Replica cytology in cancer of the larynx: an evaluation of a replica method in the diagnosis of laryngeal malignancy

Dopamine, noradrenaline and adrenaline were measured in plasma and in urine, using double-isotope derivative techniques, in 46 normal subjects and in 17 tetraplegic patients with physiologically complete cervical spinal cord transections above the sympathetic outflow. Dopamine was present in plasma in normal subjects in a concentration of 0.33 mug/l +/- 0.06 (SEM). Twenty-four hour urinary excretion of dopamine averaged 248 mug +/- 22. There was a significant correlation between the 24 h urinary excretion of dopamine and of noradrenaline. In the normal subjects plasma dopamine and the urinary excretion of dopamine did not change during three days of fasting while urinary excretion of adrenaline increased twofold. In the normal subjects exercise significantly increased plasma dopamine from 0.25 mug/l to 0.43 mug/l, but significantly decreased the urinary excretion of dopamine. Exercise significantly increased the excretion of noradrenaline. In the tetraplegic patients the plasma dopamine concentration and the urinary excretion of dopamine were lower but not significantly different from the corresponding values in the normal subjects. Plasma noradrenaline and the urinary excretion of noradrenaline and adrenaline were significantly lower in the tetraplegic patients. It is concluded that dopamine is present in human plasma in concentrations similar to that of noradrenaline. Free dopamine in plasma and urine of normal subjects is not dependent on foot intake. Urinary dopamine may be derived from circulating dopamine. Urinary dopamine does not necessarily appear to reflect changes in plasma dopamine. The relationship between plasma dopamine and changes in adrenergic nervous activity deserves further investigation.     

Urinary excretion of apo(a) fragments in NIDDM patients

Lp(a), one of the most atherogenic lipoproteins, is believed to contribute significantly to vascular diseases in non-insulin-dependent diabetic (NIDDM) patients. Contradictive data have been published on these patients concerning plasma concentrations of Lp(a) and their relation to renal function. Since apo(a) fragments appear in urine, we measured urinary apo(a) in 134 NIDDM patients and 100 matched controls and related urinary apo(a) concentrations to plasma Lp(a) levels and kidney function. Plasma Lp(a) values were found to be significantly higher in NIDDM patients. NIDDM patients also secreted significantly more apo(a) into their urine as compared to control subjects. There was no correlation between creatinine clearance or albumin excretion and urinary apo(a) concentrations. Patients with macroalbuminuria exhibited a twofold higher apparent fractional excretion of apo(a) in comparison to patients with normal renal function. Urinary apo(a) values in both patients and control subjects were highly correlated to plasma Lp(a), yet no correlation was found with HbA1c or serum lipoproteins. It is concluded that urinary apo(a) excretion is correlated to plasma Lp(a) levels but not to creatinine clearance in patients suffering from NIDDM.     

Effects of citrate on the different phases of calcium oxalate crystallization

Urinary citrate appears to be an important factor in the crystallization process of calcium oxalate and calcium phosphate. The urinary excretion of citrate was found to be significantly lower in patients with calcium oxalate stone disease as compared with normal subjects, and about 30 per cent of the calcium stone formers can be considered as hypocitraturic. The lowest excretion of citrate was recorded in urine collected during the night. Citrate has significant effects on supersaturation with respect to both calcium oxalate and calcium phosphate, it also inhibits the growth of these crystals. In addition, citrate appears to be capable of inhibiting the aggregation of crystals composed of calcium oxalate, brushite, and hydroxyapatite. The heterogenous growth of calcium oxalate on calcium phosphate is also counteracted by citrate. As a consequence of the crucial role of citrate in these processes, stone prevention with alkaline citrate has become an attractive form of treatment in patients with recurrent stone formation. Single evening dose administration of sodium potassium citrate resulted in an of sodium potassium citrate resulted in an increased excretion of citrate, reduced levels of the calcium/citrate ratio as well as supersaturation with respect to calcium oxalate and a decreased rate of stone formation. However, conflicting results of stone preventive treatment with alkaline citrate have been reported by different groups, and long-term follow-up of patients treated in a randomized way is necessary to definitely assess the efficacy of alkaline citrate.     

