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Maternal ingested methadone, body fluid methadone, and the neonatal withdrawal syndrome.

The relationship between the quantity of methadone ingested by the pregnant mother, the quantity of methadone in maternal and neonatal body fluids, and the subsequent neonatal withdrawal course was studied. The severity of the neonatal withdrawal syndrome was found to be related to the total dose of methadone ingested by the mother during the last 12 weeks of pregnancy (p less than 0.02), the maternal dose of methadone at delivery (p less than 0.01), and the intrapartum serum methadone levels (p less than 0.01). The cord blood levels of methadone were consistently lower than the maternal serum levels. Amniotic fluid methadone levels were not constantly related to maternal or neonatal serum methadone levels. Concentrations of methadone 10 to 60 times greater than that of cord blood were found in neonatal urine.

Amniotic Fluid

Effects of nonsteroidal anti-inflammatory drugs (NSAID) on renal excretion of sodium and water, and on body fluid volume in rats.

Effects of nonsteroidal anti-inflammatory drugs (NSAID) on urine volume and urinary sodium excretion, and on plasma volume and extracellular fluid volume were examined in conscious rats. The basal urine volume and urinary sodium excretion were decreased and the increased urine volume and urinary sodium excretion elicited by saline load (25 ml/kg) and by hydrochlorothiazide (10 mg/kg) were inhibited after oral administration of NSAID in doses which inhibited the rat carrageenin-induced hind paw edema (indomethacin, 1--10 mg/kg; tolmetin, 3--30 mg/kg; phenylbutazone, 3--30 mg/kg; aspirin, 30--300 mg/kg), but aminopyrine (30--300 mg/kg) did not show such an effect. The inhibitory activity on renal function was diminished gradually with repeated administration of NSAID. NSAID (indomethacin, 3 mg/kg; tolmetin, 10 mg/kg; phenoxybenzamin, 10 mg/kg; aspirin, 100 mg/kg) increased plasma volume and extracellular fluid volume of rats after repeated medication for 3 or 5 days, but the body fluid volume expansion disappeared with further repeated administration of NSAID. These results suggest that NSAID may inhibit the intrarenal role of prostaglandins and decrease sodium and water excretion in urine with resulting increased body fluid volume. Tolerance to these actions of NSAID developed after repeated administration.

Animals

Vanadium in foods and in human body fluids and tissues.

Using neutron activation analysis, vanadium was analysed in a range of foods, human body fluids and tissues. On the basis of these results and those of other workers, it was concluded that daily dietary intake amounts to some tens of micrograms. Analysis of body fluids (including milk, blood and excreta) and organs and tissues provided an estimate for the total body pool of vanadium in man of about 100 microgram. Vanadium was not detectable in blood and urine at the level of 0.3 ng/g, while low levels were found in muscle, fat, bone, teeth and other tissues. The relationship between dietary intake to pulmonary absorption is discussed in relation to the occurrence of vanadium in man-made air particulates. The very low levels found in milks and eggs suggest minimal vanadium requirements in growth. The findings are discussed in the light of previous results and also in relation to the possible essentiality of vanadium.

Air

On the question of body fluid volume or sodium status influencing renin release.

1. The extent to which renin release is affected by simultaneous changes in body Na and body fluid volume was studied in six sheep. 2. The animals' water intake was restricted for 10-17 days after which they were offered solutions containing varying amounts of NaCl. 3. Plasma renin concentration (PRC) of water restricted sheep was 2-3 times normal. 4. The changes in PRC following drinking were inversely related to the amount of sodium consumed, Na excretion and plasma Na concentration. There was no correlation between the changes of PRC and of plasma volume in so far as the latter is reflected by alterations in plasma protein concentration. 5. We conclude that changes in renin release were related to the animals' handling of NA, and not to alterations in body fluid volume. 6. These findings are compatible with the proposition that renin release was mediated by a macula densa mechanism.

Animals

Body fluid compartments.

The terms mole, molality, molarity, osmole, osmolality, osmolarity, osmolar gap and anion gap are defined and their clinical usefulness indicated. The following body fluid compartments are described: total body water (TBW), extracellular fluid (ECF), intracellular fluid (ICF), transcellular fluid TCF), plasma volume, red cell volume and interstitial fluid volume. Isotope-dilution techniques are briefly discussed and representative normal values for the various compartments according to sex and age are indicated. The physiological mechanisms that maintain the distinctive ionic compositions of the various fluid spaces are briefly outlined. New concepts of the function of the gel matrix and of the lymph drainage of the interstitium are presented. Opposing models to the sodium-potassium membrane pump are briefly described.

