bluuebunny/crossref_metadata_2025_split huggingface dataset:
Epidemiological, clinical features and susceptibility pattern of shigellosis in the buea health district, Cameroon
Authors: Njunda Anna L , Assob Jules CN , Nsagha Dickson S , Kamga Henri LF , Awafong Maghah P , Weledji Elroy P 
Published: January 2012

Abstract

Background
Shigellosis is an acute invasive enteric infection caused by bacteria belonging to the genus Shigella; it is clinically manifested by bloody diarrhoea. Shigellosis is endemic in many developing countries including Cameroon and also occurs in epidemics causing considerable morbidity and mortality. This study evaluated the epidemiological and clinical features of Shigella and the resistance pattern of isolates to commonly used antibiotics in the Buea Health District in Cameroon, from April to August, 2010.

Results
Of the 223 stool samples cultured, 10 (4.5%) yielded Shigella species. Isolation rate was observed to be more in children below 15 years (7.89%), and also higher in rural areas (6.35%). All 10 isolates showed resistance to at least two antibiotics and 9 (90%) were multi-drug resistant. The highest resistance rates were encountered with cotrimoxazole (90%) and amoxicillin (80%). Least resistance was observed with azithromycin (10%).

Conclusion
Shigellosis is more prevalent in children below 15 years in the Buea District. There is a high level of resistance to most of the antibiotics used for the treatment of shigellosis including extended-spectrum beta-lactamases (ESBLs) as well as evidence of resistance to quinolones. Azithromycin was found to be the drug of choice for shigellosis in this setting.
Beta-catenin is selectively required for the expansion and regeneration of mature pancreatic acinar cells
Authors: Keefe Matthew , Wang Hui , De La O Jean-Paul , Khan Ameena , Firpo Matthew A. , Murtaugh L. Charles 
Published: January 2012

SummaryThe size of the pancreas is determined by intrinsic factors, such as the number of progenitor cells, and by extrinsic signals that control the fate and proliferation of those progenitors. Both the exocrine and endocrine compartments of the pancreas undergo dramatic expansion after birth, and are capable of at least partial regeneration following injury. Whether the expansion of these lineages relies on similar mechanisms is unknown. Although we have shown that the Wnt signaling component β-catenin is selectively required for generation of exocrine acinar cells in utero, this gene has been ascribed various functions in the postnatal pancreas including proliferation and regeneration of islet as well as acinar cells. To address whether β-catenin remains important for the maintenance and expansion of mature acinar cells, we have established a system to follow the behavior and fate of β-catenin-deficient cells during postnatal growth and regeneration. We find that β-catenin is continuously required for the establishment and maintenance of acinar cell mass, extending from embryonic specification through juvenile and adult self-renewal and regeneration. This requirement is not shared with islet cells, which proliferate and function normally in the absence of β-catenin. These results make distinct predictions for the relative role of Wnt/β-catenin signaling in the etiology of human endocrine and exocrine disease. We suggest that loss of Wnt/β-catenin activity is unlikely to drive islet dysfunction, as occurs in type 2 diabetes, but that β-catenin is likely to promote human acinar cell proliferation following injury, and may therefore contribute to the resolution of acute or chronic pancreatitis.
Saphenopopliteal ligation and stripping of small saphenous vein: does extended stripping provide better results?
Authors: Samuel N , Carradice D , Wallace T , Smith G E , Mazari F A K , Chetter I 
Published: January 2012