Cytokine and cytotoxic pathways of NK cell rejection of class I-deficient bone marrow grafts: influence of mouse colony environment

OBJECTIVE: To identify biochemical and dietary factors which may play a role in the low incidence of stone formation in the black South African population. SUBJECTS AND METHODS: The study included 31 semiurbanized black and 29 urbanized white subjects. The protocol and modern laboratory techniques used to assess recurrent stone formers were followed. Urinary sodium, potassium, creatinine, calcium, phosphate and urate levels were measured, and urinary citrate, oxalate and cystine assessed. RESULTS: Black subjects ate a diet significantly higher in sodium (P < 0.04); there was no difference in serum levels but urinary sodium was significantly higher (P < 0.001) in black than in white subjects. Urinary potassium, calcium, citrate, phosphate and cystine were all significantly lower in black than in white subjects (P < 0.001 for the first four and P < 0.03 for cystine). CONCLUSION: Certain intrinsic factors in South African black subjects may account for their lower frequency of stone formation than in white subjects. Of these, the very low urinary calcium, decreased urinary cystine and different interactions between sodium and calcium/cystine are probably important.     

Sodium excretion in children with lithogenic disorders

INTRODUCTION: The causes of nephrolithisis are multifactorial and have not yet been enough investigated [1]. Hypercalciuria is the most common cause of metabolic nephrolithiasis [2-4]. Close relationship between urinary calcium and urinary sodium has been a subject of reported observations in the past, showing that high urinary sodium is associated with high urinary calcium [5-7]. Hyperoxaluria, hyperuricosuria and cystinuria are also metabolic disorders that can lead to nephrolithiasis. Recent studies have indicated that urinary elimination of cystine is influenced by urinary sodium excretion. Based on these observations it has been hypothesised that patients with high urinary sodium excretion are at high risk of urinary stone disease. The purpose of the study was to investigate sodium excretion in a 24-hour urine and first morning urine collected from children with lithogenic metabolic abnormalities (hypercalciuria, hyperoxaluria, hyperuricosuria, cystinuria), both with nephrolithiasis and without it, in order to determine its significance in urinary calculi formation. PATIENTS AND METHODS: Urinary sodium excretion was investigated in 2 groups of children: patients with lithogenic metabolic abnormalities, but without urinary stone disease (L group) and patients with nephrolithiasis (C group). Both groups were divided into 2 subgroups: patients with hypercalciuria and without it. There were 22 patients in group L (mean age 11.97 +/- 4.13 years), of whom 17 formed a hypercalciuric subgroup and 5 formed a non-hypercalciuric subgroup (3 patients with hyperuricosuria and 2 patients with hyperoxaluria). Group C consisted of 21 patients with nephrolithiasis (mean age 12.67 +/- 3.44 years), of whom 6 formed a hypercalciuric subgroup and 15 formed a non-hypercalciuric group (2 patients with cystinuria and 13 patients without lithogenic metabolic abnormalities). Control group consisted of 42 healthy age-matched children. All subjects had a normal renal function. A detailed history and clinical examination were done, and ultrasonography was performed in all patients. A 24-hour urine, first morning urine and serum specimen were analysed for sodium, potassium, calcium, uric acid, urea and creatinine. Fractional excretion of sodium, as well as urinary sodium to creatinin ratio and urinary sodium to potassium ratio, were calculated from the findings. Sodium and potassium levels were determined by flame photometry, calcium was measured by atomic absorption technique (Beckman Atomic Spectrophotometer, Synchron CX-5 model, USA), uric acid by carbonate method and creatinine by Jaffe technique. Cystine and dibasic amino acids were quantified by ion chromatography. Urinary oxalate excretion was determined by enzyme spectrophotometry. Hypercalciuria was defined by 24-hour calcium excretion greater than 3.5 mg/kg per day and/or calcium to creatinine ratio greater than 0.20 [8]. Uric acid excretion was expressed as uric acid excretion factored for glomerular filtration, according to Stapleton's and Nash's formula [9]. Normal values were lower than 0.57 mg/dl of glomerular filtration rate in 24-hour samples. Mean values were statistically analyzed by Pearson's linear correlation and analysis of variance (ANOVA). RESULTS: Urinary sodium concentration values including urinary sodium to potassium ratios, are shown in Table 1. We found that urinary sodium excretion was significantly increased in patients of both L and C groups when compared with controls (p < 0.05). Further analysis of the subgroups showed that urinary sodium excretion was significantly higher only in patients with hypercalciuria of both L and C groups in comparison to controls (p < 0.05) (Table 2). A significant positive correlation was found between 24-hour urinary sodium to creatinine ratio and urinary calcium to creatinine ratio (r = 0.31; p < 0.001) (Graph 1), as well as between urinary sodium to potassium ratio in 24-hour and first morning urine (r = 0.69; p < 0.001) (Graph 2). (A     

