Porcine recombinant factor VIII (Obizur; OBI-1; BAX801): product characteristics and preclinical profile.

INTRODUCTION: Acquired haemophilia A (AHA) is a rare, often severe, auto-immune bleeding disorder caused by the development of inhibitory antibodies (inhibitors) to factor VIII (FVIII). Bypassing agents, recombinant activated FVII or activated prothrombin complex concentrate, are currently recommended as first-line treatments to control bleeding events in patients with AHA. AIM: A plasma-derived porcine FVIII (Hyate:C, Ipsen, UK) was used as a first-line treatment for AHA but was discontinued in 2004 due to viral safety concerns. A recombinant pFVIII (rpFVIII), Obizur (OBI-1; BAX801), which is expected to have a similar efficacy profile to Hyate:C but with a superior safety profile was developed and recently approved by the US Food and Drug Administration for the treatment of AHA. METHODS: Obizur manufacturing begins with the expression of B domain deleted rpFVIII by genetically modified baby hamster kidney-derived cells. The final purified and lyophilized drug product has a negligible risk of viral contamination and contains no animal-derived plasma proteins. Obizur was evaluated for immunogenicity, tolerability, pharmacokinetics and bleeding times in preclinical models including in haemophiliac dogs, cynomolgus monkeys and FVIII-knockout mice. RESULTS: Preclinical animal studies show that the efficacy and immunogenicity of Obizur are similar to that of Hyate:C and that Obizur has a more favourable safety profile. CONCLUSIONS: Obizur is a highly purified recombinant porcine FVIII drug product that has been demonstrated to have a favourable safety and efficacy profile when compared with Hyate:C and can be a valuable treatment option for control of bleeding in AHA patients.

A comparison of biphasic insulin aspart and insulin glargine administered with oral antidiabetic drugs in type 2 diabetes mellitus--a systematic review and meta-analysis.

OBJECTIVE: It is uncertain whether the addition of biphasic insulin analogues to oral antidiabetic drugs (OADs) is as effective and safe as basal insulin in patients with type 2 diabetes mellitus (T2DM). We performed a systematic review to compare glycaemic control and selected clinical outcomes in T2DM patients inadequately controlled with OADs whose treatment was intensified by adding biphasic insulin aspart (BIAsp 30) or insulin glargine (IGlar). METHODS: The analysis included randomised controlled trials (RCTs) identified by a systematic literature search in medical databases (MEDLINE, EMBASE, The Cochrane Library and other sources) up to March 2013. Studies met the inclusion criteria if they compared BIAsp 30 vs. IGlar added to at least one OAD in T2DM patients. Trials applying different OADs in both treatment arms were also included. Results were presented as weighted mean difference (WMD) or odds ratio (OR) with a 95% confidence interval (CI). RESULTS: Five trials, including a total number of 1758 patients followed up from 24 to 28 weeks, were identified. Quantitative synthesis demonstrated that BIAsp 30 reduced HbA1c level more efficiently than IGlar [5 RCTs; WMD (95% CI): -0.21% (-0.35%, -0.08%)]. Differences were observed in favour of BIAsp for lower mean prandial glucose increment [3 RCTs; WMD (95% CI): -14.70 mg/dl (-20.09, -9.31)]; no difference was observed for fasting plasma glucose [3 RCTs; WMD (95% CI): 7.09 mg/dl (-15.76, 29.94)]. We found no evidence for higher risk of overall [2 RCTs; 63% vs. 51%; OR = 1.77 (0.91; 3.44)] and severe hypoglycaemic episodes [4 RCTs; 0.98% vs. 1.12%; OR (95% CI) = 0.88 (0.31, 2.53)] in the BIAsp 30 group as compared with IGlar group. Twice-daily administration of BIAsp 30 resulted in larger weight gain [2 RCTs; WMD (95% CI) = 1.78 kg (1.04; 2.52)]. CONCLUSIONS: BIAsp 30 added to OAD therapy results in a better glycaemic control as compared with IGlar in T2DM patients. BIAsp 30 use is associated with slightly larger weight gain but no rise in risk of severe hypoglycaemic episodes.

Impact of FTO genotypes on BMI and weight in polycystic ovary syndrome: a systematic review and meta-analysis.

