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Magnetization transfer contrast on gradient echo MR imaging of the temporomandibular joint.

Thirty-nine temporomandibular joints (TMJ) from 20 patients with suspected internal derangements were imaged by a 1.5 T MR imager. The on-resonance binomial magnetization transfer contrast (MTC) pulse was applied to gradient echo images with a dual receiver coil (9 s/section). With the use of an opening device, a series of sequential images were obtained at increments of mouth opening and closing. The tissue signal intensities with (Ms) and without (Mo) MTC were measured and subjective image analysis was performed. Compared with the standard images, MTC technique provided selective signal suppression of disks. The average of Ms/Mo ratio of the disks (0.56) was lower than that of the retrodiskal pad (0.79) and of the effusion (0.89). With MTC technique, fluid conspicuity was superior to standard image. However, no significant superiority was found in disk definition subjectivity.

Adolescent↗

Ret gene silencing is associated with Raf-1-induced medullary thyroid carcinoma cell differentiation.

Mutations in the ret proto-oncogene constitute the germ line defect in patients with inherited forms of medullary thyroid carcinoma (MTC) and are also present in tumor DNA from a subset of patients with sporadic forms of MTC. We now show that the TT cell line of human MTC can be induced within 48 h to resemble mature C cell differentiation by activation of the raf-1 signal transduction pathway. Within this time period, expression of both the mutant and wild-type ret gene alleles, present in these cells, are silenced at the mRNA and protein levels. This definition of a signal transduction pathway that can regulate ret gene expression, and of the position of ret gene expression in endocrine differentiation, should help clarify the precise role of this gene in normal neuroendocrine development and in the formation of MTC.

Calcitonin↗

Hereditary medullary thyroid carcinoma.

The most well-known form of familial thyroid cancer is hereditary medullary thyroid carcinoma (MTC). This neoplasm is often associated with pheochromocytoma and hyperparathyroidism, a combination known as the multiple endocrine neoplasia syndrome type 2A (MEN 2A). The rare association of MTC and pheochromocytoma with multiple mucosal neuromas is called multiple endocrine neoplasia syndrome type 2B (MEN 2B). Of those who present with clinical signs and symptoms, almost half die of the disease and others may suffer significant morbidity. By contrast, early diagnosis by screening of family members allows for treatment with thyroidectomy and/or adrenalectomy, which are often curative. Measurement of serum calcitonin before and after stimulation with pentagastrin and/or calcium is mandatory for the diagnosis of MTC. Testing of first-degree relatives of patients with MTC should be started by the age of 3 to 5 years. In families with the MEN 2B syndrome, screening should be started during the first year after birth and include a search for the characteristic phenotype. The mapping of the MEN 2A gene to the centromeric region of chromosome 10 has provided an alternative approach to the diagnosis of MEN 2A gene carriers. Genetic screening using linked markers can now be done with an accuracy of 95% in informative families. Surgery is the treatment of choice for cases of MEN 2, but the extent of surgical resection of the involved endocrine organs is still a subject of debate.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

Ligand mediated activation of ectopic EGF receptor promotes matrix protein adhesion and lung colonization of rat mammary adenocarcinoma cells.

Increased expression of EGF receptor (EGFR) in metastases of human mammary carcinoma as compared to cells of the primary cancer suggests a contribution of EGFR to mammary carcinoma metastasis. To test for a positive causative link, we investigated 13762NF rat mammary adenocarcinoma cloned tumor cell lines of high (MTLn3) or low (MTC) metastatic potential. While MTC cells expressed barely detectable amounts of EGFR, MTLn3 cells expressed readily detectable levels of functional receptors. A full length cDNA of the human EGFR (HER) was introduced by infection with a retroviral vector into MTC cells. Expression of HER was stable and receptors were functional with respect to surface expression, ligand binding and EGF-stimulated phosphorylation. Independent clones of the transfectants were isolated and characterized. Ligand stimulation of MTC HER cells and derived clones led to enhanced adhesion of cells to extracellular matrix proteins. Implantation of cells intravenously into female nu/nu mice revealed ligand-dependent enhancement of lung colonizing potential of EGFR-expressing cells.

