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PubMed1998

Genotype-phenotype correlation of patients with multiple endocrine neoplasia type 2 in Japan.

BACKGROUND: Multiple endocrine neoplasia type 2 (MEN 2) is a hereditary syndrome characterized by medullary thyroid carcinoma (MTC), pheochromocytoma and hyperparathyroidism. MEN 2 is caused predominantly by germ-line mutations of the RET proto-oncogene. This study aimed to clarify the genotype-phenotype correlation in MEN 2 patients in Japan in order to modify the clinical management according to the genotype. METHODS: Constitutive DNA of 64 MEN 2 patients (48 kindreds) were searched for mutations at exons 10, 11, 13, 14 and 16 of the RET proto-oncogene using polymerase chain reaction-single strand conformation polymorphism (PCR-SSCP), direct sequencing and restriction enzyme digestion. The clinical characteristics of the patients were obtained from a previous nationwide questionnaire survey. RESULTS: Overall, 62 (96.9%) out of 64 patients had a germ-line point mutation at the hot spots. MTC and pheochromocytoma occurred equally in every genotype except C630S. Specific genotype had a correlation between tumor size and age at the operation for MTC or extent of MTC, i.e. C618S developed late onset type of MTC as compared with that of C634R, C634Y and M918T. Small MTC in C634R may be less aggressive than those in C634Y and M918T. CONCLUSIONS: DNA testing has good clinical implications for the management of patients with MEN 2 and the timing and operative procedures of thyroidectomy can be modified according to the genotype.

Adrenal Gland Neoplasms↗
PubMed1996

Immunohistochemical study of primary and recurrent basal cell and metatypical carcinomas of the skin.

We investigated cell proliferation and expression of cytoskeletal proteins in 32 cases of primary basal cell carcinomas (BCC), 10 cases of recurrent BCC, and 10 cases of metatypical carcinomas (MTC). Paraffin-embedded biopsies were evaluated immunohistochemically with a battery of antibodies. Antibodies to proliferating cell nuclear antigen (PCNA) demonstrated comparatively low numbers of proliferating cells in 25 of 32 cases of primary BCC. In contrast, both recurrent BCC and MTC exhibited three to four times higher levels of proliferating cells than primary BCC. PCNA-positive cells were usually distributed uniformly throughout the lobules; at times, however, they were localized to the outer areas of those neoplasms, with a comparatively low level of proliferation index. Antibodies to keratin 17 strongly stained cells of all BCC cases, and antibodies to keratin 8 reacted with most of them. In contrast, the staining intensity of both types of keratin in MTC was decreased six to eight times as compared with all BCC. In addition, cells of eight BCC and three MTC reacted with antibodies to smooth muscle alpha-actin and myosin, neoplasms that did not differ by the number of PCNA-positive nuclei from carcinomas without contractile proteins. The differences in cell proliferation and keratin expression between BCC and MTC may be useful criteria for further distinguishing these carcinomas. The appearance of contractile proteins in some BCC and MTC may be the result of, or implies, myoepithelial differentiation.

Actins↗
PubMed1998

C-cell hyperplasia and medullary thyroid carcinoma in patients routinely screened for serum calcitonin.

Routine screening of calcitonin serum levels in patients with nodular thyroid disorders has led to an increased rate of total thyroidectomies. We investigated prevalence and interrelationship of C-cell hyperplasia (CCH) and medullary thyroid carcinoma (MTC) in patients with thyroid and parathyroid disorders that showed increased calcitonin serum levels detected by routine screening. Within two years, 30 (mean age, 60 +/- 14 years) of 667 patients had a pentagastrin-stimulated calcitonin level of more than 100 pg/mL. All 30 underwent total thyroidectomy and were tested for germ-line mutations of the ret protooncogene. Entire surgical specimens were blocked, and C-cell disorders were assessed using conventional histology and immunohistochemistry. C-cell hyperplasia was defined by the presence of more than 50 C cells/l low-power field in both lobes and was classified as focal, diffuse, nodular, or neoplastic. Nineteen patients (female/male = 14/5) had MTC, and 11 males but no females had CCH only. Six of 16 patients with sporadic MTC had concomitant CCH. Three patients were index cases of new MTC families. We conclude that MTC with concomitant CCH is an unreliable marker for hereditary MTC risk and that CCH has a preneoplastic potential in the absence of germ-line mutations. In this series, CCH alone was not found in females.

