Skeletal involvement in female acromegalic subjects: the effects of growth hormone excess in amenorrheal and menstruating patients.

Bone involvement is a common clinical feature in acromegalic patients, though previous studies gave divergent results possibly because of the different gonadal status of the patients studied. To study the influence of estrogen milieu in these patients, we evaluated 23 acromegalic patients with active disease, subdivided into two groups: menstruating and amenorrheal patients, comparable for duration and activity of disease. Forty-two matched women served as controls. Skeletal involvement was studied by measuring: (a) the main biomarkers of bone turnover: serum alkaline phosphatase total activity (AP), bone GLA protein (BGP), serum carboxy-terminal propeptide of type I collagen (PICP), serum type I cross-linked N-telopeptide (ICTP), and urinary pyridinoline and deoxypyridinoline corrected for creatinine (Pyr/Cr, D-Pyr/Cr) and urinary calcium/creatinine ratio (Ca/Cr); (b) bone mineral density (BMD), as measured by quantitative computed tomography both at lumbar spine and distal radius, and by dual X-ray absorptiometry both at lumbar spine and at three femoral sites (Ward's triangle, femoral neck, and great trochanter). AP, BGP, ICTP, Pyr/Cr, D-Pyr/Cr were significantly higher in patients than in controls, independent of the menstrual pattern. Higher PICP levels were found in the whole group and in menstruating acromegalics when compared with control women; no difference was found in amenorrheal patients, who in turn showed higher urinary Ca/Cr values. When patients were considered all together, BMD at spine, femoral neck, and trochanter was higher than in controls. In contrast, when the gonadal status was taking into account and, menstruating and amenorrheal subjects were considered separately, BMD at spine, but not in other sites, was significantly higher in menstruating patients than in controls. In contrast, no difference of BMD values at any site was observed between amenorrheal patients and controls. The mean BMD Z scores allowed us to detect an unequal involvement of different skeletal sites. Our results show that bone turnover is increased in acromegalic women and suggest that GH anabolic effect on bone is more evident in the presence of estrogens and that different skeletal sites may be affected differently by hormone excess.

Altered bone mass and turnover in female patients with adrenal incidentaloma: the effect of subclinical hypercortisolism.

The strategy of treatment for patients with adrenal incidentalomas (AI) may depend upon the presence of hormonal hypersecretion. Although alterations of bone turnover have been recently reported, data on bone mineral density (BMD) are not available in AI patients. We evaluated bone turnover and BMD in 32 female AI patients and 64 matched controls. Spinal and femoral BMD were similar in patients and controls. Serum bone GLA protein (6.8+/-3.5 vs. 8.8+/-3.2 ng/mL; P<0.005) and PTH (48.8+/-15.1 vs. 37.2+/-10.9 pg/mL; P<0.0001) were different in patients and controls. Patients were then subdivided into 2 groups: with (n = 8; group A) or without (n = 24; group B) subclinical hypercortisolism. PTH was higher (P<0.05) in group A than in group B and in both groups than in controls (57.1+/-13.6, 46.0+/-14.8, and 37.2+/-10.9 pg/mL, respectively), and bone GLA protein was lower in group A than in group B and controls (3.8+/-2.3, 7.5+/-3.1, and 8.8+/-3.2 ng/mL, respectively; P<0.05). Serum type I cross-linked C telopeptide and fasting urinary deoxypyridinoline/ creatinine were not different in the three groups. BMD at each site was lower (P<0.05) in group A than in group B and controls. Bone mass and metabolism are altered in AI patients with subclinical hypercortisolism and should be taken into account, therefore, when addressing the treatment of choice for these patients.

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.

Plasma beta-endorphin response to exercise in patients with congestive heart failure.

