ANTIFON-CLIC®, a new clinical decision support system for the treatment of invasive aspergillosis: is it clinically relevant?

BACKGROUND: Invasive aspergillosis (IA) is increasing especially in new groups of patients. Despite advances in management, morbidity and mortality related to IA remain high. Thus, Clinical Decision Support System (CDSS) dedicated to IA are needed to promote the optimal antifungal for each group of patients. PATIENTS AND METHODS: This was a retrospective multicenter cohort study involving intensive care units and medical units. Adult patients who received caspofungin, isavuconazole, itraconazole, liposomal amphotericin B, posaconazole, or voriconazole, for the treatment of IA were eligible for enrollment. The primary objective was the concordance between the clinician's prescription and the prescription recommended by the CDSS. The secondary objective was the concordance according to different hospitals, departments, and indications. RESULTS: Eighty-eight patients (n=88) from three medical hospitals were included. The overall concordance was 97% (85/88) including 100% (41/41) for center A, 92% (23/25) for center B, and 95% (21/22) for center C. There was no significant difference in concordance among the hospitals (P=0.973), the departments (P=1.000), and the indications (P=0.799). The concordance was 70% (7/10) for isavuconazole due to its use as an empirical treatment and 100% (78/78) for the other antifungals. DISCUSSION: The concordance rate was high whatever the hospital, the department, and the indication. The only discrepancy was attributed to the use of isavuconazole as an empirical treatment which is a therapeutic option not included in the CDSS. CONCLUSIONS: This new CDSS dedicated to IA is meeting the clinical practice. Its implementation in routine will help to support antifungal stewardship.

Effects of dietary supplementation with a mixed blueberry and grape extract on working memory in aged beagle dogs.

Cellular oxidative damage is thought to be one of the key mechanisms underlying age-related cognitive impairment in dogs. Several nutritional interventions to limit cognitive decline are reported in the literature. To our knowledge, the association of grape and blueberry extracts has never been tested in aged dogs. Our objective was to evaluate the effect of a polyphenol-rich extract from grape and blueberry (PEGB) on oxidative status and cognitive performances in aged dogs. A total of thirty-five beagle dogs (aged 8·0-14·5 years) were fed a basal diet with PEGB at either 0 parts per million (ppm) (n 11; control), 240 ppm (n 12; PEGB1) or 480 ppm (n 12; PEGB2) for 75 d. To investigate the effects of PEGB supplementation on cognition and oxidative status, a delayed non-matching to position (DNMP) test and RT-PCR on genes involved in oxidative stress were evaluated. The dogs fed PEGB1 showed a higher superoxide dismutase mRNA expression compared with dogs fed PEGB2 (P = 0·042) and with the control group (P = 0·014). Moreover, the dogs fed PEGB2 showed higher nuclear factor-like 2 (Nrf2) mRNA expression compared with the dogs fed PEGB1 (P = 0·027). Concerning the DNMP test, the proportion of dogs showing cognitive improvements relative to their baseline level was significantly higher in dogs fed the PEGB, regardless of the dosage, than in dogs receiving no supplementation (P = 0·030). The results obtained in the DNMP test suggested a potential benefit of the PEGB on working memory. However, this hypothesis should be further investigated to confirm this cognitive effect.

Sodium in feline nutrition.

High sodium levels in cat food have been controversial for a long time. Nonetheless, high sodium levels are used to enhance water intake and urine volume, with the main objective of reducing the risk of urolithiasis. This article is a review of current evidence of the putative risks and benefits of high dietary sodium levels. Its secondary aim is to report a possible safe upper limit (SUL) for sodium intake. The first part of the manuscript is dedicated to sodium physiology, with a focus on the mechanisms of sodium homeostasis. In this respect, there is only few information regarding possible interactions with other minerals. Next, the authors address how sodium intake affects sodium balance; knowledge of these effects is critical to establish recommendations for sodium feed content. The authors then review the consequences of changes in sodium intake on feline health, including urolithiasis, blood pressure changes, cardiovascular alterations and kidney disease. According to recent, long-term studies, there is no evidence of any deleterious effect of dietary sodium levels as high as 740 mg/MJ metabolizable energy, which can therefore be considered the SUL based on current knowledge.

