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Biomedical subjects

X Luo

Publications and source records attributed to X Luo.

At least 127 records · Page 7Linked to original sources
PubMed1999

[Effect of arginine on deep partial-thickness burn in rats].

To investigate the therapeutic effect of arginine on burn, a randomized controlled trial in 20% TBSA deep partial-thickness burned rats was designed. The rats' wound healing, cellular immunity and nitrogen balance were evaluated at appointed postburn days. The results showed that the arginine group got better wound healing and faster recovery of cellular immunity, and achieved positive nitrogen balance. These suggest that supplement of exogenous arginine after burn may be beneficial to the victim in promoting would healing, reducing postburn immune suppression and enhancing anabolism of protein.

Animals↗
PubMed1999

[Effects of alumina particle-size on mechanical properties of alumina-glass composite].

OBJECTIVE: To study the effects of alumina particle-size on mechanical properties of alumina-glass composite. METHODS: Alumina compacts were prepared by isostatic press method and sintered at 1400 degrees C for 2 hours with two various particle-size alumina. Alumina-glass composite was made by infiltrating partially sintered porous alumina with glass at 1200 degrees C for 4 hours. RESULTS: The strength and fracture toughness of nanometre alumina-glass composite were 358.2 MPa, 2.38 MPam1/2 respectively. The strength and fracture toughness of micrometer alumina-glass composite were 432.2 MPa, 5.12 MPam1/2 respectively. Image analysis of SEM micrograph showed that porous rate was about 11.5% in the nanometer alumina-glass composite, 1.2% in the micrometer alumina-glass composite, and there was more glass composition in the nanometer alumina-glass composite than that in the micrometer alumina-glass composite. CONCLUSION: The alumina volume percentage and porous rate play an important role in the strength and fracture toughness of alumina-glass composite.

Aluminum Oxide↗
PubMed1999

[Preliminary study on the levels of natural antibodies against Schistosoma japonicum in Microtus fortis in Dongting lake area].

AIM: To explore the detection rate and the levels of natural antibodies to cercarial antigen(CA), juvenile antigen(JA), adult worm antigen (AWA) and soluble egg antigen (SEA), respectively, derived from Schistosoma japoncum in Microtus fortis distributed in Dongting Lake area. METHODS: The antibodies in wild Microtus fortis(WMF), laboratory-bred Microtus fortis (BMF) and laboratory-bred Microtus fortis 15 days after S. japonicum infection (BMFi15) were detected by indirect ELISA and a comparison of the antibody levels between Microtus fortis including WMF, BMF, BMFi15 and albino mice without infection (AM), 15 days after infection(AMi15) and 42 days after infection (AMi42) was made. RESULTS: The positive rates of detection for anti-JA-Ab in WMF and BMF were 94.6% and 94.4%, respectively, followed by 85.5% and 83.3% for anti-AWA-Ab, 58.1% and 59.4% for anti-SEA-Ab, and 14.3% and 13.9% for anti-CA-Ab. The levels of antibodies to the above four antigens in BMFi15 increased significantly, the detection rates being 100% for anti-JA-Ab and anti-AWA-Ab, 84.4% for anti-SEA-Ab and 65.6% for anti-CA-Ab. The levels of antibodies in WME, BMF and BMFi15 had the similar trend(JA > AWA > SEA > CA), and those in BMFi15 to CA, JA, AWA and SEA increased by 1.9, 2.2, 2.1 and 1.5 folds, respectively, when compared with BMF. CONCLUSION: Natural antibodies to Schistosoma japonicum were found in wild and labortorybred Microtus fortis. The levels of antibodies in BMFi15 to four above antigens were apparently higher than those in AMi15.

Animals↗
PubMed1998

[Reference value of urinary arsenic for nonoccupational exposed subjects in Henan].

