Predicting Amputation and Multiple Debridements in Tooth Knuckle Injuries.

BACKGROUND: Tooth knuckle injuries can be expensive to treat and may necessitate amputation in some cases. Several limitations exist in the literature regarding our knowledge around the factors predicting amputation and the need for multiple debridements in treating this injury. METHODS: A historic cohort study of 321 patients treated for tooth knuckle injuries was undertaken. Twenty-one demographic, clinical and laboratory variables were collected. Two outcome measurements were collected - the need for amputation and the need for more than one surgical debridement. A multivariate logistic regression was performed to determine the relationship between the predictor variables and the outcome measurements. RESULTS: Of the 321 patients examined, 1.6% required amputations and 25% required multiple debridements. Osteomyelitis was found to be a major predictor for amputation in these patients (OR = 35). Delayed presentation (OR = 1.1) and diabetes (OR = 2.6) were found to significantly increase the risk of requiring multiple debridements. CONCLUSIONS: Our models were able to predict what patients were at the greatest risk for amputation and multiple debridement. Reducing rates of osteomyelitis and delays in presentation may help reduce the incidence of amputation and reoperation in this injury.

Predicting serious complications and high cost of treatment of tooth-knuckle injuries: a systematic literature review.

PURPOSE: The tooth-knuckle injury (TKI) is a serious and potentially costly injury seen in orthopaedic practice. The aim was to conduct a systematic literature review on the factors associated with serious complications and high treatment costs in tooth-knuckle injuries. METHODS: MEDLINE, Scopus and CINAHL were used as the literature sources. INCLUSION CRITERIA: Original research papers that reported on factors predicting serious complications and high treatment costs in TKIs were included. There were no restrictions placed on study size, language, study design or date of publication. EXCLUSION CRITERIA: Case studies, case series and review articles were not included. RESULTS: After duplicates were removed, 403 unique studies remained; after titles and abstracts were screened, 48 titles remained and were retrieved in full text. Of these, 14 titles met the inclusion criteria and were included in the data synthesis. Tenosynovitis, septic arthritis, osteomyelitis and residual stiffness were common serious complications occurring in up to 36.3, 70.0, 47.6 and 65.3 % of cases, respectively. Amputation was also common in up to 18.0 % of injuries. Treatment costs were measured by length of hospital stay and the number of debridements required. On average, patients required 3.8-8 days of admission and 1.3-2.7 debridements each. CONCLUSION: Increased time delay from injury to treatment, deeply penetrating injuries, proximal interphalangeal joint (PIPJ) injuries and, possibly, E. corrodens infections were associated with serious complications in TKIs. Delayed treatment, inadequate treatment, PIPJ injuries and deeply penetrating injuries predicted higher treatment costs. SYSTEMATIC REVIEW REGISTRATION NUMBER: PROSPERO CRD42016029949 ( http://www.crd.york.ac.uk/PROSPERO/display_record.asp?ID=CRD42016029949 ).

Differential development of tolerance to the functional and behavioral effects of repeated baclofen treatment in rats.

Baclofen, a gamma-aminobutyric acid (GABA)B receptor agonist, has been used clinically to treat muscle spasticity, rigidity and pain. More recently, interest in the use of baclofen as an addiction medicine has grown, with promising preclinical cocaine and amphetamine data and demonstrated clinical benefit from alcohol and nicotine studies. Few preclinical investigations, however, have utilized chronic dosing of baclofen, which is important given that tolerance can occur to many of its effects. Thus the question of whether chronic treatment of baclofen maintains the efficacy of acute doses is imperative. The neural substrates that underlie the effects of baclofen, particularly those after chronic treatment, are also not known. In the present study, therefore, rats were treated with either a) vehicle, b) acute baclofen (5 mg/kg) or c) chronic baclofen (5 mg/kg, t.i.d. for 5 days). The effects of acute and chronic baclofen administration, compared to vehicle, were assessed using locomotor activity and changes in brain glucose metabolism (a measure of functional brain activity). Acute baclofen significantly reduced locomotor activity (horizontal and total distance traveled), while chronic baclofen failed to affect locomotor activity. Acute baclofen resulted in significantly lower rates of local cerebral glucose utilization throughout many areas of the brain, including the prefrontal cortex, caudate putamen, septum and hippocampus. The majority of these functional effects, with the exception of the caudate putamen and septum, were absent in animals chronically treated with baclofen. Despite the tolerance to the locomotor and functional effects of baclofen following repeated treatment, these persistent effects on functional activity in the caudate putamen and septum may provide insights into the way in which baclofen alters the reinforcing effects of abused substances such as cocaine, alcohol, and methamphetamine both in humans and animal models.