[Severe PERM syndrom mimicking tetanus]. / PERM syndrome sévère mimant un tétanos.

We report the case of a 55-year-old man without significant medical history admitted to the ICU for a progressive paralysis mimicking life-threatening tetanus. Evolution with classical tetanus treatment was negative, with the need for ventilator support and worsening condition being life threatening. Uncommon evolution revealed a rare glycin antibody-associated hyperekplexia (progressive encephalomyelitis with rigidity syndrome). Patient dramatically improved with immunosuppressive therapy including plasmatic exchanges, cyclophasmid and high dose corticoid infusions. Intensivists should be aware of this very rare syndrome whose treatment is the opposite of tetanus while presentation is very close. Optimal and treatment could lead to prolonged survival.

Influence of dietary protein content and source on colonic fermentative activity in dogs differing in body size and digestive tolerance.

Low-consistency, high-moisture feces have been observed in large dogs (Canis lupus familiaris), compared with small dogs, and particularly in sensitive breeds (e.g., German Shepherd dogs). The aim of this work was to determine if greater colonic protein fermentation is responsible for poorer fecal quality in large sensitive dogs. Twenty-seven bitches were allotted to 4 groups based on size and digestive sensitivity: small, medium, large tolerant, and large sensitive. Five experimental diets varying in protein source [highly digestible wheat gluten (WG) vs. medium digestible poultry meal (PM), and protein concentration from 21.4 to 21.6 (LP) to 38.2 to 39.2% CP (HP)] were tested. Diets were fed for 14 d and followed by a 12-d transition period. Digestive fermentation by-products were investigated in fresh stools [ammonia, phenol, indole, and short chain fatty acids including acetate, propionate, and butyrate (C2 to C4 SCFA), branched-chain fatty acids (BCFA), and valerate] and in urine (phenol and indole). Bacterial populations in feces were identified. The PM diets resulted in greater fecal concentrations of ammonia, BCFA, valerate, indole, and C2 to C4 SCFA than WG diets (P = 0.002, P < 0.001, P = 0.039, P = 0.003, and P = 0.012, respectively). Greater concentrations of ammonia, BCFA, and valerate were found in the feces of dogs fed HP compared with LP diets (P < 0.001, P < 0.001, and P = 0.012, respectively). The concentrations of ammonia, valerate, phenol, and indole in feces of large sensitive dogs were greater (P < 0.001, P < 0.001, P = 0.002, and P = 0.019, respectively) compared with the other groups. The Enterococcus populations were greater in feces of dogs fed with PMHP rather than WGLP diets (P = 0.006). Urinary phenol and indole excretion was greater when dogs were fed PM than WG diets (P < 0.001 and P = 0.038, respectively) and HP than LP diets (P = 0.001 and P = 0.087, respectively). Large sensitive dogs were prone to excrete a greater quantity of phenol in urine (P < 0.001). A diet formulated with highly digestible protein, such as WG, led to reduced concentrations of protein-based fermentation products in feces together with improved fecal quality in dogs, especially in large sensitive ones. Poor fecal quality in large sensitive dogs could be partly related to the pattern of protein fermentation in the hindgut.

Influence of dietary protein content and source on fecal quality, electrolyte concentrations, and osmolarity, and digestibility in dogs differing in body size.

