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Rapid immobilization after acute spinal cord injury (SCI) leads to increased bone resorption, net calcium efflux from the bone, hypercalciuria, depressed parathormone (PTH) and increased calcitonin release. However, the effects, if any, of long-standing SCI on calcium regulatory system is not well understood. We measured plasma concentrations of 25 hydroxy (OH) vitamin D, 1,25(OH)2 vitamin D (calcitriol), intact PTH molecule, calcitonin, ionized calcium [Ca++] and phosphorus in 40 clinically stable men with long-standing SCI of 3-year to 50-year duration (22 persons with paraplegia and 18 persons with quadriplegia). The results were compared with those obtained in 14 able-bodied control men. Plasma PTH concentration in the SCI group was significantly lower than that found in the able-bodied controls despite virtually identical concentrations of ionized calcium. Likewise, plasma calcitriol concentration in the SCI group was significantly lower than the value found in the able-bodied control group and lower in persons with quadriplegia than in those with paraplegia. In contrast, plasma calcitonin concentration in the quadriplegic group was significantly higher than that in persons with paraplegia and insignificantly higher than that in the control group. No significant difference was noted in serum ionized calcium between the study groups. PTH and calcitriol levels were positively related to one another (r = 0.35, p < .01) and negatively related to the level of injury (r = -0.43, p < .002 and r = -0.54, p < .001, respectively). In conclusion, long-standing SCI is associated with significant depression of calcitriol and PTH concentrations despite normal ionized calcium concentration.(ABSTRACT TRUNCATED AT 250 WORDS)

Arterial hypertension (HTN) increases the risk of cerebral coronary, and other vascular complications that frequently involve platelet activation and blood coagulation. Several key proteins in the blood coagulation, fibrinolytic and inhibitory systems were studied in 29 men with HTN (aged 45 +/- 3 yr) and 15 normal men of the same age. Plasma levels of high-molecular-weight kininogen and factors XII, IX, VII, X, II, and XIII, as well as von Willebrand factor (vWF), fibrinogen, fibronectin, alpha 2-antiplasmin, tissue-plasminogen activator, D-dimer, platelet factor-4, and protein C were measured by the use of appropriate functional and immunologic assays before and after a cardiopulmonary exercise stress test. The concentrations of vWF, alpha 2-antiplasmin, and D-dimer were significantly (P < 0.02) higher in the HTN group as compared with the control group. The exercise stress test resulted in significant rises in the plasma vWF, alpha 2-antiplasmin, and tissue-plasminogen activator levels in the two groups. The concentrations of vWF and D-dimer were related to diastolic blood pressure (r = 0.44 and 0.40, respectively; P < 0.02). Levels of vWF also were related to left ventricular mass index and left ventricular posterior wall and septal thickness (r = 0.34, 0.43, and 0.34, respectively; P < 0.05). The constellation of these findings suggests a low-grade fibrin formation and degradation, the magnitude of which is related to the diastolic blood pressure. The observed abnormalities can potentially contribute to the cardiovascular complications of untreated HTN.

Earlier studies have revealed a variety of coagulation abnormalities in patients with long-standing spinal cord injury (SCI) and end-stage renal disease (ESRD). The present study was undertaken to examine the fibrinolytic and protease inhibitory systems in this population. Twelve spinal cord injured men with ESRD were studied. All patients had chronic active urinary tract infections, pressure ulcers and were practically bed-bound. The results were compared with those obtained in a group of 32 normal volunteers. Plasma plasminogen and unstimulated tissue-type plasminogen activator (t-PA) concentrations in the SCI-ESRD group were comparable with those found in the control group. No significant difference was found in plasma plasminogen activator inhibitor (PAI) activity in the two groups. In contrast, plasma alpha 2-antiplasmin antigen concentration and antiplasmin activity were significantly reduced in the study population. In addition, plasma alpha 1-antitrypsin activity and antigen concentration were significantly increased while the alpha 2-macroglobulin activity-to-antigen concentration ratio was significantly reduced in the SCI-ESRD group. Although the mechanism of the observed reduction in alpha 2-antiplasmin and total antiplasmin activity is uncertain, its presence could enhance fibrinolysis in this otherwise thrombosis-prone population. Likewise, elevated alpha 1-antitrypsin could attenuate tissue damage by leukocyte-derived proteases in the face of persistent suppurative infections. The reduced alpha 2-macroglobulin activity-to-antigen concentration ratio was thought to reflect the presence of alpha 2-macroglobulin complexes with various proteases generated by the activation of leukocytes, coagulation, fibrinolytic and other proteolytic systems.

