Toe Web Infections, the Microbiome, and Toe Web Psoriasis: A Review.

OBJECTIVE: To present the toe web space as an anatomically, physiologically, and pathologically unique part of the human body; characterize toe web infections and discuss why they occur; and highlight toe web psoriasis as an uncommon condition that providers should consider if toe web intertrigo does not respond to treatment. DATA SOURCE: This review encompassed many years of clinical observation and photographs; medical textbooks; and a literature search of MEDLINE, PubMed, and Google Scholar. STUDY SELECTION: Primary research keywords included intertrigo, toe web intertrigo, toe web infection, tinea pedis, microbiome, skin microbiome, toe web microbiome, ecology, psoriasis, psoriasis microbiome, intertriginous psoriasis, and Wood's lamp. More than 190 journal articles met the search criteria. DATA EXTRACTION: The authors sought data relating to what makes for a healthy toe web space and what makes for disease. They extracted and collated relevant information to compare and contrast among sources. DATA SYNTHESIS: After understanding the normal toe web space and the microorganisms that normally reside there, the authors investigated why infections occur, how they should be treated, what complications may result, and what other diseases occur in the toe web area. CONCLUSIONS: This review of toe web infection illustrates the effect of the microbiome and reports a rare form of psoriasis that is usually misdiagnosed as athlete's foot. The toe web space is a unique part of the human body that can be affected by a variety of both common and unusual conditions.

Optical frequency stabilization with a synchronous frequency-to-voltage converter.

Between a frequency comb mode and a continuous-wave (cw) laser, we demonstrate that a frequency-to-voltage converter can be used to transfer frequency instability in the 10-14 range for integration times τ between 0.25 and 2100 s. The technique is relevant when the optical beat between laser signals is weak and a high level of frequency stability is required both in the short term and long term, as in the case of laser cooling with very narrow transitions. The impressive stability transfer arises through the use of a synchronous voltage-to-frequency converter that relies on an external CMOS oscillator. Aided by an atomic reference to the frequency comb, the method grants long-term stability to the cw laser, superior to that achieved with most optical cavities.

Heart-Lung Transplantation From Donation After Circulatory Death Using Mobile Normothermic Regional Perfusion.

Combined heart-lung transplant (HTLx) is the most durable treatment available for end-stage heart and lung failure. Many patients are unable to receive combined organs due to organ availability and allocation policies prioritizing separate heart or lung transplantation. While an average of 45 HTLxs have been performed per year in the United States half the listed patients do not receive organs. Recently, donation after circulatory death (DCD) utilizing normothermic regional perfusion (NRP) has been utilized for heart allografts with excellent results, and here, we present a case utilizing mobile NRP to procure a heart and lung block from a circulatory death donor and successful implantation for a recipient in a separate center.

Does direct admission from an emergency department with on-site neurosurgical services facilitate time critical surgical intervention following a traumatic brain injury in children?

OBJECTIVES: To compare the proportion of trauma craniotomies performed within 4 hours of presentation to emergency departments (ED) with and without on-site neurosurgery. DESIGN: A retrospective cohort analysis of data collected prospectively between January 2005 and April 2010 from patients with traumatic brain injury who were admitted to the paediatric intensive care unit (PICU) following traumatic brain injury. METHODS: Times for admission to ED, PICU and theatre were obtained through analysis of prospectively collected data management systems. Emergency department admission to neurosurgical theatre lag time was calculated using Microsoft Excel. Statistical analysis was performed using R (version 2.11.0). Subjects. Fifty-seven cases were identified. Twenty patients were admitted directly from ED to an on-site neurosurgical unit. The remaining 37 were transferred from regional EDs. RESULTS: Thirty-one craniotomies were performed. Thirteen in-patients admitted directly to hospital with neurosurgery on site. Eighteen in patients admitted at the local hospital and then transferred to the neurosurgical unit. Thirteen of Thirty-one (42%) craniotomies were performed within 4 hours. In the on-site group 10 of 13 (77%) craniotomies were performed within 4 hours compared to 3 of 18 (17%) in those transferred from regional ED (p = 0.001232) (Fisher exact test). Eleven patients were transferred directly from ED to neurosurgical theatre for emergency craniotomies. Within this subgroup, seven patients came from the cohort of admissions to a hospital with on-site neurosurgery. The remaining four patients were transferred from regional ED. There were eight extradural haematomas, one subdural haematoma and two intraparenchymal haemorrhages. The mean time from ED presentation to theatre was 1.68 hours and 5.46 hours for the on-site and regional transfer groups, respectively. There were no mortalities. CONCLUSIONS: Forty-two per cent of trauma craniotomies are performed within 4 hours. However, presentation to an ED with on-site neurosurgical services significantly facilitates time critical surgery in children following a traumatic brain injury.

