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W Becker

Publications and source records attributed to W Becker.

At least 91 records · Page 5Linked to original sources

Monitoring allergen immunotherapy of pollen-allergic patients: the ratio of allergen-specific IgG4 to IgG1 correlates with clinical outcome.

BACKGROUND: Although allergen immunotherapy has been established as a treatment of type I allergy back in 1911, until now the underlying mechanisms have not been fully understood, nor are there any parameters which would allow one to monitor an ongoing treatment or to assess therapeutic success in the meantime. OBJECTIVE: We wanted to define allergen-specific parameters that change due to treatment in correlation with the clinical outcome. METHODS: We conducted a controlled study with grass pollen-allergic children and compared allergen-specific antibody titres before and 1 year after the onset of immunotherapy in contrast with untreated allergic and healthy children. Two recombinant forms of the major allergen group V of Phleum pratense (Phl p 5) served as model allergens. RESULTS: No change in IgE levels and no significant reduction of skin prick test (SPT) reactivity were seen. On the other hand, a significant reduction of symptom scores in the treated group and a significant rise in allergen-specific IgG1, IgG2 and IgG4 due to the treatment could be observed, but in neither case could we establish a correlation between the increasing amounts of the single antibody classes and the reduction of symptom scores. But most interestingly, when comparing the ratio of IgG4 to IgG1 with the symptom scores, we found significant correlations. Nevertheless, treated allergic patients still differ considerably from healthy controls as nonatopics have hardly any measurable allergen-specific IgG antibodies and no IgE antibodies at all. CONCLUSION: The ratio of IgG4 to IgG1 can serve as a valuable parameter that allows us to assess the success of immunotherapy already 1 year after the onset. The increase of specific IgG1 in relation to IgG4 during treatment reflects a possible influence of this subclass on the induction of tolerance towards allergens.

Allergens↗

Evaluation of procollagen III peptide as a marker of tissue hyperthyroidism in long-term treated women with TSH suppressive doses of thyroxine.

Increased serum concentrations of the aminoterminal propeptide of collagen III (PIIINP) are found in overt hyperthyroidism. Thus, measurement of serum PIIINP might be useful as an early marker of tissue hyperthyroidism in patients with TSH suppressive thyroxine treatment. In a prospective study we evaluated female patients followed in the thyroid outpatient clinic. Serum PIIINP concentrations were analysed in three groups: patients with TSH suppressive thyroxine treatment for more than 6 months (n = 33, TSH < 0.1 mU/l), patients with thyroxine substitution for hypothyroidism for more than 6 months (n = 20, TSH 0.2-4.0 mU/l) and spontaneous hyperthyroid patients (n = 8, TSH < 0.03 mU/l, increased freeT4 and/or T3). Beside TSH, thyroid hormones and serum PIIINP we measured serum SHBG and a clinical score. Hyperthyroid patients had clearly elevated serum PIIINP and SHBG values and a higher clinical score when compared with other study groups (p < 0.001). Patients with TSH suppressive thyroxine treatment had higher fT4 and T3 concentrations than the thyroxine substitution group (fT4 22 +/- 4.8 pmol/l vs. 17 +/- 2.6 pmol/l, T3 2.2 +/- 0.4 nmol/l vs. 1.8 +/- 0.3 nmol/l, p < 0.001) and also elevated serum SHBG values (77.6 +/- 27.5 nmol/l vs. 58.4 +/- 18 nmol/l, p < 0.01). However, serum PIIINP concentrations and the clinical score were very similar in both thyroxine treated groups (PIIINP in TSH suppression group 3.0 +/- 0.67 microg/l vs. 2.8 +/- 0.65 microg/l in the substitution group, clinical score 2 +/- 1.8 pts. vs. 1.7 +/- 1.5 pts. p = n.s.). In conclusion, serum PIIINP is not a reliable early marker for detection of tissue hyperthyroidism in long-term thyroxine treated women with suppressed TSH.

Adult↗

In vivo stability and metabolism of 99Tcm-labelled anti-CD4 monoclonal antibodies and Fab' fragments.