Urinary excretion of extracellular matrix proteins in insulin dependent diabetes mellitus

The purpose of the study was to assess urinary excretion of extracellular matrix proteins and proteolytic enzymes in 12 subjects with IDDM with albuminuria, 12 subjects with IDDM without microalbuminuria and 10 normal healthy subjects. Urinary excretion of FN was significantly higher in subjects with IDDM and albuminuria as compared to patients with IDDM without microalbuminuria and healthy subjects (223.6 +/- 143.2 vs. 103.2 +/- 59.7 vs. 58.3 +/- 12.0 ng/mg creatinine, p < 0.01). Urinary level of type IV collagen was significantly elevated in subjects with IDDM and albuminuria as compared to IDDM without microalbuminuria and healthy subjects of cathepsin B was significantly higher in diabetic patients with albuminuria as compared to patients without microalbuminuria and healthy subjects (0.82 +/- 0.53 vs. 0.25 +/- 0.17 vs. 0.22 +/- 0.05 mlU/mg creatinine, p < 0.01). Urinary activity of plasmin was significantly elevated in diabetic patients with albuminuria as compared to subjects without microalbuminuria and healthy control (0.477 +/- 0.37 vs. 0.194 +/- 0.09 vs. 0.21 +/- 0.02 mlU/mg creatinine, p < 0.01). Our data indicate that increase in the urinary excretion of extracellular matrix proteins may be the useful tool for monitoring glomerular injury.     

Endoscopic endonasal dacryocystorhinostomy: indications, technique and results

To understand the changes of urinary endothelin-1 (ET-1) concentrations in acute renal failure (ARF) and to investigate the origin of human urinary ET-1, we studied urinary ET-1 excretion in 70 normal children and 12 children with ARF caused by tubular dysfunction. Urinary ET-1 excretion was expressed as a ratio of urinary ET-1 to urinary creatinine (ET-1/Cr). Among healthy children, the highest urinary ET-1/Cr values were found during infancy. In patients with ARF, there was a positive correlation between urinary ET-1/Cr values and daily total urinary ET-1 (r = 0.42, n = 26, p < 0.05). Plasma ET-1 concentrations were elevated in children with ARF during the period of peak serum creatinine concentration. During the course of ARF, the lowest urinary ET-1/Cr value occurred during the period of peak serum creatinine, whereas the plasma ET-1 concentration declined after the peak. These results provide insight into the developmental changes of urinary ET-1 values in normal children, and illustrate the pattern of changes in plasma and urinary ET-1 concentrations during the course of ARF in children. The results suggest that renal production, rather than clearance from the circulation by glomerular filtration, may be the source of urinary ET-1.     

Trypanosoma cruzi meningoencephalitis in AIDS mimicking cerebral metastases: case report

