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PubMed2005

Acute effects of lead, mercury and manganese on the central and peripheral nervous system in rats in combination with alcohol exposure.

Heavy metals, due to their numerous applications in industrial processes, agrochemicals and household articles, have caused a widespread pollution and can be found in different foods. One of their target organs is the central nervous system. The toxic effects of heavy metals can be modified by lifestyle-originated factors such as consumption of alcohol. The aim of this study was to investigate the changes in spontaneous cortical activity (ECoG), cortical sensory evoked potentials (EPs) and peripheral nerve action potentials, recorded in rats pre-treated with alcohol and acutely treated with lead, mercury and manganese by intraperitoneal injection. In the ECoG, Hg2+ caused a massive shift to lower frequencies while the effect of Mn2+ and Pb2+ was slight, and alcohol pre-treatment altered the effect of the metals minimally. The amplitude of EPs increased upon the application of heavy metals, and the peak latency lengthened. The effect of Hg2+ was the strongest and that of Pb2+ the weakest, and these effects were potentiated by alcohol. Exposure to heavy metals, together with alcohol consumption, can aggravate the known neurotoxic effects.

Action Potentials↗

PubMed2006

A phase II study of docetaxel and carboplatin in Thai patients with advanced non-small-cell lung cancer.

OBJECTIVE: This phase II study aimed to assess the effectiveness of the docetaxel plus carboplatin combination in chemotherapy-naive Thai patients with advanced non-small-cell lung cancer (NSCLC). MATERIAL AND METHOD: Forty patients with Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0-1, stage IIIB/IV NSCLC were enrolled in a phase H study between August 2001 and April 2003. Docetaxel 75 mg/m2 and Carboplatin AUC = 6 were given every 3 weeks. Response to treatment and toxicity were graded using standard WHO criteria. The Thai Functional Living Index Cancer (T-FLIC) scale was used to assess the Quality of Life (QoL) of all treated patients. RESULTS: Forty patients (median age: 55 years, range, 39-68 years; PS:0-1) were enrolled: one had stage IIIB disease with effusion, while thirty-nine had stage IV disease. Five patients were non-evaluable due to death within the first cycle; two dying of febrile neutropenia and sepsis, two of pulmonary infection, and one of unknown etiology. Partial response (PR) was seen in 28.6% patients, stable disease (SD) in 25.7%, and progressive disease (PD) in 45.7%. The median survival time was 32 weeks and the 1-year survival rate was 30.7%. Body mass index (BMI) was the only factor associated with survival time (univariate analysis: p = 0.006; multivariate analysis: p = 0.004). Other factors (gender, age, histology, ECOG PS, and glomerular filtration rate) were not predict for survival. The major treatment-related toxicities were neutropenia (from 152 treatment cycles there were grade 4: 19.7%; grade 3: 23.7%), febrile neutropenia (from 152 treatment cycles there was 3.95%), and diarrhea (grades 3/4: 0.66%). The QoL scores improved significantly throughout the treatment period. CONCLUSION: The regimen of docetaxel and carboplatin is active in advanced NSCLC and may be considered for first-line therapy.

Adult↗

PubMed1991

Effect of acutely-induced lactic acidemia on fetal breathing movements, heart rate, blood pressure, ACTH and cortisol in sheep.

Experiments were conducted in 8 chronically-catheterized fetal sheep at 125-135 days gestation in order to determine the effect of exogenously administered lactic acid to the fetus on fetal heart rate, blood pressure, breathing movements (FBM), electrocortical activity (ECOG), plasma immunoreactive (IR-ACTH) and cortisol concentrations. When fetal arterial pH decreased from 7.37 +/- 0.01 during the control period to 7.20 +/- 0.01, there was an initial bradycardia followed by tachycardia but no change in blood pressure. The amplitude of FBM increased 2-fold initially in association with an increase in PCO2 from 47.9 +/- 2.1 mmHg to 58.8 +/- 3.6 mmHg at 5 min into the lactate infusion. There was no change in the incidence of FBM or low-voltage ECOG and there was no change in the plasma concentrations of IR-ACTH and cortisol with the infusion of lactate. We conclude that the major effects of acutely elevating circulatory lactate concentrations in fetal sheep are to increase the amplitude of FBM and to cause an initial bradycardia followed by a tachycardia.

