IL-12 inhibits TNF-α induced osteoclastogenesis via a T cell-independent mechanism in vivo

It has been reported that TNF-α plays an important role in bone resorption in pathological conditions. IL-12, which is a T cell mediator, is also an important inflammatory cytokine. We previously reported that IL-12 induces apoptosis in bone marrow cells treated with TNF-α in vitro via an interaction between TNF-α-induced Fas and IL-12-induced Fas ligand (FasL), and that, as a result, osteoclastogenesis is inhibited. The purpose of this study was to investigate the effects of IL-12 on TNF-α-mediated osteoclastogenesis in vivo. We administered TNF-α with and without IL-12 into the supracalvaria in mice. The numbers of osteoclasts in the sutures in the calvaria were higher in mice administered TNF-α than in control mice not administered TNF-α. The numbers of osteoclasts in mice administered both TNF-α and IL-12 were lower than those in mice administered only TNF-α. Next, we determined the levels of mRNAs for cathepsin K and tartrate-resistant acid phosphatase (TRAP). mRNA levels were increased in mice administered TNF-α compared with control mice, but not in mice administered both TNF-α and IL-12. We also evaluated the amounts of tartrate-resistant acid phosphatase 5b (TRACP 5b) in mouse sera. The levels of TRACP 5b in mice administered TNF-α were higher than those in control mice. On the other hand, in mice administered both TNF-α and IL-12, the levels were lower than those in mice administered TNF-α alone. Fas and FasL expression levels were analyzed by real-time RT-PCR. The levels of Fas mRNA were increased in the calvaria of mice administered TNF-α compared with control mice, while those of FasL mRNAs were increased in the calvaria of mice administered IL-12. In TdT-mediated dUTP-biotin nick end-labeling (TUNEL) assays, many apoptotic cells were found in the sutures in the calvaria of mice administered both TNF-α and IL-12. IL-12 also inhibited TNF-α-induced osteoclastogenesis in mice whose T cells were blocked by anti-CD4 and anti-CD8 antibodies. These results suggest that IL-12 inhibits TNF-α-mediated osteoclastogenesis and induces apoptotic changes through an interaction between TNF-α-induced Fas and IL-12-induced FasL, in vivo, via a T cell-independent mechanism.     

Transient isolation of Burkholderia multivorans and Burkholderia cenocepacia from a Brazilian cystic fibrosis patient chronically colonized with Burkholderia vietnamiensis

Fifteen serial Burkholderia cepacia complex isolates recovered over a period of 4 years from a single cystic fibrosis patient were analysed for genomovar status by means of recA sequence determination, and genetic relatedness by RAPD-PCR. Twelve isolates were assigned as Burkholderia vietnamiensis, two as Burkholderia cenocepacia and one as Burkholderia multivorans. B. vietnamiensis persisted in the airways during 4 years, except in three occasions when B. cenocepacia or B. multivorans were isolated. The patient was chronically colonized by B. vietnamiensis with the RAPD-profile 12 and transiently by the RAPD-profile 15.     

Lichtheimia corymbifera subcutaneous infection successfully treated with amphotericin B, early debridement, and vacuum-assisted closure

Lichtheimia corymbifera (syn. Absidia corymbifera, Mycocladus corymbifer) is an ubiquitous cosmopolitan mold that can cause primary cutaneous and deep tissue infection in healthy individuals. We report a subcutaneous L. corymbifera infection in a 13-year-old immune-competent child, with a severe traumatic injury, with a successful outcome after early diagnosis and treatment with lipid amphotericin B, early debridement, and vacuum-assisted closure (VAC).     

