Efficacy of fibrin glue therapy for abscess-associated enteric fistulas.

BACKGROUND: Abdominal abscess that result from bowel injury may require treatment with percutaneous drainage. In some cases, an abscess-associated fistula develops between the injured bowel and the drainage catheter. Fistulas that fail to resolve may require surgery; however, fibrin glue therapy (FGT) may be a suitable alternative. METHODS: We retrospectively identified patients undergoing FGT for an abscess-associated enteric fistula between 2004 and 2015. Success was defined as closure of the fistula tract without need for additional intervention. A multivariable logistic regression analysis was utilized to identify factors associated with success. RESULTS: We identified 34 patients with a median age of 54 (23-87) years and 24 (71 %) males. FGT was successful in 23 (67 %) patients. On multivariate analysis, a tract width less than 5 mm (OR 19.2, 95 % CI 1.7-214.5) and removal of the drain (OR 13.8, 95 % CI 1.2-157.6) predicted FGT success. The time from initial FGT to resolution was significantly decreased for the patients who were successfully treated compared to those who failed 24 (14-38) days vs. 99 (71-175) days, respectively (p < 0.001). CONCLUSIONS: Fibrin glue therapy for abscess-associated enteric fistula results in successful and accelerated healing in the majority of cases. Factors associated with successful fibrin glue therapy were identified.

Chemical induction of silent biosynthetic pathway transcription in Aspergillus niger.

Manipulation of the fungal epigenome is hypothesized to be an effective method for accessing natural products from silent biosynthetic pathways. A library of epigenetic modifiers was tested using the fungus Aspergillus niger to determine the impact of small-molecule inhibitors on reversing the transcriptional suppression of biosynthetic genes involved in polyketide (PKS), non-ribosomal peptide (NRPS), and hybrid PKS-NRPS (HPN) production. Examination of expressed sequence tag libraries from A. niger demonstrated that >70% of its PKS-, NRPS-, and HPN-encoding gene clusters were transcriptionally suppressed under standard laboratory culture conditions. Using a chemical epigenetic methodology, we showed that treatment of A. niger with suberoylanilide hydroxamic acid and 5-azacytidine led to the transcriptional upregulation of many secondary-metabolite-encoding biosynthetic gene clusters. Chemical epigenetic modifiers exhibited positional biases for upregulating chromosomally distal gene clusters. In addition, a phylogenetic-based preference was noted in the upregulation of reducing clade I PKS gene clusters, while reducing clade IV PKS gene clusters were largely unaffected. Manipulating epigenetic features in fungi is a powerful method for accessing the products of silent biosynthetic pathways. Moreover, this approach can be readily incorporated into modern microbial screening operations.

Epitope mapping using the X-ray crystallographic structure of complement receptor type 2 (CR2)/CD21: identification of a highly inhibitory monoclonal antibody that directly recognizes the CR2-C3d interface.

Complement receptor type 2 (CR2)/CD21 is a B lymphocyte cell membrane C3d/iC3b receptor that plays a central role in the immune response. Human CR2 is also the receptor for the EBV viral membrane glycoprotein gp350/220. Both C3d and gp350/220 bind CR2 within the first two of 15-16 repetitive domains that have been designated short consensus/complement repeats. Many mAbs react with human CR2; however, only one currently available mAb is known to block both C3d/iC3b and gp350/220 binding. We have used a recombinant form of human CR2 containing the short consensus/complement repeat 1-2 ligand-binding fragment to immunize Cr2(-/-) mice. Following fusion, we identified and further characterized four new anti-CR2 mAbs that recognize this fragment. Three of these inhibited binding of CR2 to C3d and gp350/220 in different forms. We have determined the relative inhibitory ability of the four mAbs to block ligand binding, and we have used overlapping peptide-based approaches to identify linear epitopes recognized by the inhibitory mAbs. Placement of these epitopes on the recently solved crystal structure of the CR2-C3d complex reveals that each inhibitory mAb recognizes a site either within or adjacent to the CR2-C3d contact site. One new mAb, designated 171, blocks CR2 receptor-ligand interactions with the greatest efficiency and recognizes a portion of the C3d contact site on CR2. Thus, we have created an anti-human CR2 mAb that blocks the C3d ligand by direct contact with its interaction site, and we have provided confirmatory evidence that the C3d binding site seen in its crystal structure exists in solution.

Structural studies in solution of the recombinant N-terminal pair of short consensus/complement repeat domains of complement receptor type 2 (CR2/CD21) and interactions with its ligand C3dg.

