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Effects of dobutamine on oxygen transport and consumption in the adult respiratory distress syndrome.

OBJECTIVE: To determine if oxygen consumption (VO2) in patients with adult respiratory distress syndrome (ARDS) is dependent on, and thus limited by, oxygen transport (TO2) rather than O2 demand. DESIGN: Prospective study. SETTING: Intensive care unit of a tertiary referral center. PATIENTS: 12 patients with ARDS and sepsis syndrome. INTERVENTIONS: Routine intensive care unit monitoring including pulmonary and radial artery catheters. MEASUREMENTS: Dobutamine was used to increase cardiac output, thereby directly varying TO2 under conditions of constant O2 demand. After baseline measurements of TO2 and VO2, dobutamine was infused intravenously at progressively increasing doses of 5, 10, 15 and 20 micrograms/kg/min and measurements of TO2 and VO2 were repeated after 30 min at each dose. RESULTS: Dobutamine increased TO2 in 8 of the 12 patients, by 29% at 5 micrograms/kg/min and by 45% (net) at 10 micrograms/kg/min, but not at higher doses. In these 8 patients dobutamine also increased VO2 by 15% at 5 micrograms/kg/min, but did not further increase VO2 at higher doses. There was no correlation between baseline blood lactate concentration and the response of either TO2 or VO2 to dobutamine. CONCLUSIONS: In some but not all patients with ARDS and sepsis syndrome, short-term infusion of low-dose dobutamine can increase both TO2 and VO2. Achievement of a TO2-independent level of VO2 could not be convincingly demonstrated in any individual patient. The response of TO2 and VO2 to dobutamine could not be predicted from baseline blood lactate concentration. Determination of the impact on patient outcome of a more prolonged infusion of dobutamine requires further study.

Adult↗

Heat shock protein changes in hibernation: a similarity with heart failure?

Myocardial hibernation is an adaptive phenomenon occurring during ischaemia. Patients with hibernating myocardium often have a history of an acute ischaemic insult, followed by prolonged hypoperfusion and symptoms of congestive heart failure (CHF), which is a complex syndrome involving several adaptational mechanisms. We tested the hypothesis that these two conditions evoke the myocardial expression of heat shock protein 72 (hsp72) as an adaptive response at the molecular level. Short-term acute hibernation was induced in isolated and perfused rat hearts subjected to 8 min total ischaemia followed by 292 min low-flow ischaemia (coronary flow: 1.0 ml/min), followed by 60 min of reperfusion. Total ischaemia caused quiescience. Subsequent low-flow resulted in a temporal early increase of lactate release, no re-establishment of developed pressure, no increase in diastolic pressure. Reperfusion resulted in 85.7 +/- 7.2% recovery of developed pressure, a small washout of lactate and CPK, no contracture, confirming that viability was maintained despite prolonged hypoperfusion. This sequence of events was linked to an increase in hsp72 content in the right (from 18.1 +/- 3.8% to 34.6 +/- 2.3%. P < 0.01) and left (from 19.7 +/- 2.6% to 37.6 +/- 3.3%, P < 0.01) ventricles. Three-hundred min of low-flow perfusion of the rat heart in absence of the short period of total ischaemia caused irreversible damage and failed to induced hsp72. CHF was induced in rats by intraperitoneal administration of monocrotaline. As a result, right ventricular weight increased from 171.3 +/- 7.2 to 412.3 +/- 18.7 mg. P < 0.001, peripheral and pleural effusion were evident and measurable, plasma arterial natriuretic peptide increased from 15.2 +/- 1.9 to 123.5 +/- 5.4 pg/ml, P < 0.001, confirming the occurrence of the syndrome of CHF. This was concomitant with significant expression of hsp72, more evident in the right (from 5.0 +/- 0.9% to 39.4 +/- 1.6%, P < 0.001) than in the left (from 3.5 +/- 0.6% to 13.0 +/- 1.2%, P < 0.001) ventricle. These data suggest that an adaptational process occurs at myocardial level during either hibernation or CHF. The expression of hsp72 could be viewed as a stereotyped adaptational reaction of the cardiac cell to stress conditions.

