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PubMedDate not supplied

Carpal tunnel syndrome: assessment by turbo spin echo, spin echo, and magnetization transfer imaging applied in a low-field MR system.

PURPOSE: The purpose of this work was to evaluate patients with carpal tunnel syndrome (CTS) using a low-field extremity MR system (E-MRI: 0.2 T). METHOD: Twenty-two patients with typical findings of CTS and 30 control persons were imaged on an E-MRI. Axial T2-weighted turbo SE (TSE), T1-weighted SE sequences, and 2D GRE magnetization transfer (MTC) sequences were compared. SE and MTC sequences were obtained before and after contrast agent administration (0.1 mmol/kg body wt of Gd-DTPA). Two readers evaluated typical MR findings of CTS independently. RESULTS: Patients with CTS demonstrated palmar bowing of the flexor retinaculum significantly more often. The normal or edematous median nerve was best identified on TSE and MTC scans (kappa = 0.59 and 0.8). The MTC sequences showed perineural enhancement significantly better than respective T1-weighted SE sequences but were rated second in comparison with T2-weighted TSE scans. CONCLUSION: At low-field strength, median nerve edema is best depicted on T2-weighted TSE sequences, whereas MTC sequences are most sensitive to perineural contrast enhancement.

Carpal Tunnel Syndrome↗
PubMed1995

Polymerase chain reaction detection of the t(11;14) translocation involving the bcl-1 major translocation cluster in mantle cell lymphoma.

The utility of polymerase-mediated assays in the detection of the t(11;14) involving the bcl-1 major translocation cluster (bcl-1 MTC) was evaluated by analyzing DNA from 33 patients with mantle cell lymphoma, 14 patients with other non-Hodgkin's lymphomas, and five patients with reactive lymphoid hyperplasia. The polymerase chain reaction (PCR) assay was performed using a consensus immunoglobin heavy-chain joining region primer in conjunction with a chromosome 11 specific oligonucleotide primer flanking the translocation site. The sensitivity and specificity of the assay were confirmed by correlation of the (PCR) assay data with restriction analysis. Rearrangements at the bcl-1 MTC were detected in 13 (39%) of 33 cases of mantle cell lymphoma by PCR and in 13 (48%) of 27 cases by restriction analysis. Amplicons were detectable by PCR in 85% (11 of 13) of the cases shown to be bcl-1 rearranged by restriction analysis. Failure to detect amplification products in DNA samples from non-mantle cell lymphomas and reactive follicular hyperplasia further confirmed the specificity of the assay. Sequential hybridization of the PCR products with oligonucleotide probes 3' to the bcl-1 MTC primer revealed that the breakpoints in the bcl-1 MTC were clustered around an Sst I restriction site over a range of 170 base pairs. The study demonstrates that PCR-mediated assay for the detection of the t(11;14) at the bcl-1 MTC is specific and sensitive and can be used as an adjunct to restriction analysis in routine diagnostics.

Base Sequence↗
PubMed1998

Molecular methods for detecting t(11;14) translocations in mantle-cell lymphomas.

The t(11;14)(q13;q32) and its molecular counterpart, bcl1/JH, are characteristic of mantle-cell lymphomas (MCL). Molecular detection of the translocation is useful in diagnosis and classification, and also shows promise in detecting minimal residual disease. The purpose of this study was to determine the frequency of detecting bcl1/JH by polymerase chain reaction (PCR) compared with Southern blot analysis in cases proven by cytogenetic analysis to harbor t(11;14). Southern blot analysis using two probes targeting the major translocation cluster (MTC) and a third probe targeting the p94 region was performed, along with PCR using two different bcl1 MTC primers, on 18 cases of MCL known to have t(11;14). Southern blot analysis revealed bcl1 rearrangement in 13 of 18 cases (72%), 12 with MTC breakpoints and 1 with a p94 breakpoint. The 2.1-kb MTC probe "b" was superior to the smaller 700-bp probe "a" in detecting these rearrangements. The MTC translocation was identified by PCR in 10 of 12 cases, and both primer sets that were tested performed equally well. This study illustrates the frequency with which molecular methods detect known t(11;14) translocations in MCLs. These results may help clinical laboratory scientists optimize their procedure for detecting bcl1 translocations by molecular methods at initial diagnosis and for purposes of detecting minimal residual disease.

