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M Cozzolino

Publications and source records attributed to M Cozzolino.

15 recordsLinked to original sources
PubMed2003

Cardiac and pulmonary calcification in a hemodialysis patient: partial regression 4 years after parathyroidectomy.

AIMS: The reversibility of extraskeletal calcifications in dialysis patients is an important and unresolved issue. Although periarticular calcifications have been shown to be reversible, little data are available on vascular or parenchymal calcifications. CASE HISTORY: A patient on maintenance hemodialysis with severe hyperparathyroidism, hypercalcemia and hyperphosphatemia was admitted to undergo parathyroidectomy. A preoperative total body bone scintigraphy was performed to better evaluate a lytic lesion in the pelvis, the histology of which proved to be a "brown tumor". The scan showed the typical findings of renal osteodystrophy, but also a diffuse extra-skeletal uptake of bone tracer in the lungs, kidneys, femoral arteries and myocardium. After surgery, good control of serum calcium, phosphate (Ca x P product < 50 mg2/dl2) and PTH levels was maintained during 4 years of follow-up. Bone scans were repeated after 2 and 4 years, showing marked improvement of periarticular uptake at the ends of long bones. Extraosseous calcium deposition was still markedly evident, but progressively decreased (at 4 years: heart -36%, lungs -18%). CONCLUSION: In this dialysis patient, extraskeletal calcification of visceral organs (particularly in the heart and the lungs) due to prolonged hypercalcemia and hyperphosphatemia was partially reversible by parathyroidectomy followed by good long-term control of serum phosphate and calcium.

Adult↗
PubMed2001

p21WAF1 and TGF-alpha mediate parathyroid growth arrest by vitamin D and high calcium.

BACKGROUND: High dietary phosphorus (P) worsens uremia-induced parathyroid (PT) hyperplasia through increases in the growth promoter transforming growth factor-alpha (TGF-alpha). In contrast, P restriction prevents PT hyperplasia by inducing the cell cycle inhibitor p21. Since 1,25(OH)2D3-antiproliferative action in various cell types involve increases in p21, we studied whether induction of p21 by 1,25(OH)2D3 or the vitamin D analog, 19-Nor-1,25(OH)2D2, could counteract the PT hyperplasia induced by high dietary P in early uremia. METHODS: Normal (N) and uremic (U; 5/6 nephrectomized) female Sprague-Dawley rats were fed high P (HP), low P (LP) or high Ca (HCa) diets and administered intraperitoneally (IP) either vehicle or vitamin D metabolites for seven days, as follows: N-HP; U-HP + vehicle; U-HP + 1,25(OH)2D3 (4 ng/day); U-HP + 19-Nor-1,25(OH)2D2 (30 ng/day); U-LP; U-HCa. Serum PTH and PT gland weight assessed secondary hyperparathyroidism. Immunohistochemical quantitation of two markers of mitotic activity, Ki67 and PCNA measured PT hyperplasia. Immunohistochemical expression of PT p21 and TGF-alpha addressed potential mechanisms regulating PT cell growth. RESULTS: 1,25(OH)2D3 and 19-Nor-1,25(OH)2D2 were effective in suppressing both PTH secretion and PT hyperplasia induced by uremia and high dietary P independent of increases in ionized Ca. Both vitamin D compounds enhanced PT p21 expression and prevented high P-induced increases in PT TGF-alpha content. Induction of PT p21 and reduction of TGF-alpha content also occurred when uremia-induced PT hyperplasia was suppressed by high dietary Ca. CONCLUSIONS: In early uremia, vitamin D suppression of high P-induced PT hyperplasia and high dietary Ca arrest of PT growth involve induction of PT p21 and prevention of increases in TGF-alpha.

Animals↗
PubMed2000

Activation of TrkA tyrosine kinase in embryonal carcinoma cells promotes cell compaction, independently of tyrosine phosphorylation of catenins.