Health and safety of the older worker.

BACKGROUND: In the UK, increasing numbers of paid employees are over 60 years with further increases expected as the state pension age rises. Some concern surrounds possible increased work-related illness and accidents for people working beyond the age of 60. AIMS: To identify the available evidence for health and safety risks of workers over age 60 years with respect to factors associated with injuries and accidents. METHODS: Databases searched included PUBMED, OSHUpdate, National Institute for Occupational Safety and Health (NIOSHTIC-2), SafetyLit, the UK The Health and Safety Executive (HSELINE) and the Canadian Centre for Occupational Health and Safety until December 2009. Inclusion criteria were workers aged over 60 years. Findings were grouped into occupational accidents and injuries and individual and workplace factors that may have influenced risk of injury to the over-60s. RESULTS: Very little direct evidence was found concerning safety practices and health risks of workers over age 60. Some safety risks were associated with specific physical declines such as age-related hearing loss. Overall, these workers had fewer accidents and injuries but these were more likely to be serious or fatal when they occurred. There was no strong evidence that work patterns, including shift work or overtime, affected safety. Protective, compensatory strategies or experience may maintain safe working practices. CONCLUSIONS: Implications for health and safety risks cannot be assessed without longitudinal research on workforces with substantial numbers of workers over age 60 in order to address the healthy worker effect.

Identification of tryptic peptides unique to a 110,000-molecular weight polyprotein encoded by the T-8 isolate of murine leukemia virus.

Mink cells nonproductively-infected with the weakly-transforming T-8 isolate of murine leukemia virus (MuLV) express a 110,000 mol wt polyprotein designated T-8 P110. By immunoprecipitation analysis, T-8 P110 is shown to contain AKR-MuLV amino terminal gag gene-specific components (p15, p12) but to lack p30, p10, gp70, and p15(E) antigenic determinants. These observations are further substantiated by tryptic peptide analysis indicating T-8 P110 to share approximately six lysine-containing tryptic peptides with AKR-MuLV Pr65gag, and none with AKr-MuLV Pr82env. Furthermore, of seven methionine-containing T-8 P110 tryptic peptides, at least four can be conclusively shown not to be present in either AKr-MuLV Pr180gag/pol or Pr82env. A clonal mink cell line nonproductively infected by T-8, and expressing high levels of P110, although not morphologically transformed, is shown to lack elevated levels of tyrosine-specific protein kinase activity and reduction of epidermal growth factor binding sites characteristic of cells transformed by many other RNA-transforming viruses. These findings argue either that the T-8 viral genome contains acquired cellular sequences encoding a portion of P110, or that T-8 P110 represents an inphase deletion of AKR-MuLV Pr180gag/pol with extensive posttranlational modification and that an as yet unidentified protein is responsible for T-8 associated transformation.

Anemia- and polycythemia-inducing isolates of Friend spleen focus-forming virus. Biological and molecular evidence for two distinct viral genomes.