OBJECTIVE: To determine whether the net release of beta-endorphin during exercise, similar to that of norepinephrine, is related to functional disability in patients with congestive heart failure. BACKGROUND: Plasma beta-endorphin and norepinephrine levels are elevated at rest in patients with heart failure, reflecting a functional disability. The net release of beta-endorphin during exercise in patients with heart failure is unknown. METHODS: We measured plasma beta-endorphin and norepinephrine levels (respectively: radioimmune and radioenzymatic assay) at rest and during graded exercise testing in 28 patients with congestive heart failure (Weber's class A, 10; B, 9; and C, 9) and in 9 normal subjects. RESULTS: At rest, plasma beta-endorphin levels were higher in patients in classes B and C than in normal subjects (p < 0.05 and < 0.01, respectively). At peak exercise, patients in different functional classes and normal subjects reached similar beta-endorphin levels. However, the net release of beta-endorphin during exercise was lower in patients in classes B and C than in those in class A and normal subjects (p < 0.01 for both). At rest, plasma norepinephrine levels were significantly higher in patients than in normal subjects (p < 0.01). At peak exercise, norepinephrine levels were significantly lower in class C patients than in normal subjects (p < 0.05), and tended to be lower in patients in classes A and B (p = NS). The net release of norepinephrine during exercise was lower in patients than in normal subjects (p < 0.01). In patients, releases of both beta-endorphin and norepinephrine during exercise were related to peak oxygen consumption and duration of exercise, but not to resting left ventricular ejection fraction. CONCLUSIONS: In patients with congestive heart failure, the net release of plasma beta-endorphin during exercise is decreased, like norepinephrine, and reflects a functional disability.

Increased risk of neurological relapse in acute lymphoblastic leukemias with high levels of cerebrospinal fluid thymidine kinase at diagnosis.

Cerebrospinal fluid thymidine kinase (CSF-TK) was measured at diagnosis in 62 patients with acute lymphoblastic leukemia (ALL) without initial neurological manifestations, who achieved a complete remission after chemotherapy. During the follow-up period, 10 patients developed central nervous system (CNS) involvement. At the onset of the disease mean CSF-TK levels in these subjects were found to be significantly higher than those observed in patients without subsequent CNS complications. In particular, 7/10 (70%) of these patients who presented CSF-TK levels above the upper limit of normal (1.4 U/microliters) had evidence of a neurological relapse, while 49/52 (94.2%) of subjects with presenting CSF-TK levels of up to 1.4 U/microliters did not develop a neurological leukemic disease (p < 0.00001). The white blood cell count at diagnosis was significantly increased, but not directly correlated to CSF-TK levels, in the group with CNS involvement, while age, serum thymidine kinase levels and lactic dehydrogenase, FAB classification or immunophenotype were not different in patients with or without neurological relapse. In conclusion, increased levels of CSF-TK at presentation correlate with a high risk of subsequent CNS involvement in patients with responsive ALL.

PSA and bone scintigraphy.

The authors evaluate the role of prostate specific antigen (PSA) and bone scintigraphy in the follow-up of radical prostatectomy-treated and radiotherapy-treated patients. 784 patients were evaluated by simultaneous PSA assay and bone scans. The correlation between PSA levels and extension of bone metastases was good. The frequency of extraskeletal metastases was low: only 13 patients had soft tissue metastases without bone involvement and 33/138 patients with bone metastases had also extraskeletal metastases. The results underline the importance of PSA and the possibility to omit bone scan when the PSA level is below 8 ng/ml in patients who did not undergo anti-androgenic treatments.

Preliminary clinical evaluation of free/total PSA ratio by the IMMULITE system.

The role of free (F) and complexed serum PSA is now under investigation. In the present study, we evaluated the clinical significance of F-PSA and F/Total (T) PSA ratio in a preliminary series of samples from 88 patients with prostate cancer (PC), 113 with benign prostatic disease (BPD), and 98 with non-prostatic disease (NP). We used the F-PSA and third generation T-PSA (DPC, Los Angeles, USA) chemiluminescent enzyme immunometric assays with the IMMULITE automated system. At the 10 ng/ml cutoff for T-PSA levels, we obtained a sensitivity of 83% with a specificity of 100% in NP and 80% in BPD. The addition of the F/T ratio--rather than F-PSA levels--was useful to better discriminate PC and BPD in the cases erroneously classified by T-PSA alone: 44/68 samples (65%) were correctly diagnosed. Moreover, the F/T ratio was particularly effective in the critical T-PSA range between 4.1-9.9 ng/ml; 26/40 cases (65%) were correctly evaluated. In conclusion, the F/T ratio seems to be an interesting auxiliary test to T-PSA, to be reserved for selected cases where additional diagnostic information is necessary.

Bone formation markers and pain palliation in bone metastases treated with strontium-89.

