Biomedical subjects

D Montani

Publications and source records attributed to D Montani.

At least 19 recordsLinked to original sources

PubMed2006

[Cellular signalling pathways and pathophysiology of pulmonary arterial hypertension].

INTRODUCTION: Pulmonary arterial hypertension (PAH) is a disease of complex aetiology involving in varying degrees both genetic and environmental factors. BACKGROUND: Thanks to progress in biology over the past 15 years the physiological consequences of cellular and molecular abnormalities are much better understood. Recent work has allowed better understanding of the different cellular signalling pathways controlling pulmonary vascular tone and cell growth. It appears that these pathways form a dense and complex network involving several groups of molecules of which NO, cGMP, ET-1 and its receptors, are at the most important. VIEWPOINT: The pathophysiology of PAH may be regarded as a disorder of cellular signaling where molecular abnormalities disturb the balance between the different factors controlling vascular tone and cell proliferation. CONCLUSIONS: PAH may be viewed as a disease of cellular signalling where the molecular abnormalities not only affect a single signalling pathway but involve multiple cross-talks between groups of molecules controlling vascular smooth muscle tone and cell growth and differentiation.

3',5'-Cyclic-GMP Phosphodiesterases↗

PubMed2005

[Treatment of pulmonary arterial hypertension].

Pulmonary arterial hypertension (PAH) is characterized by vasoconstriction, in situ thrombosis, and vascular remodeling of small pulmonary arteries. It induces a fixed pulmonary arterial obstruction, persistent elevation of pulmonary arterial resistance, and eventually right heart failure. Conventional therapy is based on simple measures (exercise limitation) and nonspecific treatments (warfarin, diuretics, and oxygen). Pure vasodilators, such as calcium channel blockers, are effective only in a minority of patients who have an acute response to vasodilator testing. Intravenous prostacyclin (epoprostenol) and endothelin receptor blockers have vasodilator and antiproliferative properties. Epoprostenol therapy has significantly improved PAH prognosis and remains the first-line treatment for patients with the most severe disease. Bosentan is an interesting first-line treatment for NYHA functional class III patients. Availability of novel specific drugs (endothelin receptor type A antagonists, prostacyclin analogues, type 5 phosphodiesterase inhibitors) is opening new perspectives in PAH treatment. The long-term benefit of these drugs remains to be evaluated and their respective place in treatment of these patients is still uncertain. The evolution of therapy from vasodilators to antiproliferative agents reflects the advancement in our understanding of the mechanisms mediating pulmonary arterial hypertension.

Algorithms↗

PubMed2005

[Pulmonary arterial hypertension].

INTRODUCTION: Pulmonary arterial hypertension (PAH) is a rare condition characterised by progressively elevated pulmonary arterial resistance leading to right heart failure. STATE OF THE ART: A recent classification distinguishes idiopathic PAH, familial PAH and PAH secondary to other conditions (connective tissue disease, congenital heart disease, portal hypertension, human immunodeficiency virus infection or appetite suppressant exposure). Echocardiography is the initial investigation of choice for non-invasive detection of PAH but measurement of pulmonary pressures and cardiac output during right-heart catheterization are necessary to confirm the diagnosis of PAH. Conventional treatment includes non-specific drugs (warfarin, diuretics, oxygen). Intravenous epoprostenol is the first-line treatment for the most severely affected patients. In less severe cases, the first-line treatment may include bosentan or a prostacyclin analogue. PERSPECTIVES AND CONCLUSIONS: Recent advances in the management of PAH have markedly improved prognosis. The avai-lability of novel specific drugs including type 5 phosphodiesterase inhibitors offers novel therapeutic perspectives but their exact role in the treatment of PAH is still uncertain. The evolution of therapy from vasodilators to antiproliferative agents reflects the advancement in our understanding of the mechanisms mediating pulmonary arterial hypertension.

Antihypertensive Agents↗

PubMed2005

Reversibility of pulmonary arterial hypertension in HIV/HHV8-associated Castleman's disease.

The present study describes a case of pulmonary arterial hypertension (PAH) associated with multicentric Castleman's disease in a patient infected with HIV type 1 and human herpes virus 8. Therapy included highly active antiretroviral therapy, warfarin, diuretics, continuous i.v. epoprostenol and 12-monthly pulses of cyclophosphamide. The patient's condition improved dramatically with complete reversibility of PAH, allowing weaning of continuous i.v. epoprostenol therapy. After 5 yrs, both Castleman's disease and PAH have not relapsed. This supports the hypothesis that control of inflammation and retroviral replication may be of interest in the context of PAH, complicating the course of an inflammatory condition associated with viral infection. In conclusion, further studies should help in characterising the best candidates for anti-inflammatory treatment in the setting of pulmonary arterial hypertension.

Adult↗

PubMed2004

[Treatments for pulmonary arterial hypertension].