Urinary arsenic levels of 2065 nonoccupational exposed subjects in Henan were determined by spectrophotometric analysis. The results showed: (1) The difference was not significant among Zhengzhou, Luoyang, Anyang, Xinyang and Shangqiu (0.01 < P < 0.025). (2) The difference was not significant among different ages(0.01 < P < 0.025) and between sexes(P > 0.05). (3) The distribution was positive skewness. The median of urinary arsenic was 17.8 micrograms/L. The arithmetic mean was 20.7 micrograms/L. The standard deviation was 15.2 micrograms/L. The geometric mean was 17.3 micrograms/L. (4) It is suggested that the reference upper limit value of urinary arsenic for nonoccupational exposed subjects in Henan in 56 micrograms/L.

Adolescent↗
PubMed1998

Bid, a Bcl2 interacting protein, mediates cytochrome c release from mitochondria in response to activation of cell surface death receptors.

We report here the purification of a cytosolic protein that induces cytochrome c release from mitochondria in response to caspase-8, the apical caspase activated by cell surface death receptors such as Fas and TNF. Peptide mass fingerprinting identified this protein as Bid, a BH3 domain-containing protein known to interact with both Bcl2 and Bax. Caspase-8 cleaves Bid, and the COOH-terminal part translocates to mitochondria where it triggers cytochrome c release. Immunodepletion of Bid from cell extracts eliminated the cytochrome c releasing activity. The cytochrome c releasing activity of Bid was antagonized by Bcl2. A mutation at the BH3 domain diminished its cytochrome c releasing activity. Bid, therefore, relays an apoptotic signal from the cell surface to mitochondria.

Amino Acid Sequence↗
PubMed1998

The 40-kDa subunit of DNA fragmentation factor induces DNA fragmentation and chromatin condensation during apoptosis.

We report here the reconstitution of a pathway that leads to the apoptotic changes in nuclei by using recombinant DNA fragmentation factor (DFF), a heterodimeric protein of 40 and 45 kDa. Coexpression of DFF40 and DFF45 is required to generate recombinant DFF, which becomes activated when DFF45 is cleaved by caspase-3. The cleaved fragments of DFF45 dissociate from the DFF40, the active component of DFF. Purified DFF40 exhibited an intrinsic DNase activity that was markedly stimulated by chromatin-associated proteins histone H1 and high mobility group proteins. DFF40 also triggered chromatin condensation when incubated with nuclei. These data suggest that DFF40 is sufficient to trigger both DNA fragmentation and chromatin condensation during apoptosis.

Amino Acid Sequence↗
PubMed1998

Retinoblastoma protein-overexpressing HL60 cells resistant to 1,25-dihydroxyvitamin D3 display increased CDK2 and CDK6 activity and shortened G1 phase.

Drug resistance that occurs during cancer chemotherapy has been a major problem in controlling neoplastic progression. To study the cellular mechanisms of acquired drug resistance we developed 1,25-dihydroxyvitamin D3 (1,25D3)-resistant sublines of promyelocytic leukemia HL60 cells which have increased proliferation rates (Exp. Cell Res., 224, 312, 1996; Cancer Res., 50, 5513, 1996). We report here that the resistant sublines display varying degrees of shortening of the G1 phase as compared to the parental HL60-G cells. Protein levels of cyclins E, D1, D2 and D3 are elevated in these resistant cell lines, and cyclin D1 is especially high in 40AF cells, which has the shortest G1 length. The protein levels of cyclin-dependent kinase (Cdk)2, Cdk4 and Cdk6 are not altered in the resistant sublines. Both Cdk2 and Cdk6-associated kinase activites are increased in the resistant sublines, but not Cdk4 kinase activity. Protein levels of p27Kip1 are not consistently altered in the resistant sublines as compared to the parental HL60-G cells, but are reduced relative to HL60-G cells arrested by 96 h treatment with 1,25D3. Interestingly, the resistant cell lines constitutively express high levels of retinoblastoma protein (pRb), and pRb is highly phosphorylated, indicating that the G1 cyclin/Cdk complexes in the resistant cells are physiologically active. The results suggest that the increased activity of cyclin D/Cdk6, and perhaps cyclin E/Cdk2, lead to rapid hyperphosphorylation of pRb and consequently a shorter early G1 phase, and that in the resistant cells the increased ratio of cyclin E to p27Kip1 results in activation of Cdk2 and contributes to the abrogation of the 1,25D3-induced block to the S phase entry. Additionally, it is apparent that constitutively increased levels of pRb are compatible with increased rates of cell proliferation.

