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Biomedical subjects

M W Anderson

Publications and source records attributed to M W Anderson.

At least 19 recordsLinked to original sources

Apoptosis in the regenerate produced by mandibular osteodistraction in the mature rat.

UNLABELLED: AUTHORS: Liu ZJ, Anderson MW, Gu GM, King GJ. OBJECTIVE: Little is known about the contribution of apoptosis to the formation of the regenerate in distraction osteogenesis. This study investigated the role of apoptosis in the regulation of osteogenesis in relation to mandibular distraction rate and recovery time. METHODS: One hundred and twenty-nine 3-month rats received unilateral mandibular ramus osteotomy and distraction device placement. After 3-day latency, these were distracted for 5 days. The slow group was distracted a total of 1 mm (0.2 mm/day), the moderate 2 mm (0.4 mm/day), the rapid 3 mm (0.6 mm/day), and the sham was not distracted (0.0 mm/day). Eight to nine rats from each group were killed at 6 (mid-distraction), 10 (early-consolidation), 24 (mid-consolidation) and 38 (late-consolidation) days following device placement. Baseline data were obtained from an additional eight rats killed at day 3 (end of latency). Sagittal sections (7 mum) of the harvested hemi-mandibles were embedded in paraffin, double-stained with the DeadEnd(TM) Colorimetric TUNEL system for apoptotic cells and tartrate-resistant acid phosphatase for osteoclasts. Cell counts of apoptotic cells and osteoclasts (apoptotic or otherwise) were preformed at 40x magnification using a calibrated grid at the middle regions of the caudal, central and rostral parts of the distraction gap. Counting reproducibility was verified as <13%. RESULTS: Counts from all three regions were combined because no significant regional difference was found. The majority of the fibrous matrix regenerate was seen at days 6 and 10 while osseous regenerate occurred mainly at days 24 and 38. Significantly higher levels of apoptotic activity were seen at day 24. Apoptotic osteoclasts also peaked at day 24. Apoptotic cell numbers in the slow and moderate groups most closely followed the pattern of the sham in which the apoptosis activity peaked at days 10 or 24. However, those in the rapid group showed delayed peaks at days 24 or 38. CONCLUSIONS: Chalmers Street, Surry Hill, NSW 2010, Australia. gshe6437@mail.usyd.edu.au The transition from fibrous to osseous regenerate during mandibular distraction osteogenesis is accompanied by an increase in cell clearance via apoptosis. A slow to moderate distraction rate allows for the most typical pattern of bone healing while a rapid rate prolongs the healing process.

Animals↗

Zeolitisation of diatoms.

The development of low cost hierarchical porous materials based upon the zeolitisation of diatomaceous earth for fluid waste benification is described. Two preparative approaches invole: first, using the diatom as a support for zeolite nanocrystals; second, direct pseudomorphic transformation of the diatom into a zeolite. These hierarchical porous materials are potentially useful for important industrial processes in ion-exchange, catalysis and waste benefication.

Crystallization↗

A major lung cancer susceptibility locus maps to chromosome 6q23-25.

Lung cancer is a major cause of death in the United States and other countries. The risk of lung cancer is greatly increased by cigarette smoking and by certain occupational exposures, but familial factors also clearly play a major role. To identify susceptibility genes for familial lung cancer, we conducted a genomewide linkage analysis of 52 extended pedigrees ascertained through probands with lung cancer who had several first-degree relatives with the same disease. Multipoint linkage analysis, under a simple autosomal dominant model, of all 52 families with three or more individuals affected by lung, throat, or laryngeal cancer, yielded a maximum heterogeneity LOD score (HLOD) of 2.79 at 155 cM on chromosome 6q (marker D6S2436). A subset of 38 pedigrees with four or more affected individuals yielded a multipoint HLOD of 3.47 at 155 cM. Analysis of a further subset of 23 multigenerational pedigrees with five or more affected individuals yielded a multipoint HLOD score of 4.26 at the same position. The 14 families with only three affected relatives yielded negative LOD scores in this region. A predivided samples test for heterogeneity comparing the LOD scores from the 23 multigenerational families with those from the remaining families was significant (P=.007). The 1-HLOD multipoint support interval from the multigenerational families extends from C6S1848 at 146 cM to 164 cM near D6S1035, overlapping a genomic region that is deleted in sporadic lung cancers as well as numerous other cancer types. Parametric linkage and variance-components analysis that incorporated effects of age and personal smoking also supported linkage in this region, but with somewhat diminished support. These results localize a major susceptibility locus influencing lung cancer risk to 6q23-25.

