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Biomedical subjects

U Martinowitz

Publications and source records attributed to U Martinowitz.

At least 55 records · Page 3Linked to original sources
PubMed1998

Continuous infusion therapy in haemophilia.

The application of coagulation factor therapy by continuous infusion (CI) was first suggested by Brinkhous in the early 1950s. The recent introduction of this mode of therapy to everyday practice was made possible after the demonstration of a good stability of most factor concentrates which were also found safe regarding potential bacterial contamination. Other developments included a better understanding of the pharmacokinetics of factors concentrates as well as the availability of a new delivery system. Continuous infusion was shown to be superior to bolus injection (BI) in achieving a stabile haemostatic effect, in the prevention of post-operative bleeding and was found to save between 20-50% in the required factor. This mode of therapy was found effective in haemophilia A and B as well as among patients with inhibitors to FVIII and with von Willebrand disease (vWD).

Factor IX↗
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↗
PubMed1997

Reattachment of extraocular muscles using fibrin glue in a rabbit model.

PURPOSE: Reattaching extraocular muscles by the conventional suturing method may be complicated by scleral perforation. The attachment of extraocular muscles, using fibrin sealants, avoids such risk. The authors evaluated the use of fibrin sealant in a laboratory rabbit model. METHODS: Fifty-eight eyes of 29 rabbits were used in the study. In both eyes of each rabbit, the superior rectus muscle was disinserted, recessed, and either sutured or reattached to the globe by fibrin sealant. Two groups of eyes were compared. In one group (42 eyes), the recessed muscle was reattached using fibrin sealant. In the second group (16 eyes), sutures were used to reattach the recessed muscle to the globe. The insertion of the superior rectus muscle was examined 14 days after surgery, and histopathologic evaluation was performed 6 weeks after the surgery. RESULTS: Although in the sutured muscle group no slippage from the original placement was found, it was found in the group in which fibrin glue was used. The muscle slippage was greater at the small muscle recessions and smaller at the large muscle recessions. For muscle recession of 6 mm or more, the average muscle slippage was 0.12 +/- 0.28 mm, which was not statistically different from the suture group (P = 0.0828). CONCLUSIONS: Fibrin sealant was found to be effective for extraocular muscle reattachment only in large muscle recessions. However, in small muscle recessions the glue was not strong enough to overcome the contractive strength of the muscle.

Animals↗
PubMed1997

Fibrin tissue adhesives.

FTA is a promising adjunct treatment in many fields of surgery, mainly in patients with acquired and congenital bleeding disorders or in procedures with high risk of postoperative bleeding or leaking of air, blood, fluids. Numerous report exist for variety of indications, however, very few are well controlled and conclusive. There is controversy and contradicting data that stem from variability in FTA formulation the selection and design of the operative indication the methodology of application including the application devices and the skills of the surgeon. Understanding of all these differences and the requirements for the certain indication are important for the successful use of FTA. It is important to remember that FTA is a blood product and even with more than one viral inactivation techniques there should have a clear indication for its use. If no clinically important benefit is proven for a certain indication it means that contraindication exists.

Fibrin Tissue Adhesive↗
PubMed1997

Orthotic management of the knee in patients with hemophilia.

The knee joint is the most frequently affected articulation in patients suffering from hemophilia. Before the availability of active coagulation factors, orthotic use was aimed at corrective functions. Orthotics in the modern era play a protective and preventative role, and they are used in the treatment of hemarthroses and in joints affected by chronic synovitis. Because levels of availability of clotting factors and orthotic material vary extensively world-wide, an overview is provided whereby each group of therapists can adapt themselves to the principles.

Acute Disease↗
PubMed1996

[Oral surgical procedures during anticoagulant therapy].

