Antimicrobial Activity of the Quinoline Derivative HT61 against Staphylococcus aureus Biofilms.

Staphylococcus aureus biofilms are a significant problem in health care settings, partly due to the presence of a nondividing, antibiotic-tolerant subpopulation. Here we evaluated treatment of S. aureus UAMS-1 biofilms with HT61, a quinoline derivative shown to be effective against nondividing Staphylococcus spp. HT61 was effective at reducing biofilm viability and was associated with increased expression of cell wall stress and division proteins, confirming its potential as a treatment for S. aureus biofilm infections.

Immunological profiling of key inflammatory drivers of nasal polyp formation and growth in chronic rhinosinusitis.

BACKGROUND: Chronic rhinosinusitis (CRS) is a chronic inflammatory condition of the upper airways, often associated with the formation of nasal polyps (CRSwNP). It is well established that macroscopically normal (non-polypoidal) sinonasal mucosa in CRSwNP patients can undergo polypoidal change over time, turning into frank polyps. However, little is known about what drives this process. This study aimed to investigate potential drivers of nasal polyp formation or growth through comparison of the immunological profiles of nasal polyps with contiguous non-polypoidal sinonasal mucosa, from the same patients. METHODS: The immune profiles of three types of tissue were compared; nasal polyps and adjacent non-polypoidal sinonasal mucosa from 10 CRSwNP patients, and sinonasal mucosa from 10 control patients undergoing trans-sphenoidal pituitary surgery. Nasal polyp and control samples were also stimulated with Staphylococcus aureus enterotoxin B (SEB) using a nasal explant model, prior to cytokine analysis. Real time quantitative polymerase chain reaction (IL-5, T-bet, IL-17A, FoxP3, TLR-4, IL-8, IL-1beta and IL-6) and Luminex (IFNgamma, IL-5 and IL-17A) were used to quantify pro-inflammatory responses. RESULTS: Nasal polyps and contiguous non-polypoidal sinonasal mucosa from CRSwNP patients displayed a very similar pro-inflammatory profile. When stimulated with SEB, nasal polyps displayed a Th2/Th17 mediated response when compared to controls. CONCLUSIONS: In CRSwNP, nasal polyps and non-polypoidal sinonasal mucosa from the same patient displayed a similar pro-inflammatory profile skewed towards the Th2/Th17 pathway in nasal polyps following SEB stimulation, with evidence of disordered bacterial clearance. These factors may contribute to enhanced survival of bacteria and development of a chronic inflammatory milieu, potentially driving new polyp formation and recurrence following surgical removal.

Invasive Propionibacterium acnes infections in a non-selective patient cohort: clinical manifestations, management and outcome.

An increasing number of reports suggest that Propionibacterium acnes can cause serious invasive infections. Currently, only limited data exist regarding the spectrum of invasive P. acnes infections. We conducted a non-selective cohort study at a tertiary hospital in the UK over a 9-year-period (2003-2012) investigating clinical manifestations, risk factors, management, and outcome of invasive P. acnes infections. Forty-nine cases were identified; the majority were neurosurgical infections and orthopaedic infections (n = 28 and n = 15 respectively). Only 2 cases had no predisposing factors; all neurosurgical and 93.3 % of orthopaedic cases had a history of previous surgery and/or trauma. Foreign material was in situ at the infection site in 59.3 % and 80.0 % of neurosurgical and orthopaedic cases respectively. All neurosurgical and orthopaedic cases required one or more surgical interventions to treat P. acnes infection, with or without concomitant antibiotic therapy; the duration of antibiotic therapy was significantly longer in the group of orthopaedic cases (median 53 vs 19 days; p = 0.0025). All tested P. acnes isolates were susceptible to penicillin, ampicillin and chloramphenicol; only 1 was clindamycin-resistant. Neurosurgical and orthopaedic infections account for the majority of invasive P. acnes infections. Most cases have predisposing factors, including previous surgery and/or trauma; spontaneous infections are rare. Foreign material is commonly present at the site of infection, indicating that the pathogenesis of invasive P. acnes infections likely involves biofilm formation. Since invasive P. acnes infections are associated with considerable morbidity, further studies are needed to establish effective prevention and optimal treatment strategies.

A sex difference in the leucocyte count.

In a study of a group of 325 blood donors between the ages of 18 and 65 years, the total leucocyte and polymorph counts of the females aged 50 to 65 years were found to be significantly lower than those of the corresponding group of male donors. In the whole series of female donors, there were significantly lower total leucocyte and lymphocyte counts with increasing age and a less significant (P [unk] 0.1) fall in the polymorph count. No age variation in the male counts was found. Analysis of large numbers of leucocyte counts performed on hospital patients has confirmed the sex difference in the total leucocyte count found in the blood donors. The factors responsible for the differences are discussed.

