Validation of placental vascular sonobiopsy for obtaining representative placental vascular indices by three-dimensional power Doppler ultrasonography.

OBJECTIVE: Placental vascular sonobiopsy has been proposed for obtaining a representative sample of the placental vascular tree when evaluation of the whole placenta is not feasible. We tested the hypothesis that placental vascular indices from sonobiopsy correlate well with those from the entire placenta. METHODS: Three-dimensional power Doppler ultrasound examinations were performed in 120 singleton pregnancies at 11-14 weeks' gestation. The VOCAL program was used to calculate placental vascularization index (VI), flow index (FI) and vascularization flow index (VFI) from stored images of each placenta by whole placenta evaluation and placenta vascular sonobiopsy. The mean of each index from four spherical sonobiopsies were compared to those from evaluation of the entire placenta for their degree of correlation and agreement. RESULTS: The mean VI and VFI from the two techniques were similar (13.9 [95% CI 12.3-15.8] versus 14.3 [95% CI 12.1-17.0], p = 0.62 and 6.1 [95% CI 5.2-7.1] versus 6.1 [95% CI 5.0-7.4], p = 0.93, respectively) and significantly correlated (Pearson's r = 0.70 [95% CI 0.60-0.78, p < 0.001] and r = 0.69 [95% CI 0.58-0.77, p < 0.001], respectively). The mean FI from the two techniques were significantly different (44.5 [95% CI 42.9-46.1] versus 41.3 [95% CI 39.6-43.0], p = 0.001), but correlated (r = 0.59 [95% CI 0.46-0.70, p < 0.001]). CONCLUSION: Our findings suggest that placenta vascular indices from sonobiopsy have a good correlation with those from evaluation of the entire placenta. Sonobiopsy may be a valid alternative for evaluation of the placental vascular tree when visualization of the entire placenta is not feasible. Measurements of VI and VFI appear to be more reliable than FI in sonobiopsy specimen.

Blocking swelling-activated chloride current inhibits mouse liver cell proliferation.

A non-transformed mouse liver cell line (AML12) was used to show that blocking swelling-activated membrane Cl- current inhibits hepatocyte proliferation. Two morphologically distinguishable cell populations exhibited distinctly different responses to hypotonic stress. Hypotonic stress (from 280 to 221 mosmol kg(-1)) to rounded, dividing cells activated an ATP-dependent, outwardly rectifying, whole-cell Cl- current, which took 10 min to reach maximum conductance. A similar anionic current was present spontaneously in 20 % of the dividing cells. Hypotonic stress to flattened, non-dividing cells activated no additional current. The Eisenman halide permeability sequence of swelling-activated anionic current in the dividing cells was SCN(-) > I(-) > Br(-) > Cl(-) > gluconate. Addition of either 4,4'-diisothiocyanatostilbene-2,2'-disulfonate (DIDS), 5-nitro-2-(3-phenylpropylamino) benzoic acid (NPPB), tamoxifen or mibefradil inhibited swelling-activated anionic current. Hyperosmolarity by added sucrose inhibited the spontaneous anionic current in dividing cells. Added Cl- channel blockers NPPB (IC50 = 40 microM), DIDS (IC50 = 31 microM), tamoxifen (IC50 = 1.3 microM) and mibefradil (IC50 = 7 microM) inhibited proliferative growth of AML12 as determined by cell counts over 4 days or by protein accumulation over 2 days. Only the inhibitory effects of NPPB and mibefradil reversed with the drug washout. Hyperosmolarity by added sucrose (50 and 100 mM) also inhibited cell proliferation. Of the hydrophobic inhibitors neither NPPB at 40 microM nor tamoxifen at 1.3 microM, added for 48 h, reduced cellular ATP; however, DIDS at 31 microM significantly reduced cellular ATP with an equivalent increase in cellular ADP. We conclude that those membrane Cl- currents that can be activated by hypotonic stress are involved in mechanisms controlling liver cell growth, and that NPPB, tamoxifen and mibefradil at their IC50 for growth do not suppress the metabolism of mouse hepatocytes.

Generalised muscular weakness after botulinum toxin injections for dystonia: a report of three cases.

