Pharmacokinetics of prednisolone in children with the nephrotic syndrome

The aim of this study was to establish whether the criteria for the clinical effectiveness of steroids are correlated with the pharmacokinetics of prednisolone in children treated with prednisone during an attack of idiopathic nephrotic syndrome (INS). Thirteen patients with nephrosis were included. Prednisolone, prednisone and cortisol levels were measured using a specific high-performance liquid chromatography assay after an oral dose of 1 mg/kg body weight of prednisone taken at the onset of the disease. All the pharmacokinetic parameters, including the conversion of prednisone to prednisolone were similar to the data already published in children with INS. No correlation was found between the values of pharmacokinetic parameters and criteria of clinical effectiveness. Hypo-albuminaemia was significantly correlated with the area under the plasma-concentration curve but not with the elimination half-life of prednisolone. Moreover, the prednisolone elimination half-life correlated with the urinary exretion of 17-hydroxycorticosteroids achieved in the first 6h. The present study suggests that routine measurements of prednisolone kinetics do not help when assessing the treatment of children with INS.     

Metabolic myocardial viability assessment with iodine 123-16-iodo-3-methylhexadecanoic acid in recent myocardial infarction: Comparison with thallium-201 and fluorine-18 fluorodeoxyglucose

The best test presently available to ascertain residual viability within an infarct-related area involves the use of fluorine-18 fluorodeoxyglucose (FDG) to detect the persistence of some cellular metabolism. Rest reinjection of thallium-201 is a less accurate alternative but is easy to perform. Iodinated fatty acids, which are used with standard gamma cameras, are proposed as markers of cellular metabolism. This study was performed to assess the value of 16-iodo-3-methyl-hexadecanoic acid (MIHA) as a marker of the residual cellular metabolism by comparison with FDG in patients with a recent myocardial infarction, and to evaluate its contribution compared with the²⁰¹Tl stress-redistribution-reinjection technique. Stress-redistribution-reinjection²⁰¹T1 imaging, rest MIHA imaging and glucoseloaded FDG imaging were performed in 22 patients with recent myocardial infarction. Out of the 628 myocardial segments obtained from the left ventricular analysis, 400 were hypoperfused (relative uptake <0.75 of maximum uptake on stress²⁰¹T1 imaging), 177 of which were severely hypoperfused (relative uptake <0.50). Receiver operating characteristic (ROC) curves for predicting metabolic myocardial viability with FDG were derived from the results in respect of (a)²⁰¹T1 activity during exercise, redistribution and reinjection and (b) MIHA up-take, using the two FDG thresholds most commonly considered to define metabolic viability (0.50 and 0.60). Analysis of the 400 hypoperfused segments demonstrated that²⁰¹T1 reinjection was the most accurate test in predicting the presence of myocardial viability (area under the ROI curves=0.85 and 0.86 at the 0.50 and 0.60 FDG thresholds, respectively;P<0.05 vs other tests). The global predictive values of MIHA and²⁰¹T1 reinjection were, respectively, 0.87 and 0.89 at the 0.50 FDG threshold (NS), and 0.82 and 0.87 at the 0.60 FDG threshold (NS). When only the 177 severely hypoperfused segments were considered,²⁰¹T1 reinjection remained the most accurate test (accuracy 0.84 at the 0.50 FDG threshold and 0.82 at the 0.60 FDG threshold), while the accuracy of MIHA decreased significantly (0.78 at the 0.50 FDG threshold and 0.73 at the 0.60 FDG threshold,P<0.05 vs²⁰¹T1 reinjection). In all circumstances, MIHA was less specific than²⁰¹T1 reinjection for the detection of metabolic viability. In conclusion, in patients with recent myocardial infarction, MIHA accurately detects the persistence of metabolic viability, but is not superior to²⁰¹T1.     

Life-threatening respiratory failure due to cranial dystonia after dental procedure in a patient with multiple system atrophy.

We report on a woman with a an 8-year history of multiple system atrophy with predominance of parkinsonism who developed jaw-locking oromandibular dystonia within hours after insertion of ill-fitting dentures. Dystonia spread rapidly to involve other facial muscles and the larynx causing stridor with respiratory failure necessitating crush intubation.     

Transcutaneous bilirubin measurement in preterm infants]

Transcutaneous bilirubinometry is an effective screening tool for neonatal jaundice in full-term babies. But its accuracy is not shown yet in preterm infants. METHODOLOGY: We carried out a prospective study in a neonatal intensive care unit. The study included 47 preterm infants. From birth, a transcutaneous bilirubin measurement (BTc) using the BiliCheck was made on the forehead of each newborn every 8 h. Blood sampling for determination of total serum bilirubin (BS) was combined with BTc: 1) if value of BTc was higher than limits values for phototherapy; 2) on the second day of life and 3) 4 hours after cessation of phototherapy. RESULTS: Mean gestational age was 30 week and mean birth weight was 1419 g. We studied 151 pairs of BTc and BS. Mean values obtained by BTc and BS were respectively 160.6+/-50 mumol/L and 190.6+/-61.4 mumol/L. A significant correlation between BTc and BS was found. But the limits of agreement were very wide. The negative predictive value (NPV) of BTc was above 90% in each group of gestational age. DISCUSSION: The need for phototherapy cannot be determined by BTc in preterm infants. But the BTc is reliable when its value is under the limits for phototherapy. CONCLUSION: With a very high incidence of neonatal jaundice (87%) in our cohort, a value of BTc under the limits for phototherapy has a good NPV in preterm infants.     