Body Fluid Compartments

Preinfarction diagnosis of acute mesenteric ischemia by simple measurement of inorganic phosphate in body fluids.

Acute mesenteric ischemia is extremely difficult to diagnose because peritoneal signs are absent until the bowel becomes necrotic and irretrievably damaged. So far the only reliable diagnostic procedure has been mesenteric angiography. The present study verifies that significant elevations of serum inorganic phosphate concentrations occur in dogs after mesenteric occlusion; the authors' initial clinical studies in humans support these experimental findings. Detailed analysis of body fluid and soft tissue phosphate content shows that the high phosphate load originates in the sloughing intestinal mucosa; if this phosphate escapes filtration by the liver it enters the systemic circulation. Simple measurement of the inorganic phosphate concentrations of the serum and peritoneal fluid may lead to earlier diagnosis of acute intestinal ischemia and a successful revascularization procedure to prevent its progression to infarction.

Acute Disease

Detection of bacterial metabolites in spent culture media and body fluids by electron capture gas-liquid chromatography.

Electron capture gas-liquid chromatography, when used to analyze derivatized extracts of spent culture media and body fluids under specified conditions, holds promise as a tool for use by physicians, hospitals, and clinical laboratories in identifying certain diseases and disease-producing organisms. The detection of certain disease processes and the identification of disease-producing organisms are based on qualitative or large quantitative differences in EC-GLC profiles or a combination of both. Various practical procedures are given for extracting and derivatizing compounds, such as carboxylic acids, hydroxy acids, alcohols, amines, and nitrosamines. The characteristics of the parameters essential for successful analysis are discussed. Species and, in some cases, strains have been differentiated by comparing EC-GLC profiles. Metabolic products are affected by change in substrate. Media that can be reproduced from lot to lot are essential in some studies. The volatile components detected by EC-GLC in spent culture media consist mostly of bacterial metabolites, but the volatile compounds detected in body fluids may be bacterial metabolites, volatile components produced by the host in response to an infection, metabolites of cells associated with host defense, or a combination of two or more of these groups of compounds. The EC-GLC profiles obtained by analysis of synovial and cerebrospinal fluids appear to have good potential for use in diagnosing certain forms of arthritis and meningitis. Well-documented samples are essential to establishing EC-GLC profiles representative of a particular disease. A moderately priced computer would greatly aid in data processing and could be especially useful in compensating for minor changes in the retention times of peaks, which can occur as a result of column aging or when columns are renewed. An approach to the identification of components detected by EC-GLC, which makes use of electron capture gas chromatography-mass spectrometry, is presented.

Alcohols

Comparisons of body fluid volumes, plasma renin activity, hemodynamics and pressor responsiveness between juvenile and aged patients with essential hypertension.

Body fluid volumes, cardiac output, PRA and pressor responses to angiotensin II (AT) and norepinephrine (NE) were compared between untreated patients with essential hypertension aged younger than 35 (EH-I) and those aged older than 36 years (EH-II). Men blood volume, total body water and extracellular volume were not significantly different between the patients with essential hypertension and normotensive subjects. There were no difinite differences in each volume between the EH-I and EH-II patients either. However, the distribution of blood volume was significantly larger in the essential hypertensive patients than in the normotensive subjects, suggesting that the changes in blood volume might not be homogenous in essential hypertension. In addition, blood volume was noted to have a significant inverse correlation with PRA. Cardiac output at rest was slightly but not significantly less in the EH-I and EH-II groups than in the normotensive group. A decline in blood pressure following 'bed-rest' was accompanied by a decrease in total peripheral resistance index (TPRI). Thus, elevated peripheral vascular resistance seems to be responsible for the mild to moderate hypertension even in the younger patients. PRA and its increases in response to standing or furosemide were normal in the EH-I patients, while they were markedly suppressed in the EH-II patients as compared to the age-matched normotensive subjects. In addition, PRA had a significant inverse correlation with the blood pressure and the scores of the severity of hypertension in the patients with essential hypertension. Thus, it seems likely that low renin in essential hypertension is secondary to long-lasting hypertension. Pressor response to AT significantly correlated with mean blood pressure and that to NE did so with 24 hours' urinary sodium excretion in essential hypertensive patients. The influence of aging on the pressor responses were obscure: the relationships of the pressore responses to blood pressure or to urinary sodium excretion were not different between the EH-I and EH-II groups. The examinations were repeated in 16 patients with essential hypertension (16 to 48 year-old) in 11 to 30 days after the initial study. Twelve of the 16 patients had declines in blood pressure and TPRI at the second study. In 7 of the patients whose blood pressure declined following 'bed-rest', there were significant decreases in pressor response to AT and in blood volume and a significant increase in PRA (group A). The other 5 patients showed a significant decrease in PRA and an enhanced pressor response to NE (group B). The blood volume in the group A was significantly larger than that in the group B at the initial study. It is suggested that the cause of essential hypertension is not homogeneous in that the increased vascular resistance may have been attributed to sodium excess in some patients and to an increased sympathetic activity in others. Some additional factors remain to be taken into account to clarify the complicated aspects of essential hypertension.