Adenocarcinoma↗

[Medullary carcinoma of the thyroid: a case of multiple endocrine neoplasia type 2A].

Medullary thyroid carcinoma (MTC) is a neoplasm derived from thyroid C-cells. It can appear under different variants; in the 20-30% of the cases, it's a familial variant. Nevertheless, the MTC appearing in MEN 2-A has a better prognosis compared to MEN 2-B. Usually, the diagnosis of MEN 2-A is done at the age of 20, and frequently (in the 50% of the cases) these patients develop, in a second time, adrenal hyperplasia and/or pheochromocytoma. The case we are talking about, concerns a patient of 49 years old, who came to our observation with a history of bilateral adrenalectomy for pheochromocytoma. What attracted our attention was the presence, in his family, of a brother, who died from pheochromocytoma, and the mother, died for a MTC. During the admit in our section, the patient has undergone a screening for the thyroid function, also if there wasn't a sign or symptom of interest of the gland. It has been possible to single out some nodular formations that, together with the high value of the calcitonin found, allowed the diagnosis of MTC. It has been very important to make diagnosis of MEN 2-A because we can introduce the patient and his family to a program of screening to precociously single out the presence of the typical signs of this pathology. In MEN 2-A a precocious diagnosis allows to sensibly improve the prognosis.

Adrenal Gland Neoplasms↗

Peritoneal resting is beneficial in peritoneal hyperpermeability and ultrafiltration failure.

Ultrafiltration failure (UFF) is one of the most frequent causes of continuous ambulatory peritoneal dialysis (CAPD) dropout and is a common consequence of peritoneal hyperpermeability secondary to inappropriate regeneration of mesothelial cells. In this paper we present the results of 25 peritoneal resting periods of 4 weeks in 16 patients who showed UFF. The mean duration of CAPD was 44 +/- 22 months. All patients had been free of peritonitis for at least 3 months when included in the peritoneal resting trial. UFF was always defined as a long-lasting decrease of UF capacity such that dry weight could no longer be achieved by CAPD. The former incidence of peritonitis was 3.9 +/- 2.3 episodes. Results compared to the preresting data: urea MTC (mass transfer coefficient) decreased from 24.9 +/- 6.8 to 21.0 +/- 6.1 (p < 0.05), creatinine MTC from 16.5 +/- 6.0 to 13.8 +/- 4.0 (p < 0.05), and UF increased from 493.8 +/- 278.0 to 881.3 +/- 388.1 (p < 0.001). The response in terms of UF in patients with low permeability ultrafiltration (creat MTC less than 13) was heterogeneous and lower than in patients with criteria of hyperpermeability (greater than 13): 720 +/- 396 to 1150 +/- 533 (NS) versus 491 +/- 310 to 808 +/- 205, respectively. Simultaneously, creatinine MTC did not change in the former group (10.2), while hyperpermeability patients showed a remarkable decrease (19 +/- 5 to 15 +/- 2, p < 0.05). In conclusion, peritoneal resting is a useful tool in the management of ultrafiltration failure in CAPD patients, primarily in those with peritoneal hyperpermeability.

Adult↗

Detection of the chromosomal translocation t(11;14) by polymerase chain reaction in mantle cell lymphomas.

The t(11;14)(q13;q32) and its molecular counterpart, BCL1 rearrangement, are consistent features of mantle cell lymphoma (MCL). Rearrangement is thought to deregulate the nearby CCND1 (BCL1/PRAD1) proto-oncogene, a member of the cyclin G1 gene family, and thereby to contribute to tumorigenesis. We and others have previously shown that the BCL1 locus is rearranged in 55% to 60% of MCL patients and that, on chromosome 11, more than 80% of the breakpoints are localized within a 1-kbp DNA segment known as the major translocation cluster (MTC). We have determined the nucleotide sequence for a portion of the MTC region, and constructed chromosome 11-specific oligonucleotides that were in conjunction with a consensus immunoglobulin (Ig) heavy chain joining region (JH) primer used to perform the polymerase chain reaction (PCR) to amplify t(11;14) chromosomal junctional sequences in DNA from 16 MCL patients with breakpoints in the MTC region. 15 of the 16 breakpoints that occurred at the MTC region were amenable to PCR detection. The sizes of the amplified bands, the existence or not of a Sac I site in the PCR products, and nucleotide sequencing of the amplified DNA from four patients showed that the breakpoints share a remarkable tendency to tightly cluster within 300 bp on chromosome 11, some of them occurring at the same nucleotide. On chromosome 14, the breakpoints were localized within the Ig JH. Our findings indicate that a BCL1 rearrangement can be detected using this approach in roughly one half of the MCL patients. This has implications for both the diagnosis and the clinical management of MCL.

