Invasive Disease (invasive + disease)

Distribution by Scientific Domains
Distribution within Medical Sciences

Selected Abstracts

Bacteraemia as a result of Campylobacter species: a population-based study of epidemiology and clinical risk factors

H. Nielsen
Abstract Invasive disease as a result of Campylobacter is rarely reported. We reviewed 46 cases of blood stream infection with Campylobacter in a Danish population with complete follow-up. The incidence was 2.9 per 1 million person-years with a peak incidence in the age group above 80 years. In the population, the ratio of notified bacteraemia/enteritis patients with Campylobacter infection was 0.004. Patients with bacteraemia were older and had higher comorbidity, e.g. alcoholism, immunosuppression, previous gastrointestinal surgery or HIV infection. We found 26% of blood isolates resistant to ciprofloxacin. The length of hospitalization was significantly longer in bacteraemia patients, whereas the outcome was favourable with 28-day mortality of 4% in bacteraemia patients and 1% in enteritis patients. None of the bacteraemia patients relapsed within 365-day follow-up. [source]

Prevention of pneumococcal disease in children.

Pneumococcal conjugate vaccines: their use globally could have a major impact on public health
Pneumococcal disease is a major cause of morbidity and mortality in infants and young children worldwide. New pneumococcal conjugate vaccines include 7 to 11 serotypes, which are the most common cause of paediatric disease in most parts of the world. The efficacy of a 7-valent conjugate vaccine was 97.4% (95% CI, 82.7,99.9) against invasive pneumococcal disease, and 57% (95% CI, 44,67) against otitis media, caused by vaccine serotypes. Evidence shows that the vaccine has the potential to prevent pneumonia. Pneumococcal conjugate vaccination has also been shown to reduce nasopharyngeal carriage of vaccine serotypes (particularly serotypes associated with antibiotic resistance). Thus widespread use of pneumococcal conjugate vaccine could substantially reduce the burden of invasive disease and would have the potential to control the global spread of antibiotic resistance in pneumococci. Conclusion: It is important that these highly effective vaccines should be made available to children in the developing countries. [source]

Epidemiology of invasive and other pneumococcal disease in children in England and Wales 1996,1998

E Miller
The results of enhanced national surveillance of pneumococcal disease in children <15y of age in England and Wales are reported for the period 1996,1998. Of the 1985 cases of laboratory-confirmed invasive disease (annual incidence 6.6 per 100000 overall and 39.7 per 100000 in infants <1 y of age), 485 (24%) were meningitis (annual incidence of 1.6 per 100000 overall and 15.7 per 100000 in infants <1 y of age). Fifty-nine deaths in children with invasive disease were identified-3% of the total reports. Thirty-one different serogroups/types were identified, with organisms in the 7-valent conjugate vaccine responsible for 69% of the infections in children <5 y of age; this rose to 77% and 82%, respectively, for the 9-and 11-valent vaccines. Resistance to penicillin varied from 2.3% to 6.2% in different years, but erythromycin resistance remained constant at 17%. The vast majority of resistant isolates were in vaccine serotype/groups. Computerized hospital admission records for all children <15 y of age with a discharge diagnosis code indicating probable pneumococcal disease were also analysed for 1997. The annual incidence for cases with a code specifically mentioning S. pneumoniae was 9.9 per 100000 compared with 71.2 per 100000 for lobar pneumonia; the mean duration of stay for both was < 1 wk. The incidence of admission for pneumococcal meningitis (1.9 overall and 19.6 for infants < 1 y of age) was similar to that derived from laboratory reports and resulted in an average duration of stay of 2 wk. Conclusion: This surveillance has confirmed the substantial burden of morbidity attributable to pneumococcal disease in British children and the potential public health benefits that could be achieved by the use of pneumococcal conjugate vaccines. [source]

How predictive is a cervical smear suggesting invasive squamous cell carcinoma?

S. J. Johnson
How predictive is a cervical smear suggesting invasive squamous cell carcinoma? Features have been described in severely dyskaryotic cervical smears that suggest frankly invasive or microinvasive squamous cell carcinoma. These are reported in three separate categories in our department. The aim of the current study was to assess the positive predictive value of these categories for invasive disease on histology. All smears reported in these categories over a five year period were correlated with the histology results. 527 smears were assessed. The positive predictive value of a smear suggesting frank invasion was 55.7% for all invasive squamous carcinomas and 40% for stage IB or above. Smears suspicious of invasion or microinvasion predicted invasive disease in 22.3% and 17.2%, respectively, most carcinomas being stage IA. Invasive squamous cell carcinoma may be predicted to a limited degree by cervical cytology especially when the smear suggests frank invasion. [source]