Two distinct clones of Friend spleen focus-forming virus (SFFV), differing in their erythroleukemic potential, are described. These isolates have been cloned free of their associated helper viruses and shown to be replication-defective. Both SFFV isolates have been rescued from rat fibroblast nonproducer cell clones with cloned replication-competent viruses, F-MuLVA and F-MuLVP, obtained from the anemia- or polycythemia-inducing isolates of Friend virus complex, respectively. These rescued viruses induce a rapid proliferative disease associated with the appearance of macroscopic spleen foci and splenomegaly. In addition, each is subject to regulation by the W, Steel (Sl), and Fv-2 host gene loci. These two isolates of SFFV can, however, be distinguished by both biological and molecular criteria. Friend SFFVP induces a rapid polycythemia associated with the appearance of large numbers of erythropoietin (EPO)-independent erythroid colony-forming cells in the marrow and spleen. In contrast, SFFVA induces a rapid anemia associated with a progressive decrease in the number of EPO-dependent erythroid colony-forming cells in marrow, and a rapid increase in the number of EPO-dependent erythroid colony-forming cells in spleen. Furthermore, the nature of the disease induced by the two isolates of SFFV is independent of the Friend helper virus: SFFVP, rescued from a nonproducer cell clone with either F-MuLVA or F0MuLVP, induced a polycythemic transformation, whereas SFFVA, rescued with either F-MuLVA or F-MuLVP, induced an anemic transformation. The two Friend SFFV isolates can also be discriminated on the basis of translational products encoded by their gag and env genes: SFFVP encodes the amino-terminal gag-gene protein p15, whereas SFFVA encodes the gag-gene proteins p15, p12, and p30. In addition, the SFFV isolates encode nonidentical 55,000-mol wt env gene-related proteins that can be distinguished by analysis of their methionine-containing tryptic peptides.

Transformation induced by Abelson murine leukemia virus involves production of a polypeptide growth factor.

Rat embryo fibroblasts transformed by Abelson murine leukemia virus (MuLV) produce and release a transforming growth factor (TGF). Production of this factor is correlated with a tyrosine-specific protein kinase that is functionally active and is associated with the major Abelson MuLV gene product, P120. Transformation-defective mutants of Abelson MuLV do not transform cells, do not have their virus coded transforming gene product phosphorylated in tyrosine, and do not induce TGF production. Abelson MuLV-induced TGF morphologically transforms cells in culture, competes with 125I-labeled epidermal growth factor (EGF) for binding to cell receptors, and induces phosphorylation of tyrosine acceptor sites in the 160,000-dalton EGF membrane receptor. After purification to homogeneity, Abelson virus-induced TGF migrates as a single polypeptide with an apparent size of 7400 daltons as determined by sodium dodecyl sulfate-polyacrylamide gel electrophoresis.

Late presentation of medium-chain acyl-CoA dehydrogenase deficiency.

Medium-chain acyl-CoA dehydrogenase (MCAD) deficiency is the commonest disorder of fatty acid metabolism, with a high incidence of morbidity and mortality at presentation. We report a 16 year old girl with first presentation of MCAD deficiency following an alcoholic binge and subsequent period of starvation. Presentation was as acute encephalopathy progressing to coma. Renal, cardiac and hepatic failures were managed with intensive supportive care including mechanical ventilation, inotropic support, blood products and renal replacement therapy. Diagnosis of MCAD deficiency was confirmed on day 6. The patient was discharged from hospital on day 20 with a mild proximal myopathy, which subsequently resolved. The diagnosis of MCAD deficiency requires a high index of suspicion at all ages. Precipitating factors in later life may include alcohol.

Evidence that the phl gene encodes a 160,000-dalton phosphoprotein with associated kinase activity.