Adult↗
PubMed1989

Exercise produces sensitivity to metocurine.

Chronic muscle disuse decreases the sensitivity of skeletal muscle to nondepolarizing relaxants, such as metocurine (MTC). In this study, the authors determined whether chronic conditioning would produce the opposite effect and increase the sensitivity of skeletal muscle to MTC. Five dogs were exercised by daily running over a period of 5 weeks. At the conclusion of this training period, a pharmacokinetic and pharmacodynamic study of the MTC dose-response relationship was performed. The same analysis was performed on four dogs housed in the same kennel who did not undergo conditioning. Neuromuscular blockade was measured and recorded bilaterally in both gastrocnemius muscles while the animal was anesthetized with nitrous oxide and pentobarbital, 30 ml.kg-1. Plasma concentrations of MTC were measured by radioimmunoassay. The MTC concentration estimated in the effect compartment which produced 50% paralysis was 0.114 +/- 0.008 micrograms.ml-1 (mean +/- SD) in exercised dogs and 0.189 +/- 0.038 micrograms.ml-1 in nonexercised dogs, which was significant at P less than 0.005). The MTC concentration versus response curves were parallel. This supports the authors' hypothesis that exercise increases sensitivity to the nondepolarizing muscle relaxant metocurine.

Animals↗
PubMed1982

The importance of early diagnosis in patients with hereditary medullary thyroid carcinoma.

Ninety-two patients from 12 kindreds with hereditary medullary thyroid carcinoma (MTC) were evaluated. We sought to determine if the stimulated plasma calcitonin (CT) level at the time of diagnosis was of prognostic significance. The patients were divided into four groups according to their preoperative stimulated plasma CT levels (1) 250-1,000 pg/ml (n=25); (2) 1,000-5,000 pg/ml (n=36); (3) 5,000-10,000 pg/ml (n=8); (4) greater than 10,000 pg/ml (n=23). Compared between the four groups were several parameters, including incidence of regional lymph node metastases, incidence of residual MTC post-thyroidectomy (as indicated by increased (greater than 300 pg/ml) plasma CT levels after operation), incidence of distant metastases, and incidence of death. Also compared were the incidences of microscopic or gross MTC in thyroidectomy specimens. The incidence of regional lymph node involvement ranged from a minimum of one (4%) of 25 patients in Group 1 to 13 (57%) of 23 patients in Group 4. Similarly, plasma CT levels were elevated in only one (4%) of 25 patients in Group 1 compared to 14 (61%) of 23 patients in Group 4. There was no evidence of distant metastases or death in the patients in Groups 1, 2, or 3. In the 23 patients in group 4, however, four (17.4%) had distant metastases and two (8.7%) died of disease during the period of observation. Of th 25 patients in Group 1, MTC was evident only by microscopic examination in 14 (56%). Eleven (44%) of the patients in Group 1 had macroscopically evident medullary thyroid carcinoma. This is in contrast with patients in Group 4 where all 23 had grossly evident MTC. These data indicate that the stimulated plasma CT level at the time of diagnosis is an excellent prognostic indicator of the extent of a disease in patients with hereditary MTC. Aggressive screening of kindred members at risk is of critical importance for establishing the diagnosis and instituting therapy at a time when the neoplasm is confined to the thyroid gland.

Calcitonin↗
PubMed1998

Effective long-term palliation of symptomatic, incurable metastatic medullary thyroid cancer by operative resection.