Minor oral surgery, in patients being treated with anticoagulant therapy, constitutes a problem for the oral and maxillofacial surgeon. 77 patients getting coumarin underwent 168 oral surgical procedures (tooth extraction, apicoectomy, crown-lengthening, excision of lesions) without lowering the dose of anticoagulant. Local hemostasis was achieved in all cases by silk suture. For tooth extraction gelfoam was used as well. In 12 patients who presented with postoperative bleeding, it was controlled in all by gauze pressure with tranexamic acid and/or biologic glue and/or surgical splinting. Postoperative bleeding was not correlated with the international normalized ratio (INR), but with degree of local inflammation. The study shows that interruption of anticoagulant therapy in such cases is not justified, and the use of tranexamic acid or biological glue can control bleeding.

Adult↗
PubMed1996

Multiple joint procedures in a single operative session on hemophilic patients.

Hemophilia is a coagulation disorder wherein frequent hemarthroses result in premature joint degradation. This hemophilic osteoarthropathy is polyarticular, and despite modern coagulation possibilities, acute hemarthroses and chronic synovitis are common. Because repair of a single joint in polyarthritic conditions may not improve the patient's functional ability a policy has been adopted to create a functional limb. This therapeutic protocol succeeded in gaining the objectives of a functional limb, and it was noted that the complication rate was less than expected and that the rehabilitation period was relatively short.

Adult↗
PubMed1996

Role of fibrin sealants in surgical procedures on patients with hemostatic disorders.

Fibrin sealants have until now been used to a very limited extent in patients with a bleeding diathesis. The authors have accumulated experience from 8 minor and 40 major surgical procedures, plus 10 circumcisions and 118 tooth extractions in 106 patients suffering from hemophilia A, B, or von Willebrand's disease. Most of the patients had the severe form of the disease. The authors were able to show a reduction of blood loss and of requirements for replacement therapy with factor concentrates. The literature on the application of fibrin sealants in this group of patients, which mainly deals with dental procedures, is reviewed and compared with data from the current study. The composition of the glue is of major significance and is discussed in detail.

Blood Coagulation Disorders↗
PubMed1996

Fibrin sealant.

Fibrin sealant consists of fibrinogen and thrombin solutions, which generate a crosslinked fibrin clot in a process that mimics the last stage of the physiologic coagulation system. Fibrin sealants have been used widely in Europe in the past two decades for hemostasis, sealing, and as a vehicle for drugs and growth factors, and as a biologic glue. This review discusses the various types of fibrin sealants (autologous, homologous, commercial), their composition, mechanism of action, functional characteristics, experimental and clinical uses, limitations, complications, adverse reactions, and viral safety.

Animals↗
PubMed1996

Feasibility of using recombinant factor VIIa in continuous infusion.

Recombinant factor VIIa (rFVIIa; NovoSeven) is a recent addition to the hemostatic alternatives for the treatment of hemophiliacs with inhibitors. A drawback in the use of rFVIIa has been its half-life of only about 2 h, which necessitates very frequent and punctual injections. We evaluated the stability of reconstituted, but not further diluted, rFVIIa in 3 infusion systems (WalkMed 350 and CADD-Plus minipumps and Meddex 2001 syringe pump). The factor VII (F VII) activity was maintained for at least 3 days at room temperature with only a minor and clinically insignificant increase in oxidized forms of rFVIIa and minimal leaching of the plastic softeners dibutylphthalate and di-octylphthalate after 24-48 h. Addition of heparin, 5-10 U/ml, to reconstituted rFVIIa caused a loss of about 50% of the activity within 4 h of storage in the infusion system, whereas low molecular weight heparin had no such effect. Repeated samples showed that the infusion systems maintained sterility. Reconstituted rFVIIa did not support bacterial growth when inoculated with Staphylococcus aureus or Escherichia coli to any greater extent than did reconstituted factor VIII, lidocaine in saline or heparin in saline. Two patients were treated with continuous infusion of rFVIIa on 4 occasions (total knee arthroplasty, wound revision, and twice straightening of a 90 degrees contracture of the knee under general anaesthesia). A preoperative pharmacokinetic evaluation was performed, and the clearance was used to calculate the maintenance dose, aiming at a FVII level of 10 U/ml, which proved to be a hemostatic level. The first patient had no change in the clearance during the two treatment episodes. He suffered from repeated thrombophlebitis at the infusion site. The second patient had a progressive decrease of the clearance from 86.4 to 24.7 ml/h/kg. He received during the first treatment a parallel infusion with heparin (approximately 250 U/24 h) to the same venous access and did not develop thrombophlebitis during 3.5 days of therapy. For the second episode low molecular weight heparin was added directly to the infusion bag, and no adverse effects were observed. Continuous infusion with rFVIIa is thus feasible with the minipumps used by us, eliminates the need for 2 h injections and reduces the total dose of rFVIIa by 50-75%, depending on the behaviour of the clearance.