Three patients are reported on who developed transient generalised weakness after receiving therapeutic doses of botulinum toxin for cervical dystonia (one case) and symptomatic hemidystonia (two cases) respectively. Clinical and electrophysiological findings were in keeping with mild botulism. All patients had received previous botulinum toxin injections without side effects and one patient continued injections without recurrence of generalised weakness. The cause is most likely presynaptic inhibition due to systemic spread of the toxin. Patients with symptomatic dystonia may be more likely to have this side effect and botulinum toxin injections in these patients should be carried out cautiously.

Paroxysmal kinesigenic choreoathetosis: a report of 26 patients.

Paroxysmal kinesigenic choreoathetosis (PKC) is a neurological condition which results in abnormal involuntary movements that are precipitated by sudden movement. Because of its rarity, large case series of PKC have not been published. We studied 26 patients with PKC, which represents the largest series thus reported. We reviewed our cases with respect to attack characteristics, aetiology, family history, and treatment response. Our population consisted of 23 men and 3 women. Seven patients had a family history of paroxysmal dyskinesia. None of our patients had clear evidence of symptomatic PKC. Two-thirds of our patients had attacks lasting between 30-60 s, and over one-half experienced one to ten attacks per day. Attack distribution varied widely, and most experienced pure dystonia rather than choreodystonic movements. Most patients responded very well to anticonvulsant therapy. We also report the PET results from two of our patients and Bereitschaftspotential abnormalities recorded from two others.

Further studies using higher doses of botulinum toxin type F for torticollis resistant to botulinum toxin type A.

OBJECTIVE: A previous study of botulinum toxin type F (BTX-F) treatment for torticollis had shown a dose of 520 MU to be effective, but for a much shorter duration than is usual with botulinum toxin type A (BTX-A). The objective was to assess the effect of a higher dose of BTX-F. METHODS: Four of the previously treated patients, plus an additional patient, were treated with a higher dose of 780 MU BTX-F. All were secondary nonresponders to BTX-A due to neutralising antibodies. A test injection of 40 MU BTX-F was also given into the extensor digitorum brevis muscle (EDB), to examine the time course of the biological effect of the toxin electrophysiologically. Patients were followed up at two, four, eight, and 12 weeks. RESULTS: All patients reported subjective improvement lasting from seven to 11 (mean 8.6) weeks accompanied by a significant reduction in mean clinical severity scores at two weeks. Four patients had pain which was substantially reduced. The electrophysiological studies confirmed biological sensitivity to the toxin in all patients, showing a significant change beginning at two weeks and returning to baseline at 12 weeks. The time course of this effect paralleled roughly that of the clinical response. The four patients who had previously received 520 MU BTX-F reported that the response was better and longer in duration with 780 MU. Dysphagia was more common than reported with the lower dose. CONCLUSION: Better results are possible with higher doses of BTX-F but the duration of benefit is still shorter than with BTX-A, seemingly due to a shorter duration of neuromuscular junction blockade.

Lumbrical-interosseous latency comparison in the diagnosis of carpal tunnel syndrome.

We examined 66 hands referred with suspected carpal tunnel syndrome (CTS) using the second lumbrical-interosseous distal motor latency difference (2LI-DML) as well as standard tests: Forty-nine cases of CTS were diagnosed by the standard tests, 48 of whom had an abnormal median-ulnar palmar velocity comparison and 48 an abnormal 2LI-DML. The results of these 2 tests were closely correlated. The 2LI-DML supported the diagnosis of CTS in all cases except one, where the result was borderline. In one suspected case the 2LI-DML was the only abnormality. In 9 severe cases no median palmar responses could be obtained but an abnormal 2LI-DML was found. We conclude that the 2LI-DML is as sensitive as the palmar comparison and thus will support the diagnosis of CTS made by standard tests by providing an additional abnormality but that its routine use is unlikely to increase the diagnostic yield. Its value therefore may be in mild cases where the median-ulnar palmar comparison is normal or equivocal and in severe cases where standard test responses are unobtainable. It has also proved useful as a quick and simple screening test for CTS on the asymptomatic side.

Synergistic effects of fish oil diet and dimethylthiourea in acute adriamycin nephrosis.

