Urinary excretion of pyridinium cross-links and serum osteocalcin levels in patients with primary high-grade osteosarcoma.

Osteosarcoma is the most frequent primary high grade bone tumor, usually occurring in adolescents and children. The aim of the present study was to investigate parameters of bone turnover as urinary excretion of pyridinoline (Pyr), and deoxypyridinoline (D-Pyr), serum osteocalcin (OC), and total alkaline phosphatase (AP) in patients with osteosarcoma. Thirty-five patients aged 7-22 (median age 14) with primary high-grade osteosarcoma of the extremity entered the study. A control population of age- and sex-matched healthy individuals was studied. Urinary excretion of Pyr, D-Pyr was measured on fasting urine specimens, corrected for creatine excretion (Ucr), and expressed as pM/microM UCr. At the same time as urine collection, blood samples were taken for measurement of AP and OC. In patients with osteosarcoma the urinary excretion of D-Pyr (74.5 +/- 41) was significantly higher (P = 0.005) than in controls (38.2 +/- 22.5). The serum level of OC was significantly lower (P < 0.001) in patients with osteosarcoma than in controls. Moreover, significantly (P = 0.03) higher excretion of D-Pyr (85.3 +/- 43) was found in patients who relapsed after surgical removal of the tumor and chemotherapeutic treatment compared with those (58.1 +/- 22) who remained continuously free of disease. The present study showed significant abnormalities of urinary excretion of pyridinium crosslinks and serum OC level in patients with osteosarcoma. The relation between urinary excretion of D-Pyr and biological tumor aggressiveness observed in the present study requires further investigation.

Correlation between cystatin C and serum creatinine as markers of renal function in patients with neoplasms of the locomotor system.

Creatinine levels and clearance are used to monitor renal function in clinical practice. Cystatin C is produced by most nucleated cells in a consistent manner, uninfluenced by inflammatory processes, sex, age, eating habits or nutritional status. Serum cystatin C concentrations are mainly dependent on glomerular activity and are an endogenous biochemical marker of glomerular filtration. The aim of this study was to test the efficiency of cystatin C assay as an alternative marker of renal function. Statistical analysis of our results showed that cystatin C levels were significantly correlated to creatinine and creatinine clearance levels. However, it is still premature to suppose that cystatin C can replace creatinine in routine tests. Establishing cystatin C levels can be useful in cases in which it is not possible to determine creatinine clearance.

Bone turnover in short-term and long-term home parenteral nutrition for benign disease.

6 mo afterward. Long-HPN was assessed only at baseline. In short-HPN, there was a hyperkinetic turnover at baseline. At follow-up, OC was similar to baseline, whereas cross-links, urinary calcium and magnesium decreased (P < 0.03), and parathyroid hormone increased (P < 0.001). The variation of urinary calcium correlated with that of cross-links (r = 0.73, P < 0.04). In long-HPN, OC was low or low-normal in almost all the patients, and cross-links were normal. Mean OC was lower than that of short-HPN both at baseline (P < 0. 003) and at follow-up (P < 0.002). The results suggest that in the early period of HPN bone metabolism improved from a hyperkinetic turnover to a positive balance. A low bone-formation rate appeared to be a characteristic feature of long-term HPN.

[Determination of carbohydrate trasferrin (CDT) in the legal medical assessment of being fit to drive]. / Il dosaggio della transferrina carboidrato carente (CDT) nella valutazione medico-legale dell'idoneità alla guida.

BACKGROUND: According to the literature carbohydrate-deficient transferrin (CDT) is thought to be the most sensitive and specific marker of alcohol abuse, but must always be combined with other laboratory tests. Until now the amount of CDT that indicates a state of chronic alcoholism has not been established. Therefore, our aim was to quantify the percentage of CDT that discriminates social drinkers from alcoholics. METHODS: A retrospective study was carried out covering a period of four months on patients who came to us after having their driving licenses suspended for drink driving: 100 male and female subjects aged between 21 and 65 years were examined. This population was compared to a control group of 50 subjects matched for age, who consumed a moderate amount of alcohol, and had never had their driving licenses suspended. RESULTS: The percentage of CDT was found by heterogenous enzyme immunoassay that involves column separation and turbidimetry. There was a notable difference in the amount of CDT between the two groups. The ANOVA and Levene tests were used for statistical analysis. CONCLUSIONS: The authors found the percentage amount of CDT that discriminates the two groups, highlighting the important role of this marker of alcohol abuse in a relevant social context.