Objective Saphenopopliteal ligation (SPL) for venous insufficiency is a challenging procedure, with mixed results being reported. The role of stripping of the small saphenous vein (SSV) is contentious. This prospective observational study aimed to assess the risks and benefits of this procedure. Methods Fifty patients underwent SPL under general anaesthesia by a single surgeon in a tertiary referral vascular centre. The aim was to perform inversion stripping in each case, but in a proportion this was not possible. Patients were grouped into SPL with short segment excision ≤5 cm ( n = 23) and SPL with extended stripping >5 cm ( n = 27). Outcome measures included venous clinical severity scores (VCSS), quality of life (QoL), Aberdeen varicose vein questionnaire (AVVQ), patient satisfaction, recurrence and complication rates. Results Intragroup analysis demonstrated statistically significant improvements in VCSS ( P < 0.001), and QoL measures (generic and disease-specific AVVQ) ( P < 0.050) with both treatments. Intergroup analysis demonstrated statistically significant superior VCSS scores at one year ( P = 0.001), AVVQ at three months and one year ( P < 0.05), and cosmetic satisfaction at one year ( P = 0.011) in the SPL extended stripping group. There was no difference in clinical recurrence 1/23 (4.3%) versus 1/27 (3.7%) ( P = 0.900) or complication rates ( P > 0.050). Conclusions SPL with or without stripping is an effective procedure improving clinical severity and QoL in the short term. Early outcomes favour SPL with extended stripping to offer greater improvement in disease-specific QoL, venous severity and cosmesis. With this small sample, there is no evidence of increased complications following stripping, or increased short-term recurrence without it. Greater numbers and follow-up are required to make firm conclusions.
Diagnosis of subclinical central hypothyroidism in patients with hypothalamic–pituitary disease by Doppler echocardiography
Authors: Doin Fabio Casanova , Rosa-Borges Mariana , Martins Manoel R A , Moisés Valdir A , Abucham Julio 
Published: January 2012

ObjectiveThe diagnosis of subclinical central hypothyroidism in hypothalamic–pituitary patients cannot be established by serum markers of thyroid hormone action. Myocardial function by echocardiography has been shown to reflect thyroid hormone action in primary thyroid dysfunction. We evaluated the performance of echocardiography in diagnosing subclinical central hypothyroidism.DesignCross-sectional and before and after.MethodsEchocardiography and serum thyroid hormones were assessed in overt primary (n=20) and central (n=10) hypothyroidism, subclinical primary hypothyroidism (n=10), hypothalamic–pituitary disease with normal free thyroxine (FT4;n=25), and controls (n=28). Receiver operating characteristic (ROC) curves were generated using overt hypothyroidism patients and selected cut-off values were applied to detect both primary and central subclinical hypothyroidism. After levothyroxine (l-T4) intervention, patients were echocardiographically reevaluated at predefined targets: normal thyrotropin (TSH) in primary hypothyroidism, normal FT4in overt central hypothyroidism, and higher than pretreatment FT4in echo-defined subclinical central hypothyroidism.ResultsParameters with highest areas under the ROC curves (area under the curve (AUC) ≥0.94) were as follows: isovolumic contraction time (ICT), ICT/ejection time (ET), and myocardial performance index. Highest diagnostic accuracy (93%) was obtained when at least one parameter was increased (positive and negative predictive values: 93%). Hypothyroidism was echocardiographically diagnosed in eight of ten patients with subclinical primary hypothyroidism and in 14 of 25 patients (56%) with hypothalamic–pituitary disease and normal serum FT4. Echocardiographic abnormalities improved significantly afterl-T4and correlated (0.05<P<0.001) with changes in FT4(−0.62<r<−0.55) and TSH (0.63<r<0.68) in primary hypothyroidism and with FT4in central hypothyroidism (−0.72<r<−0.50).ConclusionEchocardiography can be useful in diagnosing subclinical central hypothyroidism in patients with hypothalamic–pituitary disease.
Progressively increased patterns of subclinical cortisol hypersecretion in adrenal incidentalomas differently predict major metabolic and cardiovascular outcomes: a large cross-sectional study
Authors: Di Dalmazi Guido , Vicennati Valentina , Rinaldi Eleonora , Morselli-Labate Antonio Maria , Giampalma Emanuela , Mosconi Cristina , Pagotto Uberto , Pasquali Renato 
Published: January 2012