CDC2-CDC28 Kinases↗
PubMed1998

Relationship between topotecan systemic exposure and tumor response in human neuroblastoma xenografts.

BACKGROUND: Topotecan is a topoisomerase I inhibitor with activity against xenografts of childhood solid tumors and established clinical activity against neuroblastoma and rhabdomyosarcoma. We have studied the relationship between systemic exposure to and the antitumor activity of topotecan lactone (the active form of the drug) in the xenograft models. Furthermore, we determined whether the responses seen in these models occur at systemic exposure levels that are tolerable in children. METHODS: Neuroblastoma xenografts derived from the tumors of six different patients were established subcutaneously in immune-deprived mice. Topotecan was administered by intravenous bolus injection 5 days a week for 2 consecutive weeks, repeated every 21 days for three cycles. The minimum daily doses that induced complete responses (CRs) and partial responses (PRs) were determined. Topotecan lactone pharmacokinetic studies were performed in both tumor-bearing and nontumor-bearing mice. RESULTS: The minimum doses associated with CRs and PRs in four of the six neuroblastoma xenografts were 0.61 and 0.36 mg/kg body weight, respectively. The topotecan lactone single-day systemic exposures associated with these doses were 88 and 52 ng x hr/mL, respectively. There was an approximately sixfold difference in topotecan lactone systemic exposure (290 ng x hr/mL versus 52 ng x hr/mL) associated with achieving CRs in the least-sensitive and most-sensitive tumors, respectively. CONCLUSIONS: Neuroblastoma xenografts are highly sensitive to topotecan therapy, and responses in mice are achieved at systemic exposures similar to those that are clinically effective and tolerable in children. These results support the concept of deriving preclinical data relating systemic exposure to antitumor activity in xenograft models. Such data may be valuable in making informed decisions regarding the clinical development of new agents.

Adrenal Gland Neoplasms↗
PubMed1998

Clinical effects and pharmacokinetics of the fusion protein PIXY321 in children receiving myelosuppressive chemotherapy.

UNLABELLED: A hemopoietin with the ability to accelerate both platelet and granulocyte recovery after intensive chemotherapy would have great clinical utility. The recombinant fusion protein composed of human granulocyte-macrophage colony-stimulating factor and interleukin-3 (PIXY321), showed some promise in early adult trials. However, studies for pediatric patients are limited, and there are no systematic data on the pharmacokinetics of PIXY321 given over prolonged periods at current dosage levels. PURPOSE: To determine the safety, clinical effects and plasma concentrations of increasing doses of PIXY321 in children treated with myelosuppressive chemotherapy. METHODS: A total of 39 children with relapsed or high-risk solid tumors were enrolled in this phase I/II study. PIXY321 was administered once or twice daily by subcutaneous injection in total doses of 500 to 1000 microg/m2 per day for 14 days after each course of chemotherapy with ifosfamide, carboplatin, and etoposide (ICE). Pharmacokinetic studies were performed on day 1 of the first course in 33 patients and repeated on day 14 in 13 patients (once-daily schedule only). RESULTS: Although mild local skin reactions and fever were frequent, no dose-limiting toxicity was identified at the maximum dose studied (1000 microg/m2 per day). There were no statistically significant differences in chemotherapy-induced hematologic toxicity with increasing doses of PIXY321 or with twice-daily vs once-daily dosing. On day 1, the median PIXY321 clearance was 657 ml/min per m2 (range 77 1804 ml/min per m2) and the median half-life was 3.7 h (range 2.1-20.8 h). On day 14, clearance increased in all patients studied (median increase 63%), with a corresponding decrease in the median 12-h concentration (from 1.2 to 0.25 ng/ml). Maximum concentrations were < 1 ng/ml in 81% of patients, and only two patients had maximum plasma concentrations equivalent to those required for consistent activity in vitro. CONCLUSIONS: The recombinant fusion protein PIXY321 proved safe in children treated with myelosuppressive ICE chemotherapy but had no demonstrable clinical benefits. The pharmacokinetic studies suggest that the observed lack of hematologic benefit may be explained by low plasma concentrations resulting from increased clearance with prolonged administration. Moreover, the significant increase in PIXY321 systemic clearance in the absence of increased circulating myeloid cells suggests that the upregulation of either extravascular compartment hematopoietic progenitor cells or nonhematopoietic cells may play an important role in controlling circulating concentrations of this unique cytokine. These findings highlight the importance of a thorough assessment of the systemic disposition of cytokines when determining the dose and schedule necessary to achieve clinical activity in patients.