Group II metabotropic glutamate receptors in the striatum of non-human primates: dysregulation following chronic cocaine self-administration.

A growing body of evidence has demonstrated a role for group II metabotropic glutamate receptors (mGluRs) in the reinforcing effects of cocaine. These receptors are important given their location in limbic-related areas, and their ability to control the release of glutamate and other neurotransmitters. They are also potential targets for novel pharmacotherapies for cocaine addiction. The present study investigated the impact of chronic cocaine self-administration (9.0mg/kg/session for 100 sessions, 900 mg/kg total intake) on the densities of group II mGluRs, as assessed with in vitro receptor autoradiography, in the striatum of adult male rhesus monkeys. Binding of [(3)H]LY341495 to group II mGluRs in control animals was heterogeneous, with a medial to lateral gradient in binding density. Significant elevations in the density of group II mGluRs following chronic cocaine self-administration were measured in the dorsal, central and ventral portions of the caudate nucleus (P<0.05), compared to controls. No differences in receptor density were observed between the groups in either the putamen or nucleus accumbens. These data demonstrate that group II mGluRs in the dorsal striatum are more sensitive to the effects of chronic cocaine exposure than those in the ventral striatum. Cocaine-induced dysregulation of the glutamate system, and its consequent impact on plasticity and synaptic remodeling, will likely be an important consideration in the development of novel pharmacotherapies for cocaine addiction.

Serotypes, intimin subtypes, and antimicrobial resistance patterns of atypical enteropathogenic Escherichia coli isolated in England from 1993 to 1996.

The aim of this study was to characterise the atypical enteropathogenic Escherichia coli (EPEC) strains isolated during a study of intestinal infectious disease in the UK by serotyping, intimin subtyping, and antimicrobial resistance typing. Serotypes, intimin subtypes, and resistance patterns of strains from cases were then compared with those from the control group. A wide range of serotypes, intimin subtypes, and antimicrobial resistance patterns was identified in isolates from both cases and controls, with O70:H11 and O111:H- being the most frequently detected serotypes. The most common intimin types were gamma and gamma(2). Thirty-six percent of the EPEC isolates were resistant to at least one antimicrobial agent. No significant differences in the characteristics of EPEC strains isolated from patients with symptoms of gastrointestinal disease versus those isolated from healthy controls were detected, although strains harbouring the beta-intimin subtype were more commonly isolated from children under 5 years of age (p=0.002). The compilation of data on atypical EPEC strains presented here indicates the need for further study of their virulence and epidemiology in order to assess their significance as human pathogens.

Distribution of norepinephrine transporters in the non-human primate brain.

Noradrenergic terminals in the central nervous system are widespread; as such this system plays a role in varying functions such as stress responses, sympathetic regulation, attention, and memory processing, and its dysregulation has been linked to several pathologies. In particular, the norepinephrine transporter is a target in the brain of many therapeutic and abused drugs. We used the selective ligand [(3)H]nisoxetine, therefore, to describe autoradiographically the normal regional distribution of the norepinephrine transporter in the non-human primate central nervous system, thereby providing a baseline to which alterations due to pathological conditions can be compared. The norepinephrine transporter in the monkey brain was distributed heterogeneously, with highest levels occurring in the locus coeruleus complex and raphe nuclei, and moderate binding density in the hypothalamus, midline thalamic nuclei, bed nucleus of the stria terminalis, central nucleus of the amygdala, and brainstem nuclei such as the dorsal motor nucleus of the vagus and nucleus of the solitary tract. Low levels of binding to the norepinephrine transporter were measured in basolateral amygdala and cortical, hippocampal, and striatal regions. The distribution of the norepinephrine transporter in the non-human primate brain was comparable overall to that described in other species, however disparities exist between the rodent and the monkey in brain regions that play a role in such critical processes as memory and learning. The differences in such areas point to the possibility of important functional differences in noradrenergic information processing across species, and suggest the use of caution in applying findings made in the rodent to the human condition.