Chromosome Mapping↗

Macro-cellular silica foams: synthesis during the natural creaming process of an oil-in-water emulsion.

The room-temperature synthesis of a macro-mesoporous silica material during the natural creaming process of an oil-in-water emulsion is reported. The material has 3-dimensional interconnected macropores with a strut-like structure similar to meso-cellular silica foams with mesoporous walls of worm-hole structure. The material has very high surface area (approximately 800 m2 g(-1)) with narrow mesopore size distribution.

Journal Article↗

Wildtype Kras2 can inhibit lung carcinogenesis in mice.

Although the ras genes have long been established as proto-oncogenes, the dominant role of activated ras in cell transformation has been questioned. Previous studies have shown frequent loss of the wildtype Kras2 allele in both mouse and human lung adenocarcinomas. To address the possible tumor suppressor role of wildtype Kras2 in lung tumorigenesis, we have carried out a lung tumor bioassay in heterozygous Kras2-deficient mice. Mice with a heterozygous Kras2 deficiency were highly susceptible to the chemical induction of lung tumors when compared to wildtype mice. Activating Kras2 mutations were detected in all chemically induced lung tumors obtained from both wildtype and heterozygous Kras2-deficient mice. Furthermore, wildtype Kras2 inhibited colony formation and tumor development by transformed NIH/3T3 cells and a mouse lung tumor cell line containing an activated Kras2 allele. Allelic loss of wildtype Kras2 was found in 67% to 100% of chemically induced mouse lung adenocarcinomas that harbor a mutant Kras2 allele. Finally, an inverse correlation between the level of wildtype Kras2 expression and extracellular signal-regulated kinase (ERK) activity was observed in these cells. These data strongly suggest that wildtype Kras2 has tumor suppressor activity and is frequently lost during lung tumor progression.

Animals↗

Adductor insertion avulsion syndrome (thigh splints): spectrum of MR imaging features.

OBJECTIVE: "Thigh splints," also known as the adductor insertion avulsion syndrome, is a painful condition affecting the proximal to mid femur at the insertion of the adductor muscles of the thigh. Scintigraphic findings in this syndrome have been described; we report a spectrum of MR imaging abnormalities involving this portion of the femur in a group of patients presenting with hip, groin, or thigh pain. CONCLUSION: Symptoms of vague hip, groin, or thigh pain may be associated with stress-related changes in the proximal to mid femoral shaft (thigh splints). When interpreting MR imaging studies of the pelvis in patients presenting with these symptoms, careful attention should be directed to this portion of the femur. This is especially important because the findings may be subtle, and this region is often at the distal edge of most MR imaging studies of the pelvis and hip.

Accidents, Occupational↗

A germ-line p53 mutation accelerates pulmonary tumorigenesis: p53-independent efficacy of chemopreventive agents green tea or dexamethasone/myo-inositol and chemotherapeutic agents taxol or adriamycin.

Recent evidence indicates that individuals with a p53 germ-line mutation (Li-Fraumeni syndrome) have a 50% risk of developing lung cancer by age 60. In this study, p53 heterozygous knockout mice and p53 transgenic mice carrying a dominant negative mutant were crossed with the A/J mouse, which is highly susceptible to lung tumor induction, to investigate whether a p53 germ-line mutation is a predisposing gene for carcinogen-induced pulmonary adenomas in mice. The number of lung tumors was not significantly increased in (TSG-p53 x A/J)F1 p53 heterozygous knockout mice as compared with that in (TSG-p53 x A/J)F1 wt mice 16 weeks after exposure to N-nitrosomethylurea (MNU). In contrast, an average of 22 lung tumors were observed in (UL53-3 x A/J)F1 mice carrying a mutant p53 transgene (135Valp53) compared with an average of 7 lung tumors seen in (UL53-3 x A/J)F1 wt mice after treatment with N-nitrosomethylurea. Similar enhancement of lung tumor multiplicity (approximately 3-fold) was seen when mutant versus wt mice were treated with the tobacco-related carcinogens benzo[a]pyrene or 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone. These results suggest that the mutant p53 transgene may have a dominant negative effect on the wt p53. The potential usefulness of this new mouse model in lung cancer chemoprevention and chemotherapy was examined. The chemopreventive efficacy of the green tea or a combination of dietary dexamethasone and myoinositol and the chemotherapeutic efficacy of Taxol or Adriamycin was examined in wt mice or mice with a mutation in the p53 gene. Mice treated with dexamethasone/myo-inositol and green tea displayed an average of 70 and 50% inhibition of lung tumors, respectively, regardless of p53 status. Similarly, when mice bearing established lung adenomas were treated with Taxol or Adriamycin, a decrease in tumor volume of approximately 70% was observed independent of p53 mutation status. Thus, the (UL53-3 x A/J)F1 p53 transgenic mouse seems to be an excellent model for human carriers of p53 germ-line mutations (Li-Fraumeni syndrome). Furthermore, the lung adenomas generated in this model possess mutations in both the K-ras proto-oncogene and the p53 tumor suppressor gene. This model should prove directly useful for chemoprevention and chemotherapy studies.

