The application of controlled intracranial hypertension in slit ventricle syndrome patients with obstructive hydrocephalus and shunt malfunction.

When a shunted patient with slit-ventricle syndrome (SVS) presents with a shunt malfunction or infection, the third ventricle may not be of sufficient caliber, despite the shunt malfunction, to allow atraumatic passage of an endoscope to the floor of the third ventricle. We describe four slit ventricle syndrome patients with respectively 24, 12, 18 and 2 prior shunt revisions who presented with shunt infection. In each patient the shunt was externalized and controlled intracranial hypertension (CIH) was applied over an average of 5.8 days by raising the height of the external ventricular drain (EVD) bag to a mean height of 18.8 cm above EAM. This increased the mean transverse third ventricular diameter from an average of 0.28 cm on admission to 1.13 cm after application of CIH. Endoscopic third ventriculocisternostomy (ETV) was satisfactorily performed in three of the four patients who remain shunt free after a mean follow-up of 21.3 months. CIH followed by ETV is an option in selected SVS patients who present with shunt malfunction or infection.     

Assessment of microvascular endothelial function in human skin.

Endothelial dysfunction is an important factor in many cardiovascular diseases, and is commonly associated with impaired endothelium-mediated vasodilatation. Information about the mechanisms behind this dysfunction has come largely from animal studies or, in humans, through invasive techniques that are not specific to one vascular bed. We have developed protocols to assess endothelial function non-invasively in the cutaneous microcirculation by measuring blood flow responses to four receptor-specific vasoactive compounds. Cumulative doses of acetylcholine, methacholine, bradykinin and substance P were administered iontophoretically to the forearm skin of healthy volunteers on two to three occasions. Dose-dependent increases in skin microvascular blood flow in response to these drugs were measured with laser Doppler imaging. Vascular responses to acetylcholine and methacholine were reasonably consistent, with coefficients of variation of approx. 17%. The coefficients of variation for bradykinin and substance P were much poorer, as high as 70% for some doses. This might partly be a consequence of the more unpredictable effects of histamine release in the vasoactive behaviour of these two agonists. Although it might be advantageous to find other agonists with which to test the function of different receptor pathways, we have shown that just acetylcholine and methacholine can currently be used with iontophoresis to allow sensitive and reproducible assessment of endothelial function.     

Intracranial Dural Sinus Thrombosis: Novel Use of a Mechanical Thrombectomy Catheter and Review of Management Strategies

Management of intracranial dural sinus thrombosis with involvement of multiple sinuses is complex, often involving not only the primary problem (thrombosis) but acute adverse events consequent to the disease. We highlight the novel use of an endovascular device (typically for suction thrombectomy in the peripheral vascular system) used in our patient with a life-threatening multi-sinus thrombosis. As there is no standard treatment yet for cranial sinus thrombosis, our review of the literature highlights some effective management strategies. A 35-year-old woman developed associated complications of cranial sinus thrombosis that included intracranial hypertension caused by an expanding intracranial hematoma, pulmonary embolism treated by placement of filters in superior and inferior vena cava to eliminate intra- and extracranial sources of emboli, and procedure-related retroperitoneal hematoma that necessitated peripheral vascular intervention. After failure of several common devices during mechanical thrombolysis, a thrombectomy catheter (typically for peripheral vascular intervention to aide in the clot removal) was used. Our case highlights the fine balance of anticoagulation and thrombolysis and the proactive, aggressive approach used by our multispecialty team to manage concurrent factors.     

Negative effect of DNA hypermethylation on the outcome of intensive chemotherapy in older patients with high-risk myelodysplastic syndromes and acute myeloid leukemia following myelodysplastic syndrome.

PURPOSE: Promoter hypermethylation of, for example, tumor-suppressor genes, is considered to be an important step in cancerogenesis and a negative risk factor for survival in patients with myelodysplastic syndromes (MDS); however, its role for response to therapy has not been determined. This study was designed to assess the effect of methylation status on the outcome of conventional induction chemotherapy. EXPERIMENTAL DESIGN: Sixty patients with high-risk MDS or acute myeloid leukemia following MDS were treated with standard doses of daunorubicin and 1-beta-d-arabinofuranosylcytosine. Standard prognostic variables and methylation status of the P15(ink4b) (P15), E-cadherin (CDH), and hypermethylated in cancer 1 (HIC) genes were analyzed before treatment. RESULTS: Forty percent of the patients achieved complete remission (CR). CR rate was lower in patients with high WBC counts (P = 0.03) and high CD34 expression on bone marrow cells (P = 0.02). Whereas P15 status alone was not significantly associated with CR rate (P = 0.25), no patient with hypermethylation of all three genes achieved CR (P = 0.03). Moreover, patients with CDH methylation showed a significantly lower CR rate (P = 0.008), and CDH methylation retained its prognostic value also in the multivariate analysis. Hypermethylation was associated with increased CD34 expression, but not with other known predictive factors for response, such as cytogenetic profile. CONCLUSIONS: We show for the first time a significant effect of methylation status on the outcome of conventional chemotherapy in high-risk MDS and acute myelogenous leukemia following MDS. Provided confirmed in an independent study, our results should be used as a basis for therapeutic decision-making in this patient group.     