Blotting, Southern↗
PubMed1998

Attenuated metoclopramide-induced vascular hyperreactivity to cold stress in athletic subjects.

We have previously reported a metoclopramide-induced vascular hyperreactivity to the cold pressor test (CPT) in normotensive and hypertensive subjects. The present study was designed to determine whether the state of physical training influences the cardiovascular responses to the CPT in normotensive subjects under metoclopramide (MTC) treatment. In 20 untrained subjects and 32 athletes (football players and runners), the blood pressure and heart rate responses to the CPT were studied after a 30-minute infusion of MTC (7.5 microg/kg per minute) and two placebo periods, before and after MTC, with 5% glucose solution. Under placebo conditions, the CPT produced significant increases of systolic blood pressure (SBP) in the untrained subjects and the runners, but not in the football players (17.2, 17.8, and 6.5 mm Hg for untrained subjects, runners, and football players, respectively). The runners responded with a lesser increase in diastolic blood pressure (DBP) during the CPT than did the others (15.8, 17.9, and 18.2 mm Hg for runners, untrained subjects, and football players, respectively). In the presence of MTC, the CPT induced a larger increase in blood pressure (SBP/DBP) in the untrained subjects (21.4/24.1 mm Hg) than in the football players (10/18.7 mm Hg) and runners (18.7/13.9 mm Hg). MTC diminished the hyperreactivity responses to the CPT in the trained subjects (41 and 56% for football players and runners, respectively). Our conclusions are as follows: (1) Vascular responses to cold stress are attenuated in athletic subjects compared with untrained subjects. (2) The metoclopramide-induced vascular hyperreactivity, formerly reported for normotensive and hypertensive subjects, seems to be absent in trained subjects. (3) It is suggested that a probable dopaminergic system adaptation occurs during exercise.

Adult↗
PubMed2004

Surgical treatment of liver injury with microwave tissue coagulation: an experimental study.

OBJECTIVE: The purpose of this study was to examine whether microwave tissue coagulation (MTC) therapy is capable of stopping bleeding from severe liver injury in pigs. METHODS: Ten pigs (38 +/- 4 kg) underwent a 30-mL/kg isovolemic exchange transfusion with 3% low-molecular-weight dextran to produce dilutional coagulopathy, and then a through-and-through laceration injury measuring approximately 8 cm in length was induced in the right hepatic lobe. Immediately after inflicting the injury, the animals were randomly divided into two groups: Group A (n = 5, MTC was repeated along the liver laceration at intervals of 2.0 cm with manual compression) or Group B (n = 5, the injured lobe was manually compressed without MTC therapy for 1 minute). All animals received lactated Ringer's solution to maintain the mean arterial pressure at 75 mm Hg for 1 hour after the abdominal closure. The intraperitoneal blood loss, mean arterial pressure, volume of lactated Ringer's solution, and hematologic variables were compared between the groups. For further laboratory evaluation, three additional experimental animals were treated with the MTC therapy after inflicting the injury and then were allowed to survive for 14 days. RESULTS: Mean arterial pressure declined from a mean value of 88 +/- 10 mm Hg (range, 75-107 mm Hg) to 62 +/- 3 mm Hg (range, 50-75 mm Hg) after the induction of liver injury. The total blood loss in Group A was 192 +/- 58 g (range, 120-250 g), which was lower (p < 0.01) than that of 448 +/- 138 g (range, 260-650 g) in Group B. The resuscitation fluid volume of Group A animals was 304 +/- 204 mL (range, 100-600 mL), which was smaller (p < 0.01) than that of 1,320 +/- 654 mL (range, 900-2,250 mL) in Group B. At 14 days, all three animals that were treated in the additional study were found to be in good health. Their necropsies showed no evidence of an intrahepatic abscess, hematoma, or biloma. CONCLUSION: MTC therapy was thus found to provide simple, rapid, and definitive hemorrhage control in cases of severe liver injury without the need for reoperation.