When fed the same diet, large-breed dogs tend to produce feces of poorer quality compared with small-breed dogs. Moreover, German shepherds, although having a BW similar to Giant Schnauzers, are particularly prone to digestive intolerance, producing feces of poor consistency and increased moisture. Digestive tolerance reflects the reaction of the animal to the diet, and it can be assessed by determining fecal quality (consistency, moisture, volume, odor, and color). This study was conducted to assess the effect of protein source and content on fecal quality, and to determine whether greater digestibility and lesser fecal osmolarity and electrolyte concentrations are associated with improved fecal quality in dogs differing in body size and digestive tolerance. Twenty-seven healthy female dogs were divided into 4 groups according to BW and digestive tolerance: small, medium, large tolerant, and large sensitive. Five diets, varying in protein source (wheat gluten, poultry meal, and a 50:50 mixture of both sources) and concentration (22, 29, and 39% CP on a DM basis for low, medium, and high, respectively) were tested. The present study was divided in 2 phases: 2 diets were studied in a crossover design in phase I, and 3 diets were studied in a Latin square design in phase II. Diets were fed for 14 d, followed by a 12-d transition period. Fecal score (1 = dry and hard feces, to 5 = liquid diarrhea), moisture, electrolytes (Na and K), and osmolarity, and digestibility of DM, energy, fat, CP, and ash were determined. Fecal score and moisture (P < 0.001) were less and overall digestibility (P < 0.001 for DM, CP, fat, ash, and energy) was greater for wheat gluten than for poultry meal diets. Large dogs had the greatest fecal score and moisture (P < 0.001), together with the greatest overall digestibility (P < 0.001 for DM, P = 0.054 for CP, P = 0.005 for ash, and P = 0.003 for energy). Osmolarity was less for wheat gluten-based diets (P < 0.001), and was not affected by dog size. Fecal electrolyte concentration varied mainly with dog group (P = 0.005 for Na, and P < 0.001 for K), being greater in large sensitive dogs compared with small dogs. Wheat gluten was proved to be a suitable protein source for modulating fecal quality in dogs, particularly in sensitive breeds. Poorer fecal quality in large sensitive dogs can be related to greater digestibility and greater fecal electrolyte concentrations, but not to fecal osmolarity.

Hypertriglyceridaemic insulin-resistant obese dog model: effects of high-fat diet depending on age.

In humans, obesity is closely associated with insulin resistance (IR) and dyslipidaemia. The purpose of this study was to explore the effect of age on metabolic disturbances related to obesity in dogs (n = 25). Three age-groups of dogs (puppies, young adults and mature adults) were overfed to induce obesity, and body composition, insulin sensitivity index (I(IS)) (euglycaemic-hyperinsulinaemic glucose clamp) and plasma lipids were measured. Fat mass was similar in the three obese groups (30 +/- 1% in puppies, 34 +/- 1% in young adults and 39 +/- 1% in mature adults). In mature adults, body weight (BW) increased (+45%, p < 0.001) and I(IS) decreased (-60%, p < 0.001) over 22 weeks. In young adults, BW gain was similar but slower (60 weeks) and I(IS) decreased to a lesser extent (-49%, p < 0.001). Overfed puppies weighed 30% more (p < 0.01) than normally-fed control puppies, but there was no change in I(IS). Unlike young and mature adults, obese puppies did not exhibit significant changes in triglycerides (TG) and free fatty acid concentrations. In conclusion, as in humans, obese dogs develop IR that is associated with high TG levels; however, younger animals may be better able to balance energy needs with energy consumption.

Liver lipid metabolism.

The liver plays a key role in lipid metabolism. Depending on species it is, more or less, the hub of fatty acid synthesis and lipid circulation through lipoprotein synthesis. Eventually the accumulation of lipid droplets into the hepatocytes results in hepatic steatosis, which may develop as a consequence of multiple dysfunctions such as alterations in beta-oxidation, very low density lipoprotein secretion, and pathways involved in the synthesis of fatty acids. In addition an increased circulating pool of non-esterified fatty acid may also to be a major determinant in the pathogenesis fatty liver disease. This review also focuses on transcription factors such as sterol-regulatory-element-binding protein-1c and peroxisome proliferator-activated receptor alpha, which promote either hepatic fatty acid synthesis or oxidation.

Adipose tissue gene expression in obese dogs after weight loss.

