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PubMed1990

Estrogen induces hyperlipidemia in fasted chicks.

To determine whether the estrogen-induced hyperlipidemia is affected by fasting, male growing chicks were administered subcutaneously a single dose of 17 beta-estradiol (25 mg/kg body wt), and the hormone treatment lasted for 2 days with or without feed (Experiment 1). In the second experiment, chicks were initially fasted for 1 or 3 days, and then treated with the same dosage of 17 beta-estradiol as in Experiment 1 for 2 days without feed. Plasma and liver lipids, and the activities of hepatic malic enzyme, glucose-6-phosphate dehydrogenase, and hormone-sensitive lipase in the adipose tissue were determined. Compared with fed control chicks, estrogen treatment in fed birds resulted in a marked elevation of plasma lipids, especially triglyceride during the 2-day period (137 vs 2263 mg/dl). In fasted chicks, the present finding that estrogen also induced a marked hyperlipidemia is noteworthy. Upon estrogen treatment (Experiment 1), the level of plasma triglyceride in fasted birds increased about 16 times over that of the fasted control group (133 vs 2093 mg/dl). Even in chicks fasted for 5 days (Experiment 2), estrogen treatment resulted in a persistent hypertriglyceridemia (75 vs 1369 mg/dl). In fed chicks, estrogen treatment also induced a fatty liver with massive accumulation of triglyceride, but the liver of estrogen-treated/fasted chicks appeared to be normal. In both fed and fasted chicks, malic enzyme was found to be the major NADPH producing enzyme in the liver. Upon fasting, both malic enzyme and glucose-6-phosphate dehydrogenase activities decreased significantly (P less than 0.05). In fed chicks, the total activities of both enzymes increased with estrogen treatment, whereas the effect of hormone on these enzymes was less obvious in fasted chicks. The hormone-sensitive lipase activity in the adipose tissue was much lower in fed chicks compared with that of fasted birds (0.15 vs 0.33 nmol of oleic acid released/min/mg protein). Estrogen treatment in fed chicks had no effect on the hormone-sensitive lipase activity, but its activity was enhanced by the hormone treatment in fasted chicks. The present finding that hyperlipidemia persisted in estrogenized chicks during the fasting seems to indicate the complex nature of this hormonal influence on lipid metabolism.

Adipose Tissue↗
PubMed2003

Effects of L-glutamate supplementation mimic effects of fasting in the ischemic heart.

Endogenous glycogen stores are essential to maintain cell functions during myocardial ischemia.. Fasting and L-glutamate improve left ventricular function after an ischemic episode. We studied their effects on myocardial glycogen depletion during ischemia and on left ventricular function and glycogen resynthesis during reperfusion. We allocated 185 Wistar rats to 4 groups: 1) Control, 2) Fasting, 16-20 hours (Fast) 3) L-glutamate supplementation [100 mM] (Glt) or 4) Fasting + L-glutamate supplementation [100 mM]. n = 8-10 in each group. Hearts were mounted in an isolated perfused rat hearts model for 20 min stabilisation, 10/20/30 min ischemia and 60 min reperfusion. At each time point hearts were frozen in liquid nitrogen (-196 degrees C) within 2 seconds and myocardial contents of glycogen, lactate, alanine and glutamate were determined. Left ventricular pressure was measured continuously. Fasting and L-glutamate supplementation improved LV function after ischemia (Fast: p < 0.05, Glt: p < 0.01) and delayed myocardial glycogen depletion (Fast: p < 0.05, Glt: p < 0.01) compared to control. Decreased lactate accumulation and increased alanine content during ischemia were found in fasted (lactate: p < 0.05, alanine: p < 0.05) and L-glutamate supplemented (lactate: p < 0.01, alanine: p < 0.01) hearts compared to control. We did not find any additive effects of fasting and L-glutamate supplementation. In conclusion fasting and L-glutamate supplementation improve left ventricular function during reperfusion and delay myocardial glycogen depletion during ischemia. There were no additive effects of Fasting and L-glutamate supplementation. These finding suggest common metabolic pathways underlying the effects of L-glutamate supplementation and fasting.

Animals↗
PubMed1990

UK Prospective Diabetes Study 7: response of fasting plasma glucose to diet therapy in newly presenting type II diabetic patients, UKPDS Group.

