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R Cohen

Publications and source records attributed to R Cohen.

At least 163 records · Page 9Linked to original sources

Prognostic factors for survival and for biochemical cure in medullary thyroid carcinoma: results in 899 patients. The GETC Study Group. Groupe d'étude des tumeurs à calcitonine.

BACKGROUND: Prognostic factors of sporadic or inherited medullary thyroid carcinoma (MTC) are still controversial and have been assessed in old and small series. A better knowledge of these factors would improve patient management. OBJECTIVE: To evaluate factors involved in the prognosis of MTC in a large series of cases, using uni- and multivariate analysis. DESIGN AND PATIENTS: Clinical, biological, surgical and epidemiological data on 899 MTC patients, diagnosed between 1952 and 1996, were collected by the French Calcitonin Tumors Study Group (GETC) with a standardized questionnaire, and processed in a national database. MEASUREMENTS: Survival and biochemical cure (i.e. normal basal post-operative serum calcitonin levels) were analysed with Kaplan and Meier and log-rank test statistical procedures. Data are presented as adjusted rather than observed survival, to consider only patients who died of MTC. Cox's forward-stepping proportional hazard model was used to analyse factors with a significant influence on survival by univariate analysis. RESULTS: Apart from the large proportion of familial forms (43%), the general characteristics of our population were similar to those in other studies: mean age at surgery = 43.4 years; sex ratio = 1 male/1.35 female; stage I = 20.8%; stage II = 21.2%; stage III = 46.5% and stage IV = 11.5%. 863 (96%) patients underwent surgery; 43% of operated patients were biochemically cured. Adjusted survival was 85.7 +/- 1.5% at 5 years and 78.4 +/- 2.1% at 10 years. Multivariate analysis showed that age and stage were independent predictive factors of survival. Gender, type of surgery, type of familial form were predictive only in univariate analysis. Biochemical cure predicts a survival rate of 97.7% at 10 years. Authentic recurrence, that is subsequent elevation of calcitonin (CT) after post-operative normalization, was found in 4.9%. In non-cured patients (57%), survival was still good: 80.2% (+/- 2.2%) and 70.3% (+/- 2.9%) at 5 and 10 years, respectively. Similarly, prediction of biochemical cure was solely dependent on stage. CONCLUSION: Survival of these medullary thyroid carcinoma patients appears better than expected even in non-cured patients. Considering the strong impact of stage, the necessity for pre-operative diagnosis of MTC is obvious.

Adult↗

Sporadic medullary microcarcinoma of the thyroid: a retrospective analysis of eighty cases.

Clinical characteristics and prognosis of 80 patients (53 women and 27 men) with sporadic medullary thyroid carcinomas (MTC), less than 1 cm in size (micro-MTC), operated on between 1971 and 1996 are reported (73 total and 7 partial thyroidectomies). These patients, obtained from a national database of 899 patients with MTC, were compared with 357 cases of sporadic MTC greater than 1 cm and 149 subjects with familial MTC less than 1 cm (familial micro-MTC). Median age at surgery was 52.5 years, a distribution similar to larger sporadic MTC. Micro-MTC was identified due to elevated calcitonin (47.5%), clinically identified lymph node (10.0%), distant metastases (6.3%) or pathologic finding at surgery (36.2%). Diarrhea and/or flushing were observed in 6 patients including 4 with clinically identified lymph node. Among patients who had lymph node dissection at surgery (68.8%), lymph node involvement with tumor was observed in 30.9%, and was significantly more frequent in multifocal (7/11) than in unifocal micro-MTC (p < 0.03). All sporadic micro-MTC were unilateral. Survival rate was 93.9% +/- 4.4% (SE) at 10 years, greater than that observed in sporadic macro-MTC (p = 0.04). Normal postoperative basal calcitonin (CT) was obtained in 71.1% of micro-MTC patients versus 33.6% in sporadic macro-MTC (p < 0.01). Sporadic micro-MTC is much more frequent than expected, 15% of MTC in our series. Although specific survival rate and percentage of biological cure in micro-MTC are significantly better than for larger tumors, the frequency of lymph node involvement, however, justifies an aggressive surgical approach including total thyroidectomy and bilateral central lymph node dissection.

Adolescent↗

Calcitonin receptor mRNA is expressed in human medullary thyroid carcinoma.