AIMS/HYPOTHESIS: FTO gene single nucleotide polymorphisms (SNPs) have been shown to be associated with obesity-related traits and type 2 diabetes. Several small studies have suggested a greater than expected effect of the FTO rs9939609 SNP on weight in polycystic ovary syndrome (PCOS). We therefore aimed to examine the impact of FTO genotype on BMI and weight in PCOS. METHODS: A systematic search of medical databases (PubMed, EMBASE and Cochrane CENTRAL) was conducted up to the end of April 2011. Seven studies describing eight distinct PCOS cohorts were retrieved; seven were genotyped for SNP rs9939609 and one for SNP rs1421085. The per allele effect on BMI and body weight increase was calculated and subjected to meta-analysis. RESULTS: A total of 2,548 women with PCOS were included in the study; 762 were TT homozygotes, 1,253 had an AT/CT genotype, and 533 were AA/CC homozygotes. Each additional copy of the effect allele (A/C) increased the BMI by a mean of 0.19 z score units (95% CI 0.13, 0.24; p = 2.26 × 10(-11)) and body weight by a mean of 0.20 z score units (95% CI 0.14, 0.26; p = 1.02 × 10(-10)). This translated into an approximately 3.3 kg/m(2) increase in BMI and an approximately 9.6 kg gain in body weight between TT and AA/CC homozygotes. The association between FTO genotypes and BMI was stronger in the cohorts with PCOS than in the general female populations from large genome-wide association studies. Deviation from an additive genetic model was observed in heavier populations. CONCLUSIONS/INTERPRETATION: The effect of FTO SNPs on obesity-related traits in PCOS seems to be more than two times greater than the effect found in large population-based studies. This suggests an interaction between FTO and the metabolic context or polygenic background of PCOS.

Iteration model of starch hydrolysis by amylolytic enzymes.

An elaborate computer program to simulate the process of starch hydrolysis by amylolytic enzymes was been developed. It is based on the Monte Carlo method and iteration kinetic model, which predict productive and non-productive amylase complexes with substrates. It describes both multienzymatic and multisubstrate reactions simulating the "real" concentrations of all components versus the time of the depolymerization reaction the number of substrates, intermediate products, and final products are limited only by computer memory. In this work, it is assumed that the "proper" substrate for amylases is the glucoside linkages in starch molecules. Dynamic changes of substrate during the simulation adequately influence the increase or decrease of reaction velocity, as well as the kinetics of depolymerization. The presented kinetic model, can be adapted to describe most enzymatic degradations of a polymer. This computer program has been tested on experimental data obtained for alpha- and beta-amylases.

[Traumatic hip dislocation complicated by soft tissue interposition--a case report and review of the literature]. / Urazowe zwichniecie stawu biodrowego powiklane interpozycja tkanek miekkich--opis przypadku i przeglad pismiennictwa.

Traumatic hip dislocation is by far less common in children than in adults. It occurs 4 times more frequently in boys than in girls. The force of the trauma leading to hip dislocation can be surprisingly small. Incomplete reduction is mainly caused by soft-tissue interposition or fragments of cartilage from the acetabulum. In such cases an X-ray examination will reveal a lateral protrusion of the femoral head. CT scans and MRI investigation play an important role in further diagnostics of the patient. The paper presents the case of a 5 year old boy with traumatic hip dislocation complicated by soft-tissue interposition. After an unsuccessful attempt of closed reduction, the hip was reduced surgically. The interposing element was removed--part of the cartilagenous insertion (size: 3 x 3 mm) of the femoral head ligament. During a follow-up examination 10 months post-op no signs of necrosis nor loss of ROM were noted.

[Functional assessment after operative treatment of femoral shaft fracture]. / Ocena wyniku czynnosciowego po operacyjnym leczeniu zlaman trzonu kosci udowej.

The paper presents results of treatment in 135 patients (aged 16-77 years) with fracture of the femoral shaft treated with one of the four techniques: open intramedullary Küntcher nailing, Zespol fixation, AO plating and closed locked and unlocked intramedullary nailing. The assessment has been based on authors' own 4-grade, 35-points scale involving 7 parameters. Closed intramedullary nailing proved to the most efficient. No reoperation in this group occurred. The percentage of excellent and good results was the highest--96.4% and such was the score--32.6 points. Open methods (Küntcher nailing, Zespol fixation, AO plating) rendered 88.2%, 31.7 points and 59% excellent and good results, 26.2 points in group without complication and reoperated one respectively.

[Dual energy X-ray absorptiometry in Ilizarov lower extremity lengthening: preliminary study]. / Metodyka badania densytometrycznego w wydluzeniach konczyn dolnych sposobem Ilizarowa--doniesienie wstepne.

Ilizarov method for lower extremity lengthening has been employed in 107 patients. Some 25% of numerous complications are bony union disturbances. Dual energy X-ray absorptiometry (DEXA) for assessment of new bone formation was introduced to reduce these problems. Detailed densitometry methodology developed on the ground of 93 measurements in 11 patients is presented. Pre-operative measurement was followed by subsequent evaluations done every 3 weeks after the onset of distraction. DEXA was capable of showing the callus 3-4 weeks earlier than conventional radiography. DEXA allows for adjusting the pace of lengthening to the extent of new bone mineralization, evaluation of lengthening achieved, determining the timing for safe removal of the apparatus. The need for temporary rearranging of the apparatus and troublesome image analysis are among the drawbacks of the method.