The synergistic effects of combining fish oil (FO) diet, which reduces thromboxane A production, with the free radical scavenger, dimethylthiourea (DMTU), were evaluated in acute adriamycin nephrosis, because proteinuria in adriamycin nephrosis is mediated by increased renal thromboxane A and free radical production. The effects of combined evening primrose oil (EPO) and DMTU were compared with the DMTU + FO combination because EPO increases prostaglandin E but not thromboxane A. After 7, 14, and 21 days, proteinuria was significantly (p < 0.05) reduced in rats receiving either DMTU + corn oil (CO) or DMTU + FO compared with untreated control rats. However, after 21 days, rats receiving DMTU + FO had significantly reduced urine protein excretion compared with those receiving DMTU + CO (103.9 +/- 20 mg daily vs 351.8 +/- 29.8 mg daily; P < 0.05). In contrast to FO, rats receiving EPO + DMTU had similar urine protein excretion to rats receiving DMTU + CO after 21 days (170.2 +/- 20.34 mg daily vs 179.45 +/- 26.38 mg daily). The mean serum cholesterol concentration was significantly (P < 0.01) reduced in rats receiving DMTU + FO (195.2 +/- 23.8 mg/dL) compared with DMTU + CO (377.9 +/- 28.5 mg/dL). Serum triglyceride levels also were significantly (P < 0.01) reduced in rats receiving DMTU + FO (52.5 +/- 26.4 mg/dL) compared with DMTU + CO (100.5 +/- 36.9 mg/dL). No significant differences in serum cholesterol concentrations or triglycerides occurred between rats receiving DMTU + CO and DMTU + EPO. Renal glutathione content was significantly (P < 0.05) increased by 23% in normal rats receiving FO diet and by 34% in rats receiving combined DMTU + FO compared with CO alone.(ABSTRACT TRUNCATED AT 250 WORDS)

Glomerular injury in end-stage liver disease--role of circulating IgG and IgM immune complexes.

The relationship of IgG- and IgM-bound circulating immune complexes and immune dysfunction to glomerular injury was evaluated in 15 children with end-stage liver disease (ESLD) awaiting liver transplantation. Compared with age-matched controls, children with ESLD had significantly (P < 0.01) increased serum IgG, IgA, and IgM levels, as well as IgG- and IgM-bound circulating immune complexes. Furthermore, they showed a significant (P < 0.05) depression of C3 and C4 levels compared with controls. Hematuria occurred in 66% of children with ESLD, and the urinary protein/creatinine ratio was also significantly (P < 0.01) increased compared with controls (4.65 +/- 2.56 vs. 0.16 +/- 0.04 mg/mg). Light microscopy of renal biopsy tissue obtained from 6 children with ESLD at the time of transplantation demonstrated mesangial proliferation and expansion with basement membrane splitting. This was associated with subendothelial deposits on electron-microscopic examination, compatible with a diagnosis of membranoproliferative glomerulonephritis. By immunofluorescence, deposition of IgG, IgA, and IgM occurred in various combinations with co-deposition of complement fragments. We conclude that membranoproliferative glomerulonephritis is a common finding in children with ESLD, probably due to entrapment of circulating IgG- and IgM-bound immune complexes.

Enhancement of renal and hepatic glutathione metabolism by dimethylthiourea.

Dimethylthiourea (DMTU), a free radical scavenger, was administered to rats to study its effect on renal and hepatic glutathione metabolism, since it is a potential sulfhydryl donor. Six hours following DMTU, renal GSH content was significantly (P < 0.05) increased (10%), and was increased further after 24 h (28%) (P < 0.001). Hepatic GSH content was also significantly (P < 0.001) elevated at 6 and 24 h (5 and 33%, respectively). Seven days of daily DMTU therapy significantly (P < 0.001) increased renal and hepatic GSH content by 36 and 54%, respectively, which was associated with a significant (P < 0.001) increase in the renal activities of glutathione peroxidase (GP) by 38%, glutathione transferase (GT) by 92%, and glutathione reductase (GR) by 19% (P < 0.05). Significantly increased activities of hepatic GP by 84% (P < 0.01) and GT by 101% (P < 0.001) also occurred in DMTU-treated rats after 7 days of continuous therapy. From these data, we conclude that DMTU stimulates renal and hepatic GSH metabolism, which may be important in mediating DMTU's protective effect against free radical-induced tissue injury.

Role of glutathione metabolism in the reduction of proteinuria by dimethylthiourea in adriamycin nephrosis.

