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PubMed2000

Haemostatic screening and identification of zebrafish mutants with coagulation pathway defects: an approach to identifying novel haemostatic genes in man.

Zebrafish were used as a model to study haemostasis, a vertebrate function of paramount importance. A limitation of the zebrafish model is the difficulty in assaying small amounts of blood to detect coagulation mutants. We report the use of a rapid total coagulation activity (TCA) assay to screen for coagulation defects in individual adult zebrafish. We screened the TCA in 1000 gynogenetic half-tetrad diploids derived from 86 clutches. Each clutch was from a single F1 female offspring of males mutagenized with ethylnitrosourea (ENU). We found 30-50% defective zebrafish among six clutches, consistent with a heritable defect. The assay developed here provided a rapid screen to detect overall coagulation defects. However, because of the limited amounts of plasma, we could not detect defects in specific pathways. Therefore, a novel, ultra-sensitive kinetic method was developed to identify specific pathway defects. To test whether the kinetic assay could be used as a screening tool, 1500 Florida wild-type zebrafish pairs were analysed for naturally occurring coagulation defects. We detected 30 fish with extrinsic pathway defects, but with intact common and intrinsic pathways. We conclude that it is now possible to identify specific coagulation pathway defects in zebrafish.

Actins↗
PubMed2000

Ascertainment of birth defects: the effect on completeness of adding a new source of data.

BACKGROUND: The Western Australian (WA) Birth Defects Registry aims for complete ascertainment of birth defects in WA, but the proportions of birth defects in rural areas and in Aboriginal children are lower than in metropolitan and non-Aboriginal children. The effect on ascertainment of adding data from the Rural Paediatric Service (RPS) was investigated. METHOD: A file of all cases of birth defects for children born 1980-1997 and recorded on the RPS database was linked to the Registry. RESULTS: The addition of this new data source had little effect on the overall prevalence of birth defects (an increase from 5.38 to 5.41%). There was a slightly greater effect on the prevalence of birth defects in rural residents (4.67%-4.76%) and Aboriginal children (4.55-4.78%), although the prevalence for each of these groups is still less than for metropolitan residents and non-Aboriginal infants, respectively. All major categories of birth defects were represented in the new cases and, in general, their addition made little difference to the prevalence of each category. The exception was fetal alcohol syndrome, which increased from 0.13 per 1000 to 0.18 per 1000 once the 21 new cases from the RPS were added. CONCLUSION: Complete ascertainment of birth defects is important in developing and evaluating preventive programs, and in investigating clusters of birth defects.

Congenital Abnormalities↗
PubMed2001

Serial evaluation of perfusion defects in patients with a first acute myocardial infarction referred for primary PTCA using intravenous myocardial contrast echocardiography.

AIMS: To investigate whether myocardial contrast echocardiography using Sonazoid could be used for the serial evaluation of the presence and extent of myocardial perfusion defects in patients with a first acute myocardial infarction treated with primary PTCA, and specifically, (1) to evaluate safety and efficacy of myocardial contrast echocardiography to detect TIMI flow grade 0--2, (2) to evaluate the success of reperfusion and (3) to predict left ventricular recovery after 4 weeks follow-up. METHODS AND RESULTS: Fifty-nine patients underwent serial myocardial contrast echocardiography, immediately before primary PTCA (MCE1), 1 h (MCE2) and 12--24 h after PTCA (MCE3). A perfusion defect was observed in 21 of 24 patients (88%) with anterior acute myocardial infarction. All but one had TIMI flow grade 0--2 prior to PTCA. Nine of 31 patients (29%) with inferior acute myocardial infarction showed a perfusion defect and all had TIMI flow grade 0-2 prior to PTCA. Restoration of TIMI flow grade 3 was achieved in 73% of the patients by primary PTCA. A reduction in size of the initial perfusion defect of at least one segment (16 segment model) or no defect vs persistent defect in patients with anterior acute myocardial infarction was associated with improved global left ventricular function at 4 weeks; mean global wall motion score index 1.29+/-0.21 vs 1.66+/-0.31 (P=0.009). Multiple regression analysis in patients with an anterior acute myocardial infarction revealed that the extent of the perfusion defect at MCE3 was a significant (P=0.0005) independent predictor for left ventricular recovery at 4 weeks follow-up. The only other independent predictor was TIMI flow grade 3 post PTCA (P=0.007). CONCLUSION: Intravenous myocardial contrast echocardiography immediately prior to primary PTCA seems safe and is capable of detecting the presence of a perfusion defect and its subsequent dynamic changes, particularly in patients with a first anterior acute myocardial infarction. A significant reduction in size of the initial perfusion defect using serial myocardial contrast echocardiography predicts functional recovery after 4 weeks and these findings underscore the potential diagnostic value of intravenous myocardial contrast echocardiography.