Cadherins are transmembrane receptors whose extracellular domain mediates homophilic cell-cell interactions, while their cytoplasmic domain associates with a family of proteins known as catenins. Although the mechanisms that regulate the assembly and functional state of cadherin-catenin complexes are poorly understood, current evidence supports a role for protein tyrosine kinase activity in regulating cell adhesion and migration. Tyrosine phosphorylation of catenins is thought to mediate loss of intercellular adhesion promoted by activation of receptor tyrosine kinases in epithelial cells. Here, we show that activation of ectopically expressed TrkA, the tyrosine kinase receptor for nerve growth factor (NGF), stimulates embryonal carcinoma P19 cells to develop extensive intercellular contacts and to assemble into closely packed clusters. Thus, activation of receptor tyrosine kinases can differentially regulate adhesiveness by cell-type-specific mechanisms. Furthermore, activation of TrkA in P19 and epithelial MDCK cells induces tyrosine phosphorylation of p120(ctn) and of beta-catenin, irrespective of the elicited cellular response. The selective Src tyrosine kinase inhibitor PP2, however, suppresses NGF- or HGF-induced tyrosine phosphorylation of catenins in both P19 and MDCK cells without interfering with the acquisition of a compacted or scattered phenotype. These findings provide a cogent argument for considering that tyrosine phosphorylation of catenins is dispensable for their interaction with cadherins and, ultimately, for the modulation of cadherin-based cell adhesion by receptor tyrosine kinases.

Amino Acid Sequence↗
PubMed2000

Twice versus thrice weekly administration of intravenous calcitriol in dialysis patients: a randomized prospective trial. Gruppo Italiano di Studio dell'Osteodistrofia Renale.

BACKGROUND: Administration of intravenous (i.v.) calcitriol three times weekly effectively controls the synthesis and secretion of PTH in most uremic patients. Administration of a single dose of 1.25(OH)2D3 reduces synthesis of PTH-mRNA for 6 days in rats. Moreover, it can lower PTH levels for up to 4 days in chronic hemodialysis patients. Therefore, a good response to the administration of i.v. calcitriol two times weekly can be expected. We studied - in a multicenter randomized study in patients with moderate to severe secondary hyperparathyroidism - the effects of the same doses of intravenous calcitriol, administered two or three times weekly. METHODS: Twenty-two hemodialysis patients were randomized into two frequencies of treatment groups: two times (G-2/w) and three times weekly (G-3/w). Both groups were treated with increasing doses of intravenous calcitriol for 3 months (first month 3 microg, second month 4 microg, third month 6 microg weekly). RESULTS: After 12 weeks of therapy with intravenous calcitriol the G-2/w group showed a significant reduction in serum PTH levels (from 821 +/- 392 to 350 +/- 246 pg/ml; mean reduction = 57.4%) comparable to the decrease observed in the G-3/w group (from 632 +/- 116 to 246 +/- 190 pg/ml; mean reduction = 61.2%). Ionized calcium (G-2/w from 1.13 +/-0.10 to 1.14 +/- 0.08 and G-3/w 1.21 +/- 0.13 to 1.26 +/- 0.18 mmol/l) and phosphate levels (G-2/w from 4.99 +/- 1.01 to 5.99 +/- 1.78 and G-3/w 5.31 +/- 0.73 to 5.81 +/- 1.18 mg/dl) did not change significantly and phosphate binders were not modified during the study. CONCLUSION: This study confirms that intravenous calcitriol is an effective therapy for moderate to severe secondary hyperparathyroidism. The administration of two doses per week of intravenous calcitriol is as efficacious as three doses per week in suppressing PTH secretion.

Adult↗
PubMed1999

Acute tubulo-interstitial nephritis requiring dialysis associated with intermittent rifampicin use: case report.

