undergoing hemodialysis may develop a secondary L-carnitine deficiency. The extent of accumulation of the metabolites trimethylamine and trimethylamine-N-oxide when L-carnitine is administered orally has not been investigated previously in this population. Oral L-carnitine at a dose of 1 g daily was administered for twelve days to six patients with end-stage renal disease undergoing hemodialysis thrice weekly. Pre-dialysis plasma concentrations of L-carnitine (mean +/- SD) increased significantly (P < 0.05) from day 1 (baseline; 32.4 +/- 6.1 microM) to day 8 (66.1 +/- 13.8 microM) remaining constant thereafter. Although plasma levels of trimethylamine remained unaltered, the pre-dialysis plasma concentrations of trimethylamine-N-oxide increased significantly (P < 0.05) from day 1 (289.1 +/- 236.1 microM) to day 12 (529.0 +/- 237.9 microM). The hemodialysis clearances for L-carnitine, trimethylamine and trimethylamine-N-oxide were 14.3 +/- 8.2, 14.1 +/- 10.6 and 12.4 +/- 5.4 L/h, respectively, indicating their efficient removal by dialysis. Oral administration of L-carnitine at a dose of 1 g daily increases plasma concentrations of this substance to physiological levels in patients with end-stage renal disease who are undergoing hemodialysis. However, concerns about the possible deleterious consequences of such a dosage regimen still remain given that plasma concentrations of trimethylamine-N-oxide were continually rising and approximately doubled in a two-week period.

Background: Double depression, the combination of major depression and dysthymia, is associated with poor health-related quality of life (HRQoL) and increased health service utilization., Objective: To determine the prevalence of double depression, its associated morbidity and use of health services and antidepressants., Methods: A random and representative sample of the South Australian general population was interviewed. The mood module of the Primary Care Evaluation of Mental Disorders (PRIME-MD), the Short-Form Health Status Questionnaire (SF-36) and Assessment of Quality of Life (AQoL) instruments were administered, and data relating to health service utilization, antidepressant use and role functioning were collected., Results: Double depression was present in 3.3% of the population. The use of health services was significantly higher in this group than those with no depression, or dysthymia or major depression alone. Only 15.2% had attended a community health service, 18.2% had seen a psychiatrist, 10.1% a psychologist, 16.2% a social worker and 9.1% any other counsellor in the last month. While 41.4% were currently taking an antidepressant, the average doses of the two most commonly prescribed antidepressants were below the maximum recommended doses, and the use of antidepressant augmentation strategies was also minimal., Conclusions: While double depression is associated with increased morbidity and use of health services, the optimum use of both pharmacological and nonpharmacological treatments is clearly lacking in this community sample.

Background: Trimethylamine (TMA) is a short-chain tertiary aliphatic amine that is derived from the diet either directly from the consumption of foods high in TMA or by the intake of food high in precursors to TMA, such as trimethylamine-N-oxide (TMNO), choline and L-carnitine. The clinical significance of TMA may be related to its potential to contribute to neurological toxicity and 'uraemic breath' in patients with end-stage renal disease (ESRD)., Methods: Concentrations of TMA and TMNO in plasma from 10 healthy adults (not on haemodialysis) and 10 adults with ESRD undergoing haemodialysis (pre- and post-dialysis) were determined by gas chromatography-mass spectrometry., Results: The concentrations of TMA and TMNO in pre-dialysis plasma (1.39+/-0.483 and 99.9+/-31.9 microM, respectively) were significantly (P<0.05) higher than the corresponding levels in healthy subjects (0.418+/-0.124 and 37.8+/-20.4 microM, respectively). However, there were no significant differences between post-dialysis and healthy subject plasma concentrations. In the ESRD patients, there was a significant (P<0.05) reduction in plasma TMA (from 1.39+/-0.483 to 0.484+/-0.164 microM) and TMNO (from 99.9+/-31.9 to 41.3+/-18.8 microM) during a single haemodialysis session., Conclusions: TMA and TMNO accumulate between haemodialysis sessions in ESRD patients, but are efficiently removed during a single haemodialysis session.

Context: Telemedicine has been used for remote management of many medical problems. Given the ever-expanding demands to provide increasing service with increasingly limited resources, quality care and practice efficiency can be enhanced by telemedicine., Objective: This study was undertaken to explore the reliability of wound assessment using computer-transmitted digital imagery compared with a traditional bedside evaluation and also to assess its potential role in healthcare delivery., Design/setting/patients: In the hospital setting, rounding vascular surgeons and a surgical resident evaluated the wounds on the service. A digital photograph was obtained with a 3.3 megapixel camera, and a wound-assessment tool was completed. A plastic surgery attending then reviewed the images at a later date and completed the same data tool., Main Outcome Measures: Wounds were rated for eschar, exposed bone, cellulitis, purulence, swelling, granulation tissue, granulation color, and depth using a standardized data collection tool. kappa statistics were computed for all variables, between raters., Results: There were 2 phases of the study. In both phases, there was 100% agreement by the rounding physicians that the digital image was representative of the wound. Phase 1 agreement between evaluators was moderate to almost perfect, as demonstrated by kappa values (range, 0.50-0.87). In phase 2, all variable kappa values were rated as almost perfect, except the ability to evaluate depth of the wound to the millimeter, which was rated as substantial., Conclusions: The ability to accurately evaluate a wound on the basis of a digital image is possible. However, it requires training of participants and is facilitated by use of an assessment tool. With these caveats, evaluation of wounds using digital images is equivalent to bedside examination. This technology can improve practice efficiency, provide needed expertise at remote sites, and is an acceptable alternative method of wound assessment.

