Radiographic evidence and surgical confirmation of a saccular aneurysm on a hypoplastic duplicated A1 segment of the anterior cerebral artery: case report

OBJECTIVE AND IMPORTANCE: True duplication of the A1 segment of the anterior cerebral artery is extremely rare, as is finding a true A1 segment saccular aneurysm. We report the angiographic and surgical findings of such a case with the additional association of a hypoplastic ipsilateral M1 segment of the middle cerebral artery. CLINICAL PRESENTATION: A 68-year-old man presented with a Hunt and Hess Grade II subarachnoid hemorrhage and symptoms of headache, nuchal rigidity, and facial paresis. INTERVENTION: Angiographic evaluation with superselective exploration revealed a small ruptured aneurysm located on a duplicated hypoplastic A1 segment of the left anterior cerebral artery with associated middle cerebral artery stenosis and secondary early moyamoya changes. Surgical clipping of the aneurysm was performed successfully while sparing the hypoplastic A1 segment. CONCLUSION: A1 aneurysms occurring on a duplicated anterior cerebral artery segment probably develop from a congenital weakness of the parent vessel and increased local shear stress. Superselective angiography was helpful in the preoperative planning and facilitated the decision to treat with surgical clipping instead of embolization.     

Angiogenesis inhibition by an oncolytic herpes virus expressing interleukin 12.

PURPOSE: Oncolytic herpes simplex viruses (HSVs) may have significant antitumor effects resulting from the direct lysis of cancer cells. HSVs may also be used to express inserted transgenes to exploit additional therapeutic strategies. The ability of an interleukin (IL)-12-expressing HSV to treat squamous cell carcinoma (SCC) by inhibition of tumor angiogenesis is investigated in this study. EXPERIMENTAL DESIGN: A replication-competent, attenuated, oncolytic HSV carrying the murine IL-12 gene (NV1042), its non-cytokine-carrying analog (NV1023), or saline was used to treat established murine SCC flank tumors by intratumoral injection. The expression of secondary antiangiogenic mediators was measured. Angiogenesis inhibition was assessed by in vivo Matrigel plug assays, flank tumor subdermal vascularity, and in vitro endothelial cell tubule formation assay. RESULTS: Intratumoral injections of NV1042 (2 x 10(7) plaque-forming units) into murine SCC VII flank tumors resulted in smaller tumor volumes as compared with NV1023 or saline. IL-12 and IFN-gamma expression in tumors was 440 and 2.2 pg/mg, respectively, at 24 h after NV1042 injection, but both IL-12 and IFN-gamma were undetectable (<0.2 pg/mg) after NV1023 or saline injections. Expression of two antiangiogenesis mediators, monokine induced by IFN-gamma and IFN-inducible protein 10, was elevated after NV1042 treatment. Matrigel plug assays of NV1042-transfected SCC VII tumor cells demonstrated significantly decreased hemoglobin content and microvessel density as compared with NV1023 and PBS. Excised murine flank tumors treated with NV1042 had decreased subdermal vascularity as compared with NV1023 and PBS. Both splenocytes and IL-12 expression by NV1042 were required for in vitro inhibition of endothelial tubule formation. CONCLUSIONS: IL-12 expression by an oncolytic herpes virus enhances therapy of SCC through antiangiogenic mechanisms. Strategies combining HSV oncolysis with angiogenesis inhibition merit further investigation for potential clinical application.     

Randomized trial of oral sodium phosphate compared with oral sodium picosulphate (Picolax) for elective colorectal surgery and colonoscopy

BACKGROUND: Sodium picosulphate (Picolax) is considered by most British surgeons as standard preparation for colonoscopy and elective surgery. Oral sodium phosphate may be better tolerated and more efficient as bowel preparation. METHODS: A randomized trial was performed to compare oral sodium phosphate (n = 76) with Picolax (n = 77) as bowel preparation for elective colorectal surgery. A parallel study randomized colonoscopy patients to sodium phosphate (n = 51) or Picolax (n = 52). Patient acceptability was measured for seven symptoms with a linear analogue score. Quality of preparation was graded by the surgeon and faecal residue was measured in resection specimens. During colonoscopy, bowel preparation has graded 0-24 using an endoscopic score. RESULTS: Abdominal pain, nausea, vomiting, embarrassment, fear and fatigue did not differ significantly between the groups. Surgeons grade of quality was judged poor or awful in 5 of 76 in the sodium phosphate group (9%) compared with 13 of 73 in the Picolax group (18%, p = 0.084). Mean faecal residue in the resection specimen was 0.1 g/cm after sodium phosphate compared with 0.45 g/cm after Picolax (p < 0.01). The endoscopic score was significantly lower using sodium phosphate (2.0 +/- 2.2) than picolax (3.1 +/- 2.9; p < 0.05). CONCLUSIONS: These results suggest that oral sodium phosphate is well tolerated and superior to Picolax in elective colorectal surgery and colonoscopy.     