Glutathione (GSH) metabolism, a tissue detoxification pathway, was evaluated in rats with adriamycin nephrosis (AN) treated with dimethylthiourea (DMTU), a free radical scavenger. After 7 days of DMTU, a significant reduction in proteinuria occurred as compared to AN controls (62.4 +/- 13.3 vs. 155.0 +/- 24.0 mg/24 h). A significant increase in renal cortical GSH content as well as glutathione peroxidase (GP) and transferase (GT) activities occurred in DMTU-treated rats as compared to controls. Glutathione monoethyl ester (GME) administration alone reduced proteinuria by 21% in AN, which was not significant despite a large increase in the renal GSH content, however, GP and GT activities were not increased by GME. We conclude that DMTU ameliorates glomerular injury in AN by stimulating GSH metabolism.

Glutathione monoethyl ester moderates mercuric chloride-induced acute renal failure.

Glutathione (GSH)-dependent reactions are an important cellular defense against ischemic or oxidative injury, although their role in toxin-induced renal cellular injury is less clear. Because of the known sulfhydryl reactivity of mercury (M), we hypothesized that GSH could modify mercuric chloride (MC)-induced acute renal failure (ARF). Therefore, we evaluated the effects of glutathione monoethyl ester (GE), which produces high intrarenal levels of GSH, on the nephrotoxicity of MC. GE treatment in normal rats did not alter their creatinine clearance (CCr), fractional sodium (CNa/CCr) or lysozyme (CLy/CCr) excretion, but histologically resulted in prominent proximal tubular vacuolization. GE pretreatment in rats with MC-induced ARF resulted in partial preservation of their CCr, CNa/CCr and CLy/CCr. Renal histology also demonstrated a reduction in tubular necrosis. M content in the renal cortex 3 following MC was lower in the MC + GE group, but levels were higher in the liver and inner stripe/inner medulla as compared to animals receiving MC alone. No differences were seen in the outer stripe at 3 h or in any of the tissues 24 h following MC injection. Thus, GE moderated MC-induced ARF, likely by providing a large intracellular sulfhydryl pool and thereby reducing M reactivity with endogenous cellular proteins and enzymes.

Amelioration of glomerular injury in doxorubicin hydrochloride nephrosis by dimethylthiourea.

The hydroxyl radical scavengers dimethylthiourea (DMTU), sodium benzoate, and dimethylsulfoxide (DMSO) were administered to rats before doxorubicin hydrochloride (ADR) (5 mg/kg, IV) to probe the role of free radicals in mediating proteinuria in doxorubicin hydrochloride nephrosis (AN). Because ADR stimulates free radical production, the role of renal glutathione was also evaluated; glutathione metabolism is involved in tissue detoxification processes. DMTU administration to rats with AN caused a significant (p less than 0.01) reduction in their proteinuria after 7 days (52.84 +/- 13.21 mg/24 hours) when they were compared with ADR controls (155.81 +/- 20.16 mg/24 hours). In similar fashion, their urine albumin excretion was also significantly reduced when compared with that of ADR controls (11.13 +/- 2.75 mg/24 hours vs 32.08 +/- 4.14 mg/24 hours; p less than 0.01). DMTU-treated rats also had significantly (p less than 0.001) reduced urinary protein and albumin excretion at 14 days when compared with rats that received ADR alone. The urinary excretion of lysozyme and N-acetyl-glucosaminidase, markers of renal tubular injury, were significantly increased after 7 or 14 days in rats with AN, despite DMTU treatment. Creatinine clearance was significantly reduced (p less than 0.05) in rats receiving ADR alone (0.223 +/- 0.011 ml/min/100 gm) when compared with that in normal controls (0.331 +/- 0.027 ml/min/100 gm) or DMTU-treated rats (0.289 +/- 0.035 ml/min/100 gm). Unlike DMTU, neither sodium benzoate nor DMSO reduced proteinuria in rats with AN.(ABSTRACT TRUNCATED AT 250 WORDS)

Renal tubular protein handling in experimental renal disease.

Competitive inhibition of renal tubular transport occurs between low- and high-molecular-weight proteins following intravenous infusion, but this relationship is less clear following de novo glomerular or renal tubular injury. The present study evaluated renal lysozyme and albumin handling following renal tubular injury induced by both low- and high-dose mercuric chloride (0.5 and 2.0 mg/kg) and maleic acid (50 and 400 mg/kg), and following glomerular injury induced by puromycin aminonucleoside (5 mg/100 g) or Adriamycin (5 mg/kg). Subtle renal tubular injury induced only mild isolated albuminuria, while severe tubular injury caused dramatic lysozymuria and moderate albuminuria. However, increased filtration of albumin in these models of glomerular injury did not inhibit lysozyme transport.

