Cervical spinal cord lesions disrupt the rhythm in human melatonin excretion.

To determine whether spinal cord lesions disrupt the diurnal activity of the human pineal, urinary melatonin levels were measured over 24 hours (4 or 8-hourly intervals) in male patients with clinical evidence of cervical spinal cord transection. During the waking state, levels of melatonin in these subjects ranged from 3.2--13.5 ng/4 hours; during sleep and darkness, values ranged from 1.8--10.5 ng/4 hours. Levels of serum cortisol, aldosterone, and growth hormone showed rhythmic variations in these subjects. The absence of significant nocturnal melatonin increases distinguishes quadriplegic subjects from normal males and from one subject with a lesion of the lumbar spinal cord. These differences may be caused by "decentralization" of the pineal organ due to a lesion within the cervical spinal cord interrupting descending sympathetic fibers. If so, the human pineal, like that of other mammals, is regulated, at least in part, by activity within the central nervous system via sympathetic nervous connections.

Accuracy of formula-derived creatinine clearance in paraplegic subjects.

The usefulness of formula-derived creatinine clearance (CC) is not well established among the paraplegic population. We prospectively collected 24-hour-urines from paraplegic subjects, obtaining 81 collections from 42 patients over 27 months. After validation, 57 collections were used to obtain measured CC. CCs were also estimated using several formulae. Measured CC and estimated CC were then compared. In the case of the Cockroft-Gault formula, the overall correlation was excellent, with an r value of 0.88 and p = 0.0001. In our study 40, 70, and 93% of the estimated CCs were within 10, 20, and 33% of the measured CCs. These numbers are similar to the ones reported by Cockroft and Gault. Also, the data on measured creatinine clearance in paraplegics compared favorably with parallel data obtained from nonparaplegics (91 24-hour-urine collections, 65 validated). We conclude that the Cockroft-Gault formula (and other formulae) estimate creatinine clearance as accurately in the paraplegic population as they do in the nonparaplegic population.

18Fluoro-2-deoxyglucose (18FDG) PET scan of the brain in type IV 3-methylglutaconic aciduria: clinical and MRI correlations.

The clinical, 18fluorodeoxyglucose positron emission tomography (18FDG PET) and the magnetic resonance imaging (MRI) brain scan characteristics of four patients diagnosed to have 3-methylglutaconic aciduria were reviewed retrospectively. The disease has a characteristic clinical pattern. The initial presentations were developmental delay, hypotonia, and severe failure to thrive. Later, progressive encephalopathy with rigidity and quadriparesis were observed, followed by severe dystonia and choreoathetosis. Finally, the patients became severely demented and bedridden. The 18FDG PET scans showed progressive disease, explaining the neurological status. It could be classified into three stages. Stage I: absent 18FDG uptake in the heads of the caudate, mild decreased thalamic and cerebellar metabolism. Stage II: absent uptake in the anterior half and posterior quarter of the putamina, mild-moderate decreased uptake in the cerebral cortex more prominently in the parieto-temporal lobes. Progressive decreased thalamic and cerebellar uptake. Stage III: absent uptake in the putamina and severe decreased cortical uptake consistent with brain atrophy and further decrease uptake in the cerebellum. The presence of both structural and functional changes in the brain, demonstrated by the combined use of MRI and 18FDG PET scan, with good clinical correlation, make the two techniques complementary in the imaging evaluation of 3-methylglutaconic aciduria.

[Study of Urinary excretion of total, free, and non-dialysable conjugated hydroxyproline in paraplegics]. / Etude de l'excrétion urinaire de l'hydroxyproline totale libre et conjuguée non dialysable chez les sujets paraplégiques.

Eighteen paraplegics with or without neurogenic osteo-arthropathy (POAN) were evaluated for variations in their urinary excretion levels of total (T), and free (L) hydroxyproline and its non-dialysable (ND) and dialysable (D) peptide fractions. Increases in urinary hydroxyproline, moderate rises in free hydroxyproline and more substantial increases in dialysable and non-dialysable peptide fractions could be observed in these patients who all were affected with osteoporosis of disuse. Only variations in dialysable hydroxyproline could be used to differentiate between POAN + and POAN - patients. Of the various ratios which were analyzed (ND/T, L/ND, and D/ND), the D/ND ratio appears to be the most useful for diagnosis and monitoring of patients with POAN.

Increased urinary nitrosamine excretion in paraplegic patients.

An increased risk of bladder cancer is a recognized complication in spine-injured patients undergoing long-term urethral catheterization to preserve renal function. Aerobic cultures from 28 of 30 paraplegic patients showed complex bacterial flora containing nitrate-reducing organisms (Escherichia coli, Proteus and Klebsiella spp.). Urine samples from 29 paraplegic patients were also found to contain volatile nitrosamines. Mean N-nitrosamine excretion levels were 0.65 +/- 0.69 micrograms/day N-nitrosodimethylamine, 0.25 +/- 0.44 micrograms/day N-nitrosopiperidine and 0.39 +/- 0.50 micrograms/day N-nitrosopyrrolidine. A mean urinary nitrite excretion of 10.4 +/- 13.2 mg/day was found in 24 out of 30 paraplegic patients. In the sterile urine of control volunteers (medical staff attending the paraplegic patients and in-patients from other wards of the hospital), no urinary excretion of volatile N-nitrosamines and nitrite was found. The results clearly demonstrate a bacterially mediated in vivo formation of N-nitroso compounds in the urinary tracts of paraplegic patients which may be an important etiological risk factor for bladder cancer in this patient group.

