Tertiary hyperparathyroidism after renal transplantation: surgical strategy

BACKGROUND: An analysis of our experience with tertiary hyperparathyroidism (III HPT) in renal transplantations between 1981 and 1996 was reviewed to examine a variety of laboratory and clinical variables in this population. METHODS: A total of 3233 kidney transplantations were performed; 48 patients underwent parathyroidectomy for III HPT. Five patients were excluded from analysis due to the development of renal dysfunction. The index 43 patients were divided into two groups. Group I consisted of 31 patients (72%) with either enlargement of all parathyroid glands (n = 26) or 3/4 gland enlargement (n = 5). These patients were assumed to have hyperplasia and underwent subtotal parathyroidectomy or total parathyroidectomy. Group II consisted of 12 patients (28%) with single (7/12; 58%) or two-gland enlargement (5/12; 42%). Group II patients underwent resection of only the enlarged glands. RESULTS: Laboratory and clinical parameters showed no difference between the groups during long-term follow-up. Most patients in groups I and II were eucalcemic after parathyroidectomy. However, postoperative hypercalcemia and hypocalcemia did occur in group I (mean postoperative calcium: group I = 9.29 +/- 0.63 mg/dL; group II = 9.42 +/- 0.58 mg/dL). CONCLUSIONS: Four gland parathyroid enlargement is a frequent finding in III HPT, although asymmetric enlargement can occur. Histologically, this represents sporadic adenomas and asymmetric hyperplasia. Intraoperative findings should dictate surgical strategy; with asymmetric enlargement only the enlarged parathyroid glands should be resected.     

Parathyroidectomy in the elderly: do the benefits outweigh the risks?

Although the incidence of hyperparathyroidism (HPT) in the elderly exceeds 1.5%, limited resources and co-morbidity inhibit referral for parathyroidectomy. To determine the risks and benefits of surgery, we examined the outcomes of elderly patients who underwent exploration for primary HPT. Data from 211 consecutive patients who underwent parathyroidectomy by one surgeon at the Johns Hopkins Hospital between August 1990 and May 1996 were recorded prospectively. Of these patients, 184 had primary HPT. Demographic and outcome data of elderly patients (> 70 years of age) (n = 36) were compared to those from younger patients (< 70 years of age) (n = 148). Preoperative symptoms of mental impairment, bone disease, and fatigue were more common in elderly patients (p < 0.05), and nephrolithiasis was more frequent in younger patients (p < 0.025). Elderly patients presented with more advanced disease, manifested by higher preoperative parathyroid hormone levels (301.9 +/- 63.3 vs. 169.2 +/- 14.3 pg/ml, p < 0.05). The cure rate (94.4%), morbidity (5.5%), and mortality (0%) in the elderly were indistinguishable from those of their younger cohorts (98%, 1.4%, and 0%, respectively). In conclusion, the more advanced disease seen in the elderly suggests that they are referred for surgery with a higher threshold than younger patients. Although several series of parathyroidectomy in elderly patients have reported high morbidity rates, significant mortality, and long length of stay (LOS), we found that parathyroidectomy in these patients can be performed with high cures, low morbidity, no mortality, short LOS, and high patient satisfaction. These data suggest that the benefits of surgery outweigh its risks and argue for a lower threshold for referral of elderly patients with primary HPT for surgical treatment.     

Maintenance of bone mass in patients receiving dialytic therapy

To determine what factors contribute to and change bone mineral density (BMD) in dialysis patients, serial lumbar spine dual x-ray absorptiometry studies were analyzed by stepwise regression analysis in 67 black dialysis patients. The patients were 50.5 +/- 2.0 years of age (mean +/- SE) and 49% were men; the patients had received dialytic therapy for 3.7 +/- 0.5 years. The mean initial BMD z-score was 0.147 +/- 0.182. By cross-sectional analysis, the BMD increased in the male and premenopausal female patients but decreased in the postmenopausal female patients by 2.5% g/cm2/decade of life, less than that observed in black patients with normal renal function. Univariate analysis and stepwise regression analysis demonstrated radiographic evidence of osteopenia (beta-coefficient = -0.180 +/- 0.050; P = 0.001) and prior parathyroidectomy (beta-coefficient = 0.133 +/- 0.070; P = 0.054) as the only variables significantly correlated to the BMD. The effects of biochemical variables and different treatments on the delta BMD, calculated as the difference between each patient's first and second BMDs divided by the interval in years, were evaluated by stepwise regression analysis in 41 patients. The mean interval between the two BMDs was 18.4 +/- 1.02 months (range, 5 to 34 months) and the delta BMD was 0.025 +/- 0.018 g/cm2/yr, increasing in 65% of the patients. By univariate and stepwise regression analysis, the mean monthly serum total alkaline phosphatase concentration was the only variable that correlated with the delta BMD (beta-coefficient = 0.0001; P = 0.030).(ABSTRACT TRUNCATED AT 250 WORDS)     