In chronic myelocytic leukemia, the human c-abl oncogene is translocated from chromosome 9 to a region on chromosome 22 designated as the breakpoint cluster region (bcr) (A. de Klein, A. Guerts van Kessel, G. Grosveld, C. R. Bartram, A. Hagemeyer, D. Bootsma, N. K. Spurr, N. Heisterkamp, J. Groffen, and J. R. Stephenson, Nature (London) 300:765-767, 1982; J. Groffen, J. R. Stephenson, N. Heisterkamp, A. de Klein, C. R. Bartram, and G. Grosveld, Cell 36:93-99.) Abnormal c-abl homologous mRNA and protein have been detected in the leukemic cells of patients with chronic myelocytic leukemia (E. Canaani, D. Stein-Saltz, E. Aghai, R. P. Gale, A. Berrebi, and E. Januszewicz, Lancet 1:593-595, 1984; S. J. Collins and M. T. Groudine, Proc. Natl. Acad. Sci. USA 80:4813-4817, 1983; R. P. Gale and E. Canaani, Proc. Natl. Acad. Sci. USA 81:5648-5652, 1984; J. B. Konopka, S. M. Watanabe, J. W. Singer, S. J. Collins, and O. N. Witte, Proc. Natl. Acad. Sci. USA 82:1810-1814, 1985). The abnormal mRNA represents a chimeric transcript consisting of 5' bcr and 3' c-abl sequences (G. Grosveld, J. Verwoerd, T. van Agthoven, A. de Klein, K. L. Ramachandran, N. Heisterkamp, K. Stam, and J. Groffen, Mol. Cell. Biol. 6:607-616, 1986; E. Shtivelman, B. Lifshitz, R. B. Gale, and E. Canaani, Nature (London) 315:550-554, 1985; K. Stam, N. Heisterkamp, G. Grosveld, A. de Klein, R. S. Verma, M. Coleman, H. Dosik, and J. Groffen, N. Engl. J. Med. 313:1429-1433, 1985). In the present study, we demonstrated that the abnormal c-abl protein is a fusion protein. In addition, the normal gene encompassing bcr sequences was shown to encode a 160,000-dalton phosphoprotein with an associated serine or threonine kinase activity. We propose that this gene be designated phl, reserving the term bcr for the region within the phl gene encompassing the Ph' translocation breakpoints.

Investigation of a tuberculosis cluster at a job centre in Manchester, United Kingdom.

During the summer of 2005, four cases of active tuberculosis from the same occupational setting were investigated in Manchester, UK. The index case had been diagnosed in December of the previous year. At that stage the closest occupational contacts had been screened, all of whom were assessed as being free from active disease, and none had met nationally recommended criteria for chemoprophylaxis for latent tuberculosis infection (LTBI). In June 2005, two work contacts developed progressive primary extrapulmonary (pleural) TB. Following a detailed risk assessment, the screening programme was widened to include 137 staff who worked at the job centre (employment agency) where the first four cases had been found. This screening programme was based on tuberculin Mantoux testing, CXR and gamma-interferon testing. Of these 137 contacts screened, one additional person was found to have active disease and six others were offered chemoprophylaxis for LTBI. The isolates from the index case and the first two secondary cases were indistinguishable on VNTR-MIRU (variable number tandem repeat--mycobacterial interspersed repetitive unit) typing at 15 loci. No samples were available for testing from the fourth case of active disease. Management of this incident has benefited from the evolving fields of both genotyping and diagnostic testing for LTBI. However, further research into the epidemiological inferences made through genotyping, as well as the significance of a positive gamma-interferon test in assessing the risk of development of active disease, is still required.

Investigation of a tuberculosis cluster at a job centre in Manchester, United Kingdom.

During the summer of 2005, four cases of active tuberculosis from the same occupational setting were investigated in Manchester, UK. The index case had been diagnosed in December of the previous year. At that stage the closest occupational contacts had been screened, all of whom were assessed as being free from active disease, and none had met nationally recommended criteria for chemoprophylaxis for latent tuberculosis infection (LTBI). In June 2005, two work contacts developed progressive primary extrapulmonary (pleural) TB. Following a detailed risk assessment, the screening programme was widened to include 137 staff who worked at the job centre (employment agency) where the first four cases had been found. This screening programme was based on tuberculin Mantoux testing, CXR and gamma-interferon testing. Of these 137 contacts screened, one additional person was found to have active disease and six others were offered chemoprophylaxis for LTBI. The isolates from the index case and the first two secondary cases were indistinguishable on VNTR-MIRU (variable number tandem repeat - mycobacterial interspersed repetitive unit) typing at 15 loci. No samples were available for testing from the fourth case of active disease. Management of this incident has benefited from the evolving fields of both genotyping and diagnostic testing for LTBI. However, further research into the epidemiological inferences made through genotyping, as well as the significance of a positive gamma-interferon test in assessing the risk of development of active disease, is still required.

Preparation and characterization of monoclonal antibodies specific for human transforming growth factor alpha.