Effectiveness of Bombesin and Saccharomyces boulardii Against the Translocation of Candida albicans in the Digestive Tract in Immunosuppressed Rats

Purpose We investigated the effects of bombesin on disseminated candidiasis, and compared the effectiveness of bombesin with Saccharomyces boulardii against Candida albicans translocation from the gastrointestinal tract in immunosuppressed rats.Methods Sixty rats were divided into five groups of 12. Group 1 was given only a laboratory pellet diet and water during the experiments; the other four groups were orally inoculated with C. albicans; and groups 3, 4, and 5 were also given prednisolone intraperitoneally. The treatment groups consisted of group 4, given S. boulardii orally, and group 5, given bombesin subcutaneously. The rats were killed after 10 days, and the large bowel, liver, spleen, and kidneys were removed for microbiological and histopathological examination. Blood samples were taken to measure tumor necrosis factor-α (TNF-α) and interleukin-1 β (IL-1β) levels, and the results were compared.Results The number of translocated C. albicans colonies from the gastrointestinal tract and the serum TNF-α and IL-β levels were significantly lower in groups 4 and 5 than in group 3 (P < 0.05). Histological analysis revealed that the bombesin-treated group (group 5) had significantly less mucosal ulceration and submucosal inflammation in the large bowel, less inflammation and necrosis in the liver, and less inflammation of the Bowman capsules in the kidney than the S. boulardii-treated group (group 4) (P < 0.05).Conclusions These findings show that both S. boulardii and bombesin inhibit the translocation of C. albicans from the gastrointestinal tract, although mucosal ulceration, submucosal inflammation in the large bowel, and dissemination in the liver and kidneys were significantly less severe in the bombesin-treated immunosuppressed rats.     

Laparoscopic revision of gastric band surgery

Aim: To identify the outcome of laparoscopic revision of gastric band surgery with respect to percentage of excess weight lost (%EWL). Methods: Analysis of a prospective database was then performed and %EWL was plotted with respect to time from initial procedure and also time from revision procedure. Results: All revision operations were performed laparoscopically. There were no patient deaths, but two serious complications. Percentage excess weight loss after replacement of the band because of prosthetic failure or dysphagia was 57% at an average follow‐up of 19 months. For repositioning of the band due to slippage, the %EWL was 72% at an average of 15 months follow‐up for those who had the existing band repositioned, and 42% at an average of 23 months follow‐up for those who had a new band repositioned. Conclusion: Revision laparoscopic gastric band surgery is a safe option for patients, and results in good %EWL at an average follow‐up period of 19 months.     

Development of selective media for the isolation of yeasts and filamentous fungi from the sputum of adult patients with cystic fibrosis (CF)

Yeasts and filamentous fungi are beginning to emerge as significant microbial pathogens in patients with cystic fibrosis (CF), particularly in relation to allergic-type responses, as seen in patients with allergic bronchopulmonary aspergillosis (ABPA), Aspergillus bronchitis and in invasive fungal disease in lung transplant patients. Four fungal media were compared in this study, including Sabouraud Dextrose Agar (SDA) and Medium B, with and without the addition of selective antibiotics, where antibiotic-supplemented media were designated with ⁺. These media were compared for their ability to suppress contaminating, mainly Gram−ve pathogens, in CF sputa (Pseudomonas aeruginosa, Burkholderia cepacia complex [BCC] organisms) and to enhance the growth of fungi present in CF sputum. Medium B consisted of glucose (16.7 g/l), agar (20 g/l), yeast extract (30 g/l) and peptone (6.8 g/l) at pH 6.3 and both SDA⁺ and Medium B⁺ were supplemented with cotrimethoxazole, 128 mg/l; chloramphenicol, 50 mg/l; ceftazidime, 32 mg/l; colistin, 24 mg/l). Employment of SDA⁺ or Medium B⁺ allowed an increase in specificity in the detection of yeasts and moulds, by 42.8% and 39.3%, respectively, over SDA when used solely. SDA⁺ had a greater ability than Medium B⁺ to suppress bacterial growth from predominantly Gram−ve co-colonisers. This is a significant benefit when attempting to detect and isolate fungi from the sputum of CF patients, as it largely suppressed any bacterial growth, with the exception of the BCC organisms, thus allowing for an increased opportunity to detect target fungal organisms in sputum and represented a significant improvement over the commercial medium (SDA), which is currently used. Overall, both novel selective media were superior in their ability to suppress bacteria in comparison with the commercially available SDA medium, which is routinely employed in most clinical microbiology diagnostic laboratories presently. Alternatively, Medium B⁺ had a great ability to grow fungi than SDA⁺ and when employed together, the specificity of combined use was 82%, with a sensitivity for yeasts, filamentous fungi, and combined overall fungi of 96.0%, 92.3% and 96.0%, respectively. Overall, when employing one fungal selective medium for the routine detection of yeasts and filamentous fungi in the sputum of CF patients, we would recommend employment of Medium B⁺. However, we would recommend the combined employment of SDA⁺ and Medium B⁺, in order to synergistically isolate and detect the greatest number of fungi present in CF sputa.     

