[Health-related quality of life: a new parameter to keep in mind].
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Biomedical subjects
Publications and source records attributed to M Esteve.
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BACKGROUND: Outbreaks of nosocomial infection by methicillin resistent Staphylococcus aureus (MRSA) are a problem in many hospitals with the control measures to be adopted being controversial. An outbreak of MRSA in a 550-bed university hospital is herein described and the impact of the adopted control measures on the evolution of the epidemic in the general hospitalization area (GHA) was analyzed. PATIENTS AND METHODS: The adopted control measures in the GHA were: microbiologic surveillance, cutaneous isolation measures, treatment of nasal carrier, and the early discharge of the cases. Hand washing was reinforced and a study of carriers was carried out on detection of sporadic cases (not related to the ICU). A molecular study of 70 strains of MRSA was performed with analysis of total plasmids, plasmid restriction pattern and chromosomic DNA analysis by pulsed field gel electrophoresis (PFGE). RESULTS: From December 1990 to December 1993, 273 cases of MRSA were reported. One hundred seventy-two cases originated in the ICU and 101 cases in the GHA (sporadic cases). The incidence of MRSA in 1991-1993 was 13.6, 14.3, and 6.6% in the ICU and 0.17, 0.36, and 0.15% in the GHA, respectively. Molecular study of MRSA isolates (1991 and 1992) demonstrated two plasmid and two chromosomic patterns. The latter had a similarity coefficient > 0.90, probably belonging to the same "clone". CONCLUSIONS: Despite the control measures adopted in the GHA the outbreak of MRSA originated in the ICU thereafter extending to the GHA. The rates of colonization detected, however, remained stable during the 3 years studied. On the other hand, the observation of a single "clone", responsible for the epidemic, suggest that most of the sporadic cases were autoctonous and due to failure in fulfillment of the established norms.
L-Alanine uptake has been studied in frog red blood cells. The present study shows the presence of different carriers for this amino acid in these cells. In the physiological concentration range, most L-alanine is taken up through the Na(+)-dependent system ASC, although the sodium-independent systems asc and L are also active. The competitive inhibition data obtained makes difficult to differentiate the two Na(+)-independent activities in a clear contrast with data from fish or mammalian erythrocytes, indicating that despite its widespread occurrence in vertebrates, these carriers show characteristics that are species specific.
OBJECTIVE: To determine the expression of carbamoylphosphate synthetase (CPS) and glutamine synthetase (GS) in two different models of obese rats: genetically obese rats and diet obese rats. SUBJECTS: Lean and genetically obese (fa/fa) Zucker rats were used. DESIGN: Lean animals (30-60 d old) were fed for 30 d with standard chow pellets or with a hypercaloric cafeteria diet. Genetically obese rats were fed with standard chow pellets. MEASUREMENTS: Enzyme activity, protein (Western blot) and mRNA (Northern blot) contents of CPS and GS were measured in liver homogenates. RESULTS: In genetically obese animals CPS mRNA content was higher, and GS mRNA content was lower than in control animals; CPS protein content did not change and CPS activity was lower than in control rats. Diet-obese rats had higher levels of CPS and GS mRNAs than control animals; GS protein content and activity was higher than in the control group and at the same time, CPS activity was very low. CONCLUSIONS: In the genetically obese animals the expression of CPS and GS is mainly regulated at the pre-translational level, whereas in the diet obese rats there is a noticeable post-translational component. A reciprocal regulation between CPS and GS can be established at pre-translational levels, whereas at post-transcriptional levels it cannot. It can be concluded that in diet-obese animals the mechanisms involved in retaining nitrogen (low CPS activity) are modulated at the post-translational level.