Base Sequence↗

Exercise-induced changes in magnetization transfer contrast of muscles.

Magnetization transfer contrast (MTC) technique provides a new type of contrast in MR imaging. The MTC method is based on the interaction between the spins of free protons and those with restricted motion. Exercise-induced changes in signal intensity and MTC were measured in the forearm muscles of 10 volunteers at 0.1 T. There was 26% increase in signal intensity of active flexor muscles after exercise when imaged with ordinary gradient echo sequence. Despite this marked intensity increase, the postexercise values of MTC did not differ from the preexercise ones.

Adult↗

[Role of non surgical therapeutics in the treatment of patients with medullary cancer of the thyroid].

Medullary thyroid carcinoma (MTC) is a rare endocrine tumour secreting the calcitonin (CT), its main tumoral marker, occuring as a sporadic or a familial disease. These diseases are associated with a 5-years prognostic from less than 50 to 100%, depending on the tumoral stage at the diagnosis time. The surgical management is demonstrated to be able to obtain a biological recovery in some patients. The other therapeutic means have no or poorly effects on the MTC evolution. Partial and transient responses are described for 15 to 20% of the patients with the use of multiple trials of chemotherapy. The external radiotherapy may have some little effects on local tumoral involvement without influence on the survival rates as compared to the surgery alone. The hormonal therapy with somatostatin analogues and the metabolic scintigraphies using MIBG, somatostatine analogues, radio-active iodine have no therapeutic effects demonstrated. The development of targeted therapy by the use of specific monoclonal antibodies, such as anti-CEA radiolabeled antibodies, is to be evaluated. The prognostic factors, as defined in large series of patients studied, does not necessary reflect the aggressiveness of the tumour. Thus, the therapeutic approach of MTC patients must take into consideration that the biologic activity of the disease does not implicate an aggressive disease. The evaluation of CT and CEA circulating levels remains of prognostic value and a useful tool for the practicians for the management of MTC patients.

Carcinoma, Medullary↗

[Therapeutic concepts and long-term outcome in thyroid gland carcinoma].

UNLABELLED: Data of all (n = 131) patients carrying thyroid carcinoma and operated on between January 1st, 1979, and September 30th, 1994 in our center were analyzed retrospectively. Patient's files were reviewed concerning histological diagnosis, TNM-classification, operation procedure and complications. Follow-up data were obtained in all cases from local cancer registry as well as from personal records. Statistical analysis was performed using PCS-software (TopSoft, Hannover). RESULTS: Follow-up data from 3-191 months (mean: 50.4 mo.) postoperatively were obtained from 72 patients with papillary thyroid carcinoma (PTC) including 27 cases of occult papillary thyroid carcinoma (oPTC, < 1.5 cm), 30 patients with follicular thyroid carcinoma (FTC), 10 patients with medullary thyroid carcinoma (MTC) and 19 patients carrying anaplastic tumor (ATC). In case of oPTC 51.8% of the patients received total thyroidectomy or lobectomy and contralateral near-total resection. In PTC, both procedures were performed in 68.9% combined with neck dissection in 31%. Radioiodine treatment was given to 59.7%. Treatment of FTC consisted mainly of thyroidectomy (60%) followed by radioiodine therapy (76.7%). In patients with MTC preference was given to thyroidectomy and bilateral neck dissection, more recently completed by mediastinal lymph node dissection. 90% of the patients with ATC were inoperable. No patient received chemotherapy pre- or postoperatively, respectively. Five-and 10-year survival of patients with PTC (oPTC) was 91.6% (93.7%) and 80.2% (93.7%), respectively. Corresponding data for FTC were 70.5% and 50.3%, and 71.6 % and 47.9%, for MTC respectively. ATC showed 10.3% 3-year survival. CONCLUSIONS: Despite therapy of choice was not performed in all patients, our long-term results generally confirm those reported by others. Despite of this, limited radical therapy should be restricted to oPTC in our opinion. In case of MTC presenting rising or elevated tumor markers postoperatively, early mediastinal lymph node dissection should be considered.