OBJECTIVE: To evaluate the short- and long-term consequences of palliative reresection of specific symptomatic lesions in patients with widely disseminated (incurable) medullary thyroid cancer (MTC). SUMMARY BACKGROUND DATA: Although reoperative neck microdissections can normalize calcitonin levels in patients with metastatic MTC confined to regional lymph nodes, there is no curative therapy for widely metastatic disease. However, these patients frequently have prolonged survival, but often with debilitating symptoms. METHODS: Between October 1981 and January 1997, 16 patients (mean age, 46 +/- 3 years; 10/16 female) underwent 21 palliative reoperations for unresectable MTC at the Johns Hopkins Hospital. All patients had significant symptom(s) or impending compromise of vital structures by a discrete lesion and had unequivocal preoperative evidence of a total disease burden that was unresectable. RESULTS: The mean interval from initial thyroidectomy to palliative surgery was 5.8 +/- 1.5 years. All patients had significant tumor burdens as evidenced by preoperative calcitonin values ranging from 900 to 222,500 pg/mL (nL < or = 17 pg/mL). The palliative operations consisted of reoperative neck dissection/mass excision (11), mediastinal mass resection (4), esophagectomy (1), liver trisegmentectomy (1), sigmoidectomy (1), bilateral simple mastectomies (1), pituitary resection (1), and subcutaneous mass excisions (1). All but two of the operative specimens contained MTC. There was no perioperative mortality. The long-term morbidity rate was limited to one recurrent laryngeal nerve injury. All patients had initial relief of the index symptom(s) after the palliative surgery, followed by a median actuarial symptom-free survival rate of 8.2 years. CONCLUSIONS: Patients with widely metastatic MTC often live for years, but many develop symptoms secondary to tumor persistence or progression. Judicious palliative, reoperative resection of discrete, symptomatic lesions can provide significant long-term relief of symptoms with minimal operative mortality and morbidity. In selected patients with metastatic MTC lesions causing significant symptoms or physical compromise, palliative reoperative resection should be considered despite the presence of widespread incurable metastatic disease.

Adult↗
PubMed1998

Novel point mutations and allele loss at the RET locus in sporadic medullary thyroid carcinomas.

Germline mutations in the RET proto-oncogene have been shown to be the underlying cause of multiple endocrine neoplasia type 2 (MEN 2A and 2B) and familial medullary thyroid carcinoma (FMTC). Some cases of sporadic medullary thyroid carcinoma (sporadic MTC) are reported to have specific codon 918, 883 and 768 mutations of the RET gene in tumor tissues. We examined RET gene mutations in 40 Japanese cases who had previously undergone surgery for sporadic MTC. DNA extracted from formalin-fixed tumor tissues and corresponding normal thyroid tissues or peripheral blood leukocytes was analyzed for mutations of exon 10, 11, 13, 14 and 16 of the RET gene by DNA sequencing and by mutation-specific restriction enzyme analysis. Germline RET point mutations were found in six of 40 cases (15%), cysteine residues at codon 618 in two, codon 634 in three and valine residue at codon 804 in one, and were newly identified as heritable MTC. Of the remaining 34 sporadic MTC cases, four (12%) had tumor-specific RET point mutations. Two were found in exon 16; one case showed an ATG to ACG (Met to Thr) mutation at codon 918, and the other showed two point mutations, ATG to ACG (Met to Thr) at codon 918 and GCA to GTA (Ala to Val) at codon 919 with loss of the wild-type allele, suggesting that both alleles at the RET locus were altered. The other two were found in exon 13; one case showed a CCG to TCG (Pro to Ser) mutation at codon 766 and the other showed a silent mutation, GTC to GTT (Val) at codon 778 with loss of the wild-type allele. There was no association of sporadic mutations with recurrence or prognosis in patients with sporadic MTC. The low rate of somatic RET mutation at codon 918 in our sporadic MTC suggests that as yet unknown factors may be involved. Genetic alterations in both alleles may have an important role in small fraction of sporadic MTCs.