Radical cystectomy after coronary artery bypass graft

Nine patients have undergone single-stage radical cystectomy and ileal conduit urinary diversion two to fifty-one months after coronary artery bypass procedures. Two patients presenting with intractable angina at the time their malignant disease was being evaluated required bypass surgery before cystectomy could be undertaken. No significant cardiac morbidity occurred postoperatively, and all remain alive without evidence of malignant disease.     

Small bowel transplantation: Effects on function of nonadrenergic, noncholinergic nerves

Previous work from our laboratory showed that spontaneous contractile activity of jejunal smooth muscle increases after small bowel transplantation. Our aim was to determine whether small bowel transplantation alters the function of nonadrenergic, noncholinergic (NANC) nerves. Seven groups of rats, (n ≥7 in each group) were studied as follows: 1 week after sham celiotomy and 1 week and 8 weeks after 45 minutes of ischemia/ reperfusion (IR1 and IR8), jejunal and ileal transection and reanastomosis (TR1 and TR8), or orthotopic small bowel transplantation (TX1 and TX8). Contractility of jejunal circular muscle strips was studied in vitro. Spontaneous contractile activity increased in the IR1, TR1, and TX1 and TX1 and TX8 groups (P<0.01). Under NANC conditions, spontaneous activity increased in TR1 and in both TX1 and TX8 (P<0.01) despite the lack of an increase in the frequency of contraction in TX1. Electrical field stimulation inhibited contractile activity at low frequencies, but under NANC conditions this inhibition persisted at higher frequencies. The calculated equieffective frequency (F₁₀₀) that produced a response equal to baseline contractile activity was similar in all groups, but under NANC conditions was greater in TX1 (P<0.025). Functional alterations of NANC nerves are partly responsible for the increase in spontaneous activity in rat jejunal circular muscle strips after a limited ischemia/reperfusion injury, after selective disruption of enteric neural continuity (transection/reanastomosis), and after small bowel transplantation. These findings may provide important insight into graft dysfunction after small bowel transplantation in humans. Supported by United States Public Health Service grant DK 39337 from the National Institutes of Health and by the Mayo Foundation.     

Novel antiepileptic drug levetiracetam decreases dyskinesia elicited by L-dopa and ropinirole in the MPTP-lesioned marmoset.

Long-term dopamine replacement therapy of Parkinson's disease leads to the occurrence of dyskinesias. Altered firing patterns of neurons of the internal globus pallidus, involving a pathological synchronization/desynchronization process, may contribute significantly to the genesis of dyskinesia. Levetiracetam, an antiepileptic drug that counteracts neuronal (hyper)synchronization in animal models of epilepsy, was assessed in the MPTP-lesioned marmoset model of Parkinson's disease, after coadministration with (1) levodopa (L-dopa) or (2) ropinirole/L-dopa combination. Oral administration of levetiracetam (13-60 mg/kg) in combination with either L-dopa (12 mg/kg) alone or L-dopa (8 mg/kg)/ropinirole (1.25 mg/kg) treatments was associated with significantly less dyskinesia, in comparison to L-dopa monotherapy during the first hour after administration. Thus, new nondopaminergic treatment strategies targeting normalization of abnormal firing patterns in basal ganglia structures may prove useful as an adjunct to reduce dyskinesia induced by dopamine replacement therapy without affecting its antiparkinsonian action.     

Cancer risk due to occupational exposure to polycyclic aromatic hydrocarbons

Polycyclic aromatic hydrocarbons (PAHs) demonstrate carcinogenic activity in animal models. Although some epidemiologic studies have implicated PAHs as risk factors for human cancer, the evidence reported to date has not been consistent. The purpose of this report is to describe the associations between occupational exposure to PAHs in the workplace and each of 14 types of cancer. A population-based, case-control study was carried out in Montreal to investigate associations between a large variety of environmental and occupational exposures on the one hand, and several types of cancer on the other. A detailed job history was obtained from each subject along with information on a number of potential confounders. Each job history was reviewed by a team of experts, who used this information to construct a corresponding history of occupational exposures. Among the PAH exposures considered were benzo(a)pyrene (B(a)P) and five categories of PAHs defined on the basis of the source material, namely, wood, petroleum, coal, other sources, and any source. Altogether, 3,730 cancer patients and 533 population controls were interviewed and their job exposure histories coded. For each of 14 types of cancer analyzed, three control groups were available: other cancer patients, population controls, and the pooled set of cancer and population controls. The associations between 14 cancer types and 6 PAH exposures were analyzed using logistic regression methods. For most types of cancer evaluated, there was no evidence of excess risk due to PAHs at the levels encountered in the occupations in which PAH exposure has been prevalent in the Montreal area. For a few cancer sites–the esophagus, the pancreas, and the prostate gland–there were suggestions of excess risk; these observations are noteworthy hypotheses for further investigation. For lung cancer, there appeared to be an increased risk due to PAHs among nonsmokers and light smokers, but not among heavy smokers.     

Urination Frequency and Cystic Pressure Resistance After Fractionated whole or Partial Irradiation of the Rabbit Urinary Bladder

Urination frequency and cystic pressure resistance have been used as end-points to assess x-ray-induced changes of bladder function. Whole or half bladders of adult male rabbits were irradiated, caudally or cranially. The absorbed dose was 33 Gy, 36 Gy or 39 Gy, given in 5 daily fractions. Animals which received a whole bladder dose of 39 Gy or 36 Gy showed increased urination frequency and enhanced bladder pressure resistance during the whole follow-up time of 100 weeks, compared with the sham-irradiated controls. At half bladder irradiation, only the highest doses (39 Gy to the cranial part of the bladder and 39 Gy or 36 Gy to the caudal part) gave rise to a slight increase in frequency at about 20 weeks after exposure.