Unilateral nephrectomy in the rat: effects on mercury handling and renal cortical subcellular distribution.

As unilateral nephrectomy (UNX) is associated with enhanced mercuric chloride nephrotoxicity, studies were undertaken to characterize the effects of UNX on the tissue content, urinary excretion, and renal cortical subcellular distribution of mercury in the rat. Animals were studied immediately, 2 days or 14 days following UNX, during separate phases of compensatory renal hypertrophy. As compared to sham surgery controls, mercury content in renal cortex was higher in all UNX groups at 24 hr following injection and in the immediate and 2-day groups at 1 or 3 hr. However, UNX was not associated with any alteration in mercury content within outer or inner medulla, liver, plasma, or red blood cells. Subcellular distribution studies demonstrated that cytosolic mercury was uniformly elevated in all UNX groups at 1, 3, and 24 hr following injection while mercury bound to "metallothionein-like" proteins or free in the cytosol was increased only at 1 or 3 hr. Nuclear, mitochondrial, or microsomal mercury content was elevated in the animals studied immediately or 14 days after UNX at 3 or 24 hr following injection, while animals studied 2 days after UNX demonstrated a nearly uniform increase at 1, 3, and 24 hr. Single-kidney urinary mercury excretion was elevated in all UNX groups while excretion per gram kidney weight was increased only in the animals studied immediately or 2 days after surgery. These studies suggest that all phases of compensatory renal hypertrophy are associated with an enhanced content of mercury within the cell cytoplasm and in critical cellular organelles, which may explain the enhanced nephrotoxicity seen following UNX.

Characterization of recumbent, ambulatory, and postexercise proteinuria in the adolescent.

To better characterize the effects of body position and exercise on urinary protein excretion, carefully defined random urine samples were obtained during recumbency and following both ambulation and exercise in healthy adolescent student athletes. Albumin, lysozyme, and N-acetyl-B-D-glucosaminidase were measured in all samples. Glomerular permeability and tubular function were assessed using the urinary albumin creatinine ratio (UAlb/UCr), the urinary lysozyme creatinine ratio (ULy/UCr), the urinary N-acetyl-B-D-glucosaminidase creatinine ratio (UNag/UCr), and the urinary lysozyme albumin ratio (ULy/UAlb). UAlb/UCr was significantly (p less than 0.001) lower in recumbent urine samples than in either ambulatory or postexercise samples, although no difference was seen between the latter two groups. Furthermore, recumbent UAlb/UCr was higher in females (p less than 0.01) and postexercise UAlb/UCr varied significantly (p less than 0.001), depending on the type of physical activity. ULy/UCr, UNag/UCr, and ULy/UAlb were unaffected by either posture or physical activity. A significant correlation was found between UAlb/UCr and UNag/UCr (r = 0.60, p = 0.0001) and also between ULy/UCr and ULy/UAlb (r = 0.84, p = 0.001). In addition, urine-specific gravity was found to have a significant negative correlation with UAlb/UCr (r = -0.33, p = 0.001). The results of this study suggest that in the adolescent, recumbent albumin excretion is higher in females and that ambulation increases glomerular permeability. Exercise does not appear to induce any additional alteration in glomerular permeability, although the effects of exercise are likely-related to the type and severity of physical activity. Renal tubular function is unaltered by either ambulation or exercise.(ABSTRACT TRUNCATED AT 250 WORDS)

Characterization of proteinuria using random urine samples.

The urinary albumin to creatinine ratio (Ualb/Ucr) was compared with quantitative albumin excretion in normal subjects and patients with renal disease. Urinary albumin excretion varied from 3.4 to 4,699 mg/m2/day and Ualb/cr from 5.3 to 6,600 micrograms/mg; the correlation was highly significant (r = .979, p less than .001, n = 20). To characterize normal proteinuria using random urine samples, specimens were obtained from 279 healthy subjects (2 months - 62 years). Total protein, albumin and lysozyme were measured in all samples. Glomerular permeability and tubular function were assessed using the random Ualb/Ucr, the urinary albumin to protein ratio (Ualb/Up) and the urinary lysozyme to albumin ratio (Uly/Ualb). Ualb/Ucr was higher in children less than four years although no age-related differences were noted for Ualb/Up or Uly/Ualb. Furthermore, no differences were seen between males and females and normal reference values are provided. The results of this study support the use of Ualb/Ucr as an estimate of urinary albumin excretion and characterizes normal proteinuria using markers of both glomerular and tubular function.