Intratumoral Heterogeneity in Microsatellite Alterations in <Emphasis Type="Italic">BRCA1</Emphasis> and <Emphasis Type="Italic">PTEN</Emphasis> Regions in Sporadic Colorectal Cancer

Background: Chromosome regions 17q21 (BRCA1) and 10q23 (PTEN) have been found deleted in colorectal cancer.Methods: We studied the frequency of loss of heterozygosity (LOH) in these 2 regions in 214 patients with only 1 sample per tumor and in 100 patients with several samples per tumor. Three microsatellite markers of each region were used for the LOH test. The polymerase chain reaction product was electrophoresed in 8% polyacrylamide gels, and band intensity was shown by silver staining.Results: The proportions of LOH in the two regions were 38.4% for 17q21 and 30.8% for 10q23 in the group of 214 and were 47.7% for 17q21 and 34.7% for 10q23 in the group of 110434_2003_Article_876. We found a high correlation between the LOH in both regions (P < .001), where 81% of LOH in 10q23 region was matched by concomitant LOH in 17q21. In the group of tumors with several samples (group of 100), 39% and 68% did not present LOH in the 17q21 and 10q23 regions, respectively, in all of their tumor samples. However, in the 20 patients with LOH in both regions in the group of 100 (several samples per tumor), all samples with LOH in 10q23 also had LOH in 17q21, whereas not all samples with LOH in 17q21 had LOH in 10q23.Conclusions: These results show that colorectal cancer is highly heterogeneous, at least for these tumors markers, and suggest a sequential acquisition pattern of these anomalies during tumor growth, in which changes in 17q21 could occur before those in 10q23.     

EAU guidelines for the management of urogenital schistosomiasis

More than 100 million people worldwide are affected by bilharziasis, caused by Schistosoma haematobium. For travellers precaution is most important. For the population in endemic areas, an integrated approach including health education is necessary. Effective pharmacologic treatment is available.     

Review: Staphylococcus aureus and MRSA in cystic fibrosis

Background

Staphylococcus aureus (S. aureus) is one of the earliest bacteria detected in infants and children with cystic fibrosis (CF). The rise of methicillin resistant S. aureus (MRSA) in the last 10 years has caused a lot of attention to this organism.

Results

The aim of this review is to provide a general overview of methicillin sensitive S. aureus (MSSA) and MRSA, discuss special aspects of S. aureus in cystic fibrosis, and to review treatment concepts. Microbiology of the organism will be reviewed along with data regarding the epidemiology of both MSSA and MRSA. Antibiotic treatments both in regards to acute management and eradication of MSSA and MRSA will be reviewed. Prophylaxis of MSSA in CF remains controversial. Treatment with anti-staphylococcal agents reduces the infection rate with MSSA but may lead to a higher rate of infection with P. aeruginosa. In regards to MRSA, there is a paucity of clinical data regarding approaches to eradication.

Conclusions

To advance the care of CF patients, controlled clinical trials are urgently needed to find the optimal approach to treating CF patients who are infected with either MSSA or MRSA.     

