Transjugular craniotomy for the management of jugular foramen tumors with intracranial extension.

OBJECTIVES: To elucidate indications and outcomes with the transjugular craniotomy for resection of jugular foramen tumors with intracranial extension. The transjugular approach is a lateral craniotomy conducted through a partial petrosectomy traversing the jugular fossa combined with resection of the sigmoid sinus and jugular bulb, which often have been occluded by disease. STUDY DESIGN: Retrospective review. SETTING: University medical center. PATIENTS: Twenty-eight patients with intracranial jugular foramen tumors who underwent a total of 30 surgical procedures. MAIN OUTCOME MEASURES: Pathologic findings, surgical approach, extent of tumor resection, rate of facial nerve mobilization and ear canal closure, facial and lower cranial nerve outcomes, and hearing preservation. RESULTS: Tumors included schwannoma (37%), meningioma (33%), glomus jugulare (23%), and chordoma (7%). The surgical approaches were tailored to maximize functional preservation, and included the transjugular (53%), translabyrinthine (17%), retrosigmoid (10%), and far lateral (7%) craniotomies. Translabyrinthine (3%) or transcondylarfar lateral (3%) approaches were occasionally used in combination with the trans-jugular approach. Most procedures were managed in a single stage (90%), but three patients with massive tumor in the neck required two stages. Microsurgical gross total and near-total tumor removal (37% each) were commonly achieved, although subtotal resections (27%) were occasionally performed. In only a minority of cases was facial nerve mobilization (7%) or ear canal closure (21%) required. If present preoperatively, Grade I facial nerve function was usually maintained (22 of 24 [92%]) and Hearing Class A or B could always be maintained (9 of 9 [100%]). As expected, new lower cranial nerve dysfunction was common (8 of 30 [27%]), although over half of the patients had complete lower nerve palsy preoperatively (16 of 30 [53%]). CONCLUSION: Most patients with jugular foramen tumors with intracranial extension can be managed with a single-stage transjugular craniotomy. Facial nerve mobilization or ear canal closure is usually not required, permitting conservation of facial function and hearing, when present preoperatively.     

Multicultural mental health services

Oregon has a significant Indochinese minority community. Seen through the eyes of this group, few of the difficulties minorities encounter when seeking culturally competent services have changed under the Oregon Health Plan.     

Relation between hippocampal gamma waves and behavioral disturbances induced by phencyclidine and methamphetamine

We compared the abilities of intact cats and cats that incurred lesions of areas 17 and 18 in adulthood, at one month of age (P28), or on the day of birth (P1), to detect and orient towards visual stimuli either moved into or illuminated in the periphery of the visual field, and to detect and orient towards a stationary, broad-band white-noise auditory stimulus. For all groups of cats, movement of a stimulus into the visual field was a more potent stimulus for evoking visually-guided orienting movements than illumination of a static light-emitting diode (LED). The potency of the auditory stimulus was also extremely high. Proficiency on both visual tasks was graded according to the age at which areas 17 and 18 were ablated in the sequence: adult, P1, P28 and intact in the sequence worst-->best performance. The superior performance of the P1- and P28-groups provided evidence for sparing of visually-guided orienting, but the sparing was incomplete because it did not match performance of intact cats. Lesions of areas 17 and 18 incurred in adulthood had no significant impact on orienting to auditory white-noise stimuli. However, orienting performance to auditory stimuli presented in the peripheral quadrants was slightly superior in the P28 group and reduced in the P1 group. Thus, the visual sparing exhibited by the P1 group may be at the expense of highly proficient orienting to auditory cues. Overall, these results extend our knowledge by showing that in addition to P1-cats, cats that incur lesions of areas 17 and 18 at one month-of-age also exhibit sparing of visually-guided orienting, and that the sparing is not confined to a single stimulation paradigm. Finally, the covariation in the magnitude of pathway modifications with the scale of the orienting proficiency in P1- and P28 cats helps to solidify the linkage between rewired brain pathways and spared visually-guided behaviors.     

