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Biomedical subjects

P Petrini

Publications and source records attributed to P Petrini.

At least 37 records · Page 2Linked to original sources
PubMed2000

Novel poly(urethane-aminoamides): an in vitro study of the interaction with heparin.

In order to obtain heparin-binding polyurethanes, tertiary amino-groups have been introduced in the polymer backbone by attributing a key-role to the chain extender, i.e. substituting butanediol, commonly used in polyurethane synthesis, with a tailor-made diamino-diamide-diol. In this work a poly(ether-urethane-aminoamide) (PEU/PIME/al) was obtained with poly(oxytetramethylene) glycol 2000, 1,6-hexamethylene-diisocyanate and the new chain extender, in the molar ratio 1:2:1. The heparin binding capacity of PEU/PIME/al was evaluated with 125I labelled heparin, using for comparison the analogous polymer obtained with a diamide-diol (i.e. the poly(ether-urethane-amide) PEU/PIBLO/al), and two commercially available biomedical polyurethanes (Pellethane 2363 and Corethane). pH and ionic strength dependence of the heparin uptake were investigated by treating all the polyurethanes with solutions of 125I heparin into buffers from pH 4 to 9 or NaCl molarity from 0.0 to 1.0. The stability of the interaction with bound heparin was investigated by sequential washing treatments (PBS, 1 N NaOH, 2% SDS solution), then analysing the residual radioactivity on the materials. Results indicated that the heparin binding of PEU/PIME/al is significantly higher and more stable than that of the other polyurethanes, with a time-dependent kinetic. The interaction with heparin appears to be prevalently ionic, with the contribution of other electrostatic and hydrophobic interactions. Activated partial thromboplastin time (APTT), performed on human plasma with polyurethane-coated, heparinized test tubes, indicated that bound heparin maintains its biological activity after the adsorption.

Animals↗
PubMed2000

In vitro stability of polyether and polycarbonate urethanes.

The in vitro structural stability of poly-ether-urethanes (PEUs) and poly-carbonate-urethanes (PCUs) was examined under strong acidic (HNO3) or alkaline (NaClO) oxidative conditions and in presence of a constant strain state. Polyurethane (PU) samples were represented by sheets solvent-cast from commercial pellets or by tubular specimens cut from commercial catheters. The specimens were strained at 100% uniaxial elongation over appropriate extension devices and completely immersed into the oxidative solutions at 50 degrees C for 7-14 days. The changes induced by the oxidative treatments were then evaluated by molecular weight analysis, tensile mechanical tests, and scanning electron microscopy. In the experiments with solvent-cast samples, the PEU Pellethane was degraded more in the alkaline oxidative conditions and mainly in the absence of an applied uniaxial stress. All the tested PCUs were, on the contrary, more affected by the acidic oxidative agent. All the PCUs proved to have overall better stability than the PEU. The susceptibility to oxidation was also dependent on the shape and bulk/surface organisation acquired by the same polymer during its processing. When the oxidative test was applied to catheters made of a PEU and a PCU, the results confirmed the better stability of poly-carbonate-urethanes.

Biocompatible Materials↗
PubMed1999

[Centralized care is the basis of care programs for hemophilia patients].

Haemophilia is a rare and potentially life-threatening disease. In Sweden, with a population of approximately 8.5 million, about 350 people suffer from the more severe forms of haemophilia or von Willebrand disease. Meticulous management is important if the patients are to be spared chronic disability and serious treatment complications. The disease is lifelong and affects psychosocial aspects of life among patients and their families. With the help of a grant from the Swedish Board of Halth and Welfare, a care programme has been designed to guarantee Swedish haemophiliacs comparable and optimal care. The programme has been drawn up by representatives of the three haemophilia centres in Sweden (at University Hospital, Malmö, Sahlgrenska University Hospital, Gothenburg, and Karolinska Hospital, Stockholm) in co-operation with the World Federation of National Haemophilia Organisations. To ensure optimal individual application of the programme, individualised management strategies and patient information leaflets have been prepared.

