Clinical response to antibiotic regimens in lower limb cellulitis: a systematic review.

There is variation in the treatment of lower limb cellulitis (LLC) with no agreement on the most effective antibiotic regimen. Many patients with cellulitis fail to respond to first-line antibiotics. This can negatively affect patient care and result in unnecessary hospital admissions. The aim of this systematic review was to determine the clinical response and safety of antibiotic regimens for the management of LLC. A systematic review for randomized controlled trials (RCTs) was conducted using OVID MEDLINE, Ovid Embase and Cochrane Central Register of Controlled Trials in January 2019. Outcomes of interest included the clinical response to antibiotic regimens (type, dose, route, duration) and the safety of antibiotics in LLC. Trial quality was identified using the Cochrane Risk of Bias tool. Four RCTs were included. All included studies showed no significant differences between the clinical response to different antibiotic type, administration route, treatment duration or dose. LLC may be overtreated and shorter courses of oral antibiotics, possibly with lower doses, may be more suitable. There is a lack of published data on the clinical response and safety of antibiotics in LLC. Three studies were high risk for bias overall. Further high-quality studies may help determine whether less intensive antibiotic regimens can effectively treat LLC.

Potentiating cutaneous wound healing in young and aged skin with nutraceutical collagen peptides.

BACKGROUND: Chronic wounds continue to be a burden to healthcare systems, with ageing linked to increased prevalence of chronic wound development. Nutraceutical collagen peptides have been shown to reduce signs of skin ageing, but their therapeutic potential for cutaneous wound healing remains undefined. AIM: To determine the potential for nutraceutical collagen peptides to promote cutaneous wound healing in vitro in the context of age. METHODS: The potential for bovine- or porcine-derived nutraceutical collagen peptides to promote wound healing of primary cutaneous fibroblasts and keratinocytes derived from young and aged individuals in vitro was assessed by two-dimensional scratch and cell-viability assays and by immunofluorescence for the cell proliferation marker, Ki67. The achievement of peptide concentrations in vivo, equivalent to those exerting a beneficial effect on wound healing in vitro, was confirmed by pharmacokinetic studies of hydroxyproline, a biomarker for collagen peptide absorption, following peptide ingestion by healthy individuals over a wide age range. RESULTS: Results demonstrated significant nutraceutical collagen peptide-induced wound closure of both young and aged fibroblasts and keratinocytes, mediated by enhanced cellular proliferation and migration. Analysis of blood levels of hydroxyproline in young and aged individuals following porcine collagen peptide ingestion revealed peak serum/plasma levels after 2 h at similar concentrations to those exerting beneficial effects on wound healing in vitro. CONCLUSION: These data demonstrate the capacity for nutraceutical collagen peptides to promote cutaneous wound closure in vitro, at pharmacologically achievable concentrations in vivo, thereby offering a potential novel therapeutic strategy for the management of cutaneous wounds in young and aged individuals.

A review of trench foot: a disease of the past in the present.

From the French Invasion of Russia in 1812, to Glastonbury festival in 2007, trench foot has been reported, yet the exact nature of the condition remains unclear. This review explores the pathogenesis and treatment of trench foot. Trench foot is considered to be a nonfreezing cold injury often complicated by infection, in which exposure to cold temperatures just above freezing, combined with moisture, results in a peripheral vasoneuropathy. The presence of physical trauma, bacterial or fungal infections, malnutrition, venous hypertension and lymphoedema mean that some individuals are at greater risk of trench foot. Trench foot may be prevented by warming the feet, changing socks, staying active, rubbing the skin with oil and regularly inspecting the feet. Avoiding risk factors may help prevent the condition. The management of trench foot is less clear. Vasodilators such as iloprost and nicotinyl tartrate or sympathectomy may help. Trench foot may lead to necrosis, cellulitis, sepsis and amputation. It remains a poorly understood condition.

A new urethral catheterisation device (UCD) to manage difficult urethral catheterisation.