Surgical Monotherapy Versus Surgery Plus Adjuvant Radiotherapy in High-Risk Cutaneous Squamous Cell Carcinoma: A Systematic Review of Outcomes

BACKGROUND Adjuvant radiotherapy (ART) has been recommended for squamous cell carcinoma (SCC) with a high risk of recurrence, particularly perineurally invasive disease. The utility of ART is unknown. This study compares reported outcomes of high-risk SCC treated with surgical monotherapy (SM) with those of surgery plus ART (S+ART). METHODS The Medline database was searched for reports of high-risk SCC treated with SM or S+ART that reported outcomes of interest: local recurrence, regional or distant metastasis, or disease-specific death. RESULTS There were no controlled trials. Of the 2,449 cases of high-risk SCC included, 91 were treated with S+ART. Tumor stage and surgical margin status before ART were generally unreported. In 74 cases of perineural invasion (PNI), outcomes were statistically similar between SM and S+ART. In 943 high-risk SCC cases in which clear surgical margins were explicitly documented, risks of local recurrence, regional metastasis, distant metastasis, and disease-specific death were 5%, 5%, 1%, and 1%, respectively. CONCLUSIONS High cure rates are achieved in high-risk cutaneous SCC when clear surgical margins are obtained. Current data are insufficient to identify high-risk features in which ART may be beneficial. In cases of PNI, the extent of nerve involvement appears to affect outcomes, with involvement of larger nerves imparting a worse prognosis. [source]

Phialemonium curvatum Prosthetic Valve Endocarditis with an Unusual Echocardiographic Presentation

Azriel Osherov M.D.
Phialemonium species, an opportunistic fungal pathogen rarely causes invasive disease, have been described as opportunistic infection agents in humans, mainly as a result of immunosuppression and very rarely involves the heart. We present a case of a patient with Phialemonium curvatum prosthetic aortic valve endocarditis with an unusual initial transesophageal echocardiography (TEE) presentation, illustrating the important role of repeat TEE for the proper diagnosis and management of infective endocarditis. [source]

Novel vaccine strategies with protein antigens of Streptococcus pneumoniae

Edwin Swiatlo
Abstract Infections caused by Streptococcus pneumoniae (pneumococcus) are a major cause of mortality throughout the world. This organism is primarily a commensal in the upper respiratory tract of humans, but can cause pneumonia in high-risk persons and disseminate from the lungs by invasion of the bloodstream. Currently, prevention of pneumococcal infections is by immunization with vaccines which contain capsular polysaccharides from the most common serotypes causing invasive disease. However, there are more than 90 antigenically distinct serotypes and there is concern that serotypes not included in the vaccines may become more prevalent in the face of continued use of polysaccharide vaccines. Also, certain high-risk groups have poor immunological responses to some of the polysaccharides in the vaccine formulations. Protein antigens that are conserved across all capsular serotypes would induce more effective and durable humoral immune responses and could potentially protect against all clinically relevant pneumococcal capsular types. This review provides a summary of work on pneumococcal proteins that are being investigated as components for future generations of improved pneumococcal vaccines. [source]

Identifying infection-associated genes of Candida albicans in the postgenomic era

Duncan Wilson
Abstract The human pathogenic yeast Candida albicans can cause an unusually broad range of infections reflecting a remarkable potential to adapt to various microniches within the human host. The exceptional adaptability of C. albicans is mediated by rapid alterations in gene expression in response to various environmental stimuli and this transcriptional flexibility can be monitored with tools such as microarrays. Using such technology it is possible to (1) capture a genome-wide portrait of the transcriptome that mirrors the environmental conditions, (2) identify known genes, signalling pathways and transcription factors involved in pathogenesis, (3) identify new patterns of gene expression and (4) identify previously uncharacterized genes that may be associated with infection. In this review, we describe the molecular dissection of three distinct stages of infections, covering both superficial and invasive disease, using in vitro, ex vivo and in vivo infection models and microarrays. [source]

A new multiparameter assay to assess HPV 16/18, viral load and physical status together with gain of telomerase genes in HPV-related cancers

Wendy Theelen
Abstract Oncogenic human papillomavirus (HPV) is the most important risk factor for cancer of the uterine cervix and a subgroup of head and neck cancers. Viral load has been associated with persistence of infection, whereas integration of HPV into the host cell genome is associated with transition to invasive disease. Viral integration is frequently correlated with loss of viral E2 and gain of the telomerase-related genes TERC and TERT. The objective of this study was to develop a rapid and sensitive multiplex ligation-dependent probe amplification (MLPA) assay for the simultaneous analysis of viral load, integration and copy number gain of TERC and TERT in HPV16/18-associated lesions. The performance of the assay was tested for HPV vs. human gene copy number ratios ranging from 0.1 to 100 and for percentages of integration ranging from 0 to 100%. The model systems used include plasmid mixtures and the HPV-positive cell lines SiHa, HeLa and CaSki described to contain a range of 2,600 viral copies per cell. In samples with low-viral load, viral integration can be reliably determined when more than 30% of the virus is integrated. Gain of the telomerase-related genes in the cell lines as determined by our MLPA assay was in accordance with data reported in the literature. Our study demonstrates that within a single MLPA-reaction viral type, load, integration and gain of TERC and TERT can be reliably determined, which will improve risk assessment for patients suspected for HPV infection. [source]