Animals↗
PubMed2007

Medullary thyroid cancer: therapeutic targets and molecular markers.

PURPOSE OF REVIEW: The present review will provide an update of important studies in medullary thyroid cancer (MTC) with an emphasis on targeted preclinical and translational research studies published over the past 2 years. RECENT FINDINGS: Recent advances in the biology of MTC, particularly in RET proto-oncogene signaling, are now being translated into promising new therapies and biomarkers. Multifunction tyrosine kinase inhibitors that target RET, plus vascular endothelial growth factor receptors and additional kinases, are now being evaluated in Phase II clinical trials in MTC. Important unanswered questions include the optimal means for selecting high-risk patients, appropriate biomarkers for monitoring kinase inhibitor trials, and trial endpoints. Similar to ABL, epidermal growth factor receptors and other kinases, individual mutant RET forms have differential sensitivity to different inhibitors. In addition to RET, an old marker, calcitonin, has assumed increasing importance, but may not adequately reflect changes in tumor burden in RET inhibitor trials. A number of new therapeutic strategies are being developed that could be appropriate for the approximately 50% of patients who lack RET mutations in their tumors. SUMMARY: Progress is being made toward effective targeted MTC therapy. Patients with advanced, progressive MTC should be considered for enrollment in clinical trials.

Antineoplastic Agents↗
PubMed1999

Molecular analysis of bcl-1/IgH junctional sequences in mantle cell lymphoma: potential mechanism of the t(11;14) chromosomal translocation.

Mantle cell lymphoma (MCL) is characterized by the t(11;14) translocation that juxtaposes the bcl-1 locus to immunoglobulin (Ig) gene sequences and leads to deregulation of cyclin D1 gene. t(11;14) is thought to result from an error of the recombinase during D-JH Ig gene assembly; however, data on the underlying mechanism and candidate recombination-targeting motifs in the major translocation cluster (MTC) of the bcl-1 gene are lacking. bcl-1/IgH junctional sequences from seven MCL patients were amplified by PCR using primers targeting MTC and JH sequences on chromosomes 11q13 and 14q32, respectively. PCR products were directly sequenced and junctional sequences were searched for homology to known germline D genes. bcl-t MTC breakpoints were searched for the presence of possible recombination target motifs; heptamers, nonamers, binding sequence of the bp45 nuclease, x-like sequences and D gene segments. bcl-1/JH junctions were found to bear homology to D gene segments (DLR3, DM and DIR5) in 3/7 MCL samples. A computer-based search in previously published and/or submitted to GenBank bcl-1/JH junctional sequences identified homology to D genes in 1/4 MCL tumour samples and 1/4 MCl cell lines; DXP4 or D23/7 and DHQ52 or D22/21 or DXP5, respectively. The MTC locus contained motifs with homology to bp45 nuclease binding sequence, x-like sequences, heptamers/nonamers, D-like DIR genes and non-homologous recombination short (6 bp) DNA sequences. The above data indicate that the t(11;14) translocation in MCL may also occur at a more mature stage of B-cell ontogeny than previously thought, i.e. during VH-to-DJH rearrangement. Various known recombination motifs within MTC may contribute to an illegitimate recombination event between bcl-1 and DJH.

Base Sequence↗
PubMed1984

Salmon and human calcitonin-like peptides in man.

