Pooling of echographic contrast agents during transcranial Doppler sonography: a sign in favor of slow-flowing giant saccular aneurysms

Transcranial Doppler (TCD) sonography is a new imaging technique allowing for non-invasive evaluation of the intracranial vascular anatomy and cerebral hemodynamics. The recent introduction of echographic contrast agents has significantly increased the sensitivity of TCD for the diagnosis of intracranial vascular lesions. We report a case of giant AComA aneurysm, undetected by color and power TCD, which became visible after echographic contrast administration as a delayed and persistent area of contrast enhancement. Knowledge of atypical or contrast-specific lesion appearances will become important if contrast-enhanced TCD is to be used routinely in the diagnosis of intracranial aneurysms.     

Cemented or uncemented hemiarthroplasty for displaced intracapsular fractures of the hip--a systematic review

Displaced intracapsular hip fractures are often treated by hemiarthroplasty, with or without cement. The aim of this study is to perform a systematic review of the literature to establish whether this influences the outcome. A comprehensive search of the English language world literature of all studies comparing cemented with uncemented hemiarthroplasty was performed. Eighteen publications addressing this issue were identified. Three were excluded from review because of poor study design and non-comparability of groups. Of the remainder, few were suitable for statistical analysis, therefore a qualitative comparison of results was carried out. The majority of studies suggested a lower revision rate, less thigh pain and better mobility in-patients in whom the prosthesis was cemented. Cemented hemiarthroplasty may be associated with increased operative time and blood loss. There appears to be no difference in general complication, or mortality rates after 3 months, between the two groups. Radiographic differences were variable and did not correlate with clinical findings. We conclude, the literature tends to support the use of cement in hemiarthroplasty for displaced intracapsular femoral neck fractures. Further prospective randomised studies are required to resolve the issue.     

Induction of histone acetylation and inhibition of growth of mouse erythroleukemia cells by S-allylmercaptocysteine

Growth-inhibitory effects on DS19 mouse erythroleukemia cells were seen in the micromolar concentration range with allicin and S-allylmercaptocysteine and in the millimolar range with allyl butyrate, allyl phenyl sulfone, and S-allyl cysteine. Increased acetylation of histones was induced by incubation of cells with the allyl compounds at concentrations similar to those that resulted in the inhibition of cell proliferation. The induction of histone acetylation by S-allylmercaptocysteine was also observed in Caco-2 human colon cancer cells and T47D human breast cancer cells. In contrast to the effect on histone acetylation, there was a decrease in the incorporation of phosphate into histones when DS19 cells were incubated with 25 microM S-allylmercaptocysteine. Histone deacetylase activity was inhibited by allyl butyrate, but there was little or no effect with the allyl sulfur compounds examined in this study. A similar degree of downregulation of histone deacetylase and histone acetyltransferase was observed when DS19 cells were incubated with S-allylmercaptocysteine or allyl isothiocyanate. The induction of histone acetylation by S-allylmercaptocysteine was not blocked by a proteasome inhibitor. The mechanism by which S-allylmercaptocysteine induces histone acetylation remains to be characterized. It may be related in part to metabolism to allyl mercaptan, which is a more effective inhibitor of histone deacetylase.     

Costs and cost-effectiveness of different DOT strategies for the treatment of tuberculosis in Pakistan. Directly Observed Treatment