Aged↗
PubMed2001

[Defect coverage of the hand and forearm with a free scapula-parascapula flap].

BACKGROUND: Complex defects of the forearm and hand are associated with the loss of important structures. Single-stage reconstruction of these defects requires composite tissue transplantations. The subscapular region offers various components for the coverage of complex defects. The scapular and the parascapular flaps can be used each as cutaneous, fasciocutaneous and osteocutaneous or as a combined flap as well. The purpose of this study was to present our experience with the combined scapular-parascapular free flap for defect coverage of the forearm and hand in 13 patients. PATIENTS AND METHOD: Evaluation of 12 patients who underwent coverage of forearm and hand defects with the combined scapular-parascapular free flap during a five-year period. Other treatment options are discussed. RESULTS: Average age of the patients was 39 years, there were ten male and two female patients. Average follow-up was 20 months. Eleven patients suffered from massive trauma, one patient from severe infection of the forearm and hand. The defect size varied from 12 x 8 cm to 45 x 20 cm. In nine cases, a cutaneous and/or fasciocutaneous scapular-parascapular flap was used, two patients underwent defect coverage with an osteocutaneous scapular-parascapular flap, and in one patient, a "four-flap-mega-flap" was transplanted. One flap developed a partial necrosis. Eight patients developed a good or very good functional outcome with their hand and forearm, two patients have a moderate degree of disability. Two patients can use their hand as a supporting hand. CONCLUSION: This study demonstrates that the combined scapular-parascapular free flap is a reliable treatment choice for early coverage of defects of the forearm and hand. The advantages are the long, large and consistent vascular pedicle, the possibility of combination with other flaps and "custom-tailoring", including whatever component is necessary to close the particular defect.

Adult↗
PubMed2001

[Autologous serum for otherwise therapy resistant corneal epithelial defects - Prospective report on the first 70 eyes].

PURPOSE: The purpose of this prospective clinical pilot study was to evaluate the efficiency, practicability and safety of topical autologous serum for therapy resistant corneal epithelial defects. METHODS: Between November 1999 and June 2001 autologous serum therapy was applied in 70 eyes of 67 consecutive patients (age 18 to 92 [average 59 +/- 18] years) with corneal epithelial defects refractory to standard clinical treatment at the Department of Ophthalmology University Erlangen-Nürnberg. We evaluated localization, size of the defect, time until epithelial wound closure and the incidence of recurrences in relation to the clinical diagnosis. The blood was obtained by venipuncture, centrifuged and the non-diluted serum was filled in sterile bottles, kept in the + 4 (o)C refrigerator and hourly applied during daytime. Simultaneous systemic and topical medication depended on the underlying disease. RESULTS: In 45 eyes corneal epithelial defects appeared after penetrating keratoplasty but in 25 eyes corneal epithelial defects were not related to a corneal transplant. The epithelial defect had a medium length of 4.2 +/- 2.4 mm and a width of 3.0 +/- 1.8 mm. Previously, the patients had been treated with maximal topical therapy (including hyaluronic acid) for 13 +/- 11 days. Treatment with autologous serum lasted from 4 to 45 (mean 16 +/- 11) days. A complete corneal re-epithelialization was achieved in 57 of 70 eyes (81 %) after 3 to 45 (mean 15 +/- 12) days. Forty-eight of these 57 eyes (84 %) had no recurrence during a follow-up of 12 +/- 4 months. In 9 eyes (16 %) a recurrent epithelial defect occurred one or two months after initial closure. These eyes were treated successfully with a second autologous serum therapy (6 x), amniotic membrane transplantation (2 x) or repeat keratoplasty (1 x). Thirteen eyes (19 %) without primary success of autologous serum applied for 11 to 50 days were finally treated successfully with amniotic membrane transplantation (10 x) or repeat keratoplasty (3 x). CONCLUSION: In persistent corneal epithelium defects, autologous serum therapy can be considered as an effective and practicable therapy without adverse reactions. Especially in eyes after complicated penetrating keratoplasty the prognosis may be improved and more invasive treatment modalities such as botulinum toxin injection, amniotic membrane transplantation or (repeat) penetrating keratoplasty may be avoided. Definitive determinants for the success of this novel therapy have not been identified, yet. However, eyes with accompanying deep stromal defects do not seem to be good candidates.