BACKGROUND: It has been suggested that citrate salts might enhance aluminum (Al) absorption from a normal diet, posing a threat of Al toxicity even in subjects with normal renal function. We have recently reported that in normal subjects and patients with moderate renal failure, short-term treatment with tricalcium dicitrate (Ca3Cit2) does not significantly change urinary and serum Al levels. However, we have not assessed total body Al stores in patients on long-term citrate treatment. OBJECTIVE: The objective of this study was to ascertain body content of Al non-invasively using the increment in serum and urinary Al following the intravenous administration of deferoxamine (DFO) in patients with kidney stones and osteoporotic women undergoing long-term treatment with potassium citrate (K3Cit) or Ca3Cit2, respectively. METHODS: Ten patients with calcium nephrolithiasis and five with osteoporosis who were maintained on potassium citrate (40 mEq/day or more) or calcium citrate 800 mg calcium/day (40 mEq citrate) for 2 to 8 years, respectively, and 16 normal volunteers without a history of regular aluminum-containing antacid use participated in the study. All participants completed the 8 days of study, during which they were maintained on their regular home diet. Urinary Al excretion was measured during a two-day baseline before (Days 5, 6) and for 1 day (Day 7) immediately following a single intravenous dose of DFO (40 mg/kg). Blood for Al was obtained before DFO administration, and at 2, 5 and 24 hours following the start of the infusion. RESULTS: The median 24-hour urinary Al excretion (microgram/day) at baseline versus post-DFO value was 15.9 vs. 44.4 in the normal subjects and 13.3 vs. 35.7 in the patients. These values were all within normal limits and did not change significantly following DFO infusion (p = 0.003 and p = 0.0001, respectively). The median change of 17.1 micrograms/day in urinary Al in the normal subjects was not significantly different from the 18.7 micrograms/day change measured in the patient group (p = 0.30). Similarly, no change in the mean serum Al was detected at any time following the DFO infusion, either in the patient or control group (patients 4.1 to 4.3 ng/ml, controls 7.4 to 4.6 ng/ml). CONCLUSION: The results suggest that abnormal total body retention of Al does not occur during long-term citrate treatment in patients with functioning kidneys.     

Evaluation of the FREEDOM O2, DC Concentrator, a portable oxygen concentrator capable of operating under car battery power

Many sensitive biomarkers are available for the surveillance of the early health effects of chemicals on humans. This study was conducted to evaluate the usefulness of glycosaminoglycans (GAG) as biomarkers of early kidney effects in exposure to 2-alkoxyethanols and their acetates. GAG were compared with effects on the urinary beta-N-acetylglycosaminidase activity (NAG). According to the results of the present study, the excretion rate of GAG was higher among women than men. On the other hand, the excretion rate of GAG was lower among exposed subjects than among the controls, and the level was decreased at the tested levels of exposure. The NAG activity was higher in most of the exposed groups than in the controls. The data indicated that an appropriate urinary limit value for ethoxyacetic acid was 30 mmol/mol creatinine in postshift samples and that this value corresponded to an 8-hour exposure level of 2 cm3/m3 2-ethoxyethylacetate. Urinary butoxyacetic acid excretion of 60 mmol/mol creatinine corresponded to the inhalation exposure level of 5 cm3/m3 2-butoxyethanol and its acetate in postshift samples.     

Metabolic abnormalities in patients with caliceal diverticular calculi

PURPOSE: We determined the incidence and spectrum of metabolic abnormalities in patients with caliceal diverticular calculi. MATERIALS AND METHODS: Five men and 9 women with caliceal diverticular calculi underwent metabolic evaluation, including determination of serum electrolytes, calcium, phosphate and uric acid, and 24-hour urinary volume, creatinine, calcium, oxalate, uric acid and citrate. RESULTS: Of the 14 patients 7 (50%) had urinary excretion abnormalities promoting stone formation, including hypercalciuria in 3, hyperoxaluria in 1, hypercalciuria combined with hyperuricosuria in 1 and hyperoxaluria combined with hyperuricosuria in 2. Two patients had a history of gout while another had radiographic evidence of medullary sponge kidney. Of the patients 9 (64.3%) had a history of synchronous or metachronous calculi distant from the involved caliceal diverticular stone and 5 (55.6%) of these 9 had definable metabolic disorders. However, there was no statistically significant difference in urinary excretion values between patients with or without a history of additional extra diverticular stones. CONCLUSIONS: Urinary stasis alone does not explain stone formation in a significant number of patients with caliceal diverticular calculi. Rather, the local physiological environment of the urine likely has a predisposing role and evaluation for metabolic abnormalities should be considered. In some patients cure may be effected by treating the stone and any associated metabolic disorders rather than the diverticulum.     