A series of monoclonal antibodies (mAbs) against transforming growth factor alpha (TGF alpha) have been produced. The generation of these reagents, as well as their biochemical and immunochemical characterization is described. TGF alpha peptides, mutant recombinant TGF alpha proteins and two-site immunoradiometric assays were used to identify the epitopes recognized by each antibody. This approach has allowed the specific localization of immunodominant domains on the molecule. Certain mAbs were found to be useful for selected procedures. mAb 134A-2B3 was used for immunoblotting both the precursor and mature forms of TGF alpha from conditioned media of tumor cells. One mAb 189-2130.1, which reacted with the carboxyl terminal seventeen amino acids, was able to block TGF alpha binding to the EGF receptor. mAb 213-4.4 was used for immunohistochemical detection of TGF alpha in fixed tumor cells. mAbs 137-178 and 134A-2B3 were used to develop a two-site immunoradiometric immunoassay which was sensitive to 1 ng ml-1 and detected TGF alpha from a variety of tumor cells. A series of mAbs such as these could prove useful in studying the biochemical properties as well as the immunochemical localization of TGF alpha in normal tissues and tumors.

Immunological identification and distribution of parathyroid hormone-like protein polypeptides in normal and malignant tissues.

Monoclonal and polyclonal antibodies recognizing human parathyroid hormone-like protein (PTHLP) have been produced using a series of recombinant and synthetic PTHLP peptides. These antibodies have been used to develop a two-site immunometric enzyme immunoassay which detects PTHLP[1-87] and PTHLP[1-141] but not PTH. The immunoassay detected PTHLP in extracts of squamous carcinomas and normal tissues at concentrations from 7-515 ng PTHLP[1-87]/mg protein. Immunoblotting of the extract which showed the highest immunoreactivity, a squamous carcinoma of the lung from a patient with hypercalcemia, revealed a major band having an apparent mol wt of 26,500 and several other higher mol wt bands. Similar polypeptides were observed by immunoblotting cell extracts from a cell line, SCaBER, which secretes immunoreactive PTHLP into its medium and also from tumors in nude mice derived from this cell line. Chaotropic agents did not alter the immunoblotting pattern, and antibodies to three different epitopes of PTHLP recognized these bands, indicating PTHLP expression in the extracts. Immunohistochemical staining of normal human tissue with these antibodies revealed several PTHLP-containing tissues and confirmed the results of the immunoassay, suggesting a paracrine role for PTHLP. Staining was observed in several neoplastic tissues including squamous cell carcinomas, lung carcinoma, bladder carcinoma, osteogenic sarcoma, and adenocarcinoma of the colon.

Synthesis of a gene encoding parathyroid hormone-like protein-(1-141): purification and biological characterization of the expressed protein.

PTH-like proteins (PTHLP), which are associated with humoral hypercalcemia of malignancy, have recently been purified. Isolation of their corresponding cDNAs has revealed that they are derived from a single gene. In this report a synthetic gene encoding PTHLP-(1-141), a 141-amino acid protein corresponding to the most abundant PTHLP cDNA detected in human tumors, was expressed in bacteria and purified to homogeneity. Recombinant (r) PTHLP-(1-141) migrates with an aberrantly high mol wt on sodium dodecyl sulfate-polyacrylamide gel electrophoresis, presumably as a result of its unusually basic pI. rPTHLP-(1-141), like PTH, induced hypercalcemia in rats, caused release of 45Ca from fetal rat bones, and stimulated the synthesis of cAMP by rat osteosarcoma cells and canine renal membrane preparations. A comparison of the abilities of rPTHLP-(1-141) and bovine PTH-(1-34) to stimulate cAMP synthesis indicated rPTHLP-(1-141) to be 5-fold more potent in the osteosarcoma assay, while nearly 30-fold less active in the renal membrane adenylate cyclase assay. Although 100-fold less potent than bovine PTH-(1-34) in promoting bone resorption, rPTHLP-(1-141) was a potent calcemic factor in vivo, inducing a rise in serum calcium from 10.4 to 14.5 mg/dl when infused into rats at 1.3 micrograms/h. These results support previous assumptions that PTHLP is the humoral factor responsible for humoral hypercalcemia of malignancy. In addition, they suggest substantial differences between PTHLP and PTH in the regulation of calcium homeostasis.

