Quantitative evaluation of the metabolic formation of methylhydrazine from acetaldehyde-N-methyl-N-formylhydrazone,the main poisonous compound of Gyromitra esculenta

The amounts of methylhydrazine in the peritoneal fluids of mice treated orally with acetaldehyde-N-methyl-N-formylhydrazone, the main poisonous compound of the mushroom Gyromitra esculenta Fr. ex. Pers., were determined in order to estimate quantitatively the metabolic formation of methylhydrazine from this compound. For the experiments 2.0 ml of saline was injected into the peritoneal cavities of experimental animals immediately after the dosing. The animals were sacrificed at different time points and their peritoneal cavities flushed with saline. From this fluid methylhydrazine was determined as benzaldehyde-N-methylhydrazone by gas liquid chromatography. For comparison, an identical test procedure was carried out on mice treated orally with methylhydrazine. The results indicate that more than 25%, or a toxicologically significant amount of acetaldehyde-N-methyl-N-formylhydrazone is metabolically hydrolysed to methylhydrazine.     

Diagnostic value of ultrasound, computed tomography, and angiography in ruptured aortic aneurysms

Some ruptural aneurysms cause nonspecific symptoms and the patients are referred for radiological examination because of the problems of differential diagnosis from conditions such as renal colic, diverticulitis, herniated disc, aortic dissection etc. Seven such patients have been examined either with ultrasonography, computed tomography or angiography. The diagnostic methods are compared. The more recent US and CT imaging methods are sufficiently rapid and reliable for diagnostic purposes, which should improve the prognosis for patients requiring immediate surgery for ruptured aortic aneurysms.     

Contrast-enhanced magnetic resonance imaging for the detection of acute haemorrhagic necrotizing pancreatitis

Eleven piglets with haemorrhagic necrotizing pancreatitis and nine piglets with oedematous pancreatitis were imaged using a multi-breath-hold TurboFLASH (TR 6.5 ms, TE 3 ms, TI 300 ms, flip angle 8 °, three slices) pre-excited T1-weighted sequence with an IV bolus injection of gadopentetate dimeglumine (Gd-DTPA, 0.3 mmol/kg) as a contrast agent to show dynamic contrast enhancement of the pancreas by MRI. All piglets were imaged according to the same protocol before inducing the disease. Following the IV Gd-DTPA bolus, time-enhancement curve of the pancreas during haemorrhagic necrotizing pancreatitis was significantly lower than during oedematous pancreatitis. The enhancement curves for the healthy piglets and piglets with oedematous pancreatitis did not differ significantly. Each piglet served as its own control. Because the results of this initial study are similar to those obtained with contrast-enhanced CT, we conclude that our results may encourage further clinical trials, and contrast-enhanced dynamic MRI may be an alternative to the established method of CT for diagnosing acute haemorrhagic necrotizing pancreatitis. Received 12 April 1995; Revision received 16 January 1996; Accepted 18 January 1996     

Thrombolytic therapy in acute ischemic stroke - basic concepts

Thrombolytic therapy with alteplase in acute ischemic stroke is currently established within 3 h from symptom onset in carefully selected patients. Expansion of the time window is being assessed in trials with alteplase and desmoteplase. Also, tenecteplase, reteplase and staphylokinase are being evaluated in stroke patients. A better understanding of the coagulation and fibrinolytic systems may provide insight into drug development, interactions, complications, and may ultimately improve patient triage and treatment regimens. Future adjuvant and additional therapies could prove useful for patients who do not benefit from standard thrombolytic treatment or may augment the overall gain.     

Reorganization of the composition of brain oscillations and their temporal characteristics in opioid dependent patients

In the present study, we examined the composition of electroencephalographic (EEG) brain oscillations in broad frequency band (0.5–30 Hz) in 22 opioid-dependent patients and 14 healthy subjects during resting condition (closed eyes). The exact compositions of brain oscillations and their temporal behavior were assessed by the probability–classification analysis of short-term EEG spectral patterns. It was demonstrated that EEG of patients with opioid dependence was characterized by (a) significant reorganization of brain oscillations with increase in the percentage of beta- and mostly fast-alpha-rhythmic segments, (b) longer periods of temporal stabilization for alpha and beta brain oscillations and by shorter periods of temporal stabilization for theta and polyrhythmic activity when compared with control subjects, and (c) right-sided dominance (significantly larger relative presence of particular spectral patterns in EEG channels of the right hemisphere). These effects were widely distributed across the cortex with the maximum magnitude in the occipital, right parietal, temporal, and frontal areas. Taken together the present study suggested (a) an allostatic state with neuronal activation, and (b) high sensitivity of the right hemisphere to adverse opioid effects.     