Drug Stability↗
PubMed1996

Design and assessment of clinical trials on continuous infusion.

Continuous infusion of coagulation factors is becoming increasingly popular, and is mirrored by the accelerating rate of publications on this topic. However, several questions remain, particularly regarding efficacy. For this purpose, well designed trials are required. Some guidelines for such trials are presented here.

Clinical Trials as Topic↗
PubMed1996

Review of pumps for continuous infusion of coagulation factor concentrates: what are the options?

Continuous infusion of coagulation factor concentrates has become more popular in recent years because it can substantially reduce the cost of surgery for a patient with hemophilia. This technique has also been used successfully for treatment of severe bleeds, induction of immune tolerance and short-term prophylaxis. The large selection of devices complicates the choice of an infusion system for this delivery approach. However, choosing the best type of device for a particular situation may determine the success or failure of continuous infusion.

Factor VIII↗
PubMed1995

Hepatitis E virus infection in hemophiliacs.

Israel is endemic for hepatitis E virus (HEV), the causative agent of enteric non-A, non-B hepatitis. Transmission is via the feco-oral route but the possibility of transmission through blood transfusion has been raised. This question was addressed by examining sera from 188 hemophilic patients in Israel, screening was performed with an enzyme immunoassay (EIA) for antibody against hepatitis E virus (anti-HEV) and confirmed with a neutralization test. Sixteen patients (9%) were seropositive for anti-HEV. A statistically significant difference was not found between the seroprevalence in this group and that of a healthy Israeli control population, matched for sex and age. The anti-HEV-seropositive hemophiliacs had the same seroprevalence of antibodies to hepatitis B and C virus and to HIV and the same number of cases with chronic hepatitis as among the anti-HEV-seronegative patients. The seroprevalence of antibodies to hepatitis A virus (anti-HAV) was, on the other hand, higher in the anti-HEV-seropositive group. This study indicates that HEV is not transmitted by cryoprecipitate or lyophilized factor concentrates. High prevalence of coinfection with hepatitis A supports our conclusion that HEV infection in Israeli hemophiliacs was due mainly to feco-oral transmission.

Adolescent↗
PubMed1995

Preliminary clinical experience: pharmacokinetics and tolerance of a double-virus-inactivated factor VIII preparation.

The incorporation of viral inactivation steps into the manufacture of factor VIII concentrates has markedly improved the safety margin of the product, but in order that viruses, such as hepatitis A, are not transmitted by infusion of factor VIII preparation, some manufacturers include a further process step, such as heat inactivation. There is the possibility that such a step will change the final factor VIII product and it was investigated whether there are any pharmacokinetic differences between the products Octavi S/D and Octavi S/D+heat treatment. It is concluded that Octavi S/D+heat treatment can be given in doses equal to Octavi S/D or other factor VIII concentrates.

Antiviral Agents↗
PubMed1995

Fibrin sealant in surgery of patients with a hemorrhagic diathesis.

The utilization of fibrin sealants in patients with hemostatic disorders has hitherto been very limited. Our experiences from 40 major and 8 minor surgical procedures, 10 circumcisions and 118 tooth extractions in 106 patients with hemophilia A, B or von Willebrand's disease, almost exclusively of the severe form, respectively, demonstrate the benefits regarding reduction of blood loss and requirements for systemic replacement therapy. The literature on the use of fibrin sealants in this group of patients, which mainly concerns dental procedures, is reviewed and compared with our data. The importance of the composition of the glue is also discussed in detail.

Blood Loss, Surgical↗