Recent warming by latitude associated with increased length of ragweed pollen season in central North America.

A fundamental aspect of climate change is the potential shifts in flowering phenology and pollen initiation associated with milder winters and warmer seasonal air temperature. Earlier floral anthesis has been suggested, in turn, to have a role in human disease by increasing time of exposure to pollen that causes allergic rhinitis and related asthma. However, earlier floral initiation does not necessarily alter the temporal duration of the pollen season, and, to date, no consistent continental trend in pollen season length has been demonstrated. Here we report that duration of the ragweed (Ambrosia spp.) pollen season has been increasing in recent decades as a function of latitude in North America. Latitudinal effects on increasing season length were associated primarily with a delay in first frost of the fall season and lengthening of the frost free period. Overall, these data indicate a significant increase in the length of the ragweed pollen season by as much as 13-27 d at latitudes above ~44°N since 1995. This is consistent with recent Intergovernmental Panel on Climate Change projections regarding enhanced warming as a function of latitude. If similar warming trends accompany long-term climate change, greater exposure times to seasonal allergens may occur with subsequent effects on public health.

Synergistic effects of ascorbic acid and thiazolidinedione on secretion of high molecular weight adiponectin from human adipocytes.

AIM: To test the hypothesis that ascorbic acid (AA) and thiazolidinedione (TZD) would have additive effects on HMW adiponectin secretion by virtue of different modes of action. METHODS: We determined the effects of supplementation of AA and/or TZD on expression and secretion of total and HMW adiponectin from human Simpson-Golabi-Behmel syndrome (SGBS) adipocytes in the absence or presence of the proinflammatory cytokine TNFα. RESULTS: AA supplementation significantly increased secretion of HMW adiponectin (1.7-fold) without altering adiponectin expression or total adiponectin secretion. TZD significantly increased expression (3-fold) and secretion of total (1.4-fold) but not HMW adiponectin. Combined supplementation resulted in a significant increase in expression (3-fold) and secretion of total (1.8-fold) and HMW (5-fold) adiponectin. Similar results were seen in cells co-treated with TNFα. CONCLUSIONS: These data show that AA and TZD have synergistic rather than simple additive effects on secretion of HMW adiponectin from human adipocytes and raise the possibility that differences in AA levels may contribute to the variability in adiponectin multimer profiles and efficacy of TZD in humans. Our results also provide a rationale for longitudinal clinical trials investigating the effects of AA supplementation with or without TZD on adiponectin and metabolic profiles.

Cellular pathophysiology and therapy of pulmonary hypertension.

The identification of several mutations of the bone morphogenetic protein receptor 2 (BMPR2) gene, a member of the transforming growth factor beta receptor family, gives hope for new insights into the pathophysiology of pulmonary hypertension. Genetic predisposition might dictate the responses of pulmonary artery fibroblasts, smooth muscle cells, and endothelial cells, as well as platelets and leukocytes, or their specific interactions with different extrinsic factors. These cells possess distinct subtypes and interact with each other. Pulmonary hypertension is associated with vasoconstriction, remodeling, and in situ thrombosis of the pulmonary arteries, but the initial events and their relationship to the genetic background are presently unknown. Current therapeutic approaches are based on our knowledge of the physiologic regulation of pulmonary artery tone, pathophysiologic changes, and our clinical experience with different treatment strategies. Beyond diuretics and anticoagulants, prostaglandins are generally accepted therapeutic agents for primary pulmonary hypertension and related diseases, whereas high-dose calcium-channel blockers are reserved for a small subset of patients, those who respond favorably to vasodilators in an acute test. Long-term intravenous prostacyclin infusion has become the most important specific therapy for primary pulmonary hypertension and associated diseases. However, this therapy is hampered by catheter complications and systemic side effects. Alternative application routes of prostacyclin or its stable analogs may avoid these problems. Inhaled application of the prostacyclin analog iloprost results in predominant pulmonary vasodilation with few systemic side effects and may possess clinical efficacy similar to that of intravenous prostacyclin. Inhaled nitric oxide is widely accepted as a screening agent for active responders to vasodilators and has a similar hemodynamic profile as inhaled iloprost, although the percentage of responders is considerably lower. However, there are unsolved toxicologic questions and practical difficulties concerning the safe long-term application of nitric oxide. Combining inhaled vasodilators with phosphodiesterase inhibitors may prolong the duration of the effects and improve the convenience of inhaled therapy for pulmonary hypertension. Therapeutic approaches in the future may aim at the transforming growth factor beta pathway and at the identification of early stages of the disease to prevent further disease progression.

Bacteriologic and clinical efficacy of high dose amoxicillin/clavulanate in children with acute otitis media.