Timing-dependent modulation of the posterior parietal cortex-primary motor cortex pathway by sensorimotor training

Interplay between posterior parietal cortex (PPC) and ipsilateral primary motor cortex (M1) is crucial during execution of movements. The purpose of the study was to determine whether functional PPC-M1 connectivity in humans can be modulated by sensorimotor training. Seventeen participants performed a sensorimotor training task that involved tapping the index finger in synchrony to a rhythmic sequence. To explore differences in training modality, one group (n = 8) learned by visual and the other (n = 9) by auditory stimuli. Transcranial magnetic stimulation (TMS) was used to assess PPC-M1 connectivity before and after training, whereas electroencephalography (EEG) was used to assess PPC-M1 connectivity during training. Facilitation from PPC to M1 was quantified using paired-pulse TMS at conditioning-test intervals of 2, 4, 6, and 8 ms by measuring motor-evoked potentials (MEPs). TMS was applied at baseline and at four time points (0, 30, 60, and 180 min) after training. For EEG, task-related power and coherence were calculated for early and late training phases. The conditioned MEP was facilitated at a 2-ms conditioning-test interval before training. However, facilitation was abolished immediately following training, but returned to baseline at subsequent time points. Regional EEG activity and interregional connectivity between PPC and M1 showed an initial increase during early training followed by a significant decrease in the late phases. The findings indicate that parietal-motor interactions are activated during early sensorimotor training when sensory information has to be integrated into a coherent movement plan. Once the sequence is encoded and movements become automatized, PPC-M1 connectivity returns to baseline.     

Multimodality treatment programs for malignant pleural mesothelioma using high-dose hemithorax irradiation.

The characteristic of malignant pleural mesothelioma is a tumor that grows by plate-like extension over the pleura, and invades adjacent tissues and organs. Radical surgical removal of the tumor is generally not possible, and most treatment regimens involve combined chemotherapy and radiotherapy, as well as debulking surgery. We have prospectively evaluated five locally-aggressive multi-modality treatment programs, using different hemithorax irradiation schedules and chemotherapy regimens. One hundred patients with confirmed malignant pleural mesothelioma entered the study between 1977 and 1989. The treatment programs, which can consecutively, were: I, 20 Gy (10 x 2 Gy) to the hemithorax + CYVADIC (cyclophosphamide 500 mg/m2 d 1, vincristine 1 mg/m2 d 1 and 5, adriamycin 40 mg/m2 d 1 and dacarbazine 200 mg/m2 d 1 and 5, several cycles before and after irradiation); II, 55 Gy (25 x 2.2 Gy) to the hemithorax + 15 Gy (6 x 2.5 Gy) to the tumor + CYVADIC (2 cycles before, 1 cycle during, and 2 cycles after irradiation); III, Mitoxantrone (14 mg/m2 q 28 d, < or = 6 cycles) followed by 70 Gy (56 x 1.25 Gy, twice a day); IV, 4-Epirubicin (110-130 mg/m2 q 28 d, < or = 6 cycles) followed by 35 Gy (28 x 1.25 Gy twice a day) to the hemithorax + 36 Gy (9 x 4 Gy every 2 days) to the tumor; V, Etoposide (150 mg/m2 1, 3, 5 q 28 d) followed by 38.5 Gy (11 x 3.5 Gy) to the hemithorax. A new system for evaluating tumor response in pleural mesothelioma was applied. None of the combined treatment programs prevented local invasive growth or the spread of mesothelioma outside the hemithorax. The median survival time was slightly increased from 8 to 12 months for those patients who completed the protocol treatments, but progressive disease was the invariable outcome. Radiation pneumonitis and fibrosis were severe and compatible with results of total loss of lung function on the irradiated side. We conclude that data relating to therapeutic responses and treatment programs in malignant mesothelioma should be better correlated internationally, if the problems associated with the evaluation of treatment and the management of patients with mesothelioma are to be improved.