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Biomedical subjects

P Altieri

Publications and source records attributed to P Altieri.

At least 19 recordsLinked to original sources
PubMed1999

Corticosteroids in IgA nephropathy: a randomised controlled trial.

BACKGROUND: IgA nephropathy is progressive in most cases and has no established therapy. In this randomised trial, we assessed the efficacy and safety of a 6-month course of steroids in this disorder. METHODS: Between July, 1987, and September, 1995, we enrolled 86 consecutive patients from seven renal units in Italy. Eligible patients had biopsy-proven IgA nephropathy, urine protein excretion of 1.0-3.5 g daily, and plasma creatinine concentrations of 133 micromol/L (1.5 mg/dL) or less. Patients were randomly assigned either supportive therapy alone or steroid treatment (intravenous methylprednisolone 1 g per day for 3 consecutive days at the beginning of months 1, 3, and 5, plus oral prednisone 0.5 mg/kg on alternate days for 6 months). The primary endpoint was deterioration in renal function defined as a 50% or 100% increase in plasma creatinine concentration from baseline. Analyses were by intention to treat. FINDINGS: Nine of 43 patients in the steroid group and 14 of 43 in the control group reached the primary endpoint (a 50% increase in plasma creatinine) by year 5 of follow-up (p<0.048). Factors influencing renal survival were vascular sclerosis (relative risk for 1-point increase in score 1.53, p=0.0347), female sex (0.22, p=0.0163), and steroid therapy (0.41, p=0.0439). All 43 patients assigned steroids completed the treatment without experiencing any important side-effects. INTERPRETATION: A 6-month course of steroid treatment protected against deterioration in renal function in IgA nephropathy with no notable adverse effects during follow-up. An increase in urinary protein excretion could be a marker indicating the need for a second course of steroid therapy.

Administration, Oral↗
PubMed1999

N-(4-hydroxyphenyl) retinamide inhibits cystogenesis by polycystic epithelial cell lines in vitro.

Primary tubular epithelial cells develop spherical monolayered cysts when cultured in collagenI matrix, a model that has been used to study the mechanism of cystogenesis. In an attempt to block cystogenesis, we have evaluated the effect of N-(4-hydroxyphenyl) retinamide (HPR), a synthetic derivative of retinoic acid, on both formation and growth of cysts in a human model of polycystic kidney cells. Number, dimension and submicroscopical characteristics of cysts were evaluated after 2 and 4 weeks from treatment with HPR. A marked inhibitory effect of HPR on cystogenesis was found at concentration of 1 microM, while a complete block was observed at concentration between 5 and 10 microM. Furthermore, treatment with HPR of already formed cysts resulted in their disruption. HPR at 10 microM also induced apoptosis of several tubular epithelial cell models suggesting a correlation between the two phenomena. Taken together these observations demonstrate that HPR blocks cystogenesis by polycystic kidney cells "in vitro" and that it also reverts the fate of already formed cysts. Apoptosis may be the mechanism which mediates the inhibitory effect on cystogenesis in this model.

Animals↗
PubMed1998

Bleeding patterns in recent postmenopausal outpatients with uterine myomas: comparison between two regimens of HRT.

OBJECTIVES: To evaluate and to compare the bleeding patterns obtained with two regimens of hormone replacement therapy given to early postmenopausal women with asymptomatic uterine leiomyomas. METHODS: In this randomised prospective 1-year study 50 early postmenopausal women with one to four asymptomatic uterine leiomyomas were enrolled into two study-groups to take two regimens of hormone replacement therapy for 12 28-day cycles: (A) Tibolone, 2.5 mg/day; (B) conjugated equine estrogens (CEE), 0.625 mg/day plus medroxyprogesterone acetate (MPA), 5 mg/day. The bleeding patterns and the changes in uterine volume of the 47 outpatients who completed the study were evaluated and compared. RESULTS: Amenorrhea incidence was higher in group A (75.0% of the cycles) than in group B (65.6% of the cycles), while irregular bleeding and irregular spotting incidences were higher in group B (29.7 and 4.7% of the cycles, respectively) compared to group A (22.6 and 2.4% of the cycles, respectively). The mean bleeding and spotting lengths were not statistically different between patients in group A and those in group B. Finally, at the end of the study period transvaginal ultrasonography showed no significant change in leiomyoma size. CONCLUSIONS: The results demonstrate that, in early postmenopausal patients with asymptomatic uterine leiomyomas, Tibolone treatment seems to be preferable compared to CEE-MPA continuous combined treatment in relation to the lesser occurrence of irregular bleeding. Furthermore, neither Tibolone nor CEE-MPA therapy, at the doses used here, promote fibroid growth.