High Skp2 expression characterizes high-risk neuroblastomas independent of MYCN status.

PURPOSE: Amplified MYCN oncogene defines a subgroup of neuroblastomas with poor outcome. However, a substantial number of MYCN single-copy neuroblastomas exhibits an aggressive phenotype similar to that of MYCN-amplified neuroblastomas even in the absence of high MYCN mRNA and/or protein levels. EXPERIMENTAL DESIGN: To identify shared molecular mechanisms that mediate the aggressive phenotype in MYCN-amplified and single-copy high-risk neuroblastomas, we defined genetic programs evoked by ectopically expressed MYCN in vitro and analyzed them in high-risk versus low-risk neuroblastoma tumors (n = 49) using cDNA microarrays. Candidate gene expression was validated in a separate cohort of 117 patients using quantitative PCR, and protein expression was analyzed in neuroblastoma tumors by immunoblotting and immunohistochemistry. RESULTS: We identified a genetic signature characterized by a subset of MYCN/MYC and E2F targets, including Skp2, encoding the F-box protein of the SCF(Skp2) E3-ligase, to be highly expressed in high-risk neuroblastomas independent of amplified MYCN. We validated the findings for Skp2 and analyzed its expression in relation to MYCN and E2F-1 expression in a separate cohort (n = 117) using quantitative PCR. High Skp2 expression proved to be a highly significant marker of dire prognosis independent of both MYCN status and disease stage, on the basis of multivariate analysis of event-free survival (hazard ratio, 3.54; 95% confidence interval, 1.56-8.00; P = 0.002). Skp2 protein expression was inversely correlated with expression of p27, the primary target of the SCF(Skp2) E3-ligase, in neuroblastoma tumors. CONCLUSION: Skp2 may have a key role in the progression of neuroblastomas and should make an attractive target for therapeutic approaches.     

Management of platinum-based chemotherapy-induced acute nausea and vomiting: is there a superior serotonin receptor antagonist?

OBJECTIVE: The last decade has witnessed the great impact of 5-hydroxytryptamine-3 receptor (5-HT(3))antagonists in revolutionizing the management of platinum-based chemotherapy-induced acute nausea and vomiting (CINV). However, despite the availability of a variety of 5-HT(3) antagonists, little data is published to support superiority of one drug over another, leaving the choice of serotonin receptor antagonist largely empirical. The National Comprehensive Cancer Network and American Society of Clinical Oncology guidelines for management of chemotherapy-associated nausea and vomiting cleary endorse the use of serotonin receptor antagonist; however, no single agent is preferred over the rest. METHODS: Data for patients (n=159) receiving platinum-based chemotherapy regimens were retrospectively collected . Patients getting 5-HT(3) antagonists without steriods or those with known history of brain metastasis, gastroparesis, and intestinal obstruction were not eligible for the study. Patient characteristics including age, gender, primary diagnosis, history of heavy alcohol intake, chemotherapy regimen administered , number of cycles, and Eastern Cooperative Group performance status at the start of therapy were noted. Primary outcome was the complete control of platinum-induced acute nausea and vomiting. Secondary outcome measures included control of > or = grade 1 nausea or vomiting, comparison of two doses of dexamethasone, and antiemetic eficacy among various platinum drugs. National Cancer Institute Common Toxicity Criteria version 2.0 was used to assess toxicity. RESULTS: A total of 126 patients received 369 cycles of platinum-based therapy. Dolasetron ( n=157), granisetron ( n=81), and ondansetron ( n=131) achieved complete control of vomiting in 89.8, 95.5, and 92.3% (p=0.67) of cycles, respectively. Respectively, complete nausea control was observed in 68.1, 75.3 and, 69.4% (p=0.50). Dexamethasone 20 mg was not superior to 10 mg in complete control of nausea and vomiting ( p= 0.15 and p=0.63, respectively). However, complete nausea control was signinficantly better in the subgroup of patients getting cisplatin-compared with carboplatin-based regimens (78.8% vs. 67.7%, p<0.05). CONCLUSION: No significant difference exists in the antiemetic efficacy of the three 5-HT(3) antagonists studied in controlling CINV when administered in combination with dexamethasone. Choicce of antiemetic regimen should therefore be based on drug cost.     

The importance of central corneal thickness measurements and decision making in general ophthalmology clinics: a masked observational study

Background  

To assess the impact of knowing central corneal thickness (CCT) on glaucoma management in a United Kingdom district general hospital.     

Diaphragmatic rupture: A complication of violent cough

The cough is a complex physiologic response designed to protect airways from unwanted secretions and foreign materials. Violent and paroxysmal coughs are associated with many complications. In this article, we will discuss a patient who sustained diaphragmatic rupture as a result of violent coughing. The possible mechanisms of this rare complication are explained.