Clinical pictures of body fluid imbalances.
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Chromatographic separation of highly polar basic drugs with ideal ionspray mass spectrometry volatile mobile phases is a difficult challenge. A new quantification procedure was developed using hydrophilic interaction chromatography-mass spectrometry with turbo-ionspray ionization in the positive mode. After addition of deuterated internal standards and simple clean-up liquid extraction, the dried extracts were reconstituted in 500 microL pure acetonitrile and 5 microL was directly injected onto a Waters Atlantis HILIC 150- x 2.1-mm, 3-microm column. Chromatographic separations of cocaine, seven metabolites, and anhydroecgonine were obtained by linear gradient-elution with decreasing high concentrations of acetonitrile (80-56% in 18 min). This high proportion of organic solvent makes it easier to be coupled with MS. The eluent was buffered with 2 mM ammonium acetate at pH 4.5. Except for m-hydroxy-benzoylecgonine, the within-day and between-day precisions at 20, 100, and 500 ng/mL were below 7 and 19.1%, respectively. Accuracy was also below +/- 13.5% at all tested concentrations. The limit of quantification was 5 ng/mL (%Diff < 16.1, %RSD < 4.3) and the limit of detection below 0.5 ng/mL. This method was successfully applied to a fatal overdose. In Switzerland, cocaine abuse has dramatically increased in the last few years. A 45-year-old man, a known HIV-positive drug user, was found dead at home. According to relatives, cocaine was self-injected about 10 times during the evening before death. A low amount of cocaine (0.45 mg) was detected in the bloody fluid taken from a syringe discovered near the corpse. Besides injection marks, no significant lesions were detected during the forensic autopsy. Toxicological investigations showed high cocaine concentrations in all body fluids and tissues. The peripheral blood concentrations of cocaine, benzoylecgonine, and methylecgonine were 5.0, 10.4, and 4.1 mg/L, respectively. The brain concentrations of cocaine, benzoylecgonine, and methylecgonine were 21.2, 3.8, and 3.3 mg/kg, respectively. The highest concentrations of norcocaine (about 1 mg/L) were measured in bile and urine. Very high levels of cocaine were determined in hair (160 ng/mg), indicating chronic cocaine use. A low concentration of anhydroecgonine methylester was also found in urine (0.65 mg/L) suggesting recent cocaine inhalation. Therapeutic blood concentrations of fluoxetine (0.15 mg/L) and buprenorphine (0.1 microg/L) were also discovered. A relatively high concentration of Delta(9)-THC was measured both in peripheral blood (8.2 microg/L) and brain cortex (13.5 microg/kg), suggesting that the victim was under the influence of cannabis at the time of death. In addition, fluoxetine might have enhanced the toxic effects of cocaine because of its weak pro-arrhythmogenic properties. Likewise, combination of cannabinoids and cocaine might have increase detrimental cardiovascular effects. Altogether, these results indicate a lethal cocaine overdose with a minor contribution of fluoxetine and cannabinoids.
Eight normotensive white middle-aged men were given low, moderate, and high salt diets with constant potassium intakes each for periods of at least 4 weeks. There was a tendency for body weight, serum sodium, exchangeable sodium, and inulin space to increase. Indirect blood pressure measurements revealed no change in blood pressure, either supine or upright measurements, during the 3 study intervals. Inulin clearance (and presumably glomerular filtration rate) rose with increase in dietary salt. Urinary potassium excretion rose progressively as salt intake increased. Total body potassium tended to decrease with increase in dietary salt. There was no changes in the excretion of calcium, magnesium, phosphorus, nor were there changes in the blood level of potassium. There was no change in total body water. The serum cholesterol and triglyceride levels were not appreciably affected by the different dietary sodium intakes. Plasma renin activity and urinary aldosterone excretion rose progressively with the two levels of sodium restriction. These studies indicate that normal man is able to compensate for large differences in sodium intake with minor metabolic changes. These changes do not necessarily lead to hypertension over a one-month period. Nevertheless, many hemodynamic and hormonal compensatory mechanisms come into play. It is evident that hypertension might result should the sodium load not be excreted, the circulating volume become too great for the excretory capacity, or if neural or endocrine adjustments be inadequate.
The problem solving approach to decision making is a logical and useful tool to use. Tracy Scales illustrates the use of this approach by discussing the problem of protecting staff from the ever increasing risk of infection from the patient's body fluids.