Somatic mutations of adenomatous polyposis coli gene and nuclear b-catenin accumulation have prognostic significance in invasive urothelial carcinomas: Evidence for Wnt pathway implication

Efstathios Kastritis
Abstract Wnt pathway signaling is crucial in many cancers and data indicate crosstalk with other key cancer pathways, however in urothelial carcinogenesis it has not been extensively studied. We searched for mutations in adenomatous polyposis coli (APC), a key regulator of the pathway, and studied b-catenin expression and interactions with the expression of other markers of apoptosis, angiogenesis, and proliferation in patients with invasive urothelial cancer. The mutation cluster region of APC was directly sequenced in 70 patients with muscle invasive disease who were treated with surgery and adjuvant chemotherapy. COX-2, p53, Ki67, and b-catenin were studied immunohistochemically and micro vessel density was quantified by CD105 expression. Single somatic amino-acid substitutions (missense) were found in 9 (13%) and frameshift deletions in 2 (3%) tumors, all located in regions adjacent to b-catenin binding sites. Patients having either APC missense mutations or b-catenin nuclear accumulation had less frequent COX-2 overexpression (24% vs. 76%, p = 0.043) and more frequent lymph node involvement (75% vs. 38%, p = 0.023). Patients with either APC mutations or b-catenin accumulation had shorter disease-free interval (13.4 vs. 28 months, p = 0.07), whereas in multivariate analysis they had shorter disease-specific survival (60.5 vs. 20.6 months, p = 0.048). Somatic APC missense mutations are not rare in advanced urothelial neoplasms. Either APC mutations and/or aberrant expression of b-catenin are associated with worse outcome. Further study of the role of the Wnt pathway, potential crosstalk with other pathways and potential candidate therapeutic targets in urothelial cancer is needed. 2008 Wiley-Liss, Inc. [source]

HPV related VIN: Highly proliferative and diminished responsiveness to extracellular signals

Lindy A.M. Santegoets
Abstract Vulvar intraepithelial neoplasia (VIN) is a premalignant disorder caused by human papillomaviruses. Basic knowledge about the molecular pathogenesis of VIN is sparse. Therefore, we have analyzed the gene expression profile of 9 VIN samples in comparison to 10 control samples by using genome wide Affymetrix Human U133A plus2 GeneChips. Results were validated by quantitative real-time RT-PCR analysis and immunostaining of a few representative genes (TACSTD1, CCNE2, AR and ESR1). Significance analysis of microarrays (SAM) showed that 1,497 genes were differentially expressed in VIN compared to controls. By analyzing the biological processes affected by the observed differences, we found that VIN appears to be a highly proliferative disease; many cyclins (CCNA, CCNB and CCNE) and almost all prereplication complex proteins are upregulated. Thereby, VIN does not seem to depend for its proliferation on paracrine or endocrine signals. Many receptors (for example ESR1 and AR) and ligands are downregulated. Furthermore, although VIN is not an invasive disease, the inhibition of expression of a marked number of cell,cell adhesion molecules seems to indicate development towards invasion. Upon reviewing apoptosis and angiogenesis, it was observed that these processes have not become significantly disregulated in VIN. In conclusion: although VIN is still a premalignant disease, it already displays several hallmarks of cancer. 2007 Wiley-Liss, Inc. [source]

Role of ureteroscopic biopsy in the management of upper urinary tract malignancy

Abstract Background:, The aim of the study presented here was to examine the accuracy of ureteroscopic biopsy in the diagnosis of upper urinary tract transitional cell carcinoma (TCC) and whether nephron-sparing management (holmium YAG laser, transurethral resection or partial ureterectomy) is possible or not based on pathological diagnosis. Methods:, Forty consecutive patients underwent ureteroscopic biopsy with the use of 3-Fr cold cup forceps. Pathological diagnosis of the biopsy sample and grade or stage of surgically resected tumors were compared. In patients with grade 1 or 2 TCC diagnosed by ureteroscopic biopsy, the disease-free and survival rates determined whether nephron-sparing management was performed or not. Results:, There were no major complications associated with ureteroscopic biopsy. The pathological grading of the biopsy specimen was almost the same as that of the surgically resected specimen. Eighty five percent of grade 2 or 3 TCC showed muscle invasive disease. There were no significant differences in the disease-free and survival rates between the nephroureterectomy and the nephron-sparing management groups, except for grade 3 or pT3 tumors. Conclusion:, Ureteroscopic biopsy is safe and accurate if sufficient tissue sample is obtained. Ureteroscopic biopsy should be performed in patients who require nephron-sparing management. Nephroureterectomy can be avoided if the tumor is confirmed as low-grade. [source]