Anabolic Agents↗
PubMed1998

Transforming growth factor beta blocks cystogenesis by MDCK epithelium in vitro by enhancing the paracellular flux: implication of collagen V.

Transforming growth factor beta (TGFbeta) determines a nearly complete inhibition of cystogenesis by MDCK cells grown in collagen I-enriched matrices in vitro. In order to elucidate the mechanism implicated in this phenomenon, we performed a series of experiments aimed at discovering a relevant role of extracellular matrix. TGFbeta (2 ng/ml) played a marked stimulatory effect on the expression of extracellular matrix by MDCK with a selective effect on collagen V (three to fourfold increase of protein and mRNA) and in parallel inhibited cystogenesis by 95%. Cotreatment with TGFbeta and anti-collagen V antibodies restored a normal cystogenesis. In analogy, when MDCK cells were grown in three-dimensional matrices containing collagen I and minor (10%) amounts of collagen V, cystogenesis was once again inhibited by 95%. To characterize the molecular mechanism activated by TGFbeta and collagen V, we looked at the electrophysiological characteristics of MDCK monolayers and found a drastic fall of transepithelial electrical resistance (TER) in both conditions. In parallel with the decrease in TER, TGFbeta and collagen V also induced the leakage of two high molecular weight tracers, i.e., [3H]-inulin and 150 kD FITC-Dextran, suggesting a perturbation of the paracellular permeability. Finally, TGFbeta at the relevant concentration did not stimulate apoptosis in our cellular model, as judged by propidium iodide staining and by in situ end labeling of DNA fragments. These observations suggest that TGFbeta inhibits cystogenesis by MDCK cells in vitro by altering the collagenic composition of the three-dimensional milieu where MDCK cells grow and form cysts. The molecular mechanism responsible for inhibition of cystogenesis is the increase of paracellular flux which overcomes the active transport of solutes and water inside cysts.

Animals↗
PubMed1998

Cell-specific regulation of alpha1(III) and alpha2(V) collagen by TGF-beta1 in tubulointerstitial cell models.

BACKGROUND: TGF-beta1 modulates the cellular expression of extracellular matrix (ECM) in several renal cell systems in vitro and is considered a determinant of ECM accumulation in tubulointerstitial fibrosis. METHODS: We evaluated the effects of TGF-beta1 on collagen transcription, expression, and removal of the relevant collagens by rat tubuloepithelial cells (NRK 52E) and both rat and monkey interstitial fibroblasts (NRK 49F, CV1) in vitro. RESULTS: TGF-beta1 upregulated the expression of alpha1(III) collagen by fibroblasts (+300%) without affecting its removal. In parallel, a threefold increment of COL3A1 mRNA was found. Experiments of cell transfection employing CV1 fibroblasts as the unique suitable model, and chimaeric constructs of COL3A1 and COL5A2 promoters fused to the luciferase reporter gene, demonstrated a twofold stimulation of a large 1436 COL3A1 promoter construct and negligible effects on shorter fragments, suggesting the presence of a positive responsive element in a region of COL3A1 promoter between -1375 and -579. TGF-beta1 did not influence COL5A2 mRNA and the relative promoter activity in renal fibroblasts. With NRK 52E cell line, TGF-beta1 induced comparable increment of both alpha1(III) collagen expression (+300%) and COL3A1 mRNA (+300%) without affecting the COL3A1 promoter activity of any constructs. TGF-beta1 also upregulated the expression of alpha2(V) collagen chain (+500%) and COL5A2 mRNA (+500%) with a stimulatory effect (+100%) on a 1177 bp fragment of COL5A2 promoter. In this case a relevant inhibitory effect of TGF-beta1, on removal of alpha2(V) by supernatants of NRK 52E was also observed, indicating a double regulatory role of the cytokine on both transcription and removal of this component of ECM. CONCLUSION: Taken together these data indicate that TGF-beta1 is a potent stimulator of alpha1(III) collagen expression by renal fibroblast cell lines in vitro, the basic mechanism being stimulation of COL3A1 transcription. With renal epithelial cell lines, TGF-beta1 mainly upregulated the expression of type V collagen with the most relevant effect on stimulation of collagen transcription and inhibition of its removal. Tubular epithelial cells and renal fibroblasts should play distinct roles in renal fibrosis induced by TGF-beta1 in vivo.