Foodborne general outbreaks of Salmonella Enteritidis phage type 4 infection, England and Wales, 1992-2002: where are the risks?

Foodborne outbreaks of Salmonella enterica serovar Enteritidis phage type 4 (PT4) infection (n=497), reported to the Health Protection Agency Communicable Disease Surveillance Centre between 1992 and 2002, were compared with other pathogens (n=1148) to determine factors (season, setting, food vehicles, food safety faults) associated with this pathogen. Logistic regression was applied to control for potential confounding. Foodborne general outbreaks of S. Enteritidis PT4 infection were more likely to occur in the spring and summer, and were more often linked to schools, private residences and residential institutions. Eggs, egg products and the use of raw shell egg were strongly associated with this pathogen. Most outbreaks were linked to cross-contamination and inadequate heat treatment. This paper describes the decline in the S. Enteritidis PT4 epidemic, providing evidence that control measures introduced, e.g. improved biosecurity and vaccination, have worked. Continued surveillance of human and veterinary salmonellosis is essential to detect future problems.

Modelling the epidemiology of Verocytotoxin-producing Escherichia coli serogroups in young calves.

We investigate the epidemiology of 12 Verocytotoxin-producing Escherichia coli (VTEC) serogroups observed in a calf cohort on a Scottish beef farm. Fitting mathematical models to the observed time-course of infections reveals that there is significant calf-to-calf transmission of VTEC. Our models suggest that 40% of all detected infections are from calf-to-calf transmission and 60% from other sources. Variation in the rates at which infected animals recover from infection by different VTEC serogroups appears to be important. Two thirds of the observed VTEC serogroups are lost from infected calves within 1 day of infection, while the rest persist for more than 3 days. Our study has demonstrated that VTEC are transmissible between calves and are typically lost from infected animals in less than 1 week. We suggest that future field studies may wish to adopt a tighter sampling frame in order to detect all circulating VTEC serogroups in similar animal populations.

Orexin-saporin lesions of the medial septum impair spatial memory.

The medial septum and diagonal band of Broca (MSDB) provide a major input to the hippocampus and are important for spatial learning and memory. Although electrolytic MSDB lesions have prominent memory impairing effects, selective lesions of either cholinergic or GABAergic MSDB neurons do not or only mildly impair spatial memory. MSDB neurons are targets of orexin-containing neurons from the hypothalamus. At present, the functional significance of orexin afferents to MSDB is unclear, and the present study investigated a possible involvement of orexin innervation of the MSDB in spatial memory. Orexin-saporin, a toxin that damages neurons containing the hypocretin-2 receptor, was administered into the MSDB of rats. Rats were subsequently tested on a water maze to assess spatial reference memory and a plus maze to assess spatial working memory. At 100 ng/microl, orexin-saporin destroyed primarily GABAergic septohippocampal neurons, sparing the majority of cholinergic neurons. At 200 ng/microl, orexin-saporin almost totally eliminated GABAergic septohippocampal neurons and destroyed many cholinergic neurons. Spatial reference memory was impaired at both concentrations of orexin-saporin with a dramatic impairment observed for 24-h retention. Short-term reference memory was also impaired at both concentrations. Rats treated with 200 ng/microl, but not 100 ng/microl, of orexin-saporin were also impaired on a spontaneous alternation task, showing a deficit in spatial working memory. Our results, together with previous studies, suggest that orexin innervation of the MSDB may modulate spatial memory by acting on both GABAergic and cholinergic septohippocampal neurons.

Irritant threshold and histological response of epidermis to irritant application.

Individuals vary in their ability to react to irritants, which can be demonstrated for sodium lauryl sulfate (SLS) using the irritant threshold (IT) test. We aimed to study whether the histological and immunohistochemical features of the skin following SLS exposure varied with subject's IT. 8 subjects were recruited. Their IT was measured. Biopsies were taken after 2 hr and 4 hr of occlusion with 20% SLS and control. The specimens were stained with haematoxylin and eosin and for Langerhans cells. At 4-hr, low-threshold subjects developed changes to a greater extent than high-threshold subjects. The relationship of histological reaction to IT could be related to a differential pro-inflammatory cytokine response in subjects. Low IT has been previously associated with a tumour necrosis factor alpha promoter region polymorphism.