Despite data favouring a role of dietary fat in colonic carcinogenesis, no study has focused on tissue n3 and n6 fatty acid (FA) status in human colon adenoma-carcinoma sequence. Thus, FA profile was measured in plasma phospholipids of patients with colorectal cancer (n = 22), sporadic adenoma (n = 27), and normal colon (n = 12) (control group). Additionally, mucosal FAs were assessed in both diseased and normal mucosa of cancer (n = 15) and adenoma (n = 21) patients, and from normal mucosa of controls (n = 8). There were no differences in FA profile of both plasma phospholipids and normal mucosa, between adenoma and control patients. There were considerable differences, however, in FAs between diseased and paired normal mucosa of adenoma patients, with increases of linoleic (p = 0.02), dihomogammalinolenic (p = 0.014), and eicosapentaenoic (p = 0.012) acids, and decreases of alpha linolenic (p = 0.001) and arachidonic (p = 0.02) acids in diseased mucosa. A stepwise reduction of eicosapentaenoic acid concentrations in diseased mucosa from benign adenoma to the most advanced colon cancer was seen (p = 0.009). Cancer patients showed lower alpha linolenate (p = 0.002) and higher dihomogammalinolenate (p = 0.003) in diseased than in paired normal mucosa. In conclusion changes in tissue n3 and n6 FA status might participate in the early phases of the human colorectal carcinogenesis.
BACKGROUND: Few studies have evaluated the influence of colectomy on antineutrophil cytoplasmic antibody (ANCA) positivity in ulcerative colitis (UC). In small series of patients it has been suggested that ANCA positivity in UC might be predictive for development of pouchitis after colectomy. AIMS: To assess the prevalence of ANCA in UC patients treated by colectomy and a Brooke's ileostomy (UC-BI) or ileal pouch anal anastomosis (UC-IPAA), and the relation between the presence of ANCA, the type of surgery, and the presence of pouchitis. SUBJECTS: 63 UC patients treated by colectomy (32 with UC-BI and 31 with UC-IPAA), 54 UC, and 24 controls. METHODS: Samples were obtained at least two years after colectomy. ANCA were detected by indirect immunofluorescent assay. RESULTS: There were no differences between patients with (36.3%) or without pouchitis (35.0%) and between patients with UC (55%), UC-BI (40.6%), and UC-IPAA (35.4%). However, ANCA prevalence significantly decreases in the whole group of operated patients (38.0%) compared with non-operated UC (p = 0.044). CONCLUSIONS: The prevalence of ANCA in operated patients was significantly lower than in non-operated UC, suggesting that it might be related either to the presence of inflamed or diseased tissue. ANCA persistence is not related to the surgical procedure and it should not be used as a marker for predicting the development of pouchitis.
BACKGROUND: 5-Lipoxygenase products play a part in inflammatory response. AIMS: The effect of intracolonic administration of zileuton (a 5-lipoxygenase inhibitor) on colonic damage and eicosanoid local release was assessed in a rat model of colitis. METHODS: Ninety rats with trinitrobenzenesulphonic acid induced colitis were randomised to receive placebo, 5-aminosalicylic acid (50 mg/kg), or zileuton (50 mg/kg) intracolonically for four weeks. Local eicosanoid release was monitored by intracolonic dialysis throughout the study. The colon was removed for macroscopic and histological assessment at weeks 1, 2, and 4 after colitis induction in 10 rats of each group. RESULTS: Zileuton significantly reduced macroscopic damage score after four weeks of treatment in comparison with the other two groups (p = 0.034). In addition, zileuton administration significantly increased the intracolonic release of both thromboxane B2 at week 1 (p = 0.05) and prostaglandin E2 at weeks 2 and 4 (p < 0.05). Zileuton and 5-aminosalicylic acid decreased leukotriene B4 release by 90% at day 3. CONCLUSIONS: Intracolonic zileuton, compared with 5-aminosalicylic acid and placebo, seems to improve the course of the disease in a model of chronic colitis. This effect may be related to an increased and maintained production of prostaglandin E2 together with inhibition of leukotriene B4 synthesis.
The present study investigates the regulation of Na+/K+ pump activity and alanine uptake in trout hepatocytes. Pump activity increased when cells were incubated in an amino-acid-free medium, while it was reduced in cells from fasted animals. Short-term exposure (3 h) to glucagon modified the activity of the pump in a complex seasonally dependent pattern: in experiments carried out in autumn and winter there was some inhibition, while in spring the pump was activated by this hormone. Pharmacological modification of levels of two intracellular signal transducers, namely cyclic AMP and Ca2+, always led to a reduction in pump activity. These experiments were conducted in May, when activation of the pump by glucagon exposure occurred. There is no apparent explanation for the mechanism by which this hormone modifies the activity of the pump. Glucagon also regulates the activity of system ASC (a Na+-dependent amino acid carrier with short-chain neutral amino acids as preferred substrates). This regulation also showed a seasonally dependent pattern, although the pattern was opposite to that found for the regulation of Na+/K+ pump activity.