Adenocarcinoma, Follicular↗

Quantitation of galactosemic cataracts in dogs using magnetization transfer contrast-enhanced magnetic resonance imaging.

PURPOSE: Magnetic resonance imaging (MRI) is becoming increasingly important for the diagnosis and characterization of ocular pathologies. A drawback to this technique is that image contrast between different regions of tissue can be obscured because of the similarity of their nuclear magnetic resonance relaxation parameters. This problem is addressed by magnetization transfer contrast (MTC) enhancement, a MRI technique that generates high-contrast images based on characteristic tissue differences resulting from the interaction of water and macromolecules. The purpose of this study was to investigate the feasibility of using MTC-enhanced imaging to monitor quantitatively the lens changes associated with sugar cataract formation in galactose-fed dogs. METHODS: Male beagles fed a diet containing 30% galactose were periodically examined by MRI for changes in tissue character. Each examination included a gradient recalled echo image (M0), an MTC-enhanced gradient recalled echo image (Ms), a T1 image determined from a one-shot T1 imaging sequence, and a T1-weighted image taken from the raw T1 data. Average values were obtained for several regions of interest and tabulated. These were correlated with cataractous stages visually observed by slit lamp biomicroscopy and retroillumination photography. RESULTS: Enhanced image details of the lens and anterior segment that documented osmotic changes from initial cortical vacuole formation to cortical and nuclear changes associated with advanced sugar cataracts were characterized from measurements of parameters obtained from M0, Ms, T1-weighted, and T1 images. Changes in the cross-sectional areas of lenses during sugar cataract formation also were documented. The magnetic resonance images showed visible changes from the onset of cortical vacuole formation. Region of interest (ROI) analysis of the images showed tissue changes occurring throughout the cataract progression. CONCLUSIONS: The MTC-enhanced MRI technique is well suited to detecting lens changes associated with cataractogenesis. All but the earliest changes were readily apparent from the images with no further analysis. Graphic ROI analysis was able to detect regional changes associated the cataract progression for all degrees of severity. Furthermore, the images demonstrated changes in size and shape that would not be detectable by visual inspection.

Animals↗

Peritoneal functional changes induced by dialysate containing bicarbonate instead of lactate.

Lactate (L)-containing dialysate has a low pH, responsible for its poor biocompatibility. Dial-ysate-containing bicarbonate (B) with a physiological pH is available. We compare the peritoneal functional effects of these two solutions. Eight patients were studied two weeks apart using two consecutive peritoneal kinetic tests to determine convective and diffusive mass transfer coefficient (MTC) capacities for different solutes. Both L and B solutions were identical, except for pH and buffer content. Peritoneal equilibration values at four-hour dwell time were similar for all solutes, except for urea (B: 0.91 +/- 0.05 vs L: 0.87 +/- 0.06, p < 0.05). Peritoneal MTC (B vs L) values for urea (19.6 +/- 6.6 vs 18.2 +/- 4.5), creatinine (8.8 +/- 4.8 vs 7.8 +/- 3.5), phosphate (7.7 +/- 4.6 vs 6.0 +/- 2.2), and potassium (13.3 +/- 5.6 vs 11.7 +/- 5.0) were slightly higher for B (NS). Glucose-MTC was slightly lower for B (6.2 +/- 3.3 vs 7.5 +/- 3.2, NS). Ultrafiltration (UF) was lower for B (drained volume: 2120 +/- 204 vs 2443 +/- 285 mL after 4 hr, p < 0.05). Higher transperitoneal calcium [11 +/- 22 L vs -3.1 +/- 11.0 (positive balance) mg, p < 0.05] and sodium (48 +/- 30 L vs 13 +/- 20 mEq) removal were evident. With L, the loss of 43.0 +/- 6.3 mEq of bicarbonate appeared. The linear regression analysis of MTC values showed higher r coefficients for the bicarbonate solution. These results suggest that bicarbonate dial-ysate improves the diffusion capacity of the peritoneum with respect to lactate.