Adult↗
PubMed1995

Prevalence of sporadic medullary thyroid carcinoma: the importance of routine measurement of serum calcitonin in the diagnostic evaluation of thyroid nodules.

OBJECTIVE: The prevalence of sporadic forms of medullary thyroid carcinoma (MTC) has been studied in patients living in an area of moderate iodine deficiency. Such forms of MTC are usually diagnosed after surgery and have little chance of definitive cure. Using the measurement of basal serum calcitonin (CT) levels in a large series of patients with both thyroid disease and normal 24-hour urinary iodine excretion, we assessed the prevalence of MTC and, in patients affected with the disease, we also evaluated the stage of the disease according to surgical findings and post surgical plasma CT levels. PATIENTS: A prospective study of 657 patients with thyroid disease (469 with nodular and 188 with non-nodular thyroid disease). As controls, 40 normal subjects were also studied. MEASUREMENTS: In all patients: (1) measurement of basal serum CT, free T4, total T3, TSH levels and serum TSH-receptor, peroxidase and thyroglobulin (Tg) antibody concentrations, (2) thyroid ultrasonography, (3) fine needle aspiration cytology (FNAC). In patients with increased basal CT levels: (1) measurement of serum CT levels during pentagastrin test prior to surgery, (2) histological examination and immunostaining with both anti-CT and anti-Tg antibodies of all the nodular thyroid tissue surgically removed, (3) measurement of basal and pentagastrin stimulated serum CT values after surgery. RESULTS: All the patients with non-nodular thyroid disease had normal basal CT levels. Four patients (0.84%) with nodular thyroid disease (2 with uninodular and 2 with multinodular goitre) had both elevated basal and pentagastrin stimulated CT levels. In the two patients with uninodular goitre, FNAC was suggestive of MTC in 1 (nodular diameter 8.0 cm) and of follicular carcinoma in 1 (nodular diameter 2.5 cm). Histological examination of the nodules confirmed these histotypes. Immunostaining with anti-CT antibodies was positive in the former patient but also in the latter. FNAC was suggestive of benign adenomatous tissues in the two patients with multinodular goitre. Histological examination of all the thyroid nodules confirmed the cytological findings. However, serial sections through the gland in each of these two patients showed an occult follicular carcinoma which had, however, positive staining with anti-CT antibodies. Furthermore, immunostaining with anti-Tg antibodies was negative in the patient with MTC but positive in the 3 patients with follicular carcinoma. Finally, both basal and pentagastrin stimulated CT levels remained elevated after total thyroidectomy only in the patient with FNAC suggesting MTC. CONCLUSIONS: This study demonstrates a surprisingly high prevalence of sporadic forms of medullary thyroid carcinoma in patients with nodular thyroid disease. Such forms of medullary thyroid carcinoma seem to be unrelated to iodine intake and may be pure or mixed with a follicular carcinoma. In these mixed thyroid carcinomas, only the neoplastic follicular pattern was seen on both cytological and histological examination. Routine measurements of serum calcitonin levels should therefore be considered an integral part of the diagnostic evaluation of thyroid nodules. Indeed, increasing the accuracy of diagnosis of medullary thyroid carcinoma encourages the surgeon to perform more radical treatment, thus achieving more frequent normalization of post-operative serum calcitonin levels.

Adolescent↗
PubMed2004

Medullary thyroid carcinoma.

Medullary thyroid carcinoma (MTC) arises from parafollicular or C cells that produce calcitonin (CT), and accounts for 5-10% of all thyroid cancers. MTC is hereditary in about 25% of cases. The discovery of a MTC in a patient has several implications: disease extent should be evaluated, phaeochromocytoma and hyperparathyroidism should be screened for and whether the MTC is sporadic or hereditary should be determined by a direct analysis of the RET proto-oncogene. In this review, pathological characteristics, tumour markers and genetic abnormalities in MTC are discussed. The diagnostic and therapeutic modalities applied to patients with clinical MTC and those identified with preclinical disease through familial screening are also described. Progresses concerning genetics, initial treatment, follow-up, screening and treatment of pheochromocytoma have permitted an improvement in the long-term outcome. However, there is no effective treatment for distant metastases, and new therapeutic modalities are urgently needed.