Adolescent

Tissue culture cytotoxicity assay for cyclophosphamide metabolites in rat body fluids.

An in vitro cytotoxicity assay for cyclophosphamide metabolites in rat body fluids is described. Of the two tissue culture tumor cell lines employed, the Walker-256 rat carcinosarcoma was more sensitive to metabolite levels than the L-1210 mouse lymphocytic leukemia. The Walker-256 system detected cyclophosphamide metabolite levels two orders of magnitude lower than the commonly used 4-(p-nitrobenzyl)pyridine analytical procedure.

Animals

Profiling of human body fluids in healthy and diseased states using gas chromatography and mass spectrometry, with special reference to organic acids.

This review summarizes recent advances in the application of gas chromatography and mass spectrometry to the study of human diseases. Emphasis is placed upon the organic acid profiles of the various body fluids. Methods for sample work-up prior to separation and mass spectrometric analysis are reviewed, and artifacts and pitfalls are discussed. Organic acid profiles, obtained with packed or capillary columns attached to mass spectrometers with or without computer systems, have led to the discovery of new normal metabolites, new metabolic disorders, and to new knowledge about a number of other diseases. Stable isotopes and gas chromatography--mass spectrometry are suitable for quantitative analysis of many compounds in the body fluids, and well suited for investigation of metabolic pathways.

Adult

Body fluid changes during hypertonic lactated saline solution therapy for burn shock.

The body fluid changes of 12 burn patients treated with Hypertonic Lactate Saline solution (HLS group) were compared with 26 burn patients receiving isotonic therapy (iso Na group). 1) Total infusion volume during the first 48 hours postburn in the HLS group was only one-half to two-thirds of that in the iso Na group, although the sodium loads were nearly equal. 2) HLS therapy maintained sufficient functional extracellular fluid volume (f-ECFV) in the shock period and protected the excess increase of f-ECFV in the postresuscitative period, in contradistinction to the iso Na group. In this paper, some clinical problems such as a rapid shift of ECF water into the ICF space and hypernatremia following HLS administration are discussed.

Adult

Comparative effects of ticrynafen and hydrochlorothiazide on blood pressure, renal function, serum uric acid and electrolytes, and body fluid spaces in hypertensive man.

25 hypertensive subjects underwent a double-blind, randomized study to compare the effects of ticrynafen (TCNF) with hydrochlorothiazide (HCTZ) on blood pressure (BP), renal function, serum uric acid (UA) and electrolytes, and body fluid spaces. BP was similarly lowered by TCNF and HCTZ. Neither TCNF nor HCTZ had a significant effect on true or regular creatinine, inulin, or PAH clearances. TCNF lowered UA, whereas HCTZ elevated UA. Both produced similar electrolyte disturbances. Neither TCNF nor HCTZ, according to our methods, had a significant effect on plasma volume, extracellular fluid, or total body water. The primary advantage of TCNF compared with HCTZ is its profound hypouricemic effect.