A relationship between the composition of the urine and that of urinary tract calculi in spinal patients.

Chemical analysis was carried out on 42 urinary phosphatic calculi obtained from 14 spinal cord patients (two to seven stones per patient) and on small samples taken from different sites in a further 17 large phosphatic calculi. In 'early' stones (removed up to 30 months after onset of the cord lesion) the ratio of calcium to magnesium was significantly higher than in 'late' stones. Samples taken from sites nearer to the centres of calculi contained more calcium and less magnesium than did those from more peripheral sites. This change in the composition of urinary calculi with time corresponds with the known alterations in urinary calcium and magnesium following spinal cord injury.

Mineral metabolism in spinal cord injury.

In 10 paraplegic and 10 quadroplegic subjects, bone resorption was investigated by determining urinary excretion of hydroxyproline, calcium, and phosphorus. Measurements were performed weekly from the onset to 4 months after injury. During the first 7 weeks following injury, urinary excretion of calcium in paraplegic and quadriplegic subjects reached the highest level (380 +/- 180 mg/24hr). From 7 to 16 weeks after injury average urinary excretion of calcium (245 +/- 72 mg/24hr) remained significantly greater than that in controls (100 +/- 25 mg/24hr; p less than 0.05). Urinary hydroxyproline was elevated in paraplegic subjects (80 +/- 18 mg/24hr) for 8 weeks and in quadriplegic subjects (102 +/- 37 mg/24hr) for the entire 16 weeks following injury compared with that in controls (48 +/- 12 mg/24hr; p less than 0.05). Both paraplegic and quadriplegic subjects excreted more phosphorus (1.6 +/- 0.4 gm/24hr) than controls (0.85 +/- 0.2 gm/24hr; p less than 0.05) only during the first 2 weeks following spinal cord injury. During the acute phase of the injury (0-3 months), urinary excretion of calcium and magnesium was significantly higher (p less than 0.05) in subjects with complete compared with incomplete spinal cord lesions.

Haemodynamic, hormonal and urinary responses to postural change in tetraplegic and paraplegic man.

We have studied the haemodynamic, hormonal and urinary effects of postural change in 6 tetraplegic patients, 6 paraplegic patients and 6 normal subjects. Measurements of blood pressure and heart rate, plasma renin activity, plasma aldosterone, urine volume and electrolyte excretion were made for 60 minutes while sitting and 60 minutes while recumbent. In tetraplegics the blood pressure was lower when sitting and rose during recumbency, unlike paraplegics and normal subjects. Plasma renin activity and aldosterone were higher in tetraplegics when sitting compared to normal subjects and did not fall during recumbency. Urine output increased significantly after recumbency in tetraplegics, but not in paraplegics or normal subjects. Both urinary sodium and potassium excretion were lower in tetraplegics and higher in paraplegics compared to normal subjects when sitting. In paraplegics the fall in both sodium and potassium excretion did not appear to be related to change in posture. Our observations indicate that recumbency induces a diuresis in tetraplegics but not in paraplegics or in normal subjects. The diuresis in tetraplegics may be related to the accompanying haemodynamic and hormonal changes induced by recumbency.

Citrate excretion in spinal cord patients.

Low urinary citrate is a risk factor in calcium renal stone disease. The aim of this work was to identify the factors responsible for the low excretion of citrate frequently observed in patients with spinal cord lesions. Thirty male patients with spinal cord lesions were studied by blood and urine biochemistry. The most important single factor related to urinary citrate was urinary potassium. The presence or absence of urinary stone disease and variations in urinary volume also contributed significantly to variations in citrate excretion. Determination of plasma and urinary citrate, urinary sodium and bacteriological culture of urine permitted complete discrimination of the 7 stone formers from the other patients.

The effect of diclofenac sodium on urinary concentration of calcium, uric acid and glycosaminoglycans in traumatic paraplegics.

Non-steroidal anti-inflammatory drugs (NSAID) have been shown to decrease calcium excretion in the experimental animal, in human volunteers and in calcium stone formers. Paraplegics tend to be hypercalciuric during the first 2 years after their injury and this is said to be a predisposing factor for stone formation in these patients. The effect of the NSAID diclofenac sodium was studied in 12 traumatic paraplegics who had sustained their injury 1 to 6 months previously; 24-h urine samples collected before and 2 weeks and 4 weeks after oral diclofenac sodium 50 mg tds were analysed for calcium, uric acid, glycosaminoglycans (GAGs) and volume. There were no significant changes in urinary volume, uric acid and GAGs excretion. However, urinary calcium concentration and 24-h calcium excretion decreased significantly following 2 weeks' and 4 weeks' treatment with diclofenac sodium.