PURPOSE: Pulmonary arterial hypertension (PAH) is characterized by vasoconstriction, in situ thrombosis and vascular remodeling of small pulmonary arteries inducing a fixed pulmonary arterial obstruction and persistent elevation of pulmonary arterial resistance. Conventional treatment is based on simple measures (exercise limitation) and non-specific drugs (warfarine, diuretics, oxygen). CURRENT KNOWLEDGE AND KEY POINTS: Pure vasodilators like calcium channel antagonists have little or no effect on the vast majority of patients, presumably because fixed pulmonary arteriopathy predominate over vasoconstriction. Intravenous prostacyclin (epoprostenol) and endothelin receptor antagonists have vasodilator and antiproliferative properties. Epoprostenol therapy has resulted in significant improvements in prognosis of this disease and this drug remains the first-line treatment of the most severe patients. Bosentan is an interesting first-line treatment for NYHA functional class III patients. Availability of novel specific drugs (endothelin receptor type A antagonists, prostacyclin analogues, type 5 phosphodiesterase inhibitors) open new perspectives in treatment of PAH. The long-term benefit of these drugs remains to be evaluated and their respective place in treatment of these patients is still uncertain. We here present the different therapeutic alternatives available in the PAH and propose an algorithm for treatment of these patients. FUTURE PROSPECTS AND PROJECTS: The evolution of therapy from vasodilators to antiproliferative agents reflects the advancement in our understanding of the mechanisms mediating pulmonary arterial hypertension.

Algorithms↗

PubMed2004

[Pulmonary hypertension: from genetics to treatments].

Pulmonary hypertertension (PHT) is a rare disease defined by increased resistance of the pulmonary arteries inevitably leading to right heart failure if specific treatment is not given. This disease can occur sporadically (idiopathic or primary PHT), within a familial context (familial PHT, BMPR2 gene mutation), or occur as a complication of other diseases (connective tissue disease, congenital cardiomyopathy, human immunodeficiency virus infection, portal hypertension, use of anorexigenic agents). The incidence of primary PHT is 2 million cases per year, probably an underestimation due to the low specificity of clinical signs, predominantly exercise-induced dyspnea. Recent therapeutic advances (prostacyclin and endothelin receptor antagonists administered in continuous infusion) have improved the prognosis of this orphan disease. Inhaled iloprost and type 5 phosphodiesterase inhibitors should be evaluated for this indication. Lung transplantation is reserved for patients unresponsive to medical treatment.

Bone Morphogenetic Protein Receptors, Type II↗

PubMed1997

One-stage reconstruction of war wounds with free osteocutaneous flaps.

Thirty-one patients with traumatic osteocutaneous defects of the extremities sustained during the war in Croatia and Bosnia and Herzegovina were treated at the Institute of Plastic-Reconstructive and Breast Surgery in Zagreb. Injuries were categorised using the Mangled Extremity Syndrome Index (MESI). The average length of bone defect was 5.9 cm (range 4-12 cm). Patients were divided in two groups according to the time they had reconstruction with a free osteocutaneous flap: group 1, within 6 days after injury, and group 2, after more than 6 days. The mean time to reconstruction in group 2 was 5.2 weeks. Average time to solid bone union was 13.3 weeks in group 1 and 16.6 weeks in group 2. Functional outcome was better in group 1 with fewer complications, smaller number of operations and shorter hospital stay. One-stage reconstruction of osteocutaneous defects with free composite flaps provides reliable treatment solution with good functional outcome.

Adult↗

PubMed1994

Location of an inducible nitric oxide synthase mRNA in the normal kidney.

An inducible nitric oxide synthase (iNOS) mRNA was found primarily in the outer medulla of normal rat kidney. Identification of the mRNA was based upon the specificity of the oligonucleotide primers used for PCR amplification, PCR-Southern blot analysis and the nucleic acid sequence of the cloned PCR product. In addition to the outer medulla, glomeruli prepared from normal rat kidney contained significant amounts of an iNOS mRNA. These results suggest that there may be tonic influences in the outer medulla of the normal rat kidney resulting in the "steady-state" presence of an iNOS mRNA. Cortical tubules and the inner medulla were found to contain detectable but lesser amounts of the iNOS mRNA. The outer medulla was microdissected into proximal straight tubule (PST), medullary thick ascending limb (MTAL), medullary collecting duct (MCD) and vasa recta bundle (VRB). The iNOS mRNA was found primarily in the MTAL with minor amounts in the MCD and VRB of normal rat kidney. Animals were injected with lipopolysaccharide (LPS) and sacrificed 24 hours later. Treatment with LPS caused at least a 20-fold increase in the amount of iNOS mRNA in the liver or in macrophages isolated from the peritoneum. Endotoxin treatment led to over a 10-fold increase in iNOS mRNA content in glomeruli and the inner medulla. The iNOS mRNA level of the outer medulla was increased two- to threefold due to LPS treatment.

Amino Acid Oxidoreductases↗

PubMed1994

The management of war wounds to the extremities.