In several bone disorders, including those with metastatic involvement, changes in procollagen type I C-terminal and type III N-terminal peptides are detected, as indications of altered bone metabolism. Assessment of bone turnover could play a role in the evaluation of response to Strontium-89 used as palliative treatment in symptomatic bone metastases from various primary tumors. A correlation between bone formation rate markers procollagen I and III and efficacy of ionic Strontium-89 was shown in a group of 13 patients who underwent treatment with 4 mCi of Strontium-89 for painful bone metastases: 5 from breast, 7 from prostate, and 1 from lung carcinoid cancer. Assessed as a modification of analgesic intake, pain, and ambulation, there were 6 complete remissions, 3 partial remissions, and 4 nonresponders. The duration of the response was from 2 to 11 months. Procollagen I and III levels were found to be highly abnormal in those with no benefit from Strontium-89 administration but were in the normal range or only slightly elevated in those achieving complete or partial pain control, thus correlating with the clinical response.

Scintigraphic oesophageal clearance in diabetics: clinical usefulness.

The whole digestive tract is one of the sites most involved in diabetic autonomic neuropathy. The aim of this work was to validate the clinical usefulness of oesophageal scintigraphy in the early detection of this complication of diabetes. Eighty-one diabetic patients without oesophageal symptoms were studied by solid meal scintigraphic test (SMST) and 35 out of them also by liquid meal scintigraphic test (LMST). As controls, 20 normal volunteers were studied by LMST and 14 by SMST. Forty-seven diabetics studied by SMST were also evaluated by cardiovascular tests (CT) and for the presence of retinopathy and peripheral neuropathy. The most statistically significant difference between diabetics and controls was found at 75s with SMST. SMST results showed a statistically significant correlation with CT. No correlation was found with the presence of retinopathy or peripheral neuropathy. We conclude that SMST is a useful, safe, low-cost diagnostic tool in the detection of diabetic autonomic neuropathy.

Reduction of mononuclear cytokine production in hemodialysis patients treated with steam-sterilized low-flux polysulphone membranes.

An increased cytokine production, correlated with long term complications of uremic disease, has been described during hemodialysis. To identify possible differences in the cytokine release of differently sterilized membranes, we enrolled six uremic patients on chronic hemodialysis. The patients underwent dialysis with ETO-sterilized low-flux polysulphone membranes (F6, Fresenius AG) for at least three months (A1), they were then switched to steam-sterilized polysulphone membranes (F6-HPS Fresenius AG) and further evaluations after one (B1) and two months (B2) were carried out. A final evaluation (A2) was made one month after switching back to F6 dialyzers. At each time period, samples were drawn to measure IL-1beta released by cultured mononuclear cells (MN). Moreover, dialysate samples were collected to test endotoxin levels. C3a and C5a levels were assessed at 0, 5, 15 and 60 min from starting hemodialysis. Anti-ETO IgE levels were also assayed at A1, B1 and A2. The LAL test revealed a good quality dialysate. The mean pre-dialysis IL-1beta levels were 215 pg/million cells at A1; falling to 49 at B1, and 54 at B2 (p<0.01); there was then a sharp rebound at A2: 284, p<0.01. Post-dialysis levels followed the same pattern. No correlation between the dialysate endotoxin level and cytokine release was found. Complement activation did not change and in all the phases of the study no anti-ETO IgE was detected in any of the subjects. Our data suggest that the steam sterilized polysulphone membrane induces a lower cytokine release than the ETO sterilized membrane, although the mechanism by which it does so remains to be clarified.

Is steam sterilization really making any difference in dialysis-induced cytokine release?