Rifampicin is one of the most effective antibiotics used for the treatment of tuberculosis and severe staphylococcal infections. Intermittent administration of high doses of rifampicin has been associated with frequent adverse reactions, including hepatotoxicity and nephrotoxicity, sometimes resulting in acute renal failure. We describe a case of rifampicin-associated acute renal failure, with biopsy findings of tubulointerstitial nephritis; inflammatory cells were characterized by immunohistochemistry, which showed immunoreactivity for CD3 and CD5 (T lymphocytes) and for CD68 (macrophages). The patient presented with a very rapid systemic reaction to the offending drug and rapid deterioration of renal function, which required dialysis treatment. The response to rifampicin discontinuation was excellent: no further therapy was required, as renal function began to improve within several days and returned to normal values (serum creatinine 1.17 mg/dl) seven months after the onset of symptoms. When prescribing rifampicin the physician should investigate previous use of the drug, because re-exposure is a critical factor in predicting the possibility of drug-induced acute renal failure.

Acute Disease↗
PubMed1995

Neuronal differentiation of P19 embryonal cells exhibits cell-specific regulation of neurotrophin receptors.

During development, the regulation of expression of the Trk family of tyrosine kinase receptors plays an important role in defining the cellular responses to neurotrophin action. We report here that neurotrophin receptors are differentially expressed in distinct populations of retinoic acid-differentiated P19 cells. TrkB, the tyrosine kinase receptor for brain-derived neurotrophic factor, and LNGFR, the low-affinity receptor for all neutrophins, are preferentially expressed in P19-derived neurones. In contrast, retinoic acid induces the expression of TrkA, the high-affinity receptor for nerve growth factor, and of a non-catalytic form of TrkB, in non-neural subsets of differentiated cells. We propose P19 cells as a model system to study the mechanisms controlling the expression of neurotrophin receptors and the responsiveness of developing neurones to a specific neurotrophin.

Animals↗
PubMed1995

Uncomplicated central vein catheterization of high risk patients with real time ultrasound guidance.

Internal jugular vein cannulation has become a routine and clinically important aspect of medical care of critically ill patients. The landmark guided technique usually affords rapid and easy vascular access, but is not always successful and may be complicated by arterial puncture, hematoma, or pneumothorax. Some categories of patients, in particular patients with no external landmarks and patients with coagulopathies, appear to be at an increased risk of complications. We report the experience of internal jugular vein cannulation by a single operator with the external landmark technique in 10 patients and with ultrasound guidance in 31 patients, including 12 high risk patients. These patients had severe coagulopathies due to hepatic failure, HELLP syndrome, excess of anticoagulation treatment, or they had no external anatomic landmarks because of anasarca or obesity, were unable to maintain the horizontal position, or were external landmark catheterization failures. With the availability of the ultrasound device, success and complication rates improved markedly, suggesting that the ultrasound technique is easy to learn and rapidly produces an improvement over the external landmark method. In particular the 13 cannulations performed in 12 high risk patients were all successful at the first attempt, with no complications. In the overall population successful cannulations improved from 80% to 100%, first attempt success from 20% to 87% and carotid punctures decreased from 33% to 3.2%. Our results confirm that ultrasound guided cannulation of the internal jugular vein allows safer operation in high risk patients or when access problems are anticipated.

Adult↗
PubMed1995

[Leiomyosarcoma of the mesenteric root. A case report].

Although smooth muscle tumors are the most common mesentery neoplasms, they are lesions of infrequent occurrence. The main clinical features of these malignancies are an insidious onset and an aspecific symptomatology, usually presenting themselves as quite large masses. The preoperative diagnosis is difficult, but selective angiography and CT scan may be of great value for this purpose. Since these malignancies are usually not responsive either to radiotherapy or chemotherapy, once diagnosed, the only hope of cure lies in surgical resection. The authors report case of leiomyosarcoma of the mesentery root, treated with radical surgery and still alive and disease free 12 months after resection.

Follow-Up Studies↗
PubMedDate not supplied

Sevelamer reduces calcium load and maintains a low calcium-phosphorus ion product in dialysis patients.