Animals↗

Cortisol response of green sturgeon to acid-infusion stress.

Cortisol and lactate are classic indicators of stress in fishes and their interactive effects on metabolism during recovery from stress have recently become a subject of more intense study. We examined how stressing green sturgeon through acid infusion affected the cortisol response and lactate metabolism in green sturgeon (Acipenser medirostris). Both lactic acid (0.3 M) and HCl (0.3 N) infusion (infusion volumes 1.5 ml kg(-1)) elicited an immediate cortisol response (21.61+/-4.61 ng ml(-1) and 17.50+/-3.00 ng ml(-1), respectively). Lactic acid prolonged the cortisol response compared to HCl (90 min vs. 25 min). Neutralized lactate (0.23 M; with 1 N NaOH; final pH 7.8) and NaCl (0.9%) infusion (infusion volumes 1.5 ml kg(-1)) did not affect plasma cortisol. Sturgeon infused with lactic acid showed a faster rate of lactate disappearance from plasma than those with neutralized lactic acid. We relate these findings to lactate metabolism following exercise, acid-infusion and air immersion stress in fishes.

Acid-Base Equilibrium↗

[Effect of supplementary artificial illumination with visible rays on biochemical indices in the blood serum, milk yields and fertilization during lactation].

Comparative investigations were made with two groups of cows (a control) and an experimental one) aiming to establish the effect of prolonged day length during the autumn-winter and the early spring periods on the physiological state of the cows, the yield of milk and fertilization during the lactation period. Results obtained indicate that supplementary illumination with visible rays at a rate of 5 w/m2 from the floor and a 16 h day length including the natural day period, enhances the content of Ca, inorganic P and vitamin D and A of the blood serum, stabilizes at a constant level the quantity of total protein and rises the content of albumins and gamma-globulins. As a result of these and probably of some other changes in the organism, the physiological state of the cows is either maintained normal or is improved, a fact leading to 13% higher milk yield on the average for the lactation period, service period shortened to 87 days and increased number of pregnant cows following the first insemination.

Animals↗

Plasma thyrotropin-releasing hormone, prolactin, thyrotropin, and thyroxine concentrations following the intravenous or oral administration of thyrotropin-releasing hormone.

In a further evaluation of the use of oral thyrotropin-releasing hormone (TRH) in puerperally lactating women, a radioimmunoassay for its measurement has been developed. Its concentration in plasma as well as that of prolactin (PRL), thyrotropin (TSH) and thyroxine (T4) were measured following either intravenous or oral administration of TRH. Basal concentrations of TRH in 14 normally cycling women ranged from less than 5 to 17 pg/ml. Two luteal phase studies produced peaks in plasma TRH 5 to 10 minutes after 100 micrograms of TRH administered intravenously with a return to basal concentrations within 2 to 3 hours. In 10 normally menstruating women, ingestion of 10 mg of TRH orally resulted in plasma TRH which peaked at 423 +/- 123 pg/ml (standard error of the mean) at 30-minutes. Plasma PRL, TSH, and T4 also increased and remained slightly elevated at 4 hours. These 8-hour studies were performed in a puerperal lactating woman who had ingested 10 mg of TRH orally twice a day for 7 days prior to blood sampling. TRH concentrations declined throughout each day while TSH rose slightly in the first 1 to 2 hours but remained within normal limits. The prolonged administration of 10 mg of TRH orally twice daily to three puerperally lactating women resulted in elevations in plasma TRH 2 to 3 hours following hormone administration, yet no significant increases in plasma TSH were observed. Both endogenous TRH and TSH were measured before and after 22 nursing events in nine puerperally lactating women. There was no change in the concentration of either substance and all values were similar to those obtained in normally menstruating women.

Administration, Oral↗

Blood biochemical alterations during recovery from competitive marathon running.

