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PubMed2006

Permanent renal parenchymal defects after febrile UTI are closely associated with vesicoureteric reflux.

The finding of scintigraphic renal defects in children with febrile urinary tract infection (UTI) even in the absence of vesicoureteric reflux (VUR) has led to the conclusion that VUR is a weak predictor of renal defects in these patients. We used isotopic cystography (IC) for diagnosis of VUR in children with febrile UTI. Dimercaptosuccinic acid renal scintigraphy was performed 6 months after cure of the last UTI. Renal defects were defined by the finding of focal defects of radionuclide uptake and/or by a split renal function <43%. The study included 206 children with primary VUR and 77 without VUR. Among the subjects with and without VUR, respectively, renal defects were found in 40 and 6% (p=0.0001), focal uptake defects in 33 and 5% (p=0.0001) and split renal function <43% in 26 and 5% (p=0.0001). Permanent renal defects in children with febrile UTI are closely associated with VUR. The possibility that a child will have permanent renal defects can reasonably be ruled out on the basis of the absence of VUR by IC.

Female↗
PubMed2005

Long-term consequences of first vaginal delivery-induced anal sphincter defect.

PURPOSE: This study was designed to investigate the long-term consequences of anal sphincter defects detected after a first vaginal delivery. METHODS: A cohort of 197 primiparous females was evaluated for anal continence and anal sphincter defects in 1997. In June 2003 (6 years later), a postal questionnaire was sent to 74 females of this cohort, and answers from 54 (73 percent) were analyzed. RESULTS: In 1997, a transanal ultrasound found 66 anal sphincter defects (33.5 percent). Twenty-one females (10.6 percent) had persistent signs of anal incontinence 12 weeks after the index delivery. There was a significant correlation between the presence of anal sphincter defect and anal incontinence. Six years later, 11 of 54 females reported signs of anal incontinence: 50 percent of females with anal sphincter defect and only 8.1 percent of females without (P = 0.002). Large defects were more frequently associated with anal incontinence. Anal incontinence after the index vaginal delivery also was significantly associated with anal incontinence six years later. Multivariate analysis showed anal sphincter defect to be the only variable predictive of anal incontinence (odds ratio, 10.5; 95 percent confidence interval, 2.1-52.4). CONCLUSIONS: Anal sphincter defects detected after the first vaginal delivery appear as the main risk factor for anal incontinence six years later.

Adult↗
PubMed2006

Atrophy and defects detection of the external anal sphincter: comparison between three-dimensional anal endosonography and endoanal magnetic resonance imaging.

PURPOSE: Using endoanal magnetic resonance imaging, atrophy of the external anal sphincter can be established. This aspect has not been thoroughly investigated using three-dimensional anal endosonography. The purpose of this study was to compare prospectively three-dimensional anal endosonography to magnetic resonance imaging in the detection of atrophy and defects of the external anal sphincter in patients with fecal incontinence. In addition, we compared both techniques for anal sphincter thickness and length measurements. MATERIALS AND METHODS: Patients with fecal incontinence underwent three-dimensional anal endosonography and magnetic resonance imaging. Images of both endoluminal techniques were evaluated for atrophy and defects of the external anal sphincter. External anal sphincter atrophy scoring with three-dimensional anal endosonography depended on the distinction of the external anal sphincter and its reflectivity. External anal sphincter atrophy scoring with magnetic resonance imaging depended on the amount of muscle and the presence of fat replacement. Atrophy score was defined as none, moderate, and severe. A defect was defined at anal endosonography by a hypoechogenic zone and at magnetic resonance imaging as a discontinuity of the sphincteric ring and/or scar tissue. Differences between three-dimensional anal endosonography and magnetic resonance imaging for the detection of external anal sphincter atrophy and defects were calculated. In addition, we compared external anal sphincter thickness and length measurements in three-dimensional anal endosonography and magnetic resonance imaging. RESULTS: Eighteen patients were included (median age, 58 years; range, 27-80; 15 women). Three-dimensional anal endosonography and magnetic resonance imaging did not significantly differ for the detection of external anal sphincter atrophy (P = 0.25) and defects (P = 0.38). Three-dimensional anal endosonography demonstrated atrophy in 16 patients, magnetic resonance imaging detected atrophy in 13 patients. Three-dimensional anal endosonography agreed with magnetic resonance imaging in 15 of 18 patients for the detection of external anal sphincter atrophy. Using the grading system, 8 of the 18 patients scored the same grade. Three-dimensional anal endosonography detected seven external anal sphincter defects and magnetic resonance imaging detected ten. Three-dimensional anal endosonography and magnetic resonance imaging agreed on the detection of external anal sphincter defects in 13 of 18 patients. Comparison between three-dimensional anal endosonography and magnetic resonance imaging for sphincter thickness and length measurements showed no statistically significant concordance and had no correlation with external anal sphincter atrophy. CONCLUSION: This is the first study that shows that three-dimensional anal endosonography can be used for detecting external anal sphincter atrophy. Both endoanal techniques are comparable in detecting atrophy and defects of the external anal sphincter, although there is a substantial difference in grading of external anal sphincter atrophy. Correlation between three-dimensional anal endosonography and magnetic resonance imaging for thickness and length measurements is poor. Inconsistency between the two methods needs to be evaluated further.