Long-term outcome of surgical management for diffuse jejunoileal Crohn's disease.

BACKGROUND: In diffuse jejunoileal Crohn's disease, resectional surgery may lead to short-bowel syndrome. Since 1980 strictureplasty has been used for jejunoileal strictures. This study reviews the long-term outcome of surgical treatment for diffuse jejunoileal Crohn's disease. METHODS: The cases of 46 patients who required surgery for diffuse jejunoileal Crohn's disease between 1980 and 1997 were reviewed. RESULTS: Strictureplasty was used for short strictures without perforating disease (perforation, abscess, fistula). Long strictures (<20 cm) or perforating disease was treated with resection. During an initial operation, strictureplasty was used on 63 strictures in 18 patients (39%). After a median follow-up of 15 years, there were 3 deaths: 1 from postoperative sepsis, 1 from small-bowel carcinoma, and 1 from bronchogenic carcinoma. Thirty-nine patients required 113 reoperations for jejunoileal recurrence. During 75 of the 113 reoperations (66%), strictureplasty was used on 315 strictures. Only 2 patients experienced the development of short-bowel syndrome and required home parenteral nutrition. At present, 4 patients are symptomatic and require medical treatment. All other patients are asymptomatic and require neither medical treatment nor nutritional support. CONCLUSIONS: Most patients with diffuse jejunoileal Crohn's disease can be restored to good health with minimal symptoms by surgical treatment that includes strictureplasty.

Antibodies against Mycobacterium paratuberculosis in Crohn's disease.

Until recently the investigation of serological responses to mycobacteria in patients with Crohn's disease has been hindered by the considerable degree of cross-reactivity between antigens of M. paratuberculosis, and other mycobacterial subspecies. We evaluated the serological response of Crohn's disease patients to a recently identified species-specific 18 kDa protease-resistant antigen corresponding to M. paratuberculosis bacterioferritin. The 18 kDa antigen was purified from M. paratuberculosis as previously described. Serum was obtained from 40 patients with Crohn's disease, 15 with ulcerative colitis, 25 coeliac patients, and 21 normal blood donors. Antibody levels were measured by enzyme-linked immunosorbent assay (ELISA), with anti-human IgA and IgG alkaline phosphatase conjugate. Antibody titres were expressed as the dilution giving 1/3 of the plateau binding value of a standard positive serum (MT/3). Disease activity of the Crohn's disease cases was assessed using the Harvey-Bradshaw index. There was no statistically significant elevation of the mean IgG or IgA MT/3 titres of Crohn's disease patients over controls. No patients had antibody titres greater than two standard deviations above the mean control MT/3 titres, and there was no significant correlation between Crohn's disease activity and level of antibody titres. These findings make it unlikely that M. paratuberculosis is of primary pathogenic importance in Crohn's disease.

Carcinoma in a rectovaginal fistula in a patient with Crohn's disease.

A patient with Crohn's disease underwent resection for internal fistulas. Later a rectovaginal fistula developed that persisted with minimal symptoms for 10 years before causing pain and induration in the posterior vaginal wall, due to carcinoma developing within the fistula.

Natural history of perianal Crohn's disease. Ten year follow-up: a plea for conservatism.

A 10 year follow-up of 109 patients with histologic Crohn's disease and anal lesions is reported. Fourteen patients (13 percent) have died, 7 from unrelated disorders. Ten required excision of the rectum, but only 5 for perianal disease (4.5 percent). Of the remaining 85 patients, 61 have been followed up to proctoscopy and rectal biopsy. Anal skin tags were still evident in 25 of 37 patients (68 percent), but new tags have appeared in only 2 patients. Ten of 53 fissures (19 percent) were still present at 10 years, and there were no new fissures. Seven of 21 patients (33 percent) still had fistulas but were asymptomatic; the remainder of the fistulas had healed spontaneously (8) or after operation (6). New fistulas have appeared in five patients. None of the patients have been in continent. These results indicate that perianal manifestations of Crohn's disease pursue a relatively benign course and are rarely an indication for proctectomy.

Progression of ulcerative proctosigmoiditis: incidence and factors influencing progression.