Adolescent↗
PubMed2002

[Bone defects in revision total knee arthroplasty: classification and management].

The goal of bone reconstruction in revision total knee arthroplasty is to provide a stable support for the implant and to re-establish the correct joint line. Therefore, a useful, therapy-based classification of the defects is necessary. According to Stockley et al. (1992), the defects are classified into contained and uncontained defects. Uncontained defects can be reconstructed using structural allografts or metal wedges. In contained defects, cancellous allograft can be used. For aseptic loosening of total knee arthroplasty, the defect classification according to Engh and Parks (1994) can be helpful because of its recommendations for reconstruction. In case of the more common first or second graded defects, reconstruction is performed using modular revision components or allografts. For the rare third graded defects, bulk allografts or modular tumour endoprostheses are recommended. On the basis of more than 150 revision total knee arthroplasties performed in our hospital the classification of bone defects and their clinical consequences are presented in this review.

Arthroplasty, Replacement, Knee↗
PubMed2003

[Direct MR arthrography of the wrist- value in detecting complete and partial defects of intrinsic ligaments and the TFCC in comparison with arthroscopy].

PURPOSE: To assess the value of two-compartment magnetic resonance (MR) wrist arthrography in comparison with diagnostic arthroscopy for the evaluation of defects of the triangular fibrocartilage complex (TFCC) and intrinsic ligaments in patients with refractory wrist pain. The direct MR arthrographies were evaluated following arthroscopic classification with consideration of complete and partial defects. The distinction between these types of lesions has clinical implications for treatment procedures such as cast immobilization, arthroscopic debridement, surgical repair or partial intercarpal arthrodesis. MATERIALS AND METHODS: Seventy-five patients (25 female, 50 males, mean age 38.3 years) who suffered from refractory wrist pain without radiography evidence of carpal instability underwent two-compartment wrist MR arthrography. Under aseptic conditions a solution of gadopentate dimeglumine and iodinated contrast agent (concentration 2.5 mmol/l) was injected into the radiocarpal and midcarpal joints under fluoroscopy guidance. Using a scanner of 1.5 T field strength and a wrist-coil following sequences were acquired: coronary and sagittal T (1)-weighted spin-echo (SE) sequences (TR 500 ms, TE 25 ms, matrix 512 x 512.3 mm) and coronary fast low angle shot (FLASH) 3D sequences (TR 24 ms, TE 11 ms, matrix 256 x 256, 1.5 mm, flip angle 50 degrees). All patients underwent subsequent arthroscopy of the wrist. The direct MR arthrographies were evaluated retrospectively by two observers experienced in the diagnosis of wrist pathology. They were not aware of the clinicial, arthrographic and arthroscopic findings. Pathology of the scapholunate ligament was classified according to the guidelines of the German Society of Hand Surgery (DGH), lesions of the lunotriquetral ligament according to Hempfling and lesions of the TFCC according to Palmer. RESULTS: Twenty-five complete and 47 partial defects were detected arthroscopically (TFCC: 21/20, scapholunate ligament: 3/18, lunotriquetral ligament: 1/9). The TFCC showed a higher prevalence for degenerative lesions (11 type 2C-lesions and 20 type 2A/B lesions) than for traumatic lesions (5 type 1A lesions, 5 type 1D lesions). For direct MR arthrography, the obtained sensitivities and specificities in assessing complete defects were 96 % and 99.6 % (T (1)-weighted SE) and 92 % and 100 % (FLASH 3D), respectively. For all partial defects, sensitivities and specificities were 68.1 % and 93.3 % (T (1)-weighted SE) and 63 % and 96.1 % (FLASH 3D), respectively. For depicting partial defects of the scapholunate ligament the T (1)-weighted SE sequence (83.3/95.5 %) was superior to the FLASH 3D sequence (64.7/96.6 %), p < 0.05. For the evaluation of the TFCC (T (1)-weighted SE: 65/94.4 %, FLASH 3D: 70/94.6 %) and the lunotriquetral ligament (T (1)-weighted SE: 44/89.4 %, FLASH 3D: 44 /96.7 %), direct MR arthrography showed an insufficient correlation with arthroscopy. CONCLUSION: Direct MR arthrography proved to be of equal value compared with diagnostic arthroscopy in detecting complete defects of the intrinsic ligaments and the TFCC. The method has the potential of replacing diagnostic arthroscopy for the evaluation of the intrinsic ligaments and the TFCC. The T (1)-weighted SE sequence appeared to be superior to the FLASH 3D sequence in evaluating partial defects of the scapholunate ligament. Direct MR arthrography did not reliably detect partial defects of the TFCC and the lunotriquetral ligament.

Adult↗
PubMed1999

Prothrombin G20210A gene mutation, heparin cofactor II defects, primary (essential) thrombocythemia, and thrombohemorrhagic manifestations.

This article addresses the issue of thromboembolic disorders associated with the prothrombin G20210A gene mutation, with heparin cofactor II (HC-II) defects and with primary (essential) thrombocythemia. The prothrombin gene mutation is of recent discovery, is inherited as an autosomal dominant disorder, and seems to be highly prevalent in the general white population. The incidence is almost as high as that known for factor V Leiden. Both venous and arterial thromboses are noted, especially deep venous thrombosis, including cerebral venous events and myocardial infarction. As with other congenital thrombophilic states, additional risk factors or multiple defects seem to precipitate the events. Although initially elevated plasma prothrombin levels were described in these patients, this is no longer valid for all patients. At this time there is no easy screening test to detect this defect, but, because of the high prevalence, prothrombin G20210A gene mutation should routinely be assayed for in thrombophilic patients. The association between HC-II defects and thromboembolism is more controversial, and reports both confirming and denying this association have been described. The congenital form of HC-II defect is autosomal dominant. HC-II can be determined by its activity and immunologically. HC-II defects very likely play a role in conjunction with other congenital or acquired defects. Acquired HC-II defects are found in association with systemic disseminated intravascular coagulation (DIC) but not with local activation of the hemostasis system. HC-II levels are also decreased in preeclamptic women, and newborns have physiologically low levels. HC-II defects in thrombophilic patients should be considered after the more common disorders have been ruled out. Primary (essential) thrombocythemia can be associated with both thromboembolic events and bleeding. Typical thrombotic manifestations are erythromelalgia and microvascular thrombosis. Also, pregnant females suffer high rates of complications, such as spontaneous abortion. A number of treatment modalities are at present available to not only decrease platelet counts but also manage thromboembolic events.

Family Health↗
PubMed1987

[Study of early glaucomatous visual field defects with the automatic perimeter Topcon SBP-1000. Comparative study with the Octopus 201 perimeter].