Surgical management of intra-abdominal desmoid tumours

BACKGROUND: Intra-abdominal desmoids are uncommon neoplasms. The aggressive nature of these tumours and the potential for major morbidity secondary to resection can present a difficult surgical dilemma. METHODS: Patients with histologically confirmed intra-abdominal desmoid tumours undergoing laparotomy were identified from a prospective database. Clinical features and outcomes in this group were evaluated. RESULTS: The study group comprised 24 patients. Sixteen patients underwent complete resection of the tumour while eight had biopsy only, with or without intestinal bypass. Small intestinal resection was performed in 12 patients, including three who had a near-total enterectomy. Median follow-up was 62 months, with an actuarial overall survival rate of 73 per cent at 10 years. There was no difference in survival rate between completely resected and unresected patients (P = 0.73). There were seven deaths in the entire group, of which four were in those undergoing complete resection. CONCLUSION: Operation can cure patients with intra-abdominal desmoid tumours, but may result in significant morbidity, especially from loss of small intestine. No other therapy is a predictably good alternative to operation but the natural history of desmoids is often characterized by prolonged periods of stability or even regression. A period of watchful waiting, until significant symptoms develop, may be the most appropriate course in patients who risk mesenteric vascular injury or substantial enterectomy with attempts at resection.     

Electrocardiographic ST-segment changes during acute, severe isovolemic hemodilution in humans

BACKGROUND: Controversy exists regarding the lowest blood hemoglobin concentration that can be safely tolerated. The authors studied healthy resting humans to test the hypothesis that acute isovolemic reduction of blood hemoglobin concentration to 5 g/dl would produce an imbalance in myocardial oxygen supply and demand, resulting in myocardial ischemia. METHODS: Fifty-five conscious healthy human volunteers were studied. Isovolemic removal of aliquots of blood reduced blood hemoglobin concentration from 12.8 +/- 1.2 to 5.2 +/- 0.5 g/dl (mean +/- SD). Removed blood was replaced simultaneously with intravenous fluids to maintain constant isovolemia. Hemodynamics and arterial oxygen content (Cao2) were measured before and after removal of each aliquot of blood. Electrocardiographic (ECG) changes were monitored continuously using a Holter ECG recorder for detection of myocardial ischemia. RESULTS: During hemodilution, transient, reversible ST-segment depression developed in three subjects as seen on the electrocardiogram during hemodilution. These changes occurred at hemoglobin concentrations of 5-7 g/dl while the subjects were asymptomatic. Two of three subjects with ECG changes had significantly higher heart rates than those without ECG changes at the same hemoglobin concentrations. When evaluating the entire study period, the subjects who had ECG ST-segment changes had significantly higher maximum heart rates than those without ECG changes, despite having similar baseline values. CONCLUSION: With acute reduction of hemoglobin concentration to 5 g/dl, ECG ST-segment changes developed in 3 of 55 healthy conscious adults and were suggestive of, but not conclusive for, myocardial ischemia. The higher heart rates that developed during hemodilution may have contributed to the development of an imbalance between myocardial supply and demand resulting in ECG evidence of myocardial ischemia. However, these ECG changes appear to be benign because they were reversible and not accompanied by symptoms.     

Preliminary results of a randomized study on therapeutic gain by concurrent chemotherapy for regionally-advanced nasopharyngeal carcinoma: NPC-9901 Trial by the Hong Kong Nasopharyngeal Cancer Study Group.

PURPOSE: This randomized study compared the results achieved by concurrent chemoradiotherapy (CRT) versus radiotherapy (RT) alone for nasopharyngeal carcinoma (NPC) with advanced nodal disease. PATIENTS AND METHODS: Patients with nonkeratinizing/undifferentiated NPC staged T1-4N2-3M0 were randomized to CRT or RT. Both arms were treated with the same RT technique and dose fractionation. The CRT patients were given cisplatin 100 mg/m2 on days 1, 22, and 43, followed by cisplatin 80 mg/m2 and fluorouracil 1,000 mg/m2/d for 96 hours starting on days 71, 99, and 127. RESULTS: From 1999 to January 2004, 348 eligible patients were randomly assigned; the median follow-up was 2.3 years. The two arms were well-balanced in all prognostic factors and RT parameters. The CRT arm achieved significantly higher failure-free survival (72% v 62% at 3-year, P = .027), mostly as a result of an improvement in locoregional control (92% v 82%, P = .005). However, distant control did not improve significantly (76% v 73%, P = .47), and the overall survival rates were almost identical (78% v 78%, P = .97). In addition, the CRT arm had significantly more acute toxicities (84% v 53%, P < .001) and late toxicities (28% v 13% at 3-year, P = .024). CONCLUSION: Preliminary results confirmed that CRT could significantly improve tumor control, particularly at locoregional sites. However, there was significant increase in the risk of toxicities and no early gain in overall survival. Longer follow-up is needed to confirm the ultimate therapeutic ratio.     