Biomarkers, Tumor↗
PubMed2006

Occurrence of the Cys611Tyr mutation and a novel Arg886Trp substitution in the RET proto-oncogene in multiple endocrine neoplasia type 2 families and sporadic medullary thyroid carcinoma cases originating from the central region of Portugal.

OBJECTIVE: Medullary thyroid carcinoma (MTC) occurs both sporadically and in the context of autosomal dominantly inherited multiple endocrine neoplasia type 2 (MEN2) syndromes: MEN2A, MEN2B, and familial medullary thyroid carcinoma (FMTC), which are caused by activating germline mutations in the RET proto-oncogene. The aim of this study was to characterize the RET mutational spectrum in MEN2 families and apparently sporadic MTC (AS-MTC) cases originating from the central region of Portugal. SUBJECTS AND METHODS: We studied a total of 82 individuals (64 affected and 18 family members), comprising five MEN2 families (four MEN2A and one MEN2B), as well as 53 AS-MTC cases. RET germline mutations were screened using PCR-DNA sequencing, SSCP and RFLP. The haplotypes associated with recurrent mutations were determined by fragment analysis of microsatellite markers, and by RFLP, in the case of intragenic polymorphisms. RESULTS: Frequency of the Cys611Tyr (TGC-TAC) mutation was significantly increased in this region of Portugal, due to the fact that three apparently unrelated MEN2A/FMTC families, out of the five in which mutations were identified, harboured this specific mutation. Haplotype analysis revealed that a common haplotype was shared between two of these three families. We have also characterized a novel RET mutation, Arg886Trp, located in the tyrosine kinase domain, which was found in an AS-MTC case. CONCLUSIONS: There are regional specificities in the relative frequency of RET mutations, which are consistent with a cluster-like distribution of specific disease-causing mutations, as a result of the inheritance of a shared haplotype. These data, along with the finding of a novel RET mutation (Arg886Trp), have important implications towards facilitating and improving the molecular diagnosis of hereditary MTC on a regional basis.

Adult↗
PubMed1985

Tubular carcinoma of the breast. A long term follow-up.

The aim of this study is to provide a long-term follow-up of patients with tubular carcinoma and to investigate whether the separation of the mixed type of tubular carcinoma, tubular component more than 75%, from invasive ductal carcinoma with a major tubular component (ductal carcinoma MTC), tubular component 50 to 75%, is supported by long term follow-up. For this study 388 consecutive breast carcinomas were selected from the files of the Department of Pathology, Bispebjerg Hospital, Denmark for the years: 1956-59. Twenty tubular carcinomas were found and 16 ductal carcinomas MTC were also identified. For each patient with tubular carcinoma and ductal carcinoma MTC, two controls with ductal carcinoma NOS were selected. The patients in these four groups were followed until 1 April 1982. None of the patients were lost to follow-up. Among the 20 patients with tubular carcinoma, 10 died within this period compared to 37 of the 40 controls. Of the 16 patients with ductal carcinoma MTC, 15 died compared to 29 of the 32 controls. The difference in Kaplan-Meier survival curves between the tubular carcinomas and their controls is highly significant. There is no significant difference between ductal carcinomas MTC and their controls. These findings are not changed significantly when 5, 10, and 20 year survival rates are corrected for expected survival. This study demonstrates long-term survival for patients with tubular carcinoma as compared to ductal carcinoma NOS. There is no difference in long-term survival between ductal carcinoma MTC, tubular component between 50 and 75%, and ductal carcinoma NOS. It therefore seems appropriate to set 75% tubular component as a reasonable cut-off point for the mixed type of tubular carcinoma.