The automatic perimeter TOPCON SBP-1000 uses light emitting diodes (LED's) for stimulus generation and thus completely differs from the projection type perimeter OCTOPUS 201. In order to get some first idea about the capabilities of the TOPCON SBP-1000 22 eyes of 18 patients with early glaucomatous visual field defects were examined both with the glaucoma program/TOPCON SBP-1000 and program 31/OCTOPUS 201. Field defects were divided into three groups according to the total loss (program DELTA/OCTOPUS 201): group I with a total loss of 0 dB, group II with a total loss of 1-200 dB, group III with a total loss greater than 200 dB. Evaluation and comparison of visual field results is done after discussing the most important technical parameters and fundamental aspects of methods and strategies using the total percentage of "normal" test points, "small relative defects", "deep relative defects" and "absolute defects". We could show that specificity and sensitivity for the detection of earliest field defects are quite equal both in the TOPCON SBP-1000 and in the OCTOPUS 201. Concerning the detection of more pronounced visual field defects the TOPCON-perimeter has a somewhat smaller sensitivity as a result of the different definition of the category "normal"; at the same time there is a tendency for showing up more "absolute defects" instead of "deep relative defects". Technical parameters and strategies are discussed critically taking into consideration the practical experience obtained during this first routine testing.

Adult↗
PubMed1999

Functional and aesthetic objectives in the reconstruction of lip defects.

The reconstruction of lip defects presents a challenge to the surgeon. Apart from attaining a good aesthetic result, preserving the function of the oral sphincter is an essential objective. A variety of techniques and modifications of procedures for reconstructing lip defects have been reported in the literature. It is up to the surgeon to select the reconstruction procedure ensuring optimum functional and cosmetic results, depending on the location, size, and depth of the defect. The division of the lips into aesthetic subunits can prove very beneficial in designing lip reconstruction procedures. The upper lip is divided into three aesthetic subunits: two lateral subunits and a median subunit, the philtrum. The lower lip constitutes a single subunit. In this study established reconstruction techniques are discussed, and a concept serving to facilitate the appropriate choice of technique is introduced. This concept differentiates between vermilion defects on the one hand and partial-thickness and full-thickness lip defects on the other hand. For the lower lip the full-thickness defects are classified as defects involving one third and one third to two thirds of the lower lip width and between two thirds and complete loss of lip tissue. For the upper lip a distinction is made between isolated defects of the central and lateral subunits and combined defects of the central and lateral subunits. Important principles of surgery and the advantages and disadvantages of different reconstruction techniques are discussed.

Esthetics↗
PubMed2004

An ab initio study of structural properties and single vacancy defects in Wurtzite AlN.

The cell parameters, bulk moduli and electronic densities-of-states (DOS) of pure and vacancy defect AlN were computed using generalized-gradient approximation (GGA) and hybrid functional (B3LYP) computational methods within both plane wave-pseudopotential and localized Gaussian basis set approaches. All of the methods studied yielded cell parameters and bulk moduli in reasonable agreement with experiment. The B3LYP functional was also found to predict an optical band gap in excellent agreement with experiment. These methods were subsequently applied to the calculation of the geometry, defect state positions and formation energies of the cation (V(Al)) and anion (V(N)) single vacancy defects. For the V(Al) defect, the plane wave-pseudopotential predicted a significant retraction of the neighboring N away from the vacancy, while for the V(N) defect, only slight relaxations of the surrounding Al atoms towards the vacancy were predicted. For the computed DOS of both vacancy defects, the GGA methods yielded similar features and defect level positions relative to the valence band maximum, while the B3LYP method predicted higher separations between the defect levels and the valence and conduction bands, leading to higher energy occupied defect levels.

Journal Article↗
PubMedDate not supplied

Maternal residential exposure to hazardous wastes and risk of central nervous system and musculoskeletal birth defects.