We studied 92 spinal cord injured (SCI) men (50 paraplegics and 42 quadriplegics) with normal renal function, 38 of whom had single or multiple pressure ulcers. The results were compared with those of 28 able-bodied normal controls. Serum concentrations of calcium and magnesium were measured by atomic absorption spectrometry, and 25(OH)-vitamin D was quantitated by a specific competitive binding assay using a sensitive vitamin D binding protein and tritiated 25(OH)-vitamin D. The SCI group exhibited significant reductions in serum 25(OH)-vitamin D and total calcium concentrations as compared to the normal control group. Although the mean serum concentration of 25(OH)-vitamin D in the quadriplegic patients as a whole was lower than that found in the entire paraplegic group, the difference did not attain statistical significance. Similar observations were made when the ulcer-free subgroups of paraplegics and quadriplegics were compared. The SCI subgroup which was least physically active, i.e., those with pressure ulcers, showed the greatest depression of serum 25(OH)-vitamin D, calcium, and magnesium concentrations. The observed reduction in serum 25(OH)-vitamin D in SCI patients appears to be partly related to reduced cutaneous vitamin D biosynthesis from sunlight deprivation occasioned by physical disability and hospitalization. In addition, nutritional deficiency and altered intestinal transport may be involved. The reduction in serum calcium concentration may be related to abnormal vitamin D metabolism and hypoalbuminemia (reduced protein-bound calcium).

This study was performed to compare metabolic and endocrine characteristics of untreated hypertensive patients and normal controls. Measurements were made in age-matched, body mass index (BMI) matched, normotensive patients with (n = 40; age = 53; BMI = 28) and without (n = 39; age = 54; BMI = 27) a family history of hypertension and hypertensive patients with (n = 38; age = 53; BMI = 28) and without (n = 25; age = 54; BMI = 29) a family history of hypertension. Norepinephrine, renin activity, and total cholesterol blood concentrations were similar in normotensive patients with a positive family history of hypertension and in hypertensive patients with or without a family history. Similarly, there were no differences in plasma insulin concentrations or insulin/glucose ratios between the normotensive patients with a family history of hypertension and hypertensive patients with or without a family history. But in all three groups the values were significantly greater (at least p0.05 for each) than in the normotensive patients without a family history. Increases in systolic blood pressure during treadmill testing were 51 +/- 4 mm Hg in the normotensive patients with a family history, 50 +/- 3 mm Hg in hypertensives with a family history, and 45 +/- 5 mm Hg in hypertensives without a family history; these changes were all less (p0.05 for each) than in normotensives without a family history (65 +/- 3 mm Hg).(ABSTRACT TRUNCATED AT 250 WORDS)

Cardiovascular risk factors associated with hypertension include alterations in arterial compliance and an increased tendency to thrombosis. In this study we examined the relationship between arterial compliance and endothelial derived components of the hemostatic system: von Willebrand factor (vWF) and tissue plasminogen activator (t-PA). Ten males (4 normal and 6 untreated hypertensives, 41 +/- 12 years) were studied. Compliance of proximal (large vessel) and distal (small vessel) arteries was measured by intraarterial pulse wave analysis; left ventricular wall thickness by echocardiography; and vWF and t-PA by immunoassay of plasma obtained before and immediately after maximum treadmill exercise. Baseline t-PA and vWF correlated inversely with distal compliance (r = -0.74, p = 0.01; r = -0.56, p = 0.09). Exercise strengthened the relationship between vWF and both distal compliance (r = -0.56 to r = -0.86) and proximal compliance (r = -0.44 to r = -0.70). Moreover, post-exercise levels of vWF and t-PA were each significantly related to left ventricular posterior wall and septal thickness. Of note, these protein concentrations correlated more strongly with arterial compliance and left ventricular wall thickness than with blood pressure. Thus, arterial compliance and left ventricular wall thickness appear to be more powerful than blood pressure as predictors of the endothelial release of vWF and t-PA in response to exercise. These findings indicate that some of the key cardiac and arterial characteristics of hypertension might be linked to increased endothelial reactivity to hemodynamic stress.

Patients with spinal-cord injury (SCI) may have or develop the same diseases, including a variety of metabolic disorders, as their still-ambulatory counterparts. The complications or sequelae of these conditions may compound or aggravate those related to the SCI itself. Impotence is a common complication of many metabolic disturbances, especially diabetes mellitus, and since diabetes is quite a prevalent disease, sexual dysfunction related to it may be a serious problem for SCI patients. This article will address the impact of diabetes mellitus, liver disease, and several miscellaneous metabolic disorders on sexual function.