We recently reported the presence of a truncated form (h-CTR2) of the human calcitonin receptor (CTR) in TT cells, a cell line derived from medullary thyroid carcinoma (MTC). This form (h-CTR2), characterized by the absence of 16 amino acids in the first intracellular domain, was also detected in two cases of MTC. In the present study we determined the expression of CTR mRNA in a larger sample, representative of the different clinical forms of MTC, and in normal thyroid. h-CTR2 was expressed in all MTC specimens (both sporadic and familial) and in the normal thyroid samples. The expression of the receptor mRNA was higher in MTC compared with normal thyroid. Moreover, CT and CTR mRNA levels were modified significantly during proliferation. This result suggests that CT may be involved in proliferation of MTC via autocrine/paracrine regulation. Calcitonin secretion by MTC may play a role in the development and spread of these tumors.

Carcinoma, Medullary↗

Pentagastrin testing in patients with renal insufficiency: normal responsivity of mature calcitonin.

Calcitonin (CT) is the most sensitive tumor marker for medullary thyroid carcinoma available, but it lacks specificity. Chronic renal failure (CRF) is known to be associated with elevations of serum immunoreactive calcitonin. Using an immunoradiometric assay to detect only mature CT, we evaluated the basal CT level and its response to pentagastrin in 30 patients with CRF and compared these data with those obtained in 71 controls. Basal mature CT was significantly higher (p < 0.05) in patients with CRF (3.55 pg/mL) than in controls (2.00). Among these patients, 20% had basal CT levels more than 10 pg/mL with a maximum of 51 pg/mL. Peak CT values (highest value obtained 3 or 5 minutes after pentagastrin) were comparable in the two groups. Among patients with CRF, 10% had peak CT values greater than 30 pg/mL with a maximum of 53 pg/mL. In this group of patients, no correlation was found between CT (at any time during the test) and parathyroid hormone, calcium, phosphate, or creatinine clearance. Men had significantly higher CT values compared with women at each time point tested, including peak values. Patients with CRF, who have not yet undergone dialysis, have moderately elevated basal CT levels, but have normal pentagastrin-stimulated peak CT levels.

Calcitonin↗

Memory processes in depressed geriatric patients with and without subcortical hyperintensities on MRI.

In this study, 12 patients over age 60 with depression with moderate to severe subcortical hyperintensities (SH) localized to the periventricular white matter were identified by quantitative MRI. Using the California Verbal Learning Test, they were compared with 12 age-, education-, and severity-matched patients with depression with minimal white matter changes on specific aspects of memory performance. Patients with cortical lesions, neurologic or systemic illness affecting cognition, and history of substance abuse were excluded. Patients in the group with high SH showed reduced use of semantic encoding strategies (p < 0.05), reduced learning efficiency (p < 0.05), and a greater discrepancy between free recall and recognition discriminability (p < 0.05) than their low SH counterparts. This pattern of performance on memory tasks is similar to that found in previous studies to be associated with subcortical degenerative disorders such as Huntington's and Parkinson's diseases. Geriatric patients with depression with SH may represent a subgroup with greater subcortical involvement, with associated cognitive and functional decline.

Aged↗

Learning and memory in rape victims with posttraumatic stress disorder.

OBJECTIVE: Studies have shown memory deficits among combat veterans with posttraumatic stress disorder (PTSD); however, high rates of comorbid conditions, including alcoholism, make it difficult to definitively associate these findings with the PTSD diagnosis. In this study the authors examined memory functioning among rape survivors without alcoholism or substance abuse but with PTSD. METHOD: Rape victims with (N = 15) and without (N = 16) PTSD were compared to age- and education-matched nontraumatized comparison subjects (N = 16) on measures of learning and memory. RESULTS: The subjects with PTSD performed significantly worse than the other groups on delayed free recall. The deficits were ameliorated by cueing and recognition testing. CONCLUSIONS: Recall deficits in noncombat PTSD patients strengthen the theory that memory deficits are associated with the PTSD diagnosis. The deficits were mild and were not attributable to comorbid depression, anxiety, or substance abuse.

Adult↗

A service for women with schizophrenia.

A program for women with schizophrenia that combines inpatient, outpatient, and outreach services is described. The program was established at the Clarke Institute of Psychiatry at the University of Toronto in 1995. Services include a comprehensive patient and family assessment, with subsequent recommendations to the treating clinician about differential diagnosis, psychopharmacologic and psychosocial treatments, and patient management during pregnancy and early parenthood. Other components of the program are home-based outreach services, substance abuse counseling, instruction of new mothers and parenting training, sex education, relationship-focused groups, and self-protection in an urban environment to prevent victimization. The clinic has established liaisons with pediatricians and gynecologists in the community to provide care to clinic patients. Linkages have also been established with agencies and facilities to fill gaps in the service spectrum, such as fitness programs and leisure activities and children's aid and protection.

Adult↗

[Atenolol/nifedipine combination: efficacy and tolerability of low dose synergistic bitherapy in the treatment of arterial hypertension].