Adolescent↗
PubMed1998

Evidence of ED-B+ fibronectin synthesis in human tissues by non-radioactive RNA in situ hybridization. Investigations on carcinoma (oral squamous cell and breast carcinoma), chronic inflammation (rheumatoid synovitis) and fibromatosis (Morbus Dupuytren).

The splicing variant of fibronectin containing the ED-B domain (oncofoetal fibronectin) occurs in foetal tissues, reparative processes, organ fibrosis and in tumour tissues. Consequently, a supportive effect of ED-B+ fibronectin for tissue remodelling and tumour progression is assumed. A non-radioactive RNA-RNA in situ hybridization protocol for the investigation of ED-B+ fibronectin synthesis applicable in human tissues is introduced. The ED-B+ fibronectin synthesis was investigated in human disease processes, for which the occurrence of ED-B+ fibronectin is well demonstrated by immunohistochemistry (rheumatoid arthritis, oral squamous cell carcinoma, invasive ductal carcinoma of the breast and nodular palmar fibromatosis). The ED-B+ fibronectin synthesis could be shown in lining cells and in endothelial cells of synovial villi in rheumatoid arthritis, in stromal cells of oral squamous cell carcinoma and invasive ductal carcinoma and in fibro-/myofibroblasts in the proliferative and early involutional phase of nodular palmar fibromatosis. By means of double labelling (alpha-smooth muscle actin immunostaining - ED-B+ fibronectin in situ hybridization), the ED-B+ fibronectin synthesis could be shown to be a typical feature of myofibroblasts. In contrast to the often diffuse ED-B+ fibronectin immunostaining, only a few synthetically active stromal cells were observed focally accentuated within the tumour, which were interpreted as hot spots of tumour-stroma interaction.

Arthritis, Rheumatoid↗
PubMed1998

Protein tyrosine phosphatase gene expression analysis in Swiss 3T3 fibroblasts.

The aim of this study was to identify protein tyrosine phosphatases (PTPs) expressed in Swiss 3T3 fibroblasts and to examine their expression levels as well as to characterize quantitative aspects of RT-PCR based on degenerate deoxyoligonucleotides. By using an RT-PCR assay based on degenerate deoxyoligonucleotide primers, expression of mRNAs for two cytoplasmic- and six transmembrane-type PTPs in Swiss 3T3 cells was detected. The sequences of two of them are new. Among nine analyzed PTPs expressed to widely varied extends, only three have mRNA levels high enough to be seen on Northern blots with 10 microg of total RNA per lane. The frequencies with which the examined PTPs are represented among the PCR amplification products, correlate stronger with the primer fidelity, defined as the number of mismatches between the primer- and the cDNA target-sequences, rather than with the PTP expression levels. In conclusion, an RT-PCR assay based on degenerate primers can be successfully used to sample the expressed PTPs and to identify new members of this gene family. However, reliable quantification of their mRNA levels can only be achieved using the classical approaches, like Northern, RNase protection assay or nondegenerate quantitative RT-PCR.