Shedding patterns of verocytotoxin-producing Escherichia coli strains in a cohort of calves and their dams on a Scottish beef farm.

Rectal fecal samples were taken once a week from 49 calves on the same farm. In addition, the dams of the calves were sampled at the time of calf birth and at the end of the study. Strains of verocytotoxin-producing Escherichia coli (VTEC) were isolated from these samples by using PCR and DNA probe hybridization tests and were characterized with respect to serotype, verocytotoxin gene (vtx) type, and the presence of the intimin (eae) and hemolysin (ehxA) genes. A total of 170 VTEC strains were isolated during 21 weeks from 130 (20%) of 664 samples from calves and from 40 (47%) of 86 samples from their dams. The characteristics of the calf strains differed from those strains isolated from the dams with respect to verocytotoxin 2 and the presence of the eae gene. In addition, no calf shed the same VTEC serogroup (excluding O?) as its dam at birth or at the end of the study. The most frequently detected serogroups in calves were serogroup O26 and provisional serogroup E40874 (VTEC O26 was found in 25 calves), whereas in dams serogroup O91 and provisional serogroup E54071 were the most common serogroups. VTEC O26 shedding appeared to be associated with very young calves and declined as the calves aged, whereas VTEC O2 shedding was associated with housing of the animals. VTEC O26 strains from calves were characterized by the presence of the vtx1, eae, and ehxA genes, whereas vtx2 was associated with VTEC O2 and provisional serogroup E40874. The high prevalence of VTEC O26 and of VTEC strains harboring the eae gene in this calf cohort is notable because of the association of the O26 serogroup and the presence of the eae gene with human disease. No association between calf diarrhea and any of the VTEC serogroups was identified.

Intra-individual variation of irritant threshold and relationship to transepidermal water loss measurement of skin irritation.

Irritant susceptibility studies have used either visual assessment or transepidermal water loss (TEWL) to determine subject response. We have developed a visual assessment method which determines subject irritant threshold. We examined the relationship between sodium lauryl sulfate (SLS) irritant threshold and TEWL measurements from normal skin and SLS patch tests. 19 subjects were recruited. The irritant threshold of each subject was measured and TEWL measurements made from the applied SLS patch tests. Individuals with a lower irritant threshold (easily irritated skin) had elevated TEWL levels compared to those with higher thresholds. The irritant threshold test had a low intraindividual variation. This study showed that the 2 methods grouped patients in a similar manner. The variation seen may reflect the different outcomes measured: irritant threshold visually assesses the skin inflammatory response while TEWL measures skin barrier modification.

Temporal shedding patterns and virulence factors of Escherichia coli serogroups O26, O103, O111, O145, and O157 in a cohort of beef calves and their dams.

This study investigated the shedding of Escherichia coli O26, O103, O111, O145, and O157 in a cohort of beef calves from birth over a 5-month period and assessed the relationship between shedding in calves and shedding in their dams, the relationship between shedding and scouring in calves, and the effect of housing on shedding in calves. Fecal samples were tested by immunomagnetic separation and by PCR and DNA hybridization assays. E. coli O26 was shed by 94% of calves. Over 90% of E. coli O26 isolates carried the vtx(1), eae, and ehl genes, 6.5% carried vtx(1) and vtx(2), and one isolate carried vtx(2) only. Serogroup O26 isolates comprised seven pulsed-field gel electrophoresis (PFGE) patterns but were dominated by one pattern which represented 85.7% of isolates. E. coli O103 was shed by 51% of calves. Forty-eight percent of E. coli O103 isolates carried eae and ehl, 2% carried vtx(2), and none carried vtx(1). Serogroup O103 isolates comprised 10 PFGE patterns and were dominated by two patterns representing 62.5% of isolates. Shedding of E. coli O145 and O157 was rare. All serogroup O145 isolates carried eae, but none carried vtx(1) or vtx(2). All but one serogroup O157 isolate carried vtx(2), eae, and ehl. E. coli O111 was not detected. In most calves, the temporal pattern of E. coli O26 and O103 shedding was random. E. coli O26 was detected in three times as many samples as E. coli O103, and the rate at which calves began shedding E. coli O26 for the first time was five times greater than that for E. coli O103. For E. coli O26, O103, and O157, there was no association between shedding by calves and shedding by dams within 1 week of birth. For E. coli O26 and O103, there was no association between shedding and scouring, and there was no significant change in shedding following housing.