Alleles↗

Magnetic resonance imaging of denervated muscle: comparison to electromyography.

The purpose of the study is to further assess the usefulness of short TI (time to inversion) recovery (STIR) magnetic resonance imaging (MRI) in detecting denervation of skeletal muscle compared to needle electromyography (EMG). Ninety subjects with clinical evidence of peripheral nerve injury or radiculopathy underwent STIR MRI and EMG of the affected limb. In 74 (82%) of these subjects, a positive correlation was found between STIR MRI and EMG (P < 0.009). STIR MRI has a relative sensitivity of 84% and specificity of 100% for detecting denervation. A subset of 28 subjects underwent quantitative assessments of signal intensity ratio (SIR) from the STIR MRI. The rank order correlation coefficient between the SIR and abnormal spontaneous activity on EMG was 0.70 (P < 0.001). Increased signal intensity on STIR MRI corresponds closely with spontaneous activity on EMG in denervated muscle. Although less sensitive than EMG in detecting muscle denervation, STIR MRI may be a useful adjunctive diagnostic tool in this setting.

Adult↗

Safety and efficacy of mangafodipir trisodium (MnDPDP) injection for hepatic MRI in adults: results of the U.S. multicenter phase III clinical trials (safety).

The short-term safety of mangafodipir trisodium (MnDPDP) injection was studied in 546 adults with known or suspected focal liver lesions. An initial contrast-enhanced computed tomography examination was followed by unenhanced magnetic resonance imaging (MRI), injection of MnDPDP (5 micromol/kg), and enhanced MRI. Adverse events were reported for 23% of the patients; most were mild to moderate in intensity, did not require treatment, and were not drug related. The most commonly reported adverse events were nausea (7%) and headache (4%). The incidence of serious adverse events was low (nine events in six patients) and not drug related. Injection-associated discomfort was reported for 69% of the patients, and the most commonly reported discomforts included heat (49%) and flushing (33%). Changes in laboratory values and vital signs were generally transient, were not clinically significant, and did not require treatment. There were no clinically significant short-term risks from exposure to MnDPDP.

Abdominal Pain↗

Efficacy and safety of mangafodipir trisodium (MnDPDP) injection for hepatic MRI in adults: results of the U.S. Multicenter phase III clinical trials. Efficacy of early imaging.

The efficacy of contrast-enhanced magnetic resonance imaging (MRI) for detecting and characterizing, or excluding, hepatic masses was assessed in 404 patients, following the intravenous administration of mangafodipir trisodium (MnDPDP) injection, a hepatic MRI contrast agent. An initial contrast-enhanced computed tomography (CT) examination was followed by unenhanced MRI, injection of MnDPDP (5 micromol/kg IV), and enhanced MRI at 15 minutes post injection. Agreement of the radiologic diagnoses with the patients' final diagnoses was higher for enhanced MRI and for the combined unenhanced and enhanced MRI evaluations than for unenhanced MRI alone or enhanced CT using the clinical diagnosis as the gold standard. Mangafodipir-enhanced MRI uniquely provided additional diagnostic information in 48% of the patients, and patient management was consequently altered in 6% of the patients. MnDPDP-enhanced MRI was comparable or superior to unenhanced MRI and enhanced CT for the detection, classification, and diagnosis of focal liver lesions in patients with known or suspected focal liver disease.

Adult↗

Association of posterior tibial tendon abnormalities with abnormal signal intensity in the sinus tarsi on MR imaging.