The occurrence of possible prolonged alterations in plasma levels of cortisol, epinephrine, norepinephrine, selected energy metabolites, and water and electrolyte balance was assessed in six highly trained male marathon runners by measuring blood biochemical constituents on the 10th day before and for the three days following the running of a marathon. Post-race changes in hemoglobin, hematocrit, and protein levels indicated that a hemodilution had occurred, possibly as a result of elevated sodium levels. Epinephrine remained elevated until the second day. Cortisol was depressed on the first and third post-race days while variable levels were observed on the second day. No prolonged alterations were noted in norepinephrine, FFA, glycerol, triglycerides, glucose, lactate, and pyruvate.

Blood Glucose↗

Brain metabolism after electroshock seizure in the neonatal dog: a [31P]NMR study.

In vivo [31P] nuclear magnetic resonance (NMR) spectroscopy disclosed that a 10 second electroshock seizure in oxygenated neonatal dogs produced prolonged alteration of brain phosphocreatine (PCr), inorganic phosphate (Pi), and lactate. The slow return of these metabolites to baseline may be related to lower endogenous stores of high energy phosphates, or less developed pathways for their regeneration.

Adenosine Triphosphate↗

Hantavirus pulmonary syndrome: a clinical description of 17 patients with a newly recognized disease. The Hantavirus Study Group.

BACKGROUND: In May 1993 an outbreak of severe respiratory illness occurred in the southwestern United States. A previously unknown hantavirus was identified as the cause. In Asia hantaviruses are associated with hemorrhagic fever and renal disease. They have not been known as a cause of human disease in North America. METHODS: We analyzed clinical, laboratory, and autopsy data on the first 17 persons with confirmed infection from this newly recognized strain of hantavirus. RESULTS: The mean age of the patients was 32.2 years (range, 13 to 64); 61 percent were women, 72 percent were Native American, 22 percent white, and 6 percent Hispanic. The most common prodromal symptoms were fever and myalgia (100 percent), cough or dyspnea (76 percent), gastrointestinal symptoms (76 percent), and headache (71 percent). The most common physical findings were tachypnea (100 percent), tachycardia (94 percent), and hypotension (50 percent). The laboratory findings included leukocytosis (median peak cell count, 26,000 per cubic millimeter), often with myeloid precursors, an increased hematocrit, thrombocytopenia (median lowest platelet count, 64,000 per cubic millimeter), prolonged prothrombin and partial-thromboplastin times, an elevated serum lactate dehydrogenase concentration, decreased serum protein concentrations, and proteinuria. Rapidly progressive acute pulmonary edema developed in 15 of the 17 patients (88 percent), and 13 patients, all of whom had profound hypotension, died (case fatality rate, 76 percent). Increases in the hematocrit and partial-thromboplastin time were predictive of death. CONCLUSIONS: Infection with a newly described hantavirus causes the hantavirus pulmonary syndrome, which is characterized by a brief prodromal illness followed by rapidly progressive, noncardiogenic pulmonary edema.

Adolescent↗

The effect of alterations in ketone body availability on the utilization of beta-hydroxybutyrate by developing rat brain.

The effect of alterations in ketone body availability during the early postnatal period on the in vitro and in vivo utilization of beta-hydroxybutyrate (beta OHB) by developing rat brain was determined. Ketone body availability was prolonged by feeding a high fat diet during pregnancy and lactation and to pups after weaning. Availability was decreased by early weaning pups at 16 days to a low fat liquid diet. In the in vitro studies, oxidation of [14C]beta OHB to CO2 and incorporation into brain lipid was determined at 7, 14, 21, and 35 days of age. In the in vivo studies incorporation of [14C]beta OHB and [3H]glucose into brain lipid was measured. The results indicate that it is possible to alter the brain's utilization of beta OHB for lipid synthesis and energy metabolism during the developmental period. This was particularly evident in the in vivo studies. The in vivo results also suggest a relationship between beta OHB availability in the blood and incorporation into brain lipid. When availability was decreased by early weaning pups to the low fat diet, incorporation of beta OHB into lipid was also decreased. Likewise, when availability was increased, such as was seen in the high fat feeding study, incorporation was increased.