Animals↗
PubMed1998

A randomized study comparing methylprednisolone plus chlorambucil versus methylprednisolone plus cyclophosphamide in idiopathic membranous nephropathy.

To assess whether chlorambucil or cyclophosphamide may have a better therapeutic index in patients with idiopathic membranous nephropathy, we compared two regimens based on a 6-mo treatment, alternating every other month methylprednisolone with chlorambucil or methylprednisolone with cyclophosphamide. Patients with biopsy-proven membranous nephropathy and with a nephrotic syndrome were randomized to be given methylprednisolone (1 g intravenously for 3 consecutive days followed by oral methylprednisolone, 0.4 mg/kg per d for 27 d) alternated every other month either with chlorambucil (0.2 mg/kg per d for 30 d) or cyclophosphamide (2.5 mg/kg per d for 30 d). The whole treatment lasted 6 mo; 3 mo with corticosteroids and 3 mo with one cytotoxic drug. Among 87 patients followed for at least 1 yr, 36 of 44 (82%; 95% confidence interval [CI], 67.3 to 91.8%) assigned to methylprednisolone and chlorambucil entered complete or partial remission of the nephrotic syndrome, versus 40 of 43 (93%; 95% CI, 80.9 to 98.5%) assigned to methylprednisolone and cyclophosphamide (P = 0.116). Of patients who attained remission of the nephrotic syndrome, 11 of 36 in the chlorambucil group (30.5%) and 10 of 40 in the cyclophosphamide group (25%) had a relapse of the nephrotic syndrome between 6 and 30 mo. The reciprocal of plasma creatinine improved in the cohort groups followed for 1 yr for both treatment groups (P < 0.01) and remained unchanged when compared with basal values in the cohort groups followed for 2 and 3 yr. Six patients in the chlorambucil group and two in the cyclophosphamide group did not complete the treatment because of side effects. Four patients in the chlorambucil group but none in the cyclophosphamide group suffered from herpes zoster. One patient per group developed cancer. It is concluded that in nephrotic patients with idiopathic membranous nephropathy both treatments may be effective in favoring remission and in preserving renal function for at least 3 yr.

Adolescent↗
PubMed1998

Acute renal failure after massive ingestion of gliclazide in a suicide attempt.

Gliclazide, a sulfonlyurea class molecule, is used to control glycaemic levels in non-insulin-dependent diabetes mellitus. Acute and chronic toxicity studies, conducted in various animal species, have demonstrated a very low toxicity. We report a patient who developed acute renal failure due to acute tubular necrosis following a massive ingestion of gliclazide in an suicide attempt. The patient ingested 28 grams of gliclazide; the normal dose of gliclazide is 80 mg one or twice a day. At admission the patient was hypoglycaemia and in a few days became oliguric with an increase in the serum creatinine concentration, but with a normal blood urea nitrogen level. He underwent dialysis and ten days after ingestion of gliclazide, his renal function improved rapidly.

Adult↗
PubMed1997

On-line predilution hemofiltration versus ultrapure high-flux hemodialysis: a multicenter prospective study in 23 patients. Sardinian Collaborative Study Group of On-Line Hemofiltration.

The aims of the present prospective multicenter study were to assess the clinical tolerance and well being, the correlation between nPCr and Kt/V and the pretreatment beta 2-microglobulin level in patients sequentially treated with high-flux dialysis with ultrapure bicarbonate hemodialysis (HD; phase 1) and predilution hemofiltration (HF) with on-line prepared bicarbonate substitution fluid (phase II). The same monitor (Gambro AK 100 ULTRA) and membrane (polyamide) were used. Twenty-three patients, all in a stable clinical condition, entered the study. The treatment was targeted to an equilibrated Kt/V (eqKt/V) of 1.4 for HD and 1.0 for HF. No mortality or relevant morbidity were observed. The number of hypotensive episodes was 1.78 +/- 2.8 per patient and month during HD vs. 1.17 +/- 3.1 during HF (p = 0.003) and the number of the hypertensive episodes 1.28 +/- 2.8 during HD vs. 0.42 +/- 0.8 during HF (p = 0.04). Incidences of arrhythmia, muscular cramps and headache were significantly less frequent during HF. Interdialytic cramps, arthralgia and fatigue were also significantly less frequent during the HF period. The average beta 2-microglobulin level was 27.1 +/- 14.7 mg/dl at the start of the study, 22.9 +/- 4.9 mg/dl at the beginning of phase II and 22.4 +/- 4 mg/dl at the end of phase II (p = 0.01 compared to the start). A significant linear correlation between the normalized protein catabolic rate and eqKt/V was obtained faster during HD than during HF (45 vs. 120 days) indicating that HF affects the nutritional status with mechanisms different from HD. The present study is in agreement with the hypothesis that HF gives and adequate nutritional status with improved clinical stability and well being at a lower Kt/V compared to HD. Both therapies were efficient in controlling the pretreatment beta 2-microglobulin level.