Adrenocorticotropic Hormone↗

PubMed2006

Development and validation of the Functional Assessment of Cancer Therapy-Kidney Symptom Index (FKSI).

The Functional Assessment of Cancer Therapy (FACT)-Kidney Symptom Index (FKSI) was developed and validated to enhance treatment decision-making, practice guidelines, symptom management, and treatment efficacy for kidney cancer patients. Thirty-four symptoms related to the disease were identified and tested. An equal weighting of patient and clinician ratings of the relative importance of each of these items led to production of a 15-item index (FKSI-15) and a 10-item abbreviated option (FKSI-10). To assess psychometric properties, patients completed the FKSI, Functional Assessment of Cancer Therapy-General (FACT-G), Eastern Cooperative Oncology Group-Performance Status Rating (ECOG-PSR), and a Global Rating of Change Scale (GRCS). Patient responses to the FKSI were analyzed for internal consistency, test-retest reliability, convergent and discriminant validity, and responsiveness to change in clinical status. The FKSI-10 showed high internal consistency; correlations between both FKSI-10 and the physical and functional well being domains of the FACT-G were high. The FKSI-10 differentiated patients grouped by ECOG-PSR (all P < 0.001) and discriminated patients based on their GRCS rating. The minimally important difference (MID) range estimate for the FKSI-10 was 2-4 points; the psychometric properties of the FKSI-15 were very similar (MID range, 3-5 points).Thus, the FKSI-15 and FKSI-10 are reliable and valid symptom indices for evaluating kidney cancer patients.

Adult↗

PubMed2006

[Prognostic analysis of 62 cases of nasal NK/T-cell lymphoma].

BACKGROUND & OBJECTIVE: Extranodal NK/T-cell lymphoma of nasal type (ENKTL) is a rare disease entity with unique biological behavior, of which definitive characteristics are still unknown. This study was to investigate the clinical features and prognostic factors of ENKTL in the population of southern China. METHODS: Records of 62 patients with pathologically confirmed ENKTL, treated in Cancer Center of Sun Yat-sen University from Jan. 1999 to Dec. 2004, were reviewed. Detailed clinical and laboratory data were included in univariate analysis, and statistically significant factors in univariate analysis were then included in multivariate analysis. RESULTS: Of the 62 patients, 47 were men, and 15 were women, with the median age of 42; 92% of the patients had localized disease, and 76% had international prognostic index (IPI) of 0 or 1. Before treatment, 26% of the patients had anemia, 92% had ECOG performance status (PS) score of 0-1, and 53% presented B symptoms. With a median follow-up duration of 18 months, the median overall survival time was 27 months (95% CI: 10-45 months). In multivariate analysis, hemoglobin (Hb) <110 g/L, B symptoms, and ECOG PS score >1 were statistically significant unfavorable prognostic factors. CONCLUSION: Hb together with B symptoms and PS score may be independent prognostic factors for ENKTL.

Adolescent↗

PubMed2006

Chemotherapy with gemcitabine, paclitaxel, and cisplatin in the treatment of patients with advanced transitional cell carcinoma of the urothelium.

