Three methods for gradual cervical dilatation prior to vacuum aspiration in late first trimester pregnancy

Sixty healthy women at 8 to 12 weeks of gestation were divided into three groups of 20 women each to evaluate three methods for gradual cervical dilatation prior to vacuum aspiration — Group I: Laminaria tent; Group II: Isaptent, and Group III: 250 ug 15-methyl-PGF₂ alpha intramuscular injection. The three methods showed comparable cervical dilatation (10.46 mm) over a mean period of 3 hours 40 minutes. Administration of 15-methyl-PGF₂ alpha, though relatively simple, had significant gastrointestinal side effects and bleeding per vaginum (P < 0.001) prior to vacuum aspiration and greater blood loss (P < 0.01) during vacuum aspiration as compared with the other two groups. No sequelae, immediate or delayed, were encountered. Isaptent indigenously made and relatively inexpensive is a reliable, safe and effective method for gradual dilatation of cervix for 8 to 12 weeks of gestation prior to vacuum aspiration and is the cervical dilator of choice.     

Trp53R172H and KrasG12D cooperate to promote chromosomal instability and widely metastatic pancreatic ductal adenocarcinoma in mice

To define the genetic requirements for pancreatic ductal adenocarcinoma (PDA), we have targeted concomitant endogenous expression of Trp53(R172H) and Kras(G12D) to the mouse pancreas, revealing the cooperative development of invasive and widely metastatic carcinoma that recapitulates the human disease. The primary carcinomas and metastases demonstrate a high degree of genomic instability manifested by nonreciprocal translocations without obvious telomere erosion-hallmarks of human carcinomas not typically observed in mice. No mutations were discovered in other cardinal tumor suppressor gene pathways, which, together with previous results, suggests that there are distinct genetic pathways to PDA with different biological behaviors. These findings have clear implications for understanding mechanisms of disease pathogenesis, and for the development of detection and targeted treatment strategies.     

Carotid endarterectomy in patients with chronic renal insufficiency: a recent series of 184 cases

BACKGROUND: The published results of carotid endarterectomy (CEA) in chronic renal insufficiency (CRI) patients are contradictory, mostly because of the relatively small number of patients in these studies. To better assess the neurologic complications and mortality, we reviewed a recent and substantially larger series of CRI patients who underwent CEAs. METHODS: From March 2000 to March 2003, 675 consecutive primary CEAs were performed in 609 patients (346 men, 57%) under general anesthesia. Asymptomatic carotid artery stenosis accounted for 71% of cases. CRI (serum creatinine level > or = 1.5 mg/dL) was detected in 166 patients (27%) who underwent 184 CEAs. The remaining 443 patients (73%) had 491 CEAs. RESULTS: Patients with CRI were different in age (76 +/- 8 years vs 72 +/- 9 years, P < .001), male gender (73% vs 51%, P < .001), coronary artery disease (50% vs 28%, P < .001), and diabetes mellitus incidence (38% vs 27%, P < .02). No significant difference in stroke rates was observed between the CRI patients and the control group (1.2% vs 0.5%). The mortality rate for CRI patients was 3%, whereas it was 0% for the control group ( P < .002). The 143 CRI patients with serum creatinine levels from 1.5 to 2.9 mg/dL had a 0.7% mortality rate, whereas it was 17% for 23 patients with serum creatinine levels of 3 mg/dL or more ( P < .001). The stroke rate for the former group was 0.7% and 4.3% for the latter group (NS). Asymptomatic (16) and symptomatic (7) patients with serum creatinine levels of 3 mg/dL or more had mortality rates of 13% and 28%, respectively, with P = .6. CONCLUSION: The high mortality rate observed in patients with serum creatinine levels of 3 mg/dL or more after CEA calls for a nonoperative approach in the management of asymptomatic patients.     

