p53 overexpression as a marker of poor prognosis in mantle cell lymphomas with t(11;14)(q13;q32)

The t(11;14)(q13;q32) translocation, which juxtaposes the BCL1 oncogene with the Ig heavy chain locus, has been associated with an uncommon subtype of non-Hodgkin's lymphoma (NHL) termed mantle cell lymphoma (MCL). To date, no molecular marker that serves as an indicator of tumor progression or clinical prognosis has been described for NHLs with this translocation. We examined a panel of NHLs with t(11;14) for overexpression of p53 and correlated the results with single-strand conformation polymorphism (SSCP) analysis, karyotypic features, and clinical course. NHLs with t(11;14) were identified from 30 patients. The diagnosis was MCL for 23 of 30, small lymphocytic lymphoma for 4 of 30, and diffuse large-cell lymphoma for 3 of 30 cases. The results of immunohistochemistry analysis using a monoclonal anti-p53 antibody on paraffin-embedded specimens were compared with the SSCP data, the tumor karyotypes, and clinical course of each patient. DNA sequencing of exons was performed on cases that showed conformational changes by SSCP analysis. NHLs from 5 of 23 patients with MCL were positive for p53 overexpression. Deletions of chromosome 17p were identified in 2 of 30 cases, both of which were MCLs showing p53 overexpression. Two of the five MCLs with p53 overexpression showed evidence for TP53 mutations. None of the 18 MCLs negative for p53 overexpression showed conformational changes by SSCP. For these 18 patients with MCLs that did not overexpress p53, the median survival was 63 months, compared with 12 months for the 5 patients with MCLs positive for p53 overexpression (P < .001). These results suggest that p53 overexpression in MCL with t(11;14)(q13;q32) may serve as a marker of poor prognosis.     

NS11021, a novel opener of large-conductance Ca2+-activated K+ channels,enhances erectile responses in rats

Background and purpose:

Large-conductance Ca²⁺-activated K⁺ channels (BK_Ca), located on the arterial and corporal smooth muscle, are potential targets for treatment of erectile dysfunction (ED). This study investigated whether NS11021 (1-(3,5-Bis-trifluoromethyl-phenyl)-3-[4-bromo-2-(1H-tetrazol-5-yl)-phenyl]-thiourea), a novel opener of BK_Ca channels, relaxes erectile tissue in vitro and enhances erectile responses in intact rats. The effects were compared with sildenafil, an inhibitor of phosphodiesterase type 5.

Experimental approach:

Patch clamp was used to record whole cell current in rat isolated corpus cavernosum smooth muscle cells (SMCs) and human umbilical vein endothelial cells (HUVECs). Isometric tension was measured in intracavernous arterial rings and corpus cavernosum strips isolated from rats and men, and simultaneous measurements of intracellular Ca²⁺ concentration ([Ca²⁺]_i) and tension were performed in intracavernous arteries. Erectile response was measured in anaesthetized rats.

Key results:

In patch clamp recordings, NS11021 increased currents sensitive to the selective BK_Ca channel blocker, iberiotoxin (IbTX) in SMCs, but did not modulate K⁺ current in HUVECs. NS11021 reduced [Ca²⁺]_i and tension in penile arteries. IbTX inhibited the vasorelaxation induced by NS11021 and sildenafil in human erectile tissue. NS11021 and sildenafil but not vehicle increased erectile responses in anaesthetized rats, an effect which was abolished after pretreatment with tetraethylammonium.

Conclusions and implications:

NS11021 leads to relaxation of both intracavernous arteries and corpus cavernosum strips primarily through opening of BK_Ca channels. It is also effective in facilitating erectile responses in anaesthetized rats. These results suggest a potential for use of BK_Ca openers in the treatment of ED.     

bcl～Xs基因转移联合顺氯氨铂对卵巢癌细胞生长作用的研究

目的 采用以复制缺陷型腺病毒为载体的ｂｃｌ－Ｘｓ基因（Ａｄｖ－ｂｃｌ－Ｘｓ）对卵巢癌细胞进行基因转移,同时使用顺氯氨铂,观察其对卵巢癌细胞生长的抑制作用,方法 用不同浓度的Ａｄｖ－ｂｃｌ－Ｘｓ感染卵巢癌细胞株ＮｕＴｕ－１９,同时使用顺氯氨铂,３ｄ后,用四甲基偶氮唑蓝比色法检测存活细胞,并用流式细胞仪计数细胞周期百分比。结果 Ａｄｖ－ｂｃｌ－Ｘｓ对卵巢癌细胞生长的抑制作用随病毒浓度的增加而增大,至浓     

Arteriovenous fistula of the internal maxillary artery: treatment with transarterial embolization

Six patients with arteriovenous fistulas of the internal maxillary artery were treated with transarterial embolization. The patients ranged in age from 19 to 47 years, with a mean of 26.5 years. Each had a lifelong history of symptoms suggestive of a congenital origin of symptoms. There was no history of trauma. The most common initial symptoms were bruit (83%), pulsatile mass (67%), and pain (50%). In one patient prior surgical ligation of the external carotid artery had been attempted, but it led to aggravation of headaches. All patients were treated with placement of a detachable balloon at the fistula site. In one patient the balloon migrated through the fistula, which was retreated with coils. Complete obliteration of the fistula was achieved in all patients. The follow-up ranged from 2 months to 10 years, with a mean of 5.2 years. Congenital arteriovenous fistulas of the internal maxillary artery are rare and can be treated effectively with transvascular techniques.     

Dural fistulas involving the transverse and sigmoid sinuses: results of treatment in 28 patients

Twenty-eight symptomatic dural fistulas involving the transverse and sigmoid sinuses were treated between 1978 and 1986 with a variety of treatment modalities. Occipital artery compression therapy resulted in a complete cure in two of nine patients (22%) and improvement in three of nine (33%). There were no complications from this treatment. Patients who were excluded or in whom compression therapy failed were treated with embolization alone or in conjunction with surgery. Of the 17 patients who underwent embolization alone, ten were cured and six were improved. Six patients had a combination of embolization and surgery; four patients were cured and two improved. There were three complications in this series, one related to surgery and two related to embolization.     

AIDS-MEDICOLEGAL ASPECTS

AIDS/HIV Positivity has been the most widely debated disease of this century. Reasons for this are manifold, viz-the non-availability of cure and consequent 100% mortality of a full blown case; its mode of transmission-homosexual and heterosexual activities; widespread occurrence amongst ‘main liners’; and patients receiving blood and blood products etc. These aspects have created a dreaded halo around AIDS as well as social stigma. Even the medical community is not exempt from these problems. Unfortunately, legislatures around the world, more so in India, have lagged behind in clarifying many legal issues involved by not enacting specific laws pertaining to AIDS. Consequently many legal & ethical doubts arise in the minds of doctors when confronted with a case of AIDS either in a live patient or in a dead body. In addition, the disease being incurable & 100% fatal, makes it essential to adopt effective preventive measures which in turn need thorough knowledge of social aspects of the epidemic. Certain medicolegal, and ethical aspects of the problem of AIDS are recapitulated in this article for the benefit of the medical community.KEY WORDS: Access, AIDS, Confidentiality