Body weight (BW) mainly depends on a balance between fat storage (lipogenesis) and fat mobilization (lipolysis) in adipocytes. BW changes play a role in insulin resistance (IR), the inability of insulin target tissue to respond to physiological levels of insulin. This results in inhibition of lipogenesis and stimulation of lipolysis. Weight gain leads to IR whereas, weight loss improves insulin sensitivity (IS). The aim of this study was to evaluate the effect of weight loss and recovery of IS on the expression of genes involved in lipogenesis and lipolysis in weight losing dogs. Gene expression was studied in both subcutaneous and visceral adipose tissue. Obese dogs received a hypoenergetic low fat high protein diet (0.6 x NRC recommendation). Before and after weight loss, IS was assessed using the euglycaemic hyperinsulinaemic clamp. Gene expression of IRS-2, SREBP, intracellular insulin effectors, ACC, FAS, FABP, ADRP, PEPCK, lipogenesis key proteins, perilipin and HSL, lipolysis key proteins were quantified using real-time RT-PCR in subcutaneous and visceral fat. BW decreased from 15.2 +/- 0.5 to 11.4 +/- 0.4 kg (p < 0.05) over 78 +/- 8 days. When obese, dogs were insulin resistant. After weight loss, IS was improved. In the subcutaneous adipose tissue, the expression of only the IRS-2 was increased. In the visceral adipose tissue, the expression of the genes involved in the lipogenesis was decreased whereas one of the genes implied in the lipolysis did not change. The expression profile of genes involved in lipid metabolism, as measured after weight loss, is indicative for a lower lipogenesis after weight loss than in obese dogs. Our results also confirm dramatic differences in the lipid metabolism of visceral and subcutaneous fat. They should be completed by comparing gene expression during weight losing and normal weight steady state.

H. pylori and transient lower esophageal sphincter relaxations induced by gastric distension in healthy humans.

The role of Helicobacter pylori infection in the control of lower esophageal sphincter (LES) motility, especially the occurrence of transient LES relaxations (TLESRs), was studied in eight H. pylori-positive and eight H. pylori-negative healthy subjects. During endoscopy, biopsy specimens were taken from the cardia, fundus, and antrum for determinations of H. pylori status, gastritis, and proinflammatory cytokine mucosal concentrations. LES motility was monitored during three different 30-min periods: baseline, gastric distension (barostat), and gastric distension with CCK infusion. Gastric distension significantly increased the TLESR rate, whereas CCK increased the rate of distension-induced TLESRs further and reduced resting LES pressure without significant differences between infected and noninfected subjects. H. pylori status did not influence resting LES pressure or gastric compliance. Cytokine mucosal concentrations were increased in infected patients, but no correlation was found with the TLESR rate, which was also independent of inflammation at the cardia, fundus, and antrum. These results suggest that H. pylori-associated inflammation does not affect the motor events involved in the pathogenesis of gastroesophageal reflux.

Interleukin-8 increases acetylcholine response of rat intestinal segments.

BACKGROUND: Interleukin-8 (IL-8) is a pro-inflammatory cytokine highly expressed in inflammatory bowel diseases, but whose effects on intestinal motility are unknown. AIM: To characterize the role of IL-8 in the contraction of rat intestinal segments. METHODS: Contractile response to acetylcholine (ACh 10-6 M) in terminal ileal segments (including mucosa) from Wistar rats was measured before and after incubation (15, 30, 60 or 90 min) with IL-8 (1 ng/mL), and after 60 min of incubation with different doses of IL-8 (0, 0.1, 0.5, 1, 10 and 100 ng/mL). The effects of blocking neural transmission with tetrodotoxin (TTX) and inhibiting protein synthesis (cycloheximide) were tested. The contractile response of longitudinal muscle-myenteric plexus preparations (i.e. without mucosa) was measured after 60 min of incubation with 0.1 and 1 ng/mL of IL-8. RESULTS: IL-8 increased ileal contraction induced by ACh 10(-6) M. This augmentation was significant after 60 min of incubation (58%, P=0.01) and persisted after 90 min (18%, P=0.04). A 60-min incubation period showed a dose-related effect, beginning at 0.5 ng/mL (30%, P=0.003) and reaching a peak at 1 ng/mL (58%, P=0.01). The same effect was also observed on colonic segments. TTX did not affect the IL-8 increase of ACh-induced contractions, which was completely abolished by cycloheximide. IL-8 had no significant effect on longitudinal muscle-myenteric plexus preparations. CONCLUSION: In vitro, IL-8 increases contractile response of the ileum to ACh in a dose-dependent manner. This effect is not neurally mediated, but seems to involve protein synthesis by intestinal mucosa.

