Limb sparing surgery for pediatric musculoskeletal tumors

There has been an unprecedented improvement in the survival outcome of children with extremity sarcoma as well as a corresponding increase in percentage of limb-sparing surgeries being performed over the past many decades. This has been, in part, due to the improved imaging modalities, newer surgical techniques, and advences in neoadjuvant chemotherapy. Limb-sparing surgery for primary bone and soft-tissue malignancies in children is becoming an acceptable option of surgical treatment in most cases today. This article outlines the demographics, classification, clinical presentation, imaging, and molecular genetics of pediatric mosculoskeletal tumors and discusses the current treatment principles with emphasis on the state-of-the-art surgical management and limb-sparing techniques for children with extremity sarcoma.     

Alpha 1A-adrenergic receptor polymorphism and vascular response

OBJECTIVE: The alpha(1A)-adrenergic receptor is highly expressed in human vasculature including resistance arteries and veins, and its stimulation is primarily responsible for adrenergically mediated smooth muscle contraction. Variability in sensitivity to phenylephrine, an alpha(1A) adrenergic agonist, has a large genetic component. We examined the hypothesis that a common polymorphism of alpha(1A)-adrenergic receptor (Arg347Cys) affects in vivo response. METHODS: We measured vascular sensitivity to phenylephrine using the dorsal hand vein linear variable differential transformer technique and determined alpha(1A)-adrenergic receptor genotype in 74 healthy, nonsmoking adults (28 Arg/Arg, 30 Arg/Cys, and 16 Cys/Cys). RESULTS: Sensitivity to phenylephrine, expressed as the dose of phenylephrine resulting in 50% venoconstriction (Phe(50)), was not significantly different in subjects with the 3 alpha(1A) adrenergic receptor genotypes: Phe(50) geometric mean (95% confidence interval) was 513 ng/min (287-918 ng/min) for Arg/Arg, 431 ng/min (274-680 ng/min) for Arg/Cys, and 471 ng/min (197-1124 ng/min) for Cys/Cys (P =.90). CONCLUSION: We conclude that the Arg347Cys receptor polymorphism does not alter agonist-mediated venoconstriction in vivo.     

Magnitude and impact of treatment delays on weeknights and weekends in patients undergoing primary angioplasty for acute myocardial infarction (the cadillac trial)

In 2,082 patients in the CADILLAC trial, the outcomes of patients presenting during peak hours were compared with those presenting during peak hours (Monday to Friday 8a.m. to 8 p.m., n = 1,047, 51%) were compared with those of patients presenting during off-peak hours (weeknights from 8 p.m. to 8 a.m. and weekends, n = 989, 49%). Although treatment times to percutaneous coronary intervention (PCI) were delayed approximately 21 minutes, in patients with acute myocardial infarctions occurring on weeknights and weekends, this modest delay did not adversely affect procedural success, myocardial recovery, or survival after PCI.     

Cyclin-dependent kinase 5 increases perikaryal neurofilament phosphorylation and inhibits neurofilament axonal transport in response to oxidative stress

Cyclin-dependent kinase 5 (cdk5) phosphorylates the high molecular weight neurofilament (NF) protein. Overexpression of cdk5 inhibits NF axonal transport and induces perikaryal accumulation of disordered phospho-NF cables. Experimental and clinical motor neuron disease is characterized by oxidative stress, increased cdk5 activity, and accumulation of phospho-NFs within perikarya or proximal axons. Because oxidative stress increases cdk5 activity in experimental motor neuron disease, we examined whether oxidative stress induced cdk5-mediated NF phosphorylation. Treatment of cultured neuronal cells with hydrogen peroxide inhibited axonal transport of green fluorescent protein-tagged NF subunits and induced perikaryal accumulation of NF phosphoepitopes normally confined to axons. These effects were prevented by treatment with the cdk5 inhibitor roscovitine or transfection with a construct expressing the endogenous cdk5 inhibitor peptide. These findings indicate that oxidative stress can compromise NF dynamics via hyperactivation of cdk5 and suggest that antioxidants may alleviate multiple aspects of neuropathology in motor neuron disease.     