The cost of urethral catheterisation injury (UCI) is significant, but the true incidence of patient care error is difficult to establish in the absence of specific hospital codes recording difficult urethral catheterisation (DUC) and UCI. For many years urologists are familiar passing a non-traumatic hydrophilic guidewire blindly into the bladder to aid urethral catheter insertion in difficult circumstances. However, so far, no purpose-built regulated medical device was available on the market and clinicians had to improvise. Urethrotech filled that gap and developed the Urethral Catheterisation Device (UCD®), which integrates a standard hydrophilic Nitinol guidewire into a 3-way 16F Silicone urethral catheter design to enable safe second-line urethral catheterisation when first-line catheterisation with a standard urethral catheter is unsuccessful. The safety and efficacy of UCD® catheterisation were evaluated in consecutive cohorts of men undergoing cardiac surgery and compared to the incidence of DUC and UCI with standard Foley catheterisation. A simple new Male Catheterisation Algorithm is proposed that can deliver a safe male urethral catheterisation treatment protocol for all clinical settings of healthcare services, which is easy to implement and integrate into standard catheterisation training programs to manage DUC and avoid UCI, empowering a frontline workforce to deliver better patient care.

Lower limb cellulitis: low diagnostic accuracy and underdiagnosis of risk factors.

Accurate diagnosis and recognition of predisposing factors has been shown to be challenging in lower limb cellulitis (LLC). Assessment of 1746 consecutive patients with cellulitis presenting to a UK university hospital showed increasing overdiagnosis, with only 31.9% of patients referred during the period 2015-2018 having the diagnosis of LLC confirmed. Recognition of at least one predisposing factor increased from 61% to 89% following introduction of more specific screening questions. This identified a need for better primary care dermatology education and the benefit of a proforma with specific screening questions for reversible predisposing factors for LLC.

Medical students and interns' knowledge about and attitude towards homosexuality.

BACKGROUND AND RATIONALE: Medical professionals' attitude towards homosexuals affects health care offered to such patients with a different sexual orientation. There is absence of literature that explores the attitudes of Indian medical students or physicians towards homosexuality. AIM: This study aimed to evaluate Indian medical students and interns' knowledge about homosexuality and attitude towards homosexuals. MATERIALS AND METHODS: After IEC approval and written informed consent, a cross-sectional study was conducted on a purposive sample of undergraduate medical students and interns studying in one Indian medical college. The response rate was 80.5%. Only completely and validly filled responses (N = 244) were analyzed. The participants filled the Sex Education and Knowledge about Homosexuality Questionnaire (SEKHQ) and the Attitudes towards Homosexuals Questionnaire (AHQ). SEKHQ consisted of 32 statements with response chosen from 'true', 'false', or 'don't know'. AHQ consisted of 20 statements scorable on a 5-point Likert scale. Multiple linear regression was used to find the predictors of knowledge and attitude. RESULTS: Medical students and interns had inadequate knowledge about homosexuality, although they endorsed a neutral stance insofar as their attitude towards homosexuals is concerned. Females had more positive attitudes towards homosexuals. Knowledge emerged as the most significant predictor of attitude; those having higher knowledge had more positive attitudes. CONCLUSION: Enhancing knowledge of medical students by incorporation of homosexuality related health issues in the curriculum could help reduce prejudice towards the sexual minority and thus impact their future clinical practice.

Wetting of a Stepped Platinum (211) Surface.

Steps stabilize water adsorption on metal surfaces, providing favorable binding sites for water during wetting or ice nucleation, but there is limited understanding of the local water arrangements formed on such surfaces. Here we describe the structural evolution of water on the stepped Pt(211) surface using thermal desorption, low-energy electron diffraction, and scanning tunneling microscopy to probe the water structure. At low coverage water forms linear structures comprising zigzag chains along the steps that are decorated by H-bonded rings every one or two units along the terrace. Simple 2-coordinate H-bonded chains are not observed, indicating the Pt step binds too weakly to compensate entirely for a low water H-bond coordination number. As the coverage increases, water chains assemble into a disordered (2 × 1) structure, likely made up of the same narrow water chains along the steps with little or no H-bonding between adjacent structures. The chain structure disappears as water adsorption saturates the surface to form an incommensurate, disordered network of water rings of different size. Although the steps on Pt(211) clearly stabilize water adsorption and direct growth, the surface does not support the simple 1D chains previously proposed or an ordered 2D network such as seen on other surfaces. We discuss reasons for this and the factors that determine the behavior of the first water layer on stepped metal surfaces.

Merkel cell carcinoma.