Human complement receptor type 2 (CR2, CD21) is a cell surface receptor that binds three distinct ligands (complement C3d, Epstein-Barr virus gp350/220, and the low-affinity IgE receptor CD23) via the N-terminal two of fifteen or sixteen short consensus/complement repeat (SCR) domains. Here, we report biophysical studies of the CR2 SCR 1-2 domain binding to its ligand C3dg. Two recombinant forms of CR2 containing the SCR 1-2 and SCR 1-15 domains were expressed in high yield in Pichia pastoris and baculovirus, respectively. Circular dichroism spectroscopy showed that CR2 SCR 1-2 receptor possessed a beta-sheet secondary structure with a melting temperature of 59 degrees C. Using surface plasmon resonance, kinetic parameters for the binding of either CR2 SCR 1-2 or the full-length SCR 1-15 form of CR2 showed that the affinity of binding to immobilized C3d is comparable for the SCR 1-15 compared to the SCR 1-2 form of CR2. Unexpectedly, both the association and dissociation rates for the SCR 1-15 form were slower than for the SCR 1-2 form. These data show that the SCR 1-2 domains account for the primary C3dg binding site of CR2 and that the additional SCR domains of full-length CR2 influence the ability of CR2 SCR 1-2 to interact with its ligand. Studies of the pH and ionic strength dependence of the interaction between SCR 1-2 and C3d by surface plasmon resonance showed that this is influenced by charged interactions, possibly involving the sole His residue in CR2 SCR 1-2. Sedimentation equilibrium studies of CR2 SCR 1-2 gave molecular weights of 17 000, in good agreement with its sequence-derived molecular weight to show that this was monomeric. Its sedimentation coefficient was determined to be 1.36 S. The complex with C3d gave molecular weights in 50 mM and 200 mM NaCl buffer that agreed closely with its sequence-derived molecular weight of 50 600 and showed that a 1:1 complex had been formed. Molecular graphics views of homology models for the separate CR2 SCR 1 and SCR 2 domains showed that both SCR domains exhibited a distribution of charged groups throughout its surface. The single His residue is located near a long eight-residue linker between the two SCR domains and may influence the linker conformation and the association of C3d and CR2 SCR 1-2 into their complex. Sedimentation modeling showed that the arrangement of the two SCR domains in CR2 SCR 1-2 is highly extended in solution.

Phase variation of HpuAB and HmbR, two distinct haemoglobin receptors of Neisseria meningitidis DNM2.

We have previously described HpuAB, a two-component receptor that mediates binding to haemoglobin (Hb), haemoglobin-haptoglobin (Hb-Hp) and apo-haptoglobin (Hp). In this communication, we constructed non-polar mutations in the hpuA and hpuB loci to examine the individual roles of HpuA and HpuB. Our results indicate that both HpuA and HpuB are required for the acquisition of Fe from Hb and Hb-Hp. We isolated Hb utilization-positive (Hb+) variants of our Hb utilization-negative (Hb-) hpu mutants at a frequency of 10(-3) and demonstrated that the Hb+ phenotype resulted from the expression of a second Hb receptor, HmbR. Expression of HmbR in DNM2 was found to be controlled by translational frameshifting involving a polyguanine (G) tract located within the hmbR locus. The hpuA locus also contains a poly(G) tract, which suggested that meningococci could phase vary each Hb receptor independently by slip-strand mispairing in the poly(G) tracts found in hpuA and hmbR. Thus, we isolated a naturally occurring Hb- variant of DNM2, designated DNM2 Hb-, which did not express either HpuAB or HmbR. Hb+ variants of DNM2Hb- were selected and examined for HpuAB and HmbR expression. In each instance, acquisition of HpuAB or HmbR expression was correlated with phase variation in the poly(G) tract of each Hb receptor.

Transport of intact porphyrin by HpuAB, the hemoglobin-haptoglobin utilization system of Neisseria meningitidis.

The meningococcal hemA gene was cloned and used to construct a porphyrin biosynthesis mutant. An analysis of the hemA mutant indicated that meningococci can transport intact porphyrin from heme (Hm), hemoglobin (Hb), and Hb-haptoglobin (Hp). By constructing a HemA- HpuAB- double mutant, we demonstrated that HpuAB is required for the transport of porphyrin from Hb and Hb-Hp.

Primary repair of dog bites to the face: 40 cases.