OBJECTIVE: To determine whether adipose tissue removes a significant proportion of circulating insulin in the obese rat in vivo. DESIGN: Blood samples were obtained from the carotid artery and the venous side of hind leg muscle, epididymal fat pads and liver (portal and suprahepatic veins), they were used for estimation of insulin disappearance across the tissue. SUBJECTS: Anaesthetized Zucker lean (Fa/?) and obese (fa/fa) adult male rats. MEASUREMENTS: Blood flow, glycaemia and insulinaemia. RESULTS: In lean rats, the liver accounted for practically all insulin extraction (498 +/- 149 fmol.s-1), removing more than half of the portal insulin in a single pass. In the obese rats, the liver extracted a similar amount in absolute terms (397 +/- 108 fmol.s-1), representing only 16% of portal insulin. In the hind leg muscle of both groups and in the adipose tissue of lean rats, insulin balances were not different from zero; but in obese rats, adipose tissue extracted a similar amount of insulin (405 +/- 127 fmol.s-1) to that removed by the liver. CONCLUSIONS: In the Zucker obese rat, peripheral adipose tissue removes as much insulin from the blood as the liver does, in contrast with lean rats, in which the latter is responsible for practically all insulin extraction.
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E-4695, (-)-7-[3-(R)-amino-2-(S)-methyl-1-azetidinyl]-1-cyclopropyl-1,4- dihydro-6-fluoro-4-oxo-1,8-naphthyridine-3-carboxylic acid, is a new fluorinated naphthyridine with an azetidine moiety. The MICs of E-4695 at which 90% of the isolates were inhibited (MIC90s) were 0.06 to 0.5 microgram/ml for gram-positive cocci, including species of the genera Staphylococcus, Streptococcus, and Enterococcus, and the MIC90s against gram-negative pathogens such as members of the family Enterobacteriaceae (with the exception of Providencia spp. [MIC90, 8 micrograms/ml]) and Pseudomonas aeruginosa were 0.015 to 0.5 microgram/ml. E-4695 inhibited 90% of the Clostridium perfringens and Bacteroides fragilis isolates at 0.25 and 4 micrograms/ml, respectively. Against gram-positive cocci the potency of E-4695 was 2- to 8-fold higher than that of ciprofloxacin, 4- to 8-fold higher than that of ofloxacin, and 8- to 16-fold higher than that of fleroxacin. Against enteric bacteria and P. aeruginosa the potency of E-4695 was, in general, similar to that of ciprofloxacin and eightfold higher than those of ofloxacin and fleroxacin. E-4695 was four- and eightfold more potent than ciprofloxacin against C. perfringens and B. fragilis isolates, respectively. E-4695 and ciprofloxacin showed similar properties when the effects of pH or magnesium concentration were tested on them. E-4695 and ciprofloxacin had substantial reductions of activity only when pH decreased below 4.8. E-4695 and ciprofloxacin activities were not markedly affected by the presence of 5 or 10 mM Mg2+. The presence of serum and human urine at pH 7.2 decreased the activity of E-4695 between two- and fourfold. After an oral dose of 50 mg/kg of body weight, the maximum level in serum, the biological half-life, and the area under the concentration-time curve from 0 to 10 h for E-4695 were 13.2 microgram/ml, 3.3 h, and 45.6 microgram . h/ml, respectively. The area under the concentration-time curve from 0 to 4 h for ciprofloxacin was 2.3 microgram . h/ml at the same dose. Fifty-percent effective doses (ED50S) against Staphylococcus aureus HS-93 infections in mice were 4.5 mg/kg with E-4695 and 37.6 mg/kg with ciprofloxacin. Infection with Streptococcus pneumoniae 29206 was more effectively treated with E-4695 (ED50, 41,2 mg/kg) than with ciprofloxacin (ED50, 200 mg/kg). The ED50 of E-4695 for infections with Streptococcus pneumoniae 1625 was 132.2 mg/kg; ciprofloxacin was ineffective at 400 mg/kg against this strain. E-4695 was also more potent than ciprofloxacin in treatment of infections caused by gram-negative organisms such as Escherichia coli HM-42 (ED50S, 1.0 and 3.9 mg/kg, respectively). The ED50S of E-4695 and ciprofloxacin were 33.0 and 145.5 mg/kg against P. aeruginosa HS-116 and 9.6 and 18.9 mg/kg against P. aeruginosa B-120, respectively. The therapeutic efficacy of E-4695 may depend not only on its in vitro activity but also on its improved pharmacokinetic properties.