Adenocarcinoma↗
PubMed1995

Pheochromocytoma in multiple endocrine neoplasia type 2: European study. The Euromen Study Group.

OBJECTIVES: Pheochromocytoma (pheo) is the second component of the multiple endocrine neoplasia type 2 (MEN 2) syndrome. Clinical expression is sometimes poor, and chronology between medullary thyroid carcinoma (MTC) and pheo is not well evaluated. Therefore, a retrospective study was done in eight European countries in order to precise the main characteristics of pheo in MEN 2. SUBJECTS: Data from 300 MEN 2 patients with pheo (274 MEN 2 A and 26 MEN 2 B) were obtained from cases registered by the EuroMen study group, and collected by a medical standardized questionnaire. These cases occurred between 1969 and 1992. RESULTS: Mean age at diagnosis of pheo was 39.5 years (range 14-68 years) in MEN 2A and 32.4 years (range 15-41 years) in MEN 2B patients. Pheo occurred first in 25.1% of the cases (2-15 years before diagnosis of MTC) and after MTC in 40.2% (2-11 years). In other cases (34.7%), MTC and pheo were diagnosed at the same time. Involvement was bilateral in 67.8% of cases. Malignancy was only 4%. Thirty-nine deaths occurred in these 300 patients, 64.1% were linked in pheo, 23.1% to MTC and 12.8% to other causes. Surgery was unilateral in 39.7% of the cases and bilateral adrenalectomy was the first procedure in 48.4%. A bilateral adrenalectomy in two steps had to be done in 11.9% of cases. In conclusion, these results justify systematic and prolonged biochemical screening of pheo during follow-up of MTC and address some questions about the best mode of surgery.

Adolescent↗
PubMed1997

The mechanism of tubulin-colchicine recognition--a kinetic study of the binding of a bicyclic colchicine analogue with a minor modification of the A ring.

2-Methoxy-5-(2',3',4'-trimethoxy)-2,4,6-cycloheptatrien-1-one (MTC) is a colchicine analogue that lacks the B ring. 2-Methoxy-5-(2',4'-dimethoxyphenyl)-2,4,6-cycloheptatrien-1-one (MD) is an A-ring analogue of MTC, in which one methoxy group is replaced by a hydrogen atom. This paper describes the kinetic features of MDC binding to tubulin, and compares its behaviour with MTC to analyse the effect of the A-ring modification on the recognition process by tubulin. Binding is accompanied by a strong enhancement of MDC fluorescence and quenching of protein fluorescence. The kinetic and thermodynamic parameters were obtained from fluorescence stopped-flow measurements. The kinetics are described by a single exponential, indicating that this drug does not discriminate between the different tubulin isotypes. The observed pseudo-first-order rate constant of the fluorescence increase upon binding increases in a non-linear way, indicating that this ligand binds with a similar overall mechanism as colchicine and MTC, consisting of a fast initial binding of low affinity followed by a slower isomerisation step leading to full affinity. The K1 and k2 values for MDC at 25 degrees C were 540 +/- 65 M(-1) and 70 +/- 6 s(-1) respectively. From the temperature dependence, a reaction enthalpy change (deltaH(o)1) of the initial binding of 49 +/- 11 kJ/mol(-1) and an activation energy for the second step of 28 +/- 9 kJ/mol(-1) were calculated. Displacement experiments of bound MDC by MTC allowed the determination of a rate constant of reverse isomerisation of 0.60 +/- 0.07 s(-1) at 25 degrees C and the activation energy of 81 +/- 6 kJ/mol(-1). The overall binding constant was (6.3 +/- 0.2) x 10(4) M(-1) at 25 degrees C. Combination of these results with the kinetic parameters for association gives a full characterisation of the enthalpy pathway for the binding of MDC. The pathway of MDC is shown to differ considerably from that of MTC binding. Since its structural difference is located in ring A, this result indicates the use of ring A in the first step. The kinetics of the binding of MDC in the presence of some A-ring colchicine analogues (podophyllotoxin, 3',4',5'-trimethoxyacetophenone and N-acetylmescaline) and a C-ring analogue (tropolone methyl ether) suggest that the A and C rings are involved in the binding of MDC.