Dog bites to the face can be life-threatening if major infection occurs, and traditional management consists of wound toilet and debridement, with repair only when the possibility of infection has been eliminated. Surgical opinion is now swinging towards earlier repair. We have analysed retrospectively the outcome of 40 cases that, irrespective of time delay between injury and presentation, underwent primary repair or reconstruction after wound toilet, debridement and administration of prophylactic antibiotics. The victims were 17 males and 23 females with ages ranging from 2 to 76 years (mean 25). Median delay between the injury and presentation in the emergency department was 60 minutes (range 7 minutes to 5 days). All patients received surgical treatment within 24 hours of admission, 18 being operated on within 6 hours. 31 had primary repairs and 9 patients had reconstructive procedures with local skin flaps or skin grafts. Primary healing was achieved in all but 2 patients, of whom one developed minor wound infection and one had necrosis of a composite graft. These results support the view that, for dog bites to the face, primary repair is the method of choice.

Development of a scale to measure adherence to self-monitoring of blood glucose with latent variable measurement.

OBJECTIVE: Adherence to self-monitoring of blood glucose (SMBG) is problematic for many people with diabetes. Self-reports of adherence have been found to be unreliable, and existing paper-and-pencil measures have limitations. This study developed a brief measure of SMBG adherence with good psychometric properties and a useful factor structure that can be used in research and in practice. RESEARCH DESIGN AND METHODS: A total of 216 adults with diabetes responded to 30 items rated on a 9-point Likert scale that asked about blood monitoring habits. In part I of the study, items were evaluated and retained based on their psychometric properties. The sample was divided into exploratory and confirmatory halves. Using the exploratory half, items with acceptable psychometric properties were subjected to a principal components analysis. In part II of the study, structural equation modeling was used to confirm the component solution with the entire sample. Structural modeling was also used to test the relationship between these components. It was hypothesized that the scale would produce four correlated factors. RESULTS: Principal components analysis suggested a two-component solution, and confirmatory factor analysis confirmed this solution. The first factor measures the degree to which patients rely on others to help them test and thus was named "social influence." The second component measures the degree to which patients use physical symptoms of blood glucose levels to help them test and thus was named "physical influence." Results of the structural model show that the components are correlated and make up the higher-order latent variable adherence. CONCLUSIONS: The resulting 15-item scale provides a short, reliable way to assess patient adherence to SMBG. Despite the existence of several aspects of adherence, this study indicates that the construct consists of only two components. This scale is an improvement on previous measures of adherence because of its good psychometric properties, its interpretable factor structure, and its rigorous empirical development.

Identification and molecular analysis of lbpBA, which encodes the two-component meningococcal lactoferrin receptor.

We identified lbpB, encoding the lipoprotein component of the meningococcal lactoferrin receptor. An LbpB mutant was unable to acquire Fe from lactoferrin and exhibits decreased surface binding to lactoferrin. Primer extension and reverse transcription-PCR analysis indicate that lbpB and lbpA are cotranscribed on a polycistronic Fe-repressible mRNA.

Acquired cutis laxa with dermatitis herpetiformis and sarcoidosis.

Cutis laxa is a rare condition characterized by loss of elastic tissue. We describe a patient with dermatitis herpetiformis and pulmonary and articular sarcoidosis in whom acquired cutis laxa developed. We believe this association is unique.

Brief report: recent findings on the Sexual Aversion Scale.

This study provides additional information on the psychometric properties of the Sexual Aversion Scale (SAS). Results suggest a positive relationship between sexual aversion, generalized anxiety, and history of sexual victimization. Variables such as age and religiosity were unrelated to scores on the SAS, although females reported significantly more sexual anxiety than males. The factor structure of the SAS is described and suggests that sexual aversion is a multifaceted problem with at least three and possibly four different dimensions.

Efficiency of two commercial ELISA kits compared with the BAM culture method for detecting Listeria in naturally contaminated foods.

The efficiency of 2 commercial enzyme-linked immunosorbent assay (ELISA) kits (Listeria-Tek and Tecra) for detecting Listeria in naturally contaminated foods was evaluated and compared with that of the culture method described in the Bacteriological Analytical Manual (BAM). Both ELISAs use modified University of Vermont (UVM-1) medium as a primary enrichment; the BAM method uses Listeria enrichment broth. Secondary enrichments for Listeria-Tek and Tecra, respectively, were Fraser broth and UVM-2, which contains additional acriflavin-HCl. When ELISA test results differed, secondary enrichments were tested against the other ELISA; Fraser broth was used to determine recovery rates because of its superiority over UVM-2. Of the 178 food samples examined, the presence of Listeria was detected and culturally confirmed in 38, 37, and 40 samples by the BAM, Listeria-Tek, and Tecra methods, respectively. Differences in results of the ELISAs compared with those of the BAM method were not statistically significant; however, differences between results of the 2 ELISA methods were significant. It was concluded that as rapid screening methods, the Listeria-Tek and the Tecra kits qualify as alternative methods to the BAM cultural method.