Centralized Hospital Services↗
PubMed1999

Synergistic effects of oxidative environments and mechanical stress on in vitro stability of polyetherurethanes and polycarbonateurethanes.

The in vitro structural stability of polyetherurethanes (PEUs) and polycarbonateurethanes (PCUs and PCUUs) was examined under strong oxidative conditions (0.5N HNO3, pH 0.3; and NaClO, 4% Cl2 available, pH approximately 13) and in the presence of a constant strain state. Solvent-cast dog-bone shaped specimens were strained at 100% uniaxial elongation over extension devices and completely immersed in the oxidative solutions at 50 degrees C for 15 days. Unstrained polyurethane (PU) samples were treated in the same way for comparison. The modification of the PU molecular structure was determined by DSC, GPC, ATR-FTIR, static contact angle, and surface roughness analyses. The incubation in nitric acid and sodium hypochlorite brought about a greater degradation of samples tested under the applied strain with the exception of PEU treated with nitric acid. PEU was the most affected material, showing bulk deterioration in NaClO and significant modifications in nitric acid, with the appearance of new IR bands, which were assigned to oxidation products. A higher phase separation between soft and hard domains occurred in PCUs upon incubation in nitric acid, the treatment with NaClO gave rise to new bands in the IR spectra, denoting the presence of oxidation products at the surface. The surface roughness greatly increased in strained PCUs with SEM evidence of deep cracks and holes or ragged and stretched fractures perpendicular to the direction of stress. PCUU underwent complex chemical modifications with a marked decrease of N-H and urea IR absorptions and showed a lower degradation than PEU and PCUs under mechanical constraint. From these results, sodium hypochlorite appears to be able to create an ESC-like degradation for PUs that are resistant to other aggressive chemical environments.

Microscopy, Electron, Scanning↗
PubMed1999

Polyurethane-maleamides for cardiovascular applications: synthesis and properties.

Several polyurethane-maleamides (PUMAs) containing polyether or polycarbonate soft segments, and aromatic or aliphatic hard segments were synthesized by solution or bulk polymerization, using maleic acid (MA) or a mixture of MA and butanediol as chain extenders. Using this process, activated double bonds are introduced into the polymer chains and the base polyurethanes may undergo further modification via specific grafting, thus improving their tissue compatibility. PUMAs chemicophysical properties were evaluated by gel permeation chromatography (GPC), intrinsic viscosity analyses, differential scanning calorimetry (DSC), Fourier transform infrared spectroscopy (FT-IR) and tensile mechanical tests. Polycarbonate diol (PCU)-based PUMAs showed higher molecular weights than polyether diol (PEU)-based ones. The use of butanediol in mixture with maleic acid led to an increase of molecular weights. FT-IR confirmed the presence of the bands related to the amide groups and to the conjugated double bond, yet more evident for the polymer obtained in solution. The higher crystallinity shown by this polymer was also indicative of a better phase separation. All the PCU-PUMAs exhibited similar tensile properties with a higher stiffness than PEU-PUMAs. Among the PEU-PUMAs, the highest tensile properties were shown by the polymer obtained in solution, and by the one derived from a mixture of maleic acid and butanediol.

Journal Article↗
PubMed1999

Primary prophylaxis in severe haemophilia should be started at an early age but can be individualized.