A comparison of muscarinic acetylcholine receptors coupled to phosphatidylinositol turnover and to adenylate cyclase in guinea-pig atria and ventricles

The affinities of muscarinic acetylcholine receptor agonist and antagonist compounds have been measured in studies of adenylate cyclase inhibition and phosphatidylinositol turnover in guinea-pig atria and ventricles. The affinities of all compounds tested were similar in atrial and ventricular preparations. However, three antagonists, atropine, pirenzepine and gallamine had different affinities at receptors coupled to adenylate cyclase inhibition compared with those which stimulated turnover of phosphatidylinositols. The neuromuscular blocking agents gallamine and pancuronium, which demonstrate cardioselective acetylcholine receptor antagonist activity, were competitive antagonists at receptors coupled to both second messenger systems. However, their affinities measured in both systems were lower than expected from tissue-response studies. Therefore, the cardioselectivity of these compounds cannot be explained by a simple competitive interaction with receptors coupled to either adenylate cyclase inhibition or phosphatidylinositol turnover.     

Mechanisms of the dilator action of the Erigerontis Herba on rat aorta

Ethnopharmacological relevance

Erigerontis Herba is widely used as a traditional Chinese medicine and is commonly used for neuroprotection and vascular protection.

Aim of study

In this study, the vasodilator effects of Erigerontis Herba (DZXX) were investigated using rat isolated aorta rings.

Material and method

The involvement of endothelium in the vasorelaxation was studied by comparing response of endothelium-intact and endothelium-denuded aorta rings which precontracted with U46619. The involvement of K⁺ channels was studied by pretreatment of the aorta rings with various K⁺ channel inhibitors. The involvement of Ca²⁺ channel was studied by incubating aorta rings with Ca²⁺-free solution, primed with U46619 prior to elicit contraction by addition of Ca²⁺ solution.

Results

DZXX (0.2–2 mg/ml) induced a concentration-dependent relaxation on U44619-precontracted aorta rings with EC₅₀ of 0.354±0.036 mg/ml. Removal of endothelium or pretreatment with a BK_Ca inhibitor iberiotoxin, K_IR inhibitor barium chloride or K_v inhibitor 4-aminopyridine produced no effect on the DZXX-induced vasorelaxation. However, pretreatment with a K_ATP inhibitor glibenclamide or a non-selective K⁺ channel inhibitor tetraethylammonium produced significant inhibition on the DZXX-induced vasorelaxation by 29.9% and 21.3%, respectively. Pretreatment with DZXX (0.4, 1.2 and 2 mg/ml) produced a concentration-dependent inhibition on Ca²⁺-induced vasoconstriction.

Conclusions

These results suggest that the vasodilator effect of DZXX was endothelium-independent, mediated by decreasing the influx of Ca²⁺ by calcium channel inhibition and increasing the influx of K⁺ by opening of a K_ATP channel.     

Cyclopeptide RA-V inhibits angiogenesis by down-regulating ERK1/2 phosphorylation in HUVEC and HMEC-1 endothelial cells

BACKGROUND AND PURPOSE

Anti-angiogenic agents have recently become one of the major adjuvants for cancer therapy. A cyclopeptide, RA-V, has been shown to have anti-tumour activities. Its in vitro anti-angiogenic activities were evaluated in the present study, and the underlying mechanisms were also assessed.

EXPERIMENTAL APPROACH

Two endothelial cell lines, human umbilical vein endothelial cells (HUVEC) and human microvascular endothelial cells (HMEC-1), were used. The effects of RA-V on the proliferation, cell cycle phase distribution, migration, tube formation and adhesion were assessed. Western blots and real-time PCR were employed to examine the protein and mRNA expression of relevant molecules.

KEY RESULTS

RA-V inhibited HUVEC and HMEC-1 proliferation dose-dependently with IC₅₀ values of 1.42 and 4.0 nM respectively. RA-V inhibited migration and tube formation of endothelial cells as well as adhesion to extracellular matrix proteins. RA-V treatment down-regulated the protein and mRNA expression of matrix metalloproteinase-2. Regarding intracellular signal transduction, RA-V interfered with the activation of ERK1/2 in both cell lines. Furthermore, RA-V significantly decreased the phosphorylation of JNK in HUVEC whereas, in HMEC-1, p38 MAPK was decreased.

CONCLUSIONS AND IMPLICATIONS

RA-V exhibited anti-angiogenic activities in HUVEC and HMEC-1 cell lines with changes in function of these endothelial cells. The underlying mechanisms of action involved the ERK1/2 signalling pathway. However, RA-V may regulate different signalling pathways in different endothelial cells. These findings suggest that RA-V has the potential to be further developed as an anti-angiogenic agent.