The management of stage I--II Hodgkin's disease with irradiation alone or combined modality therapy: the Stanford experience

At Stanford University, between 1968 and 1978, 230 patients with pathologic stage I--II Hodgkin's disease were treated on prospective clinical trials with either irradiation alone or irradiation followed by 6 cycles of adjuvant combination chemotherapy. The actuarial survival at 10 yr was 84% for patients in either treatment group. Freedom from relapse at 10 yr was 77% among patients treated with irradiation alone and 84% after treatment with combined modality therapy [p(Gehan) = 0.09]. Freedom from second relapse at 10 yr was 89% and 94%, respectively [p(Gehan) = 0.56]. Several prognostic factors were evaluated in order to identify patients at high risk for relapse or with poor ultimate survival after initial treatment with irradiation alone. Systemic symptoms, histologic subtype, age, and limited extranodal involvement (E-lesions) did not affect the prognosis of patients and failed to identify patients whose survival could be improved by the routine use of combined modality therapy. Patients with large mediastinal masses (mediastinal mass ratio greater than or equal to 1/3) had a significantly poorer freedom from relapse when treated with irradiation alone than when treated initially with combined modality therapy [45% versus 81% at 10 yr, p(Gehan) = 0.03). The 10-yr survival of these patients, however, was not significantly different (84% versus 74%). The implications of these observations on the management of patient with early stage Hodgkin's disease are discussed.     

The effect of age on knowledge of HIV/AIDS and risk related behaviours among army personnel

Background

HIV/AIDS has been described as the fourth largest cause of death globally and leading cause of death in Africa^. HIV/AIDS has been a devastating inferno for nearly 30 years, and has particularly impacted countries in sub-Saharan Africa^. In most African countries, it has been reported that the HIV infection amongst the military has been shown to be about 2 to 5 times higher than their civilian counterparts.

Objective

To address the knowledge level of HIV/AIDS and risk-related behaviours in military personnel, a well-described high risk groups for HIV/AIDS.

Methods

A cross-sectional study among army personnel in 82 Division Nigerian Army Headquarters Enugu, which has a population of about 1777. A random sampling in all the departments of 82 Division Nigerian Army Headquarters was done using the ballot method to select the respondents. Approval for the study was obtained from the General Officer in Command (GOC) of the 82 Division Nigerian Army Headquarters Enugu.

Results

There were no significant differences between the risk related behavior variables when comparisons were made between those under 30 years, and those 30 years and above. Furthermore, more respondents under 30 years (48.0%) did not seek medical treatment when infected with another STI before having sex again as against 45% of those above 30 years. Most of the respondents (9.1%) under the age of 30 years believed that HIV/AIDS could be contracted through mosquito bites as against 2.8% of those above 30 years.

Conclusion

The knowledge level of HIV/AIDS among the army personnel was high, though misconceptions about transmission modes like getting HIV through the bites of mosquitoes and casual body contacts were noted, especially among those under 30 years of age.     

Tyrosine kinase activation in breast carcinoma with correlation to HER-2/neu gene amplification and receptor overexpression.