Renal functional insufficiency often develops in patients with chronic spinal-cord injury (SCI), is associated with substantial morbidity, and frequently progresses to end-stage renal disease (ESRD). As renal function deteriorates, virtually all organ systems are adversely affected. Over the past ten years, there has been increasing interest in the abnormalities of sexual and reproductive function that occur in patients with ESRD (20a). The main focus of this chapter will be the impact of advanced renal failure on sexual function. Even though chronic dialysis has become more widely available, including an expanded capability for patients with SCI and renal failure, there have been no systematic observations of sexual function in patients with both SCI and advanced renal failure. Although our comments are based on observations in able-bodied patients with ESRD, there is no prima facie reason why these cannot be extended to the SCI patient with renal failure.

The kinetics of verapamil during chronic oral therapy were evaluated in a maintenance hemodialysis patient. The elimination half-lives of verapamil and its major metabolite norverapamil were 3.8 and 15.2 h. The former is shorter, while the latter is similar to that in patients with normal renal function. Hemodialysis did not affect drug half-life, and neither drug could be detected in the dialysate. Our studies suggest that verapamil kinetics are altered in end-stage renal disease and that hemodialysis does not remove significant amounts of the drug or its metabolite.

The association of hypertension with congenital renal hypoplasia (Ask-Upmark kidney) has been well established. A case is presented that clearly demonstrates the distinctive clinical, roentgenographic and pathologic features. An abnormal production of renin by the affected kidney suggested that the renin-angiotensin-aldosterone axis was involved in the genesis of the hypertension. Hypertension was cured by unilateral nephrectomy.

Acyclovir is an effective agent for the treatment of herpes virus infections, however, the pharmacokinetics of the drug are altered in renal failure. We studied this drug in a continuous ambulatory peritoneal dialysis (CAPD) patient who was immunocompromised and had cutaneous herpes infection. The elimination half-life (17.1 hours) was similar to that reported for end-stage renal disease (ESRD) patients, while the volume of the central compartment (29.6 L/1.73 m2), the steady state volume of distribution (68.1 L/1.73 m2), and the total body clearance (48.3 mL/min/1.73 m2) were greater. The mean CAPD clearance was only 4.4 mL/min, with less than 10% of an administered dose being recovered in the 24-hour dialysate. Further studies are needed to establish a dosing regimen for CAPD patients.

Examination of urinary sediment has been recommended as a useful diagnostic aid for renal amyloidosis. This procedure was evaluated in the cases of 57 patients, including 11 with proven renal amyloidosis and 13 considered very likely to have the disease. At least three types of urinary fibrillar material were observed: 10-12-nm-diameter fibrils similar to amyloid; 7-10-nm-diameter fibrils with characteristics of intracellular tonofibrils; and 15-30-nm-diameter fibrils suggestive of fibrin tendrils. Only four of 24 patients who had renal amyloidosis proven or suspected had amyloid-like fibrils in the urinary sediment, while four control patients, including three with diabetic nephropathy, had similar fibrils. Sixty-eight per cent of all urines contained material consistent with tonofibrils. Ultrastructural examination of urinary sediment as a diagnostic aid for renal amyloidosis lacks sensitivity and specificity and has very limited clinical value.

It is accepted that in patients with chronic renal failure, dietary control of salt and water balance and diuretics should be used to prevent depletion or excessive retention of salt and water.1 Similarly, there is little argument concerning the need to control dietary potassium, phosphorus, and magnesium intake, to provide calcium and vitamin supplements, and to use phosphate binders in such patients.1,2 Thus the controversy concerning the value of dietary therapy in chronic uremia relates to the management of protein intake to postpone dialysis therapy and optimize nutritional status.

A common endocrine defect in uremia is gonadal dysfunction with decreased testosterone production. Since gonadal and adrenal tissues share androgen biosynthetic pathways, we studied the stimulated adrenal androgen response in uremic patients. In contrast to the delayed or subnormal gonadal response to hCG reported by others, the adrenal response of androgens, as well as cortisol and aldosterone, to cosyntropin stimulation was unimpaired. In summary, the secretory reserve capacity of the adrenal gland for androgen, glucocorticoids and mineralocorticoids in uremia was studied with cosyntropin stimulation and found to be wall preserved.