OBJECTIVES: To determine the bacteriologic and clinical efficacy of high dose amoxicillin/clavulanate (90/6.4 mg/kg/day) against common bacterial pathogens causing acute otitis media (AOM), including penicillin-resistant Streptococcus pneumoniae (PRSP). METHODS: In this open label multicenter study, 521 infants and children with AOM [mean age, 18.6 months; age < 24 months, n = 375 (72%)] were treated with amoxicillin/clavulanate 90/6.4 mg/kg/day in two divided doses for 10 days. Bilateral otitis media, previous episodes of AOM, antibiotic treatment within 3 months and day-care attendance were recorded in 60.1, 35.7, 50.2 and 38.2% of the children, respectively. Tympanocentesis was performed before the first dose and repeated on Days 4 to 6 for all children with S. pneumoniae at 22 centers and for all children with any pathogen at 3 centers. Clinical response was assessed at end of therapy. RESULTS: Pathogens were isolated from 355 (68%) of 521 enrolled children; 180 children underwent repeat tympanocentesis and were bacteriologically evaluable. Baseline pathogens were S. pneumoniae (n = 122 enrolled/93 bacteriologically evaluable), Haemophilus influenzae (n = 160/51), both (n = 37/32) and others (n = 36/4). Pathogens were eradicated from 172 (96%) of 180 bacteriologically evaluable children. Overall 122 (98%) of 125 isolates of S. pneumoniae were eradicated, including 31 (91%) of 34 PRSP isolates (penicillin MICs 2 to 4 micrograms/ml). Seventy-eight (94%) of 83 isolates of H. influenzae were eradicated. Symptoms and otoscopic signs of acute inflammation were completely resolved or improved on Days 12 to 15 in 263 (89%) of 295 clinically evaluable children with bacteriologically documented AOM. CONCLUSIONS: On the basis of bacteriologic outcome on Days 4 to 6 and clinical outcome on Days 12 to 15, we found that high dose amoxicillin/clavulanate (90/6.4 mg/kg/day) was highly efficacious in children with AOM, including those most likely to fail treatment, namely children < 24 months of age and those with infectious caused by PRSP.

The history of migraine from Mesopotamian to Medieval times.

The first descriptions of migraine can be traced back nearly 4,000 years from the ancient civilizations of Mesopotamia (Sumeria and Babylonia) through Egyptian, Greek and Roman epochs. Through Byzantine, Arabic and Medieval times there are only patchy references until the 17th century, when European physicians first gave full case reports.

Protein synthesis in skeletal muscle of uremic patients: effect of low-protein diet and supplementation with ketoacids.

The purpose of this study was to investigate the modifications of muscle protein synthesis activity in uremic patients fed a low-protein diet and a low-protein diet supplemented with a keto acid-amino acid mixture. The protein synthesis activity was evaluated in vitro on isolated muscle ribosomes incubated in a cell-free medium with tritiated leucine. Simultaneously, nitrogen kinetics and amino acid patterns were examined. Protein synthesis activity is correlated with the protein content of the diet in uremic patients. The keto acid-amino acid supplementation enhances protein synthesis. Variations of protein synthesis can be correlated with the variations of nitrogen balance which implies a major role of protein synthesis activity in muscle protein metabolism. Variations in plasma levels of the essential amino acids, mainly leucine and valine, can be correlated with the variations of protein synthesis activity, and these amino acids seem therefore to be mediators of the dietary effects on protein synthesis in uremia.

[Nutrition, metabolic and endocrine complications during extrarenal dialysis]. / Nutrition, complications métaboliques et endocriniennes au cours de l'épuration extra-rénale.

Patients with chronic renal failure treated by maintenance dialysis often have nutritional disorders, metabolic disorders concerning lipids, proteins and carbohydrates, and disorders of endocrine systems involved in the regulation of these metabolisms. These disorders are difficult to diagnose, as their clinical symptoms are few and of little pathognomonic value. Hence the need for anthropometric measurements as well as biochemical and physiological exploration of metabolic pathways for intermittent overall evaluation and longitudinal follow-up. These patients have reduced subcutaneous fat reserves, intolerance to carbohydrates by resistance to insulin (partially corrected by haemodialysis), low levels of plasma aminoacids, notably valine, type IV hyperlipidaemia with low levels of essential fatty acids, fragile immune system and increased requirements for vitamins B, especially B6. Dietary recommendations include: food energy 35 kiloCal/kg bodyweight/day; proteins 1 to 1.2 g/kg bodyweight/day (50 p. 100 of which must be complete proteins) and supplements of vitamins. Dialysis must be optimal for clearance of nitrogen compounds and body homeostasis.

Determination of free choline in plasma and erythrocyte samples and choline derived from membrane phosphatidylcholine by a chemiluminescence method.

A sensitive chemiluminescence method for assay of choline which has been developed for analysis of erythrocyte and plasma levels of choline is reported here. This method includes a charcoal purification step which yields consistent results with plasma and erythrocyte extracts. Further, choline derived from membrane phosphatidylcholine may also be measured by an extension of this method following digestion with phospholipase D. This method has been used to study abnormal levels of erythrocyte choline that occur in cluster headache patients compared to control subjects and migraine patients. In addition, the time course of changes in plasma and erythrocyte choline following a fatty meal have been monitored. Plasma choline levels rise to a maximum between 1 and 3 h after the meal and this is followed by a rise in erythrocyte choline levels which are maximal 3 h after the meal.

Cultured rat spinal cord neurons: interaction with motor neuron disease immunoglobulins.

Conditions have been developed for the culture of rat spinal cord neurons in serum-free media supplemented with hormones and growth factors. Neurons were identified by immunofluorescence-labeled anti-neurofilament antibody, and their growth was monitored by assay of choline acetyltransferase and cholinesterase activities. Activities of these enzymes were considerably higher than those of comparable cultures in serum supplemented media in which there were visibly many more nonneuronal cells. Serum immunoglobulins from patients with motor neuron disease showed enhanced binding to rat spinal cord cells maintained in both serum-supplemented and serum-free media, as compared with those from normal healthy individuals. Enhanced binding was more marked with the latter cells, presumably because of the higher proportion of neuronal cells in these cultures. Serum immunoglobulins from patients with other neurologic disorders showed a similar binding to that of the normal controls. The results demonstrate the presence of an immune response to spinal cord cell membrane components in patients with motor neuron disease, although whether the response is primary or secondary in the disease process remains unclear.