OBJECTIVE: To assess the changing distribution of disease within the large bowel in patients presenting with ulcerative proctitis or proctosigmoiditis. To evaluate the influence of clinical exacerbations, smoking, parity and family history in disease extension. DESIGN: Retrospective single-centre study in a university hospital. METHODS: Case records of patients presenting over a 40-year period were examined to evaluate the clinical course and disease distribution from initial presentation to final follow-up. For each patient whose disease extended to the more proximal colon, an age- and sex-matched control patient was identified whose disease remained confined to the original site. Patients completed a questionnaire to provide information on family history, smoking and parity. The differences in clinical exacerbations, family history, smoking and parity were then compared between the two groups. RESULTS: Among 145 patients presenting with proctitis or proctosigmoiditis followed prospectively for a median period of 10.9 years, the disease extended in 53 patients. Using actuarial methods the disease progressed beyond the rectosigmoid area in 16% of patients at 5 years and 31% at 10 years. Among the patients whose disease progressed, progression was preceded in 68% of cases by a clinical exacerbation of the colitis. When patients whose disease progressed were compared with those whose disease remained confined to the original site, no differences were detected in the number of clinical exacerbations, smoking habit, family history or parity. CONCLUSIONS: The factors that are associated with the extension of colitis are probably different from those that predisposed an individual to develop inflammatory bowel disease initially.

The surgical treatment of gastroduodenal Crohn's disease.

Crohn's disease can affect any part of the gastrointestinal tract. Gastroduodenal involvement is uncommon and was not recognised until 1949 (1). Since then approximately 200 cases have been described in several series in the world literature. This paper describes the clinical presentation and surgical management of ten patients treated in the Birmingham General Hospital between 1970 and 1984.

Enterovesical fistulas in Crohn's disease.

A total of 19 enterovesical fistulas were recorded in a series of 799 patients with Crohn's disease (2.4%). The origin of the fistulas was: ileum (9), colon (6) and four were complex involving the small and large bowel. Only 13 patients presented with urinary symptoms: pneumaturia (9), haematuria (1) and urinary tract infection (3). Four fistulas were identified incidentally during contrast radiology, one fistula was identified during a laparotomy and one further fistula developed after a previous resection for Crohn's disease. Four patients were managed conservatively and all are asymptomatic, but it is not known whether the fistula has healed. Twelve fistulas were resected: 9 healed, 2 recurred and 1 patient died following resection for a malignant fistula complicating Crohn's disease. Early in the series three patients were managed by bypass or defunction of the fistula. In all cases the sepsis persisted resulting in mortality. Persistent symptomatic fistulas should be treated by resection of the affected segment of bowel with primary anastomosis if appropriate. The defect in the bladder should be closed over an indwelling catheter which should not be removed until there is radiological confirmation that the bladder defect has healed satisfactorily.

Impact of preoperative weight loss on postoperative morbidity.

Clinical observations in developing countries and experimental studies in animals suggest that preoperative weight loss adversely affects postoperative morbidity. Since it is not clear whether these findings can be applied to surgical series in European countries, we have studied 106 surgically-treated patients with inflammatory bowel disease. Patients were divided into three groups according to the degree of preoperative weight loss. The groups were well matched in all other respects. Postoperative morbidity was monitored independently. The outcome in all three groups was similar so that in these patients, at least, preoperative weight loss did not adversely affect the postoperative outcome.

Brevibacillus levickii sp. nov. and Aneurinibacillus terranovensis sp. nov., two novel thermoacidophiles isolated from geothermal soils of northern Victoria Land, Antarctica.

Thirteen strains of endospore-forming bacteria were isolated from geothermal soils at Cryptogam Ridge, the north-west slope of Mt Melbourne, and at the vents and summit of Mt Rittmann in northern Victoria Land, Antarctica. 16S rRNA gene sequencing, SDS-PAGE and routine phenotypic characterization tests indicated that the seven isolates from the north-west slope of Mt Melbourne represent a novel species of Brevibacillus and that the six isolates from Cryptogam Ridge and the vents and summit of Mt Rittmann represent a novel species of Aneurinibacillus. Brevibacillus strains were not isolated from the sites at Mt Rittmann or Cryptogam Ridge and Aneurinibacillus strains were not isolated from the north-west slope of Mt Melbourne. Preliminary metabolic studies revealed that L-glutamic acid, although not essential for growth, was utilized by both species. The Brevibacillus species possessed an uptake system specific for L-glutamic acid, whereas the Aneurinibacillus species possessed a more general uptake system capable of transporting other related amino acids. Both species utilized a K(+) antiport system and similar energy systems for the uptake of l-glutamic acid. The rate of uptake by the Brevibacillus species type strain was 20-fold greater than that shown by the Aneurinibacillus species type strain. The names Brevibacillus levickii sp. nov. and Aneurinibacillus terranovensis sp. nov. are proposed for the novel taxa; the type strains are Logan B-1657(T) (= LMG 22481(T) = CIP 108307(T)) and Logan B-1599(T) (LMG 22483(T) = CIP 108308(T)), respectively.