Adult↗

The genetic aspects of medullary thyroid carcinoma: recognition and management.

OBJECTIVE: To examine the extent to which clinicians recognize the genetic aspects of medullary thyroid carcinoma (MTC) and undertake appropriate investigation and management of patients and their at-risk relatives. DESIGN: retrospective review of case notes. SUBJECTS: all individuals aged 70 or under with a 'raised' calcitonin level during 1990-91. Information was obtained from a questionnaire. Forty-one cases were diagnosed in 1990-91: 10 (24%) multiple endocrine neoplasia (MEN) type 2A, four (10%) MEN type 2B, and 27 (66%) sporadic MTC. Between 1980 and 1989, 87 cases were diagnosed: 20 (23%) MEN type 2A, six (7%) MEN type 2B, four (5%) familial MTC, 53 (61%) sporadic MTC, and four (5%) of uncertain diagnosis. MAIN RESULTS: a pedigree was drawn in only 7/37 (19%) and 26/83 (31%) of cases diagnosed in 1990-91 and 1980-89, respectively, where a family history had been taken. All known hereditary cases were investigated for phaeochromocytoma. In 9/27 (33%) and 14/52 (27%) apparently sporadic cases diagnosed in the two periods respectively, no investigations were performed. Genetic counselling was offered to all known hereditary cases except one, but no offer was made in 11/25 (44%) and 16/52 (31%) apparently sporadic cases. There was no record that screening should be offered to the family in 15/35 (43%) and 25/68 (37%) cases identified from clinical investigations; in the majority it could be argued that it should have been. CONCLUSIONS: this study has shown that clinicians do not always have the necessary training or experience to undertake family studies and screening in this rare disorder.

Adolescent↗

[Effect of collagen on magnetization transfer contrast assessed in cultured cartilage].

We investigated the effect of collagen on magnetization transfer contrast (MTC) in cultured cartilage. In our culture system, only collagen synthesis was increased by the addition of vitamin C, while proteoglycan synthesis and the number of chondrocytes were unaffected. The MTC effect was assessed by using an off-resonance RF pulse (0.3 KHz off-resonance, sinc wave of 18 msec, maximum amplitude 4.61 x 10(-4)T) on a GRASS sequence. The cartilage cultured with vitamin C showed a higher MTC effect than that cultured without vitamin C. The major role of collagen on MTC was confirmed in living cartilage tissue.

Animals↗

[Long-term course of medullary thyroid gland carcinoma].

UNLABELLED: To obtain information on the outcome of medullary thyroid carcinoma (MTC) in the Berne area, a retrospective analysis of the 28 MTCs diagnosed by the Institute of Pathology of the University of Berne in the 25-year period between 1969 and 1994 was done. These 28 MTCs represented 2.4% of all thyroid malignancies diagnosed at the Bernese Institute of Pathology in the 25-year period mentioned above. 25 MTCs were sporadic and 3 associated with a multiple endocrine neoplasia (MEN) syndrome. Follow-up data were available from 27 of the 28 MTC patients. After a follow-up period of between 2 and 275 months 7 of these 27 patients had died form the MTC (among them all 4 patients with T4 tumors) and two were alive with tumor. 18 patients, including all 14 patients with T1 or T2 tumors without lymph node or distant metastases at the time of diagnosis, were alive and without evidence of tumor at the end of the follow-up period. CONCLUSIONS: MTCs are rare malignant tumors and comprise only a small fraction of all thyroid carcinomas in the Berne area. Most MTCs were sporadic, only a small minority was associated with a MEN syndrome. The TNM stage was the most important prognostic factor for patient survival. These data are in accordance with the results of similar MTC surveys done in other areas.

Adult↗

[Neural crest and multiple endocrinopathies].

