Loss of breast cancer metastasis suppressor 1 protein expression predicts reduced disease-free survival in subsets of breast cancer patients.

PURPOSE: This study aims to determine the effect of loss of breast cancer metastasis suppressor 1 (BRMS1) protein expression on disease-free survival in breast cancer patients stratified by estrogen receptor (ER), progesterone receptor (PR), or HER2 status, and to determine whether loss of BRMS1 protein expression correlated with genomic copy number changes. EXPERIMENTAL DESIGN: A tissue microarray immunohistochemical analysis was done on tumors of 238 newly diagnosed breast cancer patients who underwent surgery at the Cleveland Clinic between January 1, 1995 and December 31, 1996, and a comparison was made with 5-year clinical follow-up data. Genomic copy number changes were determined by array-based comparative genomic hybridization in 47 breast cancer cases from this population and compared with BRMS1 staining. RESULTS: BRMS1 protein expression was lost in nearly 25% of cases. Patients with tumors that were PR negative (P=0.006) or HER2 positive (P=0.039) and <50 years old at diagnosis (P=0.02) were more likely to be BRMS1 negative. No overall correlation between BRMS1 staining and disease-free survival was observed. A significant correlation, however, was seen between loss of BRMS1 protein expression and reduced disease-free survival when stratified by either loss of ER (P=0.008) or PR (P=0.029) or HER2 overexpression (P=0.026). Overall, there was poor correlation between BRMS1 protein staining and copy number status. CONCLUSIONS: These data suggest a mechanistic relationship between BRMS1 expression, hormone receptor status, and HER2 growth factor. BRMS1 staining could potentially be used in patient stratification in conjunction with other prognostic markers. Further, mechanisms other than genomic deletion account for loss of BRMS1 gene expression in breast tumors.     

Soluble CD14 at 2 yr of age: Gender-related effects of tobacco smoke exposure, recurrent infections and atopic diseases

The endotoxin receptor soluble CD14 (sCD14) has been implicated in the 'hygiene hypothesis' suggesting reduced allergic sensitization with bacterial stimulation. However, the relationship between early life sCD14 and allergic diseases is conflicting. We aimed to investigate whether possible risk factors for allergic diseases were associated with sCD14 levels at 2 yr of age. In the nested case-control study of the birth cohort studies 'Environment and Childhood Asthma study in Oslo' 411 children selected with recurrent bronchial obstruction (rBO) (n=241) and no bronchial obstruction (n=170) by 2 yr were investigated with skin prick test and structured parental interview at age 2 yr. Exposure to tobacco smoke, pets and infections was recorded semi-annually by questionnaires (0-2 yr). The sCD14 was analysed from frozen, stored serum by ELISA technique. Regression analyses were performed in all subjects with complete data (n=406, 180 girls), and in girls and in boys separately. Mean sCD14 (ng/ml) was significantly higher among girls 2035 (1973-2096) vs. 1947 (1890-2004) (boys). The sCD14 was significantly reduced among girls exposed to antenatal maternal smoking and with parental asthma, after adjusting for age, parental rhino-conjunctivitis, pet keeping and childhood infections. Recurrent otitis media (OM) increased and common colds significantly decreased sCD14 levels in girls. Boys with atopic dermatitis and rBO had reduced sCD14. Pet exposure was not significantly associated with sCD14. We report novel gender-related effects of sCD14 in early life and suggest that gender, tobacco smoke exposure, age and middle ear disease in particular should be accounted for when assessing the role of sCD14 in childhood allergic diseases.     

Effectiveness and nephrotoxicity of intravenous colistin for treatment of patients with infections due to polymyxin-only-susceptible (POS) gram-negative bacteria

The prospective case series study presented here was conducted to assess the outcome of patients with infections caused by polymyxin-only-susceptible (POS) gram-negative bacteria managed with intravenous colistin. Between July 2003 and April 2005 a total of 27 patients were infected with a POS gram-negative bacterium and received intravenous colistin at a dose of 2 million international units (MIU) (160 mg or 66.7 mg colistin base) every 8 h for a mean (±SD) duration of 13.9 (±7.5) days. Nine patients had ventilator-associated pneumonia and received, in addition to the intravenous colistin therapy, 1 MIU (80 mg or 33.3 mg colistin base) aerosolized colistin every 12 h for a mean (±SD) duration of 13 (±6.5) days. The predominant pathogens were Pseudomonas aeruginosa (n=17) and Acinetobacter baumannii (n=12); in two patients both pathogens were isolated from one clinical specimen. In-hospital mortality and clinical response were 15% and 85%, respectively. Colistin-associated nephrotoxicity was observed in two of the 27 patients. POS gram-negative pathogens represent a major threat for hospitalized patients. Colistin appears to be an effective and safe treatment, even in patients with severe underlying diseases.     

