Yellow nail syndrome in a medical clinic

Yellow nail syndrome is a very rare clinical entity usually diagnosed from a combination of yellow dystrophic nails, lymphoedema and respiratory diseases. The aetiology is not known though dysfunctional hypoplastic lymphatics is speculated. Most cases occur sporadically but few cases may be associated with systemic diseases or may be inherited. This report documents another case in a 56-year old Caribbean female who presented with a six-year history of recurrent respiratory symptoms and later yellow dystrophic nails and lymphoedema. She responded well to vitamin E and oral fluconazole. We also did a short literature review of yellow nail syndrome.     

Acute fulminant myocarditis and the 2009 pandemic influenza A virus (H1N1)

The 2009 Pandemic Novel Influenza A [HIN1] resulted in mild disease mostly but severe cases and death were associated with pneumonia, respiratory failure and multi-organ failure. We present a case of severe disease with acute heart failure and arrhythmia due to fulminant myocarditis in a 50- year old obese man with diabetes mellitus.     

In utero exposure to tributyltin chloride differentially alters male and female fetal gonad morphology and gene expression profiles in the Sprague-Dawley rat

Tributyltin (TBT) is an environmental contaminant commonly used in anti-fouling agents for boats, as well as a by-product from several industrial processes. It has been shown to accumulate in organisms living in areas with heavy maritime traffic thereby entering the food chain. Here, we determined the consequences of in utero exposure to TBT on the developing fetal gonads in the Sprague-Dawley rat. Timed pregnant rats were gavaged either with vehicle or TBT (0.25, 2.5, 10 or 20 mg/kg) from days 0 to 19 or 8 to 19 of gestation. On gestational day 20, dams were sacrificed; fetal testes and ovaries were processed for light (LM) or electron microscopic (EM) evaluation and RNA was prepared for gene expression profiling. At the highest doses of TBT the number of Sertoli cells and gonocytes was reduced, there were large intracellular spaces between Sertoli cells and gonocytes and there was an increased abundance of lipid droplets in the Sertoli cells; EM studies revealed abnormally dilated endoplasmic reticulum in Sertoli cells and gonocytes. In the intertubular region between adjacent interstitial cells, immunostaining for the gap junctional protein connexin 43 was strong in controls, whereas it was reduced or completely absent in treated rats. In the ovaries, TBT (20 mg/kg, days 0-19; 10 mg/kg, days 8-19) reduced the number of germ cells by 44% and 46%, respectively. On examining gene expression profiles in the testis, 40 genes out of 1176 tested were upregulated more than two-fold over control. While no genes were upregulated in the TBT exposed fetal ovary, eight genes were downregulated. In conclusion, in utero exposure to TBT resulted in gender-specific alterations in gonadal development and gene expression profiles suggesting that there may be different adaptive changes to toxicity in developing male and female rats.     

Prognostic significance of 18 F-fluorodeoxyglucose - positron emission tomography after treatment in patients with limited stage small cell lung cancer

Objective: Small cell lung cancer (SCLC) represents 15% to 25% of lung cancers. Despite favorable initial treatment response rates, recurrence is likely and long-term prognosis dismal. Accurate measurement of therapy response is critical to determine which patients might be spared additional treatment, and potential side effects. ¹⁸F-fluorodeoxyglucose positron emission tomography (PET) may help distinguish necrotic or fibrous tissue from residual cancer, thus informing further treatment and prognosis.Design/Setting/Participants and Methods: Retrospective chart review study of limited stage SCLC patients with PET scanning within 4 months post-chemotherapy at Marshfield Clinic, Marshfield, Wisconsin. Diagnosis of SCLC occurred from December 1, 2001 through December 31, 2007.Results: Twenty-two patients (~7%) had post-treatment PET: 11 positive, 11 negative. Median duration from last chemotherapy to PET was 36 days (range, 3 to 125 days). Median follow-up for all patients was 34.4 months (range, 6.8 to 65.9 months). Estimated median progression-free survival for all patients was 8.1 months (95% confidence intervals [CI], 4.3 to 11.9 months), 10.5 months for PET negative (95% CI, 8.1 to >57.8 months) and 4.3 months for PET positive patients (95% CI, 2.8 to >7.2 months) (P<0.007, log-rank test). Median survival for all patients was 19.2 months (95% CI, 10.3 to >65.8 months). Estimated median survival for PET negative patients was longer than PET positive (29.2 versus 10.3 months, P=0.10).Conclusion: Post-treatment PET, prognostically significant, may be underutilized.     

