Clinical associations of prenatal ischaemic white matter injury

Neuropathological examinations were carried out at necropsy on 274 cases of intrauterine death or neonatal death at or before three days after birth. Fifty six (20.4%) subjects had evidence of prenatal ischaemic brain damage. On review of the maternal case notes to ascertain antenatal clinical associations there was an increased incidence of intrauterine growth retardation, either based on birth weight for gestational age (odds ratio (OR) 2.0; 95% confidence interval (CI) 1.1 to 3.7) or diagnosed antenatally (OR 2.7; 95% CI 1.3 to 5.6). Oligohydramnios was also more common (OR 2.9; 95% CI 1.2 to 7.0). The association of intrauterine growth retardation and white matter damage remained after excluding fetuses with a major congenital anomaly (OR 2.4; 95% CI 1.1 to 5.1). The findings suggest that chronic intrauterine hypoxia may be associated with damage to cerebral white matter among fetuses and infants who die. The relation between ischaemic white matter damage and cerebral palsy among survivors remains speculative.     

Purification, crystallisation and preliminary X-ray diffraction study of ribosome inactivating protein: saporin

OBJECTIVES: To compare transesophageal atrial pacing stress echocardiography with dobutamine stress echocardiography for feasibility, safety, duration, patient acceptance and concordance in inducing wall motion abnormalities. BACKGROUND: Transesophageal atrial pacing is an effective method of increasing heart rate and has been used in the assessment of coronary artery disease. METHODS: Both tests were performed in sequence on the same patients in random order. Transesophageal atrial pacing stress echocardiography began at a heart rate of 10 beats/min above the baseline value and was increased by 20 beats/min every two min until 85% of the age-predicted maximum heart rate or another end point was reached. Dobutamine echocardiography was performed using three-min stages and a maximum dose of 40 microg/kg per min. Atropine (total dose < or =2 mg) was administered at the start of the 40 microg/kg per min stage if needed to augment heart rate or during pacing if Wenckebach heart block occurred. RESULTS: Transesophageal atrial pacing stress echocardiography was feasible in 100 of 104 patients (96%); the duration (8.6+/-3.6 min) was significantly shorter than that of dobutamine stress echocardiography (15.1+/-3.9 min) (p = 0.0001). With transesophageal atrial pacing stress echocardiography, the recovery period was shorter, symptoms and dysrhythmias were fewer, hypertension and hypotension were less common and target heart rate was more frequently achieved. No complications occurred with either test. Patient acceptance was satisfactory. Agreement between results of both tests was good for segmental wall motion scoring with a 16-segment model, scores 1 to 5 (kappa: rest, 0.79; peak, 0.57) and test interpretation (normal, ischemia, infarction or resting wall motion abnormality with ischemia) (kappa: 0.77). CONCLUSIONS: Transesophageal atrial pacing stress echocardiography is a feasible, well-tolerated alternative to dobutamine stress echocardiography. It can be performed rapidly and shows good agreement with dobutamine stress echocardiography in the induction of myocardial ischemia.     

Reaction of cytochrome P450 with cumene hydroperoxide: ESR spin-trapping evidence for the homolytic scission of the peroxide O-O bond by ferric cytochrome P450 1A2

ESR spin trapping was used to investigate the reaction of rabbit cytochrome P450 (P450) 1A2 with cumene hydroperoxide. Cumene hydroperoxide-derived peroxyl, alkoxyl, and carbon-centered radicals were formed and trapped during the reaction. The relative contributions of each radical adduct to the composite ESR spectrum were influenced by the concentration of the spin trap. Computer simulation of the experimental data obtained at various 5,5-dimethyl-1-pyrroline N-oxide (DMPO) concentrations was used to quantitate the contributions of each radical adduct to the composite ESR spectrum. The alkoxyl radical was the initial radical produced during the reaction. Experiments with 2-methyl-2-nitrosopropane identified the carbon-centered adducts as those of the methyl radical, hydroxymethyl radical, and a secondary carbon-centered radical. The reaction did not require NADPH-cytochrome P450 reductase or NADPH. It is concluded that the reaction involves the initial homolytic scission of the peroxide O-O bond to produce the cumoxyl radical. Methyl radicals were produced from the beta-scission of the cumoxyl radical. The peroxyl adduct was not observed in the absence of molecular oxygen. We conclude that the DMPO peroxyl radical adduct detected in the presence of oxygen was due to the methylperoxyl radical formed by the reaction of the methyl radical with oxygen. At a higher P450 concentration, a protein-derived radical adduct was also detected.     