The effect of von hippel-lindau gene transfer on human vascular smooth muscle cell proliferation and apoptosis

Von Hippel-Lindau (VHL) gene is a tumor suppressor gene that plays a genome "gatekeeper' role and controls several downstream effector genes. We have previously demonstrated that both in vivo and in vitro adenovirus-mediated gene transfer of tumor suppressor genes into the vascular endothelium is effective in decreasing neointimal hyperplasia and abnormal cell proliferation. The degree of apoptosis induced by these genes is critical in mediating the in vivo responses to gene therapy and the maintenance of the crucial balance between cell death and viability. Since VHL gene is known to regulate vascular endothelial growth factor (VEGF) as well as other angiogenic factors, it may exhibit a greater potential in the attenuation of vascular disorders in comparison to other tumor suppressor genes. This study focused on whether adenovirus-mediated VHL gene transfer into human vascular smooth muscle cells has an effect on cell proliferation and induction of apoptosis. Human aortic smooth muscle cells (HASMC) were grown as monolayers and transfected with varying titers of adenovirus containing the VHL cDNA (AdVHL). The negative controls were adenovirus containing green fluorescent protein (AdGFP), vector alone (AdNull), and virus-free infection medium. Adenovirus encoding wild-type p53 (Adp53) was used as positive control. Cell viability and proliferation were determined by using trypan blue exclusion and MTS-based CellTiter 96 AQ Proliferation Assay. Apoptosis was evaluated by TUNEL assay, morphologic changes, and nucleosomal DNA degradation. Following AdVHL transfection HASMCs demonstrated a dose-dependent decrease in viability as compared to negative controls (p < 0.05). AdVHL-transfected cells exhibited a decrease in their proliferative ability by 40.21 +/-1.66 (SEM)%. In cultures transfected with the positive control, Adp53, the cell viability as well as proliferation was highly reduced (p < 0.001). AdGFP and AdNull did not increase HASMC apoptosis above baseline levels. The cells exposed to adenoviruses expressing tumor suppressor genes underwent apoptosis, with Adp53 demonstrating a very high magnitude of cell death (75.27 +/-3.52 [SEM]%). AdVHL expression caused 45.36 +/-2.55 (SEM)% apoptosis in HASMC. Recombinant adenovirus-mediated VHL expression is efficacious in limiting vascular smooth muscle cell growth in vitro. Overexpression of VHL suppresses HASMC proliferation and regulates apoptosis. Further experiments are indicated to examine whether VHL may be a useful adjunct in limiting myointimal hyperplasia.     

A 10-year experience with complementary distal arteriovenous fistula and deep vein interposition for infrapopliteal prosthetic bypasses

Since up to 20% of patients undergoing lower extremity revascularization do not have an adequate venous conduit, some authors have explored the use of prosthetic grafts with adjunctive techniques for lower extremity revascularization. However, the long-term graft patency of those procedures has not been well documented. The purpose of this study was to examine the long-term patency of polytetrafluoroethylene (PTFE) bypass with adjunctive arteriovenous fistula and venous interposition (AVF/VI) for infrapopliteal revascularization. Over a 10-year period, 246 lower extremity reconstructions were performed in 176 (71.5% men) patients with critical ischemia in whom a totally autogenous vein bypass was not feasible. Seventy-six limbs had undergone 1 or more failed ipsilateral infrainguinal bypasses. Indications for surgery were chronic critical limb-threatening ischemia (86%) (rest pain, ischemic ulcer, or gangrene) or acute ischemia (14%). Ages ranged from 46 to 91 years (mean 74 +/-0.6 [SD] years). Risk factors such as diabetes, hypertension, coronary artery disease, end-stage renal disease, and use of tobacco were present in 49%, 49%, 52%, 8%, and 67% of the patients, respectively. During the follow-up, 112 cases (45%) required reinterventions. Twenty-seven patients (15%) required bypass revision twice. During the follow up, 56 limbs (23%) were amputated (above-the-knee amputation 25 (10%); below-the-knee amputation 31 (13%). To date, 150 (85%) patients of a total of 176 are deceased. The primary graft patency rates were as follows: at 1 year, 51%; at 2 years, 41%; 3 years, 35%; and 5 years, 24%. Limb salvage rates were as follows: 1 year, 79%; 2 years, 76%; 3 years 76%; and 5 years, 74%. Patient survival rates were as follows: 1 year, 69%; 2 years, 60%; 3 years, 54%; and 5 years, 40%. Amputation-free patient survival rates were as follows: 1 year, 66%; 2 years, 57%, 3 years, 51%, and 5 years, 30%. This technique appears to offer reasonable patency and limb salvage rates in patients in whom autogenous bypass grafts are not feasible.