Prospective evaluation of high-dose ifosfamide-related nephrotoxicity in young adult patients with recurrent osteosarcoma previously treated with cisplatin, methotrexate and standard-dose ifosfamide.

A prospective evaluation of high-dose ifosfamide (IFO)-related nephrotoxicity in adults and young adults previously treated with cisplatin, methotrexate (MTX) and standard-dose IFO was performed. Eighteen patients (median age 22) with recurrent osteosarcoma were studied: 11 were pretreated with MTX, cisplatin and standard-dose IFO, and seven with MTX and cisplatin. The treatment was comprised of four cycles of high-dose IFO (15 g/m2 over 5 days CI) and mesna at equivalent dose with granulocyte colony stimulating factor support. Renal function was assessed before treatment, after each IFO cycle and after chemotherapy completion. Acute nephrotubular damage was always observed after each IFO cycle with significant changes of renal tubular enzymes N-acetyl-beta-D-glucosaminidase, alanine aminipeptidase, urinary excretion and reduction of tubular reabsorption of phosphate. The appearance of glycosuria was related to the cumulative dose received. Transient and reversible renal tubular acidosis was observed in three patients. WHO grade I renal toxicity was observed in two patients. After chemotherapy completion, persistent mild glomerular and nephrotubular impairment was observed in one patient who had also received aminoglycoside antibiotics due to febrile neutropenia. Persistent and mild glycosuria was documented in another patient. No significant changes compared to baseline values were observed in the remaining patients. We conclude that a chemotherapy regimen with high-dose IFO in young adults pretreated with MTX, cisplatin and standard-dose IFO is feasible with a mild, usually reversible, nephrotoxicity.

Determination of ifosfamide by HPLC using on-line sample preparation.

The Authors have developed a novel and easily applicable HPLC method for ifosfamide (IF) determination. This method involves on-line sample processing and its solid-phase extraction by means of an automatic preparator integrated with the chromatographic system. The calibration graph of the method is linear in the concentration range 6-200 microg/ml; minimum detectable concentration is 6 microg/ml. This highly accurate and easily reproducible method was used by the Authors in the treatment of osteosarcoma with slow infusion of ifosfamide.

Lipid peroxidation and antioxidant status in adults receiving lipid-based home parenteral nutrition.

BACKGROUND: Infusion of lipid emulsions rich in polyunsaturated fatty acids (PUFAs) may increase lipid peroxidation, which is counteracted mainly by superoxide dismutase (SOD) (a zinc-, copper-, and manganese-dependent enzyme), selenium-dependent glutathione peroxidase (Se-GSHPx), and alpha-tocopherol. OBJECTIVE: We investigated lipid peroxidation and antioxidant status in patients receiving home parenteral nutrition (HPN) providing variable amounts of a lipid emulsion rich in PUFAs, and alpha-tocopherol, zinc, copper, and manganese as recommended by the American Medical Association, and no selenium. DESIGN: Serum malondialdehyde, plasma alpha-tocopherol, selenium, Se-GSHPx, PUFAs, and red blood cell Se-GSHPx and SOD were evaluated in 12 patients and in 25 healthy control subjects. Malondialdehyde was also assessed in a group of 40 healthy control subjects. RESULTS: Patients had significantly higher concentrations of malondialdehyde and SOD and lower alpha-tocopherol concentrations and selenium nutritional status. Linear regression analysis showed that malondialdehyde was associated with the daily PUFA load (r=0.69, P< 0.03) and with plasma alpha-tocopherol (r=-0.59, P< 0.05), but stepwise multiple regression analysis confirmed only the association between malondialdehyde and alpha-tocopherol; plasma alpha-tocopherol was associated with the daily PUFA load (r=-0.65, P< 0.04) and with the duration of HPN (r=-0.74, P< 0.02). CONCLUSIONS: In HPN patients, the peroxidative stress due to lipid emulsions rich in PUFAs is counteracted primarily by alpha-tocopherol. The dosages of alpha-tocopherol, zinc, copper, and manganese recommended by the American Medical Association appear sufficient to sustain SOD activity but inadequate to maintain alpha-tocopherol nutritional status. HPN formulations should be supplemented with selenium.