The response to diet of 3,044 newly diagnosed diabetic patients with a fasting plasma glucose (mean +/- 1 SD) of 12.1 +/- 3.7 mmol/L, age 52 +/- 8 years, and body weight 130% +/- 26% ideal body weight has been studied. The reduction in the fasting plasma glucose was greater in those presenting with a high initial fasting plasma glucose and in those who lost more weight, but was not related to the degree of obesity. There was considerable variation in the response to dieting, but on average, patients presenting with a fasting plasma glucose of 10 to 12 mmol/L needed to lose 28% ideal body weight (18 kg) to attain a fasting plasma glucose less than 6.0 mmol/L. Sixteen percent of all patients achieved a near-normal (less than 6 mmol/L) fasting plasma glucose after 3 months' dieting, ranging from 50% of those presenting with fasting plasma glucose of 6 to 8 mmol/L to 10% of those with fasting plasma glucose of 16 to 22 mmol/L. In those who achieved less than 6.0 mmol/L, in the second 3 months the fasting plasma glucose increased by a mean of 0.4 mmol/L even though there was a further mean weight reduction of 2.1% ideal body weight (1.4 kg) in addition to their loss of 11.6% ideal body weight (8 kg) in the initial 3 months. This confirms that the decrease in fasting plasma glucose is determined more by the restriction of energy intake than by the body weight. Those who maintained their fasting plasma glucose at less than 6.0 mmol/L in the year following the initial 3-month dietary period lost a further 3% (2 kg) ideal body weight. The data confirm the value of dieting, but in view of the large weight loss and equivalent large reduction in energy intake required in most patients, it is not surprising that few patients achieve near-normal fasting plasma glucose concentrations by diet alone.

Blood Glucose↗
PubMed1986

Effect of fasting on thyroxine, 3,5,3'-triiodothyronine, and cortisol concentrations in serum of dogs.

The present study was designed to compare basal and stimulated concentrations of 3,5,3'-triiodothyronine (T3), thyroxine (T4), and cortisol in serum of dogs fasted 12 or 18 hours (to represent overnight fasting) or 24 or 36 hours (to represent prolonged inappetence) with those of dogs that were not fasted. Twenty-five adult Beagle bitches were allotted to 5 experimental fasting groups (0, 12, 18, 24, and 36 hours). Blood samples for hormonal analyses were obtained 4, 3, 2, and 1 hour before food was removed; at the time of food removal; 1 hour after food was removed; and every 2 hours during experimental fasting until 0800 hours on the day fasting ended. Dogs were injected with 5 IU of thyrotropin, IV, and 2.2 IU of adrenocorticotropin/kg, IM, to evaluate thyroidal and adrenocortical endocrine reserves. Additional blood samples were collected 0.5, 1, 2, 3, and 4 hours after injections were given. Serum concentrations of T3, T4, and cortisol were determined by validated radioimmunoassays. Body weights and ages of the dogs and food consumption during a 2-hour preliminary feeding period before dogs were fasted did not differ among fasting groups. Length of fasting did not affect serum concentrations of T3 or T4 in dogs at 12, 18, 24, or 36 hours after food was removed. Mean serum concentrations of cortisol in dogs fasted 12 or 24 hours were lower than those in dogs that were not fasted. Serum concentrations of the hormones after thyrotropin and adrenocorticotropin were injected were not affected by fasting.(ABSTRACT TRUNCATED AT 250 WORDS)

Analysis of Variance↗
PubMed1984

Effects of four-day fast on triglyceride mobilization in human adipocytes.

To examine the effect of a four-day fast on neutral glyceride mobilization in human adipocytes, subcutaneous abdominal fat tissue was obtained from ten human volunteers after an overnight fast and then after four days of fasting. Plasma insulin concentration decreased from 31 +/- 5 microU/ml before the four-day fast to 9 +/- 1 microU/ml after the fast (P less than 0.05). Plasma free fatty acid concentration increased from 13.9 +/- 1.3 to 23.6 +/- 3.2 mg/dl (P less than 0.05). Mean average cell size was similar before and after the four-day fast. Basal lipolysis increased threefold (P less than 0.005) regardless of cell size after four days of fasting. In contrast, isoproterenol (2 microM) stimulated maximum lipolysis was not increased after a four-day fast. The concentrations of isoproterenol required for a half maximum stimulation in the presence of 50 (7 microU/ml) and 8000 pM (1150 microU/ml) insulin were lower after a four-day fast (P less than 0.05, P less than 0.03, respectively) and were uninfluenced by average cell size. Basal and maximum insulin-stimulated glucose transport were similar after a four-day fast. However, glucose incorporation into neutral glycerides was reduced by 50 percent (P less than 0.02) following a four-day fast. The reduction was uninfluenced by average cell size. The data indicate that abdominal adipocytes after a four-day fast are metabolically adapted towards increased neutral glyceride mobilization by reducing glucose incorporation into neutral glycerides, increasing sensitivity of lipolysis to isoproterenol, and increasing basal lipolysis.