Provenzano E
Background: DCIS represents preinvasive malignant change. With screening mammography DCIS has become a common entity. Its natural history is poorly understood and treatment remains controversial. Using a retrospective population based cohort, we have identified histological and molecular variables predictive of recurrence. Methods: All cases of DCIS reported in Victoria between 1988 and 1992 were entered into the Victorian Cancer Registry. In Situ and Small Cancer Register (ISSIBCR) and followed up annually regarding treatment, the event of recurrence and its nature and location. From this register a cohort of 66 DCIS lesions with subsequent recurrence as in situ or invasive disease were studied histologically, immunohistochemically and with CGH-based genetic analyses comparing them to a nested randomized control group of DCIS without recurrence matched for patient age and year of diagnosis. Recurrences have been analysed by the same techniques to compare them to the primary lesion. Results: 13 histological features were evaluated and lesion size, nuclear pleomorphism, cellular polarity, micropapillary architecture and central necrosis were all significant predictors of recurrence (p < 0.05). Immunohistochemistry showed p21 overexpression, bcl2 negativity and ERBB2 positivity to be markers of recurrence. In the case of ERBB2, positivity was a predictor of recurrence even when its overexpression was focal. Primary and recurrent DCIS lesions had similar morphological appearances, and grade of primary DCIS correlated with grade of subsequent invasive cancer. This morphological similarity was paralleled by similar protein expression and genomic changes in both in situ and invasive recurrences. Conclusion: We have identified histological and immunohistochemical markers of recurrence in DCIS, and shown similarities in morphology, protein expression and genetic changes between primary DCIS and its recurrence. [source]

Imaging mass spectrometry: Towards clinical diagnostics

Erin H. Seeley
Abstract Imaging MS (IMS) has emerged as a powerful tool for biomarker discovery. A key advantage of this technique is its ability to probe the proteome directly from a tissue section with preservation of the spatial relationships of the sample and minimal sample preparation. This allows for direct correlation of protein expression with histology. Here, we present the latest developments in imaging MS and their relevance to clinical mass spectral analysis. IMS allows for high throughput analysis of tissue samples and is fully compatible with biostatistical analysis without prior knowledge of protein expression. Several studies are presented of applications in which direct tissue mass spectral analysis has provided insight into clinical questions not readily available by other means. Examples include the determination of lymph node status from investigation of primary breast tumors, prediction of response of breast tumors to chemotherapy, classification and prediction of progression of lung lesions, and exploration of ,molecular' margins in invasive disease. [source]

Novel Clinical Trial Designs for Treatment of Ductal Carcinoma In Situ of the Breast with Trastuzumab (Herceptin)

Ricardo J. Gonzalez MD
Abstract:, Because ductal carcinoma in situ (DCIS) avidly expresses Her2/neu, the target of the monoclonal antibody trastuzumab, and because trastuzumab has been shown to be effective against invasive breast cancer, trastuzumab may be effective for reducing the tumor burden and abrogating or reversing the hypothesized transition from in situ to invasive disease in patients with DCIS. To test this hypothesis, a trial of neoadjuvant trastuzumab for DCIS has been opened at our institution. Because trastuzumab has been shown to act as a radiosensitizing agent for Her2/neu-overexpressing cancer and because there are currently no systemic treatments for estrogen-receptor-negative DCIS, it makes sense to investigate whether use of trastuzumab concurrently with postoperative radiation therapy improves local control of DCIS. The National Surgical Adjuvant Breast and Bowel Project (NSABP) is planning a trial to test this hypothesis. The risk of cardiac toxicity associated with the doses of trastuzumab planned for these trials (cumulative doses of 8 mg/kg for our trial and 14 mg/kg in the NSABP trial) is believed to be minimal, but the safety profile of these approaches will need to be closely monitored. [source]

Human papillomavirus integration: detection by in situ hybridization and potential clinical application