Heterochromatin effects on the frequency and duration of LCR-mediated gene transcription

Organ transplantation is associated with an early bone loss that subsequently increases the risk of osteopenia and bone fractures. It is not known whether bone loss continues in long-term survivors, but persistent bone demineralization could further jeopardize an already diminished bone mass. To better define long-term bone status of kidney transplant recipients (KTR), we conducted cross-sectional and longitudinal evaluations of bone mineral density (BMD) in 70 KTR with a mean posttransplantation time of 8.1 years. BMD was determined by dual-energy X-ray absorptiometry and was repeated in 55 of the patients after a mean follow-up period of 22 +/- 5 months. Lumbar and femoral osteopenia, defined as a BMD lower than 2 standard deviations from mean value of sex- and age-matched controls, was present in 28.6% and 10.5% of patients, respectively. There was a significant negative correlation between cumulative prednisone dose and adjusted lumbar as well as femoral BMD (R = 0.45, P < 0.001 and R = 0.29, P < 0.05, respectively). Five patients had a vertebral BMD below a fracture threshold of 0.777 g/cm2. Vertebral fractures (VF) were found in four men and were associated with higher prednisone dosage (P < 0.05), larger cumulative prednisone dose (P < 0.05), and significantly lower BMD values. According to World Health Organization recent criteria for women, prevalences of lumbar and femoral osteopenia and lumbar and femoral osteoporosis in female patients reach 75%, 65%, 33%, and 10%, respectively. The longitudinal part of the study showed a persistent pathological lumbar demineralization process. Over the study period, BMD, expressed as a percentage of that of controls, decreased from 89 +/- 14% to 86 +/- 14% (P < 0.001). Annual change of bone mass was -1.7 +/- 2.8% per year. Accelerated vertebral bone loss (defined as a decrease of BMD, expressed as a percentage of that of controls, of more than 1% per year) was present in 56% of patients and was associated with higher prednisone dosage (P < 0.01). In conclusion, although VF are relatively infrequent in long-term survivors of renal transplantation, osteopenia is a frequent finding, and a substantial proportion of women present lumbar osteoporosis. An ongoing demineralization process of the spine is also demonstrated and probably contributes to long-term spinal osteoporosis incidence. Prednisone dosage remains the most constantly isolated risk factor.     

Type of physical activity, muscle strength, and pubertal stage as determinants of bone mineral density and bone area in adolescent boys

The present study was conducted to evaluate the influence of different types of weight-bearing physical activity, muscle strength, and puberty on bone mineral density (BMD, g/cm2) and bone area in adolescent boys. Three different groups were investigated. The first group consisted of 12 adolescent badminton players (age 17.0 +/- 0.8 years) training for 5.2 +/- 1.9 h/week. The second group consisted of 28 ice hockey players (age 16.9 +/- 0.3 years) training for 8.5 +/- 2.2 h/week. The third group consisted of 24 controls (age 16.8 +/- 0.3 years) training for 1.4 +/- 1.4h/week. The groups were matched for age, height, and pubertal stage. BMD, bone mineral content (BMC, g), and the bone area of the total body, lumbar spine, hip, femur and tibia diaphyses, distal femur, proximal tibia, and humerus were measured using dual-energy X-absorptiometry. When adjusting for the difference in body weight between the groups, the badminton players were found to have significantly higher BMD (p < 0.05) of the trochanter and distal femur compared with the ice hockey players despite a significantly lower weekly average training. The badminton players had higher BMD compared with the control with the control group at all weight-bearing BMD sites, except at the diaphyses of the femur and tibia and lumbar spine. The independent predictors of bone density were estimated by adjusting BMC for the bone area in a multivariate analysis among all subjects (n = 64). Accordingly, the bone density of all sites except the spine was significantly related to muscle strength and height, and the bone density of the total body, neck, trochanter, distal femur, and proximal tibia was significantly related to type of physical activity (beta = 0.09-0.33, p < 0.05). The bone area values at different sites were strongly related to muscle strength and height and less strongly related to the type of physical activity and pubertal stage. In conclusion, it seems that during late puberty in adolescent boys the type of weight-bearing physical activity is an important determinant of bone density, while the bone area is largely determined by parameters related to body size. The higher BMD at weight-bearing sites in badminton players compared with ice hockey players, despite significantly less average weekly training, indicates that physical activity including jumps in unusual directions has a great osteogenic potential.     