Aged↗
PubMed1997

A randomized study comparing three cyclosporine-based regimens in cadaveric renal transplantation. Italian Multicentre Study Group for Renal Transplantation (SIMTRe).

Whether it is better to treat renal transplant patients with cyclosporine alone, combined with steroids, or combined with steroids and azathioprine is still unclear. After initial therapy with cyclosporine and steroids, 354 cadaver renal transplant recipients were randomly assigned at the post-transplant day 5 to cyclosporine alone (monotherapy), cyclosporine plus steroids (double therapy), or cyclosporine plus steroids plus azathioprine (triple therapy). Monotherapy patients, after a second acute rejection, were switched to either of the two alternative therapies. According to intention-to-treat (ITT) analysis, the 4-year patient survival was 97% in monotherapy, 91% in double therapy, and 96% in triple therapy; the graft survival including death was 84%, 77%, and 88%, respectively; and the pure graft survival was 87%, 85% and 91%, respectively (P = not significant). Acute rejections were diagnosed in 79 patients in monotherapy, 58 in double therapy, and 59 in triple therapy (P < 0.01). Of the patients on monotherapy, 52% were switched to double or triple therapy. In these patients, the 4-year graft survival including death was 68%, and the pure graft survival was 72%, in comparison with 93% and 94%, respectively, for patients who continued on cyclosporine alone. Patients with renal polycystic disease as a cause of renal failure and with low plasma creatinine at the time of randomization (5 days after transplant) had a higher probability of remaining on monotherapy, wherease those with glomerulonephritis or systemic lupus erythematosus (SLE) and with high plasma creatinine levels at randomization had a higher probability of being switched to double or triple therapy. According to ITT analysis, there were fewer ocular (P < 0.0001), osteomuscular (P < 0.002) and cardiovascular complications (P = 0.05) and fewer patients with hypercholesterolemia (P < 0.0028) in the monotherapy group, with no difference between double and triple therapy. Creatinine clearance at 3 years was lower in monotherapy, but no attrition of renal function was seen over the years in any of the groups. Cyclosporine, however used, provided good results in cadaveric renal transplantation. Triple therapy and monotherapy offered a nonsignificantly better patient and graft survival than double therapy. Patients on monotherapy had a higher risk of acute rejection but had fewer adverse events than those on double or triple therapy. Patients maintained on cyclosporine alone had the best graft survival, whereas those who were assigned to monotherapy and had to add steroids because of multiple rejections had the worst outcome. Therefore, it seems reasonable to limit the choice of monotherapy to patients without immune-mediated renal diseases and with good graft function in the early post-transplant period.

Adolescent↗
PubMed1997

Bone density changes in postmenopausal women with the administration of ipriflavone alone or in association with low-dose ERT.

Ipriflavone is a synthetic flavonoid that has been shown to exert a direct inhibitory effect on osteoclastic activity and possibly stimulate the osteoblast activity in different experimental models. The aim of the present study was to evaluate the effects of either ipriflavone alone or ipriflavone plus low dose hormone replacement therapy (HRT) in the prevention of postmenopausal bone loss. Patients were randomly allocated to different treatment groups receiving calcium (500 mg/day, control group), continuous HRT (25 or 50 micrograms/day of transdermal 17 beta-estradiol) plus medrogestone 5 mg/day for 12 days/month, ipriflavone at the standard dose of 600 mg/day, or finally ipriflavone 600 mg/day plus 17 beta-estradiol 25 micrograms/day plus medrogestone 5 mg/day for 12 days/month. No significant differences in basal levels of biochemical markers of bone turnover or in basal bone mineral density (BMD) values were evident in the different groups. In the control group after 12 months, spine BMD showed a significant (p < 0.05) 3.41% decrease. The pattern of BMD modification was significantly different from controls in the high dose HRT group (+1.84%), the ipriflavone group (+0.11%), and the combined ipriflavone/HRT group (-0.22%). Conversely, the BMD pattern in the low dose HRT group (-0.55%) was similar to that observed in controls. Thus, present results confirm that ipriflavone and 50 micrograms/day of transdermal 17 beta-estradiol are effective measures in the prevention of postmenopausal osteopenia. A lower transdermal estrogen dose is unable to increase the antiresorptive effect of ipriflavone and did not exert any further action in the prevention of postmenopausal osteopenia.