During recent decades, undeniable progress has been made with regard to the management of arterial hypertension. Larger numbers of patients are aware they have hypertension, receive treatment and benefit from this therapy. Furthermore, significant reductions have been observed in morbidity and mortality resulting from cardiovascular diseases. The objectives of hypertension treatment have been formulated on the basis of results of extensive epidemiological studies. Only a few patients receiving monotherapy actually achieve and maintain acceptable blood pressure levels. The complex pathogenesis of essential hypertension, the implications of nervous and humoral counter-regulatory effects, the heterogeneous character of individual responses to any given class of antihypertensive treatment and the onset of adverse effects all account for these failures. The search for a simple, effective and well-tolerated treatment based on a low dose combination of 2 classes of antihypertensive agents is consequently legitimate. The fixed combination of atenolol 50 mg and sustained release nifedipine 20 mg enables patients to benefit from the antihypertensive synergy of a beta-blocker and a calcium antagonist (dihydropyridine). Several open-ended or double-blind, controlled studies have shown that this combination produces a more marked antihypertensive effect than the individual components used alone or other reference monotherapies. Furthermore, it has been shown that this effect persists throughout the entire 24-hour period; this has been confirmed by 24-hour blood pressure monitoring. Short and medium term tolerability is significantly improved: the side effects commonly associated with the 2 drugs when used alone are reduced with the combination formulation since the 2 active substances have different and complementary mechanisms of action. In addition, long term studies have shown that therapeutic efficacy and tolerability remain stable and have even been seen to improve over a 12-month period. The fixed combination of atenolol-nifedipine has a role in strategies for the treatment of mild to moderate hypertension, particularly under the following conditions: when first-line monotherapy has failed to attain specific clearly defined objectives, including stabilised blood pressure levels together with acceptable tolerability. when patient compliance is jeopardised as a result of undesirable side effects. when the vascular burden is aggravated through lack of attention to individual risk factors in hypertensive patients. In more serious forms of hypertension, the atenolol-nifedipine combination can replace sequential monotherapies or other combination treatments that have failed to comply with the various criteria of therapeutic efficacy. Controlling arterial hypertension commonly requires polytherapy with 3 or even 4 different drugs in conjunction with particularly strict rules governing hygiene and diet. The addition of the fixed combination of atenolol-nifedipine simplifies the treatment of patients with arterial hypertension by limiting the daily doses and reducing laboratory monitoring.

Adrenergic beta-Antagonists↗

Dynamical aspects of the EEG in different psychopathological states in an interview situation: a pilot study.

Dynamical brain states can be characterized by non-linear measures of EEG. The present study shows that critical transitions, i.e., abrupt changes from one dynamic pattern of neural mass activity to another one, may be detected by abrupt variations in local chaoticity. Using an ambulatory device, EEG was recorded from 10 patients with a schizophrenic and two patients with an affective disorder during a series of 25-min interviews. Dynamical aspects, in particular, phase transitions in the EEG-dynamics of the EEG were characterized by means of a measure that continuously estimates the chaoticity of the EEG signal and is thus related to its predictability. Results indicate simpler dynamics of the EEG time series in paranoid-hallucinatory patients, while at the same time these patients tended to exhibit more abrupt transitions/unit of time between different dynamical EEG states. Such sudden phase transitions in brain activity were significantly enhanced prior to expressions of thought disorders that were detected by the interviewer and an observer in the conversation, compared with time periods during the interview without such symptoms.

Adult↗

Acute maduramicin toxicity in calves.

A herd of 277 beef-breed calves in three age groups was mistakenly given the poultry coccidiostat maduramicin in a total mixed ration. It caused an acute toxicosis in which sudden death was the sole clinical finding in most cases. One group of 212 calves aged five to eight months suffered a mortality of 51 per cent in eight days and a total mortality of 56 per cent during the 40 days in which mortality was recorded. Mortality of only 3 per cent was recorded in two other groups of calves aged nine to 16 months in eight days and a total mortality of 11 per cent over the 40-day period.

Age Factors↗

The prognostic application of cytokeratin typing of nonsmall cell lung carcinoma. A retrospective study.