BackgroundSubclinical Cushing's syndrome (SCS) is defined as alterations in hypothalamic–pituitary–adrenal axis without classic signs/symptoms of glucocorticoid excess. Whether SCS leads to metabolic and cardiovascular diseases is still controversial.AimTo evaluate the prevalence of hypertension, type 2 diabetes (T2D), coronary heart disease (CHD), ischemic stroke, osteoporosis, and fractures, and their relationship to increasing patterns of subclinical hypercortisolism, in patients with nonsecreting adrenal adenomas (NSA) and SCS.MethodsUsing the 1 mg dexamethasone suppression test (DST), 348 patients were classified as follows: 203 were defined as NSA and 19 SCS, using the most stringent cutoff values (<50 and >138 nmol/l respectively). Patients with cortisol post-DST (50–138 nmol/l) were considered as intermediate phenotypes and classified as minor (n=71) and major (n=55) using plasma ACTH and/or urinary free cortisol as additional diagnostic tools.ResultsSCS patients showed higher prevalence of T2D, CHD, osteoporosis, and fractures with respect to NSA. Intermediate phenotypes also showed higher prevalence of CHD and T2D with respect to NSA. The prevalence of all clinical outcomes was not different between intermediate phenotype patients, which were therefore considered as a single group (IP) for multivariate logistic regression analysis: both IP and SCS-secreting patterns showed a significant association with CHD (odds ratio (OR), 4.09; 95% confidence interval (CI), 1.47–11.38 and OR, 6.10; 95% CI, 1.41–26.49 respectively), independently of other potential risk factors. SCS was also independently associated with osteoporosis (OR, 5.94; 95% CI, 1.79–19.68).ConclusionsPatterns of increasing subclinical hypercortisolism in adrenal adenomas are associated with increased prevalence of adverse metabolic and cardiovascular outcomes, independently of other potential risk factors.
Distinct effects of pioglitazone and metformin on circulating sclerostin and biochemical markers of bone turnover in men with type 2 diabetes mellitus
Authors: van Lierop A H , Hamdy N A T , van der Meer R W , Jonker J T , Lamb H J , Rijzewijk L J , Diamant M , Romijn J A , Smit J W A , Papapoulos S E 
Published: January 2012

ObjectivePatients with type 2 diabetes mellitus (T2DM) have an increased risk of fractures and thiazolidinediones (TZDs) increase this risk. TZDs stimulate the expression of sclerostin, a negative regulator of bone formation, in vitro. Abnormal sclerostin production may, therefore, be involved in the pathogenesis of increased bone fragility in patients with T2DM treated with TZDs.MethodsWe measured serum sclerostin, procollagen type 1 amino-terminal propeptide (P1NP), and carboxy-terminal cross-linking telopeptide of type I collagen (CTX) in 71 men with T2DM treated with either pioglitazone (PIO) (30 mg once daily) or metformin (MET) (1000 mg twice daily). Baseline values of sclerostin and P1NP were compared with those of 30 healthy male controls.ResultsCompared with healthy controls, patients with T2DM had significantly higher serum sclerostin levels (59.9 vs 45.2 pg/ml, P<0.001) but similar serum P1NP levels (33.6 vs 36.0 ng/ml, P=0.39). After 24 weeks of treatment, serum sclerostin levels increased by 11% in PIO-treated patients and decreased by 1.8% in MET-treated patients (P=0.018). Changes in serum sclerostin were significantly correlated with changes in serum CTX in all patients (r=0.36, P=0.002) and in PIO-treated patients (r=0.39, P=0.020), but not in MET-treated patients (r=0.17, P=0.31).ConclusionsMen with T2DM have higher serum sclerostin levels than healthy controls, and these levels further increase after treatment with PIO, which is also associated with increased serum CTX. These findings suggest that increased sclerostin production may be involved in the pathogenesis of increased skeletal fragility in patients with T2DM in general and may specifically contribute to the detrimental effect of TZDs on bone.
Molecular Alterations Between the Primary Breast Cancer and the Subsequent Locoregional/Metastatic Tumor
Authors: Macfarlane Robyn , Seal Melanie , Speers Caroline , Woods Ryan , Masoudi Hamad , Aparicio Samuel , Chia Stephen K. 
Published: January 2012

Abstract

Learning Objectives:
After completing this course, the reader will be able to: Describe the rate of discordance of predictive marker phenotype (i.e., ER/PR, HER2) between the primary and the relapsed/metastatic breast cancer lesion.Explain the impact of a change in predictive marker phenotype between the primary and relapsed/metastatic lesion on treatment options for these patients.
This article is available for continuing medical education credit at CME.TheOncologist.com

Background.
Metastatic breast cancers have historically been presumed to have the same predictive biomarkers as the initial primary tumor. We compared the expression of these biomarkers in a large paired tissue microarray (TMA) series of primary and subsequent relapsed tumors.