Magnesium intake is inversely associated with the prevalence of tooth loss in Japanese pregnant women: the Osaka Maternal and Child Health Study.

There have only been a few studies on the role of mineral intake in tooth loss. We investigated the association between mineral intake and the prevalence of tooth loss in Japan. We used the baseline data on 1002 pregnant women who were enrolled in the Osaka Maternal and Child Health Study between November 2001 and March 2003. Tooth loss was defined as the previous extraction of one or more teeth. Nutrient intake was assessed by a validated diet history questionnaire. Prevalence odds ratios and confidence intervals were estimated by applying a multiple logistic regression model. The adjusted odds ratio upon comparison of the highest quartile with the lowest quartile of magnesium intake was 0.64 (95% confidence interval, 0.42-0.99), showing a tendency for an inverse dose-response relationship (p for linear trend = 0.05). There were no associations between the level of consumption of calcium, phosphate, iron, zinc, or copper and tooth loss. The present findings suggest that intake of magnesium is related to reduced prevalence of tooth loss among young Japanese women.     

Extranodal lymphomas presenting as soft tissue sarcomas to a sarcoma service over a two-year period.

Non-Hodgkin's lymphoma usually presents with lymphadenopathy at multiple sites but can also involve any part of the musculoskeletal system. Occasionally the presentation is with a soft tissue mass. The presentation of large, superficial lymphomatous masses is similar both clinically and radiologically to that of soft tissue sarcomas. The six cases of lymphoma presenting to the Exeter Sarcoma Service as suspected soft tissue sarcomas, over a two-year period (2002-2004), are presented. We describe the clinical and imaging characteristics of these tumours and their subsequent management. Our cases showed variability in presentation. Only one of the six cases presented with pain and one with tenderness. Four of the cases had no lymphadenopathy and the other two had lymphadenopathy restricted to one nodal basin. Overlying soft tissue swelling occurred in four cases and in distal limb swelling beyond the mass in one case. Radiologically, lymphomas are known to be likely to exhibit confluent lymphadenopathy that is rare in patients with soft tissue sarcoma. Confluent lymphadenopathy was demonstrated in only one case of this series of patients. It is thought that lymphomas infiltrate across anatomical fascial planes more readily than sarcomas and in four of our six cases this feature was present. Clinical history, examination and MRI are insufficient to differentiate between soft tissue sarcoma and lymphoma and the importance of obtaining a pathological diagnosis prior to surgery is clear. It is crucial to differentiate lymphoma from sarcoma in order to avoid unnecessary excisional procedures in lymphoma patients.     

Chronic orchialgia: Consider gabapentin or nortriptyline before considering surgery

OBJECTIVE: To establish if there is a role for gabapentin or nortriptyline in the treatment of chronic orchialgia. METHODS: Twenty-six consecutive patients with chronic orchialgia were seen in the chronic pain clinic by a multidisciplinary team. A pain questionnaire was completed prior to commencing either gabapentin or nortriptyline. They were reviewed at 3 months and a repeat questionnaire completed. A 50% improvement in pain was considered successful. RESULTS: Complete data was available for 19 patients. Overall, 61.5% of patients commenced on gabapentin and 66.6% of patients commenced on nortriptyline had a greater than 50% improvement in pain. Patients with post-vasectomy testicular pain were considered as a subgroup. None of these patients had a greater than 50% improvement in pain. However, 80% of patients in the subgroup with idiopathic chronic orchialgia had a greater than 50% improvement in pain. CONCLUSION: Although this is a small study, it appears that gabapentin and nortriptyline are effective in the treatment of idiopathic chronic orchialgia but not post-vasectomy pain.     