Adipose Tissue↗
PubMed1976

Effects of fasting on bile acid metabolism and biliary lipid composition in man.

The effects of a four to six day fast on gallbladder bile lipid composition, bile acid pool size, bile acid composition, and cholic acid metabolism have been determined in normal human subjects. Total bile acid pool size and cholic acid pool size were measured before and after fasting by a one-sample technique previously validated in our laboratory. The rate of synthesis of cholic acid and its fractional turnover rate before fasting were measured using standard techniques. Estimates of fasting cholic acid synthesis rate and fractional turnover rate were calculated as daily averages from the change in cholic acid pool size, in combination with the change in cholic acid specific activity, during the fasting period. Since these estimates are approximate, a maximum value for cholic acid synthesis rate during fasting was also determined by assuming that the entire change in cholic acid specific activity during the fasting period occurred instantaneously. The molar percent of cholesterol in gallbladder bile was reduced in eight of nine subjects after a four to six day fast (p less than .01; mean reduction 30.5%). The molar percents of bile acid and phospholipid were not significantly altered by fasting. The cholesterol saturation index, calculated on the basis of these data, was reduced by an average of 31.0% after a four to six day fast (p less than .02). The average daily cholic acid synthesis rate and the fractional turnover rate were reduced in all six subjects on whom isotope kinetic studies were carried out. The mean decrease in synthesis rate was 68.5% (p less than .05; range 55.2-79.8%) while the mean decrease in fractional turnover rate was 64.4% (p less than .05; range 30.2-100%). Reduction in synthesis rate was confirmed by the determination of maximum fasting synthesis of cholic acid, which averaged 61.1% lower than synthesis in the fed period. Fasting had no consistent effect on total bile acid pool size, cholic acid pool size, or bile acid species composition.

Adolescent↗
PubMed2004

Compensation for energy intake from fast food among overweight and lean adolescents.

CONTEXT: Fast food consumption has increased greatly among children in recent years, in tandem with the obesity epidemic. Fast food tends to promote a positive energy balance and, for this reason, may result in weight gain. However, if fast food and obesity are causally related, the question arises of why some children who frequently eat fast food do not become overweight. OBJECTIVE: To test the hypothesis that overweight adolescents are more susceptible to the adverse effects of fast food than lean adolescents. DESIGN AND SETTING: In study 1, we fed participants an "extra large" fast food meal in a naturalistic setting (a food court). The participants were instructed to eat as much or little as desired during this 1-hour meal. In study 2, we assessed energy intake under free-living conditions for 2 days when fast food was consumed and 2 days when it was not consumed. Data were collected in Boston, Mass, between July 2002 and March 2003. PARTICIPANTS: Overweight (n = 26) and lean (n = 28) adolescents aged 13 to 17 years. Overweight was defined as a body mass index exceeding sex- and age-specific 85th percentiles based on the 2000 Centers for Disease Control and Prevention growth charts. MAIN OUTCOME MEASURES: Energy intake determined by direct observation in study 1 and by unannounced 24-hour dietary recalls, administered by telephone, in study 2. RESULTS: In study 1, mean (SEM) energy intake from the fast food meal among all participants was extremely large (1652 [87] kcal), accounting for 61.6% (2.2%) of estimated daily energy requirements. Overweight participants ate more than lean participants whether energy was expressed in absolute terms (1860 [129] vs 1458 [107] kcal, P =.02) or relative to estimated daily energy requirements (66.5% [3.1%] vs 57.0% [2.9%], P =.03). In study 2, overweight participants consumed significantly more total energy on fast food days than non-fast food days (2703 [226] vs 2295 [162] kcal/d; +409 [142] kcal/d; P =.02), an effect that was not observed among lean participants (2575 [157] vs 2622 [191] kcal/d; -47 [173] kcal/d; P =.76). CONCLUSIONS: In this study, adolescents overconsumed fast food regardless of body weight, although this phenomenon was especially pronounced in overweight participants. Moreover, overweight adolescents were less likely to compensate for the energy in fast food, by adjusting energy intake throughout the day, than their lean counterparts.