Genetic forms of nephrotic syndrome

Mutations of NPHS1, NPHS2 , or WT1 may be responsible for severe forms of nephrotic syndrome in children, progressing to end-stage renal failure. Recent studies have shown that congenital nephrotic syndrome may be secondary to mutations of one of these three genes and that some patients have a digenic inheritance of NPHS1 and NPHS2 mutations. The clinical spectrum of NPHS2 mutations has broadened, with the demonstration that mutations in the respective gene podocin may be responsible for nephrotic syndrome occurring at birth, in childhood, or in adulthood. It is now well recognized that podocin mutations are found in 10%–30% of sporadic cases of steroid-resistant nephrotic syndrome with focal segmental glomerulosclerosis. Data from large cohorts indicate that the risk of recurrence of nephrotic syndrome after renal transplantation in patients with podocin mutations is very low.     

An unusual presentation of epidural Acinetobacter infection

OBJECTIVE: We report a case of spinal-cord compression caused by epidural fat infection with Acinetobacter. The initial magnetic resonance imaging (MRI) scan suggested epidural hematoma or abscess, although both were absent at surgery. CASE REPORT: A 60-year-old man had a thoracic epidural sited at the level of T8/9 for postoperative analgesia after major abdominal surgery. A mixture of bupivacaine 0.1% and fentanyl 2 microg/mL was infused at a rate of 10 mL/h for 48 hours postoperatively. The epidural catheter was then removed, but 24 hours later, the patient still had weakness and numbness in his lower limbs. An MRI scan showed cord compression secondary to a hematoma or abscess from the level of T6 to T11. At laminectomy, no hematoma or abscess was found, but edematous epidural fat was excised. This fat was sent for culture and Acinetobacter was grown. Appropriate antibiotic therapy was given. Over a period of 12 months, the patient has regained near-normal power and sensation. CONCLUSION: Epidural Acinetobacter infection may present atypically without signs of meningism. MRI imaging may be confusing in these infections and lead to incorrect radiological diagnoses. Spinal-cord compression, as a complication of epidural catheter placement, does not have to be caused by hematoma or abscess.     

<Emphasis Type="Italic">Candida albicans</Emphasis>-Infected Pancreatic Pseudocyst: Report of a Case

We report the case of a 48-year-old man with a pseudocyst infected by Candida albicans, and review the relevant literature. The patient was successfully treated by a Roux-en-Y cystojejunostomy of the pseudocyst and adjunctive therapy with amphotericin B. Candida species isolated from a pancreatic pseudocyst or abscess should be considered pathogenic, and treated aggressively.     

Associations of serologic markers of infection and inflammation with vascular disease events and mortality in American dialysis patients

Background Inflammatory markers predict cardiovascular risk and mortality in endstage renal disease. The relationship of chronic infections to inflammation and vascular disease events has not been reported among American dialysis patients. Methods We performed a cross-sectional and prospective study of a multiracial cohort of 97 chronic hemodialysis patients in California. Anti-Chlamydia pneumoniae IgA and IgG antibodies (Cp-IgA and Cp-IgG), anti-Helicobacter pylori antibodies (Hp-IgG), and highly sensitive C-reactive protein (hsCRP) levels were measured at enrollment. We ascertained the prevalence of atherosclerotic vascular (coronary artery, cerebrovascular, and peripheral vascular) disease (AVD) events, and observed participants for at least 1 year for incident events and mortality. We defined statistical significance as P < 0.01. Results Elevated hsCRP levels (77%) and seropositivity to C. pneumoniae were common (Cp-IgA, 49%; Cp-IgG, 64%), whereas the seroprevalence of Hp-IgG was relatively low (25%). The hsCRP levels did not vary with infection status. In bivariate analysis, Cp-IgA and Cp-IgG were each associated with approximately fourfold higher odds of prevalent AVD (P < 0.01). Although anti-chlamydial antibodies maintained nearly significant associations with AVD after covariate adjustment (P < 0.05), antibodies did not predict outcomes over the period of observation. However, hsCRP was a nearly significant independent predictor of prevalent AVD (P = 0.02) and of mortality during follow-up (P = 0.01). We did not detect an association of Hp-IgG with any study outcome. Conclusions Our findings generalize a possible link between C. pneumoniae and prevalent atherosclerosis in American hemodialysis patients and confirm the importance of hsCRP as a prognostic indicator. Our work does not support H. pylori as an important mediator of cardiovascular risk in dialysis patients. The abstract for a portion of this work was presented at the American Society of Nephrology 36th Annual Meeting and Scientific Exposition, San Diego, CA, USA, November 2003 Institution at which work was performed: Stanford University Medical Center, Stanford, CA, USA     