The frequency of joint bleeds and orthopaedic joint scores were evaluated in 121 patients with severe haemophilia who had started prophylactic treatment with clotting factor concentrates at least once weekly before the age of 10. 75 of the patients started before the age of 3, 31 at the age of 3-5 and 15 at the age of 6-9. Each subgroup was evaluated separately. In addition, a regimen of one infusion weekly was compared with that of two (haemophilia B) or three (haemophilia A) infusions weekly in each patient. A significant decrease in the overall number of joint bleeds per year was found after shortening the infusion interval (P<0.005), but the individual bleeding pattern varied. In survival analysis of the first pathologic joint score event, those who started prophylaxis before the age of 3 had a better outcome overall than those starting at later ages (P=0.001). However, in subgroup analysis, no significant difference was seen in the annual number of joint bleeds and the development of arthropathy between those starting with, or shifting to, the more intensive regimen before the age of 3 and those that were put on this regimen at the age of 3-5. Age at start of prophylaxis was found to be an independent predictor for the development of arthropathy (P=0.0002), whereas dose and infusion interval at start were not. Our data emphasize the importance of starting replacement therapy during the first years of life. However, it seems that when beginning the regimen it can be individualized and adjusted according to the bleeding pattern. In this way, the need for a venous access system may be assessed on an individual basis.

Age Factors↗
PubMed1998

Hepatitis C virus-infected, HCV-RNA-negative patients with bleeding disorders--relationship to age, HIV and treatment.

All 155 anti-hepatitis C-virus (HCV) positive patients with haemostatic disorders at our unit were tested for HCV-RNA in order to determine the prevalence of a negative result. The patients were also characterized in order to find predictors for a negative HCV-RNA test. The prevalence of a negative HCV-RNA test was 15.5% (24 of 155) and this was similar among anti-HIV positive and negative patients. A common denominator for the 4 HIV-infected, HCV-RNA negative haemophiliacs was treatment with azidothymidin prior to the first test. Among the anti-HIV negative patients, those < 40 y of age had a significantly greater chance of being HCV-RNA-negative than the older ones (27.3 vs 3.6%). They also had a lower consumption of plasma products than age-matched HCV-RNA positive cases. Absence of co-infection with hepatitis B was not correlated with a negative HCV-RNA test. Young age and a low requirement for factor concentrates thus seem to be predictors for a negative HCV-RNA test in patients with bleeding disorders.

Adolescent↗
PubMed1998

Port-A-Cath usage in children with haemophilia: experience of 53 cases.

Experience of the Port-A-Cath implantable venous access system in 53 children with severe or moderate haemophilia A or B from seven centres in five countries is reviewed. The cumulative duration of follow-up was 1578 months (median 30 months, range 1-114). Of the devices implanted, 70% (37/53) were used without complications (median follow-up 32 months; range 1-114) and the remaining 30% (16/53) were associated with various types of complication: infection, bacteraemia or septicaemia in 56% (9/16) of cases, i.e. a rate of 0.07 per follow-up year or 0.19 per 1000 patient days, or various technical complications occurring after a median of 32 months (range 4-75) of uncomplicated use in the remaining 44% (7/16). Of the patients with inhibitors, 64% (7/11) manifested complications. Both doctors and parents considered that the Port-A-Cath device can be used with an acceptable frequency and severity of complications, and that it enables regular prophylactic or on-demand home treatment of children with haemophilia to be begun at an early age.

Catheterization, Central Venous↗
PubMed1998

Experiences with continuous infusion of recombinant activated factor VII.

A questionnaire was sent to 28 haemophilia treatment centres known to have used recombinant activated factor VII (rFVIIa; NovoSeven, Novo Nordisk, Bagsvaerd, Denmark), to collect data on continuous infusion of this product. This mode of administration was recently introduced for rFVIIa but there are several questions which remain to be answered in order to optimize this technique. Of the 26 responding centres, 14 had used rFVIIa in continuous infusion for 40 treatment episodes over a total of 283 days. In most of the cases the treatment was targeted at a factor VII level of 10 IU/ml, monitored by the one-stage clotting assay. This seemed to be adequate for most of the haemorrhagic and surgical procedures. Pretreatment pharmacokinetic evaluation was performed in only a minority of the cases but is probably of great importance given the wide variation observed in the clearance values. A strategy was necessary to prevent local thrombophlebitis, at least for infusions in peripheral veins; parallel infusion of heparin, saline or dextrose-saline proved effective. The question of optimal monitoring needs further attention. Haemorrhagic complications were significantly less frequent when treatment was combined with the antifibrinolytic tranexamic acid.