Adolescent↗
PubMed2001

FAST sequences optimization for contrast media pharmacokinetic quantification in tissue.

The purpose of this study was to investigate the influence of the fast gradient-recalled echo (GRE) sequence parameters on the contrast dynamic range and signal sensitivity, to optimize the magnetic resonance (MR) sequence for contrast media pharmacokinetic assessment. Effects of the fast low-angle shot (FLASH), Fast acquisition at steady rate (FAST), and radiofrequency-spoiled (RF)-FAST sequence parameters were studied in vitro. The FAST sequence had the highest sensitivity in low gadolinium (Gd) concentration. The FLASH and RF-FAST sequences had a larger contrast dynamic range, but the FLASH images contained side band artifacts. Increasing the flip angle to 90 degrees raised the sensitivity of the FAST sequence and the contrast dynamic range of the RF-FAST sequence. The shortest possible TE was optimal for both contrast dynamics and imaging time. TI had an influence on the sensitivity of the FAST sequence only for small acquisition matrices. This study indicates the optimal parameters for contrast dynamics (RF-FAST, 90 degrees flip angle, shortest possible TE) and sensitivity (FAST, 90 degrees flip angle, long TI(eff)).

Contrast Media↗
PubMed1992

Changes in plasma glucagon, insulin and tissue metabolites associated with prolonged fasting in brown trout (Salmo trutta fario) during two different seasons of the year.

1. Pyrenean brown trout juveniles (Salmo trutta fario) were fasted for 50 days in late winter (experiment 1) and summer (experiment 2). Plasma insulin, glucagon and glucose and some metabolites in plasma and in tissues were analysed. 2. Glucagon increased significantly on the 3rd day of fasting in the winter experiment (controls 653.7 +/- 92.4 pg/ml, fasted 912.7 +/- 135.2 pg/ml), and the same tendency was observed on the 5th day in the summer experiment (controls 430.5 +/- 56.2 pg/ml, fasted 555.5 +/- 95.3 pg/ml). During this initial period of fasting, plasma glucose was maintained in both experiments (75.5 +/- 4.7-67.6 +/- 4.1 mg/100 ml), but from day 8, glucose and glucagon decreased simultaneously. 3. Insulin decreased from the beginning of fasting, reaching lowest values after 50 days of fasting (winter experiment: controls 6.4 +/- 0.3 ng/ml, fasted 1.6 +/- 0.1 ng/ml; summer experiment: controls 4.8 +/- 0.1 ng/ml, fasted 1.2 +/- 0.2 ng/ml). Glucagon/insulin molar ratio (G/I) increased after 3 days in the winter experiment (controls 0.21 +/- 0.02, fasted 0.39 +/- 0.05), while in the summer experiment, the ratio rose from day 5 and reached a peak at day 30 (controls 0.16 +/- 0.02, fasted 0.48 +/- 0.07). 4. Muscle proteins were significantly mobilized after 50 days of fasting. Visceral index decreased significantly after day 15 while liver glycogen was already significantly lower at day 8. However, in the summer experiment, a transitory increase of liver glycogen was observed at day 30, coinciding with the peak of G/I.

Animals↗
PubMed2006

A biomechanical comparison of the FasT-Fix meniscal repair suture system and the RapidLoc device in cadaver meniscus.