Adult↗
PubMed2002

White blood cell defects: molecular discoveries and clinical management.

In this review, we present the most recent discoveries at the molecular level in white blood cell defects, and explain how their identification helped us to understand the underlying pathophysiology and directed our approach in clinical management. These lately discovered genes, relevant to immune disorders of mononuclear phagocytes and neutrophils, include defects in the interferon gamma (IFNg)/interleukin 12 (IL-12) pathway, such as IFNg receptor (IFNgR) defects, IL-12 defect, IL-12 receptor (IL-12R) defect, and signal transducer and activator of transcription 1 (STAT-1) defect. We have also included NF-kappaB essential modifier (NEMO) defects, which lead to X-linked ectodermal dysplasia, with or without lymphedema and osteopetrosis, and a wide range of involvement of the immune system, which can mimic the hyper-IgM phenotype. Neutrophil-specific granule deficiency and neutrophil elastase deficiency are discussed, the latter being the molecular defect in both cyclic neutropenia and in some sporadic cases of severe congenital neutropenia.

Hematologic Diseases↗
PubMed1981

The inconsistent pattern of thallium defects: a clue to the false positive perfusion scintigram.

Exercise thallium myocardial scintigrams were analyzed in 76 consecutive patients with documented normal coronary arteries to identify the factors associated with abnormal or "false positive" studies. The thallium scintigrams had been judged normal in 60 patients (79 percent) and abnormal in 16 (21 percent). Analysis of the location of thallium defects in the 16 patients with abnormal scintigrams revealed a pattern that was consistent with coronary artery disease in 5, including 4 with an abnormal left ventricle, and a pattern that was inconsistent in the other 11. In 9 of these 11 patients the pattern of defects suggested soft tissue attenuation, by the diaphragm in 2 and breast or adipose tissue in 7, whereas in the other 2 patients isolated apical defects were seen. Among exercise myocardial scintigrams performed in 68 randomly selected patients with abnormal coronary arteries, 6 (9 percent) were reported to be normal. In four patients with abnormal scintigrams, the diagnosis of coronary artery disease was based on an inconsistent pattern. In three of these the pattern was related to isolated apical defects and in one it was related to apparent soft tissue attenuation. "Consistent" scintigraphic defects, seen frequently in patients with normal coronary arteries, in whom they are usually associated with an abnormal left ventricle. In patients with normal coronary arteries, "inconsistent" thallium defects are probably related to soft tissue attenuation or to normal apical thinning. Although defects caused by isolated apical abnormalities and soft tissue attenuation are also seen in patients with coronary diseases and add somewhat to scintigraphic sensitivity, they are a rare cause of diagnostic scintigraphic abnormalities in patients with coronary disease. The incidence of false positive thallium scintigrams could be reduced and overall accuracy improved by careful attention to the pattern of thallium defects.

Adult↗
PubMed1988

Relation of left ventricular perfusion and wall motion with metabolic activity in persistent defects on thallium-201 tomography in healed myocardial infarction.