In a comparative study, the in vivo metabolic profile of 99Tcm-anti-CD4 monoclonal antibodies (MAb) and Fab' fragments (direct thiol-reduction method) was investigated in rats with adjuvant arthritis. Plasma samples were obtained 1, 4 and 15 h following intravenous injection and urine was collected over 15 h. The composition of the radiolabelled molecules was analysed by gel filtration chromatography. The profile of the complete MAb was as follows. (1) Serum: a predominant peak of 150 kDa (complete MAb; approximately 80%); three minor peaks of 125, 100 and 50 kDa (presumably H2L1, H2 and H1 chains; 14%); and two small peaks of approximately 1500 and 300 Da (presumably 99Tcm-glutathione and Cys-99Tcm-Cys; 5%). (2) Urine: minor peaks of 125, 100 and 50 kDa (15%), major peaks of 1500 and 300 Da (50%), and an additional 25-kDa peak (30%). The profile of the Fab' was as follows. (1) Serum: three minor peaks of 150 kDa [conceivably F(ab')2 plus soluble-CD4], 110 kDa [F(ab')2] and 95 kDa (Fab' plus soluble-CD4; together 30%); a predominant peak of 55 kDa (Fab'; 61%); and two minor peaks of 1500 and 300 Da (8%). (2) Urine: predominantly a 55 kDa (16%) and 1500 and 300 Da peaks (74%). Also, the anti-CD4 Fab' showed higher urine excretion and lower plasma levels than the complete anti-CD4 MAb, but still more favourable tissue-to-blood ratios following scintigraphy of the arthritic joints. Thus, the complex metabolic profile of the anti-CD4 Fab' does not appear to interfere with specific targeting of the inflamed synovial membrane.

Animals↗

A new era.

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Dental Implantation↗

Five-year evaluation of implants placed at extraction and with dehiscences and fenestration defects augmented with ePTFE membranes: results from a prospective multicenter study.

BACKGROUND: Barrier membranes have been used to promote bone ingrowth on implants with dehiscences and fenestrations. Membranes also have been used to protect defects adjacent to implants placed at the time of extraction. The concept of guided bone regeneration relates to preferentially allowing cells from bone to migrate into various defects while excluding fibrous tissue and epithelium. The purpose of these procedures is to enhance bone-to-implant contact at the treated sites and to prevent mucosal complications. PURPOSE: The purpose of this article is to report clinical outcomes for implants placed at the time of extraction and augmented with expanded polytetrafluoroethylene (ePTFE) and followed for 5 years. The outcomes for implants with dehiscences and fenestrations augmented with ePTFE barriers and followed up to 5 years also are reported. METHODS AND MATERIALS: Four treatment centers participated in this study (Tucson, Gothenburg, Spokane, and Leuven). In the extraction group, teeth were removed for varying reasons, and Brånemark implants were placed and stabilized within the host bone. Defects present at the coronal implant aspect were covered with ePTFE barrier membranes. Flaps were rotated to cover the membrane-treated sites. If exposure of the material occurred prior to second-stage surgery, the membranes were removed. Barriers remaining unexposed were removed at second-stage surgery. The implants were followed up to 5 years. In the fenestration and dehiscence group, implants with exposed threads were augmented with ePTFE barrier membranes. The barriers were removed at appropriate intervals, and the patients were followed up to 5 years. Radiographic measurements were made from nonstandardized periapical radiographs at abutment connection and 1, 3, and 5-year follow-up visits. RESULTS: Forty patients participated in the extraction group. They received a total of 49 implants. Three implants failed prior to loading. The 5-year cumulative survival rates for implants placed at the time of extraction were 93.9% and 93.8%, respectively, for maxillary and mandibular implants. The average maxillary mesial and distal marginal bone loss (1-5 yr) was 0.3 mm (standard deviation [SD] = 1.5) and 0.3 mm (SD = 1.0). In mandibles, the average mesial and distal bone loss (1-5 yr) was -0.2 mm (SD = 0.5) and -0.05 mm (SD = 0.6), respectively. The dehiscence and fenestration group included 44 patients. Twenty-six were followed for up to 5 years. Eight patients experienced total implant failure. For dehiscences and fenestrations, the cumulative survival rates were 76.8% and 83.8% for maxillary and mandibular implants, respectively. The average maxillary mesial and distal bone loss (1-5 yr) was 0.4 mm (SD = 0.8) and 0.2 mm (SD = 0.9), respectively. In mandibles, the average mesial and distal marginal bone loss was 0.3 mm (SD = 0.9) and 0.3 mm (SD = 0.8), respectively. CONCLUSIONS: Implants placed at the time of extraction and augmented with ePTFE barrier membranes have favorable long-term predictability. On the other hand, long-term evaluation of implant dehiscences and fenestrations augmented with barrier membranes indicates that they have less favorable 5-year survival rates. Membrane augmentation of these may be questioned.