Assessment of urinary protein excretion in the adolescent: effect of body position and exercise.

We examined the effects of body position and exercise on the random urinary protein/creatinine ratio (Up/Ucr) in healthy adolescents, to provide reference data to be used in a simplified evaluation of proteinuria. Random urine samples were obtained during recumbency and after both ambulation and exercise in 116 subjects. The Up/Ucr was significantly (P less than 0.0001) higher with increasing levels of activity, and was widely variable, especially during the upright and postexercise periods. No sex-related differences in Up/Ucr were noted, except during recumbency, when values were significantly (P less than 0.001) higher in females. The urinary dipstick was found to be less sensitive as a tool to define abnormal degrees of recumbent proteinuria. We conclude that body position and exercise have significant effects on protein excretion, and suggest that the Up/Ucr in recumbent and upright urine samples will be useful in the evaluation of proteinuria.

The effect of hydropenia and oral water loading on renal lysozyme handling and N-acetyl-beta-D-glucosaminidase excretion in man.

To substantiate the effects of urine flow rate on renal lysozyme handling and N-acetyl-beta-D-glucosaminidase (NAG) excretion, experiments were performed in normal human subjects. Urine flow rate was varied by overnight fluid deprivation and progressive diuresis induced by oral water loading. Lysozyme measurements were made using an improved turbidimetric method and NAG determinations using a modified fluorometric assay utilising individual recovery techniques. Fractional lysozyme clearance and lysozyme excretion demonstrated a nearly linear relationship with urine flow rate (r = 0.78, r = 0.80, P less than 0.0005), and both were elevated significantly in samples obtained during diuresis. NAG excretion, however, demonstrated a significant but weak correlation (r = 0.47, P less than 0.005) with fractional urine flow rate. A significant (P less than 0.05) difference in NAG activity occurred only during the period of hydropenia, when a decrease in excretion was observed. These findings suggest that the effect of diuresis on lysozyme excretion should be considered in studies utilising this enzyme as a marker of renal injury.

The effect of unilateral nephrectomy on the nephrotoxicity of mercuric chloride in the rat.

Unilateral nephrectomy (UNX) induces a dramatic change in single-kidney structure and function. Therefore, the effects of nephrotoxins may be altered. To evaluate this possibility, mercuric chloride (2 mg/kg, sc) was given to male, Sprague-Dawley rats 2 days following either UNX or sham surgery. Nonoliguric acute renal failure developed and was qualitatively similar in both groups. Glomerular filtration rate (GFR) reached a nadir on Day 2 and was reduced to a greater extent in the UNX group. Furthermore, recovery of GFR was slower and occurred to a lesser extent by Day 10 in the animals subjected to UNX. Evidence of significant tubular dysfunction was present during the acute phase in both groups, as reflected by changes in the fractional excretion of sodium or lysozyme. Persistent tubular dysfunction was noted on Day 10 in both the sham and UNX groups, but the degree of dysfunction was greater in the UNX animals. The in vitro uptake of organic ions by renal cortical slices was reduced 24 hr following the injection of mercuric chloride although no difference was seen between the experimental groups. Mercury content within renal cortex was not increased in the UNX group at 1 or 3 hr but was higher 24 hr postinjection. Total urinary mercury excretion during the first day was not altered by UNX although single-kidney excretion was increased dramatically. These studies suggest that rats are more susceptible to mercuric chloride-induced nephrotoxicity 2 days following UNX. Although the mechanism(s) of this enhanced injury remains unclear, it does not appear to be completely related to an increase in renal cortical mercury content.

The effects of age and urine concentration on lysozyme and N-acetyl-beta-D-glucosaminidase (NAG) content in urine.

Random urine samples were obtained to evaluate potential age- or urine concentration-related differences in lysozyme or NAG content. The concentration and excretion of both enzymes was widely variable although no age-related differences were seen. Urine concentration, however, was an important variable as NAG concentration (per mL urine) and lysozyme excretion (per mumol creatinine) were significantly elevated and reduced, respectively, in samples with a higher specific gravity. The correlation coefficient between urine specific gravity and both parameters was significant. Lysozyme excretion is elevated in subjects undergoing a modest diuresis although NAG excretion is unaffected. These data may prove to be useful in the evaluation of renal dysfunction.