Urinary catheter blockage depends on urine pH, calcium and rate of flow.

Urinary catheters tend to block when biofilm from urease-producing organisms build up on the catheter surface. This is a locally-occurring process that influences and influenced by the composition of the urine. In this work we relate urine pH and calcium to catheter blockage and suggest how to reduce the rate of encrustation. Sixty patients with indwelling urinary catheters were studied, 26 of them being troubled by frequent blockage of their catheters, 34 of them not. A series of small urine samples were collected during a 24 h period. Urinary pH and calcium concentration were combined into discriminant functions designed to separate Blockers from Non-blockers and achieved a 95% correct classification. The results indicate that a high and uniform rate of fluid intake is mandatory for the patient with a tendency for catheter blockage. Excessive total fluid intake may be avoided by attention to uniformity. Other avoidable risk factors include: excess dietary calcium from certain protein supplements and antacids; excess dietary magnesium from certain beverages and antacids; alkali from effervescent tablets; excess dietary citrate from some fruit juices and cordials; intermittent dehydration from alcohol ingestion. Less tractable risk factors include infection of the urinary tract with urease-positive organisms, hypercalciuria of immobilisation, hyperhydrosis and postural oliguria. The processes involved in catheter encrustation and blockage provide a model for the formation of calculi in spinal cord injured patients. Therefore the above considerations may also be relevant to the management of stone disease in paraplegic and tetraplegic patients.

Biochemical studies in paraplegic renal stone patients. 2. Urinary excretion of citrate, inorganic pyrophosphate, silicate and urate.

The urinary excretions of citrate, inorganic orthophosphate and pyrophosphate, silicate and urate were measured in 17 paraplegic patients with renal calculous disease associated with urinary infection, in 16 paraplegics with no history of urinary calculus and in 14 healthy control subjects. The paraplegics excreted less citrate, orthophosphate and pyrophosphate than the control subjects. The stone-formers excreted more urate than the paraplegics without stone disease, but less than the control subjects. There were significant positive correlations between urinary orthophosphate and pyrophosphate and between urinary silicate and 24-h urine volume. The possible roles of increased urate and diminished excretion of citrate and inorganic pyrophosphate in the aetiology of renal calculosis in paraplegic patients deserve further investigation.

Clinical and experimental studies with oral aluminum hydroxide.

Experimental studies in 10 paraplegic patients showed highly significant reduction in urinary saturation associated with the oral administration of aluminium hydroxide. Only 50 per cent of urine samples from five patients with calculous disease were actually undersaturated, however. During clinical studies in 12 patients with renal calculous disease, four had recurrence or growth of calculi while receiving medication, three had no recurrence during therapy, but new stones appeared after the medication was stopped, and five had no growth or recurrence either during therapy or after its cessation.

3-Methylglutaconic aciduria in "optic atrophy plus".

Behr's syndrome consists of recessively inherited infantile optic atrophy, together with chronic neurological disturbances such as ataxia, extrapyramidal dysfunction, and juvenile spastic paresis. This syndrome was found to be relatively common among Iraqi Jews. For our study, 18 such patients underwent metabolic study. All 18 showed abnormally elevated excretion of 3-methylglutaconic acid in their urine. The basic enzymatic defect is as yet unknown. We recommend that patients with early optic atrophy, and especially those with motor dysfunction, be examined for this organic aciduria.

Biochemical studies in paraplegic renal stone patients. 1. Plasma biochemistry and urinary calcium and saturation.

Renal stone disease is a common problem in patients with spinal cord injury. The factors responsible are thought to include hypercalciuria and chronic urinary infection. There have, however, been no comparative studies of urinary composition in patients with neuropathic bladder with and without renal stone disease. Blood, 24-h urine samples and circadian variation of urinary composition were studied in male paraplegic patients with renal stone disease accompanied by urinary infection and in similar patients without stone disease with and without urinary infection. Two categories of stone patients were recognised, according to whether or not urinary oversaturation with magnesium ammonium phosphate occurred. The urine of all stone patients was oversaturated with calcium phosphate for part of each day. Urinary calcium was elevated in 16% and plasma urate in 30% of the paraplegics studied.

Urinary elimination of glycosaminoglycans during the immobilization osteoporosis of spinal cord injury patients.

Urinary glycosaminoglycans (GAGs) were measured in 47 paraplegics, six tetraplegics, and ten control subjects. In two paraplegics, the GAG rates were compared with those of hydroxyprolinuria and calciuria during one year. The GAG excretion rate found during the first five months after spinal cord injury increased significantly, up to three or four times the normal rate. No significant differences were found between paraplegics and tetraplegics. This increase in glycosaminoglycanuria parallels the previously reported increase in hydroxyprolinuria. The formation of a neurogenic paraosteoarthropathy showed the highest increase in hydroxyprolinuria. These biochemical assessments reflect the modifications in the bone matrix and cutaneous tissue associated with immobilization osteoporosis in spinal cord injury patients.