3-Hydroxybutyric Acid↗

Impact of antimicrobial ingredients and irradiation on the survival of Listeria monocytogenes and the quality of ready-to-eat turkey ham.

Irradiation is an effective technology in eliminating Listeria monocytogenes, but it induces quality changes in meat products at or above specific radiation doses. To minimize irradiation-induced quality changes, only low irradiation doses are recommended. However, low-dose irradiation provides a chance for some pathogens to survive and proliferate during prolonged storage. To solve this problem, antimicrobial ingredients [2% sodium lactate (SL), 0.1% sodium diacetate (SDA), 0.1% potassium benzoate (PB)] and low-dose irradiation were combined and tested for their effects on the growth of L. monocytogenes and meat quality. The log10 reductions of L. monocytogenes in hams following exposure to 1.0 to 2.5 kGy of irradiation ranged from 2.0 to 5.0. The D10 values were 0.52 kGy for control ham or ham with PB, SL, or PB + SL; 0.49 kGy for ham with SL+SDA; and 0.48 kGy for ham with PB + SL + SDA (PSS). Addition of SL + SDA or PB + SL in combination with 1.0 kGy of irradiation was effective in suppressing the growth of L. monocytogenes for about 6 wk when stored at 4 degrees C, whereas 2.0 kGy of irradiation was listeriostatic. Ham irradiated with 1 kGy in combination with PSS was listeriostatic throughout storage. SL increased firmness of turkey hams, and sensory panelists noted that the saltiness was a little higher in products containing SL, but its overall impact on quality was minimal. Amounts of benzene were detected in irradiated hams with PB, showing PB was not fit as an antimicrobial ingredient for irradiated foods. In conclusion, 2% SL and 0.1% SDA in combination with low-dose irradiation were effective in ensuring the safety of ready-to-eat meat products against L. monocytogenes.

Animals↗

Analysis of the metabolic and ventilatory response to self-paced 12-minute treadmill walking in patients with severe chronic obstructive pulmonary disease.

BACKGROUND: The 12-minute walking test is frequently used to measure exercise capacity in patients with severe chronic obstructive pulmonary disease. However, the physiological response to this test has been the subject of limited investigation. METHODS: In this study, the metabolic and ventilatory consequences of a self-paced 12-minute treadmill walking test (WT) were measured in 17 patients with severe chronic obstructive pulmonary disease (FEV1: 40 +/- 9%) and evaluated using the physiological response to symptom-limited cycle ergometry (CE). During exercise testing, heart rate, transcutaneous oxygen saturation, and lactate concentration were measured, and oxygen consumption, carbon dioxide production, tidal volume, and breathing frequency were recorded breath by breath. RESULTS: After 4 minutes walking, the peak oxygen consumption (VO2) was already 99 +/- 11% of last-minute walking VO2. Walking speed was chosen within 2 minutes and remained stable throughout the test. The WT and CE showed similar (end-) test results for all measurements, except for a higher carbon dioxide production, venous lactate concentration, and respiratory quotient after CE. However, lactate concentration was also significantly increased after WT. Severe and prolonged desaturation was shown during walking in most patients. CONCLUSIONS: The physiological stress evoked during the WT is close to the stress developed at an incremental symptom-limited test and the relatively high metabolic and ventilatory stress is sustained from at least 4 to 12 minutes during the WT. This study has shown that anaerobic metabolism not only occurs during incremental cycle ergometry, but also during the WT.

Blood Gas Analysis↗

Identification of T-2 toxin in moldy corn associated with a lethal toxicosis in dairy cattle.