Chemotherapeutic agents are active in advanced bladder cancer, and various combinations have shown promising results. The objective of this study was to evaluate the efficacy of combination chemotherapy with gemcitabine, paclitaxel, and cisplatin in patients with advanced urothelial carcinoma. Fifty-nine patients with metastatic or locally advanced transitional cell carcinoma of the urothelium were treated between 2000 and 2005. No patient had received any previous systemic chemotherapy. All patients received chemotherapy intravenously with gemcitabine at a dose of 1000 mg/m(2) on days 1 and 8, paclitaxel at a dose of 80 mg/m(2) on days 1 and 8, and cisplatin at a dose of 50 mg/m(2) on day 2. Treatment courses were repeated every 21 days. After completion of four to six courses in this regimen an intravenous application of gemcitabine was repeated every 28 days at a dose of 1000 mg/m(2). Fifty-nine patients were treated between 2000 and 2005. Nine patients (15%) had >or=1 visceral site of metastases, and no patient had received any previous systemic chemotherapy. Forty-eight patients (81%) achieved objective responses to treatment (56% complete responses). The median actuarial survival was 22 months, and the actuarial 1-year and 2-year survival rates were 68% and 39%, respectively. After a median follow-up of 17.5 months, 29 patients remained alive and 25 were free of disease progression. The median progression-free survival for the entire group was 10 months. The median survival time for patients with an Eastern Cooperative Oncology Group (ECOG) status of 0, 1, and 2 was 37.5, 17, and 12 months, respectively. Grade 3-4 neutropenia occurred in 39% of the patients. The combination of gemcitabine, paclitaxel, and cisplatin is a highly effective and tolerable regimen for patients with advanced urothelial carcinoma. This treatment should be considered as a suitable option that deserves further prospective evaluation. The ECOG performance status is an important predictive factor for survival.

Aged↗

PubMed1991

Intracerebroventricular dermorphin, but not dermenkephalin, is epileptogenic in the rat.

The effects of intracerebroventricular administration of dermorphin (mu agonist) and dermenkephalin (delta agonist) were studied at the electrocorticographic (ECoG) and electromyographic (EMG) levels in free-moving rats. A very low dose of dermorphin (125 pmol) induced ECoG spiking, occasional myoclonic jerks, wet-dog shakes and catalepsy. In addition, electrical seizures were triggered with doses of 250 to 500 pmol. These signs were reversed by an i.p. injection of naloxone (1 mg kg-1). However, no epileptic-like phenomena were seen after administration of dermenkephalin up to 1 nmol. These results indicate that mu but not delta receptors are involved in the epileptogenic effect of intraventricularly administered opiates.

Animals↗

PubMed1991

[Kindling effect in models of epilepsy induced by clinrats].

In order to create chemical kindling effect model of epilepsy, fifty-six adult male SD rats were used in this experiment, and randomly divided into five groups. An intramuscular injection of various subthreshold dose of CL (0.50, 0.75, 1.00, 1.25 mg/kg) was given repeatedly per 3.5 days in the I-IV groups, V group received injections of normal saline of the same volume as control. ECoG and EHG were recorded by telemetric method through electrodes chronically implanted in the cortex and hippocampus. The behavior of them was observed at the same time. The results of experiments showed that: 1. CL can lead to the typical behavior, ECoG and EHG of epilepsy. So it is an effective chemical kindling agent of causing epilepsy, and hippocampus was more than cortex to CL. 2. The relationship between the seizure stages induced by CL various dose groups and the mean injection times had a linear correlation through linear regressive processing (r value: 0.9276-0.99732). The difference comparison of linear regressive intercept of various groups was significant (P less than 0.05), respectively. It is indicated that the more the dose of CL increase, the less the injection times of reaching seizure stages. 3. 24 rats of the experimental groups 46 rats had reached kindling criterion through 40 times injection of CL. The difference comparison between I, II and III, IV groups of kindling rats was quite significant (P less than 0.01), respectively. 4. The mean persistence time of all kindled rats was 113.42 days. The longest persistence time of them was 224 days.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1991

Effects of alcohol (ethanol) on the fetus.