Effect of oestrogen replacement therapy on serum lipid profile

BACKGROUND: Oestrogen deficiency in postmenopausal women alters the lipid metabolism unfavourably. AIM: To evaluate the effects of oral and transdermal oestrogen replacement therapy (ORT) on serum lipid profile. METHODS: Ninety hysterectomised and oophorectomised women were randomised into three equal groups (no hormones; oral conjugated equine oestrogen, 0.625 mg/day; transdermal oestradiol patches, 50 microg/day). Serum concentrations of total cholesterol, high-density lipoprotein (HDL) cholesterol, low-density lipoprotein (LDL) cholesterol and triglycerides were determined at the baseline and after 3 and 6 months of therapy. Student's t-test was used for statistical evaluation. RESULTS: Most of the hysterectomised women had abnormal serum lipid profile, especially HDL cholesterol levels (less than 40 mg/dL in 87%). A significant decline in the levels of serum cholesterol (total) as well as LDL and a significant increase in HDL cholesterol levels were observed following ORT by both modes, the response being comparatively rapid with oral route. After 3 and 6 months, the number of cases with HDL cholesterol levels above 40 mg/dL increased from initial 13 to 63% and 87% (oral) and 30 and 60% (transdermal), respectively. Serum triglyceride levels declined significantly with transdermal therapy but increased with oral ORT. CONCLUSIONS: Oestrogen replacement therapy either via oral or transdermal route has a beneficial effect on serum lipid profile of menopausal women. Whereas the oral route is more effective in increasing HDL cholesterol levels, the transdermal route is better for reducing the serum triglyceride level; hence, the latter should be the route of choice in women with high serum triglyceride levels.     

Pelviureteric junction obstruction: how much is the extent of the upper ureter with defective innervation needing resection?

Background/Purpose: It is well realized that Anderson-Hyne’s pyeloplasty fails to improve the drainage pattern and renal functional parameters in a few cases of hydronephrosis because of pelviureteric junction (PUJ) obstruction. The purpose of this study is to delineate the lower extent of the abnormally innervated pelviureteric junction by S-100 immunohistochemistry, which requires surgical removal.Methods: Thirty pelviureteric junction (PUJ) specimens were analyzed by histology and by S-100 immunohistochemistry after serial sectioning of the resected ureter and compared with the variables age, calyceal separation, parenchymal thickness, differential renal function, glomerular filtration rate (GFR), and the measured constricted ureteral segment on gross examination.Results: No significant correlation was noted (P > .05) when the histology was analyzed to find any association with any of the variables studied. The length of the visible constricted segment ranged from 2 mm to 15 mm (mean, 5.37 mm). The abnormally innervated segment was much longer than the length of the visible constricted segment in 24 and of the same length in 5 specimens. However, in 1 case, the abnormal innervation segment was shorter than the macroscopic constriction by 3 mm. The maximum difference in length between the visible constriction and the lower limit of defective innervation was 8 mm.Conclusions: The abnormally innervated ureteral segment below the PUJ in hydronephrosis is longer than the visible constricted segment at the time of surgery, and the ureter should be excised at least 8 mm or more beyond the visible lower limit of the constricted segment in cases of Anderson-Hyne’s pyeloplasty.     

Synthetic and antibacterial studies on some new furanopeptides

A series of new furanopeptides (3) are prepared by the coupling of arylsubstituted furoic acids (1) with amino acid methyl esters, di and tetra-peptide methyl esters using dicyclohexyl carbodiimide (DCC) as coupling agent. Some of the newly synthesized compounds are characterized on the basis of IR, 1H NMR, mass spectral data and elemental analysis. Some of the selected compounds are also tested for their antibacterial properties.