The authors used a case-control design to evaluate the risk of central nervous system and musculoskeletal birth defects relative to exposure to solvents, metal, and pesticide contaminants from hazardous waste sites. Cases included 473 central-nervous-system-defect births and 3305 musculoskeletal-defect births to residents of 18 counties in New York State; controls comprised 12,436 randomly chosen normal births. For each address at birth, the authors assigned a probability of exposure to solvents, metals, and pesticides from hazardous waste sites in the study area (n = 643). They also rated residences by proximity to air releases from industrial facilities and by contamination of community water supplies. Compared with individuals for whom a low probability of exposure existed, mothers who resided in areas assigned a medium or high probability of exposure to hazardous waste contaminants did not show an increased risk of either type of birth defects. After adjusting for mother's race and age, prenatal care initiation, and population density, the resulting relative risks were as follows: central nervous system defects and exposure to solvents, 0.8 (95% confidence interval [CI] = .4, .6); central nervous system and metals, 1.0 (95% CI = 0.7, 1.7); musculoskeletal defects and solvents, 0.9 (95% CI = 0.5, 1.3); and musculoskeletal defects and pesticides, .8 (95% CI = .5, 1.3). With respect to central nervous system defects, there was an elevated risk associated with living near industrial facilities that emitted solvents (odds ratio = 1.3 [95% CI = 1.0, 1.7]) or metals (OR = 1.4, [95% CI = 1.0, 1.8]) into the air. The low proportion of individuals who had a medium or high probability of residential exposure to hazardous waste-site contaminants limited the investigation of particular pathways, disease subgroups, and/or geographic areas. Associations between central nervous system defects and industrial releases of solvents and metals need to be investigated further.

Adolescent↗
PubMed2001

Influence of bone marrow on membrane-guided bone regeneration of segmental long-bone defects in rabbits.

Defects 10 mm long were created in long bone in the diaphysis of both radii of 18 rabbits (test and control side). On the test side, ingrowth of bone marrow into the defects was hindered or delayed by: plugging the opening of the cut bone ends with gutta-percha points (n = 7); plugging with Gelfoam (n = 6); or by removing the bone marrow by flushing with saline (n = 5). The defects on both test and control side were covered with an expanded polytetrafluoroethylene membrane, shaped as a tube. Healing was followed with radiographs for four to five months, after which the animals were killed and ground sections of the areas of the defects were prepared for histological examination. On the control side, nine of 18 animals had complete osseous bridging of the defect, and a small transverse non-mineralised zone remained in the centre of the healed defect in the other animals. This zone consisted of loose connective and cartilagenous tissue as well as connective tissue obviously derived from the outside of the membrane. By preventing or delaying the ingrowth of bone marrow we retarded the regeneration of mineralised bone, particularly in the gutta-percha and flushed bone marrow groups. The principle of guided tissue regeneration may be used to achieve regeneration of extensive long-bone defects. Any attempts to delay or prevent bone marrow ingrowth into the defects did retard regeneration of segmental long-bone defects.

Animals↗
PubMed2006

Oral aphthous ulcers and dental enamel defects in children with coeliac disease.

AIM: Coeliac disease is characterized by oral manifestations, such as dental enamel defects and recurrent oral aphthae. In this study we compared the prevalence of enamel defects and recurrent aphthous stomatitis (RAS) between patients diagnosed with coeliac disease and healthy controls. METHODS: A total of 72 patients with coeliac disease were studied together with 162 normal healthy subjects as controls to individualize the prevalence of enamel defects and recurrent aphthous stomatitis (RAS) in this disease. RESULTS: Dental enamel defects were found in 14/70 (20%) coeliac patients and in 9/159 (5.6%) controls. In particular, 13/53 (24.5%) coeliac patients with mixed or permanent dentition and 1/17 (5.8%) coeliac children with deciduous dentition had enamel defects. Altogether, 9/145 (6.2%) control subjects with mixed or permanent dentition had dental enamel defects. None of the controls with deciduous dentition had enamel defects. Thus, the enamel defects occurred more frequently in coeliac patients (p < 0.001). Regarding RAS, 24/72 (33.3%) coeliac patients and 38/162 (23.4%) control subjects had aphthous ulcers. Statistically significant differences were not observed between the two groups (p > 0.05). One in three coeliac subjects suffering from RAS received benefit from a gluten-free diet. CONCLUSION: In the present study, the prevalence of enamel defects was found to be greater in coeliac patients than healthy controls. Even though the prevalence of RAS in coeliac subjects varied from healthy controls, the difference was not statistically significant. However, more than 1/3 coeliac subjects suffering from RAS benefited from a gluten-free diet.

