Clinical presentation and surgical management of dissecting posterior inferior cerebellar artery aneurysms: 2 case reports

Intracranial dissection presenting with subarachnoid hemorrhage (SAH) most commonly involves the vertebral artery. The natural history of this lesion suggests frequent early rehemorrhage and need for urgent treatment. Isolated dissection of the posterior inferior cerebellar artery (PICA) is very rare. We present 2 cases of isolated PICA dissections presenting with SAH. Both patients were middle-aged men who presented with transient loss of consciousness, severe headache, and cranial neuropathies. Initial angiography showed dilatation and narrowing of PICA consistent with dissection and aneurysm formation. The vertebral arteries were normal and there was no other cause for the SAH. Repeat angiography 2 weeks after admission revealed significant enlargement of the aneurysmal dilation of the dissected segment of PICA in both patients. Both patients were treated operatively. One patient had clip reconstruction of the PICA with preservation of flow through the PICA. Follow-up angiography one year later showed no recurrence. The other patient underwent direct surgical trapping and resection of the dissected segment of PICA after passing balloon occlusion testing at the vertebral-PICA junction. Both patients have more than 2 years of clinical follow-up and remain well. Isolated PICA dissection seems to have a less ominous natural history compared to vertebral artery dissection. These lesions need to be followed carefully for evidence of aneurysmal enlargement. Direct surgical reconstruction of the dissected segment may be possible. Balloon occlusion testing may be very helpful in determining if the involved PICA segment can be sacrificed.     

‘Sorry,it's my first time!' Will patients consent to medical students learning procedures?

Context The clinical teaching of medical students is essential to medicine; however, medical students often may not inform patients of their inexperience. Hence patients do not have the opportunity to consent specifically to the procedures being performed by medical students. Objectives The purpose of this study was to determine whether patients, when informed of the inexperience of a medical student, would still consent to the procedure. Methods Adult emergency department patients (114) were enrolled if they required one of the following procedures: sutures, intravenous (i.v.) access or splinting. Patients were first surveyed about his or her perceptions of medical student performing procedures. The first-year medical student then informed the patient of their inexperience (the number of procedures they had performed successfully). Finally, the patient was asked to consent to the student performing the procedure (i.e. ‘this is my first/third time suturing, may I suture you?’) The main outcome measure was patient consent to the student performing the procedure. Results Only 48% of participants knew they could be the first patient on whom a medical student might perform a procedure. A total of 66% thought they should be told if a student was performing his or her first procedure on them. The majority of patients (90%) consented (69/80 i.v., 20/20 splints, 13/14 sutures). For 7 of the 12 refusals, it was the student's first time performing the procedure. Conclusion Most patients will allow medical students to perform minor procedures, even when informed of the student's inexperience.     

Enantiomeric fractions of chiral polychlorinated biphenyls provide insights on biotransformation capacity of arctic biota

Chiral polychlorinated biphenyls (PCBs) were measured in an arctic marine food web from the Northwater Polynya (NOW) in the Canadian Arctic to examine potential biotransformation of chiral PCB atropisomers. Organisms under investigation included pelagic zooplankton, Arctic cod (Boreogadus saida), seabirds, and ringed seals (Phoca hispida). Previous studies using achiral methods (e.g., biomagnification factors) have shown that chiral PCB congeners biomagnified in the NOW food web, but provided little information about biotransformation of PCBs except in extreme cases (i.e., high biotransformation). In this study, highly nonracemic enantiomeric fractions (EFs) were observed in several seabird species and ringed seals, but racemic EFs were found in prey (zooplankton and fish). This suggests stereoselective and species-specific biotransformation of individual PCB stereoisomers by birds and mammals. These results are consistent with previously reported biotransformation activity of chiral organochlorine pesticides, alpha-hexachlorocyclohexane, and chlordane within these organisms. This study demonstrates the utility of using chiral analysis of PCBs to investigate biotransformation within biota of arctic food webs.     

The treatment of primary central nervous system lymphoma in 122 immunocompetent patients: a population-based study of successively treated cohorts from the British Colombia Cancer Agency