The use of pamidronate in three children with renal disease

The successful use of pamidronate, a bisphosphonate, for the treatment of hypercalcemia and/or osteopenia is reported in three children with renal failure or following renal transplant. Patient 1 was an 11-year-old post renal transplant male who received a single dose of i.v. pamidronate (0.5 mg/kg) for the treatment of acute hypercalcemia associated with a pathological fracture and subsequent immobilization. Prompt resolution of the hypercalcemia was seen. He received a second course of pamidronate (0.5 mg/kg per day for 3 days) for the treatment of osteopenia and has had a subsequent 15% increase in lumbar spine bone mineral content (BMC). Patient 2, a 14-year-old male on peritoneal dialysis, presented with symptomatic hypercalcemia associated with tertiary hyperparathyroidism. A single dose of i.v. pamidronate (0.4 mg/kg) was given with prompt resolution and prolonged control of his hypercalcemia. The third patient was a 16-year-old female, also in renal failure on peritoneal dialysis. Her course had been complicated by marked osteopenia. I.v. pamidronate (0.5 mg/kg per dose) was given on 3 successive days before and after renal transplant in an attempt to stabilize her bone mineral density (BMD) around the time of renal transplantation, when additional glucocorticoid was necessary. Her total body BMC and BMD remained stable pre and post transplant. The treatment was effective and well tolerated in all three patients. Hence pamidronate is safe and effective for the management of hypercalcemia and osteopenia in children with renal failure and/or renal transplant.     

Bone disease in children and adolescents undergoing successful renal transplantation

Little is known about the extent and severity of bone disease in children undergoing successful renal transplantation. To address this issue, 47 patients with stable renal function 3.2 +/- 1.7 years after transplantation (Tx) underwent iliac crest bone biopsy. The mean age of patients was 12 +/- 2.0 years; 36 had received cadaveric renal grafts, whereas 11 had undergone living-related Tx. Immunosuppressive drugs included cyclosporine 0.17 +/- 0.4 mg/kg/day, prednisone 7.5 +/- 2.1 mg/kg/day, and either azathioprine 1.6 +/- 0.9 mg/kg/day or mycophenolate mofetil 30 +/- 3 mg/kg/day. In addition to quantitative bone histomorphometry, the bone mineral content (BMC) of the lumbar spine was measured by dual energy X-ray absorptiometry (DXA) in 24/47 patients. Thirty-one transplant recipients had normal bone formation (N-Bfr), 11 had mild hyperparathyroidism (HPT) and 5 had adynamic skeletal lesions (AD). The interval since Tx, duration of dialysis before Tx and cumulative prednisone dose did not differ among groups. Trabecular bone area was highest in subjects with HPT. Unexpectedly, eroded bone perimeter exceeded normal reference values both in patients with AD and in those with N-Bfr; the osteoid area and osteoid perimeter were also elevated in these two groups. Hyperparathyroidism improved or resolved after Tx in all 14 subjects with this skeletal lesion prior to Tx, but one patient developed AD after Tx. Bone histology did not change after Tx in those with N-Bfr during regular dialysis, but bone formation increased after Tx in two of three patients with AD during regular dialysis. Z-scores for height in pre-pubertal patients after Tx were below age-appropriate values in each histologic subgroup, but values did not differ among groups. Z-scores for bone mineral content at the lumbar spine were also less than age-predicted values, -0.67 +/- 1.2. After adjusting for the degree of growth retardation, height-adjusted z-scores for lumbar spine BMC after Tx were above normal in all three histologic groups (0.68 +/- 1.0). The results suggest that reductions in bone mass and post-transplant osteoporosis are not prominent findings in pediatric renal transplant recipients when the influence of growth retardation on bone mass measurements by DXA is carefully considered.     