Butyrate inhibits inflammatory responses through NFkappaB inhibition: implications for Crohn's disease.

BACKGROUND/AIM: Proinflammatory cytokines are key factors in the pathogenesis of Crohn's disease (CD). Activation of nuclear factor kappa B (NFkappaB), which is involved in their gene transcription, is increased in the intestinal mucosa of CD patients. As butyrate enemas may be beneficial in treating colonic inflammation, we investigated if butyrate promotes this effect by acting on proinflammatory cytokine expression. METHODS: Intestinal biopsy specimens, isolated lamina propria cells (LPMC), and peripheral blood mononuclear cells (PBMC) were cultured with or without butyrate for assessment of secretion of tumour necrosis factor (TNF) and mRNA levels. NFkappaB p65 activation was determined by immunofluorescence and gene reporter experiments. Levels of NFkappaB inhibitory protein (IkappaBalpha) were analysed by western blotting. The in vivo efficacy of butyrate was assessed in rats with trinitrobenzene sulphonic acid (TNBS) induced colitis. RESULTS: Butyrate decreased TNF production and proinflammatory cytokine mRNA expression by intestinal biopsies and LPMC from CD patients. Butyrate abolished lipopolysaccharide (LPS) induced expression of cytokines by PBMC and transmigration of NFkappaB from the cytoplasm to the nucleus. LPS induced NFkappaB transcriptional activity was decreased by butyrate while IkappaBalpha levels were stable. Butyrate treatment also improved TNBS induced colitis. CONCLUSIONS: Butyrate decreases proinflammatory cytokine expression via inhibition of NFkappaB activation and IkappaBalpha degradation. These anti-inflammatory properties provide a rationale for assessing butyrate in the treatment of CD.

Incorporation of exogenous lipids modulates insulin signaling in the hepatoma cell line, HepG2.

The lipid content of cultured cells can be experimentally modified by supplementing the culture medium with specific lipids or by the use of phospholipases. In the case of the insulin receptor, these methods have contributed to a better understanding of lipid disorder-related diseases. Previously, our laboratory demonstrated that experimental modification of the cellular lipid composition of an insulin-sensitive rat hepatoma cell line (ZHC) resulted in an alteration in insulin receptor binding and biological action (Bruneau et al., Biochim. Biophys. Acta 928 (1987) 287-296/297-304). In this paper, we have examined the effects of lipid modification in another hepatoma cell line, HepG2. Exogenous linoleic acid (LA, n-6), eicosapentaenoic acid (EPA, n-3) or hemisuccinate of cholesterol (CHS) was added to HepG2 cells, to create a cellular model in which membrane composition was modified. In this model, we have shown that: (1) lipids were incorporated in treated HepG2 cells, but redistributed differently when compared to treated ZHC cells; (2) that insulin signaling events, such as insulin receptor autophosphorylation and the phosphorylation of the major insulin receptor substrate (IRS-1) were altered in response to the addition of membrane lipids or cholesterol derived components; and (3) different lipids affected insulin receptor signaling differently. We have also shown that the loss of insulin receptor autophosphorylation in CHS-treated cells can be correlated with a decreased sensitivity to insulin. Overall, the results suggest that the lipid environment of the insulin receptor may play an important role in insulin signal transduction.