Methods.
Using the British Columbia Cancer Agency Breast Cancer Outcomes Unit database, patients with biopsy-proven relapses were identified and linked to a large TMA series of primary breast cancers from 1986–1992. Charts were reviewed, and tissue blocks of the metastatic cancer were collected to create a separate TMA. Immunohistochemical assessment with the same antibodies and conditions was performed for estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor (HER)-2 on both the primary and relapsed tumors.

Results.
One hundred sixty cases were received that had tumor adequate for analyses. Of these, 71.9% had no changes in either the ER or PR status or HER-2 status. Of the 45 (28.1%; 95% confidence interval [CI], 21.2%–35.1%) tumors that did have changes in receptor status, 7.5% were in-breast recurrences or new breast primaries, 4.4% had changes in PR status only and were therefore deemed clinically irrelevant, and 19.4% (95% CI, 13.3%–25.5%) had changes in either the ER or HER-2 status from regional or distant relapses. Five percent of tumors had a receptor status change going from ER+ or PR+ to ER− or PR−; 9.4% went from ER− or PR− to ER+ or PR+. With regard to HER-2 status, 3.8% of tumors went from positive to negative and 1.3% went from negative to positive. For all discordant cases, biopsies of the relapsed lesion were obtained prior to initiation of first-line treatment for metastatic disease. In the primary tumors that were ER+, time to relapse was significantly shorter in the discordant relapsed cases than in the concordant ones (p = .0002). Changes in loss or gain of either biomarker were seen across the discordant cases.

Conclusions.
A significant proportion of relapsed tumors had changes in either ER or HER-2 status, which would dramatically alter treatment recommendations and clinical behavior. This study suggests that biopsies of relapsed and metastatic breast cancers should be performed routinely in clinical practice.
Genomewide Pharmacogenetics of Bisphosphonate-Induced Osteonecrosis of the Jaw: The Role of RBMS3
Authors: Nicoletti Paola , Cartsos Vassiliki M. , Palaska Penelope K. , Shen Yufeng , Floratos Aris , Zavras Athanasios I. 
Published: January 2012

Abstract

Learning Objectives
After completing this course, the reader will be able to: Explain the association between bisphosphonates and osteonecrosis of the jaw.Describe the role of RBMS3 in the risk of BRONJ development.
This article is available for continuing medical education credit at CME.TheOncologist.com

Bisphosphonate-related osteonecrosis of the jaw (BRONJ) is a serious adverse drug reaction. We conducted a genomewide association study to search for genetic variants with a large effect size that increase the risk for BRONJ.

Methods.
We ascertained BRONJ cases according to the diagnostic criteria of the American Association of Oral and Maxillofacial Surgeons. We genotyped cases and a set of treatment-matched controls using Illumina Human Omni Express 12v1 chip (733,202 markers). To maximize the power of the study, we expanded the initial control set by including population and treatment-tolerant controls from publicly available sources. Imputation at the whole-genome level was performed to increase the number of single nucleotide polymorphisms (SNPs) investigated. Tests of association were carried out by logistic regression, adjusting for population structure. We also examined a list of candidate genes comprising genes potentially involved in the pathogenesis of BRONJ and genes related to drug absorption, distribution, metabolism, and excretion.

Results.
Based on principal component analysis, we initially analyzed 30 white cases and 17 treatment-tolerant controls. We subsequently expanded the control set to include 60 genetically matched controls per case. Association testing identified a significant marker in the RBMS3 gene, rs17024608 (p-value &lt; 7 × 10−8); individuals positive for the SNP were 5.8× more likely to develop BRONJ (odds ratio, 5.8; 95% confidence interval, 3.1–11.1). Candidate gene analysis further identified SNPs in IGFBP7 and ABCC4 as potentially implicated in BRONJ risk.