PURPOSE: This biomechanical study compared the fixation characteristics of horizontally or vertically implanted FasT-Fix devices (Smith & Nephew, Endoscopy Division, Andover, MA) consisting of two 5-mm PLLA suture T-bar anchors with a pretied self-sliding knot (No. 0 nonabsorbable, USP, braided polyester suture material) and the RapidLoc device (Mitek Surgical Products, Westwood, MA) consisting of a PLLA T-bar anchor or "backstop," a connecting suture (No. 2 nonbiodegradable Ethibond; Ethicon, Somerville, NJ), and a PLLA grommet, for repairing posterior third lesions in human menisci. TYPE OF STUDY: Controlled laboratory biomechanical study. METHODS: After repair of a vertical longitudinal meniscus lesion with either vertically or horizontally implanted FasT-Fix devices or RapidLoc devices, 3 groups of 6 specimens underwent cyclic loading (5 mm/minute, cycling between 5 and 50 N at 1 Hz for 500 cycles) before load to failure testing on a servo hydraulic device. One-way analysis of variance and Tukey HSD post hoc tests were used to evaluate group differences (P < .05). RESULTS: The vertical FasT-Fix device group (3.2 +/- 0.49 mm) had less displacement after cyclic testing than either the horizontal FasT-Fix (4.4 +/- 0.73 mm, P = .003) or the RapidLoc (4.6 +/- 0.22 mm, P = .002) device groups. The vertical FasT-Fix device group had greater stiffness during cyclic testing (14.4 +/- 2.1 N/mm) than the horizontal FasT-Fix (10.4 +/- 1.6 N/mm, P = .0001) or the RapidLoc (9.7 +/- 0.44 N/mm, P = .0001) device groups. During load to failure testing, the vertical FasT-Fix group (125.3 +/- 39 N) had 28% greater strength than the horizontal FasT-Fix device group (89.7 +/- 14 N, P = .02) and 30% greater strength than the RapidLoc device group (87.1 +/- 13 N, P = .028), whereas displacement and stiffness did not show statistically significant group differences. CONCLUSIONS: The vertical FasT-Fix group had superior biomechanical characteristics for meniscal fixation during cyclic and load to failure testing compared with horizontal FasT-Fix or RapidLoc devices. CLINICAL RELEVANCE: Although the RapidLoc devices provided fixation characteristics comparable to horizontally implanted FasT-Fix devices, vertically implanted FasT-Fix devices may provide superior all-inside fixation.

Absorbable Implants↗
PubMed2005

Prolongation of the fast pathway effective refractory period during cryoablation in children: a marker of slow pathway modification.

BACKGROUND: The fast pathway effective refractory period (ERP) has been reported to decrease after slow pathway modification with radiofrequency (RF) energy. How the fast pathway ERP changes during the ablation application has not been reported with either RF or cryoenergy. OBJECTIVES: Using the unique features of cryotherapy, this study assesses the short-term changes in fast pathway ERP during cryomodification of the slow pathway and examines whether these changes are a useful marker for successful slow pathway modification in children. METHODS: Nineteen pediatric patients (median age 15.1 years, range 9.6-19.6 years; weight 60.7 kg, range 35.6-130.2 kg) with anterograde dual AV nodal physiology underwent slow pathway modification with catheter-based cryoablation. Programmed stimulation was performed during cryoapplications after reaching -25 degrees C to assess fast pathway and slow pathway conduction. Data were analyzed from 59 of 237 cryoapplications where the fast pathway ERP was measured more than once (n = 13 patients). RESULTS: For 23 of 59 applications where the slow pathway was modified, the fast pathway ERP significantly increased during cryotherapy (Delta = 33.5 ms, P <.0001). The magnitude of fast pathway ERP prolongation during cryotherapy was larger when the slow pathway was modified than when there was no effect on slow pathway conduction (33.5 +/- 30.5 vs 5.8 +/- 18.9 ms, P =.0005). Prolongation of fast pathway ERP by >/=20 ms had 70% sensitivity and 72% specificity for predicting slow pathway modification. Following termination of cryoapplications, which resulted in slow pathway modification, the fast pathway ERP had significantly decreased from baseline (difference 44.5 ms, P <.0001). The effect on fast pathway ERP was not related to changes in cycle length during (R(2) = 0.04, P = .045) or after ablation (R(2) = 0.13, P = .012). CONCLUSION: The fast pathway ERP prolongs during cryoapplications that result in slow pathway modification and shortens after termination of cryoapplications. The magnitude of fast pathway ERP prolongation during cryoapplication may be useful as a marker for successful slow pathway modification.

Adolescent↗
PubMed1999

Preliminary experience with focused abdominal sonography for trauma (FAST) in children: is it useful?