The present study describes 3 patients with the simultaneous occurrence of diabetic nephropathy and immune-complex mediated glomerulonephritis. Renal manifestation included proteinuria and hematuria which were preceded by or co-existent with an infectious process. Renal manifestation included proteinuria and hematuria which were preceded by or co-existent with an infectious process. Renal histology showed the characteristic change of diabetic nephropathy along with those of immune complex glomerulonephritis. Immunofluorescence studies showed a linear pattern with a superimposed granular pattern of IgG and C3 deposits. Renal function and urinary findings improved in the 2 patients who were followed up.

Renal functional abnormalities and evidence of interstitial nephritis are common in Sjogren's syndrome, and it has been suggested that the interstitial changes may be on an immunologic basis. We report a patient with the sicca complex variety of Sjogren's syndrome who presented with renal functional insufficiency and intense interstitial nephritis. Focal tubular basement membrane (TBM) deposits were observed, and immunofluorescence showed focal TBM deposits of IgG and C3. Glomeruli contained no deposits. Therapy with prednisone and cyclophosphamide was associated with marked clinical improvement and regression of tissue leukocyte infiltration. We propose local or in situ formation of immune complexes, as in the rabbit model of autologous immune-complex interstitial nephritis, and suggest that this mechanism may be operative in some patients with Sjogren's syndrome and tubulointerstitial renal disease. Immunosuppressive therapy may have helped to preserve renal function.

While the use of magnesium-containing compounds is usually contraindicated in dialysis patients, the risk of toxicity from hypermagnesemia can be reduced by lowering the magnesium concentration in dialysate. We examined the effects of a magnesium-free dialysate on both serum magnesium level and the peritoneal removal rate of magnesium over 12 weeks in 25 stable patients undergoing continuous ambulatory peritoneal dialysis (CAPD). After 2 weeks, the serum magnesium level decreased from 2.2 to 1.9 mg/dL (0.9 to 0.8 mmol/L) (P less than .02) and the peritoneal removal rate increased from 66 to 83 mg/d (2.8 to 3.5 mmol/d) (P less than .05), with both values remaining stable thereafter. There was a strong association between these parameters (r = -0.62, P less than .05), suggesting that the serum magnesium level decreased as a result of the initial increased peritoneal removal rate. For an additional 4-week period, a subgroup of nine patients received magnesium-containing, phosphate binding agents instead of those containing only aluminum. During this phase, serum inorganic phosphorus was well controlled. The serum magnesium level increased only from 1.8 to 2.5 mg/dL (0.7 to 1.0 mmol/L) (P less than .05), due in great part to the concomitant 41% rise in peritoneal magnesium removal from 91 to 128 mg/d (3.8 to 5.3 mmol/d) (P less than .05). No toxicity was noted during the entire 16-week study period, nor did serum calcium change. Thus, serum magnesium levels remained within an acceptable range as magnesium-containing phosphate binders were given through the use of magnesium-free peritoneal dialysate.(ABSTRACT TRUNCATED AT 250 WORDS)

THERE is increasing awareness that long-term abuse of various analgesic agents is a major factor in the pathogenesis of renal papillary necrosis (RPN), which is an important cause of renal dysfunction. We describe a patient who experienced RPN while taking large doses of pentazocine in association with aspirin. Report of a Case A 49-year-old white man was admitted to the Long Beach (Calif) Veterans Administration Medical Center in October 1978 with a two-day history of lower abdominal pain radiating to both flanks. The pain was partially relieved by position change and was associated with nausea and vomiting. The only other symptom was passage of tissue via the urethra. A similar episode had occurred in August 1978. An excretory urogram obtained in April 1978 for evaluation of weight loss was normal. History included chronic alcoholism with hepatic cirrhosis, chronic pancreatitis, chemical diabetes mellitus, and cholelithiasis. He had been taking aspirin (1.8

Seventeen patients without renal failure and 14 patients receiving longterm hemodialysis were studied. Serum and bone marrow ferritin determinations were made at the time of bone marrow aspiration. A good correlation was found between serum ferritin levels and bone marrow iron stores, as well as between bone marrow ferritin levels and iron stores. Serum ferritin determinations appear to give an accurate estimation of bone marrow iron stores, thereby providing a reliable guide for iron replacement therapy and reducing the need for repeated bone marrow aspirations. Serum ferritin levels of less than 105 ng/ml suggest decreased iron stores, and values greater than 120 ng/ml indicate adequate or increased iron stores. Preliminary data also suggest that bone marrow ferritin determinations may be useful in quantitating bone marrow iron stores. ( JAMA 238:601-603, 1977)