Endogenous cholecystokinin in postprandial lower esophageal sphincter function and fundic tone in humans.

Transient lower esophageal sphincter (LES) relaxations (TLESRs) are the main underlying mechanism of gastroesophageal reflux. Although CCK acts through CCK-A receptors to increase the TLESRs induced by gastric distension, the respective roles of endogenous CCK and fundic tone in triggering postprandial TLESRs remain unknown. The aim of this study was to determine the effect of the CCK-A receptor antagonist, loxiglumide, on postprandial LES function and fundic tone in humans. LES motor events and fundic tone were simultaneously monitored in two groups of healthy volunteers. Recordings were performed during fasting and for 3 h after a liquid meal (200 ml/200 kcal) administered either orally or intraduodenally at a rate mimicking gastric emptying. Each subject received loxiglumide (10 mg. kg-1. h-1) or saline (control) in randomized order, which was started 40 min before the meal and maintained for 3 h thereafter. After the oral meal, loxiglumide significantly reduced TLESRs (P = 0.002) without significantly affecting LES pressure and fundic tone. After duodenal infusion of the meal, loxiglumide totally abolished the increase in TLESRs, reduced LES pressure fall (P < 0.02), and strongly inhibited fundic relaxation (P = 0.0001). We concluded that endogenous CCK is involved in the postprandial control of both LES function and fundic tone through activation of CCK-A receptors.

Specific adaptation of gastric emptying to diets with differing protein content in the rat: is endogenous cholecystokinin implicated?

BACKGROUND: Recent studies indicate that gastric emptying may be influenced by patterns of previous nutrient intake. Endogenous cholecystokinin (CCK), whose synthesis and release can be affected by dietary intake, has a major role in the regulation of gastric emptying. AIMS: To evaluate the influence of diets with differing protein content on gastric emptying of differing liquid test meals and plasma CCK levels in the rat and to check whether the inhibitory effect of exogenous CCK on gastric emptying is modified after long term intake of diets with differing protein content. METHODS: Rats were fed for three weeks with high protein, medium protein (regular), or low protein diet. On day 22 gastric emptying of a peptone meal was studied. In addition, basal and postprandial CCK levels after the different dietary regimens were measured by bioassay. The time course of dietary adaptation was studied and its specificity assessed through the use of different (peptone, glucose, and methylcellulose) test meals. The effect of exogenous CCK-8 on gastric emptying was studied at the end of the adaptation period (three weeks). RESULTS: Feeding the animals with a high protein diet for three weeks resulted in a significant (p < 0.05) acceleration (by 21.2 (8.2)%) of gastric emptying while feeding with a low protein diet was followed by a significant (p < 0.05) delay (by 24.0 (6.2)%) in the emptying rate. When the time course of the effect of dietary adaptation on gastric emptying was studied, it appeared that at least two weeks are required for dietary protein to be effective. The regulatory effect of dietary protein on gastric emptying proved to be dependent on meal composition. Only the emptying rate of a protein containing meal (40% peptone) was significantly modified by previous dietary intake. No significant (p > 0.05) changes were observed with glucose and methylcellulose meals whose emptying rates were similar in rats receiving a high protein or low protein diet. A peptone meal strongly and significantly (p < 0.05) increased plasma CCK levels in rats fed a medium protein (regular) diet. Results were similar in rats receiving a low protein diet (p < 0.05) but not in rats on a high protein diet (p > 0.05). As a consequence, postprandial plasma levels of CCK in rats fed with a medium or low protein diet were significantly (p < 0.05) higher than those in rats receiving a high protein diet. In rats on high and low protein diets, dose response curves to CCK-8 were virtually identical, suggesting that dietary protein intake has no influence on the effect of exogenous CCK. CONCLUSIONS: These results clearly show that gastric emptying of a protein containing meal can be modified by previous dietary protein intake. This effect, which is time dependent and meal specific, may be related to changes in endogenous CCK release which will affect emptying rate. While the exact mechanisms underlying this adaptive response need to be studied and clarified further, these results emphasise the importance of dietary history in the evaluation and interpretation of gastric emptying data.