Case-control study on symptoms and signs of "asymptomatic" primary hyperparathyroidism

BACKGROUND: Symptoms, signs, and treatment of mild primary hyperparathyroidism (HPT) are controversial. METHODS: One hundred two patients with HPT and matched controls were recruited from 5202 females attending population-based mammography screening at age 55 to 75 years. Patients' total serum calcium averaged 10.40 +/- 0.564 mg/dL and intact serum parathyroid hormone 58 +/- 33 ng/L. All patients lacked knowledge of their disease. Questions revealed traditional symptoms of HPT in 24% of cases and 43% of controls (P = .01). All individuals underwent the same biochemical analyses, bone mass determination, and questionnaires on symptoms, illnesses, medications, and background variables. RESULTS: Patients with HPT had more psychic complaints (P = .03 to .007) of lassitude, fatigue, irritability, and lack of sexual and emotional interests. They had lower bone density in total body, spine, and hip (P = .008 to .0004) and higher serum alkaline phosphatase, cholesterol (very-low-density lipoprotein), triglycerides (total, very-low-density lipoprotein), glucose, urate, and hemoglobin values (P = .02 to .0001). Patients visited physicians more often (P = .008) and had more antihypertensive therapy (P = .02). CONCLUSIONS: Mild, "asymptomatic" HPT in patients unaware of their disorder displays significant psychic symptoms, bone loss, and risk factors of cardiovascular disease.     

Effects of growth hormone (GH) replacement on bone metabolism and mineral density in adult onset of GH deficiency: results of a double-blind placebo-controlled study with open follow-up

It is known that GH stimulates bone turnover and that GH-deficient adults have a lower bone mass than healthy controls. In order to evaluate the influences of GH replacement therapy on markers of bone turnover and on bone mineral density (BMD) in patients with adult onset GH deficiency, a double-blind placebo-controlled study of treatment with recombinant human GH (rhGH; mean dose 2.4 IU daily) in 20 patients for 6 months and an extended open study of 6 to 12 months were conducted. Eighteen patients, fourteen men and four women, with a mean age of 44 years with adult onset GH deficiency were evaluated in the study. Compared with placebo, after 6 months serum calcium (2.39 +/- 0.02 vs 2.32 +/- 0.02 mmol/l, P = 0.037) and phosphate (0.97 +/- 0.06 vs 0.75 +/- 0.05 mmol/l, P = 0.011) increased and the index of phosphate excretion (0.03 +/- 0.03 vs 0.19 +/- 0.02, P < 0.001) decreased significantly, and there was a significant increase in the markers of bone formation (osteocalcin, 64.8 +/- 11.8 vs 17.4 +/- 1.8 ng/ml, P < 0.001; procollagen type I carboxyterminal propeptide (PICP), 195.3 +/- 26.4 vs 124.0 +/- 15.5 ng/ml, P = 0.026) as well as those of bone resorption (type I collagen carboxyterminal telopeptide (ICTP), 8.9 +/- 1.2 vs 3.3 +/- 0.5 ng/ml, P < 0.001; urinary hydroxyproline, 0.035 +/- 0.006 vs 0.018 +/- 0.002 mg/100 ml glomerular filtration rate, P = 0.009). BMD did not change during this period of time. IGF-I was significantly higher in treated patients (306 +/- 45.3 vs 88.7 +/- 22.5 ng/ml, P < 0.001). An analysis of the data compiled from 18 patients treated with rhGH for 12 months revealed similar significant increases in serum calcium and phosphate, and the markers of bone turnover (osteocalcin, PICP, ICTP, urinary hydroxyproline). Dual energy x-ray absorptiometry (DXA)-measured BMD in the lumbar spine (1.194 +/- 0.058 vs 1.133 +/- 0.046 g/cm2, P = 0.015), femoral neck (1.009 +/- 0.051 vs 0.936 +/- 0.034 g/cm2, P = 0.004), Ward's triangle (0.881 +/- 0.055 vs 0.816 +/- 0.04 g/cm2, P = 0.019) and the trochanteric region (0.869 +/- 0.046 vs 0.801 +/- 0.033 g/cm2, P = 0.005) increased significantly linearly (compared with the individual baseline values). At 12 months, BMD in patients with low bone mass (T-score < -1.0 S.D.) increased more than in those with normal bone mass (lumbar spine 11.5 vs 2.1%, P = 0.030, and femoral neck 9.7 vs 4.2%, P = 0.055). IGF-I increased significantly in all treated patients. In conclusion, treatment of GH-deficient adults with rhGH increases bone turnover for at least 12 months. BMD in the lumbar spine and the proximal femur increases continuously in this time (open study) and the benefit is greater in patients with low bone mass. Therefore, GH-deficient patients exhibiting osteopenia or osteoporosis should be considered candidates for GH supplementation. However, long-term studies are needed to establish that the positive effects on BMD are persistent and are associated with a reduction in fracture risk.     

