The expanding role of neurosurgeons in the management of brain metastases

BACKGROUND: Brain metastases are the most common type of intracranial tumor. Until recently, whole brain fractionated radiation therapy (WBRT) was the mainstay of treatment, thereby confining the role of neurosurgeons to resection of an occasional solitary, accessible, and symptomatic brain metastasis. Median survival after surgery and radiation typically ranged from 5 to 11 months. METHODS: We analyzed various demographic incidence reports and our series of brain metastasis patients treated with radiosurgery. During a 15-year interval (1987-2002), radiosurgery was performed on 5,032 patients of whom 1,088 (21.6%) had metastatic brain tumors. RESULTS: In the United States, 266,820 to 533,640 new cases of brain metastases will be diagnosed in the year 2003. Evidence to date demonstrates that radiosurgery provides effective local tumor control for brain metastases. Important prognostic factors affecting patient survival include the absence of active systemic disease, the patient's preoperative performance status, age, and the number of metastases. Survival and local tumor control rates attained with radiosurgery are superior to those of either conventional surgery or WBRT. The morbidity associated with radiosurgery of brain metastasis is very low, and the mortality rate approaches zero. CONCLUSIONS: Compelling evidence indicates that radiosurgery is an effective neurosurgical management strategy for intracranial brain metastases. Quite often, favorable tumor control and survival can be achieved without WBRT. With radiosurgery as a therapeutic option, neurosurgeons now have a vastly expanded armamentarium for treatment of patients with brain metastases. The large number of patients with brain metastases who require care by a neurosurgeon for optimal treatment has significant implications for both the patterns of neurosurgical training and practice in the United States.     

Virtual bronchoscopy for diagnosis of inhalation injury in burnt patients

Virtual bronchoscopy using a multislice CT scanner, is a new non-invasive imaging technique and its utility in the diagnosis of inhalation injury in burnt patients has not been reported in literature yet. Initial experience of technique is encouraging and it merits more interest. It overcomes many of the limitations of the presently established procedure of fibreoptic bronchoscopy. Ten burned patients with clinical suspicion of inhalation injury underwent this investigation and in eight of these the diagnosis was confirmed.     

Estimation of errors in determining intrathoracic blood volume using thermal dilution in pigs with acute lung injury and haemorrhage

Background. Global end diastolic volume (GEDV) has a constantand predictable relationship to intrathoracic blood volume (ITBV).The present study assesses the difference between ITBV derivedfrom GEDV and ITBV measured directly in pigs with acute lunginjury (ALI) and mild haemorrhage. Methods. We caused ALI in 12 anaesthetized pigs by i.v. injectionof oleic acid and removed 10% of estimated blood volume. EVLW,GEDV, ITBV (COLD; Pulsion Medical Systems),     

Is an early invasive approach superior to a conservative strategy in patients with acute coronary syndrome?

A best evidence topic in cardiac surgery was written according to a structured protocol. The question addressed was whether an early invasive approach (involving early coronary angiography followed by revascularisation if suitable) is superior to a conservative approach (with revascularisation only in patients with failed medical therapy) in patients with acute coronary syndrome. Altogether 282 papers were found using the reported search, of which seven presented the best evidence to answer the clinical question. The author, journal, date and country of publication, patient group studied, study type, relevant outcomes, results, and study weaknesses of these papers are tabulated. We conclude that in patients diagnosed with acute coronary syndrome, an early invasive approach is clearly superior to a conservative approach.     

What is the optimal anticoagulation management of patients post-cardiac surgery who go into atrial fibrillation?

A best evidence topic in cardiac surgery was written according to a structured protocol. The question addressed was whether anticoagulation is indicated for patients in atrial fibrillation (AF) following coronary artery bypass grafting. Altogether 166 papers were found using the reported search, of which 10 presented the best evidence to answer the clinical question. In addition the American Heart Association guidelines for management of atrial fibrillation were reviewed. The author, journal, date and country of publication, patient group studied, study type, relevant outcomes, results, and study weaknesses of these papers are tabulated. We conclude that patients post-cardiac surgery require warfarinisation while in atrial fibrillation with an INR of 2-3, and full anticoagulation should be commenced within 48 h of the onset of AF as their risk of stroke is doubled by the onset of AF.     