OBJECTIVE: To evaluate the association of abnormal signal intensity within the sinus tarsi with abnormalities of the posterior tibial tendon (PTT) on MR imaging. DESIGN AND PATIENTS: Sinus tarsi abnormalities were identified on 30 ankle MR examinations in 29 patients. The PTT and anterior talofibular ligament were retrospectively analyzed for abnormalities in these same patients. RESULTS AND CONCLUSIONS: Tears of the anterior talofibular ligament were found in 13 of 30 (43%) ankles. PTT abnormalities (complete tear, partial tear or dislocation) were seen in 14 of 30 (47%) studies, and were distributed relatively equally between those patients with and without lateral ligament tears. Our results provide evidence of an association between abnormalities of the PTT and the sinus tarsi. The finding of abnormal signal intensity within the sinus tarsi on MR imaging should alert the radiologist to potential abnormalities of the PTT.

Adolescent↗

Pedicle marrow signal intensity changes in the lumbar spine: a manifestation of facet degenerative joint disease.

OBJECTIVE: Signal intensity changes in lumbar pedicles, similar to those described in vertebral body endplates adjacent to degenerated discs, have been described as an ancillary sign of spondylolysis on MRI. The purpose of this study was to determine whether pedicle marrow signal intensity changes also occur in association with facet degenerative joint disease. DESIGN: Eighty-nine lumbar spine MRI examinations without spondylolysis were reviewed for marrow signal intensity changes in pedicles and vertebral bodies as well as for facet degenerative joint disease. RESULTS: Five percent (46/890) of lumbar pedicles in 23 patients had marrow signal intensity changes. Ninety-one percent (42/46) of the abnormal pedicles had adjacent degenerative joint disease of the facets, while only 21% (189/890) of normal pedicles had adjacent facet degenerative joint disease (p<0.001). Eighty-nine percent (41/46) of the pedicles with marrow signal intensity changes had adjacent degenerative disc disease. CONCLUSIONS: Pedicle marrow signal intensity changes are not a specific sign of spondylolysis; they are commonly seen with adjacent facet degenerative joint disease in the absence of spondylolysis. Pedicle marrow signal intensity changes are probably a response to abnormal stresses related to abnormal motion or loading caused by the degenerative changes in the spinal segment.

Adult↗

Fluoroscopy-guided sacroiliac joint injections.

The authors performed fluoroscopy-guided sacroiliac (SI) joint injections. With the patient prone and the x-ray tube perpendicular to the fluoroscopic table, the skin was marked over the distal 1 cm of the SI joint. With the tube angled 20 degrees - 25 degrees cephalad, a 22-gauge needle was inserted at the skin mark and advanced perpendicular to the fluoroscopic table toward the posterior joint. Nonionic contrast material was injected to confirm the intraarticular position of the needle. Of 31 SI joint injections, 30 (97%) were intraarticular. Mean procedure time was 108 seconds. This technique is safe, rapid, and reproducible.

Adult↗

Bone contusions of the posterior lip of the medial tibial plateau (contrecoup injury) and associated internal derangements of the knee at MR imaging.

PURPOSE: To determine if there are any predictable patterns of internal derangement associated with a bone contusion of the posterior lip of the medial tibial plateau at magnetic resonance (MR) imaging and to offer a biomechanical explanation for the findings. MATERIALS AND METHODS: A retrospective review of 215 consecutive MR examinations for knee trauma was conducted to identify contusions of the posterior lip of the medial tibial plateau. Any additional contusions and internal derangements were documented in the cases with these contusions. Medical charts and arthroscopic results, when available, were reviewed for mechanisms of injury. RESULTS: The specific medial tibial contusion was demonstrated in 25 of 215 (12%) knee MR examinations. Associated anterior cruciate ligament (ACL) tears were found in 25 of the 25 (100%) examinations. Injury to the meniscocapsular junction (14 of 25) or a peripheral tear of the posterior horn of the medial meniscus (10 of 25) occurred in a combined 96% of the cases. Lateral compartment contusions were noted in 24 (96%) cases. Pivot, twisting, or valgus forces were reported mechanisms of injury. CONCLUSION: Contusions involving the posterior lip of the medial tibial plateau may result from a contrecoup impaction injury directly following an ACL tear, as the knee reduces. These contusions are almost always associated with a far peripheral meniscal tear or with a meniscocapsular junction injury affecting the posterior horn of the medial meniscus.

Adolescent↗

Compartmental anatomy: relevance to staging and biopsy of musculoskeletal tumors.