Myocardial viability in persistent thallium (TI)-201 defect is a controversial subject. To assess metabolic activity in segments with persistent defect, stress TI-201 tomography and positron emission tomography using nitrogen-13 ammonia and fluorine-18 2-fluoro-deoxyglucose (FDG) were performed in 28 patients with healed myocardial infarction. The segments with TI-201 perfusion defect in electrocardiogram-determined infarcted areas were selected for assessment. Stress perfusion defect was detected in 61 segments by TI-201 tomography. Twenty-two patients (36%) showed transient defects with redistribution (group 1) and 39 showed persistent defects (group 2). Increase in FDG uptake was observed in 95% in group 1. Among group 2 patients, 15 segments (38%) showed an increase in FDG uptake (group 2A) while the remaining 24 (62%) did not have an increased uptake (group 2B). The decrease in nitrogen-13 ammonia perfusion was more severe in group 2B (-23 +/- 7%) than in group 2A (-13 +/- 9%) (p less than 0.005) and group 1 (-10 +/- 4%) (p less than 0.001). In addition, wall motion scores tended to be lower in group 2B (0.21 +/- 0.71), compared with group 2A (0.67 +/- 0.70) (p = 0.05) and group 1 (0.77 +/- 0.60) (p less than 0.01). These data indicate that metabolic viability was observed in approximately 40% of the segments with persistent TI-201 defect. Preservation of regional perfusion and wall motion in these areas was similar to that in areas with transient TI-201 defect.

Aged↗
PubMed1988

Developmental and protein modification defects caused by mutations in the Drosophila gene l(3)c21R.

A temperature-sensitive Drosophila mutation, l(3)c21RRW630 (abbreviated RW630), has been previously shown to have biochemical as well as developmental defects. To analyze further the relationship between the biochemical and developmental defects, recombinational mapping, deletion analysis, and complementation studies with other l(3)c21R alleles were performed. These experiments showed that the biochemical and developmental defects in RW630 can be attributed to a single mutation. Four non-temperature-sensitive l(3)c21R alleles were found to have biochemical defects similar to those seen in RW630 at restrictive temperature. In RW630 and in these four other l(3)c21R alleles, the severity of expression of the biochemical and the developmental defects was closely correlated. Temperature-shift studies of the expression of the RW630 maternal lethal effect on embryogenesis in females transheterozygous for RW630 and other l(3)c21R alleles yielded results which indicated that these defects must accumulate over a period of time before the maternal lethal effect can be detected. These data provide further support for the hypothesis that defects in protein modification produce developmental defects in l(3)c21R mutants.

Alleles↗
PubMed1993

Indentation assessment of biphasic mechanical property deficits in size-dependent osteochondral defect repair.

The apparent biphasic material properties of 10-month osteochondral defect repair tissue were determined for a series of full thickness defects of 1, 3, or 5 mm diameter, created in weight-bearing regions of 48 canine femoral condyles. Load cell recordings from indentation tests were compared with resultant contact forces computed using a corresponding linear biphasic finite element model. The spread of cartilage engagement by a spherical ended indentor was modeled by successively imposing an impenetrability kinematic boundary condition at cartilage surface nodes for which incipient indentor surface penetration was detected. For each indentation test, a least-squares-error curve fitting procedure was used to identify a set of biphasic coefficients (aggregate modulus, permeability, Poisson ratio) that closely modeled experimental behavior. In the near neighborhood of best-fit, the finite element solutions were found to be much more sensitive to aggregate modulus perturbations than to permeability permutations, suggesting that perceived permeability increase may be of lesser value as a discriminant of repair tissue inadequacy. Compared to surrounding cartilage, the repair tissue for all defect sizes had statistically significant decreases in aggregate modulus and in Poisson ratio (much more so for 3 and 5 mm defects than for 1 mm defects). The two larger defect diameters had significant increases in permeability, whereas the 1 mm defects did not. While the material property deficits were consistent, substantial and comparable to those in other recent animal models of osteochondral defect repair, the size-dependence per se of the observed constitutive differences was only modest.