Calcitonin-like peptides have been identified in the serum of normal subjects and of medullary thyroid carcinoma (MTC) patients. Using specific homologous radioimmunoassays (RIA) in combination with reversed-phase high performance liquid chromatography and gel permeation chromatography under denaturing conditions, we have recognized major components which coeluted with human calcitonin-(1-32), PDN-21, a carboxyl-terminal flanking peptide derived from the calcitonin mRNA sequence, and salmon calcitonin-(1-32). An additional 12000 molecular weight peak possibly represents a human calcitonin-PDN-21 polyprotein. In both the human calcitonin-(1-32) (normal value less than 0.043 ngEq/ml; MTC 140 +/- 80 ngEq/ml, mean value +/- SEM) and the PDN-21 (normal value less than 0.050 ngEq/ml; MTC 33.6 +/- 16.5 ngEq/ml) RIAs, serum levels were increased in MTC patients. Circulating levels of the salmon calcitonin-like peptide were indistinguishable between normal subjects (0.038 +/- 0.006 ngEq/ml) and MTC patients (0.037 +/- 0.011 ngEq/ml).

Calcitonin↗
PubMed2005

Experience of prophylactic thyroidectomy in multiple endocrine neoplasia type 2A kindreds with RET codon 804 mutations.

OBJECTIVE AND DESIGN: Genetic screening in multiple endocrine neoplasia type 2 (MEN 2) has led to specific management guidelines based on genotype-phenotype analysis. However, there is controversy regarding the appropriate age for prophylactic thyroidectomy in families with mutations in codon 804 in exon 14 of the RET proto-oncogene, where medullary thyroid cancer (MTC) may not develop until adulthood. We prospectively studied two MEN 2A families, one with the V804L and the other with the V804M RET mutation, to report our experience of genetic and biochemical screening and prophylactic thyroidectomy. Family 1 is one of the largest MEN 2A families in the literature, where 22 prophylactic thyroidectomies have been performed. PATIENTS AND RESULTS: C-cell hyperplasia (CCH) was found in 23 out of 25 thyroidectomy specimens from family members of ages 5 years and upwards. MTC was found in 10 out of 18 adults of age 25 years upwards, including the family 2 proband, who was found to have MTC with lymph node metastases at age 28. Phaeochromocytoma was only observed in one patient, but six cases of histologically confirmed hyperparathyroidism were seen in family 1. CONCLUSION: We suggest that prophylactic thyroidectomy should not be delayed until adulthood in MEN 2A families carrying codon 804 RET mutations, but should be performed when there is CCH, before the development of MTC, as close as possible to age 6 years, which is the age of the youngest reported case of MTC in '804' families.

Adolescent↗
PubMed2006

Determinants of life expectancy in medullary thyroid cancer: age does not matter.

OBJECTIVE: In medullary thyroid cancer (MTC) age is considered an important prognostic factor but survival has never been properly adjusted for baseline mortality in the general population. We aimed to identify prognostic factors by analysing patients with MTC regarding life expectancy. DESIGN: We described a retrospective cohort study with a median follow-up of 8 years (range 1-35 years). PATIENTS: We included 120 consecutive patients of whom 66 (55%) had sporadic MTC. Male/female ratio was 1 : 1; median age was 45 years (range 3-83 years). MEASUREMENTS: Measurements were overall and disease-specific survival and life expectancy expressed as survival adjusted for baseline mortality rate in the general population. RESULTS: Overall and disease-specific 10-year survival was 65% and 73%, respectively. After 10 years, 29% of patients were biochemically and 63% clinically cured. Median overall life expectancy was 0.58 (95%CI 0.37-0.80). Detectable recurrence occurred in 60 patients after a median of 36 months (range 5-518 months). On multivariate regression analysis only stage of disease and extrathyroidal extension predicted recurrence-free life expectancy. Extrathyroidal extension was the only independent predictor of overall life expectancy. Persistent biochemical MTC did not independently affect life expectancy but calcitonin doubling time of less than one year indicated worse prognosis. Patients without detectable recurrences after initial treatment had a life expectancy similar to the general population. CONCLUSIONS: In MTC patients, extrathyroidal extension and stage at diagnosis are the only independent predictors of (recurrence-free) life expectancy. Patients diagnosed in an early stage of disease and patients without detectable recurrence have favourable life expectancy independently of biochemical cure.

Adolescent↗
PubMed2006

Archaeal diversity in two thermophilic chalcopyrite bioleaching reactors.