DNA-based subtyping of verocytotoxin-producing Escherichia coli (VTEC) O128ab:H2 strains from human and raw meat sources.

AIMS: To investigate subtyping methods for verocytotoxin-producing Escherichia coli (VTEC) O128ab:H2. METHODS AND RESULTS: Eleven human and food strains isolated over a 15-year period were examined. All were intimin (eae)-negative, but all possessed enterohaemolysin and VT1-encoding sequences which in nine strains were vtx1c variant. Ten strains had VT2 genes which were all vtx2d. Plasmid profiles and randomly amplified polymorphic DNA-PCR were not discriminatory. Long-PCR restriction fragment length polymorphism of amplicons bound by the p gene and the VT2A subunit had screening potential. Pulsed field gel electrophoresis (PFGE) using XbaI gave fine discrimination although VT2 sequences were located on a 220 kbp fragment conserved in nine strains and on a 200 kbp fragment in the 10th. CONCLUSIONS: As a result of apparent clonality, PFGE proved essential for differentiation. Long-PCR has promise for screening but requires further evaluation of inter-strain variable sequences. SIGNIFICANCE AND IMPACT OF THE STUDY: A combined phenotypic and genotypic screen, and PFGE for selected strains was effective.

Subtyping of virulence genes in verocytotoxin-producing Escherichia coli (VTEC) other than serogroup O157 associated with disease in the United Kingdom.

Verocytotoxin-producing Escherichia coli (VTEC) causes a wide spectrum of disease in humans, from mild diarrhoea to haemolytic uraemic syndrome (HUS). The verocytotoxin (vtx) and intimin (eae) genes of VTEC strains, other than those of serogroup O157, were subtyped to identify common properties that may be associated with increased pathogenicity. Strains were isolated from patients with HUS, those with diarrhoea or from asymptomatic individuals. Strains of VTEC that carried vtx(2) gene subtypes vtx(2) and vtx(2c) were most commonly associated with HUS, whereas strains from patients with less severe disease and from the healthy control group were more likely to have vtx(1c) or vtx(2d) genes. The eae gene was detected more frequently in strains isolated from HUS patients than in those associated with cases of diarrhoea; beta-intimin was the most common intimin subtype in strains isolated from both groups of patients. None of the strains from the healthy control group carried the eae gene.

Detection of Escherichia coli serogroups O26, O103, O111 and O145 from bovine faeces using immunomagnetic separation and PCR/DNA probe techniques.

AIMS: The aim of this study was to isolate Escherichia coli O26, O103, O111 and O145 from 745 samples of bovine faeces using (i) immunomagnetic separation (IMS) beads coated with antibodies to lipopolysaccharide, and slide agglutination (SA) tests and (ii) PCR and DNA probes for the detection of the Verocytotoxin (VT) genes. METHODS AND RESULTS: IMS-SA tests detected 132 isolates of presumptive E. coli O26, 112 (85%) were confirmed as serogroup O26 and 102 had the VT genes. One hundred and twenty-two strains of presumptive E. coli O103 were isolated by IMS-SA, 45 (37%) were confirmed as serogroup O103 but only one of these strains was identified as Verocytotoxin-producing E. coli (VTEC). Using the PCR/DNA probe method, 40 strains of VTEC O26 and three strains of VTEC O103 were isolated. IMS-SA identified 21 strains of presumptive E. coli O145, of which only four (19%) were confirmed as serogroup O145. VTEC of this serogroup was not detected by either IMS-SA or PCR/DNA probes. E. coli O111 was not isolated by either method. CONCLUSION: IMS beads were 2.5 times more sensitive than PCR/DNA probe methods for the detection of VTEC O26 in bovine faeces. SIGNIFICANCE AND IMPACT OF THE STUDY: IMS-SA is a sensitive method for detecting specific E. coli serogroups. However, the specificity of this method would be enhanced by the introduction of selective media and the use of tube agglutination tests for confirmation of the preliminary SA results.