Adolescent↗

Formation of bone around titanium implants placed into zero wall defects: pilot project using reinforced e-PTFE membrane and autogenous bone grafts.

BACKGROUND: Guided bone regeneration (GBR) frequently is used to augment implants with various types of bone defects. The defects often are grafted with different materials, yet there is insufficient evidence that these materials enhance bone-to-implant contacts. PURPOSE: The purpose of this pilot project was to test the principle of GBR to promote bone formation adjacent to commercially pure titanium implants placed within zero-wall defects. Histologic and histomorphometric measurements were used to evaluate new bone formation. MATERIALS AND METHODS: Under appropriate anesthesia, deep, wide defects were created within the mandibles of two large dogs. Buccolingual bone was removed to the depth of the defects leaving only the mesial and distal walls. Of the eight implants placed, three were augmented with titanium-reinforced expanded polytetrafluoroethylene (e-PTFE) barriers and autogenous bone chips. Three sites were augmented with barrier membranes only, and two sites were not augmented or grafted and served as controls. Seven months after surgery the dogs were sacrificed and block sections were taken for histologic evaluation. RESULTS: Histologic and histomorphometric measurements were used to evaluate new bone formation. Results from this evaluation revealed bone formation at the membrane-only sites and the membrane-plus-bone grafted sites. The bone grafts were completely incorporated by the newly formed marginal compact bone. For all treated sites, there was poor bone-to-implant contact. Histomorphometric measurements showed a trend toward greater bone formation at membrane-treated sites compared with control sites. However, autogenous bone grafting did not seem to affect the amount of newly regenerated bone. CONCLUSIONS: Within the limits of this pilot project, findings show trends toward bone healing, indicating constant and enhanced bone regeneration over the exposed implant. Bone contact to the implant surface generally was poor.

Animals↗

Immunoreactive leptin and leptin mRNA expression are increased in rat hypo- but not hyperthyroidism.

In this study, plasma leptin concentrations were measured in rats artificially rendered hyper- or hypothyroid by administration of thyroxine or TRH, by administration of methimazole, or by thyroidectomy. Compared with those in untreated controls, leptin immunoreactivity was not affected in the hyperthyroid state, but was significantly increased in hypothyroid animals. Methimazole administration for longer time periods caused a stepwise increase in plasma leptin immunoreactivity. Greatest leptin concentrations were seen after 28 days of methimazole. Seven days after withdrawal of the methimazole, leptin concentrations no longer differed from those observed in control animals. In hypothyroid animals, expression of leptin mRNA was increased in both retroperitoneal and epididymal adipose tissue, whereas no difference was seen for subcutaneous or mesenteric fat. Incubation of rat leptin with plasma of eu- or hypothyroid rats and subsequent HPLC analysis of leptin plasma peaks gave no indication of an altered hormone stability. We conclude that, in hypothyroid rats, leptin concentrations may be increased as a result of stimulated leptin synthesis in retroperitoneal and epididymal adipose tissue.

Adipose Tissue↗

Long-term evaluation of 282 implants in maxillary and mandibular molar positions: a prospective study.