This study used a culture-independent molecular approach to investigate the archaeal community composition of thermophilic bioleaching reactors. Two culture samples, MTC-A and MTC-B, grown with different concentrations of chalcopyrite (CuFeS2), a copper sulfidic ore, at a temperature of 78 degrees C and pH 1.6 were studied. Phylogenetic analysis of the 16S rRNA genes revealed that both cultures consisted of Archaea belonging to the Sulfolobales. The 16S rRNA gene clone library of MTC-A grown with 4% (w/v) chalcopyrite was dominated by a unique phylotype related to Sulfolobus shibatae (69% of total clones). The remaining clones were affiliated with Stygiolobus azoricus (11%), Metallosphaera sp. J1 (8%), Acidianus infernus (2%), and a novel phylotype related to Sulfurisphaera ohwakuensis (10%). In contrast, the clones from MTC-B grown with 12% (w/v) chalcopyrite did not appear to contain Sulfolobus shibatae-like organisms. Instead the bioleaching consortium was dominated by clones related to Sulfurisphaera ohwakuensis (73.9% of total clones). The remaining microorganisms detected were similar to those found in MTC-A.

Biodiversity↗
PubMed2004

Molecular basis of intrinsic macrolide resistance in the Mycobacterium tuberculosis complex.

The intrinsic resistance of the Mycobacterium tuberculosis complex (MTC) to most antibiotics, including macrolides, is generally attributed to the low permeability of the mycobacterial cell wall. However, nontuberculous mycobacteria (NTM) are much more sensitive to macrolides than members of the MTC. A search for macrolide resistance determinants within the genome of M. tuberculosis revealed the presence of a sequence encoding a putative rRNA methyltransferase. The deduced protein is similar to Erm methyltransferases, which confer macrolide-lincosamide-streptogramin (MLS) resistance by methylation of 23S rRNA, and was named ErmMT. The corresponding gene, ermMT (erm37), is present in all members of the MTC but is absent in NTM species. Part of ermMT is deleted in some vaccine strains of Mycobacterium bovis BCG, such as the Pasteur strain, which lack the RD2 region. The Pasteur strain was susceptible to MLS antibiotics, whereas MTC species harboring the RD2 region were resistant to them. The expression of ermMT in the macrolide-sensitive Mycobacterium smegmatis and BCG Pasteur conferred MLS resistance. The resistance patterns and ribosomal affinity for erythromycin of Mycobacterium host strains expressing ermMT, srmA (monomethyltransferase from Streptomyces ambofaciens), and ermE (dimethyltransferase from Saccharopolyspora erythraea) were compared, and the ones conferred by ErmMT were similar to those conferred by SrmA, corresponding to the MLS type I phenotype. These results suggest that ermMT plays a major role in the intrinsic macrolide resistance of members of the MTC and could be the first example of a gene conferring resistance by target modification in mycobacteria.

Amino Acid Sequence↗
PubMed2006

Novel genetic polymorphisms that further delineate the phylogeny of the Mycobacterium tuberculosis complex.

In a previous report, we described a PCR protocol for the differentiation of the various species of the Mycobacterium tuberculosis complex (MTC) on the basis of genomic deletions (R. C. Huard, L. C. de Oliveira Lazzarini, W. R. Butler, D. van Soolingen, and J. L. Ho, J. Clin. Microbiol. 41:1637-1650, 2003). That report also provided a broad cross-comparison of several previously identified, phylogenetically relevant, long-sequence and single-nucleotide polymorphisms (LSPs and SNPs, respectively). In the present companion report, we expand upon the previous work (i) by continuing the evaluation of known MTC phylogenetic markers in a larger collection of tubercle bacilli (n = 125), (ii) by evaluating additional recently reported MTC species-specific and interspecific polymorphisms, and (iii) by describing the identification and distribution of a number of novel LSPs and SNPs. Notably, new genomic deletions were found in various Mycobacterium tuberculosis strains, new species-specific SNPs were identified for "Mycobacterium canettii," Mycobacterium microti, and Mycobacterium pinnipedii, and, for the first time, intraspecific single-nucleotide DNA differences were discovered for the dassie bacillus, the oryx bacillus, and the two Mycobacterium africanum subtype I variants. Surprisingly, coincident polymorphisms linked one M. africanum subtype I genotype with the dassie bacillus and M. microti with M. pinnipedii, thereby suggesting closer evolutionary ties within each pair of species than had been previously thought. Overall, the presented data add to the genetic definitions of several MTC organisms as well as fine-tune current models for the evolutionary history of the MTC.

