Genetics of epilepsy: epilepsy research foundation workshop report.

The Sixth Epilepsy Research Foundation workshop, held in Oxford in March 2006, brought together basic scientists, geneticists, epidemiologists, statisticians, pharmacologists and clinicians to consider progress, issues and strategies for harnessing genetics to improve the understanding and treatment of the epilepsies. General principles were considered, including the fundamental importance of clear study design, adequate patient numbers, defi ned phenotypes, robust statistical data handling, and follow-up of genetic discoveries. Topics where some progress had been made were considered including chromosomal abnormalities, neurodevelopment, hippocampal sclerosis, juvenile myoclonic epilepsy, focal cortical dysplasia and pharmacogenetics. The ethical aspects of epilepsy genetics were reviewed. Principles and limitations of collaboration were discussed. Presentations and their matched discussions are produced here. There was optimism that further genetic research in epilepsy was not only feasible, but might lead to improvements in the lives of people with epilepsy.     

Practical management of patients with non-small-cell lung cancer treated with gefitinib.

PURPOSE: The use of gefitinib, the first drug approved to inhibit the epidermal growth factor receptor tyrosine kinase, is indicated in patients with non-small-cell lung cancer with tumors progressive after chemotherapy. The unique mechanism of action of this agent leads to distinctive patterns of response and toxicity in persons with lung cancer. Many of the principles of management relevant to gefitinib are distinct from those with conventional cytotoxic drugs. To meet this need, we present practical guidelines on the use of gefitinib in patients with non-small-cell lung cancer. METHODS: This article reviews gefitinib's indications, dosing, response phenomena, and patterns of relapse in individuals with radiographic response. RESULTS: We present our recommendations for the management of rash and diarrhea caused by this agent. CONCLUSION: This information can guide practitioners and help them inform their patients about what to expect when they receive gefitinib.     

Repeat Transarterial Chemoembolization (TACE) for Progressive Hepatic Carcinoid Metastases Provides Results Similar to First TACE

Background Transarterial chemoemobolization (TACE) is commonly used to treat metastatic carcinoid tumors; however, the management of progressive disease is less clear. We sought to determine if patients with disease progression after TACE would benefit from repeat TACE. Methods The records of 27 patients undergoing repeat TACE for radiologic or symptomatic progression after TACE for metastatic carcinoid were reviewed and compared to 122 undergoing first TACE. Overall and progression-free survivals were estimated by the Kaplan–Meier method. Results Mean disease-free interval after first TACE was 11.8 months. Radiologic response was observed in 61% compared to 82% after first TACE (p = 0.058); hormone response in 64% compared to 80% (p = 0.159); and symptomatic response in 77% compared to 92% (p = 0.053). The complication rate after repeat TACE was lower than after first TACE (p = 0.03). Median overall survival was similar after repeat (28.1 months) and first TACE (33.3 months) (p = 0.53). Progression-free survival was shorter after repeat TACE but not significantly so. No factor examined could predict survival after repeat TACE. Conclusion Repeat TACE for patients with hepatic carcinoid metastases failing first TACE or having evidence of disease progression is safe and offers a viable treatment option. Presented at the 48th Annual Meeting of The Society for Surgery of the Alimentary Tract, Washington, DC, May, 2007.     

Deep vein thrombosis and pulmonary embolus associated with a ruptured popliteal aneurysm – a cautionary note

Popliteal artery aneurysms representing 80% of peripheral artery aneurysms rarely rupture (a reported incidence of 0.1–2.8 %) and second commonest in frequency after aorto-iliac aneurysms. They usually present with pain, swelling, occlusion or distal embolisation and can cause diagnostic difficulties. We report a 78 year old man who was previously admitted to hospital with a pulmonary embolus secondary to deep venous thrombosis. He was heparinized then warfarinised and was readmitted with a ruptured popliteal aneurysm leading to a large pseudo aneurysm formation. The pulmonary embolus had been due to popliteal vein thrombosis and propagation of the clot. A thorough review of literature identified only one previously reported case of ruptured popliteal artery aneurysm and subsequent large pseudo aneurysm formation. We feel it is important to exclude a popliteal aneurysm in a patient with DVT. This may be more common than the published literature suggests.     