Over a 5-month period during the winter of 1970-71, 20% of the lactating Holstein cows in a Wisconsin dairy herd died after prolonged ingestion of a diet containing 60% moldy corn infested with Fusarium tricinctum (2 x 10(5) propagules per g of moldy corn). Ethyl acetate extracts of the ground dried corn induced severe dermal reactions when applied to the skin of shaved 60-g albino rats and killed four of five 100-g rats that were force fed 1 ml in 2 ml of pure corn oil. T-2 toxin (3-hydroxy-4, 15-diacetoxy-8-[3-methylbutyryloxy]-12, 13-epoxy-Delta(9)-trichothecene) at concentrations of 2 mg per kg of dry corn was identified in purified extracts of the moldy corn by means of gas-liquid chromatography and mass spectrometry. This concentration of T-2 toxin in the moldy feed and the nature of the toxic effects observed strongly suggest a major causal relationship.

Animal Feed↗

Clinical outcomes and prognostic factors in patients with Richter's syndrome treated with chemotherapy or chemoimmunotherapy with or without stem-cell transplantation.

PURPOSE: The purpose of this study was to assess the incidence, presenting characteristics, and treatment outcomes of Richter's syndrome (RS) and factors predicting response and survival. PATIENTS AND METHODS: An electronic database search of patients with chronic lymphocytic leukemia (CLL)/small lymphocytic lymphoma (SLL) who presented at The University of Texas M.D. Anderson Cancer Center (Houston, TX) between January 1975 and June 2005 was performed, and patient medical records were reviewed. RESULTS: Of the 3,986 patients with CLL/SLL, 204 patients (5.1%) had possible RS, and 148 patients (3.7%) had biopsy- or fine-needle aspiration-proven RS. Treatment included chemotherapy alone and chemoimmunotherapy with rituximab. The overall response rate for the 130 assessable patients was 39% (chemotherapy, 34%; chemoimmunotherapy, 47%; P = .2). In multivariate analysis, factors predicting prolonged survival were Zubrod performance status 0-1 (P = .006), lactate dehydrogenase < or = 1.5x the upper limit of normal (P = .003), platelet count > or = 100,000 (P = .01), tumor size < or = 5 cm (P = .02), and fewer than two prior therapies (P = .02). The five adverse factors predicting shorter survival were used to design a model to predict an individual patient's risk of death: the RS score. A total of 20 patients underwent stem-cell transplantation (SCT). Patients who underwent allogeneic SCT as postremission therapy had longer survival than patients who achieved remission and received no additional therapy or patients who underwent allogeneic or autologous SCT as salvage therapy (P = .019). CONCLUSION: A score to predict an individual patient's risk of death is proposed. Chemotherapy and rituximab combinations are effective in RS. Patients with available donors may be considered for allogeneic SCT as postremission therapy.

Adult↗

[A female case of carnitine palmitoyltransferase deficiency].

A 17-year old woman noted myalgia after taking a long distance walk at the age of 10. In adolescence, she had several episodes of myalgia and pigmenturia after athletic activity or infection. At age 17, myoglobinuria and abnormally increased serum creatine kinase were documented after one of these episodes. The neurological examination revealed mild proximal muscle weakness of upper extremities. Electromyography showed myogenic patterns, such as brief, small abundant potentials on them. Venous lactate was raised normally on the ischemic exercise test. During prolonged fasting, plasma ketone bodies increased normally but there were abnormal elevations of plasma creatine kinase and myoglobin. Morphometric analysis of electron microscopy in muscle showed few lipid deposits and that of light microscopy revealed no abnormality. CPT activity in muscle was only 15% of normal value by the isotope-exchange assay. These results were consistent with the diagnosis of CPT deficiency. Although several cases of CPT deficiency with recurrent myoglobinuria have been reported in Western countries, our patients is the first case of Japanese showing recurrent myoglobinuria. CPT deficiency should be considered as a differential diagnosis in cases of recurrent myoglobinuria.

Acyltransferases↗

Interactions of murine macrophages with monosodium urate crystals: stimulation of lysosomal enzyme release and prostaglandin synthesis.