Ethylene oxide (ETO) is presently the most commonly used sterilization method for medical devices. Although alternative sterilization modes such as steam sterilization have been suggested, the effect of steam on dialysis-induced cytokine release is unknown. We enrolled 9 patients on chronic hemodialysis and evaluated at different intervals IL-1beta production while treated with ETO (NC 1785-Bellco) and steam sterilized NC 1785S-Bellco) Synthetically Modified Cellulose (SMC). A basal test during treatment with NC 1785 was performed (A); the same test was set up 4 weeks after treatment with NC 1785S (B) and, lastly, 4 weeks after returning to NC 1785 (C). Peripheral blood mononuclear cells (PBMC) were purified before and after the dialysis session, were isolated on a Ficoll/Hypaque gradient and incubated for 24 h. Spontaneous IL-1beta release was evaluated in the supernatant and in the lysate. In A, IL-1beta levels were (in pg/ml/10(6) cells, in supematant and lysate, respectively): 5.8 +/- 4.8 and 7.6+/-5.2 in pre-HD and 4.68 +/- 3.6 and 9.7 +/- 6.65 in post-HD. These levels showed a clear reduction in B: 2.5 +/- 2.2 and 4.4 +/- 3.1 in pre-HD, and 4.35+/- 6.6 and 7.52 +/- 7.22 in post-HD. In the C test, 4 weeks after the return to the ETO membrane, IL-1beta levels remained unchanged: 2.9 +/- 1.8 and 4.5 +/- 3.1 in pre-HD; and 2.6 +/- 3 and 5.7 +/- 6.6 in post-HD. Statistical analysis showed significant changes in the pre-HD levels both in supematant (p < 0.04) and in lysate (p < 0.04). Steam sterilization of SMC induced a lower spontaneous IL-1beta release, but this effect was not statistically significant due to the large inter-individual variation. Hence, contrary to claims of better biocompatibility, steam sterilization does not result in a reduced production of pro-inflammatory IL-1beta.

Ethylene-oxide and steam-sterilised polysulfone membrane in dialysis patients with eosinophilia.

Eosinophilia and some acute dialysis side-effects, such as itching, flushing and bronchospasm, are often associated with the presence of ethylene oxide (ETO) as dialyzer sterilizing agent. This study evaluated the effects of two different polysulfone (PS) hollow-fiber dialysers sterilized with ETO and steam in 31 chronic dialysis patients with eosinophilia. Clinical symptoms, metabolic and biochemical parameters, complement (C3a and C5a) activation and production were evaluated in each patient dialysed for two months at a time with Cuprophan dialyser, ETO-PS dialyser and steam-PS dialyser. The steam-sterilizer agent does not alter the purifying capacity of the PS membrane which maintains its superiority over Cuprophan in terms of biocompatibility. Using steam-PS, intradialytic eosinophil kinetics seems to improve. In some patients with high serum levels of ETO-specific IgE these levels tend to diminish. Generic intradialytic symptoms do not differ between the two sterilization methods, although some hypersensitivity symptoms during the first dialysis hour are considerably lower in some patients when steam-sterilized PS is used.

[The area of focal nephritis measured by echography: useful indications in patients with unexplained back pain in comparison with other assessments]. / Le aree di nefronia focale all'ecografia: utili indicazioni in pazienti con inspiegabili dolori dorsali e confronto con altre indagini.

In some patients undergoing an U.S. study of kidney for lumbodynia, it's sometime possible to visualize hypoechoic and areas poorly demarcated without distal acoustic enhancement, localized within the cortex and disrupting the cortico-medullary junction. These findings, called focal nephritis, associated to minimal retention of urine in the bladder, reflect an inflammatory process involving the renal parenchyma, in spite of normal urine analysis. To confirm this theory, 7 patients who presented these findings at US study of kidney underwent renal scintigram with labeled granulocytes. This test revealed the presence of focal bacterial nephritis in the same hypoechoic areas. Therefore US study of kidney combined with renal scintigram is useful to diagnose inflammatory process of the kidney in patients complaining lumbodynia.

Sun exposure questionnaire predicts circulating 25-hydroxyvitamin D concentrations in Caucasian hospital workers in southern Italy.

INTRODUCTION: Recent sun exposure should correlate with circulating 25-hydroxyvitamin D [25(OH)D] due to ultraviolet B (UVB)-catalyzed cutaneous synthesis of vitamin D. METHODS: A Sun Exposure Score was calculated for healthy adults using a recall questionnaire assessing daily Time in Sun (<5 min, 5-30 min, >30 min) and Skin Exposure (face/hands; face/hands and arms; face/hands and legs; and "bathing suit") for 1 week in each of the winter and summer (n=47 and 23, respectively; n=18 participated in both). Concentrations of 25(OH)D were measured by DiaSorin RIA on end-of-week sera. RESULTS: Mean serum 25(OH)D was higher in summer than winter (58.6+/-16.5 nmol/L vs. 38.8+/-29.0 nmol/L, respectively, P=0.003 unpaired). The calculated Sun Exposure Score correlated strongly with serum 25(OH)D during summer (Spearman's rho=0.59, P=0.003); based on the Pearson coefficient of determination, summer Sun Exposure Score explained 38% of the variability in summer serum 25(OH)D. The Sun Exposure Score did not correlate with 25(OH)D in the winter (rho=0.19, P=0.210). The summer correlation was largely explained by the Time in Sun (rho=0.58, P=0.004) rather than area of Skin Exposed (rho=0.10, P=0.660). Although there was a correlation between winter and summer Sun Exposure Scores (rho=0.63, P=0.005), there was no summer vs. winter correlation in serum 25(OH)D (rho=0.08, P=0.76). CONCLUSION: This simple 1-week sun exposure recall questionnaire predicted summer serum 25(OH)D concentrations, accounting for 38% of the variability in 25(OH)D among healthy Italian adults.

