The in vivo behavior and antitumor activity of doxorubicin-loaded poly(γ-benzyl l-glutamate)-block-hyaluronan polymersomes in Ehrlich ascites tumor-bearing BalB/c mice

The in vivo efficacy of doxorubicin (DOX)-loaded poly(γ-benzyl l-glutamate)-block-hyaluronan (PBLG(23)-b-HYA(10))-based polymersomes (PolyDOX) was evaluated. Samples were efficiently labeled with technetium-99m radionuclide with good stability for in vivo studies. PolyDOX enhanced circulation time compared to free DOX. Biodistribution studies revealed selective accumulation of PolyDOX in the Ehrlich ascites tumor (EAT) as a result of passive accumulation and active targeting (CD44-mediated endocytosis) in EAT-bearing mice. Toxicity studies demonstrated PolyDOX is a safe drug carrier, and no hemolysis was observed with PolyDOX equivalent to 200 μg/mL of free DOX. PolyDOX dominantly controlled tumor growth by delaying doubling time of EATs compared to free DOX over 30 days after treatment. PolyDOX also increased life span six times more than free DOX. Hence, it is reasonable to expect that higher DOX levels attributable to PolyDOX improve the therapeutic index and reduce side effects due to site-specific drug accumulation. FROM THE CLINICAL EDITOR: In this preclinical project, doxorubicin loaded polymersomes enhanced intracellular uptake of doxorubicin in a murine model of Ehrlich Ascites Tumor (EAT) through CD44 receptor mediated endocytosis, resulting in prolonged Tumor Doubling Time and increase in life span of mice.     

Prevalence and risk factors of latent tuberculosis infection among health care workers in Malaysia

Background  

Health care workers are exposed to patients with tuberculosis and are at risk of nosocomial infection. The aim of this study was to determine the prevalence and factors associated with latent tuberculosis infection among health care workers in Malaysia and also to evaluate the agreement between Quantiferon TB Gold in tube test with Tuberculin Skin Test.     

Isoproterenol-Induced Cardiomyopathy in Rats: Influence of <Emphasis Type="Italic">Acorus calamus</Emphasis> Linn.

Acorus calamus has been used as a traditional remedy since ancient days but its cardioprotective effect is not yet well characterized. The aim of this study was to assess the effect of A. calamus rhizome extract in isoproterenol-induced cardiomyopathy in rats. Male Wistar rats were treated with normal saline (0.5 ml/kg, i.p.), isoproterenol (5 mg/kg, i.p.), A. calamus (100 and 200 mg/kg, respectively, by gavage) alone, amlodipine (9.0 mg/kg, by gavage) alone, A. calamus (100 and 200 mg/kg, respectively) + isoproterenol and amlodipine (9.0 mg/kg) + isoproterenol, single dose/day for 30 days, respectively. Isoproterenol-induced cardiomyopathy was characterized by a significant (P < 0.001) increase in heart weigh/body weight ratio, calcineurin, nitric oxide, lactate dehydrogenase, and thiobarbituric acid-reactive substance levels as well as a significant (P < 0.001) decrease in reduced glutathione, glutathione peroxidase, glutathione reductase, and glutathione-S-transferase levels. Treatment with A. calamus significantly (P < 0.05 and P < 0.01) attenuated isoproterenol-induced cardiomyopathy. No significant alteration was found in A. calamus-alone groups compared with the vehicle. Amlodipine is used as standard drug in this study. Thus, the result shows that A. calamus attenuates isoproterenol-induced cardiomyopathy. This could be due to attenuating calcineurin activity and oxidative stress.     