Mark F Evans
Abstract Human papillomaviruses (HPVs) are accepted as a necessary cause of cervical neoplasia. However, the benefits of testing simply for high-risk HPV types are limited because of their high prevalence in intraepithelial lesions of all grades, the majority of which regress if left untreated. One factor considered to be of key importance for the progression of intraepithelial lesions to invasive disease is integration of HPV into the host cell genome. Although questions remain about the prevalence of integration amongst pre-invasive lesions, sensitive in situ hybridization techniques utilizing tyramide reagents may aid determination of the significance of HPV infection by enabling routine detection of both high-risk HPV and its physical status. This will provide important data relevant not only to our understanding of the biology of HPV-associated neoplasia, but also potentially to clinical testing for HPV. Copyright 2003 John Wiley & Sons, Ltd. [source]

Protein Expression of the Tumor Suppressors p16INK4A and p53 and Disease Progression in Recurrent Respiratory Papillomatosis

Truc T. Pham MD
Abstract Background: Recurrent respiratory papillomatosis (RRP) is a benign condition that rarely metastasizes as invasive squamous cell carcinoma. Although this disease is associated with human papillomavirus, the role of this virus in tumorigenesis is unclear. Objectives: The aim of this study is to assess the involvement of the tumor suppressors P16INK4A and p53 in RRP tumor progression. Design: Immunohistochemistry of p16INK4A and p53 was performed on biopsies of recurrent squamous papillomas and invasive lesions in nine patients. Results: Twenty biopsies were graded as papillomas (RP), three as papillomas with high-grade dysplasia/carcinoma in situ (HGD/CIS), and two as invasive squamous cell carcinoma (SCCA). Forty-five percent of RP and 60% of HGD/CIS/SCCA expressed p16INK4A. Fifty percent of RP and 100% of HGD/CIS/SCCA expressed p53. The difference in the frequency of p53-positive staining between HGD/CIS and SCCA (100% of tissues examined) and RP (50% of tissues examined) approached statistical significance. Neither p16INK4A nor p53 was predictive of invasive transformation. Conclusions: Expression of p16INK4A, which is a surrogate for the tumor suppressor retinoblastoma (Rb), did not immediately lead to invasive disease. There is no correlation between disease severity of RRP and level of p16INK4A. [source]

The ,Indirect' Effects of Cytomegalovirus Infection

R. B. Freeman
Cytomegalovirus (CMV) remains the most important infection in the immunocompromized host even in the era of effective therapy. CMV is usually acquired early in life and can be transmitted by contact with infected body fluids. In the immunocompetent population, primary infection is almost always of little clinical consequence. However, CMV infection in immunocompromized patients, especially those naive to CMV exposure, can cause tissue invasive disease, severe symptoms and/or death. However, beyond these direct effects, increasing in vitro evidence is accumulating that suggests CMV has many other effects on the host's immune response which may explain some of the detrimental consequences for the immunosuppressed patient, and may also be partially responsible for a variety of conditions in immunocompetent individuals. In its latent state, CMV employs several mechanisms to evade detection by the host's immune system. The virus also employs other methods to take advantage of activation of the immune system and replicate in sites of inflammation. This review focuses on the immunosuppressive and inflammatory mechanisms that have been attributed to CMV and will relate them to some of the clinical sequellae that have been associated with the indirect effects of CMV infection. [source]

Adenovirus Infection in Pediatric Liver and Intestinal Transplant Recipients: Utility of DNA Detection by PCR

Gwenn E. McLaughlin
To evaluate the incidence of adenovirus (AdV) infection in pediatric liver and intestinal transplant recipients, the records of patients with possible AdV infection were reviewed for demographic data, symptomatology, methods of diagnosis, treatment and outcome. To evaluate the impact of polymerase chain reaction (PCR) amplification and identification of AdV DNA as a diagnostic test, the incidence and outcome of AdV before and after the introduction of PCR were compared. Adenovirus infection was identified in 4.1% of liver recipients and 20.8% of intestinal transplant recipients. The overall incidence of AdV did not increase over time, even following the introduction of PCR for virus detection. The higher incidence of AdV in the pediatric intestinal transplant recipients may be attributed to the frequent application of PCR methodology to intestinal biopsy material. Detection of AdV by PCR was associated with reduced mortality compared with detection by culture, either because of earlier detection of invasive disease or because PCR detects the presence of latent as well as active AdV. [source]