Alcohol (ethanol) use during pregnancy can produce a wide spectrum of effects in the developing embryo/fetus that are dependent on the maternal drinking pattern. The effects of chronic ethanol exposure on the developing conceptus are reviewed with primary focus on ethanol teratogenesis, manifesting in the human as the fetal alcohol syndrome or fetal alcohol effects. The effects of acute ethanol exposure on the near-term fetus are described, including suppressed fetal breathing movements, electrocorticographic (ECoG) activity and electrooculographic (EOG) activity. The ethanol-induced suppression of fetal breathing movements is a very sensitive index of acute exposure of the near-term fetus to ethanol, and appears to involve a direct mechanism of action rather than an indirect mechanism involving suppression of electrocortical activity. The disposition of ethanol and its pharmacologically active proximate metabolite, acetaldehyde, and the activity of alcohol dehydrogenase and aldehyde dehydrogenase in the near-term maternal-fetal unit are described, and a pharmacokinetic model is proposed. The effects of short-term ethanol exposure on the near-term fetus include the development of tolerance to the ethanol-induced suppression of fetal breathing movements, low-voltage ECoG activity and EOG activity. The development of tolerance occurs more rapidly to the latter two fetal biophysical activities. The mechanism of tolerance development appears to be pharmacodynamic (functional) in nature, as there is no increase in the rate of ethanol elimination from the maternal-fetal unit. The role of prostaglandins (PGs) in the mechanism of the ethanol-induced suppression of fetal breathing movements is described. In the near-term fetus, there is a direct relationship between fetal blood ethanol concentration and fetal plasma PGE2 concentration, and an inverse relationship between the incidence of fetal breathing movements and each of fetal plasma and fetal cerebrospinal fluid (CSF) PGE2 concentrations. Indomethacin, a PG synthetase inhibitor, selectively blocks and reverses the ethanol-induced suppression of fetal breathing movements. These data support the postulates that the ethanol-induced suppression of fetal breathing movements is mediated by increased PGE2 concentration in the near-term fetus and that the ability of indomethacin to antagonize the ethanol-induced suppression of fetal breathing movements is due to its biochemical action to decrease fetal PGE2 concentration.(ABSTRACT TRUNCATED AT 400 WORDS)

Alcohol Drinking↗

PubMed1991

Hypoxic apnoea induced by N2 inhalation can be reversed by the aspiration reflex in anaesthetized cats.

Various cardiorespiratory and electrophysiological parameters were analysed in a model of acute respiratory failure induced by inhalation of pure nitrogen in approximately 150 anaesthetized cats. Initial hyperventilation leading to apnoea was characterized by extreme hypoxaemia, marked bradycardia and flattening of electrocortical (ECoG) activity. Artificial ventilation applied at the stage of marked mydriasis usually spontaneously prevented cardiovascular failure and normalized vital functions. Up to seven successive apnoeic attacks could be induced in the same cat. During the first 30 or 60 s of apnoea, nasopharyngeal stimulation usually elicited a typical gasp-like aspiration reflex, while tracheobronchial stimulation provoked a weak cough only in 28 and 34% of cases for 30- and 60-s apnoea, respectively. The aspiration reflex could be elicited at very low and even isoelectric ECoG activity, and its periodic provocation (without artificial ventilation) resulted, more frequently than did gasping, in recovery from hypoxic apnoea. Arousal and resuscitation induced by the aspiration reflex can provide a useful model to study the mechanisms of reversible respiratory failure and restitution of vital functions.

Administration, Inhalation↗

PubMed1990

The effects of naloxone on the changes in breathing and behaviour induced by morphine in the foetal sheep.

In the foetal sheep, administration of morphine induces apnoea followed by hyperpnoea; during hyperpnoea the foetus arouses. We tested the hypothesis that naloxone, an opiate antagonist, would block these responses. In 14 foetal sheep between 123 and 140 days of gestation, we measured electrocortical activity (ECoG), eye movements (EOG), diaphragmatic activity (EMGdi), blood pressure and amniotic pressure. Morphine (1 mg/kg) was injected in the foetal jugular vein during low-voltage ECoG. Saline or naloxone (0.1, 0.5 and 2.0 mg) were given, in randomized order, before the morphine injection, shortly after morphine injection during apnoea, and during maximum hyperpnoea. Saline alone had no effect on breathing or behaviour. When saline and naloxone preceded the morphine injection the length of apnoea was 26.6 +/- 7.7 and 19.5 +/- 7.0 min (SEM, P = 0.25) while the length of sustained hyperpnoea was 104.8 +/- 11.4 and 29.6 +/- 8.4 min respectively (P = 0.001). When administered during the maximum breathing response, naloxone decreased the length of breathing from 92.2 +/- 8.4 (saline) to 8.8 +/- 2.9 min (P = 0.001). Respiratory output (fEMGdi x f) also decreased from 6545 +/- 912 arbitrary units post saline to 3841 +/- 629 arbitrary units after naloxone (P = 0.05). Arousal disappeared with the decrease in breathing response. The negligible effect of naloxone on apnoea and its strong inhibition of hyperpnoea suggest that morphine may act on two distinct central regions or on two subtypes of opioid receptors to produce apnoea, hyperpnoea and arousal.