Subtyping intimin genes from enteropathogenic Escherichia coli associated with outbreaks and sporadic cases in the United Kingdom and Eire.

PCR-RFLP methods for subtyping the intimin gene from strains of typical and atypical enteropathogenic Escherichia coli (EPEC) and Verocytotoxin-producing E. coli (VTEC) were compared. A novel HhaI PCR-RFLP method was developed that was rapid, easy to use and amplified an 1852 bp fragment of the intimin gene from all isolates examined. This method was used to investigate the intimin sub-types of EPEC strains associated with 14 outbreaks of diarrhoeal disease between 1967 and 2001, and 20 sporadic cases between January and December 2000, in the UK and Eire. In this study, genes encoding alpha, beta, gamma, delta and zeta-intimin were detected in the EPEC strains associated with outbreaks and beta, gamma, epsilon, theta and zeta-intimin genes were identified in isolates from sporadic cases. The beta-intimin gene was the most frequently detected sub-type in both the outbreak and sporadic strains.

Temporal upregulation of prodynorphin mRNA in the primate striatum after cocaine self-administration.

Several human and rat studies suggest that the striatal dynorphin system is important for neuroadaptation following cocaine exposure. In the current study, prodynorphin (PDYN) mRNA expression was examined in monkeys at initial and chronic phases of cocaine self-administration. Adult Rhesus monkeys were trained to self-administer food (banana flavoured pellets) or cocaine (0.03 or 0.3 mg/kg per injection) on a fixed interval 3-min schedule for 5 or 100 sessions. Each session ended after 30 reinforcers were delivered. The PDYN mRNA expression was analysed in the precommissural striatum using in situ hybridization histochemistry. We found a specific activation of PDYN mRNA expression in the limbic-innervated patch/striosome compartment of the dorsal caudate and dorsal putamen during the initial (i.e. 5 day) phase of the high dose cocaine self-administration. After 100 days of the high dose exposure, the patch/striosome compartment remained activated, but an increase in PDYN mRNA levels was also evident in the sensorimotor-connected matrix compartment of the caudate. Neither self-administration phase resulted in significant changes in the corresponding striatal regions of the low dose cocaine-exposed primates. Moreover, cocaine self-administration failed to alter the PDYN mRNA expression in high- or low-expressing PDYN cell populations in the nucleus accumbens during any condition studied. These results demonstrate the vulnerability of the dorsal striatum (in particular the caudate) to neuroadaptations following long-term high dose cocaine self-administration. In addition, the temporal nature of the changes in PDYN gene expression within the striatal compartments could reflect a change in drug responsivity that occurs during the transition to drug dependence.

An eight-month study of a population of verocytotoxigenic Escherichia coli (VTEC) in a Scottish cattle herd.

AIMS: Strains of Verocytotoxin-producing Escherichia coli (VTEC) from Scottish beef cattle on the same farm were isolated during four visits over a period of eight months. Characteristics of these strains were examined to allow comparisons with strains of VTEC associated with human infection. METHODS AND RESULTS: Strains were characterized to investigate the relationship between these bovine isolates with respect to serotype, Verocytotoxin (VT) type, intimin-type, and presence or absence of the enterohaemolysin genes. VT genes were detected in 176 of 710 (25%) faecal samples tested using PCR, although only 94 (13%) VTEC strains were isolated using DNA probes on cultures. Forty-five different serotypes were detected. Commonly isolated serotypes included O128ab:H8, O26:H11 and O113:H21. VTEC O26:H11 and O113:H21 have been associated with human disease. Strains harbouring the VT2 genes were most frequently isolated during the first three visits to the farm and those with both VT1 and VT2 genes were the major type during the final visit. Of the 94 strains of non-O157 VTEC isolated, 16 (17%) had the intimin gene; nine had the gene encoding beta-intimin and seven strains had an eta/zeta-intimin gene. Forty-one (44%) of 94 strains carried enterohaemolysin genes. CONCLUSIONS: Different serotypes and certain transmissible characteristics, such as VT-type and the enterohaemolysin phenotype, appeared to be common throughout the VTEC population at different times. SIGNIFICANCE AND IMPACT OF THE STUDY: Detailed typing and subtyping strains of VTEC as described in this study may improve our understanding of the relationship between bovine VTEC and those found in the human population.