Algorithms↗
PubMed1987

T-cell activation defect in common variable immunodeficiency: restoration by phorbol myristate acetate (PMA) or allogeneic macrophages.

Common variable immunodeficiency (CVI) represents a group of familial and sporadic diseases characterized by a range of B-cell, T-cell, and macrophage defects. A defect in T-cell activation, involving reduced proliferation and IL-2 production after stimulation with OKT3 antibody, has been described previously. In the present study we found that these defects could be corrected in vitro by adding phorbol myristate acetate (PMA) to OKT3-stimulated peripheral blood mononuclear cells (PBMC) of 14 patients with CVI. PBMC of 6 out of 7 patients with CVI studied also exhibited a profound defect in IL-2 receptor expression when incubated with OKT3 antibody. IL-2 receptor expression after stimulation with PMA alone was normal, indicating that the OKT3- but not the PMA-induced pathway of IL-2 receptor expression was defective. On the RNA level, the genes for IL-2 and IL-2 receptor were expressed after stimulation with OKT3 antibody. IL-2 and IL-2 receptor gene expression were normal, indicating a possible post-transcriptional defect. To investigate whether the defect in T-cell activation was at the macrophage or the T-cell level, we prepared adherent cells and monocyte-depleted T cells (E+) from 3 patients with CVI and from normal blood donors. Incubating CVI E+ cells with normal adherent cells resulted in normal proliferation and IL-2 production in the presence of OKT3, whereas incubation of normal E+ cells with adherent cells from patients with CVI under the same conditions showed reduced IL-2 production and proliferation, suggesting the macrophage as the origin of the failure in T-cell activation in the patients with CVI studied. Inhibition by macrophage-secreted prostaglandins was excluded by failure to correct the IL-2 production and proliferation defects in the presence of indomethacin.

Adult↗
PubMed1980

Profile of multiple lymphocyte functional defects in acquired hypogrammaglobulinemia, derived from in vitro cell recombination analysis.

Immunoregulatory defects in patients can be assigned to B cells, T helper cells, or T suppressor cells by means of a modification of the in vitro PWM-stimulated Ig biosynthesis assay. When lymphocyte subpopulations from patient and normal are recombined, multiple internal comparisons within a single experiment reveal the functional activity of each subpopulation. By this technique we studied nine adult patients with acquired panhypogammaglobulinemia and one with isolated IgG deficiency. Low total Ig production by the B cell fraction was demonstrated in seven of the nine panhypogammaglobulinemic patients. In four of these seven, IgG and IgA secretion was markedly reduced compared with IgM. In the two patients with normal total Ig production, elevated IgM compensated for lower IgA and IgG. The one patient with no surface Ig+ cells had a B cell defect, but no T cell defect. Reduced T help and excessive T suppression characterized two of the four patients with the most severe B cell defects. Three patients were anergic by delayed hypersensitivity skin testing and failed to sensitize to DNCB, but the patient with the most severe T cell defects in vitro was not among them. One of these three patients showed a mild T cell help defect and suppressor excess and the other two had pure B cell defects. Thus, anergy and T regulator function were not correlated. In three instances where hypersuppression was more evident by adding patient unfractionated cells than by adding patient T cells, suppression by the T depleted fraction could be demonstrated. No cases of radiation-resistant T suppression were revealed among the seven patients tested. Subnormal total protein synthesis, noted in six of seven patients with low Ig production, was invariably less marked than the Ig defect and often affected both T and B cells. One additional patient with pure IgG deficiency of 2 yr duration was essentially normal in her in vitro lymphocyte function. The general applicability of this experimental design for analysis of positive or negative immunoregulatory abnormalities is emphasized.

Adult↗
PubMed1996

Healing of chondral and osteochondral defects in a canine model: the role of cultured chondrocytes in regeneration of articular cartilage.