Symmetric and asymmetric left ventricular hypertrophy in patients with end-stage renal failure on long-term hemodialysis

BACKGROUND: Patients with end-stage renal disease on regular hemodialysis have an increased prevalence of left ventricular (LV) hypertrophy that is associated with morbidity and mortality. Asymmetric septal hypertrophy and impairment of LV outflow can occur in these patients and may contribute to adverse outcomes. More insight into the prevalence, extent, geometry, and promoting factors of LV hypertrophy is important. METHODS: An unselected group of 62 patients (31 women), aged 55 +/- 14 years, on maintenance hemodialysis was investigated by Doppler echocardiography. Eight patients with valvular heart disease were excluded from further analysis. We assessed prevalence of LV hypertrophy and asymmetric septal hypertrophy, as well as parameters of LV geometry and LV filling and outflow dynamics. RESULTS: Prevalence of LV hypertrophy was 65%. Patients were analyzed according to LV mass and geometry. Mean LV mass index was normal (105 +/- 17 g/m2) in Group 1 without LV hypertrophy (n = 19); it was markedly elevated in Group 2 (symmetric hypertrophy, n = 22) and Group 3 (asymmetric hypertrophy with systolic anterior movement of mitral valve, n = 7), and highest (191 +/- 54 g/m2) in Group 4 (asymmetric hypertrophy without systolic anterior movement of mitral valve, n = 6, p < 0.001). Age, body mass index, and duration of hypertension were associated with LV hypertrophy and asymmetric septal hypertrophy (p = 0.01). Group 3 with systolic anterior motion of mitral valve had the smallest end-diastolic LV diameters (p = 0.02); increased heart rates, and increased ejection velocities in the LV outflow tract (p = 0.03, and p = 0.005, respectively, vs. Groups 1, 2, and 4) which pointed to an impairment of LV outflow. CONCLUSIONS: Symmetric LV hypertrophy and asymmetric septal hypertrophy are frequent in patients on maintenance hemodialysis. Predictors for LV hypertrophy were age and body mass index, and, particularly for asymmetric septal hypertrophy, age and hypertension duration. Volume withdrawal during hemodialysis may lead to symptomatic hypotension due to dynamic obstruction in some patients with severe asymmetric septal hypertrophy.     

Prediction of bone loss in patients with primary hyperparathyroidism using quantitative bone SPECT

Bone loss is a major complication of primary hyperparathyroidism (PHPT), and it has significant implications in the treatment of this disease. Bone turnover was measured in patients with PHPT, using quantitative bone SPECT (QBS), to determine if the rate of bone loss could be predicted before a significant decrease in bone mass occurs. METHODS: Forty-six patients were included in the study. QBS and bone mineral density (BMD) of the lumbar spine (LS) and femoral neck (FN) were done at baseline. The percent deviation of QBS in patients with PHPT from the values in normal matched controls was calculated. BMD was measured again after a mean of 17.5 mo in 38 patients, and in 29 patients a repeat BMD study was done after a mean of 41.4 mo. The change in BMD in patients with high and normal QBS values was compared using the nonparametric Mann-Whitney test. Regression analysis tested the correlation between baseline QBS values and BMD changes over time. RESULTS: For the FN, there was a statistically significant difference in the BMD change between patients with high and normal QBS values for short-term follow-up (-2.82%+/-4.80% versus 1.45%+/-4.67%, p < 0.05) and for long-term follow-up (-3.53%+/-5.34% versus 0.92%+/-2.40, p < 0.02). There was a negative correlation in the FN, r=-0.48 between QBS values and the percentage of change in BMD. There was no significant difference between the percentage of change in BMD in the LS in patients with high and normal QBS values for either short- or long-term follow-up. CONCLUSION: The results of this study show that QBS can predict bone loss in the FN in patients with PHPT. QBS can thus indicate the need for surgery at an early stage of the disease to prevent bone loss.     