Paul R. B. Kitchen
Background: In situ disease surrounding invasive tumours is an important consideration in the management of patients with early breast cancer. This study of screen-detected breast cancers assessed the influence of in situ disease including an extensive in situ component (defined as ductal carcinoma in situ involving more than 25% of the area within the invasive tumour) on surgical management, local recurrence and survival of a group of patients. Methods: A total of 595 cases of invasive breast cancer detected at St Vincent's BreastScreen were retrospectively reviewed to determine presence and extent of in situ disease, the surgical procedure and adequacy of excision. Outcome was examined in a cohort of 126 cases. Results: A total of 438 (74%) patients had in situ foci in or around the invasive tumour and 107 (18%) were defined as extensive in situ component (EIC)-positive. The initial procedure was mastectomy in 20% of the cases and breast-conserving surgery in 80% including 18% who underwent further surgery. Re-excision (P = 0.02) or mastectomy (P = 0.01) was more often required in patients with EIC. After definitive local excision, margins were close or involved with invasive disease in 3% but the patients with EIC were more likely to have margins close or involved with in situ disease (16 vs 2%; P = 0.001). There were seven deaths and one local invasive recurrence in the follow-up group and none of the deaths were in patients who were EIC-positive. Conclusions: EIC predicts for a higher rate of re-excision and/or mastectomy. For patients with EIC, there is an acceptably low risk of local recurrence if margins are clear. [source]

Squamous cell carcinoma in situ of the skin: History, presentation, biology and treatment

John P Arlette
SUMMARY Squamous cell carcinoma in situ (SCCIS) of the skin is a problem commonly dealt with by dermatologists. The classic presentation, originally described by Bowen, is easily recognized, but presentation on some anatomical surfaces may be associated with less than typical features. Major aetiological factors for this disease are UV light, human papillomavirus infection and immunosuppression. The natural course of SCCIS is usually prolonged, with treatment being appropriate, but not urgent. The choice of therapy requires consideration of the location of the lesion, and a desire for a high cure rate without causing loss of form, function or cosmesis. The immunomodulatory agent imiquimod has offered a significant advance for the topical treatment of SCCIS. Our improved understanding of the underlying biology of SCCIS permits us to make rational choices of treatment. In the future we may be able to determine which of these lesions may progress to invasive disease, and help us select the most effective therapy. [source]

A preliminary X-ray study of d,d -heptose-1,7-bisphosphate phosphatase from Burkholderia thailandensis E264

Mi-Sun Kim
d,d -Heptose-1,7-bisphosphate phosphatase (GmhB), which is involved in the third step of the NDP-heptose biosynthesis pathway, converts d,d -heptose-1,7-bisphosphate to d,d -heptose-1-phosphate. This biosynthesis pathway is a target for new antibiotics or antibiotic adjuvants for Gram-negative pathogens. Burkholderia thailandensis is a useful surrogate organism for studying the pathogenicity of melioidosis owing to its extensive genomic similarity to B. pseudomallei. Melioidosis caused by B. pseudomallei is a serious invasive disease of animals and humans in tropical and subtropical areas. In this study, GmhB has been cloned, expressed, purified and crystallized. X-ray data have also been collected to 2.50, resolution using synchrotron radiation. The crystal belonged to space group P6, with unit-cell parameters a = 243.2, b = 243.2, c = 41.1,. [source]

A preliminary X-ray study of sedoheptulose-7-phosphate isomerase from Burkholderia pseudomallei

Mi-Sun Kim
Sedoheptulose-7-phosphate isomerase (GmhA) converts d -sedoheptulose 7-phosphate to d,d -heptose 7-phosphate. This is the first step in the biosynthesis pathway of NDP-heptose, which is responsible for the pleiotropic phenotype. This biosynthesis pathway is the target of inhibitors to increase the membrane permeability of Gram-negative pathogens or of adjuvants working synergistically with known antibiotics. Burkholderia pseudomallei is the causative agent of melioidosis, a seriously invasive disease in animals and humans in tropical and subtropical areas. GmhA from B. pseudomallei is one of the targets of antibiotic adjuvants for melioidosis. In this study, GmhA has been cloned, expressed, purified and crystallized. Synchrotron X-ray data were also collected to 1.9, resolution. The crystal belonged to the primitive orthorhombic space group P212121, with unit-cell parameters a = 61.3, b = 84.2, c = 142.3,. A full structural determination is under way in order to provide insights into the structure,function relationships of this protein. [source]

A systematic review of intravesical bacillus Calmette-Gurin plus transurethral resection vs transurethral resection alone in Ta and T1 bladder cancer