BACKGROUND: Placement of implants into molar positions presents diagnostic, surgical and prosthetic challenges. There are few reported studies for implants placed into molar positions. The purpose of this prospective longitudinal study is to report long-term clinical outcomes for 282 implants placed into molar positions. METHODS: Two-hundred-twelve patients received 282 implants. Implant size, location, jaw shape, and bone quality were recorded for all implants placed into molar positions. Seventy implants were inserted in maxillae and 212 in mandibles. Marginal bone level changes in maxillae and mandibles were measured from non-standardized periapical radiographs taken at abutment connection and an average follow-up of 3.9 years. Mesial-distal implant measurements were made from the top of the implant cylinder to the first point of bone to implant contact. In mandibles, 39 implants were used for single molar replacements, 67 implants were placed into excellent bone quality (type I) and 113 were in good bone quality (type 11); 145 implants were placed into bone with moderate bone resorption (type B); 166 implants were placed in first molar positions and 46 in second molar sites. RESULTS: At 6 years the cumulative success rate (CSR) for mandibular implants is 91.5%, and the success rate from the 2 to 3 year follow-up is 100%. Of the 70 implants placed in maxillae, 16 replaced single molars. Thirty-two implants were placed in jaw shape B with type 2-bone quality. For maxillary implants, the 6-year CSR was 82.9% and the success rate remained steady at 100% after the 2 to 3 year follow-up. For maxillary implants, at abutment connection the average marginal bone level was 1.67 mm, while at follow-up it was 1.98 mm. These differences were statistically significant (P = 0.04), but are not considered to be clinically significant. For mandibular implants, at abutment connection the mean marginal bone level as measured from radiographs was 2.11 mm, and at follow-up was 2.02 mm. This slight gain in bone level was not statistically significant and is not considered to be clinically significant. CONCLUSIONS: Results of this prospective longitudinal study of implants placed into molar positions indicates favorable clinical outcomes. These CSR rates (91.5% mandibles, 82.9% maxillae) are less than what has been reported for implants placed into mandibular and maxillary anterior segments. Differences in outcomes between anterior and posterior locations may be related to bone quality and quantity.

Bone Density↗

Quantification of intact quadriceps tendon, quadriceps tendon insertion, and suprapatellar fat pad: MR arthrography, anatomy, and cryosections in the sagittal plane.

OBJECTIVE: The purpose of this study was to quantify quadriceps tendon length, thickness, and insertion in relation to the suprapatellar fat pad. SUBJECTS AND METHODS: We used three methods to analyze the anatomy of intact quadriceps tendons and insertions into the patellar base: MR arthrography (53 knees with intact extensor mechanisms), gross anatomy (16 cadaveric knees), and cryosections (four cadaveric knees). With an electronic cursor, two observers independently quantified the extensor mechanism on midline sagittal T1-weighted spin-echo sequences acquired on a low-field-strength (0.23 T) scanner. RESULTS: On MR arthrograms, quadriceps tendon length, determined from the superior patellar pole to the most superior part of the suprapatellar recess, measured 49 +/- 7 mm in women and 50 +/- 9 mm in men. Thickness of quadriceps tendon at three sites (suprapatellar recess, center, and superior patellar pole) measured 7 +/- 1 mm in women and 8 +/- 1 mm in men. Thickness was significantly larger in men at all measurement locations. Quadriceps tendon insertion and the suprapatellar fat pad along the patellar base measured 16 +/- 2 and 6 +/- 2 mm, respectively, in women, and 18 +/- 3 and 7 +/- 2 mm, respectively, in men. CONCLUSION: On midline MR images, sagittal thickness of the quadriceps tendon and its insertion was significantly larger in men than in women. The prevalence of the suprapatellar fat pad was 100%.

Adipose Tissue↗

Imaging osteomyelitis and the diabetic foot.