Drug Monitoring↗
PubMed1998

Treatment of acute bleeds with recombinant activated factor VII during immune tolerance therapy.

In our clinic, five patients with haemophilia A and one patient with haemophilia B and inhibitors have been treated with immune tolerance induction (ITI) since 1995. Bleeding symptoms during this period have been treated with recombinant activated factor VII (rFVIIa; NovoSeven, Novo Nordisk, Bagsvaerd, Denmark). Four of the six patients did not need rFVIIa during ITI other than for port-a-cath insertions, but two have been treated intensively because of repeated bleeding problems. The first of these developed inhibitors at the age of 2 years after 11 days of exposure to factor VIII (FVIII). He was treated for 40 bleeding episodes before ITI started, and during ITI he was treated another 24 times, including eight treatments for joint bleeds. Treatment was effective for the different types of bleeding episode. However, in spite of repeated treatment for these joint bleeds, he developed two target joints with synovitis (right knee and left elbow). The synovitis only showed signs of regression when inhibitor levels were reduced due to the ITI regimen. The second patient, now 5 years old, has severe haemophilia B. He developed inhibitors and anaphylaxia having received prophylactic treatment from the age of 1 year. He has now received ITI with 120 units/kg body weight per day of FIX for 68 weeks. In the event of trauma and bleeding he is treated promptly with rFVIIa by his parents at home. Treatment is started with 160-180 microg/kg body weight and, if needed, another dose of 90 microg/kg is given after 3 h. During 1996, 35 bleeds or traumas were treated. The total amount of rFVIIa administered to this child was 211.2 mg. All but one joint bleed and all muscle bleeds needed more than one injection. The need for another injection is judged by the parents and the child from clinical signs, such as pain and swelling. Neither of these two boys have shown any signs of thrombosis or disseminated intravascular coagulation. In summary, rFVIIa is a well tolerated and effective therapy for acute bleeding episodes during ITI. Dosing and intervals can be the same as for patients not on ITI therapy. Early intervention at home can minimize the risk of synovitis.

Acute Disease↗
PubMed1997

Chemical stability of polyether urethanes versus polycarbonate urethanes.

The relative chemical stability of two commercially available polyurethanes-Pellethane, currently used in biomedical devices, and Corethane, considered as a potential biomaterial-was investigated following aging protocols in hydrolytic and oxidative conditions (HOC, water, hydrogen peroxide, and nitric acid) and in physiological media (PHM, phosphate buffer, lipid dispersion, and bile from human donors). The chemical modifications induced on these polymers were characterized using differential scanning calorimetry (DSC), gel permeation chromatography (GPC), and Fourier transform infrared spectroscopy (FTIR). With the exception of nitric acid, all of the aging media promoted a mild hydrolytic reaction leading to a slight molecular weight loss in both polymers. When aged in water and hydrogen peroxide, Pellethane experienced structural modifications through microdomain phase separation along with an increase of the order within the soft-hard segment domains. The incubation of Pellethane in nitric acid also resulted in an important decrease of the melting temperature of its hard segments with chain scission mechanisms. Moreover, incubation in PHM led to an increase of the order within shorter hard-segment domains. FTIR data revealed the presence of aliphatic amide molecules used as additives on the Pellethane's surface. The incubation of Corethane under the same conditions promoted an almost uniform molecular reorganization through a phase separation between the hard and soft segments as well as an increase of the short-range order within the hard-segment domains. Incubation of this polymer in nitric acid also resulted in a chain scission process that was less pronounced than that measured for the Pellethane samples. Finally, lipid adsorption occurred on the Corethane sample incubated in bile for 120 days. Overall data indicate that polycarbonate urethane presents a greater chemical stability than does polyetherurethane.

Calorimetry, Differential Scanning↗
PubMed1996

Four novel mutations in deficiency of coagulation factor XIII: consequences to expression and structure of the A-subunit.