M.D. Shelley
Objective,To assess, in a systematic review, the effectiveness of intravesical bacillus Calmette-Gurin (BCG) in preventing tumour recurrence in patients with medium/high risk Ta and T1 bladder cancer. Patients and methods,An electronic database search of Medline, Embase, DARE, the Cochrane Library, Cancerlit, Healthstar and BIDS was undertaken, plus hand searching of the Proceedings of ASCO, for randomized controlled trials, in any language, comparing transurethral resection (TUR) alone with TUR followed by intravesical BCG in patients with Ta and T1 bladder cancer. Results,The search identified 26 publications comparing TUR with TUR + BCG. Six trials were considered acceptable, representing 585 eligible patients, 281 in the TUR-alone group and 304 in the TUR + BCG group. The major clinical outcome chosen was tumour recurrence. The weighted mean log hazard ratio for the first recurrence, taken across all six trials, was ,0.83 (95% confidence interval ,0.57 to ,1.08, P < 0.001), which is equivalent to a 56% reduction in the hazard, attributable to BCG. The Peto odds ratio for patients recurring at 12 months was 0.3 (95% confidence interval of 0.21,0.43, P < 0.001), significantly favouring BCG therapy. Manageable toxicities associated with intravesical BCG were cystitis (67%), haematuria (23%), fever (25%) and urinary frequency (71%). No BCG-induced deaths were reported. Conclusion,TUR with intravesical BCG provides a significantly better prophylaxis of tumour recurrence in Ta and T1 bladder cancer than TUR alone. Randomized trials are still needed to address the issues of BCG strain, dose and schedule, and to better quantify the effect on progression to invasive disease. [source]

Imaging for staging bladder cancer: a clinical study of intravenous 111indium-labelled anti-MUC1 mucin monoclonal antibody C595

O.D.M. Hughes
Objective To investigate the clinical application of an 111In-labelled anti-MUC1 mucin monoclonal antibody (mAb) imaging for staging invasive bladder cancer. Patients and methods Indirect immunohistochemistry was used to confirm the expression of the MUC1 target antigen by metastatic tumours. Twelve patients with bladder cancer (two with superficial and 10 with locally invasive/metastatic disease) underwent planar ,-scintigraphy 48 h after an intravenous injection with 111In-labelled anti-MUC1 mucin mAb C595. Results No bladder uptake was detected in the two patients with superficial disease, but scintigraphy showed primary and recurrent bladder tumours and metastases in nine of the remaining 10 patients with invasive disease. In three patients additional staging information was obtained from the mAb imaging which would have altered patient management. There were no reported side-effects. Conclusion This study confirmed the ability of the mAb technique to detect both primary and recurrent invasive bladder tumours and distant metastases. Some lesions shown by mAb imaging were not detected by other methods. The use of mAb imaging has the potential to improve clinical staging and assist in selecting those patients most likely to benefit from radical therapy. [source]

Mode of splenectomy and immunogenicity of meningococcal vaccination in patients with hereditary spherocytosis,

G. A. Stoehr
Background: Splenectomy predisposes patients to invasive disease from pneumococci, meningococci, and Haemophilus influenzae; immunization is mandatory. However, data on the impact of the splenectomy on vaccine immunogenicity are scarce. Methods: A total of 41 children with hereditary spherocytosis (aged 58,144 years) had complete (16) or near-total (25) splenectomy. All received one dose of monovalent meningococcal C conjugate vaccine (MCV-C) and, 2 months later, a tetravalent meningococcal polysaccharide vaccine (MPV-ACWY). Serum bactericidal activity and antibodies against serogroups A and C were determined before and after they received MCV-C, and 4 weeks after they received MPV-ACWY. Results: Before vaccination, only four of the 16 children who had a complete splenectomy were protected against serogroup A, compared with 15 of the 25 who had near-total splenectomy (P < 0050), with the latter responding to immunization with significantly higher serogroup A serum bactericidal activity: geometric mean (95 per cent confidence interval) 1625.5 (49.9 to 3201.1) versus 980.6 (2.00 to 6204.1) (P < 0050). All patients achieved putative protective serum bactericidal activity titres (at least 8) against serogroup C. Conclusion: Near-total splenectomy provides a favourable immunological basis for natural and vaccine-induced protection against meningococcal serogroup A and C infections. Sequential meningococcal vaccination is immunogenic in patients splenectomized for hereditary spherocytosis. Copyright 2007 British Journal of Surgery Society Ltd. Published by John Wiley & Sons, Ltd. [source]

Breast cancer in men in the United States,

CANCER, Issue 15 2010
A population-based study of diagnosis, survival, treatment
Abstract BACKGROUND: Breast cancer in men is rare, so clinical trials are not practical. Recommendations suggest treating men who are diagnosed with breast cancer using the guidelines for postmenopausal women; however, to date, no population-based studies have evaluated patterns of care. METHODS: To examine characteristics, treatment, and survival among men with newly diagnosed breast cancer, in 2003 and 2004, 512 men were identified from the Surveillance, Epidemiology and End Results Program. Data were reabstracted and therapy was verified through the patients' treating physicians. RESULTS: The majority of men (79%) were diagnosed through discovery of a breast lump or other signs/symptoms. Among men who had invasive disease, 86% underwent mastectomy, 37% received chemotherapy, and 58% received hormone therapy. In multivariate analysis, tumor size (P = .01) and positive lymph node status (P < .0001) were associated positively with the use of chemotherapy, whereas age group (P < .0001) and current unmarried status (P = .01) had negative associations. Among men who had invasive, estrogen receptor (ER)-positive/borderline tumors, the use of tamoxifen or aromatase inhibitors (AIs) was associated with age group (P = .05). Among men who had invasive disease, cancer mortality was associated with tumor size (P < .0001). Among men with ER-positive/borderline disease, increased cancer mortality was associated with tumor size (P < .0001), current unmarried status (P = .04), and decreased mortality with tamoxifen (P = .04). CONCLUSIONS: Tumor characteristics and marital status were the primary predictors of therapy and cancer mortality among men with breast cancer. Although AIs are not currently recommended, they are commonly prescribed. However, their use did not result in a decrease in cancer mortality. Research must examine the efficacy of AIs with and without gonadotropin-releasing hormone analogues. Cancer 2010. 2010 American Cancer Society. [source]