Enhanced thromboxane biosynthesis in patients with chronic obstructive pulmonary disease. The Chronic Obstructive Bronchitis and Haemostasis Study Group

Thrombotic complications of pulmonary circulation occur in patients with chronic obstructive pulmonary disease (COPD). In the present study, we sought to evaluate in vivo platelet activation through the measurement of 11/dehydro-thromboxane (Tx) B2 TxA2 major metabolite in the urine, in 29 patients with COPD, compared with 29 sex- and age-matched healthy subjects. The urinary excretion of 11-dehydro-TxB2 was significantly higher in patients with COPD than in control subjects: median (range), 753 (277-4,409) and 275 (129-612) pg/mg creatinine, respectively; p < 0.0001). Moreover, 11-dehydro-TxB2 excretion was inversely related with arterial oxygen tension (rho = -0.46; p = 0.0145). In five of the 29 patients a short-term therapeutic course with oxygen supplementation induced a significant decrease of urinary 11-dehydro-TxB2 excretion: median range, 941 (452-2,640) to 445 (166-1,560) pg/mg creatinine. Moreover, selective inhibition of platelet cyclooxygenase activity by low-dose aspirin was associated with more than 90% inhibition of thromboxane metabolite excretion, demonstrating its being of platelet origin. Plasma levels of prothrombin fragment F1 + 2 were higher in patients than in control subjects (2.6 +/- 1.5 versus 0.9 +/- 0.4 nM, p = 0.0001). No relation between 11-dehydro-TxB2 excretion and plasma F1 + 2 levels was found. We conclude that platelet TxA2 biosynthesis is enhanced in patients with COPD and may be influenced by arterial oxygen tension changes.     

External beam irradiation inhibits neointimal hyperplasia after injury-induced arterial smooth muscle cell proliferation

BACKGROUND: The high social-economic cost of nephrolithiasis wholly justifies the attempts to understand its mechanism and avoid recurrences. The influence of dietary habits and urinary risk factors has been evaluated, but the results were discrepant, probably because of differences in the methodologies used to compare patients and controls. METHODS: The aim was to assess dietary and urinary risk factors for urinary stones by comparison between 108 calcium stone formers (SF) and 210 healthy subjects (HS). All subjects were recruited during the same 1 year period. Personal characteristics, dietary habits (evaluated through a food frequency questionnaire) and urinary biochemical parameters were collected. The high predominance of men in the SF group led us to focus on the 79 SF and the 96 HS men. RESULTS: A familial history of stones was reported more frequently in SF than in HS, 42.9% vs 17.6%, P<0.005. Body weight was higher in SF, 76.8+/-12.2 kg vs 72.8+/-9.6 kg, P=0.02; and calcium intake was lower in SF, 794.8+/-294.1 mg vs 943.6+/-345.4 mg, P<0.01. For urinary parameters, calcium and oxalate output were significantly higher in SF. Urinary urea, as a reflection of daily protein intake, and uric acid were also higher in SF. Urinary citrate excretion related to body weight was lower in SF. Calciuria was significantly correlated with urinary urea in both SF and HS, but the correlation was stronger for SF. Calciuria correlated significantly with natriuria only in HS. CONCLUSIONS: The main differences between SF and HS were that SF had a family history of stones, a higher body weight, a lower daily intake of calcium, and a higher urinary output of calcium and oxalate. These results underline the combined role of genetic and nutritional factors in the pathogenesis of urinary stone formation.     

Discontinuation of some depression, migraine, and anxiety drugs can cause reactions

BACKGROUND: Measuring urinary beta 2 microglobin (B2M) and N-acetyl-beta-D-glucosaminidase (NAG) excretion is widely used as a valuable clinical tool in assessing renal tubular lesions. However, few data are available on normal values for urinary excretion of B2M and NAG in infancy. METHODS: Urinary B2M and NAG were measured in healthy infants. The logarithmic values of urinary B2M, NAG, B2M/creatinine ratio and NAG/creatinine ratio were distributed almost normally and reference ranges were calculated from the logarithms of the observed values. RESULTS: The levels of urinary B2M and B2M/creatinine ratio were highest in the 1-month-old group, followed by a decrease during the first 3 months. Urinary B2M excretions in the 3-month-old group showed rather lower levels than those of the 12-month-old and 36-month-old groups. Although urinary NAG excretions were almost constant throughout all groups, urinary NAG/creatinine ratio decreased gradually until 3 years of age. CONCLUSIONS: We suggest that these reference ranges are of importance in evaluating tubular damage due to a variety of renal diseases in infancy.     