BACKGROUND: The clinical diagnosis of osteomyelitis and the diabetic foot is in most of the patients not possible without imaging the bone. The clinical problem is to diagnose infection as early, as reliable and as cheap as possible to prevent the possible longstanding and life-threatening complications. METHODS: For imaging a lot of different radiological and nuclear medicine methods are available. This article focuses on the possible results of conventional plain radiography and tomography, computed tomography and magnetic resonance imaging as radiological methods and on bone scan, autologous white blood cell scintigraphy with 111In-oxin or 99mTc-HMPAO, antigranulocyte antibodies, 99mTc-/111In-human immunoglobulin, 67Ga-citrate and 99mTc-nanocolloids. RESULTS: Different methods offer different answers. Radiological methods give detailed pathological answers, nuclear medicine methods answer questions of specificity such as leukocytic infiltration. CONCLUSIONS: If osteomyelitis is suspected, plain radiography should be the first, three phase bone scintigraphy the second and infection specific radiopharmaceuticals the third step of examination. Only in negative images with high clinical suspicion CT or MRI should be the final imaging procedure. In the diabetic foot imaging cascade should also start with plain radiography, followed by three phase bone scintigraphy or MRI. If clinically neuropathy is present specific nuclear medicine imaging should be performed.

Bone and Bones↗

Correlation between radiation dose, synovial thickness, and efficacy of radiosynoviorthesis.

OBJECTIVE: To correlate the therapeutic efficacy of radiosynoviorthesis (RSO) to radiation doses achieved. METHODS: In 20 patients with known rheumatoid arthritis, radiosynoviorthesis was performed in 36 joints. Arthritis disease activity was assessed by "blood pool scintigraphy" (n = 29) score after injection of 370 MBq 99mTc-MDP, before and at 1, 2, and 5 months after the RSO in 12 patients. For semiquantitative measurements, a region-of-interest technique was applied. Synovial thickness and response to the RSO were evaluated by joint ultrasonography. Pain levels were evaluated semiquantitatively. Dosimetry (n = 20) was calculated using planar quantification according to the MIRD scheme. RESULTS: The mean radiation absorbed dose of 186Re-sulfate to the whole body was 5.3+/-2.7 cGy, liver 10.0+/-8.1 cGy, spleen 20.3+/-22.9 cGy, kidneys 9.4+/-11.4 cGy, and at the injected joints of the shoulder 120.5+/-32.2 Gy, hand 130.0+/-12.6 Gy, elbow 83.6+/-38.7 Gy, and talar/subtalar joint 84.1+/-30.7 Gy. In 7 cases, where mandatory immobilization of the joint was not possible, the dose to the lymph nodes (n = 25) was 25.9+/-53.8 Gy (maximum 189 Gy) and to single lymph nodes 14.6+/-11.2 Gy (maximum 63 Gy). The reduced doses to the synovia (at 40% leakage) were: 169Er-citrate 73.10+/-25.25 Gy; 90Y-citrate 59.25+/-46.45 Gy; 186Re-sulfate 65.40+/-32.55 Gy. In cases of complete immobilization, the dose to the lymph nodes was negligible: 169Er-citrate (n = 7), whole body dose 0.4 cGy, lymph nodes 2.3 Gy, finger joints 132.3+/-34.3 Gy; 90Y-citrate (n = 6), whole body dose 15.5 cGy, liver dose 26.5 cGy, splenic dose 11.9 cGy, kidney dose 67 cGy, joint knee joint dose 130.1 Gy. Regarding therapeutic effect, mean reduction of the 99mTc-MDP blood pool activity was 41% at first month, 48% at second month, 48% at the fifth month, 48% in larger joints, and 63% in finger joints. Three and 6 months after RSO, sonography showed a mean reduction in synovial swelling: in the knee joint 1.67 and 4.38 mm, respectively; in the larger joints (shoulder, elbow, hand, talar/subtalar) 0.88/1.93 mm; and in finger joints 0.53/1.76 mm. Clinically, best results were observed in the finger joints. CONCLUSION: 1. We observed a significantly higher radiation absorbed dose to the lymph nodes and lower dose to the synovia in the absence of joint immobilization. Immobilization of the joint is essential. 2. At 2 months after treatment, a significant reduction of blood pool activity and synovial swelling was observed, with further improvement in the following months, especially in the finger joints. 3. There is a strong correlation between the reduction of blood pool activity, synovial swelling, and improvement of pain.