Adolescent↗
PubMedDate not supplied

Pedunculated synovium grafts in articular cartilage defects in rabbits.

A rabbit model was used to assess the nature of healing tissues in hyaline cartilage defects and to compare the healing in defects treated with pedunculated synovium grafts to those in defects without synovial grafting. Both knees of 28 1-year-old rabbits were operated. A 3 x 2-mm cartilage defect that exposed cancellous bone was created in the non-weight-bearing area of each medial femoral condyle. Each right-knee defect was covered with a pedunculated synovial graft obtained from the same joint, and the left-knee defects were left uncovered as controls. Groups of rabbits were sacrificed at 3, 6, 12, and 24 weeks postsurgery. Sections from each knee were stained with hematoxylin-eosin and safranin O-fast green staining, and were immunohistochemically stained for type II collagen. The healing at each site was histologically scored, and the intensity of staining for type II collagen was graded. At 12 and 24 weeks, statistical comparisons of histological scores revealed significantly more hyaline cartilage tissue in the synovium-grafted defects. At 24 weeks, these same defects showed significantly more type II collagen. Thus, pedunculated synovium transplantation appears to hold promise as a method for repairing hyaline cartilage defects.

Animals↗
PubMed2002

Thyroid cancer yield in patients with Graves' disease selected for surgery on the basis of cold scintiscan defects.

Previous studies have suggested that thyroid nodules found in patients with Graves' disease (GD) have a higher likelihood of being malignant, and that thyroid cancer behaves more aggressively when associated with GD, although both of these assertions remain controversial. The purpose of this study was to assess the frequency of cold scintiscan (SC) defects in patients with GD, and to determine the prevalence of thyroid cancer in such patients. Our secondary objective was to determine if there are any risk factors for developing cold defects by comparing clinical characteristics of both GD patients with cold SC defects and age and gender-matched GD patients without cold defects. We included in this analysis patients with a confirmed diagnosis of GD for whom SC results and adequate follow-up information were available. Clinic records were available in 772 patients with GD. Of these, 325 patients met eligibility criteria. Cold defects were found in 39 of 325 (12.0%) patients. Among these, 22 (56.4%) were referred for surgery, of whom 6 (1.85% of all GD patients, 15.2% of GD patients with cold nodules, 25% of GD patients with palpable nodules, and 27.3% of those undergoing surgery) had papillary thyroid cancer (PTC) in the location corresponding to the SC defect. In 2 PTC patients, no palpable abnormality corresponded to the cold defect found to contain cancer at surgery. One PTC patient was found to have metastatic disease to bone, and 2 additional PTC patients required multiple therapies with radioiodine. Compared to age and gender-matched control patients with GD and without cold SC defects, there were no differences in radioactive iodine uptake (RAIU), goiter size, duration of disease, degree of elevation in microsomal antibody (MA) titers, or thyroid-stimulating immunoglobulin (TSI). We conclude that thyroid scintigraphy is an important preliminary test in the evaluation of patients with GD, and that the prevalence of thyroid cancer in the location corresponding to a focal cold SC defect provides justification for further diagnostic evaluation or surgical management.

Adult↗
PubMed1998

Repair of large full-thickness articular cartilage defects with allograft articular chondrocytes embedded in a collagen gel.