Blood pressure measurement in dialysis patients

The best method and timing of blood pressure (BP) measurement in end-stage renal disease are subject to controversy. This issue is especially relevant in hemodialysis patients, where unique causes of inaccuracy may exist. The lack of standardization of BP measurement in the dialysis unit may lead to misdiagnosis, so close attention must be paid to technical methods to obtain BP. A composite of BP measurements over a period of 1 to 2 weeks rather than isolated readings should be used for guidance. Interdialytic BP monitoring with an ambulatory BP monitor is the most reproducible method and is thought to best represent BP in dialysis patients. If available, ambulatory BP is a useful tool to evaluate the quality of BP control in the interdialytic period. Alternative forms of BP measurement, such as home BP, 20-minute postdialysis BP, and short (3-hour to 4-hour) ambulatory blood pressure monitoring (ABPM), could prove useful when feasible or available. In this paper, we discuss the evidence regarding BP measurement in dialysis patients, new techniques under development, and recommendations for clinical practice.     

Synthesis and anticancer activity of simplified indenoisoquinoline topoisomerase I inhibitors lacking substituents on the aromatic rings

The indenoisoquinolines are a class of cytotoxic topoisomerase I inhibitors that offer certain advantages over the camptothecins, including the greater stabilities of the compounds themselves, as well as the greater stabilities of their drug-enzyme-DNA cleavage complexes. To investigate the possible biological roles of the di(methoxy) and methylenedioxy substituents present on the aromatic rings of the previously synthesized indenoisoquinoline topoisomerase I inhibitors, a series of compounds lacking these substituents was synthesized and tested for both cytotoxicity in cancer cell cultures and for enzyme inhibitory activity. The results indicate that the aromatic substituents make a small, but consistently observable contribution to the biological activity. Molecular models derived for the binding of the unsubstituted indenoisoquinolines in ternary complex with DNA and topoisomerase I indicate that the substituents on the lactam nitrogen project out of the major groove, and the carbonyl group is directed out of the minor groove, where it is involved in a hydrogen bonding interaction with the side chain guanidine group of Arg364. The DNA cleavage patterns observed in the presence of topoisomerase I and various indenoisoquinolines were similar, although significant differences were detected. There were also variations in the DNA cleavage pattern seen with camptothecin vs the indenoisoquinolines, which indicates that these two classes of topoisomerase I inhibitors are likely to target the cancer cell genome differently, resulting in different spectra of anticancer activity. The most cytotoxic of the presently synthesized indenoisoquinolines has a 4-amino-n-butyl group on the lactam nitrogen.     

Activation of caspase-9 with irradiation inhibits invasion and angiogenesis in SNB19 human glioma cells

Glioblastoma multiforme, the most common brain tumor, typically exhibits markedly increased angiogenesis, which is crucial for tumor growth and invasion. Antiangiogenic strategies based on disruption of the tumor microvasculature have proven effective for the treatment of experimental brain tumors. Here, we have overexpressed human caspase-9 by stable transfection in the SNB19 glioblastoma cell line, which normally expresses low levels of caspase-9. Our studies revealed that overexpression of caspase-9 coupled with radiation has a synergistic effect on the inhibition of glioma invasion as demonstrated by Matrigel assay (> 65%). Furthermore, sense caspase stable clones cocultured with fetal rat brain aggregates along with radiation showed complete inhibition as compared to the parental and vector controls. During in vitro angiogenesis, SNB19 cells cocultured with human microvascular endothelial cells (HMEC) showed vascular network formation after 48-72 h. In contrast, these capillary-like structures were inhibited when HMEC cells were cocultured with sense caspase stable SNB19 cells. This effect was further enhanced by radiation (5 Gy). Signaling mechanisms revealed that apoptosis is induced by cleavage of caspase-9 by radiation, loss of mitochondrial membrane potential and activation of caspase-3. These results demonstrate that activation of caspase-9 disrupts glioma cell invasion and angiogenesis in vitro. Hence, overexpression of proapoptotic molecules such as caspase-9 may be an important determinant of the therapeutic effect of radiation in cancer therapy.