The characterization of naturally occurring mutations is one way to approach functionally significant domains of polypeptides. About 10 mutations have been reported in factor XIII (FXIII) A-subunit deficiency, but very little is known about the effects of the mutations on the expression or the structure of this enzyme. In this study, the recent crystallization of FXIII A-subunit and determination of the three-dimensional model were used for the first time to pursue the structural consequences of mutations in the A-subunit. The molecular analysis of four families from Sweden, Germany, and Denmark revealed four previously unreported point mutations. Three of the mutations were missense mutations, Arg326-->Gln, Arg252-->Ile, and Leu498-->Pro, and one was a nonsense mutation, a deletion of thymidine in codon for Phe8 resulting in early frameshift and premature termination of the polypeptide chain. In the case of the nonsense mutation, delT Phe8, the steady-state mRNA level of FXIII A-subunit was reduced, as quantitated by reverse transcriptase-polymerase chain reaction and solid-phase minisequencing. In contrast, none of the missense mutations affected mRNA levels, indicating the possible translation of the mutant polypeptides. However, by enzyme-linked immunosorbent analysis and immunofluorescence, all the patients demonstrated a complete lack of detectable factor XIIIA antigen in their platelets. In the structural analysis, we included the mutations described in this work and the Met242-->Thr mutation reported earlier by us. Interestingly, in the three-dimensional model, all four missense mutations are localized in the evolutionarily conserved catalytic core domain. The substitutions are at least 15 A away from the catalytic cleft and do not affect any of the residues known to be directly involved in the enzymatic reaction. The structural analyses suggest that the mutations are most likely interfering with proper folding and stability of the protein, which is in agreement with the observed absence of detectable FXIIIA antigen. Arg326, Arg252, and Met242 are all buried within the molecule. The Arg326-->Gln and Arg252-->Ile mutations are substitutions of smaller, neutral amino acids for large, charged residues. They disrupt the electrostatic balance and hydrogen-bonding interactions in structurally significant areas. The Met242-->Thr mutation is located in the same region of the core domain as the Arg252-->Ile site and is expected to have a destabilizing effect due to an introduction of a smaller, polar residue in a tightly packed hydrophobic pocket. The substitution of proline for Leu498 is predicted to cause unfavorable interatomic contacts and a disruption of the alpha-helix mainchain hydrogen-bonding pattern; it is likely to form a kink in the helix next to the dimer interface and is expected to impair proper dimerization of the A-subunits. In the case of all four missense mutations studied, the knowledge achieved from the three-dimensional model of crystallized FXIII A-subunit provides essential information about the structural significance of the specific residues and aids in understanding the biologic consequences of the mutations observed at the cellular level.

Adolescent↗
PubMed1994

Normal vaginal delivery is to be recommended for haemophilia carrier gravidae.

Every child with severe or moderate haemophilia A or B, born in Sweden during the period 1970-1990, was treated in the national haemophilia register, all 117 case records being surveyed for mode of delivery and perinatal complications. Of the 117 deliveries, 13 were by caesarean section and the remaining 104 vaginal. Of the 13 caesarean sections, 2 were performed because the woman was a haemophilia carrier, the remaining 11 (5 emergency, 6 elective) for other reasons. Neonatal complications were: subgaleal or cephalic haematoma (n = 12), intracranial haemorrhage (n = 4), umbilical bleeding (n = 4), haematuria (n = 1), retro-orbital bleeding (n = 1) and abnormal bleeding after surgery, injection or venepuncture (n = 28). Of the 12 infants with subgaleal/cephalic haematoma, 10 were delivered by vacuum extraction. Seven more infants were delivered by vacuum extraction and another 11 were born without abnormal bleedings after laborious (> 24 h) delivery. Of the 4 children with intracranial haemorrhage, all were sporadic cases of haemophilia, 1 was a premature birth by caesarean section in the 27th week, I was delivered by vacuum extraction and the remaining 2 vaginally. In these 4 cases there were no sequelae or only minor ones. We conclude that the risk of serious bleeding in conjunction with normal vaginal delivery is small, but that vacuum extraction should be avoided when delivering offspring of haemophilia carriers.