Two triterpene saponins from Arenaria filicaulis

Uropontin is the urinary form of osteopontin, an aspartic acid-rich phosphorylated glycoprotein. Uropontin has been previously shown to be a potent inhibitor of the nucleation, growth and aggregation of calcium oxalate crystals and the binding of these crystals to renal epithelial cells. Quantitative data defining the excretion of this protein are necessary to determine its role in urinary stone formation. In the present studies, we determined uropontin excretion rates of normal humans. Urine samples were obtained under conditions of known dietary intake from young adult human volunteers with no history, radiographic or laboratory evidence of renal disease. Urinary concentrations of uropontin were measured by a sensitive ELISA employing an affinity purified polyclonal antiserum to uropontin. Thirteen normal subjects ingested a constant diet providing 1 gram of calcium, 1 gram of phosphorus, 150 mEq of sodium and 1 gram of protein per kilogram of body wt per day during an eight day study period. The relationship of urinary volume to uropontin excretion was assessed by varying fluid intake on the last four days of the study to change the mean urine volume/24 hr by > 500 ml. Urine collected in six hour aliquots for eight days was analyzed for uropontin by ELISA, and for calcium, and creatinine. Daily uropontin excretion of 13 individual subjects was 3805 +/- 1805 micrograms/24 hr (mean +/- 1 SD). The mean urinary levels (1.9 micrograms/ml) detected in the present study are sufficient for inhibition of crystallization; our previous studies have demonstrated that the nucleation, growth and aggregation of calcium oxalate crystals and their binding to renal cells in vitro are inhibited by this concentration of purified uropontin. In contrast to the regular pattern of diurnal variation of calcium excretion seen in most subjects, uropontin excretion showed no regularity of diurnal variation and was not directly related to either calcium or creatinine excretion or changes in urinary volume. However, uropontin concentration varied inversely with urine volume (P < or = 0.001), so that the highest uropontin concentrations occurred when urine volume was the lowest. We conclude that the physiologic characteristic of an inverse relationship of uropontin concentration to urine volume favors protection from urinary crystallization of calcium oxalate by uropontin. Our quantitative definition of urinary uropontin excretion of normal adults provides the basis for the evaluation of uropontin excretion by individuals who have formed urinary stones.     

Lack of effect of methenamine in suppression of, or prophylaxis against, chronic urinary infection

Methenamine is frequently prescribed for patients who have chronic urinary infection to suppress bacterial growth during active infection or to prevent recurrence once an infection has been brought under control. We have examined the effect of methenamine mandelate and ascorbic acid on bacteriuria in para- and quadriplegics from a spinal cord unit. Patients with indwelling urinary catheters and those on a program of intermittent catheterization were included. No suppressive or prophylactic effect of this regimen was observed in any of our patients. Methenamine does not appear to be an effective antimicrobial agent in subjects who have an indwelling urinary catheter or in patients with spinal cord injury who are on intermittent catheterization. Since there appears to be reason to question the efficacy of methenamine in situations in which it is usually prescribed, evidence should be sought for a therapeutic effect in other cases. If no benefit is observed, the drug should not be used.     

Combination of enalapril and low-dose thiazide reduces normoalbuminuria in essential hypertension