3T3 Cells↗
PubMed1998

Lowering of p27Kip1 levels by its antisense or by development of resistance to 1,25-dihydroxyvitamin D3 reverses the G1 block but not differentiation of HL60 cells.

Cyclin-dependent kinase inhibitors are proteins with functions which appear to involve regulation of cell cycle traverse, and have been suggested to have a role in cell differentiation. However, there is as yet no rigorous proof that this is the case. We have addressed the participation of one of these inhibitors, p27Kip1, in the induction of differentiation and the subsequent G1 block induced in HL60 cells by 1,25-dihydroxyvitamin D3 (1,25D3). First, it was noted that sublines of HL60 cells able to grow rapidly in the presence of 1,25D3 have protein levels of p27Kip1 lower than the levels in cells subjected to 1,25D3-induced growth inhibition, but higher than in untreated parental cells. In contrast, there was no discernible relationship between the levels of p27Kip1 and the expression of differentiation markers. Further, HL60 cells treated with 1,25D3 and an oligonucleotide antisense, but not mismatched, to p27Kip1 showed an almost complete elimination of the 1,25D3-induced G1 block, but no decrease in the expression of differentiation markers. Similar results were obtained following transient transfection with an expression vector bearing the entire p27Kip1 coding sequence in the anti-sense orientation. This is the first direct demonstration that p27Kip1 plays a role in the 1,25D3-induced G1 arrest, and that partial reduction in its levels has no effect on the induction of differentiation in HL60 cells.

Calcitriol↗
PubMed1998

Retrograde transvenous neuroperfusion: a back door treatment for stroke.

BACKGROUND AND PURPOSE: Stroke is the third leading cause of death and the leading cause of adult disability in the United States. The clot-lysis drug tissue plasminogen activator is the only treatment that has been effective for acute stroke patients, yet there are significant limitations to its use and effectiveness. In this study retrograde transvenous neuroperfusion (RTN) was evaluated for its efficacy in reversing acute ischemia, preventing paralysis, and limiting pathological evidence of infarction in baboons. METHODS: Ten adult male baboons underwent 3.5 hours of reversible middle cerebral artery occlusion (MCAO) under isoflurane (0.25% to 1.5%) anesthesia. Five randomly chosen animals received RTN treatment 1 hour after start of MCAO. Somatosensory evoked potentials were recorded during MCAO. Animals were assigned daily neurological scores. Animals were killed 6 days after MCAO, and brains were quantitatively analyzed for infarct volume. RESULTS: Within 1 hour after RTN was started, treated animals showed significantly improved somatosensory evoked potentials (103.3% versus 75% of baseline; P<0.01). Likewise, the combined neurological score for the RTN-treated group was 99.2, while the combined mean score for the untreated group was 66.4 (P<0.015). The mean infarction volume was 8.8+/-3.1% (of contralateral hemisphere) for the control group and 0.3+/-0.2% for the RTN-treated group (P<0.01). No increased mortality was seen in the RTN-treated group. CONCLUSIONS: We conclude that RTN treatment during MCAO effectively reverses the pathophysiological sequelae of ischemia, even when the treatment is initiated 1 hour after the onset of ischemia. Although the infarct volume in the control group was variable when quantitatively assessed 6 days after 3.5 hours of MCAO, virtually no evidence of infarcts was seen in the RTN-treated group.

Animals↗
PubMed1998

Patient satisfaction after limb-sparing surgery and amputation for pediatric malignant bone tumors.