Health risks associated with cigar smoking

This article summarizes principal findings from a conference convened by the American Cancer Society in June 1998 to examine the health risks of cigar smoking. State-of-the-science reports were presented and 120 attendees (representing government and private agencies, academia, health educators, and tobacco control experts) participated in panels and summary development discussions. The following conclusions were reached by consensus: (1) rates of cigar smoking are rising among both adults and adolescents; (2) smoking cigars instead of cigarettes does not reduce the risk of nicotine addiction; (3) as the number of cigars smoked and the amount of smoke inhaled increases, the risk of death related to cigar smoking approaches that of cigarette smoking; (4) cigar smoke contains higher concentrations of toxic and carcinogenic compounds than cigarettes and is a major source of fine-particle and carbon monoxide indoor air pollution; and (5) cigar smoking is known to cause cancers of the lung and upper aerodigestive tract. JAMA. 2000;284:735-740     

Exostoses of the external auditory canal: a long‐term follow‐up study of surgical treatment

To determine the postoperative incidence, extent and recurrence rate of exostoses of the external auditory canal in a cohort of patients involved in different water sports. A cross‐sectional study of 31 patients (46 ears), with exostoses treated by surgery in the Royal Cornwall Hospital between 1980 and 1999. A questionnaire was used to obtain information about the type of water exposure pre‐ and postoperatively. The extent of recurrent stenosis was assessed. The mean postoperative time interval was 10 years (sd = 4.5 years). The degree of stenosis was assessed as: minimal (<30%) in 42.6%, moderate (30–60%) in 31% and severe (>60%) in 25% of ears. The Cox regression model was used to identify factors associated with a reduction in the recurrence rate of stenosis. The use of ear plugs was highly significant (P = 0.015), as was the age of the patient at the time of operation (P = 0.004), i.e. the older the patient, the faster recurrent disease developed. There was no evidence to show that either the type or seasonal pattern of water sport activity influenced recurrence of the disease postoperatively, although preoperatively, the stenosis was more marked in association with surfing and sailing. Exostoses developed faster preoperatively in those who were in the water all year round rather than just the summer months. Of five patients who stopped water sport activity completely after surgery, four of them developed significant recurrent exostoses (>50% stenosis).     

Combination antibody therapy with epratuzumab and rituximab in relapsed or refractory non-Hodgkin's lymphoma.

PURPOSE: To explore the safety and therapeutic activity of combination anti-B-cell monoclonal antibody therapy in non-Hodgkin's lymphoma (NHL). PATIENTS AND METHODS: Twenty-three patients with recurrent B-cell lymphoma received anti-CD22 epratuzumab 360 mg/m(2) and anti-CD20 rituximab 375 mg/m(2) monoclonal antibodies weekly for four doses each. Sixteen patients had indolent histologies (15 with follicular lymphoma) and seven had aggressive NHL (all diffuse large B-cell lymphoma [DLBCL]). Indolent patients had received a median of one (range, one to six) prior treatment, with 31% refractory to their last therapy and 81% with high-risk Follicular Lymphoma International Prognostic Index scores. Patients with DLBCL had a median of three (range, one to eight) prior regimens (14% resistant to last treatment) and 71% had high intermediate-risk or high-risk International Prognostic Index scores. All patients were rituximab na?ve. RESULTS: Treatment was well tolerated, with toxicities principally infusion-related and predominantly grade 1 or 2. Ten (67%) patients with follicular NHL achieved an objective response (OR), including nine of 15 (60%) with complete responses (CRs and unconfirmed CRs). Four of six assessable patients (67%) with DLBCL achieved an OR, including three (50%) CRs. Median time to progression for all indolent NHL patients was 17.8 months. CONCLUSION: The full-dose combination of epratuzumab with rituximab was well tolerated and had significant clinical activity in NHL, suggesting that this combination should be tested in comparison with single-agent treatment.     

Retinal Layers Measurements following Silicone Oil Tamponade for Retinal Detachment Surgery

This study aimed to investigate the influence of silicone oil on the retinal nerve fiber layer (RNFL) thickness in patients with primary rhegmatogenous retinal detachment who underwent vitreoretinal surgery. The study included 47 patients (eyes), who underwent a pars plana vitrectomy with the silicone oil tamponade. The control group included unoperated eye of all participants. Spectral-domain optical coherence tomography (SD-OCT) was used for the measurements of peripapilar and macular RNFL thickness. The average peripapillary RNFL thickness was significantly higher in the silicone oil filled eyes during endotamponade and after its removal. The eyes with elevated IOP had less thickening of the RNFL in comparison to the eyes with normal IOP. Central macular thickness and macular volume were decreased in the silicone oil filled eyes in comparison to the control eyes. In conclusion, silicone oil caused peripapilar RNFL thickening in the vitrectomized eyes during endotamponade and after silicone oil removal.     

2'-deoxyguanosine, 2'-deoxycytidine, and 2'-deoxyadenosine adducts resulting from the reaction of tetrahydrofuran with DNA bases

A recent study showed that tetrahydrofuran (THF), a widely used solvent, is carcinogenic in experimental animals. Despite its carcinogenic activity, there is a paucity of information regarding cellular toxicity, biomolecular damage, and genotoxicity induced by THF. We describe here the structural characterization of adducts produced by the reaction of oxidized THF with 2'-deoxyguanosine (dGuo-THF 1 and dGuo-THF 2), 2'-deoxyadenosine (dAdo-THF), and 2'-deoxycytidine (dCyd-THF). Adducts were isolated from in vitro reactions by reverse-phase HPLC and fully characterized on the basis of spectroscopic measurements. The stable derivatives obtained by the reduction of adducts with NaBH(4) (the case of dGuo-THF 1, dCyd-THF, and dAdo-THF) and the stable adduct dGuo-THF 2 were used as standards for optimization of chromatographic separations for adduct detection in DNA through HPLC/ESI/MS-MS. Using this methodology, we successfully detected the four adducts in calf thymus DNA reacted with oxidized THF. The present study also provides evidence that rat liver microsomal monooxigenases oxidize THF to the reactive electrophilic compounds that are able to damage the DNA molecule, as indicated by a significant increase in adduct dGuo-THF 1 level when NADPH was added to the THF/microsomes/dGuo incubation mixtures. Our data point to DNA-THF adducts as possible contributing factors to the toxicological effects of THF exposure.