Full-thickness articular cartilage defects are a major clinical problem; however, presently there is no treatment available to regeneratively repair these lesions. The current therapeutic approach is to drill the base of the defect to expose the subchondral bone with its cells and growth factors. This usually results in a repair tissue of fibrocartilage that functions poorly in the loaded joint environment. The use of phenotypically appropriate chondrocytes embedded in a collagen gel delivery vehicle may provide a method that could be used to repair full-thickness articular cartilage defects with functionally satisfactory hyaline cartilage. Allograft articular chondrocytes embedded in a type I collagen gel were transplanted into large (6 x 3 x 3 mm), full-thickness articular cartilage defects in condylar and patellar weight-bearing surfaces to develop clinically applicable methods to repair articular cartilage defects. Chondrocytes were isolated from the articular cartilage of 4-week-old New Zealand rabbits and embedded in type I collagen gels. This composite was transplanted into a full-thickness defect on the medial femoral condyle and patellar groove of adolescent host rabbits. The repair cartilage was assessed histologically by a semiquantitative scoring system and biomechanically with a microindentation technique of specimens 4-48 weeks after chondrocyte transplantation. Defects in both locations were repaired with histologically apparent hyaline cartilage observed from as early as 4 weeks until 48 weeks after transplantation. The repair cartilage in the medial femoral condyle was more irregular than in the patellar groove, but in all other respects was similar. The grafted tissue did not remodel and differentiate into the morphological zones seen in normal articular cartilage. No tidemark or subchondral bony plate formed even 48 weeks after transplantation. Biomechanically, the repaired cartilage demonstrated indentation values similar to normal articular cartilage 12 weeks after transplantation and remained the same 48 weeks after transplantation. By contrast, the control (i.e., empty) defects healed with tissue that exhibited very poor metachromatic staining and exhibited very high indentation values. Incomplete bonding of the repair tissue to the normal cartilage was seen, and the surface was significantly irregular with major discontinuities. These observations provide the basis for considering the use of allograft articular chondrocytes to repair articular cartilage defects in the weight-bearing regions of the knee.

Animals↗
PubMed2000

Fanconi anemia, complementation group A, cells are defective in ability to produce incisions at sites of psoralen interstrand cross-links.

The hypersensitivity of Fanconi anemia, complementation group A, (FA-A) cells to agents which produce DNA interstrand cross-links correlates with a defect in their ability to repair this type of damage. In order to more clearly elucidate this repair defect, chromatin-associated protein extracts from FA-A cells were examined for ability to endonucleolytically produce incisions in DNA at sites of interstrand cross-links. A defined 140 bp DNA substrate was constructed with a single site-specific monoadduct or interstrand cross-link produced by 4,5',8-trimethylpsoralen (TMP) plus long wavelength (UVA) light. Our results show that FA-A cells are defective in ability to produce dual incisions in DNA at sites of interstrand cross-links. Specifically, there is defective incision on the 3'- and 5'-sides of both the furan and pyrone sides of the cross-link. This defect is corrected in FA-A cells transduced with a retroviral vector expressing FANCA cDNA. At the site of a TMP monoadduct, FA-A cells can introduce incisions on both the 3'- and 5'-sides of the furan side monoadduct, but are defective in ability to produce these incisions on the pyrone side monoadduct. These studies also indicate that XPF is involved in production of the 5' incision by the normal extracts on these substrates. These results correlate with our previous work, which showed that FA-A cells are mainly defective in ability to repair psoralen interstrand cross-links with a lesser defect in ability to repair psoralen monoadducts. This defect in endonucleolytic incision at sites of TMP interstrand cross-links could be related to reduced levels of non-erythroid alpha spectrin (alphaSpIISigma*) in the extracts from FA-A cells. alphaSpIISigma* could act as a scaffold to align proteins involved in cross-link repair and enhance their interactions; a deficiency in alphaSpIISigma* could thus lead to reduced efficiency of repair and the decreased levels of incisions we observe at sites of interstrand cross-links in FA-A cells.

Adenosine Triphosphate↗