Invasive pneumococcal disease in children prior to implementation of the conjugate vaccine in the Zurich region, Switzerland

P Gessler
Abstract Objective:, To describe symptoms, disease manifestations and outcome of invasive pneumococcal disease in children prior to implementation of the pneumococcal vaccine. Patients and methods:, Analysis of children younger than 16 years of age with invasive pneumococcal disease (IPD; n = 119). Children with culture-confirmed IPD, without underlying illness at risk for invasive disease, were included. Results:, IPD in 90 children (age: median 2, mean 3.2 years) included 15 with meningitis, 16 with septicaemia, 14 with bacteraemia, 24 with pneumonia and 21 with skin, bone and joint infections. Symptoms of IPD most often described were fever and gastrointestinal symptoms (abdominal pain, vomiting, or diarrhoea), and coughing. More than 90% of children with pneumonia were coughing. Most importantly, clinical signs significantly predictive for severe IPD included tachycardia for sepsis, tachypnea for pneumonia, and meningeal signs for meningitis. Leukocyte, neutrophil and platelet counts were lower and C-reactive protein concentrations were higher on admission in children with complicated than in children with uncomplicated IPD but, due to wide overlap of these numbers, the difference was not of prognostic help to predict clinical course and outcome. Overall, 40% of children with IPD manifested complications and IPD showed a mortality rate of 6.6%. Conclusions:, IPD is a serious disease with a high complication rate and mortality. The clinical signs tachycardia, tachypnea, and meningism were highly predictive for severe IPD. The initial clinical presentation and laboratory evaluation were mostly unpredictable with respect to complications and outcome in contrast to the clinical signs. [source]

Primary tumour diameter as a risk factor for advanced disease features of differentiated thyroid carcinoma

Frederik A. Verburg
Summary Objective, To study the relationship between primary tumour size and the risk of advanced disease features (multifocal or locally invasive disease, lymph-node or distant metastases) in differentiated thyroid carcinoma (DTC). Design, A retrospective chart review study. Patients, The study sample comprised 935 papillary (PTC) and 291 follicular thyroid carcinoma (FTC) patients treated in our hospital from 1978 to 2007. Measurements, Kaplan,Meier analyses and log-rank tests were performed to calculate tumour size-adjusted cumulative risk of advanced disease features. Results, Accounting for primary tumour diameter, there were no significant differences in cumulative risks of multifocal carcinoma (P = 012) or distant metastases (P = 049) between PTC and FTC. PTC showed higher cumulative risks of local invasion (P < 00001) or lymph-node metastases (P < 00001). The cumulative risk of tumour multifocality increased 5%/cm of primary tumour diameter. The cumulative risk of local invasion or lymph-node metastases in PTC and of distant metastases in DTC increased exponentially at a threshold tumour diameter of 10 mm. In FTC, lymph-node metastases are associated almost exclusively with primary tumours showing extrathyroidal growth. Conclusions, Starting with a 1 cm primary tumour diameter, increasing tumour size is associated with an exponentially increasing risk of local invasion or lymph-node or distant metastases of DTC. The current classification of carcinomas < 2 cm as T1 is therefore questionable. [source]

Characterisation of invasive meningococcal isolates from Italian children and adolescents

P. Mastrantonio
Abstract Meningococcal invasive disease is a life-threatening infection that affects mostly children and adolescents. The present study was performed during 2003,2005 to compare the phenotypic characteristics of meningococcal isolates from these two main groups at risk with those of isolates from other age groups to assess whether strategies for treatment and prevention implemented elsewhere can also be applied in Italy. The results showed that serogroup C meningococci were predominant, and that a dramatic increase in the circulation of strains with decreased susceptibility to penicillin was associated mainly with a prevalent phenotype C:2b:P1.5,2, which belongs to the hyper-virulent ST8/A4 cluster. [source]