Multiple endocrine neoplasia type 2 (MEN 2) is a cancer syndrome which comprises three related disorders, MEN type 2A (MEN 2A), type 2B (MEN 2B) and familial medullary thyroid carcinoma (FMTC), MEN 2A is characterized by the association of MTC, a tumour arising from thyroid C-cells, pheochromocytoma and parathyroid hyperplasia. In addition to the thyroid cancer, MEN 2B associates pheochromocytoma, mucosal neuromas, ganglioneuromatosis of the digestive tract and skeletal abnormalities. In FMTC, the MTC is the sole clinical manifestation. MEN 2 is a dominantly inherited neural crest disorder caused by germline mutations of the RET proto-oncogene. The RET gene encodes a receptor tyrosine kinase, which displays a cadherin-like domain and a cysteine rich motif in its extracellular part. Missense mutations at one of five cysteines clustered in the extra-cytoplasmic domain of RET have been identified in the majority of the MEN 2A families and in two-thirds of FMTC. A single point mutation leading to the replacement of a methionine by a threonine within the tyrosine kinase domain has been detected in almost all cases of MEN 2B. We have screened 170 french MEN 2 families and a germline mutations in the RET gene have been identified in 92% of cases. Moreover, we confirmed the significant correlation between the nature, the position of the RET mutations and the clinical phenotype. The accurate identification by DNA testing of individual predisposed to MEN 2 suggests new protocols of treatment. Thyroidectomy as early as 6 years of age in individuals with MEN 2 mutations has been recently advocated by clinicians. We further provide evidence that MEN 2A and MEN 2B mutations convert the RET proto-oncogene in a dominantly-acting transforming gene due to the ligand-independent constitutive activation of the tyrosine kinase. Finally, we have constructed transgenic mice carrying the RET gene carrying a MEN 2A mutation fused to the calcitonin gene related peptide/calcitonin promoter. Animals of three independent transgenic lines developed C-cell hyperplasia and subsequently MTC with a complete penetrance. Taken together, these findings indicate that MEN 2A form of RET is oncogenic in thyroid C-cells, and suggest that these transgenic animals should prove a valuable model for hereditary MTC. Future work should yield insights in the signaling pathways subverted by the RET-MEN 2 proteins.

Animals↗

Meeting lipid needs of infants with allergy and gastrointestinal diseases.

Infant formulas containing medium chain triglycerides (MTC) have been used for the nutritional management of infants with fat malabsorption. The optimal proportion of MTC in the formula remains to be determined. Three infant formulas with varying proportion of MTC in the fat blend were studied in children with cystic fibrosis, cholestasis or persistent diarrhea. The formula containing 48% of the total energy from fat and 55% of the fat component as MTC was found to be the most suitable for the needs of those infants. It leads to an adequate essential fatty acid status and to improved recovery in those conditions.

Dietary Fats↗

Assessment of breast cancer with dynamic gadolinium-enhanced MR imaging combined with magnetization transfer contrast using a newly developed breast surface coil for the supine position.

To assess the value of dynamic gadolinium-enhanced MR imaging combined with magnetization transfer contrast (MTC) of breast cancer by SPGR sequence, 15 patients with breast cancer were imaged in the supine position with the newly developed breast coil in a 1.5 Tesla imager. Dynamic gadolinium-enhanced MR imaging combined with MTC (10 cases) and conventional dynamic gadolinium-enhanced MR imaging (5 cases) were performed after the administration of Gd-DTPA (0.2 ml/kg). Sagittal images were obtained every 22 seconds during the first 264 seconds. Thus, a total of 15 images were obtained in each lesion. The signal intensity ratio (SIR) of lesion to mammary glarid was calculated for each image as follows: (SI lesion/SI mammary gland)/(SI (pre)lesion/SI (pre)mammary gland). Dynamic gadolinium-enhanced MR imaging with MTC always allowed better SIR at 88 seconds than conventional dynamic gadolinium-enhanced MR imaging after bolus injection (p < 0.01). Dynamic gadolinium-enhanced MR imaging with MTC improved detection of the boundary of the lesion and mammary gland.

Adult↗