We surveyed 65 patients age 13 years or older who had been treated for malignant bone tumors and were in remission at least 1 year after limb-sparing surgery (LS) or amputation (AMP) to assess general satisfaction with the surgical outcome and its impact on various areas of functioning. Of 130 eligible patients, 65 responded (61 treated for osteosarcoma, 3 for Ewing's sarcoma, and 1 for mesenchymoma). The median current age of the cohort was 25.8 years (range, 14.2 to 47.5 years). The median time from surgery was 14.2 years (range, 4.0 to 30.4 years) for the AMP group, and 5.5 years (range, 2.0 to 13.8 years) for the LS patients. Questionnaire responses of patients treated with AMP compared to those who had LS surgery showed no significant differences in the impact of the surgical procedure on educational and occupational status, functional limitations, pain intensity and degree of pain interference, emotional distress, interpersonal/social interactions and self-image, rehabilitation experience, and overall satisfaction with the surgical procedure. Functional limitation was significantly related to pain interference, as well as emotional distress, self-image, and interpersonal difficulties for the entire cohort. Our findings highlight procedure-related advantages and difficulties that may potentially enhance decision making regarding the selection of the surgical procedure for individual patients with malignant bone tumors of an extremity.

Activities of Daily Living↗
PubMed1998

Increased mortality after successful treatment for Hodgkin's disease.

PURPOSE: To determine the impact of treatment toxicity on long-term survival in pediatric Hodgkin's disease. PATIENTS AND METHODS: We studied late events in 387 patients treated for pediatric Hodgkin's disease on four consecutive clinical trials at St Jude Children's Research Hospital from 1968 to 1990. Relative risks, actuarial risks, and absolute excess risks for cause-specific deaths were calculated. RESULTS: As of April 1997, 316 (82%) of patients were alive, with a median follow-up of 15.1 (range, 2.9 to 28.6) years. In this cohort, which represented 5,623 person-years of follow-up, 71 fatal events resulted from Hodgkin's disease (n=36), second malignancies (n=14), infections (n=7), accidents (n=7), cardiac disease (n=6), and asphyxiation (n=1). The 5-year estimated event-free survival (EFS) for the entire cohort was 79.6%+/-2.1 %, which declined to 63.1%+/-4.4% by 20 years. Cumulative incidences of cause-specific deaths at 25 years were 9.8%+/-1.6% for Hodgkin's disease, 8.1%+/-2.6% for second malignancy, 4.0%+/-1.8% for cardiac disease, 3.9%+/-1.5% for infection, and 2.1%+/-0.8% for accidents. Standardized incidence ratios showed excess risk for all second malignancies (12; 95% confidence interval [CI], 8 to 17), acute myeloid leukemia (81; 95% CI, 16 to 237), solid tumors (11; 95% CI, 7 to 16), and breast cancer (33; 95% CI, 12 to 72). Standardized mortality ratios also showed excess mortality from cardiac disease (22; 95% CI, 8 to 48) and infection (18; 95% CI, 7 to 38). CONCLUSION: Compared with age- and sex-matched control populations, survivors of pediatric Hodgkin's disease who were treated before 1990 face an increased risk of early mortality related to second cancers, cardiac disease, and infection.

Adolescent↗
PubMed1998

Late vascular occlusion of central lines in pediatric malignancies.