Animals↗

PubMed1990

Effect of hyperoxia (PaO2 50-90 mmHg) on fetal breathing movements in the unanaesthetized fetal sheep.

Hypoxia inhibits fetal breathing movements but after birth it stimulates breathing. These differences have long been thought to involve central nervous inhibitory mechanisms. Such mechanisms might exert a tonic inhibition of fetal breathing movements at normal fetal PaO2 and the rise in PaO2 at birth might lift this inhibitory effect. To test this hypothesis 7 fetal sheep were chronically instrumented at 125-130 days for recording electrocortical activity (ECoG), and the electromyograph (EMG) activity of the diaphragm and neck muscles. Catheters were placed in a fetal carotid and a brachial artery and in the fetal trachea. For an extracorporeal membrane oxygenation system a 12 F gauge silastic catheter was placed in the right atrium for draining fetal blood and a 9.6 F gauge catheter was placed in a carotid artery to return oxygenated blood. Three days after operation the fetuses were connected to the extracorporeal membrane oxygenation system and fetal PaO2 was raised to 65.2 +/- 4.4 mmHg (SEM) for 6 to 19 h without changing pH or PaCO2. Neither the incidence of high voltage ECoG (48.5 +/- SEM 2.0% vs 52.8 +/- 3.3%) nor of fetal breathing movements (37.3 +/- 2.6% vs 23.8 +/- 5.9%) changed during the periods of hyperoxia. Since fetal breathing movements did not become continuous, we conclude that the lower PaO2 in the fetus compared to the neonate does not exert a tonic inhibitory influence on fetal breathing movements.

Animals↗

PubMedDate not supplied

[Degree of homogeneity of the forms of statistical relationship between the EEG and spike currents of neurons].

The correlation between the spike activity and the waves of surface ECoG was studied in the visual and motor cortex of alert non-immobilized rabbits. A comparison was made between the forms of the obtained correlation functions for the cells with different horizontal and vertical distances between them. The analysis revealed the similarity of such functions in neurones of V-VI cortical layers, situated vertically under each other along the microelectrode track. Similar in form statistic connections between the ECoG and the background spike activity were also found, beginning with the depth of 1.000 mc, in the neurones situated at the same horizontal cortical level; however, with the increased distance between the cells the degree of similarity of these connections decreases in a non-linear way. On the basis of the obtained data a conclusion is made that the tangential sizes of the background functional ensembles of the cortical neurones are within the range of 140-300 mc.

Animals↗

PubMed1979

Mechanism of the cerebrocortical vasodilatation during anoxia.

The possible role of cerebrocortical ion homeostasis, NAD/NADH redox state and of cortical oxygen tension was investigated in the initiation of hypoxic cortical vasodilatation. In addition, changes in cerebrocortical extracellular concentrations of Na+, K+, and Cl- during anoxia were studied. The results were as follows. a) The cerebrocortical reflectance decrease, e.g. cerebral vasodilatation, lagged behind the cortical pO2 decrease by 1-2 sec, but preceded the decrease of arterial blood pressure and ECoG as well as the extracellular Na+, K+, Cl- increases by 20-30 sec. Since the cortical pO2 decreased first and the ion changes lagged behind the onset of vasodilatation by 20-30 sec, it is suggested that the CBF increase in hypoxia is mediated via the cortical pO2 decrease. b) A significant NAD reduction was already present after 20 sec. of nitrogen breathing. Since the ECoG and MABP decreased, and K+ activity increased much later than this, it is presumed that the NAD reduction during the first 30-40 sec of anoxia indicates an increased rate of glycolysis, but not mitochondrial hypoxia. c) In the predepolarization phase a 17% K+, 4% Na+, 5% Cl- increase is probably the result of a reduction of the extracellular spaces caused by water movement and by the migration of Na+ and Cl- from the extracellular to the intracellular space. The large K+, Na+, Cl- changes during terminal depolarization can be interpreted as a result of the failure of the membrane bound Na+ -K+ pump and of the altered ion permeability of the cell membranes.