Glomerulonephritis associated with acute pneumococcal pneumonia: a case report

Streptococcus pyogenes is the most common cause of post-infectious glomerulonephritis. There have been isolated case reports of nephritis following infections with Streptococcus pneumoniae. We report here the case of a 6-year-old white female who presented with blood culture-confirmed pneumococcal pneumonia associated with glomerulonephritis. Her acute renal failure improved over several days, and renal function was normal by 8 weeks post-hospitalization. This case serves to reinforce the concept that other organisms besides Streptococcus pyogenes can trigger a similar post-infectious glomerulonephritis and should be considered in the differential diagnosis of any child who presents with acute glomerulonephritis and respiratory findings. Additionally, pneumococcus group 7 may be a nephritogenic strain and requires further investigation.     

Alcohol consumption and the risk of breast cancer among BRCA1 and BRCA2 mutation carriers

Alcohol consumption increases the risk of breast cancer among women in the general population, but its effect on women who carry a BRCA gene mutation is unclear. We conducted a case-control study of 1925 matched pairs of predominantly premenopausal women who carry a BRCA1 or a BRCA2 mutation. Information on current alcohol consumption was obtained from a questionnaire administered during the course of genetic counselling or at the time of enrolment. A modest inverse association between breast cancer and reported current alcohol consumption was observed among women with a BRCA1 mutation (OR = 0.82, 95% CI 0.70–0.96), but not among women with a BRCA2 mutation (OR = 1.00; 95% CI 0.71–1.41). Compared to non-drinkers, exclusive consumption of wine was associated with a significant reduction in the risk of breast cancer among BRCA1 carriers (p-trend = 0.01). Alcohol consumption does not appear to increase breast cancer risk in women carrying a BRCA gene mutation.     

Single-Nucleotide Polymorphisms and Haplotypes of Bone Morphogenetic Protein Genes and Peripheral Bone Mineral Density in Young Korean Men and Women

Bone morphogenetic proteins (BMPs) play critical roles in osteoblast differentiation. To investigate the association between common single-nucleotide polymorphisms (SNPs) of BMPs and bone mineral density (BMD), a cross-sectional study was conducted in healthy Korean men (n = 237) and women (n = 276) aged 20–39 years. Calcaneus and distal radius BMD were measured by dual energy X-ray absorptiometry. SNPs of BMP2 (-1103C>A, c.584G>A, IVS1-2744A>G, c.893T>A), BMP4 (c.712T>C, IVS1-160C>T), and BMP6 (c.1283C>G, IVS4-6838A>G, IVS5 + 24C>T) were determined using the 5′-nuclease assay. Significant associations were observed between BMP2 c.584G>A, c.893T>A genotypes and male calcaneus as well as female distal radius BMD. Men with the BMP2 c.893 AA genotype had a 16% higher BMD at the calcaneus (P for trend = 0.014), whereas women with this genotype had a 7% lower BMD at the distal radius than the other genotypes (P for trend = 0.010). A significant association was also observed between BMP4 IVS1-160C>T and male calcaneus BMD (P for trend = 0.024). When the association between haplotypes and BMD was investigated, the AAGA haplotype of BMP2 was significantly associated with low bone mass in female distal radius (P for trend = 0.013). These results suggested that one or more SNPs of BMP2 and BMP4 are associated with peripheral BMD in Korean men and women. However, this association is dependent on anatomical sites and gender. Thus, larger studies with complete coverage of SNPs are needed in the future.