High-performance liquid chromatography assay of N,N-dimethyl-p-toluidine released from bone cements: evidence for toxicity.

Five commercially available bone cements were analysed by high-performance liquid chromatography for detecting the residual content of an accelerator, the amine N,N-dimethyl-p-toluidine (DMPT), after curing. It was found that the concentration of DMPT in aqueous extracts decreases with time, being almost absent 7 days after curing. Differences were noticed among the cements; residual DMPT is higher in cements prepared with higher content of the amine. It is verified that DMPT's toxic effect on cell cultures is dose-related; a delay in the cell replication cycle is induced in vitro. Damage is reversible, thus justifying the low bone cement toxicity that is clinically ascertained.

[A prospective study on nephrotoxicity induced by continuous infusion of high-dose ifosfamide (15/m2)]. / Studio prospettico della tossicità renale da alte dosi di ifosfamide (15/m2) in infusione continua endovenosa.

BACKGROUND: A good response rate to high-dose ifosfamide (HDIFO) has been reported in metastatic osteosarcoma and soft tissue tumors. As standard dose of IFO (< 12 g/m2) can give several renal complications and patients previously treated with nephrotoxic drugs are at high risk of nephrotoxicity, a prospective study to evaluate the pattern of nephrotoxicity induced by HDIFO was carried out. METHODS: Twelve patients (11 metastatic osteosarcoma, 1 synovial sarcoma; mean age 17, R 14-34) were treated with 4 courses of HDIFO/ MESNA (15 g/m2, IV 5 day continuous infusion with bicarbonate and K supplements). All but two were previously treated with cisplatin and methotrexate. Several parameters of renal function were measured before treatment, after each HDIFO course and two months after chemotherapy completion. RESULTS: Significant changes in the urinary excretion of beta 1-microglobulin, beta 2-microglobulin, Alanine Aminopeptidase, N-Acetil-beta, D-glucosaminidase and a significant reduction in phosphate tubular absorbtion according to the cumulative dose of IFO infused, were observed. Phosphaturia and hypophosphatemia occurred in all the patients studied. In 5 patients, CrCl fell below 70 ml/min with normal serum creatinine level after 45 g/m2 IFO. Plasma bicarbonate concentration less than 20 mmol/l was observed in 5 of 48 HDIFO courses. Glycosuria was detected in 4 patients. Two months after chemotherapy completion, mild glycosuria and slightly reduced CrCl persisted in two patients, whereas the other parameters of renal function studied were similar to the baseline values. An acute, usually reversible subclinical nephrotoxicity involving glomerule and renal tubule was demonstrated in all the patients treated with HDIFO. A persisting subclinical renal impairment was shown with mild glycosuria (2/12 patients) and slightly reduced CrCl (2/12 patients).

Methotrexate serum concentration and histological response to multiagent primary chemotherapy for osteosarcoma of the limbs.

The authors investigated the influence of methotrexate (MTX) serum concentration on (histologically evaluated) tumor necrosis, induced by a primary multiagent chemotherapy, including MTX, for osteosarcoma. MTX serum peaks in 151 patients, preoperatively treated with MTX (8-12g/m2), cisplatin (120mg/m2) and Adriamycin (60mg/m2), were analyzed. Significantly (p < 0.01) higher serum MTX mean peaks were observed in patients with complete tumor necrosis (MTX 773.8 mumol/l) compared to patients with 90-99% tumor necrosis (639.8 mumol/l), 50-89% tumor necrosis (649.1 mumol/l) or less than 50% tumor necrosis (610 mumol/l). Complete tumor necrosis was observed in 9% of patients with MTX peaks of less than 600 mumol/l, in 27% of patients with serum MTX peaks between 600 and 699 mumol/l and in 37% of those with MTX peaks ranging from 700 to 799 mumol/l. Higher MTX peaks (800-899, 900-999, > 1000 mumol/l) were not associated with a further increase of cases with complete tumor necrosis. 40% of patients with an MTX peak greater than 700 mumol/l had complete tumor necrosis, compared to 15.5% of patients who did not reach this value (p < 0.002). At a multivariant analysis including age, sex, tumor site and volume, pretreatment serum alkaline phosphatase and lactic dehydrogenase levels, MTX peaks of 700 mumol/l and, less significantly, the histologic type (telangiectatic osteosarcoma), were independent factors influencing tumor necrosis. The authors conclude that MTX serum peaks significantly influence chemotherapy-induced tumor necrosis in osteosarcoma. In a primary treatment consisting of cisplatin, Adriamycin and MTX, complete tumor necrosis can be obtained in 40% of patients with MTX peak concentrations > or = 700 mumol/l.