The HER-2/neu oncogene encodes a transmembrane receptor with intrinsic tyrosine kinase activity. A pilot study was performed to investigate downstream effects of HER-2/neu (or related growth factor receptor) activation by identifying phosphorylated tyrosine. Fifty-four breast carcinomas were evaluated for HER-2/neu overexpression by the HercepTest (Dako, Carpinteria, CA) and the monoclonal CB11 antibody (Ventana, Tucson, AZ). Phosphotyrosine (an indication of tyrosine kinase activity) was detected by an antiphosphotyrosine mouse monoclonal antibody (Upstate Biotechnology, Lake Placid, NY). The gene amplification status was evaluated in 50 of the 54 cases by fluorescence in situ hybridization (FISH) using the Ventana gene probe. The HER-2/neu oncogene amplification was detected in 28% (14 of 50) of cases. Of the 14 cases showing oncogene amplification, tyrosine kinase activity was detected in 9 (64.2%) cases. There was moderate agreement between HER-2/neu gene amplification and tyrosine kinase activity (kappa = 0.43). Immunohistochemical staining of 3+ (with both HercepTest and CB11) showed better agreement with HER-2/neu oncogene amplification and increased tyrosine kinase activity than 2+ immunohistochemical staining. Overall, oncogene amplification and overexpression correlated with increased tyrosine kinase activity, supporting the mechanism of tyrosine kinase activation by HER-2/neu amplification and overexpression. However, 7 cases showing increased tyrosine kinase activity did not show gene amplification or 3+ receptor expression (by either HercepTest or CB11), raising the possibility of other growth factor receptors operating via the tyrosine kinase pathway. There was no apparent correlation between tyrosine kinase activity and hormone receptor status (estrogen or progesterone). Increased tyrosine kinase activity is more commonly associated with higher-grade tumors and thus may correlate with aggressive biologic behavior in breast carcinoma. The results of this pilot study suggest that a larger-scale investigation into downstream activation of tyrosine kinase and correlation to clinical outcome or response to Herceptin therapy may identify subsets of patients whose clinical response or outcome may be predicted by tyrosine kinase activation.     

受体介导的凝血酶对成骨细胞增殖及分化的作用

目的 通过凝血酶对成骨细胞的增殖及分化作用的研究来探讨受体介导的凝血酶的功能.方法 原代成骨细胞分别取自于蛋白酶激活受体(protease-activated receptor,PAR)-1敲除鼠和野生对照鼠的头颅骨.并利用凝血酶,人工合成的PAR-1或PAR-4特异性激活短肽对细胞进行处理,通过对5.溴-2-脱氧尿嘧啶的嵌入及细胞碱性磷酸酶活性的测定探讨PAR-1或PAR-4激活对细胞增殖和分化的影响.结果 在野生鼠成骨细胞,凝血酶及PAR-1激活肽均能促进的细胞增殖和降低碱性磷酸酶的活性,但PAR-4激活肽却无这些作用.然而在PAR-1 敲除鼠的成骨细胞无论是凝血酶还是PAR-4激活肽均不能改变细胞的增殖及碱性磷酸酶的活性.结论 本研究结果 表明凝血酶促进成骨细胞增殖及抑制其分化是通过PAR-1介导的.其他凝血酶受体并不具有此作用.     

Duplex ultrasound analysis of operated carotid arteries in baboons

Duplex ultrasound analysis, which combines high-resolution B-mode imaging and Doppler spectral flow analysis, was used to examine 3 to 4 mm in diameter normal [n = 24] and mechanically manipulated baboon carotid arteries (endarterectomies [n = 10], construction of interposition vascular grafts [n = 10], and placement of endovascular stents within interposition grafts [n = 4]). Patency or occlusion was definitively confirmed by direct visualization and palpation during surgical exploration at defined intervals or by postmortem histologic examination. Duplex examination accurately demonstrated postoperative hemodynamic changes and with only one exception correctly identified patency and occlusion. We conclude that this technique is superior to more invasive methods for verification of the outcome of operations on small arteries in experimental animals.     

Inhibition of 125I-labeled ristocetin binding to Micrococcus luteus cells by the peptides related to bacterial cell wall mucopeptide precursors: quantitative structure-activity relationships

Quantitative structure-activity relationships (QSAR) of N-Ac amino acids, N-Ac dipeptides, and N-Ac tripeptides in inhibition of 125I-labeled ristocetin binding to Micrococcus luteus cell wall have been developed to probe the details of the binding between ristocetin and N-acetylated peptides. The correlation equations indicate that (1) the binding is stronger for peptides in which the side chain of the C-terminal amino acid has a large molar refractivity (MR) value, (2) the binding is weaker for peptides with polar than for those with nonpolar C-terminal side chains, (3) the N-terminal amino acid in N-Ac dipeptides contributes 12 times that of the C-terminal amino acid to binding affinity, and (4) the interactions between ristocetin and the N-terminal amino acid of N-acetyl tripeptides appear to be much weaker than those with the first two amino acids.