OBJECTIVE: To determine whether thrombi or vascular occlusion represent a late complication persisting several years after removal of central venous lines (CVLs) in children and adolescents treated for childhood cancer. METHODS: Children whose treatment for malignancy included placement of a CVL that had been removed at least 2 months previously were studied during scheduled follow-up that included contrast-enhanced computed tomography. Spiral volume acquisition was used to obtain 3-mm images from the chest apices through the right hilum, and three-dimensional reconstruction of angiograms was performed. Thrombosis/occlusion was defined as narrowing, obstruction, or filling defect of the deep venous system, with or without the formation of collateral veins. Charts were reviewed to document patient characteristics, previous CVL complications, administration of hyperalimentation, use of urokinase, and family history of venous thrombosis. RESULTS: Twenty-three patients treated for solid tumors and 2 treated for B-cell acute lymphocytic leukemia or lymphoma were studied. Lines had been in place from 0.2 to 36 months (median, 7.4) and were removed at 2.3 to 121.8 months (median, 32.5) before study. Nine patients received hyperalimentation for periods ranging from 2 to 38 weeks (median, 12). Four patients had required urokinase instillations, and one developed superior vena cava syndrome; 4 had a CVL-related infection (two superficial and two Candida line infections). Occlusion was seen on computed tomography angiograms in 3 of the 25 patients (12%; 95% confidence interval: 4.5-31%). One of the patients with occlusion had superior vena cava syndrome; none had a family history of thrombosis, use of a double lumen CVL, or multiple instillations of urokinase. CONCLUSIONS: Persistent asymptomatic vascular occlusion does occur as a late complication of CVL placement for treatment of childhood malignancies, although the frequency appears low among patients treated primarily for solid tumors. Prospective studies of large numbers of patients with a broader spectrum of diagnoses are necessary to define the incidence of and risk factors for this complication and to assess the need for prevention with anticoagulation or other therapy. Pediatricians caring for patients with a history of cancer and CVLs should be aware that these patients may have persistent vascular occlusion that could predispose them to recurrent thrombosis or postphlebitic syndrome.

Adolescent↗
PubMed1998

Diabetic nephropathy in hypertransfused patients with beta-thalassemia. The role of oxidative stress.

OBJECTIVE: Pathogenesis of diabetes-related microvascular complications involving oxidative damage by free radicals has been demonstrated. Free radical generation has been shown to derive largely from iron. Our objectives, therefore, were to determine if there is an increased incidence and/or an accelerated course of nephropathy in patients with diabetes, secondary to transfusional hemochromatosis, and to examine whether free radical activity contributes to the development of this complication. RESEARCH DESIGN AND METHODS: We evaluated nine patients with homozygous beta-thalassemia, complicated by clinically overt diabetes, for diabetic nephropathy over a 7-year period. Lipid peroxidation was quantified by measuring the presence of 20 saturated and unsaturated aldehydes, and results were compared with five normotensive type 1 diabetic patients without iron overload. RESULTS: Nephropathy developed in five of nine patients (55%) after a mean duration of overt diabetes of 3.6 +/- 2.0 years. Three patients showed evidence of progressive microalbuminuria over a 7-year period (24.7-46.2, 52.2-430.1, and 17.7-54.3 micrograms/min, respectively). Two patients with borderline microalbuminuria (19.9 and 14.5 micrograms/min, respectively) demonstrated stable albumin excretion rates over the follow-up period. Total aldehyde concentration was significantly higher in beta-thalassemia diabetic patients, compared with nonthalassemic diabetic control subjects (8,106 +/- 1,280 vs. 4,594 +/- 247 nmol/l; P < 0.0001). The three patients with progressive microalbuminuria demonstrated significantly higher total aldehyde concentration, compared with the other beta-thalassemia diabetic patients with stable albumin excretion (9,428 +/- 337 vs. 7,445 +/- 1,003 nmol/l; P < 0.01). Serum vitamin E concentrations were significantly lower in beta-thalassemia patients with diabetes, compared with diabetic patients without iron overload (12.1 +/- 6.0 vs. 25.9 +/- 11.4 mumol/l; P = 0.02). Serum vitamin C concentrations did not differ between the two groups. Multiple regression analysis demonstrated total aldehyde concentration to be the most significant predictor for the development of microalbuminuria (P = 0.01), followed by the duration of diabetes (P = 0.02) and glycemic control (P = 0.02). CONCLUSIONS: Early development and an accelerated course of diabetic nephropathy in iron-loaded patients with beta-thalassemia are observed. These findings may be attributed to high oxidative stress in these patients, which is secondary to iron-derived free radicals and to the patients' diminished antioxidant reserves.

Adult↗