BACKGROUND: Sevelamer HCl, a non-aluminum, non-calcium containing hydrogel, has proved an effective phosphate binder in North American hemodialysis patients. This single-center, open-label, dose titration study assessed the efficacy of sevelamer in a cohort of European hemodialysis patients with different dietary habits, in particular with lower phosphate intake. The aim of the study was to obtain a calcium x phosphate product lower than 60 mg2/dL2 in all patients. METHODS: Administration of calcium- or aluminum-based phosphate binders was discontinued during a two-week washout period. Nineteen patients whose serum phosphate level at the end of washout was greater than 5.5 mg/dL (1.78 mmol/L) qualified to receive sevelamer for six weeks. Based on the degree of hyperphosphatemia during washout, patients were started on 403 mg sevelamer capsules with a dose schedule different from previous studies. Only one capsule was administered at breakfast, and the rest of the phosphate binder was divided equally at the two main meals. Sevelamer could be increased by two capsules per day every two weeks, if necessary. A second two-week washout period followed. RESULTS: Mean serum phosphorus rose from a baseline of 5.3 +/- 1.0 to 7.4 +/- 1.4 mg/dL at the end of washout, then declined to 5.4 +/- 0.8 mg/dL (p < 0.001) by the end of the six-week treatment period and rebounded significantly to 7.1 +/- 1.1 mg/dL after the second two-week washout. Calcium x phosphate product showed a similar pattern, decreasing significantly from 64.1 +/- 14.1 to 46.9 +/- 7.4 mg2/dL2 (p < 0.001) after six weeks of sevelamer. A level of less than 50 mg2/dL2 was reached by 68% of patients, and 95% had less than 60 mg2/dL2. The mean dose of sevelamer at the end of treatment was 3.1 +/- 0.6 g per day. As expected, calcium declined from 9.2 +/- 0.5 to 8.7 mg/dL (p < 0.01) during the initial washout after stopping calcium-based phosphate binders, but remained stable thereafter. Ionized calcium did not change significantly throughout the washout and sevelamer treatment. However, interruption of calcium salts led to a 81% reduction of total calcium intake. CONCLUSIONS: We confirmed in an European sample of hemodialysis patients that sevelamer can reduce phosphate levels without inducing hypercalcemia. The drug can also be successfully used to reduce mean calcium x phosphate levels below 50 mg2/dL2, closer to normal values. Although similar results can be obtained with other phosphate binders, a concomitant accumulation of aluminum, calcium or magnesium could be detrimental to patients.

Aged↗
PubMedDate not supplied

[Mechanism of uremic osteodystrophy and prevention of hyperparathyroidism in the uremic patient].

The management of secondary hyperparathyroidism is of crucial importance in the treatment of end stage renal disease (ESRD) patients. In particular, hypercalcemia, hyperphosphatemia, and elevated calcium x phosphate (Ca x P) product should be taken into consideration during administration of vitamin D metabolites for the control of PTH secretion. During the last 10 years, many authors have been studying the efficacy of new non-calcemic vitamin D analogs on suppressing secondary hyperparathyroidism in ESRD patients. In this brief review, we analyzed three new vitamin D analogs: 22-oxacalcitriol (Maxacalcitriol), 19-nor-1a, 25(OH)2D2 (Paracalcitriol), and 1a (OH)2D2 (Doxacalciferol). In addition, calcimimetic agents may represent a new pharmacologic choice to the treatment of secondary hyperparathyroidism, binding parathyroid calcium sensing receptors (CaSR) and reducing PTH secretion. These compounds may represent an important tool for the treatment of both secondary hyperparathyroidism and soft tissue calcifications in ESRD patients. In conclusion, a combined use of non calcemic phosphate binders, new vitamin D analogs and calcimimetics should be seriously considered to further improve the already known therapy of secondary hyperparathyroidism in ESRD patients.

Calcitriol↗