Adult

Distribution and fate of alpha-naphthl-isothiocyanate (ANIT) in the organs and body fluids of the rat.

alpha-Naphthyl-isothiocyanate (ANIT) is a well known toxic substance which induces characteristic hepatic lesions. Its distribution in some organs and body fluids was investigated by using spectrophotometry, gas-chromatography and thin-layer chromatography. The results indicate that ANIT concentrates in the liver, kidneys and blood but not in the brain, urine and bile. Another five ANIT-like substances have also been examined, but no trace of them has been found in these organs and body fluids. The authors suppose that ANIT is metabolized to an unknown metabolite which is responsible for the toxic action of ANIT. None of the ANIT-like substances examined by us can be indentified with this metabolite.

1-Naphthylisothiocyanate

Thin-layer and gas-liquid chromatographic procedures for the determination of perazine and its metabolites in human body fluids.

The quantitative determination of perazine, a neuroleptic drug, and its metabolites in body fluids is difficult in view of the low concentrations to be expected under therapeutic conditions as well as of the problem of convenient detectors. Different methods for extraction and measurement of perazine concentration in blood samples are discussed, with special consideration of partition coefficients and the properties of the chromatographic systems (thin-layer and gas-liquid chromatography). A new and simple method for rapid gas chromatographic determination of perazine is presented.

Antipsychotic Agents

Melatonin assays in body fluids.

A variety of methods now exist for the assay of melatonin in body fluids. Their relative merits are compared and the validation of one in particular (RIA) described. Physiological studies of melatonin by RIA have shown probable modulation of its secretion by gonadal steroids. The circadian activity maximum in the dark phase of one of the pineal melatonin synthesizing enzymes, N-acetyltransferase, is reflected in peripheral melatonin levels. Man, like all other species studied so far, has a dark phase rise in circulating melatonin. During the menstrual cycle, melatonin shows a luteal phase rise. Further evidence of pineal rhythmicity is found in seasonal melatonin variations in man. The study of the rhythmic properties of peripheral melatonin in man may provide important information on central nervous function.

Acetyltransferases

Determination of lithium in microlitre amounts of human body fluids at therapeutic and normal levels by stable isotope dilution and field desorption mass spectrometry.

The use of field desorption mass spectrometry for the determination of lithium in body fluids at therapeutic levels--ppm region--as well as at the normal level--ppb region--has been developed. The use of a stable isotope enriched internal standard, together with the outstanding sensitivity of field desorption for alkali cations and the high specificity of mass spectrometry, allows a quantitative determination of lithium in microlitre amounts of body fluids, such as plasma, saliva and urine. The assay allows a determination of lithium even at ultratrace concentrations where routine spectroscopic procedures cannot be applied. Analysis of plasma required a simple protein precipitation, whereas saliva and urine could be analysed without treatment. The precision of the data obtained ranged from 2--10%. The time consumption for one analysis in routine work is about 20--30 min.

Humans

[Determination of "middle molecules" presenting vitamin B12 molecular size in normal and uremic body fluids (author's transl)].

Uremic solutes with the molecular size of vitamin B12 are assumed to be toxic. An analytical method is proposed to detect and separate these solutes in body fluids using two combined techniques: gel filtration on Sephadex G-15 and ion-exchange chromatography on DEAE-Sephadex A-25. The vitamin B12 molecular size has been localized by ultrafiltration through membranes with a defined cut-off. Normal and uremic body fluids (urine, plasma, hemodialysis fluid) have been separated into 9 ultraviolet-absorbing peaks (a to i) by high-speed gel filtration. Peaks b and c present the molecular size of vitamin B12, 10--15 A molecular diameter in pH7 aqueous solution. Peak b, which correlates with uremic neuropathy, is separated into 6 sub-peaks (b1 to b6) by ion-exchange chromatography, sub-peak b4.2 is the only one to correlate with uremic neuropathy. The coefficient of variation in the integrated area of a single peak is 16%. This method gives the chromatographic prolife of the vitamin B12 molecular size from 500 microliter of uremic plasma or 100 microliter of normal urine within one hour.

Chromatography, Gel

Radiometric determination of the concentration of amphotericin B in body fluids.

A new assay was developed to determine the concentration of amphotericin B in body fluids. The Bactec radiometric system was used to measure CO(2) production by a test strain, Candida albicans MDA 448, in the presence of amphotericin B. After 5-h incubation, drug concentrations as low as 0.2 mug/ml could be detected. The results are comparable to those of the commonly used agar diffusion assay with Paecilomyces varioti.

Amphotericin B