Merkel cell carcinoma (MCC) is a rare neuroendocrine carcinoma. The cellular origin of MCC may include Merkel cell precursors. The incidence of MCC has increased significantly however trends may have been confounded by evolving diagnostic criteria. The two key aetiologies of MCC are ultraviolet radiation and Merkel cell polyoma virus (MCPyV). Both have unique mechanisms of carcinogenesis. MCC presents non-specifically as a rapidly growing, red-to-violet nodule on sun-exposed areas. Diagnostic accuracy has improved through immunohistochemical markers such as CK-20. Lymph nodes should be evaluated in MCC through examination and sentinel biopsy. USS, CT, MRI and CT-PET may be useful in staging. Management depends on tumour location, stage and comorbidities. MCPyV status may guide treatment strategy in the future. Treatment for the primary MCC is commonly wide local excision followed by radiotherapy, guided by anatomical constraints. There is uncertainty about surgical margins. Treatments for nodal disease have not been determined through trials. They include nodal dissection or radiotherapy for clinically or radiologically apparent disease, and adjuvant nodal irradiation for negative nodes, microscopic disease or following nodal dissection for definite disease. Patients with loco-regional advanced inoperable disease should be considered for combination therapy including chemotherapy, radiotherapy, surgery and immunotherapy. Systemic therapy for advanced disease includes immune checkpoint inhibitors targeting the PD-1/PD-L1 pathway. Avelumab can improve survival in metastatic MCC. Immunotherapy may result in longer disease control. Various other immunotherapeutic and molecular agents are undergoing trials. MCC continues to have a high mortality characterized by high recurrence and early metastases.

Continuous Paravertebral Infusions as an Effective Adjunct for Postoperative Pain Management in Living Liver Donors: A Retrospective Observational Study.

We analyzed the effectiveness of paravertebral-block for immediate postoperative pain control in living liver donors. Specifically, we sought to determine whether or not the addition of paravertebral catheters with continuous ropivacaine infusion would decrease postoperative opioid use and reduce the incidence of adverse effects and complications. We reviewed the records of 26 patients who underwent right-lobe living donor hepatectomy (RLDH): 16 with and 10 without such catheters. The primary outcome was opioid use on postoperative day (POD) 1 through 3. For each of those 3 days, we calculated each patient's opioid use in morphine equivalents (mg). We also noted pain scores, adverse effects, and complications. The rate of decrease in morphine equivalents was higher in the catheter group (rate of change = -22.72; P = .038) for POD 1 (0-24 hours) and POD 2 (25-48 hours) than in the noncatheter group. For POD 2 alone, the catheter group used, on average, 20.98 mg fewer morphine equivalents than the noncatheter group (P = .023). The catheter group had a markedly reduced pain trajectory postoperatively (P = .014) than the noncatheter group. The catheter placement procedure itself was safe.

Mechanisms for D-glucose inhibition of myo-inositol influx into rat lens.

Myo-Inositol depletion as a result of hyperglycemia is considered one of the leading contributors to chronic diabetic complications. We investigated the possible mechanisms through which elevated extracellular glucose levels affect the loss of intracellular myo-inositol in rat lens. Short-term incubation (up to 4 h) in solutions with elevated glucose concentrations revealed a concentration-dependent inhibition of myo-inositol influx. This inhibition was caused by both an increase of the transport coefficient and a decrease of maximal flux and thus was a mixed competitive and noncompetitive inhibition. If polyol accumulation was prevented with sorbinil, an aldose reductase inhibitor, the inhibition of myo-inositol influx was partially reduced. The remaining inhibition was the result of an increased transport coefficient without a change in maximal flux and therefore represents a strictly competitive inhibition. A similar competitive inhibition was observed with the nonmetabolizable glucose analogue L-glucose, which cannot be converted to polyol. Longer exposure (16 h) to solutions with high glucose concentrations resulted in an inhibition that correlated with high lens polyol levels. This inhibition persisted after the lenses were returned to solutions with normal glucose concentrations and was the result of a decrease of maximal flux without a significant change in transport coefficient, a strictly noncompetitive inhibition. The noncompetitive inhibition associated with polyol accumulation and the competitive inhibition due to extracellular glucose were additive. Lens myo-inositol depletion after exposure to elevated glucose concentrations thus resulted from a competitive inhibition caused by the interaction of extracellular glucose with the myo-inositol carrier and a noncompetitive inhibition associated with polyol accumulation.

Characterisation of the in vitro responsiveness of lymphocyte subsets to locomotor stimuli by immunocytochemical methods.