Animals↗
PubMedDate not supplied

Incorporating direct and indirect evidence using bayesian methods: an applied case study in ovarian cancer.

OBJECTIVE: To demonstrate the application of a Bayesian mixed treatment comparison (MTC) model to synthesize data from clinical trials to inform decisions based on all relevant evidence. METHODS: The value of an MTC model is demonstrated using a probabilistic decision-analytic model developed to assess the cost-effectiveness of second-line chemotherapy in ovarian cancer. Three clinical trials were found that each made a different pair-wise comparison of three treatments of interest in the overall patient population. As no common comparator existed between the three trials, an MTC model was used to assess the combined weight of evidence on survival from all three trials simultaneously. This analysis was compared to an alternative approach that combined two of the trials to make the same comparison of all three treatments using a common comparator, and an informal approach that did not synthesize the available evidence. RESULTS: By including all three trials using an MTC model, the credible intervals around estimated overall survival were reduced compared with making the same comparison using only two trials and a common comparator. Nevertheless, the survival estimates from the MTC model result in greater uncertainty around the optimal treatment strategy at a cost-effectiveness threshold of 30,000 pounds per quality-adjusted life-year. CONCLUSIONS: MTC models can be used to combine more data than would typically be included in a traditional meta-analysis that relies on a common comparator. They can formally quantify the combined uncertainty from all available evidence, and can be conducted using the same analytical approaches as standard meta-analyses.

Antineoplastic Agents↗
PubMed2002

Simultaneous identification of Mycobacterium genus and Mycobacterium tuberculosis complex in clinical samples by 5'-exonuclease fluorogenic PCR.

Early diagnosis of tuberculosis and screening of other mycobacteria is required for the appropriate management of patients. We have therefore developed a 5'-exonuclease fluorogenic PCR assay in a single-tube balanced heminested format that simultaneously detects Mycobacterium tuberculosis complex (MTC) and members of the Mycobacterium genus (MYC) using the 16S ribosomal DNA target directly on clinical samples. One hundred twenty-seven clinical samples (65 smear negative and 62 smear positive) with a positive culture result from 127 patients were tested, including 40 negative control specimens. The finding of both a positive MTC and probe value and a positive MYC probe value confirmed the presence of MTC or mycobacteria with a 100% positive predictive value. However, a negative value for MTC or MYC did not discount the presence of mycobacteria in the specimen. Interestingly, the addition of the MYC probe allowed the diagnosis of an additional 7% of patients with tuberculosis and rapid screening of nontuberculous mycobacteria (NTM). Thus, over 75% of the patients were diagnosed with mycobacterial disease by PCR. The sensitivity was much higher on smear-positive samples (90.3%) than smear-negative samples (49.2%) and was slightly higher for MTC than NTM samples. With regard to the origin of the sample, MTC pulmonary samples gave better results than others. In conclusion, we believe this test may be useful for the rapid detection of mycobacteria in clinical samples and may be a valuable tool when used together with conventional methods and the clinical data available.

DNA, Bacterial↗
PubMed1988

Methylprednisolone versus metoclopramide for prevention of nausea and vomiting in breast cancer patients treated with intravenous cyclophosphamide methotrexate 5-fluorouracil: a double-blind randomized study.