Axillary recurrence is low in patients with breast cancer who do not undergo completion axillary lymph node dissection for micrometastases in sentinel lymph nodes

Completion axillary lymph node dissection (CLND) is presently the standard of care after a positive sentinel lymph node biopsy (SLNB). We hypothesize that the incidence of axillary recurrence in patients who do not undergo CLND for micrometastases is low, and CLND is not necessary for locoregional control. We performed a retrospective chart review of patients with invasive breast carcinoma and micrometastases detected on SLNB. The Memorial Sloan Kettering Nomogram (MSKN) predicting the likelihood of nonsentinel lymph node (NSN) metastases was compared with the incidence of positive NSN. There were 61 patients identified with a mean follow-up of 70 months. The average tumor size was 2 cm. The median number of positive SLNs was one. Twenty-eight (46%) patients had a CLND; of these, 20 patients had one positive NSN (2 of 28 [7%]) and the mean MSKN score was 12 per cent. There were 33 (54%) patients who had SLNB alone, and their mean MSKN score was 13 per cent. Axillary recurrence in this group was 1.6 per cent. We conclude the incidence of axillary recurrence in patients with micrometastases detected by SLN biopsy who do not undergo CLND is low. The use of a predictive nomogram to estimate likelihood of metastatic disease to NSN may overestimate the actual incidence of positive NSN in patients with micrometastases.     

The impact of Improving Outcomes Guidance on the management and outcomes of patients with carcinoma of the penis

INTRODUCTION

The Improving Outcomes Guidance (IOG) for patients with carcinoma of the penis states that treatment should be provided supraregionally to populations of 4 million or greater who treat over 25 cases of penis cancer each year. This study assesses the impact of this guidance on the management and outcomes of patients with the disease in our region.

PATIENTS AND METHODS

We retrospectively compared the records of 44 patients with carcinoma of the penis treated in our institution between 1969 and 1990 with 101 patients treated between 2002 and 2006, i.e. after supraregional centralisation of the service.

RESULTS

There was no significant change in the stage or grade of the tumours. However, the results show that, in modern times, there was a significant increase in the amount of penis-preserving and nodal surgery as well as a fall in mortality. The improved survival is greatest in patients with poorly-differentiated disease who may, therefore, have benefited from aggressive nodal surgery.

CONCLUSIONS

The centralisation of surgery for carcinoma of the penis results in improved outcomes both in terms of preservation and improved survival and this supports the IOG guidance.     

Myopathy and parkinsonism in phosphoglycerate kinase deficiency

A 25‐year‐old man with exertional myoglobinuria had no evidence of hemolytic anemia, but he had severe parkinsonism that was responsive to levodopa. Phosphoglycerate kinase (PGK) activity was markedly decreased in muscle, and molecular analysis of the PGK1 gene identified the p.T378P mutation that was recently reported in a patient with isolated myopathy. This case reinforces the concept that PGK deficiency is a clinically heterogeneous disorder and raises the question of a relationship between PGK deficiency and idiopathic juvenile Parkinson disease. Muscle Nerve, 2010     

Low-grade Fibromyxoid Sarcoma of the Talus: A Case Report

Low-grade fibromyxoid sarcoma is a rare tumor, which most commonly arises from the deep soft tissues of the lower extremities in young men. Diagnosis of this tumor can be difficult because of its deceptively benign histopathologic appearance. Specifically, the lesion is characterized by alternating fibrous and myxoid areas with variable cellularity and a whorled growth pattern. Like many soft tissue tumors, low-grade fibromyxoid sarcoma is also characterized by strong immunoreactivity to the human proto-oncogene BCL-2. Cytogenetically, the lesion has also been associated with the t (7,16) (q33;p11) translocation, with the characteristic resultant FUS and CREB3L2 fusion gene. In this report, we describe the rare case of a low-grade fibromyxoid sarcoma that appeared to develop as a primary malignancy in the neck of the talus of a young man who presented with recurrent ankle pain after a previous surgery for a cystic lesion at the same site.     

Proptosis: a rare presentation of metastatic renal cell carcinoma

We present a case of a middle-aged man who was incidentally found to have right renal solid mass while investigating for his left eye proptosis. Computerised tomography (CT) scan confirmed the diagnosis of renal cell carcinoma and the tumour was successfully excised via open surgery. The histopathology examination revealed the 10x7x8 cm mass to be a clear cell type renal cell carcinoma. The rare presentation of this metastatic renal cell carcinoma, its diagnosis and management will be discussed.