Administration, Cutaneous↗
PubMed1996

Premenopause-dependent changes.

The authors retrospectively evaluated 1,773 climacteric outpatients in order to establish: (a) criteria able to distinguish different conditions in the transitional phase before menopause (advanced fertile age and premenopause) and (b) premenopause-related changes during the transition from one to the other of several clinical and laboratory parameters. Results showed an increase in gonadotropin plasma levels, a decrease in estrogen plasma levels and a greater frequency of women complaining of hot flushes in premenopause compared to advanced fertile age, as an expression of the progressive decline of ovarian function. Premenopause-related changes were a decrease in thyroid function and an increase in the body mass index, the beginning of bone loss, an increase in glucose, total cholesterol and triglyceride serum levels and a greater frequency of women complaining of hypertension and urinary stress incontinence. An increase in total proteins, uric acid and aminotransferase serum levels was also noted.

Adult↗
PubMed1996

Double phase parathyroid technetium-99m-MIBI scintigraphy to identify functional autonomy in secondary hyperparathyroidism.

UNLABELLED: Double-phase 99mTc-methoxyisobutylisonitrile (MIBI) parathyroid scintigraphy has been proposed to detect hyperplastic parathyroid tissue, but the clinical usefulness of this technique in secondary hyperparathyroidism is still debated. METHODS: Technetium-99m-MIBI parathyroid scintigraphy associated with parathyroid echography and [99mTc]pertechnetate thyroid scans were performed on 38 patients with chronic renal failure (CRF) and secondary hyperparathyroidism. In all patients, serum calcium, phosphorus, FT3, FT4, TSH, calcitonin and intact PTH (iPTH) were determined. Nine patients eventually underwent neck exploration and 28 parathyroid glands were removed. RESULTS: Thyroid diseases were excluded in all patients. Echography revealed parathyroid enlargement in 22/38 (58%) patients, while MIBI scintigraphy was positive in 28/38 (74%), including 5 ectopic glands. Mean serum iPTH concentration was significantly higher in MIBI-positive glands compared to MIBI-negative glands, but several discrepancies were observed in single patients. A significant positive correlation between serum iPTH and gland size was observed when MIBI-positive, but not MIBI-negative, parathyroids were considered. A paradoxical positive correlation between serum calcium and iPTH concentrations was found in MIBI-positive patients. CONCLUSION: Double-phase 99mTc-MIBI scintigraphy is positive in the majority of patients with uremic hyperparathyroidism. Comparison of scintigraphic data with morphological and functional data strongly suggests that 99mTc-MIBI scans do not reveal simple parathyroid enlargement but rather, identify the presence of hyperfunctioning (autonomous) parathyroid tissue suggestive of tertiary hyperparathyroidism.

Adult↗
PubMed1996

Outgrowth of interleukin-2-dependent T cell lines with cytotoxic activity against mesothelial cells from cultures of peritoneal effluent cells of children on CPD.

Previous studies on the peritoneal immune system described the presence of activated T lymphocytes in peritoneal effluents (PE) from patients on chronic peritoneal dialysis (CPD), and showed that mesothelial cells (MC) can present antigens to T cells. In order to better define phenotypic and functional characteristics of T cells and their interactions with MC, we isolated PE cells from 15 children. At the immunophenotypic analysis, high percentages of activated T cells were identified (mean value: 15% double staining for CD3/DR; 12% CD25+). T cells with gamma/delta T cell receptor (mean 5%) and natural killer cells (mean 17%) were also present in elevated numbers. MC lines (n = 7) and interleukin-2-dependent T cell lines (9 CD4+; 1 CD8+) were also obtained by incubating PE cells under different conditions. Two cell lines showed a major histocompatibility complex (MHC) restricted cytotoxic activity against autologous MC; two lines killed allogeneic MC; one line killed both autologous and allogeneic MC. Although the hypothesis that activated T cells could kill MC after recognition of surface structures modified by dialysis fluid, or during antigen presentation, needs to be further investigated, our data suggest that the subsets of lymphocytes we identified could play an important role in the mechanisms of peritoneal membrane defense.

Adolescent↗