The antiemetic efficacy and toxicity of methylprednisolone (MP) and metoclopramide (MTC) in prevention of nausea and vomiting in breast cancer patients receiving intravenous cyclophosphamide methotrexate 5-fluorouracil (CMF) chemotherapy has been evaluated in a double-blind trial. The two antiemetic drugs (MP vs. MTC) offered the majority of patients a similar complete protection from vomiting (76.5 vs. 66.7%) and nausea (82.4 vs. 81.8%), but in older patients MTC seems more efficacious than MP. Sedation was found more frequently (p = 0.02) in patients treated with MTC. In conclusion, in patients treated with CMF the use of MP as preventive therapy of nausea and vomiting is to be preferred to MTC due to its better tolerability, but in older patients MTC should be considered if MP fails.

Adult↗
PubMed1987

Effect of metoclopramide therapy on arginine vasopressin excretion and renal water handling in premature infants.

The role of endogenous dopamine (DA) in regulating arginine vasopressin (AVP) release and renal water excretion was studied in 10 premature infants with a mean birth weight of 1,341 g (range 1,150-1,660 g) and a mean gestational age of 30.2 weeks (28-33 weeks), who were given metoclopramide (MTC), a specific DA antagonist. It was demonstrated that in response to MTC urine flow rate increased significantly from a basal value of 0.90 +/- 0.07 to 1.27 +/- 0.09 ml/min/1.73 m2 (mean +/- SE; p less than 0.01), urinary sodium excretion from 6.10 +/- 1.47 to 11.7 +/- 2.24 microEq/min/1.73 m2 (p less than 0.025) and osmolar clearance from 0.38 +/- 0.044 to 0.600 +/- 0.075 ml/min/1.73 m2 (p less than 0.01). MTC administration did not cause any alterations in free water clearance, whereas urinary AVP excretion fell significantly from 49.38 +/- 10.13 to 32.66 +/- 6.53 ng/min/1.73 m2 (p less than 0.05) after MTC. It is concluded that, contrary to adults, in low birth weight premature infants endogenous DA is enhancing rather than inhibiting AVP release and the MTC-induced water diuresis is independent of the fall of AVP since free water clearance remained unaltered after MTC.

Arginine Vasopressin↗
PubMed2005

Screw fixation compared to H-locking plate fixation for first metatarsocuneiform arthrodesis: a biomechanical study.

BACKGROUND: Several different techniques have been used for fixation of first metatarsocuneiform (MTC) joint arthrodesis, a standard treatment for arthritis, instability, and deformity of the MTC joint. Improved plating systems using locking designs are now available, but no studies have yet compared this construct with other methods. We compared load to failure with a locking plate design versus standard crossed-screw fixation. METHODS: Ten matched pairs of fresh frozen cadaver feet were used. The bone density of each pair was measured with DEXA scanning. One foot of each pair was randomly assigned to have a dorsomedial Normed H titanium locking plate (Normed Medizin-Technik Vertriebs-GmbH, D-78501 Tuttlingen, Germany) applied to the first MTC joint. On the other foot of the pair, fixation of the first MTC joint was done with crossed ACE DePuy 4.0 (DePuy/Ace, Warsaw, IN) titanium cannulated screws. The first metatarsal and first cuneiform were then isolated and planted in an epoxy resin. The specimens were loaded to failure in a four-point bending configuration using a MTS Mini Bionix test frame (MTS Systems Corp., Eden Prairie, MN). Failure was defined as displacement of more than 3 mm at the arthrodesis site. The Student t-test was used to determine any observed differences, with significance set at p <or= 0.05. RESULTS: The mean maximal load to failure was 140.08 N (SD +/- 77.1) for screw fixation alone and 58.09 N (SD +/- 11.86) for the H-locking plate. This difference was statistically significant (p = 0.008). The mean stiffness of the construct for screw fixation alone was 83.10 N/mm (SD +/- 49.8) and 19.96 N/mm for the H-locking plate. This difference also was statistically significant (p = 0.004). CONCLUSION: Screw fixation for first MTC arthrodesis created a stronger and stiffer construct than did the H-locking plate. This was likely due to the mechanical design of the implants. Compression across the MTC joint could be applied with the screws, but the plate relied on a fixed angle design with no compression.

Arthrodesis↗