The in vitro locomotion of lymphocyte subsets has previously been determined by use of highly purified cell populations. A method is now described in which mixed peripheral blood lymphocytes (PBL) migrate to the undersurface of polycarbonate filters in a 48 well microassay, the responding cells being characterised by alkaline phosphatase-anti-alkaline phosphatase immunocytochemistry. Recombinant interleukin (rIL)-1 alpha, zymosan activated plasma (ZAP) and rIL-8 were shown to induce concentration-related migration of mixed PBL in the 48 well assay and were therefore used as reference agonists. Total T cells, B cells, T helper/inducer and T suppressor/cytotoxic cells, as well as lymphocytes stained with the monoclonal antibodies UCHL1 and SN130, have now been quantified after migration to the undersurface of 8 microns pore size polycarbonate filters, in response to optimal concentrations of rIL-1 alpha, ZAP and rIL-8. The value of the analytical method was demonstrated by the selective responses seen. rIL-1 alpha selectively stimulated the migration of T helper/inducer and a small number of B cells without affecting T suppressor/cytotoxic cell locomotion. ZAP and rIL-8 significantly stimulated the migration of T helper/inducer, T suppressor/cytotoxic and B cells. ZAP and rIL-1 alpha also stimulated the migration of both UCHL1 and SN130 positively stained cells. This method may therefore be used to investigate the selective actions of lymphocyte locomotor stimuli on PBL sub-populations without the need to purify specific cell subsets, and to study the specificity of certain inhibitors or drugs on lymphocyte responses.

Modulation of aflatoxin B1 activated protein kinase C by phenolic compounds.

Several natural phenolic compounds were tested in vitro for their effect on the activity of protein kinase C isolated from liver cytosol, particulate and nuclear fractions of normal and aflatoxin B1 treated rats. Quercetin and kaempferol inhibited the enzyme activity of all these fractions at very low dose levels. These phenolics were particularly effective in inhibiting the elevated enzyme activity following aflatoxin B1 administration. Ellagic acid and curcumin were found to be inhibitory only towards particulate enzymes obtained after carcinogen treatment, while curcumin and rutin were moderately active against nuclear enzymes. Constitutive activation of protein kinase C can drive the cell to a proliferative state, thereby initiating the process of carcinogenesis, however, suppression of this activation by phenolic compounds may be an effective way to control carcinogenesis.

Eradication of Helicobacter pylori in general practice.

OBJECTIVES: To determine the current management of patients with Helicobacter pylori infection in general practice with regard to the selection of patients, testing for the presence of the organism, the choice of eradication therapy and the occurrence of symptoms during follow-up. DESIGN: Cross-sectional survey involving the retrospective collection of data from patient medical records. SETTING: Five general practices in the Fife region of Scotland during June and July 1995. MAIN OUTCOME MEASURES: The proportion of patients appropriately selected for eradication therapy and the success of treatment as assessed by remission of symptoms during follow-up. RESULTS: Of 154 patients studied, 80% received eradication therapy for peptic ulcer disease, the remainder for non-ulcer dyspepsia or gastrooesophageal reflux. Fifty-six different regimens were used, the most common combination of drugs being omeprazole plus amoxycillin. H. pylori status was known in only one-third of patients before treatment and in only 15% after treatment. More than half of patients complained of recurrent symptoms of dyspepsia during follow-up after eradication therapy and 47% required further treatment. In terms of the selection of patients and testing for H. pylori, the overall management using eradication therapy was acceptable in less than half of patients. In particular, the management of patients with ulcer disease associated with either ulcerogenic drugs or previous complications failed to provide the essential protection against the high risk of future haemorrhage or perforation. CONCLUSIONS: The findings of this study indicate an urgent need for improved education if therapy for the eradication of H. pylori is to be used appropriately and safely.

Signal transduction mechanism in response to aflatoxin B1 exposure: phosphatidylinositol metabolism.

A single dose of aflatoxin B1 (7 mg/kg body weight) to male Wistar rats significantly stimulated the hepatic activity of phosphatidylinositol kinase, a key enzyme in the cell signalling mechanism, 1-7 h following its administration. Phosphatidylinositol 4-phosphate kinase activity showed only marginal increase, whereas activities of diacylglycerol kinase and phosphatidylinositol synthetase remained unchanged. The level of diacylglycerol, however, recorded a sharp increase at 1 and 2 h after carcinogen treatment. The stimulation of phosphatidylinositol cycle with faster turnover of active second messengers might be an early step in the manifestation of toxicity and/or carcinogenicity.

Signal transduction mechanism in response to aflatoxin B1 exposure: protein kinase C activity.

