Maternal serum caffeine metabolites and small-for-gestational age birth.

To determine whether the third-trimester maternal serum concentration of paraxanthine, caffeine's primary metabolite, is associated with delivery of a small-for-gestational age infant (birth weight less than the 10th percentile for gestational age, gender, and ethnicity) and whether this association differs by smoking, the authors studied 2,515 women who participated in the Collaborative Perinatal Project from 1959 to 1966. The women provided a third-trimester serum sample and had been controls for a nested case-control study of spontaneous abortion. The mean serum paraxanthine concentration was greater in women who gave birth to small-for-gestational age infants (754 ng/ml) than to appropriately grown infants (653 ng/ml, p = 0.02). However, the linear trend for increasing serum paraxanthine concentration to be associated with increasing risk of small-for-gestational age birth was confined to women who also smoked (p = 0.03). There was no association between paraxanthine and fetal growth in nonsmokers (p = 0.48). Adjustment for maternal age, pre-pregnant weight, education, parity, ethnicity, and the number of cigarettes smoked per day did not alter the results substantially, although the p value for trend among smokers increased to 0.07. The authors conclude that maternal third-trimester serum paraxanthine concentration, which reflects caffeine consumption, was associated with a higher risk of reduced fetal growth, particularly among women who smoked.     

Oxygen Reverses Deficits of Cognitive Function and Memory and Increased Heart Rate Induced by Acute Severe Isovolemic Anemia

Background: Erythrocytes are transfused to improve oxygen delivery and prevent or treat inadequate oxygenation of tissues. Acute isovolemic anemia subtly slows human data processing and degrades memory, increases heart rate, and decreases self-assessed energy level. Erythrocyte transfusion is efficacious in reversing these effects of acute anemia. We tested the hypothesis that increasing arterial oxygen pressure (Pao2) to 350 mmHg or greater would supply sufficient oxygen to be equivalent to augmenting hemoglobin concentration by 2-3 g/dl and thus reverse the effects of acute anemia.

Methods: Thirty-one healthy volunteers, aged 28 +/- 4 yr (mean +/- SD), were tested with verbal memory and standard, computerized neuropsychologic tests before and twice after acute isovolemic reduction of their hemoglobin concentration to 5.7 +/- 0.3 g/dl. Two sets of tests were performed in randomized order at the lower hemoglobin concentration: with the volunteer breathing room air or oxygen. The subject and those administering the tests and recording the results were unaware which gas was administered. As an additional control for duration of the experiment, 10 of these volunteers also completed the same tests on a separate day, without alteration of hemoglobin concentration, at times of the day similar to those on the experimental day. Heart rate, mean arterial blood pressure, and self-assessed sense of energy were recorded at the time of each test.

Results: Reaction time for digit-symbol substitution test increased, delayed memory was degraded, mean arterial pressure and energy level decreased, and heart rate increased at a hemoglobin concentration of 5.7 g/dl (all P < 0.05). Increasing Pao2 to 406 +/- 47 mmHg reversed the digit-symbol substitution test result and the delayed memory changes to values not different from those at the baseline hemoglobin concentration of 12.7 +/- 1.0 g/dl, and decreased heart rate (P < 0.05). However, mean arterial pressure and energy level changes were not altered with increased Pao2 during acute anemia.     

Chemotherapy in patients with resectable liver metastases from colorectal cancer

New chemotherapy drugs and, more recently, targeted therapies have significantly improved the outcome of patients with resected stage III colon cancer (adjuvant chemotherapy) and patients with unresectable metastases (palliative therapy). These advances raise several questions about the place of chemotherapy after and before surgery in patients with resectable liver metastases. To date, only a combined intra-arterial plus systemic fluoropyrimidine-based chemotherapy regimen has clearly demonstrated a relapse-free survival benefit. Yet, this approach is restricted to specialized centers, mainly because of technical difficulties and locoregional toxicities. The role of systemic use of oxaliplatin- and irinotecan-based regimens is currently under investigation. Planned trials will assess the role of anti-angiogenic and anti-epidermal growth factor receptor agents. We review the main trials performed in patients with resectable metastases, and discuss their potent impact on clinical practice.     

