Monitoring of renal function in patients with spinal cord injury

OBJECTIVE: To assess the sensitivity of serum creatinine level in detecting clinically important and early deterioration of renal function in patients with spinal cord injury (SCI), and to evaluate the optimal method of determining creatinine clearance in these patients. PATIENTS AND METHODS: The serum creatinine level of 36 patients (25 paraplegics and 11 quadriplegics) was evaluated and compared with the corresponding measured creatinine clearance rate. Correlations were also assessed between the creatinine clearance measured by 24-h endogenous clearance, single-shot 99mTc-labelled diethylenetriamine pentaacetic acid (99mTc-DTPA) clearance technique, and the Cockcroft-Gault formula, to test their validity. RESULTS: Of the 36 patients 11 (31%) had a measured creatinine clearance of < 100 mL/min (mean 84.8) and a corresponding normal serum creatinine level. Creatinine clearance calculated by the Cockcroft-Gault formula did not correlate well with that measured by the 24-h endogenous clearance (r = 0.426) and 99mTc-DTPA clearance (r = 0. 366), overestimating creatinine clearance in all but three patients. The mean (SD) difference between the creatinine clearance measured by the 24-h and DTPA clearance technique was 17.7 (16.5)% and the correlation between these techniques was good (r = 0.71). CONCLUSION: Serum creatinine level is not sensitive in detecting early deterioration of renal function in patients with SCI. The Cockcroft-Gault formula generally significantly overestimates the true creatinine clearance and is not recommended. The 24-h endogenous creatinine clearance measured on appropriately collected urine samples is an acceptable accurate and practical method of determining glomerular filtration rate in patients with SCI.     

Toxicity of phorbol esters for human epithelial cells expressing a mutant ras Oncogene

Phorbol esters and related compounds provide a promising source of potential anticancer agents. The mechanism of their toxicity, however, is unclear, and interpretation has been complicated by the conflicting responses exhibited by different transformed cell lines. Previously we showed that in primary thyroid follicular cells, expression of mutant p21^ras conferred a striking sensitivity to the toxic effects of phorbol esters. We have now extended this work using a thyroid cell line with an inducible mutant ras gene to exclude the possibility that this result was a trivial consequence of the marked growth stimulation induced in these cells by mutant p21^ras. Furthermore, by assessing the action of a panel of phorbol esters and a potential chemotherapeutic agent, bryostatin, we demonstrated that this phenomenon was only a function of biologically active phorbol esters. These results provide a molecular rationale for the development of phorbol ester analogues as chemotherapeutic agents.     

Metabolic rate in febrile infants

An open circuit indirect calorimeter was used to measure resting energy expenditure in febrile infants. Twelve infants admitted to hospital with fever (axillary temperature 37.5 degrees C) were studied on admission and then again at the same time of day and in similar environmental conditions after the fever had resolved. Mean age of the infants was 0.31 years (range 0.12-0.54) and the mean body weight 6.59 kg (range 4.50-8.88 kg). On average the infants' axillary temperatures were +2.1 degrees C higher when they were febrile. Overall the mean difference in oxygen consumption (VO2), carbon dioxide production (VCO2), and resting energy expenditure (REE) between the febrile and afebrile measurements was not statistically significant. Of eight infants with a greater REE when febrile, five were diagnosed as having viral illness and three had bacterial meningitis. Of the four with a lower REE when febrile, two had viral illness and two had bacterial infection (one chest infection and one meningitis). In conclusion, there was no consistent alteration of REE during a fever in infants 1 to 6 months of age. In particular, age and type of infection were not predictors of whether REE would increase or decrease during the illness.     