In this study a canine model was developed to investigate the nature of early healing responses to both chondral and osteochondral defects and to evaluate the tissue regenerative capacity of cultured autologous chondrocytes in chondral defects. The healing response to surgically created chondral defects was minor, with little cellular infiltration. In contrast, osteochondral defects exhibited a rapid cellular response, resulting ultimately in the formation of fibrous tissue. The lack of significant cellular activity in chondral defects suggests that an evaluation of the capacity of cultured autologous chondrocytes to regenerate articular cartilage is best studied in chondral defects using the canine model. When dedifferentiated cultured articular chondrocytes were implanted into chondral defects, islands of type II collagen staining were demonstrated in the regenerative tissue within 6 weeks. The relatively early expression of cartilage specific markers by the implanted chondrocytes, coupled with the inability of untreated chondral defects to repair or regenerate, demonstrates the utility of the canine model in evaluating novel materials for cartilage repair and regeneration.

Animals↗
PubMed1995

Temporal dynamics of healing in rabbit cranial defects using guided bone regeneration.

PURPOSE: The objective of this study was to histologically evaluate the early stages of bone regeneration using rabbit calvaria defects in conjunction with guided tissue regeneration. MATERIALS: A semilunar cutaneous-periosteal flap was raised on the forehead of four rabbits exposing the top of the skull. A standardized transosseous skull defect (> or = 15 mm in diameter) was made in the area of the right parietal bone with a rotating round bur. Care was taken not to damage the underlying dura. A flat expanded polytetrafluoroethylene (ePTFE) membrane was placed to cover the defect. The membrane was tightly adapted, extending at least 4 mm onto intact bone, and the flap was sutured. One, 2, 3, and 5 weeks later, the specimens were removed and processed using standard, undecalcified, hard-tissue histologic techniques. Contact radiographs were also taken. RESULTS: Bone growth increased with time, starting at the borders of the defect. At 1 week, trabeculae of woven bone grew into the highly vascularized loose connective tissue occupying the defect. Two weeks postsurgery, isolated islands of new bone were detected in this connective tissue. Subsequently, neighboring small islands merged to form large islands. In later stages, the primary trabeculae of woven bone were reinforced by layers of regularly deposited lamellar bone. CONCLUSION: Rabbit calvaria defects treated by guided tissue regeneration heal by ingrowth of woven bone from the defect margins and by formation of bony islands within the defect area. Bone healing showed the histophysiological characteristics of intramembranous bone.

Animals↗
PubMed1992

Relation of perfusion defects observed with myocardial contrast echocardiography to the severity of coronary stenosis: correlation with thallium-201 single-photon emission tomography.

It has been previously shown that myocardial contrast echocardiography is a valuable technique for delineating regions of myocardial underperfusion secondary to coronary occlusion and to critical coronary stenoses in the presence of hyperemic stimulation. The aim of this study was to determine whether myocardial contrast echocardiography performed with a stable solution of sonicated albumin could detect regions of myocardial underperfusion resulting from various degrees of coronary stenosis. The perfusion defect produced in 16 open chest dogs was compared with the anatomic area at risk measured by the postmortem dual-perfusion technique and with thallium-201 single-photon emission tomography (SPECT). During a transient (20-s) coronary occlusion, a perfusion defect was observed with contrast echocardiography in 14 of the 15 dogs in which the occlusion was produced. The perfusion defect correlated significantly with the anatomic area at risk (r = 0.74; p less than 0.002). During dipyridamole-induced hyperemia, 12 of the 16 dogs with a partial coronary stenosis had a visible area of hypoperfusion by contrast echocardiography. The four dogs without a perfusion defect had a stenosis that resulted in a mild (0% to 50%) reduction in dipyridamole-induced hyperemia. The size of the perfusion defect during stenosis correlated significantly with the anatomic area at risk (r = 0.61; p = 0.02). Thallium-201 SPECT demonstrated a perfusion defect in all 14 dogs analyzed during dipyridamole-induced hyperemia; the size of the perfusion defect correlated with the anatomic area at risk (r = 0.58; p less than 0.03) and with the perfusion defect by contrast echocardiography (r = 0.58; p less than 0.03). Thus, myocardial contrast echocardiography can be used to visualize and quantitate the amount of jeopardized myocardium during moderate to severe degrees of coronary stenosis. The results obtained show a correlation with the anatomic area at risk similar to that obtained with thallium-201 SPECT.