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To assess the extent of CO2 storage and the changes in the acid-base status that occur during intermittent CO2 excretion in insects, total CO2 content and pH were measured in whole body homogenates (= tissue homogenates) of Hyalophora cecropia pupae at various levels of Pco2 at 20 degrees C. The CO2 dissociation curve, i.e. plot of total CO2 content in tissue homogenates against Pco2 was nearly linear in the Pco2 range from 15 to 50 Torr, the mean slope being 0.138 mM . Torr-1. This value, which constitutes the effective CO2 solubility, was nearly three times the physical solubility in the tissue homogenate which averaged 0.053 mM . Torr-1. Plots of bicarbonate concentration in whole body tissue water against pH yielded an average buffer value of 75 mmol . pH-1 per kg tissue water. The high buffer value results in a small pH change, about 0.04 units, when Pco2 varies between 20 and 45 Torr in the respiratory cycle. The absolute value of mean tissue pH at Pco2 = 30 Torr predicted from the buffer line, 6.57, agrees well with direct measurement in hemolymph samples.
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OBJECTIVES: This study was designed to investigate whether a subclinical accumulation of fluid in the lung interstitium associated with moderate congestive heart failure interferes with the patient's functional capacity, and whether furosemide treatment can promote reabsorption of the excessive fluid. BACKGROUND: In patients with moderate congestive heart failure, pulmonary overhydration may be detected by chest roentgenography even if therapy is optimized to keep the urinary output normal and to prevent weight gain and dependent edema formation. Removal of the overhydration may help define its significance. METHODS: Patients, whose regimens of digoxin, oral furosemide, and angiotensin-converting enzyme (ACE) inhibitor therapy were kept constant, were randomly allocated to receive ultrafiltration (8 cases) or an intravenous bolus of supplemental furosemide (mean dose: 248 mg; 8 cases). The amount of body fluid removed with each method approximated 1600 mL. Functional performance was assessed with cardiopulmonary exercise tests. RESULTS: Soon after fluid withdrawal by either method, the filling pressures of the two ventricles and body weight were reduced and plasma renin activity, norepinephrine, and aldosterone were augmented. After furosemide administration, hormone levels remained elevated for the next 4 days, and during this period, patients had positive water metabolism, recovery of the elevated ventricular filling pressures, and re-occurrence of lung congestion with no improvement in functional capacity. After ultrafiltration, levels of renin, norepinephrine, and aldosterone fell to below control values within the first 48 hours and water metabolism was equilibrated at a new set point (less fluid intake and diuresis without weight gain). The favorable circulatory and ventilatory adjustments consequent to the reabsorption of lung water improved the functional capacity of these patients. That may also have restored the lung's ability to clear norepinephrine, thus restraining its facilitation of renin release. The improvement continued 3 months after the procedure. CONCLUSIONS: In patients with congestive heart failure the set point of fluid balance is altered in spite of oral furosemide therapy; supplemental intravenous furosemide does not shift the set point, at least not when combined with ACE inhibition. Excessive, although asymptomatic, lung water limits the functional capacity of the patient.
1. Male and female rats were given 100 mg Ni L-1 (as nickel sulphate) in drinking water for 6 months. 2. The feeding of nickel was associated with an increased concentration of nickel in body fluids and organs. The highest concentrations of nickel were found in the liver of both male and female rats. In male rats nickel levels decreased in the order: liver > kidney = whole blood = serum > testes > urine. In female rats the decreasing order was similar: liver > kidney = whole blood = serum = plasma > urine > ovaries. 3. No significant differences were found between nickel concentrations in organs (except ovaries), blood and urine of rats exposed for 3 months and those exposed for 6 months indicating the reaching of a steady state of nickel in the rat during long-term exposure. 4. The urinary excretion of the orally administered nickel was only 2% of absorbed dose (supposing 1% Ni absorption).
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Contents of water, sodium, calcium and magnesium in different tissues of the rats stayed in space for 2 weeks in healing period of bone fracture following graded trauma of calf-bones as well as in the rats exposed to a head-down suspension (HDS) have been studied. In microgravity-exposed animals there were no significant changes in fluid-electrolyte composition of the liver, kidney, myocardium, skin, bone (calf bone). Specific "functional load" on the system of fluid-electrolyte homeostasis in the form of operation and subsequent healing of bone fracture did not result in additional changes in fluid and electrolyte contents of body tissues. In the HDS animals there was a significant change in fluid-electrolyte composition of skin, kidney and bone tissue.