Animals↗
PubMed1985

Mitomycin-induced lethality of Escherichia coli cells containing the ColE1 Plasmid: involvement of the kil gene.

Escherichia coli cells containing the ColE1 plasmid or related plasmids are killed by considerably lower levels of mitomycin C (MTC) than are plasmid-free cells. Since exposure to MTC induces high levels of synthesis of the plasmid-encoded colicin toxin, it was originally thought that the killing effect was due to the increased levels of colicin. This possibility was discounted when it was shown that deletion mutations in the plasmid lacking most of the colicin (cea) gene still sensitized host cells to MTC. Only when the region containing the cea gene promoter was deleted did the killing effect disappear. This led to the suggestion that transcription originating from the cea gene promoter and not the colicin protein itself was required for killing. Transcription-blocking mutations in the cea gene support this suggestion. It was proposed that there is a gene (kil) located downstream from the cea gene in the same operon that is responsible for MTC killing and colicin transport. The precise location of the kil gene in ColE1 can be predicted by piecing together published sequence information. We used available sequence data to construct a number of well-defined plasmid mutants to further examine the relevance of transcription from the cea promoter and the kil gene to drug-induced killing and colicin transport. The most informative mutant had a small insertion in the kil gene. This mutant behaved as predicted; cells containing it had a greatly lowered sensitivity to MTC and were severely inhibited in the transport of colicin.

Bacteriocin Plasmids↗
PubMed2001

Insertional mutagenesis in the n-alkane-assimilating yeast Yarrowia lipolytica: generation of tagged mutations in genes involved in hydrophobic substrate utilization.

Tagged mutants affected in the degradation of hydrophobic compounds (HC) were generated by insertion of a zeta-URA3 mutagenesis cassette (MTC) into the genome of a zeta-free and ura3 deletion-containing strain of Yarrowia lipolytica. MTC integration occurred predominantly at random by nonhomologous recombination. A total of 8,600 Ura(+) transformants were tested by replica plating for (i) growth on minimal media with alkanes of different chain lengths (decane, dodecane, and hexadecane), oleic acid, tributyrin, or ethanol as the C source and (ii) colonial defects on different glucose-containing media (YPD, YNBD, and YNBcas). A total of 257 mutants were obtained, of which about 70 were affected in HC degradation, representing different types of non-alkane-utilizing (Alk(-)) mutants (phenotypic classes alkA to alkE) and tributyrin degradation mutants. Among Alk(-) mutants, growth defects depending on the alkane chain length were observed (alkAa to alkAc). Furthermore, mutants defective in yeast-hypha transition and ethanol utilization and selected auxotrophic mutants were isolated. Flanking borders of the integrated MTC were sequenced to identify the disrupted genes. Sequence analysis indicated that the MTC was integrated in the LEU1 locus in N083, a leucine-auxotrophic mutant, in the isocitrate dehydrogenase gene of N156 (alkE leaky), in the thioredoxin reductase gene in N040 (alkAc), and in a peroxine gene (PEX14) in N078 (alkD). This indicates that MTC integration is a powerful tool for generating and analyzing tagged mutants in Y. lipolytica.

Alkanes↗
PubMed1999

Fluorescence In situ hybridization assay using peptide nucleic acid probes for differentiation between tuberculous and nontuberculous mycobacterium species in smears of mycobacterium cultures.