OBJECTIVE: To examine the effect of the combination of enalapril with a very low dose of hydrochlorothiazide versus atenolol on urinary albumin excretion in normoalbuminuric patients with mild to moderate essential hypertension. A secondary objective was to compare the effects of the two regimens in patients with different levels of albuminuria. DESIGN: A 12 weeks, randomized, double-blind, double-dummy, multicenter, comparative study with two parallel groups. SETTING: General practices in Denmark and Finland. PATIENTS: The subjects comprised 174 patients with mild to moderate essential hypertension, normal serum creatinine and no proteinuria. INTERVENTIONS: Enalapril/hydrochlorothiazide (20/6 mg) daily or atenolol (50 mg) daily. MAIN OUTCOME MEASURES: Urinary albumin: creatinine ratio and blood pressure. RESULTS: At baseline, normoalbuminuria was found in 74 and 85 patients in the enalapril/hydrochlorothiazide and atenolol groups, respectively. Blood pressure was reduced similarly by both treatments. The ratio of urinary albumin to creatinine in normoalbuminuric patients was significantly reduced during treatment with enalapril/hydrochlorothiazide at 20/6 mg (from geometic mean x/divided by antilog SD of 0.53 x/divided by 1.77 to 0.47 x/divided by 1.58 mg/mmol, P=0.02) but was unchanged during atenolol treatment (0.55 x/divided by 1.74 and 0.58 x/divided by 1.87 mg/mmol). The difference between the two treatments was statistically significant (P=0.03) and was predominantly achieved through a reduction of albuminuria in the upper-normal range during enalapril/hydrochlorothiazide treatment. CONCLUSIONS: Therapy with enalapril/hydrochlorothiazide at 20/6 mg and atenolol at 50 mg once daily reduced blood pressure similarly in patients with essential hypertension. Suppression of urinary albumin excretion within the normoalbuminuric range was observed during treatment with enalapril/hydrochlorothiazide at 20/6 mg.     

Increased 24-hour endothelin-1 urinary excretion in patients with chronic obstructive pulmonary disease

Abnormalities in endothelin-1 (ET-1) pulmonary metabolism have been reported in patients with pulmonary hypertension, asthma and chronic obstructive pulmonary disease (COPD). In this study we have evaluated the 24-hour urinary excretion of ET-1 in COPD patients both during acute exacerbation and stable phase of the disease. ET-1 plasma and urinary levels were measured in 13 COPD patients on admission to the hospital for an acute exacerbation and at the recovery period. Ten healthy volunteers were also studied. Determination of plasma and 24-Hour urinary ET-1 levels were carried out with a radioimmunoassay test. Plasma ET-1 levels in COPD patients were similar during exacerbation and recovery and were not significantly different from those in the healthy subjects. 24-hour urinary excretion of ET-1 was increased in COPD patients during acute exacerbation; it decreased during recovery, but remained elevated when compared to normal subjects. A negative correlation was found between arterial oxygen pressure and ET-1 excretion; no correlation was found between plasma and urinary ET-1 values. In conclusion, COPD patients excrete higher amounts of ET-1 compared to healthy subjects. Urinary ET-1 values are further increased during acute exacerbation of the disease.     

Exaggerated urinary excretion of aquaporin-2 in the pathological state of impaired water excretion dependent upon arginine vasopressin

The present study was undertaken to determine whether urinary excretion of aquaporin-2 (UAQP-2) is of value to diagnose the pathological state of water retention and hyponatremia. UAQP-2 under ad libitum water drinking was 429 fmol/mg creatinine in the patients with water retention, a value significantly greater than that of 153 fmol/mg creatinine in the normal subjects. An acute oral water load test (20 mL/kg BW) was performed in 7 normal subjects (22-25 yr old) and 10 patients with water retention and hyponatremia (55-75 yr old). The percent excretion of the water load was only 30% in the patient group compared with 70% in the control group (P < 0.01). In the control group, minimal urinary osmolality was as low as 131 mosmol/kg H2O, which was responsible for the decrease in plasma arginine vasopressin (AVP) levels after the reduction in plasma osmolality. In the patient group, minimal urinary osmolality was 320 mosmol/kg H2O, and free water clearance remained below 0.6 mL/min after the water load. This impaired water excretion was consistent with the nonsuppressible levels of plasma AVP despite hypoosmolality. The nadir of UAQP-2 was obtained at 60-90 min. The minimal UAQP-2 was reduced to 284 fmol/mg creatinine, a value significantly greater than that of 76 fmol/mg creatinine in the control group. Similar results were obtained in the 6 patients with hypopituitarism, who had impaired water excretion and marked hyponatremia. Water excretion was totally normalized after the replacement of hydrocortisone (excretion of water load, 31% vs. 102%; P < 0.01). Hydrocortisone replacement also significantly reduced the minimal UAQP-2 from 225 to 49 fmol/mg creatinine after the acute oral water load, a value comparable to that in the control subjects. These results indicate that UAQP-2 is a potent marker to diagnose the pathological state of impaired water excretion and hyponatremia, dependent upon AVP, in patients with water retention and hypopituitarism.     