Bone mineral density in patients on long-term therapy with levothyroxine

The aim of the study was to determine the influence of replacement and suppressive thyroxine therapy on bone mineral density (BMD). 30 postmenopausal women; 19 on replacement therapy (dose 1.22 +/- 0.35 micrograms/kg; duration 11.4 +/- 7.2 years) and 11 on suppressive therapy (dose 1.45 +/- 0.71 micrograms/kg; duration 9.5 +/- 7.2 years). Controls were 60 healthy women matched for age and menopausal status. BMD at the lumbar spine (L2-L4), femoral neck, Ward's triangle and trochanter was measured by dual-energy absorptiometry. Forearm BMD at distal site was measured by single-photon absorptiometry. Mean thyroid hormone values and TSH were within normal limits, although the patients on suppressive therapy had significantly higher T3 (p < 0.05) than the patients on replacement therapy. BMD on each site was significantly lower in the replacement treated group than in controls. BMD in patients on suppressive therapy was lower, but not significantly, compared to controls. Thyroxine therapy could have an adverse effect on BMD. The magnitude of bone loss depends on the serum level of thyroid hormones and on the functional state of thyroid hormone receptor in bone tissue, as well.     

Evaluation of low density spine software for the assessment of bone mineral density in children

Pediatric dual-energy X-ray absorptiometry spine scans often cannot be analyzed with standard software due to a failure to identify the bone edges of low density vertebrae. Low density spine (LDS) software improves bone detection compared with standard software. The objective of this study was to compare bone mineral density (BMD) measurements obtained with the standard and LDS software in 27 healthy nonobese, 32 obese, and 41 chronically ill children, ages 2-18 years. Lumbar spine (L1-L4) BMD, measured by standard analysis, ranged from 0.531-1.244 gm/cm2. Reanalysis with the LDS software resulted in a systematic increase (mean +/- SD) in estimated bone area of 17.0+/-5.0%, an increase in bone mineral content of 6.1+/-6.3%, and a mean decrease in BMD of 8.7+/-1.7% (all p < 0.001). This resulted in a mean decrease in BMD Z score of 0.7+/-0.2. Linear regression models, predicting standard BMD from LDS BMD, were fit for the three subject groups (R2 = 0.993-0.995). Small differences in slopes were detected across groups (p = 0.07); LDS BMD predicted higher standard BMD in obese subjects. In conclusion, LDS analysis resulted in a clinically significant decrease in measured BMD. The association between analysis methods was exceptionally high (R2 > 0.99), indicating that LDS BMD accurately predicts standard BMD. Although LDS BMD in obese subjects predicts higher standard BMD results than in nonobese subjects, the small difference is of questionable clinical significance. LDS software is a useful tool for the assessment of BMD in children.     

Preserved antioxidative defense of lipoproteins in renal failure and during hemodialysis

Contact to artificial surfaces during hemodialysis activates leukocytes, which then form oxidized arachidonic acid products and free radicals. This might promote the oxidative modification of low-density lipoproteins (LDL) that play a key role in the initiation of atherosclerosis. Thus, leukocyte activation could specifically contribute to the high mortality from atherosclerotic complications on long-term hemodialysis. Therefore monitored LDL and high-density lipoprotein (HDL) resistance to copper-stimulated oxidation in patients with end-stage renal disease on maintenance hemodialysis with cellulose acetate or polysulfone membranes (n = 12), in patients with chronic renal failure (n = 13) and in healthy controls (n = 12). Six of the dialysis patients were restudied during a single cuprophane dialysis. Circulating leukocytes were reversibly reduced early in hemodialysis with cellulose acetate (minimum, 83.6% +/- 7.4% of baseline values at 30 minutes after dialysis start), polysulfone (minimum, 80.4% +/- 10.5% at 15 minutes; P < 0.05) and cuprophane (minimum, 24.5% +/- 8.5% at 60 minutes; P < 0.0001). Despite the leukocyte activation, LDL oxidation lag time was not shortened in comparison with healthy controls and was even prolonged at the end of cellulose acetate (P < 0.05) and cuprophane (P < 0.05) dialysis. HDL oxidation lag time increased (12.6% +/- 0.9%; P < 0.0001) 15 to 60 minutes after start of hemodialysis and returned to predialysis values thereafter. In patients with chronic renal failure, the lag time of HDL oxidation was significantly prolonged (13.34 minutes +/- 0.9) compared with healthy controls (10.91 +/- 2.0 minutes; P < 0.01) as well as compared with the dialysis patients at baseline (9.9 minutes +/- 1.4; P < 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)     