Arthritis, Rheumatoid↗

Periodontal regeneration: myth or reality?

One of the goals of periodontal therapy is regeneration. During the past 20 years, several materials and techniques have been developed and tested for enhancing periodontal regeneration. This paper evaluates flap debridement, allogenic and alloplastic grafting, and the use of nonresorbable and resorbable barrier membranes as regenerative techniques. One of the most predictable regenerative therapies is treatment of the three-walled intrabony defect. This defect can be repaired with 2 to 2.5 mm of bone fill and results in significant gains in clinical probing attachment and decreases in probing depths. There is a slightly greater improvement in periodontal measures with barrier membranes. Commercial preparations of allogenic bone and alloplastic fillers have a long, safe history of use and are primarily osteoconductive. They decrease probing depths and provide short-term gains in clinical attachment levels. Barrier membranes provide short-term evidence of improving Class II furcation invasions, however there is insufficient evidence that these improvements are sustained long-term. Class III furcations are not predictably treated by regenerative therapies. To date, there is an absence of clinical evidence that regenerative therapy increases the long-term life span of teeth.

Alveolar Bone Loss↗

Radiolabeled peptides for targeting cholecystokinin-B/gastrin receptor-expressing tumors.

UNLABELLED: The high sensitivity of pentagastrin stimulation in detecting primary or metastatic medullary thyroid cancer (MTC) suggests widespread expression of the corresponding receptor type on human MTC. Indeed, autoradiographic studies have demonstrated cholecystokinin (CCK)-B/gastrin receptors not only in more than 90% of MTCs but also in a high percentage of small cell lung cancers, some ovarian cancers, astrocytomas and potentially a variety of adenocarcinomas. The aim of this study was to systematically screen and optimize, in a preclinical model and a pilot clinical study, suitable radioligands for targeting CCK-B receptors in vivo. METHODS: A variety of CCK/gastrin-related peptides, all bearing the C-terminal CCK receptor-binding tetrapeptide sequence Trp-Met-Asp-PheNH2 or derivatives thereof, were studied. They were radioiodinated by the lodogen or Bolton-Hunter procedures. The peptides were members of the gastrin or CCK families, which differ by the intramolecular position of a tyrosyl moiety. Their stability and affinity were studied in vitro and in vivo; their biodistribution and therapeutic efficacy were tested in nude mice bearing subcutaneous human MTC xenografts. Diethylenetriamine pentaacetic acid (DTPA) derivatives of suitable peptides were synthesized successfully, and their preclinical and initial clinical evaluations were performed, labeled with 111In. RESULTS: All members of the CCK or gastrin families were stable in serum (with half-lives of several hours at 37 degrees C); nevertheless, the stability of those peptides bearing N-terminal pGlu residues or D-amino acids was significantly higher. In accordance with their comparably low affinity, nonsulfated members of the CCK family showed fairly low uptake in the tumor and other CCK-B receptor-expressing tissues. Sulfated CCK derivatives performed significantly better but also displayed a comparably high uptake in normal CCK-A receptor-expressing tissues. This effect was probably due to their similar affinity for both CCK-A and CCK-B receptors. Best tumor uptake and tumor-to-nontumor ratios were obtained with members of the gastrin family because of their selectivity and affinity for the CCK-B receptor subtype. Pilot therapy experiments in MTC-bearing animals showed significant antitumor efficacy compared with untreated controls. DTPA derivatives of minigastrin were successfully developed. In a pilot clinical study, radioiodinated and 111In-labeled derivatives showed excellent targeting of physiological CCK-B receptor-expressing organs, as well as all known tumor sites. CONCLUSION: CCK/gastrin analogs may be a useful new class of receptor-binding peptides for diagnosis and therapy of CCK-B receptor-expressing tumors, such as MTC or small cell lung cancer. Nonsulfated gastrin derivatives may be preferable because of their CCK-B receptor selectivity, hence lower accretion in normal CCK-A receptor-expressing organs.

Adult↗