TB PNA FISH is a new fluorescence in situ hybridization (FISH) method using peptide nucleic acid (PNA) probes for differentiation between species of the Mycobacterium tuberculosis complex (MTC) and nontuberculous mycobacteria (NTM) in acid-fast bacillus-positive (AFB+) cultures is described. The test is based on fluorescein-labelled PNA probes that target the rRNA of MTC or NTM species applied to smears of AFB+ cultures for microscopic examination. Parallel testing with the two probes serves as an internal control for each sample such that a valid test result is based on one positive and one negative reaction. TB PNA FISH was evaluated with 30 AFB+ cultures from Denmark and 42 AFB+ cultures from Thailand. The MTC-specific PNA probe showed diagnostic sensitivities of 84 and 97%, respectively, and a diagnostic specificity of 100% in both studies, whereas the NTM-specific PNA probe showed diagnostic sensitivities of 91 and 64%, respectively, and a diagnostic specificity of 100% in both studies. The low sensitivity of the NTM-specific PNA probe in the Thai study was due to a relatively high prevalence of Mycobacterium fortuitum, which is not identified by the probe. In total, 63 (87%) of the cultures were correctly identified as MTC (n = 46) or NTM (n = 17), whereas the remaining 9 were negative with both probes and thus the results were inconclusive. None of the samples were incorrectly identified as MTC or NTM; thus, the predictive value of a valid test result obtained with TB PNA FISH was 100%.

Base Sequence↗
PubMed2004

Dendritic cell vaccination in medullary thyroid carcinoma.

PURPOSE: Prognosis and treatment effectiveness for medullary thyroid carcinoma (MTC) are strictly related to tumor stage. Palliative treatment options show no significant benefit. A promising treatment approach for human cancer is based on the vaccination of autologous dendritic cells (DCs). EXPERIMENTAL DESIGN: The objective of this study was to evaluate the effectiveness of DC vaccines in MTC patients. Therefore, we generated autologous tumor lysate-pulsed DCs from 10 patients suffering from advanced MTC for repeated vaccination. Mature DCs were derived from peripheral blood monocytes by using CD14 magnetic bead selection and subsequent culture in the presence of granulocyte macrophage colony-stimulating factor, interleukin 4, and tumor necrosis factor alpha with or without addition of IFN-gamma. DCs were loaded with tumor lysate and further injected into a groin lymph node. Toxicity, tumor marker profile, immune response, and clinical response were determined. RESULTS: Vaccination was well tolerated and induced a positive immunological response in all of the tested patients as evaluated by in vivo delayed-type hypersensitivity reactivity or in vitro intracytoplasmic IFN-gamma detection assay. Three patients had a partial response, 1 patient presented a minor response, and 2 patients showed stable disease. The remaining 4 patients had progressive disease. CONCLUSIONS: These data provide strong evidence that vaccination with tumor-lysate pulsed DCs results in the induction of a specific immune response in patients suffering from MTC. Objective clinical responses could be observed even for far-advanced disease. Therefore, we suggest that MTC is particularly suited for DC-based immunotherapy.

Adult↗
PubMed1991

The antiemetic activity of high-dose metoclopramide and high-dose alizapride in combination with lorazepam in patients receiving cancer chemotherapy. A prospective, randomized, double-blind study.

The antiemetic efficacy of metoclopramide and lorazepam (MTC + L) versus alizapride and lorazepam (ALZ + L) was compared in 100 patients receiving chemotherapy, in a prospective randomized double-blind study. In highly emetogenic (HE) regimen (including platinum) patients received MTC 1 mg/kg or ALZ 3 mg/kg x 4 doses, and lorazepam 2.5 mg 30 min before therapy. In moderately emetogenic (ME) regimen patients received MTC 0.5 mg/kg or ALZ 1.5 mg kg x 3 doses, and lorazepam 2.5 mg 30 min before therapy. In both HE and ME regimen groups there was no statistically significant difference between MTC + L and ALZ + L treatments as regards the number of vomiting episodes, the duration of emesis and nausea, the intensity of nausea and side effects, but a statistically significant difference between treatments was found in the HE group where MTC-L was superior to ALZ + L in obtaining complete protection from vomiting (37 vs 11%, p = 0.05). No significant difference in side effects was observed.

Adolescent↗