The remucosalizing alar cartilage flap: a reconstructive option for repairing nasal septal perforations

The objective of this study is to assess the results of repairing septal perforations with a vascularized pedicled alar cartilage island flap. Using the external rhinoplasty approach, a vascularized flap of alar cartilage, harvested as a cephalic trim and pedicled on the ascending columellar branches of the superior labial artery was raised. Bilateral mucoperichondrial septal flaps were elevated and the alar flap was transposed and secured within the defect and bilaterally overlaid with temporalis fascia. Silastic sheets were placed and remained in situ until the grafts were revascularized from the peripheries of the defect as well as centrally from the alar flap. The revascularized temporalis fascia acted as a scaffold for nasal remucosalization. The alar flap also increased the long-term structural robustness of the repair. Between 1999 and 2003, 14 patients with septal perforations ranging from 10 to 31 mm underwent septal reconstruction using this technique. There were nine males and five females. The flap was successfully raised in all cases and long-term closure was maintained in 12 patients (86%). The alar cartilage flap is an effective technique for repairing septal perforations in selected patients. It provides vascularized tissue which nourishes the grafts during remucosalization, and a cartilaginous framework, which affords long-term structural support to the repair. It also obviates the need to transpose nasal mucosa and create a secondary defect. The rhinoplasty approach furthermore permits additional nasal deformities to be corrected at the same time. Presented at the British Association of Plastic Surgeons Summer Scientific Meeting, Sheffield, UK (12 July 2006).     

Within-gene interaction between c.135 G/A genotypes and RET proto-oncogene germline mutations in HSCR families.

Hirschsprung disease (HSCR) is considered a model for a complex inheritance disorder. Several genes, including the major HSCR-susceptibility RET proto-oncogene, play an aetiological role in the development of HSCR. Genetic linkage analysis in familial HSCR with both long- and short-segment phenotypes has demonstrated a tight linkage to the RET locus, while the phenotype within a HSCR family is characterised by an incomplete penetrance or a variable extension of the aganglionosis. Therefore, additional genetic alterations of RET are postulated in the aetiology or modification of the HSCR phenotype. In this study, the coding region of all 21 exons of the RET proto-oncogene, including the flanking intronic sequences, were investigated by direct DNA sequencing in a HSCR population. We genotyped the c.135 G/A polymorphism and resolved haplotypes comprising the mutation locus and the c.135 G/A polymorphism. Twenty different mutations were detected in 18 of 76 HSCR patients. In ten families the mutations were inherited from the parents, while only four patients had a positive family history for the disease. Moreover, in all ten families an incomplete penetrance of the HSCR phenotype was observed. We have investigated the effect of the non-mutated wild-type allele as well as the c.135 G/A polymorphism on the phenotype within the HSCR families. Our findings support the notion that both RET alleles are involved in the pathogenesis of a subgroup of HSCR patients in a dose-dependent fashion. Additionally, we have shown a modifying effect of the c.135 G/A polymorphism on the HSCR phenotype within HSCR families.     

Liver and lung resection for colorectal metastasis

Aim: To examine the survival benefit of liver and lung resection for colorectal metastasis and the potential prognostic factors that affect patient survival. Methods: All patients who had resection of lung or liver metastasis for colorectal metastasis in Queen Elizabeth Hospital, Hong Kong from 1995 to 2004 were retrospectively reviewed. The overall and disease‐free survival was analysed, in particularly between liver and lung metastasis. All factors that may have affected the survival were entered into Cox's proportional hazards regression model to identify significant variables associated with survival. Results: At 5 years, the overall survival of patients who had resection of lung and liver metastasis was 44% and 38%, respectively; the disease‐free survival was 26% and 24%, respectively. Overall and disease‐free survival of patients with resection of lung metastasis was comparable to those with resection of liver metastasis. The differentiations of primary tumour and time to metastasis were shown to be significant prognostic factors influencing overall survival. Those patients with systemic chemotherapy after resection of colorectal metastasis demonstrated a significantly higher probability of overall survival. Conclusion: Resection of lung and liver metastases from colorectal origin was safe and both procedures improved survival. The use of chemotherapy after resection of metastasis significantly improved the overall survival.