A single dose of the carcinogen aflatoxin B1 (7 mg/kg body weight) to male Wistar rats significantly enhanced the hepatic activity of protein kinase C in the particulate and nuclear fractions. The particulate fraction showed stimulation at 4 and 7 h, while the nuclear activity was increased at 17 h following administration of aflatoxin B1. The enzyme activity in cytosol revealed a significant decline corresponding to stimulation in particulate fraction. The carcinogen-activated protein kinase C stimulated autophosphorylation, and was found to accelerate in vitro phosphorylation of two model DNA synthesizing enzymes--the Klenow fragment of replicative DNA polymerase of E. Coli and a DNA primase-polymerase complex of yeast mitochondrial origin. Prior phosphorylation of these enzymes led to significant enhancement of their activities. The results imply that activation of protein kinase C and consequently the activation of DNA synthesizing enzymes may play an important role in the initiation of carcinogenesis.

Myo-inositol transport in the lens of galactose-maintained rats.

Lens myo-inositol (MI) content is regulated by a pump-leak system consisting of an active Na-dependent MI transport and its passive permeability through the membrane. We measured the active MI uptake and membrane permeability in lenses of rats maintained on a 50% galactose diet for 1, 3 and 7 days. After only 1 day of galactose feeding, active MI uptake in the lens was reduced dramatically by 74% compared to age-matched control lenses; by day 3, active MI transport was decreased by 89% and it was undetectable by day 7. The passive membrane permeability was determined by measuring (a) the passive MI influx and (b) the 3H-sorbitol flux. After 1 day of galactose feeding, the membrane permeability increased such that within 3 days it increased to 5-6 fold. Galactose feeding also led to a rapid increase in lens polyol content. After 1 day, lens polyol increased to 53 mumol/g wet wt compared to a control value of 0.35 mumol/g wet wt and increased further to 65 and 72 mumol/g wet wt after 3 and 7 days of galactose feeding respectively. Lens galactose accumulation was low (3 mumol/g wet wt) up to 7 days; however, it was rapidly increased after 7 days. Our results indicate that galactose feeding rapidly interfered with MI homeostasis by a severe depression of active MI transport and a rapid increase in membrane permeability. These interferences of MI homeostasis correlate with the appearance of high polyol levels.

Studies on transformations of plutonium-239 and americium-241 in three major Indian soils.

These studies were carried out to elucidate the behaviour of 239Pu and and 241Am in three major soil groups of India, namely oxisol, vertisol-pellustert and entisol-haplaquent, over extended periods up to 400 days. The influences of soil characteristics, addition of organic matter and the chemical form of the radionuclides added to soils were investigated. A large fraction, ranging from 60 to 90% of the soluble radionuclides added as nitrates, underwent rapid conversion to precipitated hydrous oxides and hydroxides (0.3 M sodium citrate-dithionite extracts). At 3 h after contamination, ion-exchangeable forms (0.1 M MgCl2 extracts) contained low levels of total added Pu (0.7 to 19.1%) and from 0.1 to 2.8% of total Am. These levels decreased further with increasing periods of incubation of up to 400 days. In contrast, on addition of chelated forms of radionuclides (as DTPA and EDTA complexes) up to 85% of total Pu, and about 50% of total Am were associated with 0.1 M MgCl2 extracts 3 h post-contamination and significant amounts were extractable when maintained over extended periods of incubation of up to 400 days. The levels of Pu and Am associated with organic-bound forms (0.1 M NaOH extracts) did not show consistent trends, although in all three soil types the contents of these radionuclides in the insoluble residue fraction (including refractory compounds) generally increased with time of incubation.

Role of proteins and cholesterol in human senile cataractogenesis.

Cataracts are a major cause of blindness in man with far reaching personal, social and economic consequences. The clarity of the lens is dependent upon the maintenance of the integrity of the fiber cell plasma membrane whose important component is cholesterol. In the present study, we have demonstrated that cataract formation influences the cholesterol and protein distribution within the lens.

Plasma electrolytes and enzymes in country liquor poisoning.

Plasma sodium, potassium, bicarbonate, calcium, magnesium, pseudocholinesterase, amylase and alkaline phosphatase were estimated in 43 cases of country-liquor poisoning and 29 normal controls. In the poisoned subjects, plasma potassium, magnesium and amylase levels were elevated, while plasma bicarbonate levels were diminished; and plasma pseudocholinesterase and alkaline phosphatase were not affected. Plasma calcium and pseudocholinesterase were elevated in poisoned patients who recovered; however, these were diminished in fatal cases. Plasma bicarbonate and amylase were affected depending upon the severity of poisoning.