An economic study was conducted alongside a clinical trial at three sites in Pakistan to establish the costs and effectiveness of different strategies for implementing directly observed treatment (DOT) for tuberculosis. Patients were randomly allocated to one of three arms: DOTS with direct observation by health workers (at health centres or by community health workers); DOTS with direct observation by family members; and DOTS without direct observation. The clinical trial found no statistically significant difference in cure rate for the different arms. The economic study collected data on the full range of health service costs and patient costs of the different treatment arms. Data were also disaggregated by gender, rural and urban patients, by treatment site and by economic categories, to investigate the costs of the different strategies, their cost-effectiveness and the impact that they might have on patient compliance with treatment. The study found that direct observation by health centre-based health workers was the least cost-effective of the strategies tested (US dollars 310 per case cured). This is an interesting result, as this is the model recommended by the World Health Organization and International Union against Tuberculosis and Lung Disease. Attending health centres daily during the first 2 months generated high patient costs (direct and in terms of time lost), yet cure rates for this group fell below those of the non-observed group (58%, compared with 62%). One factor suggested by this study is that the high costs of attending may be deterring patients, and in particular, economically active patients who have most to lose from the time taken by direct observation. Without stronger evidence of benefits, it is hard to justify the costs to health services and patients that this type of direct observation imposes. The self-administered group came out as most cost-effective (164 dollars per case cured). The community health worker sub-group achieved the highest cure rates (67%), with a cost per case only slightly higher than the self-administered group (172 dollars per case cured). This approach should be investigated further, along with other approaches to improving patient compliance.     

Is Intrathecal Methotrexate Necessary in the Treatment of Primary CNS Lymphoma?

Systemic high-dose methotrexate (HD-MTX) is the most effective chemotherapeutic agent in the treatment of primary central nervous system lymphoma (PCNSL). Leptomeningeal involvement is common and intrathecal methotrexate (IT-MTX) is frequently used in combination with HD-MTX, but its benefits are not established. Using a case-controlled retrospective study, matching patients treated with HD-MTX with or without IT-MTX, we found no difference in survival, disease control, or neurotoxicity.     

Ductal lavage and ductoscopy: the opportunities and the limitations

Two related techniques of breast epithelial sampling have emerged in the past several years: ductal lavage, in which fluid-yielding nipple ducts are cannulated at their orifices and lavaged with saline while the breast is intermittently massaged; and ductoscopy, in which discharging or fluid-yielding duct orifices are dilated, intubated with a microendoscope, and the lumen directly visualized. Both of these techniques have significant potential in terms of allowing the repeated sampling of ductal epithelium over time and, as such, have generated considerable enthusiasm. However, data regarding the impact of these techniques on the detection of significant breast disease is very scant. It is important at the outset of the assessment of this new technology that breast cancer clinicians and clinical researchers think carefully about the standards of evidence that need to be met regarding the benefits of these procedures before they are widely adopted. In this review of the rationale and early results of these procedures, we attempt to define some of these evidentiary requirements.     

Influence of lipopolysaccharide exposure on airway function and allergic responses in developing mice

Exposure to endotoxin has been associated with an exacerbation of asthmatic responses in humans and animal models. However, recent evidence suggests that microbial exposure in early life may protect from the development of asthma and atopy. In this study, we sought to evaluate the effects of lipopolysaccaride (LPS) on airway function in developing mice. In addition, we evaluated the influence of LPS on subsequent allergen sensitization and challenge. Under light anesthesia, 2-3-week-old Balb/c mice received a single intranasal instillation of LPS or sterile physiologic saline. Measurements of airway function were obtained in unrestrained animals, using whole-body plethysmography. Airway responsiveness was expressed in terms of % enhanced pause (Penh) increase from baseline to aerosolized methacholine (Mch). In additional studies, we assessed the functional and cellular responses to ovalbumin sensitization and challenge following prior exposure to LPS.We found that exposure to LPS induced transient airway hyperresponsiveness to Mch. These functional changes were associated with the recruitment of neutrophils and lymphocytes into the bronchoalveolar lavage (BAL) fluid. Airway responsiveness after allergen sensitization and challenge was decreased by prior exposure to LPS. The analysis of BAL cells and cytokines (interferon-gamma and interleukin-4) did not reveal alterations in the overall Th1/Th2 balance.Our findings suggest that LPS leads to airway hyperresponsiveness in developing mice, and may protect against the development of allergen-driven airway dysfunction.