Current status and influence of operation on perianal Crohn's disease.

Two hundred and two patients with Crohn's disease have been examined during the year 1984 to assess the frequency of perianal disease. One hundred and ten have had evidence of perianal complications (54%). In 30% of patients with perianal disease, the anal manifestations preceded any evidence of intestinal disease. Perianal disease was associated with pain in only 39%. Operations for perianal disease rarely achieved healing and were frequently associated with complications. Attempts to lay open a fistula-in-ano caused healing in only one of 12 cases and 6 developed incontinence. A high proportion of patients with Crohn's ulcers and strictures required proctectomy (87%). Proctectomy was performed in 27 patients with perianal disease of whom only 8 (30%) had primary healing of the proctectomy wound compared with complete healing in all 9 patients having a proctectomy without perianal disease (p less than 0.01). These results imply that patients with perianal Crohn's disease should be treated conservatively and that proctectomy, particularly in patients with rectal strictures, is associated with very high incidence of persistent perineal sinus.

Crohn's disease of the distal ileum.

A clinical and statistical analysis has been undertaken in a consecutive series of 227 patients with Crohn's disease involving the distal ileum under long-term review between 1944 and 1978. We have determined the long-term prognosis, cumulative reoperation rates after each resection, mortality rates, and their causes. Actuarial analysis has shown that the reoperation rates are similar after first, second, and third resections. There was no evidence that additional operations increase the risk of yet more resections. Reoperation rates were very little influenced by the age at diagnosis of the underlying Crohn's disease. A short interval from diagnosis of Crohn's disease to the first resection tended to increase the reoperation rate in the short term but there was no overall long-term effect. There was a two-fold increase in mortality risk when compared with the general population. Half the deaths were unrelated to the underlying Crohn's disease and, in this group, the incidence and causes were similar to those expected in the general population matched for age, sex, and years at risk. Of the disease related deaths many occurred in the early years of experience. Only four patients in the series have died of Crohn's disease in the last 10 years. One hundred and ninety-three patients are still alive after a mean interval of 16.1 years from the diagnosis of Crohn's disease. Full information is available on 185, of whom 161 are well and symptom free. Seven have minor problems, while 17 are unwell (nine with radiological evidence of recurrent disease).

Diffuse jejunoileitis of Crohn's disease.

Diffuse jejunoileitis is an uncommon, but important manifestation of Crohn's disease because of the associated high morbidity and challenges in medical management. Despite this there have been no studies of prognosis or management of diffuse jejunoileitis for nearly 20 years. This study analysed the outcome among 34 patients (20 women and 14 men) with diffuse jejunoileitis diagnosed between 1960 and 1991 including clinical features, medical and surgical management, death rates, current status, and prognosis. Diffuse jejunoileitis presents in younger patients (mean age at diagnosis 26.4 years) than those with distal ileal Crohn's disease (mean age at diagnosis 33.3 years). Nearly all presented with clear cut abdominal symptoms including a combination of colicky abdominal pain (91%), weight loss (62%), and diarrhoea (53%). Most patients had severe symptoms reflected by the fact that 77% had been treated with corticosteroids for periods of more than six months at some stage during their follow up. The mean follow up from diagnosis was 16 years. Twenty eight patients (82%) had at least one operation for diffuse jejunoileitis and two thirds of the patients (n = 21) required two or more operations. The frequency of surgical intervention was particularly high in the younger patients (r = 0.71, p < 0.001). The proportion of patients requiring surgery was highest in the first year after diagnosis. The annual operative rate was 15% for the first 10 years and then it fell to 5.2% in years 11-15, and 2.6% in years 16-20. The data suggest that the disease does burn itself out over time. The increasing use of strictureplasty for short strictures and the minimal use of resection has eliminated problems associated with the short small bowel syndrome. The longterm prognosis of this patients is good. Only two patients died (one of perforation of the jejunum and another of an unrelated bronchogenic carcinoma). After a mean interval from diagnosis of 16 year, 24 of 32 living patients are well and symptom free. Only eight have abdominal symptoms of whom three are receiving corticosteroid treatment and one azathioprine. The combination of anti-inflammatory drugs with the relief of recurrent obstructive symptoms by strictureplasty can together produce a good longterm prognosis in most patients with diffuse jejunoileitis.