Zucker lean and obese rats were injected under pentobarbital anesthesia with 125I-labeled insulin; at timed intervals from 30 to 120 sec, blood samples were extracted and used for the estimation of insulin levels by RIA. A group of rats from each series was maintained under a constant infusion of noradrenaline. For each insulin determination, a duplicate blood sample containing the same amount of insulin as that used in the RIA, but without the radioactive label, was used as a blank for insulin measurement. The radioactivity in these tubes was then used for the measurement of insulin label per ml blood. From plasma label decay curves and insulin concentrations, the insulin pool size, half-life, and rate of degradation were calculated. Obese rats had higher insulin levels (2.43 nM) and showed less effect of noradrenaline than their lean counterparts, in which insulin distribution volume shrank with noradrenaline treatment. The half-life of plasma insulin was similar in all groups (range, 226-314 sec). Pool size and overall degradation rates were higher in obese (198 femtokatals) than in lean rats (28 femtokatals). It is postulated that obese rats synthesize and cleave much more insulin than lean controls despite their higher circulating levels of insulin.
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The balances and content of essential elements (iron, copper, zinc, chromium and manganese) in the body of Wistar, Zucker lean and Zucker obese rats fed a reference or cafeteria diet from day 30 to 60 after birth have been studied. Intestinal iron absorption compensated for low iron content of the cafeteria diet and the extra needs of growth and fat deposition. It can be assumed that the altered energy regulation processes that afflict the genetically obese rat are not directly related to altered iron metabolism. Obese Zucker rats had lower copper tissue concentrations than lean rats, but when fed a cafeteria diet the differences between Zucker rats strains disappear. This cannot be traced to large differences in diet copper concentration. A low diet availability of zinc--such as that of cafeteria-fed fa/fa rats--is easily compensated for by increasing absorption. So, as a consequence, we can conclude that genetic obesity did not impair zinc absorption. There was no deficit of zinc in any of the groups studied; the rats have enough capacity to extract zinc within a wide range of dietary concentrations. The absorption of dietary chromium was inversely proportional to its concentration. The ability to extract chromium from the diet and the very low urinary losses are a consequence of its scarcity in most dietary items. Despite wide variations in the manganese of the diets, the absorption rates were practically unchanged except for obese rats fed the cafeteria diet. It seems that this low absorptive capacity is enough to supply the rat with the manganese it needs, since a sizeable--but subjected to 8-fold-span variations--proportion is lost in the urine. This alone points towards a considerable excess of manganese in both diets studied. Obesity does not have a significant effect on the abilities to absorb and retain minerals, since these processes were more related to dietary availability. Management of essential metals by obese rats depends whether this condition is genetic or induced by diet. Most of the differences observed can be related to differences in diet concentration, to the excess fat content or different metabolic attitude to use substrates of obese animals. The data presented show that the cafeteria diet used adequately serves the mineral needs of the rat, since the rat adapts its absorbing and retaining strategies to match the dietary availability of these minerals.
The energy balance and nutrient selection strategies of 30-day-old Wistar rats offered a reference pellet and a seven-item cafeteria diet were studied in two consecutive 15-day periods: 30-45 and 45-60 days after birth. Cafeteria-fed rats grew faster, incorporating more fat and water, but a similar amount of protein to reference-fed animals. In the second 15 days all rats ate less and produced less heat than in the first 15 days. Reference-fed rats also deposited less energy in their bodies, in contrast to the tendency towards higher carcass energy deposition in cafeteria-fed rats. Cafeteria-fed rats selected much more fat and sugars than controls, with similar protein and less starch; in the second period studied, cafeteria-fed rats significantly increased their sugar consumption, with no change in fat or protein. It is suggested that the switch to selecting more sugars may be an essential factor in the shift towards increased fat deposition at the expense of heat production in cafeteria-fed rats.