Carbamazepine Side Effects in Children and Adults

Summary: Most of the side effects associated with carbamazepine (Tegretol^®, USP, Geigy Pharmaceuticals) therapy are mild, transient, and reversible with an adjustment in dosage or rate of dosage increase. Direct reports to Geigy Pharmaceuticals for the period 1975 to 1986 totaled 371 hematologic, 396 dermatologic, and 156 hepatic and pancreatic occurrences out of more than 4 million patients treated. These include 27 cases of aplastic anemia and 10 of agranulocytosis. In a study of the incidence of side effects in 220 children below the age of 16 years who were receiving carbamazepine, drowsiness, loss of coordination, and vertigo were the most commonly observed side effects and were almost always transient and dose related. The findings of this study are comparable with those of other series assessing carbam-azepine-associated adverse reactions in children and adults. Overall, 30 to 50% of children and adults were reportedly free of side effects in these studies. Recommendations for carbamazepine therapy include education of patients and parents in the nature and likelihood of possible serious adverse reactions and routine monitoring to detect laboratory abnormalities.     

Plasma lyso-phosphatidylcholine concentration is decreased in cancer patients with weight loss and activated inflammatory status

Background  

It has been observed that ras-transformed cell lines in culture have a higher phosphatidylcholine (PC) biosynthesis rate as well as higher PC-degradation rate (increased PC-turnover) than normal cells. In correspondence to these findings, the concentrations of the PC-degradation product lyso-phosphatidylcholine (LPC) in cancer patients were found to be decreased. Our objective was the systematic investigation of the relationship between LPC and inflammatory and nutritional parameters in cancer patients. Therefore, plasma LPC concentrations were assessed in 59 cancer patients and related to nutritional and inflammatory parameters. To determine LPC in blood plasma we developed and validated a HPTLC method.     

Effects of the phosphodiesterase inhibitor rolipram on the acoustic startle response in rats

Systemic administration of the phosphodiesterase inhibitor rolipram (0.05–10.0 mg/kg, IP) produced a rapid and dose-related increase in the amplitude of the acoustic startle response in rats. The (−) isomer was more potent than the (+) isomer in enhancing startle amplitude. Rolipram increased startle responses that were elicited by brief electrical stimulation of the ventral cochlear nucleus or nucleus reticularis pontis caudalis, two brainstem relay nuclei of the startle neural circuit. A low (5 μg) dose of rolipram produced an excitatory effect on startle following spinal (lumbar intrathecal) infusion but not following supraspinal (lateral ventricle) infusion. Rolipram (0.5 mg/kg, IP) excitation of startle was not blocked by drugs which differentially disrupt the release of monoamines (DSP4, reserpine + alpha-methylpara-tyrosine, reserpine + para-chloro-phenylalanine) or by drugs which differentially block monoamine receptors (haloperidol, prazosin, idazoxan, cinanserin, or cyproheptadine). The marked increase in startle seen following systemic rolipram injection is attributable, at least in part, on an action in the lumbar spinal cord that directly or indirectly facilitates neural transmission along the reticulospinal component of the startle reflex neural pathway. The startle reflex should be a useful behavioral test system for studying the mechanism of action of rolipram and related compounds purported to selectively inhibit calmodulin-independent forms of phosphodiesterase.     

Comparing health system performance assessment and management approaches in the Netherlands and Ontario,Canada

Background  

Given the proliferation and the growing complexity of performance measurement initiatives in many health systems, the Netherlands and Ontario, Canada expressed interests in cross-national comparisons in an effort to promote knowledge transfer and best practise. To support this cross-national learning, a study was undertaken to compare health system performance approaches in The Netherlands with Ontario, Canada.     

Proteolysis in severe sepsis is related to oxidation of plasma protein.

OBJECTIVE: To test the hypothesis that the oxidation of proteins is part of the mechanism of proteolysis in catabolic states. DESIGN: Prospective, observational study. SETTING: Critical care unit at a university teaching hospital, New Zealand. PATIENTS: 13 patients (6 male, 7 female; median age 61, range 26-76 years) who were admitted to the Department of Critical Care Medicine at Auckland Hospital with a diagnosis of severe sepsis. The median APACHE II score during the first 24 hours after admission was 22 (range 15-34). Control values of protein carbonyl in plasma were established in 15 healthy volunteers. INTERVENTIONS: We made serial measurements of total body protein (by neutron activation analysis) and plasma protein carbonyl (by ELISA) concentrations over a period of 10 days. MAIN OUTCOME MEASURE: Plasma protein carbonyl concentration and total body protein. RESULTS: The total amount of body protein decreased significantly over the 10 days (p < 0.001). Plasma protein carbonyl concentrations were significantly higher in the septic patients than in the control group throughout the study period (p < 0.0001). There was a significant reduction in plasma protein carbonyl concentration over the study period (p < 0.008). The early increase in the concentration of protein carbonyl formation was followed by an ongoing loss of body protein. There was a significant positive correlation between total body protein and plasma protein carbonyl (p < 0.03). CONCLUSIONS: Severe sepsis results in oxidation of plasma proteins and this precedes and is related to the loss of body protein.