Conclusion.
Our findings suggest that genetic susceptibility plays a role in the pathophysiology of BRONJ, with RBMS3 having a significant effect in the risk.
Phase II Trial of Simple Oral Therapy with Capecitabine and Cyclophosphamide in Patients with Metastatic Breast Cancer: SWOG S0430
Authors: Schott Anne F. , Barlow William E. , Albain Kathy S. , Chew Helen K. , Wade James L. , Lanier Keith S. , Lew Danika L. , Hayes Daniel F. , Gralow Julie R. , Livingston Robert B. , Hortobagyi Gabriel N. 
Published: January 2012

Abstract

Learning Objectives
After completing this course, the reader will be able to: Compare outcomes in patients treated with capecitabine plus CPA with those of capecitabine monotherapy and combination therapy with bevacizumab, sorafenib, or ixabepilone.Identify patients for whom single-agent capecitabine is recommended.
This article is available for continuing medical education credit at CME.TheOncologist.com

Background.
Interest in oral agents for the treatment of metastatic breast cancer (MBC) has increased because many patients prefer oral to i.v. regimens. We evaluated a simple oral combination of capecitabine with cyclophosphamide (CPA) for MBC.

Methods.
The trial was designed to determine whether or not combination therapy would achieve a 42% response rate (RR) using the Response Evaluation Criteria in Solid Tumors (RECIST) in MBC. Patients with two or fewer prior chemotherapy regimens for MBC were eligible. Those with estrogen receptor–positive MBC had to have progressed on endocrine therapy. Patients had measurable disease or elevated mucin (MUC)-1 antigen and received CPA, 100 mg daily on days 1–14, and capecitabine, 1,500 mg twice daily on days 8–21, in 21-day cycles.

Results.
In 96 eligible patients, the median progression-free survival (PFS) interval was 5.9 months (95% confidence interval [CI], 3.7–8.0 months) and median overall survival (OS) time was 18.8 months (95% CI, 13.1–22.0 months). The RR was 36% (95% CI, 26%–48%) in 80 patients with measurable disease. The MUC-1 antigen RR was 33% (95% CI, 20%–48%), occurring in 15 of 46 patients with elevated MUC-1 antigen. Toxicity was mild, with no treatment-related deaths.

Conclusions.
PFS, OS, and RR outcomes with capecitabine plus CPA compare favorably with those of capecitabine monotherapy and combination therapy with bevacizumab, sorafenib, or ixabepilone. The addition of these other agents to capecitabine does not improve OS time in MBC patients, and this single-arm study does not suggest that the addition of CPA to capecitabine has this potential in an unselected MBC population. When OS prolongation is the goal, clinicians should choose single-agent capecitabine.
Should the Denosumab Metastasis Prevention Trial Change Practice for Men with Nonmetastatic Prostate Cancer?
Authors: Saylor Philip J. , Michaelson M. Dror 
Published: January 2012

Abstract

Presentation of the Case
A 68-year-old man presents for management of prostate-specific antigen (PSA)-recurrent prostate cancer. His PSA level had become undetectable after prostatectomy for a high-risk localized tumor but began to rise 8 months later. This later led to the initiation of androgen deprivation therapy (ADT), which he has received for the last 3.5 years. After initially falling in response to ADT, his PSA level again trended steadily upward and is now 13.2. Restaging with an abdominal and pelvic computed tomography scan and a bone scan reveals no evidence of metastases. Is this man likely to benefit from denosumab?
Bone is the most common site of metastasis for advanced prostate cancer. Bone metastases can cause considerable morbidity in the form of pain, pathologic fractures, and even spinal cord compression. Two bone-targeted therapies (zoledronic acid and denosumab) have been shown to reduce the risk for skeletal events (SREs) among men with bone metastases and a rising PSA level despite a testosterone level &lt;50 ng/dL (castration-resistant prostate cancer [CRPC]). Until recently, no therapy had been shown to reduce the risk for developing bone metastases for the first time. Denosumab 147 was a randomized, placebo-controlled, phase III trial that enrolled 1,432 men with CRPC, no bone metastases, and at least one feature consistent with a high risk for the development of bone metastases (PSA ≥8 ng/mL or PSA doubling time ≤10 months). Participants were treated every 4 weeks with s.c. denosumab (120 mg) or placebo.
The trial was positive because denosumab led to a 4.2-month significantly longer bone-metastasis-free survival time relative to placebo (median, 29.5 months versus 25.2 months; hazard ratio [HR], 0.85; 95% confidence interval [CI], 0.73–0.98; p = .028) [1]. The time to first bone metastasis and risk for symptomatic bone metastasis were also significantly better with denosumab treatment. Dror Michaelson and Philip Saylor discuss the potential implications of this trial.