BACKGROUND: The objective of this study was to evaluate the clinical outcome of a population-based cohort of immunocompetent patients with primary central nervous system lymphoma (PCNSL) treated with 3 different strategies over 13 years. METHODS: One hundred twenty-two consecutive patients (median age, 66 years) with PCNSL were identified. Three treatment strategies were employed: 1) whole-brain irradiation with (from January, 1990, to June, 1991) or without (from April, 1995, to December, 1999) cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP)-type chemotherapy (n=50 patients); 2) combined-modality therapy, including 1 g/m2 methotrexate plus whole-brain irradiation (from July, 1991, to March, 1995; n=34 patients); and 3) 8 g/m2 methotrexate alone (from January, 2000, to March, 2003) with whole-brain irradiation reserved for those with progressive disease (n=38 patients). Treatment failure was defined as progressive disease, disease recurrence, death from toxicity or lymphoma, or toxicity that necessitated a change in primary treatment. RESULTS: The median failure-free survival was 7 months, and the median overall survival (OS) was 17 months. The median OS was similar in all 3 eras. In this population-based analysis, one-third of patients did not receive the treatment strategy of the era. Therefore, the data also were analyzed by treatment received. On multivariate analysis (including era of treatment), 3 factors-age > 60 years, lactate dehydrogenase > normal, and omission of methotrexate-were associated significantly with poorer OS (hazard ratio: 2.3, 2.2, and 2.3, respectively). CONCLUSIONS: Outcomes for a general population with PCNSL remained constant despite different treatment strategies over three eras. For the two-thirds of patients who could receive potentially curative treatment, age, lactate dehydrogenase level, and receipt of > or = 1 g/m2 methotrexate appeared to be important determinants of OS.     

Gene expression profiling allows distinction between primary and metastatic squamous cell carcinomas in the lung

Lung neoplasms commonly develop in patients previously treated for head and neck carcinomas. The derivation of these tumors, either as new primary lung cancers or as metastatic head and neck cancers, is difficult to establish based on clinical or histopathologic criteria since both are squamous cell carcinomas and have identical features under light microscopy. However, this distinction has significant treatment and prognostic implications. Gene expression profiling was performed on a panel of 52 sequentially collected patients with either primary lung (n = 21) or primary head and neck (n = 31) carcinomas using the Affymetrix HG_U95Av2 high-density oligonucleotide microarray. Unsupervised hierarchical clustering with Ward linkage and the Pearson correlation metric was performed. To assess robustness, bootstrap resampling was performed with 1,000 iterations. A t test of the normalized values for each gene was used to determine the genes responsible for segregating head and neck from lung primary carcinomas, and those with the most differential expression were used for later analyses. In the absence of a large "test" set of tumors, we used a supervised leave-one-out cross-validation to test how well we could predict the tumor origin. Once a gene expression profile was established, 12 lung lesions taken from patients with previously treated head and neck cancers were similarly analyzed by gene expression profiling to determine their sites of origin. Unsupervised clustering analysis separated the study cohort into two distinct groups which reliably remained segregated with bootstrap resampling. Group 1 consisted of 30 tongue carcinomas. Group 2 consisted of 21 lung cancers and 1 tongue carcinoma. The clustering was not changed even when normal lung or tongue profiles were subtracted from the corresponding carcinomatous lesions, and a leave-one-out cross-validation showed a 98% correct prediction (see Supplementary Data 1). A minimum set of 500 genes required to distinguish these groups was established. Given the ability to segregate these lesions using molecular profiling, we analyzed the lung tumors of undetermined origin. All cases clearly clustered with either lung or tongue tumor subsets, strongly supporting our hypothesis that this technique could elucidate the tissue of origin of metastatic lesions. Although histologically similar, squamous cell carcinomas have distinct gene expression profiles based on their anatomic sites of origin. Accordingly, the application of gene expression profiling may be useful in identifying the derivation of lung nodules and consequently enhances treatment planning.     

Milk thistle and prostate cancer: differential effects of pure flavonolignans from Silybum marianum on antiproliferative end points in human prostate carcinoma cells

Extracts from the seeds of milk thistle, Silybum marianum, are known commonly as silibinin and silymarin and possess anticancer actions on human prostate carcinoma in vitro and in vivo. Seven distinct flavonolignan compounds and a flavonoid have been isolated from commercial silymarin extracts. Most notably, two pairs of diastereomers, silybin A and silybin B and isosilybin A and isosilybin B, are among these compounds. In contrast, silibinin is composed only of a 1:1 mixture of silybin A and silybin B. With these isomers now isolated in quantities sufficient for biological studies, each pure compound was assessed for antiproliferative activities against LNCaP, DU145, and PC3 human prostate carcinoma cell lines. Isosilybin B was the most consistently potent suppressor of cell growth relative to either the other pure constituents or the commercial extracts. Isosilybin A and isosilybin B were also the most effective suppressors of prostate-specific antigen secretion by androgen-dependent LNCaP cells. Silymarin and silibinin were shown for the first time to suppress the activity of the DNA topoisomerase IIalpha gene promoter in DU145 cells and, among the pure compounds, isosilybin B was again the most effective. These findings are significant in that isosilybin B composes no more than 5% of silymarin and is absent from silibinin. Whereas several other more abundant flavonolignans do ultimately influence the same end points at higher exposure concentrations, these findings are suggestive that extracts enriched for isosilybin B, or isosilybin B alone, might possess improved potency in prostate cancer prevention and treatment.