BACKGROUND/PURPOSE: Most pediatric surgeons and pediatric radiologists consider computed tomography (CT) the best radiological test for the evaluation of children with suspected intraabdominal injury. The majority of injured children evaluated with CT will be found to have a normal scan. Focused abdominal sonography for trauma (FAST) has been shown to be a useful screening test in the evaluation of adult patients with suspected intraabdominal injury. Limited data exist regarding the use of FAST in children. Our aim was to evaluate the usefulness of FAST as a screening test in the evaluation of children with suspected intraabdominal injury in an attempt to minimize the number of normal CT scans performed. METHODS: Hemodynamically stable children evaluated for suspected intraabdominal injury were prospectively screened with FAST. FAST, real-time sonography at four sites, was performed by staff pediatric radiologists. The average duration of the examination was 2 minutes. Positive and negative FAST scan findings were defined prospectively. The result of each FAST was recorded (positive or negative) and then all patients underwent CT as a control. All management decisions were based on CT results. RESULTS: Forty-six patients were included in the study. FAST identified four children with positive findings (free intraperitoneal fluid), whereas CT showed 13 children with injuries (nine with associated free intraperitoneal fluid and four with only solid organ injury and no associated intraperitoneal fluid). There were nine false-negative and no false-positive FAST scans. The sensitivity of FAST was 0.3 and the specificity was 1.0. Injuries missed by FAST included liver laceration, adrenal hematoma, renal laceration, small bowel injury and splenic laceration. CONCLUSION: Preliminary results suggest that FAST alone is not a useful screening test in the evaluation of children with suspected intraabdominal injury.

Abdominal Injuries↗
PubMedDate not supplied

Fast-food habits, weight gain, and insulin resistance (the CARDIA study): 15-year prospective analysis.

BACKGROUND: Fast-food consumption has increased greatly in the USA during the past three decades. However, the effect of fast food on risk of obesity and type 2 diabetes has received little attention. We aimed to investigate the association between reported fast-food habits and changes in bodyweight and insulin resistance over a 15-year period in the USA. METHODS: Participants for the CARDIA study included 3031 young (age 18-30 years in 1985-86) black and white adults who were followed up with repeated dietary assessment. We used multiple linear regression models to investigate the association of frequency of fast-food restaurant visits (fast-food frequency) at baseline and follow-up with 15-year changes in bodyweight and the homoeostasis model (HOMA) for insulin resistance. FINDINGS: Fast-food frequency was lowest for white women (about 1.3 times per week) compared with the other ethnic-sex groups (about twice a week). After adjustment for lifestyle factors, baseline fast-food frequency was directly associated with changes in bodyweight in both black (p=0.0050) and white people (p=0.0013). Change in fast-food frequency over 15 years was directly associated with changes in bodyweight in white individuals (p<0.0001), with a weaker association recorded in black people (p=0.1004). Changes were also directly associated with insulin resistance in both ethnic groups (p=0.0015 in black people, p<0.0001 in white people). By comparison with the average 15-year weight gain in participants with infrequent (less than once a week) fast-food restaurant use at baseline and follow-up (n=203), those with frequent (more than twice a week) visits to fast-food restaurants at baseline and follow-up (n=87) gained an extra 4.5 kg of bodyweight (p=0.0054) and had a two-fold greater increase in insulin resistance (p=0.0083). INTERPRETATION: Fast-food consumption has strong positive associations with weight gain and insulin resistance, suggesting that fast food increases the risk of obesity and type 2 diabetes.

Adolescent↗
PubMed2003

Electrostatic control and chloride regulation of the fast gating of ClC-0 chloride channels.

The opening and closing of chloride (Cl-) channels in the ClC family are thought to tightly couple to ion permeation through the channel pore. In the prototype channel of the family, the ClC-0 channel from the Torpedo electric organ, the opening-closing of the pore in the millisecond time range known as "fast gating" is regulated by both external and internal Cl- ions. Although the external Cl- effect on the fast-gate opening has been extensively studied at a quantitative level, the internal Cl- regulation remains to be characterized. In this study, we examine the internal Cl- effects and the electrostatic controls of the fast-gating mechanism. While having little effect on the opening rate, raising [Cl-]i reduces the closing rate (or increases the open time) of the fast gate, with an apparent affinity of >1 M, a value very different from the one observed in the external Cl- regulation on the opening rate. Mutating charged residues in the pore also changes the fast-gating properties-the effects are more prominent on the closing rate than on the opening rate, a phenomenon similar to the effect of [Cl-]i on the fast gating. Thus, the alteration of fast-gate closing by charge mutations may come from a combination of two effects: a direct electrostatic interaction between the manipulated charge and the negatively charged glutamate gate and a repulsive force on the gate mediated by the permeant ion. Likewise, the regulations of internal Cl- on the fast gating may also be due to the competition of Cl- with the glutamate gate as well as the overall more negative potential brought to the pore by the binding of Cl-. In contrast, the opening rate of the fast gate is only minimally affected by manipulations of [Cl-]i and charges in the inner pore region. The very different nature of external and internal Cl- regulations on the fast gating thus may suggest that the opening and the closing of the fast gate are not microscopically reversible processes, but form a nonequilibrium cycle in the ClC-0 fast-gating mechanism.