Detection of Listeria spp. in Naturally Contaminated Seafoods Using Four Enrichment Procedures.

Four enrichment procedures were evaluated for the recovery of Listeria spp. from 211 samples of raw and processed seafoods. The presence of Listeria spp. was determined in all four methods by a commercial enzyme-linked immunosorbent assay kit. The enrichments used were 1) Listeria enrichment broth (LEB); 2) buffered LEB (BLEB); 3) BLEB transferred to the same enrichment after 24 h (BLEB 24-h transfer); and 4) modified University of Vermont medium (UVM-1) transferred after 24 h to UVM-1 medium containing additional acriflavin (UVM-2). All four enrichments were incubated for a total of 48 h at 30°C. To determine the efficiency of each protocol, we compared our recovery results with those obtained by using a modified version of the Bacteriological Analytical Manual (BAM) cultural method, as described in the Federal Register of November 1, 1988. Statistical analysis showed that recovery of Listeria spp. using nonbuffered LEB for 48 h without transfer did not differ significantly from that obtained with the revised BAM method.

Assessing sexual aversion in college students: the Sexual Aversion Scale.

This study describes a 30-item questionnaire, the Sexual Aversion Scale, that was used to assess sexual fears and avoidance in college students. The construct of sexual aversion was based on the newly listed DSM-III-R criteria for sexual aversion disorder. Results were obtained from 382 college students. The questionnaire was shown to have good internal consistency and test-retest reliability. Female students reported significantly more sexual anxiety. They expressed more fear of intercourse and the negative social consequences of their sexual behavior. They were also more inclined to avoid situations where they might become sexually involved. Conversely, males appeared to be more sexually frustrated and said they would become more sexually active were it not for fear of catching a sexually transmitted disease. It is concluded that sexual fears are fairly widespread among college students and are being fueled by the current AIDS crisis. One implication of these findings is that sexual aversion disorder may become a prevalent problem, especially if the AIDS epidemic continues to spread to the heterosexual population.

Treatment of eczema by EMG biofeedback and relaxation training: a multiple baseline analysis.

Five adults who suffered from eczema for at least five years were treated in a multiple baseline design with EMG biofeedback and progressive relaxation. Treatment consisted of five weekly EMG training sessions combined with regular home practice of relaxation. Three dependent measures were used to assess treatment effects: (1) daily self-monitoring of symptom irritation levels, (2) pre and post assessments of eczema affected areas and (3) the Spielberger Trait Anxiety Questionnaire which was also administered on a pre-post basis. Results showed clinically meaningful improvements in all five participants which were maintained at a two month follow-up. A second follow-up two years later showed that three of subjects were asymptomatic. The other two subjects could not be located. Taken together, the study provides evidence that EMG biofeedback combined with home practice of progressive relaxation can help to reduce the severity of eczema and the irritation associated with the disorder.

Experience with the van der Meulen one-stage hypospadias repair.

The van der Meulen one-stage hypospadias repair for distal hypospadias with minimal or nor chordee is described. It has been used in 65 cases and the results were good or excellent in 50 patients. There were no instances of postoperative urethral fistula.

Dysmorphophobia--a long-term study.

This study examines the mental health of 187 patients who had a rhinoplasty fifteen years earlier. Of 101 who had the operation following disease or injury 9 are now severely neurotic and one schizophrenic; of 86 who had the operation for aesthetic reasons 32 are now severely neurotic and 6 schizophrenic. The differences between the two groups are significant, and show that dysmorphophobia is an ominous symptom.

The incidence of schizophrenia and severe psychological disorders in patients 10 years after cosmetic rhinoplasty.

Body image disturbance may be an early sign of schizophrenia. The significance of this and dysmorphophobia with relation to patients seeking cosmetic rhinoplasty is discussed. Results of a follow-up of patients 10 years after cosmetic surgery to see whether they developed schizophrenia or serious psychological disorder are presented. The literature, significance of the findings and the clinical implications are all discussed.