Albumins↗
PubMed1990

Defects in the prostaglandin-system--heredity, prevalence and vascular risk analysis.

2180 healthy adults, 620 patients (90% with cardiovascular disease, 10% others), 143 newborns and 351 relatives of persons in whom any abnormality of the prostaglandin (PG)-system had been discovered were involved in the Viennese Initiative for Prostaglandin (VIP)-Screening from 1984 through May 1989. The defects discovered were either inborn or acquired ones and were either familial or non-familial. The highest number of defects (54.8% of the total) identified were associated with PGI2. They indicated a lack of the PGI2-synthesis stimulating plasma factor (PF)-activity (n = 17) and PGI2-stabilizing capacity in plasma (defect 'Vienna-Döbling', n = 4, 12.9% of total), absence of high-affinity PGI2-binding sites on platelet membranes and lack of response of platelets to PGI2 (defect 'Vienna-Hietzing', n = 2, 6.5% of total). Furthermore, a lack of cyclooxygenase (n = 2, 6.5% of total), 12-lipoxygenase (defect 'Vienna-Penzing', n = 3, 9.7% of total) and thromboxane synthetase (n = 3, 9.7% of total) activities were diagnosed. In newborn screening, the PF-absence amounted to 2.8% (4/143), the lack of PGI2-stabilizing capacity to 0.7% (1/143). In adults, the prevalence is difficult to assess. Nevertheless, our findings indicate a frequency of 0.93% (26/2800) of defects in the PG-system among the adult Viennese population. The lack of PF-activity seems to be by far the most frequent one (0.46%, 13/2800). Other defects are much less common. It is not clear whether the incidence in healthy subjects or in patients with cardiovascular disease is different from each other. Further, it remains to be assessed whether there is a causative relation to vascular events or just an association. More intensive screening activities should validate the diagnostic, pathogenetic and therapeutic impact of the various defects in the PG-system.

Adult↗
PubMed2004

Paternal age and the risk of birth defects in Norway.

PURPOSE: We studied 1,869,388 births from The Medical Birth Registry of Norway to assess the effect of father's age on risks of birth defects in offspring. METHOD: Thirteen separate categories were studied including pooled categories of neural tube defects and any type of defect. We used logistic regression models to adjust for maternal age, year of birth, maternity institution, parity, and correlation between siblings. RESULTS: There was little evidence of increased risk by high paternal age for any category of defects, except for a category of "other central nervous system" where risk estimates were 2.5-fold (95% CI: 1.2-5.5) for fathers aged between 45 and 49 years compared with the reference age group (25-29 years). The risk for neural tube defects was 1.3-fold (95% CI: 1.1-1.5) when the father was aged between 20 and 24 years relative to the reference. A pattern of moderately higher risks for younger fathers was consistent for anencephaly and spina bifida. Increased risk of heart defects was also estimated among children of young fathers. CONCLUSIONS: This study does not show consistent evidence that paternal ageing is a risk for birth defects among offspring. Low paternal age, or factors associated with younger parents, may however be associated with increased risk of neural tube defects in their offspring.

Adult↗
PubMed2005

Repair of osteochondral defect with tissue-engineered chondral plug in a rabbit model.