We present our experience in the treatment of war wounds in 174 patients treated in the Institute of Plastic and Reconstructive Surgery, Department of Surgery, Clinical Hospital Center in Zagreb. The wounds were divided into four categories depending on the type of injury and the extension of the soft tissue defect which showed the differences in primary excision and reconstruction of wounds. Patients were placed in one of two groups depending on their primary treatment and time of definitive reconstruction. Group A comprised 79 patients who were initially treated by plastic surgeons and whose reconstructive procedure was done within five days. Group B comprised 95 patients who were initially treated in a field hospital and referred later to the plastic surgery unit for definitive reconstruction more than five days after the injury. Sixty-nine (87%) of the patients in group A had only one or two debridements before definitive closure and stayed in hospital 20 days or less. In group B, 59 (62%) of the patients required three or more debridements before definitive closure and remained in hospital more than 21 days (p < 0.001). Proper primary treatment and early reconstruction result in significantly shorter duration of hospital stay and lead to more effective rehabilitation and recovery of the patients. A knowledge in terminal ballistics is important in the understanding of the pathophysiology of war wounds.

Adolescent↗

PubMed1993

High-energy war wounds: flap reconstruction.

In this article, we emphasize that knowledge of terminal ballistics is essential for understanding the pathophysiology of war wounds. We present our own experiences in treatment of high-energy war wounds in 75 patients treated in the Institute of Plastic and Reconstructive Surgery, Department of Surgery, Clinical Hospital Center in Zagreb. Patients were divided into three groups with regard to the time of definite reconstruction, using local or free microvascular flaps. About 12% of patients underwent flap reconstruction in the acute phase, associated with low complication rate and the shortest hospital stay. Group II was comprised by 18% of the patients and, considering the number of complications, presented the most unfavorable time for reconstruction. Flap reconstruction in the chronic phase resulted in a substantial prolongation of the hospital stay in 82% of patients. Therefore, we advocate proper primary treatment of wounds aimed at early flap closure. This type of management results in a significantly shorter hospitalization and leads to more effective rehabilitation and recovery of patients.

Adolescent↗

PubMed1989

Protein kinase-A and the effects of parathyroid hormone on phosphate uptake in opossum kidney cells.

Current evidence indicates that signal transduction after receptor binding of PTH involves the stimulation of adenylate cyclase as well as stimulation of phosphoinositide metabolism. Recent studies, showing that PTH alters phosphate transport in opossum kidney cells at concentrations which do not increase cAMP production and that activators of protein kinase-C also alter phosphate transport, have led to the suggestion that there is a dual mechanism for the regulation of phosphate transport by PTH, namely, protein kinase-C at physiological levels of PTH and cAMP at higher levels of PTH. The present studies were designed to evaluate the relationship between cAMP-dependent protein kinase (PK-A), a more sensitive indicator of alterations in cAMP metabolism than measurements of total cellular cAMP, and phosphate transport in opossum kidney cells, in response to bovine (b)PTH 1-34 and [Nle8,Nle18,Tyr34]bPTH 3-34 amide. While bPTH 1-34 markedly stimulated cAMP accumulation (half-maximal stimulation between 1 and 10 nM), PTH 3-34 analog did not. Phosphate transport was inhibited in a dose-dependent manner by bPTH 1-34, with half-maximal effect occurring between 0.1 and 1 nM. [Nle8,Nle18,Tyr34]bPTH 3-34 amide also altered phosphate transport, although this peptide was 3 orders of magnitude less potent than bPTH 1-34. PK-A activity increased in response to bPTH 1-34 and correlated closely with the effects of PTH on phosphate transport. [Nle8,Nle18,Tyr34]bPTH 3-34 amide, which did not appear to increase cAMP, also resulted in a significant increase in the activity of PK-A. Studies of inhibition of cAMP accumulation using 2',5'-dideoxyadenosine demonstrated that while this agent markedly inhibited the accumulation of cAMP in response to PTH, the effects of PTH on phosphate transport were not altered. However, in spite of the reduction in cAMP the activation of PK-A was similar to control. These data indicate that the effects of PTH peptides on phosphate transport are more closely related to changes in the activity of PK-A than to levels of total cAMP. Activation of PK-A in response to PTH is demonstrable at the lowest doses of PTH that alter phosphate transport.

Animals↗

PubMed1989

[An anatomic study of the septofascial layer in the forearm].

In the anatomical investigation the authors dissected 20 fresh cadaveric forearms to study septofascial layers. It's vascularization was based on radial artery and concomitant veins. We perfused those flaps with methylene blue in the proximal part of radial artery. In 10 cases we found fine vascular network colored in blue. In the second group we isolated free septofascial tissue which was perfused with radiopaque contrast Hexabrix. Five flaps were perfused in the proximal part of vascular pedicle and five in the distal part. Afterwards the radiographs confirmed good vascular network, independent of flow direction. Fascia dimension in the proximal part of the forearm varied from 7-15 cm and in the distal part from 6-10 cm, depending on the forearm size. Fascia length varied from 21-27 cm. The authors found thicker and stronger fascia in the ulnar part of the forearm. The length of vascular pedicle was reversely proportional with the flap dimension. This anatomical investigation may find it's greatest application in plastic and reconstructive surgery.

Adolescent↗

PubMed1988