Mechanism of the radiation-protective effect of indralin

Output from the interpositus nucleus can inhibit the inferior olive, probably via the GABA-ergic nucleo-olivary pathway. It has been suggested that the function of this inhibition might be to regulate synaptic plasticity resulting from parallel fibre/climbing fibre interaction in cerebellar Purkinje cells, by providing negative feedback information to the olive. Thus, when a learned response, generated by the interpositus nucleus, reaches a sufficient amplitude, the olive would be inhibited and further learning blocked. This suggestion was tested in a classical conditioning paradigm. Decerebrate ferrets were trained using electrical skin stimulation of the forelimb as the conditioned stimulus (CS) and periorbital stimulation as the unconditioned stimulus (US). Climbing fibre responses evoked in Purkinje cells by the US were recorded as surface field potentials in the part of the c3 zone controlling eyeblink. It was found that the CS did not inhibit the olive at the beginning of training, but when conditioned responses were large, the olive was inhibited by the CS in some animals. After a number of unpaired CS presentations, which caused extinction of the conditioned response, the inhibition disappeared. The size of individual conditioned responses correlated negatively with the size of the climbing fibre responses evoked by the US. Climbing fibre responses evoked by direct stimulation of the olive were also inhibited. It was concluded that cerebellar output during performance of a conditioned response inhibits the inferior olive. The results thus support the hypothesis of a cerebellar locus of conditioning and are consistent with the proposed role of cerebello-olivary inhibition.     

CHOP vs. ProMACE-CytaBOM in the treatment of aggressive non-Hodgkin's lymphomas: long-term results of a multicenter randomized trial.(PETHEMA: Spanish Cooperative Group for the Study of Hematological Malignancies Treatment, Spanish Society of Hematology)

From May 1985 to May 1989, 175 patients with previously untreated aggressive non-Hodgkin's lymphoma were randomized to receive CHOP or ProMACE-CytaBOM. Eligibility criteria included follicular large-cell diffuse small cleaved-cell, diffuse mixed, diffuse large-cell and immunoblastic lymphoma with an Ann Arbor stage II, III or IV. One hundred and forty-eight patients were evaluable. There were no significant differences between the 2 treatments in response rate (83.5% [57.5% CR] for CHOP vs. 88% [62% CR] for ProMACE-CytaBOM), time to treatment failure (29% vs. 31% at 5 yr), or overall survival (42% in both groups at 5 yr). Furthermore, there were no significant differences between the 2 regimens when response rates and outcome were analyzed for different prognostic subgroups. Toxicity was not significantly different between the 2 regimens, although only 1 patient died as result of treatment-related toxicity in the CHOP arm compared to 6 patient in the ProMACE-CytaBOM group (p = 0.126). In conclusion, in this study ProMACE-CytaBOM has not proved to be superior to CHOP in aggressive lymphomas. This trial gives support to the notion that CHOP still is the standard chemotherapy for aggressive lymphomas, and that new treatment approaches for these lymphomas should be compared to CHOP.     

Chronic abdominal pain: role of video-laparoscopic adhesiolysis

Adhesions have been suggested as a possible cause of chronic abdominal pain, but the reports of their etiological role conflict. Lysis of adhesions has been proposed as the therapeutic modality of choice, although the reports of success are controversial. The aim our prospective study was to determine whether laparoscopic adhesiolysis ameliorates chronic abdominal pain in patients with abdominal adhesions. Forty-one patients with chronic abdominal pain lasting for more than 6 months, but with no abnormal findings other than adhesions found at laparoscopy, underwent laparoscopic adhesiolysis. 37 patients (90.2%) were available for follow-up after a median time interval of 18 months (range: 12-41 months). Twenty-two patients (59.4%) were free from abdominal pain and 9 (24.3%) patients reported significant amelioration of their pain. Six (16.2%) patients had no amelioration. In conclusion the laparoscopy is an effective tool for the evaluation of patients with chronic abdominal pain, and laparoscopic adhesiolysis cures of ameliorates chronic abdominal pain in more than 80% of patients.