[Determination of thymidine kinase in the cerebrospinal fluid as a marker of leukemic meningosis]. / Determinazione della Timidina Kinasi nel liquor cerebrospinale quale marker della meningosi leucemica.

Levels of Thymidine Kinase (TK) in cerebrospinal fluid (CSF) were longitudinally evaluated in 68 patients with acute leukemia. Values significantly above the normal range were found in all cases with meningeal involvement (in two subjects before the cytological evidence of leukemic cells in CSF). Such high levels decreased until normal values after an effective treatment. Two patients with multiple cerebral neoplastic nodules without infiltration of meninges showed normal CSF-TK values. No false positive cases were observed. Both kinetic activity and mass of leukemic cells appeared to influence CSF-TK levels. Thus, CSF-TK appears to be a promising marker in diagnosing and monitoring meningeal disease in the course of acute leukemia.

Evaluation of the use of ultrasonography in the study of liquid gastric emptying.

Gastric emptying of two different test liquid meals (500 ml isotonic saline and 500 ml skimmed milk, 1.8% fat) has been measured in 10 (saline) and in 19 (milk) normal volunteers by means of real-time ultrasonography (RUS) and scintigraphy, employed simultaneously. In each subject, saline and milk contained 37 MBq of diethylenetriaminopentacetic acid (DPTA) marked with 99mTc. Determinations were made thereafter every 5 min up to 45 min with saline and every 30 min up to a maximum of 220 min with milk. The determination of gastric emptying by RUS was obtained indirectly through the measurement of gastric dimensions, with a single scan performed at the epigastrium, while the subject was kept in a standing position. At each observation, the percent decrease of gastric measurements and the decay in radioactivity over the gastric region were calculated, blind, by two independent examiners. Linear regression and correlation coefficient were subsequently computed for gastric measurements and decay in radioactivity. The results show that the values obtained with RUS do not differ grossly from the ones obtained with scintigraphy. This suggests that the ultrasonographic determination of gastric dimensions with a single section of the stomach may be a valuable method for use in the evaluation of gastric emptying of liquids.

Are the lower oesophageal sphincter relaxations in achalasia always incomplete? A manometric and scintigraphic study.

In two patients with achalasia we found intermittent, complete lower oesophageal sphincter (LES) relaxations at manometric evaluation. These patients had no weight loss, minimal oesophageal dilation, lower LES pressure and faster radionuclide oesophageal emptying when compared with other achalasia patients. Concurrent performing of radionuclide oesophageal emptying and manometry showed that the complete relaxations (CRs) were too short and functionally unsuccessful. Our findings suggest that these patients may be at an earlier disease stage and that intermittent CRs of LES may occasionally occur in achalasia.

Gallbladder function and gastric liquid emptying in achalasia.

Because of evidence that the abnormalities in achalasia are not restricted to the distal esophagus, we investigated gallbladder function by cholescintigraphy in the steady state and in response to CCK and the scintigraphic gastric emptying of a liquid caloric meal in 10 individuals with achalasia and 10 normal controls. No abnormalities were found during the filling phase of the gallbladder but seven of the 10 patients showed a 50% reduction in the ejection fraction (39.4% +/- 30.4 vs 80.3 +/- 8.3 of controls, mean +/- SD, P = 0.007) and a slower than normal ejection phase (9.1%/min +/- 6.6 vs 18.1 +/- 4.5, P = 0.02. In eight of the 10 patients, gastric liquid emptying was accelerated with a T1/2 of 41.5 min +/- 15.4 vs 74.7 min +/- 11.5 in the controls (P = 0.007). It is concluded that in some achalasia patients extraesophageal functional abnormalities of the gastrointestinal tract may be found. Whether these findings are promoted by degenerative charges of extraesophageal nerve fibers as well as their clinical significance require further investigations.