Exposure of murine peritoneal macrophages to crystals of monosodium urate monohydrate (MSUM) stimulated release of inflammatory mediators from the cells. There was an early, rapid burst of prostaglandin E2 (PGE2) synthesis which was complete by 2 h. Release of N-acetyl glucosaminidase (NAG), a lysosomal enzyme, was evident within 1 h and was maximal by 8 h. Early release of lysosomal enzymes (1-2 h) was not accompanied by leakage of cytoplasmic enzymes; however, treatment with high concentrations of MSUM, or prolonged exposure to crystals, provoked release of the cytoplasmic enzyme lactate dehydrogenase, presumably as a result os cell lysis. Responses of macrophages to MSUM occurred in the absence of serum but were modified by serum proteins. Prior exposure of crystals to IgG potentiated release of NAG and PGE2. Exposure to albumin slightly enhanced release of PGE2 induced by MSUM but did not affect NAG release. However, albumin prevented enhancement of NAG release by IgG. The interaction of MSUM with macrophages, and subsequent release of inflammatory mediators, may contribute to the inflammation association with both acute and chronic gouty arthritis.

Acetylglucosaminidase↗

Changes in serum creatine kinase, lactate dehydrogenase and aldolase activities following supramaximal exercise in athletes.

While it is well known that prolonged intense exercise raises serum enzyme activities, the effects of short duration intense exercise on enzyme activity changes have not been clearly described. Three successive standard 30 s Wingate anaerobic cycle ergometer tests separated by 6-8 min rest intervals were performed by competitive male middle- and long-distance runners or cyclists (no. = 33), and matched healthy control subjects (no. = 30). Immediately before and 6 h after the tests, blood samples were before and 6 h after the tests, blood samples were taken to assess the effects of exercise on serum creatine kinase (CK), lactate dehydrogenase (LD) and aldolase (ALS) enzyme activities. Serum CK activities were found to be significantly higher in athletes than in the controls, both before and 6 hours after the test (p < 0.001), as were ALS activities (p < 0.01 before and p < 0.05 after the test), whereas LD activities were significantly higher (p < 0.05) in the athletes only after the test. Following the test, increases in LD activities (p < 0.01) were observed in athletes and rises in CK activities (p < 0.05) were seen in the controls. Significant correlations between pre- and post-exercise serum enzyme activities were established for both groups. In conclusion, following a supramaximal exercise test, increases in serum LD activities of athletes and in CK activities of controls appear to be more pronounced, and increases in serum CK, LD and ALS activities seem to depend more on the duration of exercise than on its intensity.

Adolescent↗

Milk production, estimated phosphorus excretion, and bone characteristics of dairy cows fed different amounts of phosphorus for two or three years.

Diets containing 0.31, 0.39, or 0.47% P on a DM basis were fed to 10, 14, and 13 multiparous Holstein cows, respectively, for a full lactation. Most of the cows (33) were fed similar amounts of P in the previous one or two lactations. The objective was to obtain information on bone integrity after prolonged feeding of different amounts of P. At the end of the experiment, a section (-20 cm) of the 12th rib was surgically removed. The bone was tested for strength and analyzed for ash and P content. The shear strength and the energy required to deform the bone to the point of fracture did not differ among treatments. Bone specific gravities were 1.50, 1.57, and 1.55 for the three treatments. Ash and P content of the bone, measured in wet weight, dry weight, and wet bone volume, were similar for the 0.39 and 0.47% P treatments, but tended to be lower with the 0.31% P treatment. Milk production of cows in all groups was high, averaging >11,900 kg for the 308-d lactation. Feeding P at 0.31% of dietary DM over two to three lactations appeared to decrease P concentration of bone, but the decrease was not severe enough to affect bone strength. Dietary P at 0.39% did not affect bone P content or strength. Dietary P content of 0.31% appears to be borderline deficient for cows producing >11,900 kg/308 d.

Animals↗