Animals↗
PubMed1996

Quantitative assessment of MRI lesion load in multiple sclerosis. A comparison of conventional spin-echo with fast fluid-attenuated inversion recovery.

In this study, we compared a fast fluid-attenuated inversion recovery (fast-FLAIR) sequence to conventional spin-echo (CSE) in the evaluation of brain MRI lesion loads of seven patients with clinically definite multiple sclerosis. Interleaved CSE (3000/20, 5 mm contiguous axial slices) and fast-FLAIR (9000/150/2200, 5 mm contiguous axial slices) sequences were performed on a 1.0 T machine. Lesions were counted consensually by two observers and then segmented independently by two other observers using a local thresholding technique, with subsequent manual editing in the case of poorly defined lesions. Four hundred and two lesions were detected in at least one of the two sequences: 128 were seen only on fast-FLAIR, 17 only on CSE. Forty-one lesions were larger on fast-FLAIR, while no lesion was considered larger on CSE. The numbers of periventricular (P = 0.05), cortical/subcortical (P = 0.02) and discrete (P = 0.05) lesions detected using fast-FLAIR were higher than those detected using CSE. The median lesion load was 7185 mm3 on CSE and 8418 mm3 on the fast-FLAIR, the average being 18% (range = 11.6-29%) higher on the fast-FLAIR images. Lesion contrast ratio was higher for lesions on the fast-FLAIR than on the CSE sequence (P < 0.0001). The percentages of poorly defined lesions which needed manual editing after the local thresholding technique was applied and the total time needed for the measurements were lower (P < 0.001) when fast-FLAIR images were used compared with CSE. This resulted in a reduced inter-rater coefficient of variation in measuring lesion volumes. Our data indicate that fast-FLAIR sequences are more sensitive than CSE in detecting multiple sclerosis lesion burden and that fast-FLAIR is a promising technique for natural history studies and clinical trials in multiple sclerosis.

Adult↗
PubMed2003

Not so FAST.

BACKGROUND: Focused assessment with sonography for trauma (FAST) as a screening tool in the evaluation of blunt abdominal trauma will lead to underdiagnosis of abdominal injuries and may have an impact on treatment and outcome in trauma patients. METHODS: From October 2001 to June 2002, a protocol for evaluating hemodynamically stable trauma patients with suspected blunt abdominal injury (BAI) admitted to our institution was implemented using FAST examination as a screening tool for BAI and computed tomographic (CT) scanning of the abdomen and pelvis as a confirmatory test. At the completion of the secondary survey, patients underwent a four-view FAST examination (Sonosite, Bothell, WA) followed within 1 hour by an abdominal/pelvic CT scan. The FAST examination was considered positive if it demonstrated evidence of free intra-abdominal fluid. Clinical, laboratory, and imaging results were recorded at admission, and FAST examination results were compared with CT scan findings, noting the discordance. RESULTS: Patients with suspicion for BAI were evaluated according to protocol (n = 372). Thirteen cases were excluded for inadequate FAST examinations, leaving 359 patients for analysis. There were 313 true-negative FAST examinations, 16 true-positives, 22 false-negatives, and 8 false-positives. Using CT scanning as the confirmatory test for hemoperitoneum, FAST examination had a sensitivity of 42%, a specificity of 98%, a positive predictive value of 67%, a negative predictive value of 93%, and an accuracy of 92%; chi analysis showed significant discordance between FAST examination and CT scan (5.85%, < 0.001). Six patients with false-negative FAST examinations required laparotomy for intra-abdominal injuries; 16 patients required admission for nonoperative management of injury. Of the 313 true-negative FAST examinations, 19 patients were noted to have intra-abdominal injuries without hemoperitoneum and 11 patients were noted to have retroperitoneal injuries. CONCLUSION: Use of FAST examination as a screening tool for BAI in the hemodynamically stable trauma patient results in underdiagnosis of intra-abdominal injury. This may have an impact on treatment and outcome in trauma patients. Hemodynamically stable patients with suspected BAI should undergo routine CT scanning.

Abdominal Injuries↗
PubMed1992

Fast Na+ channels in smooth muscle from pregnant rat uterus.