Removal of Arg141 from the alpha chain of human hemoglobin by carboxypeptidases N and M.

Both human plasma carboxypeptidase N (CPN) and membrane-bound carboxypeptidase M (CPM) released the C-terminal arginine (alpha-Arg141) of the alpha chain of human adult hemoglobin. An arginase contamination present in the hemoglobin preparation, which converted the released arginine to ornithine, was removed by gel filtration. CPM was about 20 times more efficient than CPN or its active subunit in hydrolyzing oxyhemoglobin and cleaved oxyhemoglobin twice as fast as deoxyhemoglobin. The hydrolysis of the peptide bond of alpha-Arg141 accelerated the dissociation rate of the tetramer deoxy-des-alpha-Arg141 hemoglobin to dimers 2500-fold over that of deoxyhemoglobin, as measured by haptoglobin binding. Moreover, the dissociation of the deoxy-des-alpha-Arg141 hemoglobin tetramer to dimers was not affected by 2,3-diphosphoglyceric acid. Des-alpha-Arg141 hemoglobin had a higher oxygen affinity (P50, 5.51 mm Hg; control, 19.94 mm Hg [P50 is the partial pressure of oxygen that gives 50% of the saturation of hemoglobin]) and a lower apparent cooperativity (Hill coefficient: n, 1.02; control, 2.24) than unhydrolyzed hemoglobin. After hemoglobin was incubated in human plasma, its oxygen-binding parameters, the P50, and the Hill coefficient decreased drastically due to cleavage by CPN. In the perfused rat heart, des-alpha-Arg141 hemoglobin was a more effective coronary vasoconstrictor than hemoglobin, possibly because it dissociated to dimers in the coronary vascular bed. A covalently cross-linked hemoglobin was less active than native hemoglobin. The coronary vasoconstriction was caused by multiple factors, including interference with vasodilation by nitric oxide and eicosanoids. Thus, the hydrolysis of hemoglobin by CPM and CPN demonstrated the contribution of the alpha-Arg141 residue to sustaining the tetrameric structure of hemoglobin and its normal oxygen affinity and vasoactivity.

[Expression of the gene of cholecystokinin. Demonstration from duodenal biopsies in man]. / Expression du gène de la cholécystokinine. Mise en évidence à partir de biopsies duodénales chez l'homme.

Cholecystokinin (CCK) is a peptide released after feeding. Until now, CCK gene expression has been studied only on sacrified animals on mucosa scrapped off the duodenum. OBJECTIVE--The aim of this study was to assess CCK-mRNA detection on duodenal biopsy specimens in subjects undergoing gastrointestinal endoscopy. METHODS--Six biopsy specimens were taken from 6 healthy subjects, a) after a 12-h overnight fast and b) 6 or 12 h after a fat meal, and inducing a CCK release. CCK-mRNA was analyzed by Northern blot. RESULTS--Plasma CCK levels increased from basal levels of 0.5 +/- 0.1 pmole/L to 8.2 +/- 1.5 pmole/L 10 min after the meal. The fasting CCK-mRNA levels were 44.0 +/- 0.6% and the post-prandial levels increased to 74.0 +/- 6.0% at 6 h and decreased to 47.5 +/- 0.5% at 12 h. CONCLUSIONS--Detection of CCK gene expression in human duodenal biopsy specimens is feasible. Stimulation of CCK release after a meal is followed by an increase in CCK-mRNA in the duodenal mucosa.

Nonossifying fibromyxoid tumor of soft tissue.

A firm, painless tumor of the temporal region was excised in a 3-year-old girl. The diagnosis of nonossifying fibromyxoid tumor was established on pathologic examination, which showed that most of the cells formed cords and tubulelike structures in a myxoid background. Bone and osteoid were lacking. The child is free of recurrence 4 years after surgery.