Clustering of venous thrombosis events at the start of tamoxifen therapy in breast cancer: a population-based experience

Introduction

The epidemiology of tamoxifen and venous thromboembolism (VTE) is not well understood, and most data on tamoxifen toxicity are from adjuvant clinical trials. This study examined the relationship between the duration of tamoxifen use in female patients with breast cancer and the risk of VTE in a large population-based setting.

Materials and Methods

Retrospective electronic data extraction on tamoxifen utilization was undertaken among a cohort of 3572 women with breast cancer seen at Marshfield Clinic between January 1, 1994 and June 31, 2009. Observational follow-up extended until February, 2010.

Results

On initial exposure to tamoxifen, women had a clustering of VTE events. Cox proportional hazards regression, adjusting for multiple clinically-important covariates including age, body mass index, cancer stage, and concurrent diabetes, demonstrated that as use of tamoxifen continued in those without earlier VTE events, risk of subsequent VTE gradually increased, albeit at a lower rate (hazard ratio per year of tamoxifen duration = 1.225, P < 0.0001).

Conclusions

In our study population, initiating tamoxifen coincided with an initial clustering of VTE events, with risks due specifically to tamoxifen, increasing during continued exposure. Evidence suggested that the VTE clustering occurred in high risk individuals at initiation of tamoxifen therapy. Careful selection of patients for whom tamoxifen therapy is appropriate based on susceptibility to VTE is thus required prior to initiation of therapy.     

High-sensitivity C-reactive protein (hs-CRP) as a biomarker for trastuzumab-induced cardiotoxicity in HER2-positive early-stage breast cancer: a pilot study

Monitoring of left ventricular ejection fraction (LVEF) is the current standard for detection of trastuzumab-induced cardiotoxicity; however, time-to-diagnosis and cost of assessment are suboptimal in women with early-stage breast cancer. We assessed the utility of B-type natriuretic peptide (BNP), high-sensitivity C-reactive protein (hs-CRP), and cardiac troponin I (cTnI) as serum biomarkers for early detection of trastuzumab-induced cardiotoxicity. Fifty-four women with human epidermal growth factor receptor 2 (HER2)-positive early-stage breast cancer were prospectively enrolled, and the relationship between elevated serum BNP, hs-CRP, and cTnI levels and clinically significant decreases in LVEF was examined. LVEF was monitored at 3-4 month intervals during trastuzumab treatment. Laboratory testing for candidate biomarkers was repeated every 3 weeks with each cycle of trastuzumab. Trastuzumab-induced cardiotoxicity was defined as a decrease in LVEF of ≥15% or to a value below 50%. A clinically significant decrease in LVEF was observed in 28.6% of women. Abnormal hs-CRP (≥3 mg/L) predicted decreased LVEF with a sensitivity of 92.9% (95% CI 66.1-99.8) and specificity of 45.7% (95% CI 28.8-63.4), and subjects with normal hs-CRP levels (<3 mg/L) have 94.1% negative predictive 94.1% (95% CI 70.3-99.9) suggesting that normal hs-CRP levels may be associated with low future risk for decreased LVEF; however, no association with BNP or cTnI was observed. A false positive would have a relatively low associated cost in breast cancer patients undergoing adjuvant trastuzumab therapy and would indicate continuation of routine observation during treatment through traditional means. The maximum hs-CRP value was observed a median of 78 days prior to detection of cardiotoxicity by decreased LVEF, and those with normal levels were at lower risk for cardiotoxicity. Regular monitoring of hs-CRP holds promise as a biomarker for identifying women with early-stage breast cancer at low risk for asymptomatic trastuzumab-induced cardiotoxicity. To our knowledge, this is the first study documenting the utility of a less expensive, reproducible, easily obtainable biomarker with rapid results for evaluating cardiotoxicity related to trastuzumab therapy.