A thorough understanding of compartmental anatomy is essential for accurate staging of a suspected musculoskeletal tumor with MR imaging and for avoiding potentially devastating biopsy-related complications. Imaging-guided, percutaneous needle biopsy is a safe and cost-effective technique but requires careful planning in conjunction with the surgeon who will perform the definitive surgery because it constitutes the final step in the staging process and the first step in surgical therapy.

Biopsy, Needle↗

Spinal sonography and magnetic resonance imaging in patients with repaired myelomeningocele: comparison of modalities.

The goals of this study were to evaluate the feasibility of using ultrasonography of the spine in the follow-up evaluation of patients with repaired myelomeningocele at birth and to compare sonography with the accepted modality of magnetic resonance imaging. Over a period of 4 years we performed 165 sonographic studies in 101 patients; 107 sonographic studies had MR imaging results for comparison. We collected our data prospectively. The quality of the sonograms was good in 110 of 129 studies, acceptable in 17 of 129, and poor in two of 129. The sonographic examinations failed in 33 of 165 studies (20%). Concordant information was obtained between ultrasonography and magnetic resonance imaging in the following percentage of studies: level of the distal end of the cord in 82%, position of the cord in the canal in 59%, presence of hydromyelia in 63%, cord duplication in 96%, adhesions in 16%, intradural mass in 37%, cord measurements in 85%, and dural sac measurements in 83%. At the lumbosacral level, we saw no cord pulsation in 57% of the studies in patients with cord adhesions and in 20% of those without adhesions. At the lower thoracic level, we saw no pulsation in 35% of the studies in patients with cord adhesions and in 7% of those without adhesions. Postoperative studies of cord release surgery in eight patients showed varied findings. We conclude that in those patients who have a spinal defect or interlaminar space allowing proper visualization of the lumbosacral spinal canal, ultrasound can provide fairly similar information to that obtained with magnetic resonance imaging of that area with no need for sedation and at a reduced cost. Ultrasonography seems more sensitive than magnetic resonance imaging in the detection of cord adhesions, which is particularly relevant in the diagnosis of tethering.

Adolescent↗

Effect of promoter and intron 2 polymorphisms on murine lung K-ras gene expression.

Differences in tumor formation among inbred mouse strains with high (A/J) and low (C3H) susceptibility for lung cancer have been linked to a repetitive element within the second intron of the K-ras gene. The purpose of this investigation was to determine whether differences within the K-ras gene promoter region or the intron 2 polymorphism affect K-ras gene expression in lung tumors and target alveolar type II cells isolated from A/J and C3H mice. Ribonuclease protection assays were performed using RNA isolated from 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK)-induced lung tumors from each mouse strain and alveolar type II cells isolated from A/J and C3H mice. An 838 bp fragment of the murine K-ras gene promoter region was amplified by PCR, cloned and sequenced from both mouse strains. Promoter regions from both mouse strains were inserted into a luciferase reporter gene vector, with and without the second intron polymorphism, and transfected into sensitive, intermediate and resistant lung tumor cell lines. No significant differences in K-ras gene promoter activity was found between the two strains using these specific reporter gene constructs. Consistent with these results, levels of K-ras expression did not differ between alveolar type II cells, whole lung or tumors induced by NNK in A/J or C3H mice. Moreover, in lung tumor cell lines derived from mice with differing susceptibility for lung cancer, K-ras expression did not correlate with the growth rate of tumors induced in nude mice from these cell lines. These results indicate that factors involved in modulating the rapid clonal expansion of the mutated K-ras allele from A/J mice are not directly linked to expression of this gene. Other genetic changes or losses in conjunction with hypothesized modifier loci, such as the Par1 locus, must play a significant role in establishing the phenotypic strain differences for lung tumor formation.

3T3 Cells↗

Odontogenic keratocyst of the mandible: an unusual cause of a parotid mass.

Odontogenic keratocyst (OKC) of the mandible refers to an uncommon benign lesion of the jaw that originates from dental primordia. Clinically an OKC is characterized by aggressive, local growth. The likelihood of local recurrence following initial treatment is high. The diagnosis of a mandibular OKC may be suspected based on physical examination and plain film radiographic findings. However, histopathological confirmation is required to make the diagnosis with certainty. Complete surgical removal is the preferred treatment. In the current report, we describe the management of a patient with a large mandibular OKC that produced an apparent mass in the parotid gland. In addition, the diagnosis, management, and long-term results of treatment of mandibular OKCs are reviewed.

Adult↗