The heat shock proteins and plastic surgery.

Heat shock proteins are diverse and essential components of cell physiology. Their expression is elevated in the cell undergoing stress, where they protect the cell from death by necrosis or apoptosis and accelerate recovery. Significant advances have been made in studies relevant to plastic surgery regarding these proteins and their manipulation. This review introduces the heat shock proteins and appraises these studies in skin, ultraviolet light exposure, neoplasia, wound healing, ageing, burns, and reconstructive surgery.     

The health of children of low-income families.

Childhood poverty is common in Canada: 1,114,000 children under 16 years of age live below the poverty line. The incidence is highest among children of single mothers, unemployed parents, Canadian native peoples and recent immigrants, particularly refugees. Compared with the national average, the infant mortality rate is twice as high, deaths from infectious diseases are 2.5 times more common and accidental deaths are twice as common among children of low-income families. Other problems associated with poverty are iron deficiency anemia, dental caries, chronic ear infections, mental retardation, learning disabilities, poor school performance and increased suicide rates. Health care professionals can help address the poor physical and mental health associated with poverty in children by promoting a broad range of public policies.     

Comparison of the Different Approaches to Saphenous Nerve Block

Background: The authors compared the efficacy of the different approaches to saphenous nerve block.

Methods: The following approaches to saphenous nerve block were compared in 10 volunteers: perifemoral, transsartorial, block at the medial femoral condyle, below-the-knee field block, and blockade at the level of the medial malleolus. Each volunteer underwent all five blocks, and the interval between blocks was 3-7 days. The sequence of injection was randomized by Latin square design. Sensory blockade at the medial aspects of the leg and foot and the strength of the anterior thigh muscles were noted.

Results: The transsartorial, perifemoral, and below-the-knee field block approaches were more effective than block at the medial femoral condyle in providing sensory anesthesia to the medial aspect of the leg. The transsartorial approach was more effective than block at the medial femoral condyle and below-the-knee field block in providing sensory anesthesia to the medial aspect of the foot. Compared with the perifemoral approach, the transsartorial approach did not cause weakness of the hip flexors and the knee extensors. In volunteers with partial numbness in the medial aspect of the foot, supplemental block of the medial dorsal cutaneous branch of the superficial peroneal nerve resulted in complete sensory blockade.     

Phospho-akt expression is associated with a favorable outcome in non-small cell lung cancer.

Akt, a Serine/Threonine protein kinase, mediates growth factor-associated cell survival. Constitutive activation of Akt (phosphorylated Akt, P-Akt) has been observed in several human cancers, including lung cancer and may be associated with poor prognosis and chemotherapy and radiotherapy resistance. The clinical relevance of P-Akt in non-small cell lung cancer (NSCLC) is not well described. In the present study, we examined 82 surgically resected snap-frozen and paraffin-embedded stage I to IIIA NSCLC samples for P-Akt and Akt by Western blotting and for P-Akt by immunohistochemistry. P-Akt protein levels above the median, measured using reproducible semiquantitative band densitometry, correlated with a favorable outcome (P = 0.007). Multivariate analysis identified P-Akt as a significant independent favorable prognostic factor (P = 0.004). Although associated with a favorable prognosis, high P-Akt levels correlated with high tumor grade (P = 0.02). Adenocarcinomas were associated with low P-Akt levels (P = 0.039). Akt was not associated with either outcome or clinicopathologic variables.Cytoplasmic (CP-Akt) and nuclear (NP-Akt) P-Akt tumor cell staining was detected in 96% and 42% of cases, respectively. Both CP-Akt and NP-Akt correlated with well-differentiated tumors (P = 0.008 and 0.017, respectively). NP-Akt also correlated with nodal metastases (P = 0.022) and squamous histology (P = 0.037).These results suggest P-Akt expression is a favorable prognostic factor in NSCLC. Immunolocalization of P-Akt, however, may be relevant as NP-Akt was associated with nodal metastases, a known poor prognostic feature in this disease. P-Akt may be a potential novel therapeutic target for the management of NSCLC.