Smooth muscle cells normally do not possess fast Na+ channels, but inward current is carried through two types of Ca2+ channels: slow (L type) Ca2+ channels and fast (T type) Ca2+ channels. Whole-cell voltage clamp was done on single smooth muscle cells isolated from the longitudinal layer of the 18-day pregnant rat uterus. Depolarizing pulses, applied from a holding potential of -90 mV, evoked two types of inward current, fast and slow. The fast inward current decayed within 30 ms, depended on [Na]o, and was inhibited by tetrodotoxin (TTX) (K0.5 = 27 nM). The slow inward current decayed slowly, was dependent on [Ca]o (or Ba2+), and was inhibited by nifedipine. These results suggest that the fast inward current is a fast Na+ channel current and that the slow inward current is a Ca2+ slow channel current. A fast-inactivating Ca2+ channel current was not evident. We conclude that the ion channels that generate inward currents in pregnant rat uterine cells are TTX-sensitive fast Na+ channels and dihydropyridine-sensitive slow Ca2+ channels. The number of fast Na+ channels increased during gestation. The averaged current density increased from 0 on day 5, to 0.19 on day 9, to 0.56 on day 14, to 0.90 on day 18, and to 0.86 pA/pF on day 21. This almost linear increase occurs because of an increase in the fraction of cells that possess fast Na+ channels. The Ca2+ channel current density was also higher during the latter half of gestation. These results indicate that the fast Na+ channels and Ca2+ slow channels in myometrium become more numerous as term approaches, and we suggest that the fast Na+ current may be involved in spread of excitation. Isoproterenol (beta-agonist) did not affect either ICa(s) or INa(f), whereas Mg2+ (K0.5 = 12 mM) and nifedipine (K0.5 = 3.3 nM) depressed ICa(s). Oxytocin had no effect on INa(f) and actually depressed ICa(s) to a small extent. Therefore, the tocolytic action of beta-agonists cannot be explained by an inhibition of ICa(s), whereas that of Mg2+ can be so explained. The stimulating action of oxytocin on uterine contractions cannot be explained by a stimulation of ICa(s).

Animals↗
PubMed1994

T2-weighted MR imaging of the abdomen: fast spin-echo vs conventional spin-echo sequences.

OBJECTIVE: The purpose of this study was to compare one optimized T2-weighted fast spin-echo sequence with one T2-weighted conventional spin-echo sequence to determine the impact of fast spin echo on image quality and diagnostic efficacy for evaluation of the abdomen. SUBJECTS AND METHODS: A total of 32 patients with 43 lesions involving various abdominal organs were examined. T2-weighted fast spin-echo (4000/119/4, echo train length = 16, matrix = 256 x 256) and T2-weighted conventional spin-echo (3400-3800/80/2, matrix = 128 x 256) images were compared qualitatively and quantitatively to determine whether the two types of images differed with respect to tissue contrast, conspicuousness of lesions, image quality, and artifacts. RESULTS: The signal intensity of all abdominal structures (except gallbladder and fat) was significantly lower on fast spin-echo images than on conventional spin-echo images. Qualitative liver-to-spleen contrast was significantly reduced on fast spin-echo images, whereas quantitative liver-to-spleen contrast was not significantly different. Blurring of anatomic structures, vascular pulsation, and chemical-shift misregistration artifacts were significantly reduced on fast spin-echo images. The qualitative conspicuousness and contrast-to-noise ratio for all lesions evaluated together were not significantly different (p = .5 and p = .069, respectively) on fast spin-echo vs conventional spin-echo images. However, qualitative conspicuousness and contrast-to-noise ratio of solid lesions were significantly reduced on fast spin-echo images (p = .022 and p = .01, respectively). The contrast-to-noise ratio of cystic lesions was significantly better (p = .002) on fast spin-echo images than on conventional spin-echo images. CONCLUSION: Although the fast spin-echo protocol used in this study provides better image quality and contrast-to-noise ratio for cystic abdominal lesions than does conventional spin echo, the qualitative conspicuousness and contrast-to-noise ratio of solid abdominal lesions are decreased. Fast spin echo provides high-quality images with fewer artifacts in significantly less time than is possible with conventional spin-echo images. Further evaluation is necessary to determine the optimal protocol for T2-weighted fast spin-echo MR imaging of the abdomen.

Abdominal Neoplasms↗