Action Potentials↗

PubMed1979

Intracellular oxygen tension and energy metabolism in the cat brain cortex during haemorrhagic shock.

The changes in intracellular oxygen tension and energy metabolism of the cat brain cortex were studied by surface fluororeflectometry during haemorrhagic shock. The results may be summarized as follows. (a) Intracellular oxygen tension, i.e. the maximum cortical NAD reduction obtained during nitrogen gas inhalation decreased gradually during the hypovolaemic phase of shock and finally, the brain cortex became ischaemic. (b) Partial uncoupling of the cerebrocortical mitochondrial respiration and oxidative phosphorylation appeared in the very early period of bleeding, as indicated by the overshot of the cortical NAD/NADH redox state towards oxidation subsequent to the cessation of nitrogen gas inhalation. Partial uncoupling of mitochondrial respiration and oxidative phosphorylation became more pronounced during the later phases of bleeding, finally, the mitochondrial electron transport stopped. In line with these changes the frequency and the amplitude of ECoG decreased gradually and markedly during the hypovolaemic phase of shock. (c) Microcirculation and energy metabolism of the cat brain cortex were severely and irreversibly damaged during the hypovolaemic phase of shock. This was clearly shown by the fact that in the majority of experiments the nitrogen anoxia after reinfusion failed to bring about changes in the cortical NAD/NADH redox state and the ECoG changes occurred during bleeding did not improve after reinfusion. It is concluded that the early disturbances of cerebrocortical energy metabolism play an important role in the development of neural and vascular lesions of the brain that occur during haemorrhagic shock.

Action Potentials↗

PubMed1989

[Application of the electrocochleogram in Menière's syndrome].

The results of evoked potentials (ECOG and ABR) in 92 patients with complaints of dizziness and vertigo were analysed. There were 69 cases of Menière's syndromes, among which 45 cases (75%) showed increase of the summating potentials. In 22 cases the SP/AP rate exceeded 0.37 of 23 cases of vertebral basilar arteria TIA, one case showed negative wave SP increase, one case showed SP/AP ratio exceeding 0.37 and 3 cases showed prolonged latency of I wave in ABR. It was pointed out the simultaneous use of ECOG and ABR would be of help in identifying the most probable cause of dizziness and vertigo and this method would be worthy to be used on a much broader scale.

Adult↗

PubMedDate not supplied

[Sleep and wakefulness in Greenland seal pups].

ECoG of both hemispheres, EOG, neck EMG and EKG were recorded in 2 white (age 10 days) and 2 gray pups (age 1 month) of harp seal. The active wakefulness occupied 23.4 +/- 3.8% of total recording time, the relaxed wakefulness--32.6 +/- 3.6%, drowsiness--4.8 +/- 1.1%, slow wave sleep--31.5 +/- 3.0%, paradoxical sleep--7.7 +/- 0.8%. The sleep cycle averaged 18.2 +/- 1.4 min. Interhemispheric asymmetry of the ECoG was not seen in all 4 pups. The respiration was fast and regular in the relaxed wakefulness, then long respiration pauses were alternated with episodes of hyperventilation during slow wave sleep and there was rare and irregular respiration in the paradoxical sleep. The heart rate was lowest during the paradoxical sleep. It is suggested that this pattern of sleep, allowing seals to delay their breathing during sleep for a long time may be considered as an adaptation to existence in freezing seas.

Animals↗

PubMed1989

Ontogenetic development of ketamine-induced sleeping time and electrocorticographic changes in rats.

Latency to the loss of righting reflex and sleeping time after ketamine were measured in 261 rats aged 7, 12, 18, 25 and 90 days. The sensitivity to ketamine was highest in 7-day-old animals and decreased with age. In the youngest group rats slept after the 20-mg/kg dose whereas not all adult animals lost their righting ability after a dose of 160 mg/kg. Electrocorticographic (ECoG) study demonstrated an age dependence of changes induced by ketamine. The youngest group exhibited only suppression of the originally discontinuous ECoG whereas signs of slow-wave sleep or depression appeared in older rats.

Aging↗