Placental transfer of anticonvulsants in the rabbit: the effect of maternal protein binding and fetal flow.

The fetal-to-maternal ratios of carbamazepine, antipyrine and phenytoin are principally determined by maternal protein binding, though greater lipid solubility may enhance the transfer of valproate compared to that of other drugs at high flows. Placental clearance of all anticonvulsants showed flow-dependent characteristics. This is in line with our findings for basic drugs.

Transfer of bupivacaine, lignocaine and pethidine across the rabbit placenta: influence of maternal protein binding and fetal flow.

The rabbit placenta perfused in itu was used to investigate the factors determining the placental transfer of drugs used in labour. Each doe was given an intravenous infusion of pethidine, lignocaine, bupivacaine and antipyrine concurrently, and the umbilical circulation was artificially perfused with Mammalian Krebs' bicarbonate buffer. The umbilical flow rate was varied between 0.25 and 4.0 ml/min. Drugs were analysed in maternal plasma and umbilical effluent by gas liquid chromatography . Maternal protein binding and lipid solubilities were also determined, and were high for bupivacaine, low for antipyrine and intermediate for pethidine and lignocaine. The Cuv /Cma (mean +/- s.e.) at 1.0 ml/min for antipyrine was 0.74 +/- 0.036; for pethidine, 0.64 +/- 0.04; for lignocaine, 0.5 +/- 0.026; and for bupivacaine 0.072 +/- 0.006. This is the same rank order as is observed for the drugs in humans. The placental clearance increased with flow rates up to 2.0 ml/min for antipyrine and up to 4.0 ml/min and probably more for pethidine, lignocaine and bupivacaine. Transfer rate is therefore reduced by maternal protein binding, is flow-dependent at low flows, and permeability-dependent at high flows for the less lipid-soluble compounds.

Effect of epidural blockade on indicators of splanchnic perfusion and gut function in critically ill patients with peritonitis: a randomised comparison of epidural bupivacaine with systemic morphine.

OBJECTIVES: (a) To measure gastric tonometry values in critically ill patients with peritonitis and to assess the impact of epidural analgesia on these values. (b) To assess the impact of epidural analgesia on gastro-intestinal motility by abdominal ultrasound and paracetamol absorption. (c) To observe any change in clinical outcome that may result from the use of epidural analgesia in such patients. DESIGN: A double-blinded, prospective, randomised and controlled study of general intensive therapy unit (ITU) patients. PATIENTS: Twenty-one patients admitted with peritonitis and adynamic small bowel following abdominal surgery were randomly allocated to receive either intravenous morphine or epidural bupivacaine for analgesia. MEASUREMENTS AND RESULTS: Gastric intramucosal pH (pHig) and the mucosal:arterial PCO2 gradient (Pg-PaCO2) were measured at admission and after 24 h of analgesia. Analysis of mean changes in tonometry values showed a rise in Pg-PaCO2 and a fall in pHig in the morphine group and a significant difference between groups in the Pg-PaCO2 trends (p = 0.024). Significant improvements in the ultrasound appearance of the small bowel were observed in the epidural group (p = 0.0037, Mann-Whitney U test of median changes in a locally developed scoring system). There were no significant differences between the groups in any of the variables derived from the paracetamol absorption test (n = 10); both groups showed persistently delayed gastric outflow throughout the study period. CONCLUSIONS: Epidural analgesia resulted in improvements in gastric mucosal perfusion and the ultrasound appearance of the small bowel, indicating potential clinical benefit in a group of patients in whom epidural catheterisation is traditionally contraindicated.

Ocular and cardiovascular effects of local and systemic pindolol.

Ocular and cardiovascular effects of topical and intravenous pindolol have been studied in a balanced cross-0ver double-blind trial in 6 healthy volunteers. When applied to 1 eye pindolol lowered intraocular pressure in both the treated and untreated eyes with only minimal reduction in resting pupil diameter and light reflex response. The concentration in plasma was much lower and inhibiton of exercise tachycardia about half that when the same dose was administered intravenously. The findings suggest that beta-adrenoceptor blocking drugs should not be used in the treatment of glaucoma in patients who also suffer from heart failure.