Recurrent bilateral renal calculi in a tetraplegic patient

An 18-year-old male developed C-5 complete tetraplegia following a motor-cycle accident in May 1975. The neuropathic bladder was managed by an indwelling urethral catheter. He developed recurrent episodes of urinary infection with Proteus species. In September 1975, an X-ray of the abdomen revealed small calculi in both the kidneys. In July 1976, he underwent transurethral resection of the bladder neck and division of the external urethral sphincter; subsequently, he was put on a penile sheath drainage. He continued to suffer from repeated episodes of urinary tract infection with Proteus, Providencia, and Pseudomonas species, and he was treated with antibiotics. In 1980, intravenous urography (IVU) showed two large stones in the left kidney with marked caliectasis. The IVU performed in 1984 showed an increase in the size of the calculi in the left kidney which was grossly hydronephrotic. There were clusters of small calculi in the right kidney. The left renal calculi were treated by percutaneous lithotripsy in two sessions. In 1988, an X-ray of the abdomen revealed staghorn calculus in the right kidney and recurrence of stones in the left kidney. The staghorn calculus in the right kidney was treated by percutaneous nephrostolithotomy in two sessions. In 1991, he was admitted with acute urinary infection. IVU showed a stone in the pelviureteric junction with no excretion of contrast in the left kidney. Percutaneous nephrostomy drainage was established followed by left percutaneous nephrostolithotomy. In 1992, he was found to retain large amount of urine in the bladder; subsequently, his mother was taught to perform regular intermittent catheterisations. In 1995, he was admitted with acute urine infection. Abdominal X-ray revealed recurrence of large stones in both kidneys. With multiple sessions of Extracorporeal Shockwave Lithotripsy (ESWL), about 80% clearance was achieved on the left side. Right staghorn renal stone awaits treatment. This case shows that recurrent urinary infection in spinal cord injury patients is a predisposing factor for renal lithiasis. These patients require annual urological evaluation. Urinary tract calculi, if detected, should be dealt with promptly to prevent renal damage due to urinary obstruction and urosepsis. Renal calculi can be treated effectively and safely by ESWL in spinal cord injury patients, thus avoiding the need for an invasive procedure. It is essential to achieve low-pressure, adequate emptying of the urinary bladder in patients with spinal cord injury in order to prevent recurrent urinary infection and its sequelae. Social issues involved in the care of a tetraplegic patient play a vital role in the implementation of ideal medical treatment and need to be addressed promptly to avoid any compromise in the quality of medical care.     

Mechanisms of elevation of serum and urinary concentrations of soluble thrombomodulin in diabetic patients: possible application as a marker for vascular endothelial injury

Serum and urinary levels of soluble thrombomodulin (TM) were measured in 71 patients with non-insulin-dependent diabetes mellitus (NIDDM) and 132 age-matched control subjects to elucidate the mechanisms involved in increased TM levels. We compared the TM level with urinary albumin excretion (UAE), creatinine (Cr) clearance, and indices of renal tubular damage such as urinary beta2-microglobulin. Serum TM was significantly higher in diabetic patients versus control subjects (P < .001) regardless of whether the patients had diabetic nephropathy. Urinary TM levels were also higher in diabetic patients than in control subjects (P < .001). Serum TM in diabetic patients was correlated positively with serum Cr and UAE and inversely with the Cr clearance rate (P < .001, respectively). The urinary level of TM in diabetic patients was significantly correlated with 24-hour glucose excretion and the serum level of 1,5-anhydroglucitol (1,5-AG) (P < .001). However, no correlations were found between urinary TM levels and renal function in diabetic patients. There was also no correlation between serum and urinary levels of TM in the patients. These results suggest that although the serum TM level is influenced by an impairment of the renal clearance of TM, this parameter may be a useful marker for vascular endothelial injury in diabetic patients. On the other hand, since the elevated urinary level of TM in the patients paralleled their urinary excretion of glucose, urinary TM levels do not correlate with vascular endothelial injury in diabetic patients.