The role of paraaortic node irradiation in the treatment of cancer of the cervix

One hundred and twenty-seven patients with previously untreated carcinoma of the uterine cervix underwent pretreatment laparotomy between 1971 and 1980. Thirty-one were found to have paraaortic metastasis. Twenty-seven patients received paraaortic node external supervoltage radiation to the entire paraaortic chain, 4400 cGy, over 4 1/2 weeks, with 600-800 cGy, boost over 1 week, limited to the area of metastasis as marked at laparotomy. Twenty-nine percent (8/27) of the patients with paraaortic node metastases who were irradiated have survived 5 years or more. These patients have FIGO stages IB, IIA, or IIB; all have epidermoid carcinoma. Three of five patients (60%) with microscopic metastasis and five of twenty-two patients (23%) with gross metastasis in the paraaortic lymph nodes are long-term survivors. None of our long-term survivors have suffered late complications. There have been no fatalities from treatment related complications. We present a radiation technique for paraaortic radiation in these patients, and discuss the indications for paraaortic node radiation in cancer of the cervix.     

Systematic classification of alleles of the glycophorin A (MN blood group) gene

Ten alleles (five M and five N alleles) of the MN blood group system with normal antigenicity were found by sequencing the glycophorin A (GPA) gene. This study demonstrates the systematic classification of these alleles to major or minor variations of the standard alleles. GPA-specific fragments ranging from 150 to 3.8 kb in length were amplified from the templates, and exons 1–7 and introns 1–6 were sequenced. The data were analyzed phylogenetically to classify these alleles into major groups or clusters. The ten alleles were grouped into four major clusters M10X (M101–M103), M20X (M201 and M202), N10X (N101–N104) and N20X (N201), where X represents a digit indicating minor variations. This grouping was supported by phylogenetic analysis. The cluster system of GPA alleles is highly informative for genetic screening.     

Optimal diabetes management during medical weight loss for cardiovascular risk reduction

Obesity has long been recognized as a significant risk factor for type 2 diabetes. Both obesity and type 2 diabetes are associated with an increase in cardiovascular risk. As cardiovascular disease continues to be the number one killer in the USA and western adult populations, the rise in prevalence of obesity and type 2 diabetes is alarming. This is especially disturbing in the tripling of overweight children and adolescents, accompanied by the increase in prevalence of pediatric type 2 diabetes. Optimal strategies for long-term diabetes management aim at effectively controlling, reducing and ultimately preventing obesity. This review explores the clinical recommendations in place, new clinical investigations, diet therapy, medical nutrition therapy, meal replacements, behavior therapy, exercise therapy, pharmacotherapy and surgical therapy as strategies to achieve weight-loss success in diabetic patients and ultimately reduce cardiovascular disease.     

Seroma is an expected consequence and not a complication of MammoSite brachytherapy

Seroma has long been listed as a complication of MammoSite brachytherapy. Palpable abnormalities are clinically apparent months after treatment and a vast majority of patients demonstrate seroma formation in radiologic studies. We embarked on this study to evaluate the actual sonographic incidence and eventual sonographic resolution, possible contributing factors, cosmesis, pain, and local control associated with seroma formation after MammoSite partial breast irradiation (PBI). We investigated 160 patients who underwent MammoSite PBI from 2002 to 2006 of whom 100 patients had serial sonographic information. Clinical and tumor variables, infection, pain, and cosmesis were investigated. Dosimetric data including volume of balloon, dose at balloon surface, and at skin were analyzed. After a median follow-up of 36 months, the incidence of sonographically confirmed post-radiation seroma was 78% within the first 1 year following radiation and steadily decreased with time. The average size of a seroma cavity was 2.3 cm (range 0.6-6 cm) with a decline to an average of 1.4 cm after 1 year, with complete resolution in 65% of patients at 2 years. No statistically significant correlation was found between patient characteristics, tumor variables, and volumetric or dosimetric data for seroma formation. Excellent/good cosmetic scores were achieved in 94% of women with and 92% without seroma. Local control was equivalent between patients with and without seroma. Consecutive sonographic imaging reveals a high rate of seroma formation after MammoSite PBI, with resolution in 65% of patients by 2 years without intervention. Seroma formation does not prevent an excellent cosmetic result or alter local control.     

A hypervariable STR polymorphism in the complement factor I (CFI) gene: Asian-specific alleles

In this study, a short tandem repeat (STR) polymorphism in intron 7 of the human complement factor I (CFI) gene was studied in 637 DNA samples obtained from African, German, Thai, and Japanese populations and German and Japanese families. A total of 41 alleles were observed and classified into two groups, L and H, based on size differences. Group H, which consisted of 16 alleles, was observed only in Thai and Japanese populations at frequencies of 0.162 and 0.116, respectively, and was strongly associated with c.1217A in exon 11 (CFI*Ah). The heterozygosity values ranged from 0.89 in German to 0.93 in Thai populations. This STR would be a useful supplementary marker for forensic individualization.     

Abnormal interactions of calsequestrin with the ryanodine receptor calcium release channel complex linked to exercise-induced sudden cardiac death

Catecholaminergic polymorphic ventricular tachycardia (CPVT) is a familial arrhythmogenic disorder associated with mutations in the cardiac ryanodine receptor (RyR2) and cardiac calsequestrin (CASQ2) genes. Previous in vitro studies suggested that RyR2 and CASQ2 interact as parts of a multimolecular Ca(2+)-signaling complex; however, direct evidence for such interactions and their potential significance to myocardial function remain to be determined. We identified a novel CASQ2 mutation in a young female with a structurally normal heart and unexplained syncopal episodes. This mutation results in the nonconservative substitution of glutamine for arginine at amino acid 33 of CASQ2 (R33Q). Adenoviral-mediated expression of CASQ2(R33Q) in adult rat myocytes led to an increase in excitation-contraction coupling gain and to more frequent occurrences of spontaneous propagating (Ca2+ waves) and local Ca2+ signals (sparks) with respect to control cells expressing wild-type CASQ2 (CASQ2WT). As revealed by a Ca2+ indicator entrapped inside the sarcoplasmic reticulum (SR) of permeabilized myocytes, the increased occurrence of spontaneous Ca2+ sparks and waves was associated with a dramatic decrease in intra-SR [Ca2+]. Recombinant CASQ2WT and CASQ2R33Q exhibited similar Ca(2+)-binding capacities in vitro; however, the mutant protein lacked the ability of its WT counterpart to inhibit RyR2 activity at low luminal [Ca2+] in planar lipid bilayers. We conclude that the R33Q mutation disrupts interactions of CASQ2 with the RyR2 channel complex and impairs regulation of RyR2 by luminal Ca2+. These results show that intracellular Ca2+ cycling in normal heart relies on an intricate interplay of CASQ2 with the proteins of the RyR2 channel complex and that disruption of these interactions can lead to cardiac arrhythmia.