[Early results of densitometry around the cementless stem of the Parhofer-Mönch hip endoprosthesis]. / Wczesne wyniki badania densytometrycznego tkanki kostnej wokól trzpieni endoprotez bezcementowych stawu biodrowego typu Parhofera-Möncha.

Fifty-three patients with unilateral hip arthritis (31 females, 22 males) aged from 29 to 66 years (mean 52.1 years) after total hip replacement with cementless Parhofer-Mönch endoprosthesis underwent densitometry. The content (BMC) and mineral density (BMD) of calcium within proximal end of the femur was evaluated at 8-12 days postoperatively and at 6, 12 and 18 months follow-up. Early results show various mineral changes in Gruen zones around the stem. The greatest BMC and BMD decrease was found at 6 months follow-up in zones 1 and 7 as well as 2 and 6. The BMC and BMD tendency to decrease gradually ceased and slightly positive values were found in zone 3, 4 and 5 at the final evaluation.

[Surgical treatment for Salter-Harris type II distal femoral epiphysis injury]. / Leczenie operacyjne urazowego uszkodzenia dalszej nasady kosci udowej typu II wg Saltera-Harrisa.

Results of surgical treatment for Salter-Harris type II distal femoral epiphysis injury in 4 boys aged 10-16 are presented. In 3 cases the epiphysis was fixed with two screws introduced above the growth plate. Kirschner wires inserted through epiphysis were used in one case. Healing occurred in all cases. Shortening of the femur due to the injury to the distal growth plate was observed in 2 patients. In these cases surgery was preceded by two attempts to reduce displacement conservatively. MRI and CT studies are useful in diagnostics for epiphyseal injuries and their consequences.

[Arthroscopic treatment for synovial chondromatosis of the shoulder--case report]. / Artroskopowe leczenie chrzestniakowatosci maziówkowej stawu ramiennego--opis przypadku.

A case of 15 years old schoolgirl with synovial chondromatosis of the right shoulder is presented. The diagnosis has been confirmed by MRI. At arthroscopy approximately 70 oval loose bodies 5-8 mm in size have been removed. Postoperatively, no complication occurred. The case presented demonstrates advantage of arthroscopic treatment of this rare condition.

Effect of modifying O2 diffusivity and delivery on glomerular and tubular function in hypoxic perfused kidney.

Is O2 diffusivity within renal capillaries rate limiting for O2 delivery to hypoxic renal tubules? Equations based on diffusion theory and developed here predict that soluble hemoglobin (Hb) increases O2 diffusivity by a factor of 1 + [442 Hb%/(P50 + PO2)], where P50 is the partial pressure of O2 at which the Hb is half saturated. To examine the effect of P50 and Hb concentrations on renal function, we perfused isolated rat kidneys with Hb-P35 (P50 = 35 mmHg) and Hb-P11 (P50 = 11 mmHg). Venous PO2 was lower with Hb-P11 (10 +/- 1 vs 16 +/- 1 mmHg with arterial PO2 = 35 mmHg and 28 +/- 2 vs. 40 +/- 2 mmHg with arterial PO2 = 140 mmHg; P < 0.001). Perfusate P50 did not influence vascular resistance, glomerular filtration rate, O2 consumption, Na reabsorption, protein excretion, or free water clearance. Percent glucose and phosphate excretion were lower with Hb-P11 than with Hb-P35 (P < 0.001). Urine glucose was 0.17 mmol/l with Hb-P11 and 0.77 mmol/l with Hb-P35 (P < 0.001). Hb-P35 (2%) doubled O2 delivery and lowered glucose and phosphate excretion to the level obtained with 1% Hb-P11. Thus Hb-P11 delivered O2 twice as effectively as Hb-P35 to high-affinity sodium glucose and phosphate cotransporters in the late proximal tubule (S3 segment). Hb-P11 may also have shunted O2 from the outer cortex to the outer medulla and facilitated O2 diffusion where PO2 was low. We conclude that diffusivity is a limiting factor in delivery of O2 to hypoxic tubules.

[Pathomechanics of spinal and rib cage deformity in idiopathic scoliosis]. / Patomechanika deformacji kregoslupa i klatki piersiowej w skoliozie idiopatycznej.

Idiopathic scoliosis is a triplanar deformity associated with a rib hump. The quantitative assessment of the principal elements of spinal and rib cage deformity based on the chosen parameters measured on a-p radiographs and CT scans was done in a group of 89 children with idiopathic scoliosis. The average Cobb angle was 63 degrees. In regression and correlation analysis the statistically significant correlation among spinal lateral curve, axial rotation and kyphosis/lordosis index was found. Significant correlation between the elements of spinal deformity and the size of the rib hump were also found. The rib cage may play an important role in the pathogenesis of idiopathic scoliosis.