The amino acid composition of the protein from three strains of rat (Wistar, Zucker lean and Zucker obese), subjected to reference and high-fat diets has been used to determine the mean empirical formula, molecular weight and N content of whole-rat protein. The combined whole protein of the rat was uniform for the six experimental groups, containing an estimate of 17.3% N and a mean aminoacyl residue molecular weight of 103.7. This suggests that the appropriate protein factor for the calculation of rat protein from its N content should be 5.77 instead of the classical 6.25. In addition, an estimate of the size of the non-protein N mass in the whole rat gave a figure in the range of 5.5% of all N. The combination of the two calculations gives a protein factor of 5.5 for the conversion of total N into rat protein.
The amino acid composition of the diet ingested by reference and cafeteria diet-fed lean and obese Zucker rats has been analyzed from day 30 to 60 after birth. Their body protein amino acid composition was measured, as well as the urinary and faecal losses incurred during the period studied. The protein actually selected by the rats fed the cafeteria diet had essentially the same amino acid composition as the reference diet. The mean protein amino acid composition of the rat showed only small changes with breed, age or diet. Cafeteria-fed rats had a higher dietary protein digestion/absorption efficiency than reference diet-fed rats. Obese rats wasted a high proportion of dietary amino acids when given the reference diet, but not on the cafeteria diet. In all cases, the amino acids lost as such in the urine were a minimal portion of available amino acids. In addition to breed, the rates of protein accretion are deeply influenced by diet, but even more by the age-or size-of the animals: cafeteria-fed rats grew faster, to higher body protein settings, but later protein accrual decreased considerably; this is probably due to a limitation in the 'blueprint for growth' which restricts net protein deposition when a certain body size is attained. Obese rats, however, kept accruing protein with high rates throughout. Diet composition--and not protein availability or quality--induced deep changes in amino acid metabolism. Since the differences in the absolute levels of dietary protein or carbohydrate energy ingested by rats fed the reference or cafeteria diets were small, it can be assumed that high (lipid) energy elicits the changes observed in amino acid metabolism by the cafeteria diet. The effects induced in the fate of the nitrogen ingested were more related to the fractional protein energy proportion than to its absolute values. Cafeteria-fed rats tended to absorb more amino acids and preserve them more efficiently; these effects were shown even under conditions of genetic obesity. There were deep differences in handling of dietary amino acids by dietary or genetically obese rats. The former manage to extract and accrue larger proportions of their dietary amino acids than the latter. The effects of both 'models' of amino acid management were largely additive, suggesting that the mechanisms underlying the development of obesity did not run in parallel to those affecting the control of amino acid utilization. Obesity may be developed in both cases despite a completely different strategy of amino acid assimilation, accrual and utilization.
The water balance in Wistar, Zucker obese and Zucker lean rats, aged 60 days, was measured by determining the amount of water they drank, that contained in the solid food eaten, the water lost through urine and droppings, the net water accrued (estimated from the composition of the body and the daily increase in body weight), the measurement of the water vapour lost and the calculation of metabolic water production by means of the measurement of oxygen consumption, carbon dioxide production and protein oxidation in a 24 hr period. 1. Despite widely different body weights, all three groups of animals accrued a similar proportion of their daily water budget (4.3-4.9%, i.e. 1.2-1.4% of the total rat water mass). 2. Wistar and Zucker obese rats had a similar daily water budget despite very different body weights, lean Zucker rats had lower water budgets. 3. Obese and lean Zucker rats produced a more concentrated, and excreted much less urine (the highest urea concentration was found in obese rats) than Wistar rats. 4. The water lost in the droppings was in the same range as that in urine for obese rats, slightly less for lean Zucker rats and much less in Wistar rats. Obese rats produced a higher amount of stool with respect to the amount of food eaten than the lean animals studied. 5. The contribution of metabolic water to the daily water budget was a 23.6% for Zucker obese, 22.5% for Zucker lean and 15.9% for Wistar rats.