Adolescent↗
PubMed1993

Pattern of organization of primary visual pathways in the European lizard Podarcis sicula Rafinesque.

Central visual pathways are similarly organized in all vertebrates, although differences are also evident in the distribution of retinofugal axons in mammals, birds and reptiles. We traced the retinofugal projections in the European lizard Podarcis sicula Rafinesque and compared our observations with previous findings in other reptilian species, as well as in mammals and in birds, in order to contribute to the understanding of similarities and differences in the pattern of organization of visual pathways in these vertebrate classes. Either HRP or 3H-proline injections were placed into one eye. No differences in staining pattern were observed between HRP and 3H-proline experiments. Prominent retinofugal projections were observed to the thalamic nuclei nucleus dorsolateralis, nucleus geniculatus lateralis dorsalis, nucleus geniculatus lateralis ventralis and nucleus geniculatus lateralis ventralis, pars ventralis. In the hypothalamus the suprachiasmatic nucleus, and in the pretectum nuclei geniculatus pretectalis, lentiformis mesencephali and posterodorsalis contained detectable amounts of labeled terminals. Retinal fibers were distributed to layers 14 and 12 of the optic tectum and terminated in layers 13, 11, and 8. Labeled fibers were also present in the basal optic tract, and terminals were located in the nucleus of the basal optic tract. Ipsilateral retinofugal fibers were detected in the optic tract, and terminals were observed in the same thalamic and pretectal nuclei which receive crossed projections. No terminals in the ipsilateral tectal layers could be demonstrated. Compared to the crossed projection, the ipsilateral retinofugal contingent was very small. These results confirm and extend data from previous studies in reptiles and are consistent with the distribution of retinofugal fibers found in other vertebrates. The presence of ipsilateral retinofugal projections represents a common feature of the organization of visual pathways in reptiles, although its importance for binocular interactions remains to be elucidated.

Animals↗
PubMed1992

Implantable central venous catheter facilitates prophylactic treatment in children with haemophilia.

Twelve children with a severe form of haemophilia A received a totally implantable venous access system (Port-A-Cath) to facilitate regular prophylactic treatment with factor VIII. The indication for implantation was difficulty in obtaining regular access to a peripheral vein. Postoperative bleeding around the portal site occurred in two of 12 cases. After a median duration of follow-up of 26 months (range 5-79 months), none of the systems had needed replacement due to bleeding, septicaemia or thrombosis. One child, with an inhibitor against factor VIII, had an infection at the portal site and this system was removed. None of the other children had any serious side effects. Nine of the 12 children's parents learned how to use the Port-A-Cath system, thus enabling optimal prophylactic home treatment with factor VIII to be begun early in life.

Catheterization, Central Venous↗
PubMed1991

Prophylaxis with factor concentrates in preventing hemophilic arthropathy.

Seven children with severe hemophilia A on prophylactic substitution therapy since a mean age of 5 years (group I) were investigated in 1978 (at ages 6-12 years) and in 1988 (at ages 16-22 years). The results were compared with those of seven children aged 5-12 for whom such treatment was started at a mean age of 3 years (group II). In group I, four had each had more than 20 ankle hemarthroses at the first investigation, while in group II, only one boy had experienced such a high bleeding frequency. Radiological changes in ankles were found in one of seven in group II compared with five of seven in group I. Progression of these changes was shown in eight of 10 ankles of group I at reinvestigation. Regular prophylactic therapy must start early, at ages 1-2 years, to prevent changes in ankle joints, and parents and children must learn to recognize ankle bleeding. Modern Factor VIII concentrates must be administered to children two or three times per week in dosages of 3,000 U/kg/year in order to reduce hemarthroses to a minimum. The dosages can probably be lowered if the intervals are shortened. Children on prophylactic treatment can engage in regular sports activities.

Adolescent↗