Trimethylamine (TMA) is a volatile tertiary aliphatic amine that is derived from the diet either directly from the consumption of foods containing TMA, or by the intake of food containing precursors to TMA such as trimethylamine-N-oxide (TMNO), choline and L-carnitine. Following oral absorption in humans, TMA undergoes efficient N-oxidation to TMNO, a reaction catalyzed by the flavin-containing monooxygenase (FMO) isoform 3 enzyme. TMNO subsequently undergoes excretion in the urine, although, evidence also suggests that metabolic retro-reduction of TMNO can occur. Whilst the pharmacokinetics of TMA and TMNO has not been fully elucidated in humans, a number of studies provide information on the likely fate of dietary derived TMA. Trimethylaminuria is a condition that is characterized by a deficiency in FMO3 enzyme activity, resulting in the excretion of increased amounts of TMA in bodily fluids such as urine and sweat, and breath. A human FMO3 database has been established and currently twenty-eight variants of the FMO3 gene have been reported including twenty-four missense, three nonsense, and one gross deletion mutation. Whilst TMA and TMNO are generally regarded as non-toxic substances, they are of clinical interest because of their potential to form the carcinogen N-nitrosodimethylamine.

LPS induces an up-regulation of promatrix metalloproteinase-9 (proMMP9) gene expression in cells of the monocyte/macrophage lineage. We demonstrate here that LPS preparations are also able to activate proMMP9 made by human macrophages or THP-1 cells via LPS-associated proteinases, which cleave the N-terminal propeptide at a site or sites close to the one cleaved upon activation with organomercurial compounds. LPS-associated proteinases are serine proteinases that are able to cleave denatured collagens (gelatin) and the mammalian serine proteinase inhibitor, alpha(1)-proteinase inhibitor, thereby pushing the balance of extracellular matrix turnover even further toward degradation. A low molecular mass, low affinity inhibitor of MMP9, possibly derived from the propeptide, is generated during proMMP9 activation. However, inhibition of the LPS-associated proteinases had no effect on proMMP9 synthesis, indicating that their proteolytic activity was not required for signaling the up-regulation of the proMMP9 gene.

Between July 1989 and March 1992 at a single institution 27 male and 30 female patients underwent lower urinary reconstruction with stomach. Mean patient age was 9.9 years (range 1.5 to 28 years). The diagnoses were epispadias/exstrophy complex (19 patients), myelodysplasia (11), cloacal exstrophy (6), posterior urethral valves (6), Hinman syndrome (4), sacral agenesis (3) and other (8). Indications for surgery were urinary incontinence, upper tract deterioration or undiversion. A total of 54 patients underwent augmentation gastrocystoplasty and 3 had total bladder replacement. Mean followup time was 23.2 months (range 12 to 39 months). The syndrome of dysuria and hematuria is defined as 1 or a combination of the following symptoms: bladder spasm or suprapubic, penile or periurethral pain, coffee brown or bright red hematuria without infections, skin irritation or excoriation and dysuria without infections. Telephone and clinic interviews identified 21 patients (36%) with symptoms of the dysuria and hematuria syndrome. The most common symptoms were hematuria (71%) and bladder or suprapubic pain (76%). Of the patients 18 (86%) ranked the severity of symptoms as mild to moderate and 3 (14%) ranked them as severe. No medications were required to control the symptoms in 13 patients (62%) and 3 other patients only required medications on an as needed basis. Overall patients who required no medications had lower symptom scores than those who required medications. Patients with decreased renal function may be more at risk for the dysuria and hematuria syndrome than those with normal renal function. Patients who were wet were more prone to have the dysuria and hematuria syndrome than those who were totally dry. The pathophysiology of the dysuria and hematuria syndrome is currently unknown. Patients who require urinary reconstruction with stomach tissue need to be made aware of the potential of the dysuria and hematuria syndrome.

A 20-year-old man had a spontaneous rupture of the ascending aorta while exercising. The diagnosis of Marfan syndrome, established by the gross and microscopic autopsy findings, was further supported by review of the autopsy report of the father, who had died at age 26 of a nearly identical aortic rupture. To avoid occurrences such as the above, the responsibility of the forensic pathologist should extend beyond the autopsy to appropriate counseling of families in instances where medically treatable hereditary conditions may be present in the survivors.