Magnesium sulphate in the treatment of eclampsia and pre-eclampsia: an overview of the evidence from randomised trials

Objective To evaluate the effectiveness of magnesium sulphate in the treatment of eclampsia and pre-eclampsia by a systematic quantitative overview of controlled clinical trials.
Design Online searching of the MEDLINE database between 1966 and 1995, and scanning of the bibliography of known primary studies and review articles on the use of magnesium sulphate in eclampsia and pre-eclampsia. Study selection, study quality assessment and data extraction were performed independently by two reviewers under masked conditions. Where possible outcome data from trials were pooled and summarised using the Mantel-Haenszel method.
Participants One thousand seven hundred and forty-three women with eclampsia and 2390 with pre-eclampsia included in nine randomised trials that evaluated the effects of magnesium sulphate.
Main outcome measures Seizure activity and maternal death.
Results In eclampsia, recurrence of seizures was less common with magnesium sulphate therapy compared with phenytoin (odds ratio [OR] 0.27, 95% CI 0.17.0.45,   P = 0.00  ) and diazepam (OR 0–41, 95% CI 0.30–0.57,   P = 0.00  ). As indicated by the point estimate, there was a trend towards a reduction in maternal mortality with magnesium sulphate in eclampsia (OR 0.51,95% CI 0.24–1.07,   P = 0.10  versus phenytoin; OR 0.78, 95% CI 0.41–1.45,   P = 0.52  versus diazepam). When used for seizure prophylaxis in pre-eclampsia, magnesium sulphate was found to be more effective than phenytoin (OR 0.15, 95% CI 0.03–0.72,   P = 0.01  ).
Conclusion Magnesium sulphate is a superior drug in preventing the recurrence of seizures in eclampsia and in seizure prophylaxis in pre-eclampsia.     

Autoradiographic analysis of [S]TBPS binding in entorhinal cortex-kindled rat brains

A quantitative autoradiographic analysis of [³⁵S]t-butylbicyclophosphorothionate (TBPS) binding to the γ-aminobutyric acid (GABA)- mediated chloride ionophore was carried out in 104 brain areas of entorhinal cortex-kindled and control rats. Subjects were sacrificed either 24 h or 28 days after the last kindled seizure. Kindled subjects in the 24 h group showed reductions in mean [³⁵S]TBPS binding in the lateral nucleus of the amygdala (−31%), the infralimbic cortex (−14%), and the paracentral nucleus of the thalamus (−22%). At 28 days, reductions in binding were observed in the infralimbic cortex (−15%) and the paracentral nucleus of the thalamus (−18%). These data suggest that repeated seizures (kindling) modify the GABA-mediated chloride ionophore, and that in some brain areas related to seizure generalization the modifications are very long lasting.     

Anti-RNA polymerase I antibodies in the sera of MRL lupus mice at the initial stages of disease are directed primarily against phosphorylation-dependent epitopes.

Anti-RNA polymerase I (RPI) antibodies in the sera of MRL/Mp-lpr/lpr and MRL/Mp(-)+/+ mice, which develop an autoimmune disease similar to human systemic lupus erythematosus, were screened for reactivity with purified RPI or RPI which had been dephosphorylated. In every case (n = 10), dephosphorylation of RPI resulted in a significant decrease (33-95%) in antibody binding. The anti-RPI antibodies in the sera of the same mice approximately 6 weeks later also reacted better with untreated as compared to dephosphorylated RPI but, in every case, the decrease in antibody (0-30%) caused by dephosphorylation was substantially diminished. That the proportion of anti-RPI antibodies in the sera of MRL mice decreased with progression of lupus-like disease was confirmed by closely monitoring the antibodies over the course of disease. Anti-RPI antibodies produced at the earliest stages appeared to be directed almost exclusively against phosphorylation-dependent determinants since dephosphorylation of RPI essentially abolished antibody binding. Subsequently, the percentage of the total anti-RPI antibodies in the sera of these mice directed towards phosphorylation-independent epitopes increased linearly with time. The importance of phosphorylation-dependent epitopes on RPI for the development of the anti-RPI autoimmune response was supported by the observation that treatment of mice with alkaline phosphatase partially attenuated anti-RPI antibody production.