Bone turnover in patients on home parenteral nutrition: a longitudinal observation by biochemical markers.

In order to characterize biochemical markers of bone turnover in home parenteral nutrition(HPN) patients, 8 adult patients on HPN for benign intestinal failure were studied at 0, 6 and 12 months by evaluating serum osteocalcin (bone formation marker), urinary hydroxylysyl pyridinoline, lysyl pyridinoline and beta-galactosyl hydroxylysine (bone resorption markers), serum PTH, Calcitonin, 25 vitD, 1-25vitD, serum and urinary minerals, body weight, rehabilitation degree and HPN characteristics. Three patients entered the study 2-3 months after the beginning of HPN. Their features of bone turnover were homogeneous, characterized by increased resorption associated with normal or increased formation, at baseline, and normalization of resorption associated with an increase or a parallel decrease of formation, at 6 months. At 12 months, the patterns were similar to those observed at 6 months. The patients were not of the same sex and age and had different underlying diseases and types of intestinal failure, HPN composition and serum vitamin D levels. They had weight gain that was already present at baseline and the positive outcomes of the rehabilitation and clinical status in common. Five patients entered the study more than 1 year after the beginning of HPN. They showed heterogeneous features of bone turnover that were stable throughout the study, characterized by increased resorption associated with low or normal formation in two cases, low normal resorption associated with low or normal formation in three. In one patient, who had increased resorption and low formation, the bone turnover appeared to be explained by the nutritional and clinical outcomes, which were negative. These results appeared consistent with those obtained in previous studies by bone histomorphometry, indicating that bone turnover of short-term HPN patients differed from that of long-term patients, and suggesting that the early months of HPN were associated with increased bone resorption.

[Reference values of assayable pyridinolines as markers of bone turn-over]. / Valori di riferimento delle piridinoline dosabili come marcatori del turn-over osseo.

The authors aimed to identify reference values for pyridine cross-links (HP and LP) in clinically normal populations. These cross-links are thought to be markers of bone resorption and are released by osteoclasts and eliminated in the urine. The normal values reported in the literature vary considerably. For this purpose the authors analysed groups of male and female patients, divided into age brackets, with no apparent bone metabolism disorders. Hydroxylysylpyridinoline (HP) values revealed no statistically significant differences in relation to either sex or age. Lysylpyridinoline (LP) values in subjects aged under 50 showed virtually comparable reference intervals in male and female subjects, whereas patients over 50 showed a different pattern of behaviour. In conclusion it can be said that, once reliable reference values have been identified using a urinary cross-link assay (in particular for LP), it is possible to evaluate bone resorption in postmenopausal women.

[The oral strontium load test in the assessment of intestinal calcium absorption]. / Il test da carico orale di stronzio nella valutazione dell'assorbimento intestinale del calcio.

A close correlation between calcium and strontium intestinal absorption has been described. In this study, a test using Stable Strontium has been assessed in women without abnormal calcium or bone metabolism, with no history of drugs which might affect calcium or bone metabolism. Decreasing values of Strontium intestinal absorption, according to the length of the postmenopausal period, have been observed. Besides, the Stable Strontium Test has been given in postmenopausal women with osteoporotic femur fractures. In comparison with age matched healthy women, this latter group showed a significantly lower Strontium intestinal absorption. Analogous behaviour has been reported for Calcium intestinal absorption.

[Computerized management in the surveillance of nosocomial infections]. / La gestione computerizzata nella sorveglianza delle infezioni nosocomiali.

A personal computerised system was developed for the on-going assessment and monitoring of hospital infections. The system involves the computer processing of clinical analyses. It also selects and statistically processes the data from microbiological tests conducted on hospital patients and staff. The system makes it possible to monitor the microbiological situation of the hospital environment with particular reference to the air, surfaces, instruments and material. In this way it is possible to identify the outbreak of minor hospital epidemics and to monitor their evolution and spread.