PURPOSE: The purpose of this study was to evaluate the macroscopic and histologic results of transplanting a tissue-engineered chondral plug made of atelocollagen sponge and PLLA mesh to treat osteochondral defects. TYPE OF STUDY: Controlled experimental study. METHODS: Twelve-week-old male Japanese white rabbits were used. Fresh articular cartilage slices were taken from the humeral head, and isolated chondrocytes were embedded in atelocollagen gel which does not have antigenic portions of collagen (2.0 x 10(6) cells/mL). They were seeded on the top of the atelocollagen sponge/PLLA mesh composite and cultured for 2 weeks. The culture medium was changed every 3 days and L-ascorbic acid (50 microg/mL) was added every 2 days. Culturing the composites for 2 weeks produced tissue-engineered chondral plugs. These tissue-engineered chondral plugs (4-mm diameter, 4-mm thick) were transplanted into the osteochondral defects (4 mm diameter, 4 mm deep) in the patellar grooves of the same rabbits from which the chondrocytes had been harvested (the experimental group). In the control group, the defects were treated with the plugs without chondrocytes. The rabbits were killed 4 and 12 weeks after transplantation. The repaired tissues were evaluated macroscopically and histologically, and analyzed immunohistochemically for expression of type II collagen. RESULTS: Four weeks after transplantation in the experimental group, the defects were partially repaired with cartilage-like tissue with good subchondral bone formation. Twelve weeks after transplantation, the defects were repaired with hyaline cartilage-like tissue densely stained by Safranin O. Well-organized subchondral bone formation was also observed. In the control group, the defects were covered with only soft fibrous tissue at 4 and 12 weeks macroscopically. Immunohistochemically, type II collagen was detected in about 90% of the repaired area. Histologic scores in the experimental group were significantly higher than those in the control group at both 4 and 12 weeks after transplantation. CONCLUSIONS: This study shows that the defects treated with tissue engineered chondral plug developed type II collagen in about 90% of the repaired area. CLINICAL RELEVANCE: The transplantation of a tissue-engineered chondral plug will be one option for treating osteochondral defects. The next step in testing our hypothesis is to evaluate the repaired tissue biomechanically and biochemically over a longer period of time.

Animals↗
PubMed2005

The healing of confined critical size cancellous defects in the presence of silk fibroin hydrogel.

In vitro and in vivo behaviour of an injectable silk fibroin (SF) hydrogel was studied through osteoblast cultures and after implantation in critical-size defects of rabbit distal femurs. A commercial synthetic poly(D,L lactide-glycolide) copolymer was used as control material. In vitro biocompatibility was evaluated by measuring LDH release, cell proliferation (WST1), differentiation (ALP, OC), and synthetic activity (collagen I, TGF ss1, IL-6). Bone defect healing rate and quality of the newly formed bone inside the defects were determined in vivo by measuring trabecular bone volume (BV/TV), trabecular thickness (Tb.Th), trabecular number (Tb.N), trabecular separation (Tb.Sp), mineral apposition rate (MAR) and bone formation rate (BFR/B.Pm). In vitro tests indicated that both materials significantly increased cell proliferation in comparison with the negative control. A significant increase in the TGF-beta1 level was found for SF hydrogel in comparison with the control material and negative control. Both materials promoted bone healing when used to fill critical size defects in rabbit femurs. The new-formed bone of the SF hydrogel treated defects showed significantly higher BV/TV, Tb.Th, MAR and BFR/B.Pm and lower Tb.Sp values in comparison with the control gel. At 12 weeks the re-grown bone of the SF hydrogel-treated defects appeared more similar to normal bone than that of the control synthetic polymeric material-treated defects, except for the Tb.N value that differed significantly from that of normal bone (p<0.05). MAR and BFR/B.Pm presented significantly (p<0.05) higher values for SF hydrogel-treated defects in comparison with controls treated with a synthetic polymeric material, confirming that SF hydrogel accelerated remodelling processes.

Animals↗
PubMed2005

Laboratory diagnosis of defects of creatine biosynthesis and transport.

In recent years, three inherited defects in the biosynthesis and transport of creatine have been described. The biosynthetic defects include deficiencies of L-arginine:glycine amidinotransferase and guanidinoacetate methyltransferase. The third defect is a functional defect in the creatine transporter (SLC6A8). Clinical symptoms of the three defects vary in severity, are aspecific and include mental retardation with severe speech delay, autistiform behaviour, and epilepsy. Some patients with GAMT deficiency exhibit a more complex clinical phenotype with extrapyramidal movement disorder. All three defects can be diagnosed by in vivo proton magnetic resonance spectroscopy of the brain, which shows a severe reduction or absence of creatine. Laboratory investigations for the diagnosis start with the analysis of guanidinoacetate, creatine and creatinine in body fluids (plasma and urine). Based on these findings, enzyme assays for AGAT or GAMT, or a creatine uptake assay for the transporter defect can be performed. DNA mutation analysis of the genes involved can prove the defects at the molecular level. To diagnose female patients with SLC6A8 deficiency, mutation analysis may be the only choice.

Biological Transport↗