Clinical evaluation of bone-densitometry in patients with final renal insufficiency operated for hyperparathyroidism

Because of difficulties in evaluating bone mineral mass with conventional methods in patients with final renal insufficiency before and after parathyroidectomy, bone densitometry has been tried. During a three year period ten patients have been selected for surgery. The parathyroidectomy performed was total in nine patients and subtotal in one. Bone mineral mass was significantly lower preoperatively in the operated patients than in other patients on regular hemodialysis and also lower than in a normal material. In four of ten patients there was a transient decrease in bone mineral mass after parathyroidectomy. Thereafter there was a significant increase in five of ten patients and in the whole group of patients. Thus bone densitometry was found to be of value in following patients with renal insufficiency selected for parathyroidectomy.     

In vivo semen-associated pH neutralization of cervicovaginal secretions

To determine (1) the relationship between primary hyperparathyroidism with mild hypercalcemia and psychiatric disturbances, bone density, or non-specific symptoms, and (2) the effect of parathyroidectomy on these outcomes, a systematic and critical review of the literature was conducted. Relevant citations were identified using MEDLINE (1966 to August, 1995) and PsycINFO (1967 to August, 1995). Studies were included for the overview if they described patients with mild hypercalcemia (< 12 mg/dl), and if they dealt with at least one of the following outcomes: psychiatric disturbances, bone density, joint pain, constipation, polyuria/nocturia or weight loss. Either a calculated effect size or Z score was used to estimate the effect of the disease or parathyroidectomy on these outcomes. Seven studies met the inclusion criteria for this overview. Two out of three case-control studies on psychiatric symptoms found a significant association between primary hyperparathyroidism with mild hypercalcemia and psychiatric disturbances (effect sizes; 0.17, 1.2 and 1.6). One of the three studies also examined the effect of parathyroidectomy on psychiatric symptoms, and found an effect size of 1.5. All four cross-sectional studies that measured bone mass showed significantly reduced bone density in the forearm and the lumbar spine. The bone loss ranged from 0.9 to 1.4 standard deviation below the age- and sex-adjusted mean value in the forearm, and was 0.5 in the spine. There was no relevant study regarding non-specific symptoms. Among the seven studies, five did not explicitly indicate whether the patients had classical symptoms of either osteitis fibrosa cystica or renal stones. Primary hyperparathyroidism with mild hypercalcemia is associated with psychiatric disturbances and reduced bone density. Nevertheless, further research is needed to determine the symptoms, particularly for a group of patients without either classical bone disease or renal stones. The effects of parathyroidectomy on these outcomes also remain to be determined.     

Alterations of bone turnover and bone mass at different skeletal sites due to pure glucocorticoid excess: study in eumenorrheic patients with Cushing's syndrome