[Growth disturbances after A-O cancellous screw head-neck transfixation for slipped femoral epiphysis]. / Zaburzenia wzrostowe po zespoleniu szyjkowo-glowowym sruba gabczasta AO w mlodzienczym zluszczeniu glowy kosci udowej.

The impact of head-neck A-O cancellous screw transfixation on subcapital growth plate in 20 children operated for slipped capital femoral epiphysis is presented. It was found, that early fusion of the growth plate may be attributed to the compression by A-O screw used for transfixation (p-0.0001). Resulting shortening of the femoral neck and relative overgrowth of the great trochanter did not influence the final outcome of treatment.

[Surgical treatment for femoral shaft fracture in children and adolescents with multiple trauma]. / Leczenie operacyjne zlaman trzonu kosci udowej u dzieci i mlodziezy z mnogimi obrazeniami ciala.

Results of surgical treatment for 13 femoral shaft fractures in 12 children and adolescents with multitrauma have been presented. In 12 cases plate has been used, in one case Kuntcher nail was employed. Age of the patient at the trauma was 3 years 4 months on an average. There was no infection in postoperative period. The fracture healed after 8 weeks on an average. Anatomical reduction has been achieved in all cases. Some physical activity limitation (not related to the treatment) has been found in two patients. Surgical treatment for femoral shaft fracture in children and adolescents with multitrauma rendered good results.

[Value of intraoperative diagnostic radiography in diagnosis of femoral head nail penetration]. / Wartosc sródoperacyjnej diagnostyki radiologicznej w rozpoznawaniu "przegwozdziowania" glowy kosci udowej.

Most of the complications of surgical treatment for slipped capital femoral epiphysis result from unrecognized joint penetration. Standard radiographic projections are unable to locate implants precisely since the tridimensional joint is viewed in one plane at a time. The use of a single screw placed in the center of the femoral head prevents unrecognized joint penetration.

[Fixation of neck-head with a single cannulated screw for slipped capital femoral epiphysis--preliminary report]. / Zespolenie szyjkowo-glowowe jedna kaniulowana sruba gabczasta w przewleklym mlodzienczym zluszczeniu glowy kosci udowej--doniesienie wstepne.

Results of surgical treatment in 7 patients with slipped capital femoral epiphysis have been presented. Slip angle ranged from 12(to 42(. Closed, in situ neck-head fixation with a single cannulated screw was performed. The screw was introduced percutaneously, through the anterior surface of the femoral neck into the center of the head and perpendicularly to its base. The method employed rendered very good results. No head or neck perforation occurred. No progression of the slip was observed. Soft tissue trauma was only minimal; mobilization was commenced the first postoperative day.

Pancreatic tumors in children.

Pancreatic tumors rarely present in childhood. Diagnostic difficulty and inappropriate treatment may occur due to the variable clinical appearance of the illness. A 26-year audit (1968-1994) at this institution showed five patients ranging in age from 5 to 14 years who were operated upon for pancreatic tumors, four of which were malignant. In two cases primary resection of the tumor was possible and in the remaining three, after establishing the histopathologic diagnosis, chemo- and radiotherapy were used. Three of the five children are still alive; the mean follow-up was 9 years.

[Measurement of lower extremity length using computed tomography]. / Pomiar dlugosci konczyn dolnych przy uzyciu tomografu komputerowego.

A new method for lower extremities length measurement in patients destined for surgical legalization is presented. It is based on a scan in investigational CT. Reference points are marked and the distance between them is calculated. The record is inclusive of synthetic, diminutive anterior-posterior image of the extremity along with the measurement. Since September 1990 to December 1993, 34 patient underwent this procedure. The advantage is sensitivity better than 1 mm, flexibility in choosing reference points, good reproducibility and little exposure to the radiation. The result is more precise and trustworthy then obtained with other radiological or clinical methods.

[Comparison of three different methods of axial rotation assessment in idiopathic scoliosis]. / Porównanie trzech róznych metod oceny kata rotacji osiowej w idiopatycznych bocznych skrzywieniach kregoslupa.

In a group of 20 children with idiopathic scoliosis the degree of axial rotation was measured with the use of radiography (Drerup's method), ultrasonography and computer tomography. The measurements obtained by Drerup's radiographic method and by ultrasonography were compared with the results of the CT measurements, the latter being considered as the most precise. According to the statistical analysis of the results the spinal axial rotation measurements according to the Drerup's radiographic method appeared to be more precise than the ultrasonographic method. An equation was presented permitting to calculate the tomographic rotation angle RAsag on the basis of the results of the Drerup's radiographic measurement.