The aim of the present investigation was to study the effect of glucocorticoid excess on bone mass and turnover not influenced by other diseases known to affect skeleton and/or by different gonadal status and sex. We studied several markers of bone turnover and bone mineral density (BMD) by both quantitative computed tomography (at spine and forearm) and dual x-ray absorptiometry (at spine and three femoral sites) in 18 eugonadal female patients affected by Cushing's syndrome (CS) compared to 24 eugonadal healthy female subjects matched for age and body mass index. In CS patients, serum bone Gla protein, a marker of osteoblastic function, was reduced (3.28 +/- 2.3 vs. 6.47 +/- 2.5; P < 0.01), and bone resorption was increased, as indicated by increased urinary hydroxyproline (36.6 +/- 12 vs. 29.0 +/- 9.1, P < 0.05) and urinary deoxypyridinoline (22.1 +/- 8.0 vs. 16.4 +/- 6.3; P < 0.05). BMD was significantly (P < 0.05 or P < 0.01) reduced at all sites, except cortical forearm, in CS patients compared to controls. By comparing z-scores of reduced BMD in CS patients, spinal trabecular BMD was found to be the most severely affected. Furthermore, disease activity, as measured by urinary free cortisol, was significantly correlated with bone Gla protein (r = -0.57; P < 0.02), urinary hydroxyproline (r = 0.57; P < 0.02), urinary deoxypyridinoline (r = 0.48, P < 0.05), and BMD measured at spine and femur. Our results show that compared to matched control subjects, female eumenorrheic CS patients have reduced osteoblastic function, increased bone resorption, and reduced BMD, and that the severity of these abnormalities is statistically related to the severity of disease activity, as indicated by urinary free cortisol. Moreover, our data suggest a site and tissue specificity of the effect of glucocorticoid excess on bone mass.     

Harmonic/noise ratio and spectrographic analysis in vocal abuse pathology

To evaluate the use of dual energy X-ray absorptiometry (DXA) in multiple myeloma (MM) we performed a prospective study of 34 patients with newly diagnosed MM. Most patients had advanced disease and all but two patients had osteolytic bone destructions and/or pathological fractures. Bone mineral content (BMC) and bone mineral density (BMD) of the lumbar spine (L1-L4) and hip were measured using a Hologic QDR-1000 scanner. Collapsed vertebrae were not excluded from analysis. Data from 289 healthy Danish volunteers aged 21-79 yr were used for calculation of Z-scores. Lumbar spine BMC (Z-score -0.46 +/- 0.23, p = 0.05) and lumbar spine BMD (Z-score -0.56 +/- 0.23, p = 0.02) were significantly reduced in MM patients, whereas no reduction was seen in hip BMC or BMD. Collapsed vertebrae had marked reduced BMD (Z-score -1.34 +/- 0.22, p < 0.001), as had non-fractured vertebrae in the same individuals (Z-score -1.42 +/- 0.25, p < 0.001). Lumbar spine BMD correlated with radiologically assessed bone morbidity (r -0.37, p = 0.03) and stronger with the incidence of vertebral fractures (r -0.64, p < 0.001). Thus, osteopenia of the back is common in multiple myeloma and correlates with an increased incidence of fractures. DXA may identify subjects with increased risk of vertebral fractures for more intensive chemotherapeutic or anti-resorptive treatment.     

A controlled trial of twice daily triamcinolone oral inhaler in patients with mild-to-moderate asthma

The objectives of this work was to (1) study the bone mineral density (BMD) of the lumbar spine, total skeleton, and body composition in patients with primary biliary cirrhosis (PBC) and (2) evaluate the risk factors (premature menopause, stages of the disease, hyperbilirubinemia) and bone and liver biochemical parameters for the development of osteoporosis. We studied 23 women with a compatible diagnosis of PBC. The BMD and body composition were evaluated by X-ray absorptiometry (Lunar DPX-L). The average age of the population was 56.7 +/- 10.2 years. The BMD of the lumbar spine and of the total skeleton was 1.3 SDs below the normal population matched for sex and age. In the total skeleton, the legs were the most severely affected area (Z score -1.5). The body composition showed no significant difference compared with the normal population. The BMD of 56% of the patients was less than -2.5 SDs from the average normal young values. Patients with a history of vertebral fractures had diminished mineral density of the lumbar spine, as did those who had had no fractures. Of the risk factors studied, patients with premature menopause had a lower bone mass compared with patients with normal menopausal age (Z score of the total skeleton was -2.1 +/- 1.8 versus -1.1 +/- 1.0) but the difference did not reach statistical significance. The bone mass was not affected in patients with regular menstrual cycles. There were no statistically significant differences in high levels of bilirubin, advanced stages of the disease, or the biochemical variables studied. It is concluded that patients with primary biliary cirrhosis present diminished cortical and trabecular bone mass, whereas body composition was unaffected. Premature hormone deficit, possibly triggered by the chronic hepatic pathology, is a contributing factor to the osteoporosis in this population.