BACKGROUND: In a previous study, the authors used a variety of anticytokeratin monoclonal antibodies to show that a large proportion of lung tumors cytologically diagnosed as squamous cell carcinoma contain cells expressing simple epithelial cytokeratins, suggesting that these tumors have their origin in adenocarcinoma. These findings raised the possibility that cytokeratin (CK) typing might have a diagnostic capacity not attainable by standard histopathology. The aim of the current study was to assess the value of CK typing for this purpose by determining the correlation between the diagnosis of lung tumors based on CK typing and the survival rate of the patients. METHODS: Paraffin embedded tissue sections of 66 nonsmall cell lung carcinoma (NSCLC) specimens were examined. These included 18 adenocarcinomas, 32 squamous cell carcinomas, and 16 undifferentiated carcinomas, all diagnosed surgically and histopathologically, and further classified as either Stage I or II. CK typing was performed using the streptavidin-biotin-peroxidase method, employing the following anti-CK monoclonal antibodies: Ks.B.17 (which reacts with CK 18), A3-3 (which reacts with CK 13), and E5-9 (which reacts with CK 10). RESULTS: Comparison between the 5-year survival rates (5 ysr) of patients with different NSCLC indicated that all types of Stage II tumors had a much poorer prognosis than Stage I tumors. Differences found in the 5 ysr among patients with different types of Stage I tumors were not statistically significant (adenocarcinomas, 33% 5 ysr; squamous cell carcinomas, 59% 5 ysr; undifferentiated carcinomas, 36% 5 ysr; all diagnosed by conventional histopathology). Similarly, no significant differences were noted in 5 ysr between patients with tumors stained positively or negatively with monoclonal antibodies A3-3 or E5-9 (anti-CK 13 and anti-CK 10, respectively). In contrast, highly significant differences (P = 0.002) were found in the 5 ysr between patients with Stage I tumors positively or negatively stained with monoclonal antibody Ks.B.17 (23% vs. 75% 5 ysr, respectively) regardless of the histologic types of tumors. Especially informative was a combination of immunohistochemical and histologic diagnoses, with best survival rates (87% 5 ysr) in Ks.B.17 negative tumors histologically diagnosed as Stage I squamous cell carcinomas and worst survival rates (14% 5 ysr) in Ks.B.17 positive tumors diagnosed as adenocarcinomas. CONCLUSIONS: The current study showed that CK 18 typing of lung tumors can provide a more accurate diagnosis and therefore facilitate the planning of more suitable therapeutic approaches.

Adenocarcinoma↗

Trisomy 2: confined placental mosaicism in a fetus with intrauterine growth retardation.

In a pregnancy that was monitored due to increased risk for Down syndrome in the triple test, a normal karyotype was found in amniocentesis. Follow-up by serial ultrasound examinations revealed intrauterine growth retardation (IUGR) at 20 weeks of gestation. The parents decided to terminate the pregnancy and the karyotype of the placental fibroblasts was 47,XX,+2. Analysis of polymorphic markers of chromosome 2 demonstrated (a) that trisomy 2 was confined to the placenta (CPM), (b) that the trisomy 2 cell line was a result of a meiotic I error of paternal origin, and (c) that the fetal tissues with a normal karyotype were biparental disomy 2.

Adult↗

Molecular DNA analysis for differentiation of persistence or relapse from recurrence in treatment failure of Streptococcus pyogenes pharyngitis.

In the evaluation of treatment failure in group A streptococcal pharyngitis, it is essential to distinguish persistence or relapse with homologous streptococcal strains from the acquisition of new, unrelated strains. Randomly amplified polymorphic DNA analysis and restriction fragment length polymorphism analysis of total DNA were used as epidemiological tools to compare 122 pre- and post-treatment Streptococcus pyogenes isolates obtained from 61 patients. The results obtained by molecular typing showed that bacteriological failures were due to the original strains in 43 cases (70%) and to new strains in 18 cases (30%). In the present study, restriction fragment length polymorphism analysis of total DNA appeared to be more discriminative than randomly amplified polymorphic DNA analysis. Thus, molecular analysis of DNA is an effective way to distinguish recurrence from persistence or relapse and will be useful in assessing the efficacy of new antibiotic treatments.

Adolescent↗

Using a video conference to teach clinical clerks in a one-week cardiothoracic clerkship.

BACKGROUND: Students report that their operating room experience during specialty clerkships has been less than satisfactory. To deal with this and other problems in a 1-week cardiothoracic clerkship, a video conference system was introduced. METHODS: Three teaching strategies were used: a seminar dealing with the disease process and a description of the operative procedure; bedside pre-operative assessment of the patient, with a tutor; and a live video conference of the operation. The tutor observed the live video presentation with the students, initiating interaction with the operating surgeon and facilitating questions and discussion. Video quality was maintained by one camera connected to the headlight of the surgeon and another placed above the operative field. RESULTS: Both students and staff expressed a high degree of satisfaction in debriefing sessions and on a standard faculty evaluation form. CONCLUSIONS: This innovation in surgery specialty teaching contributes to the acquisition of educational objectives in the operating room and in a cardiothoracic clerkship.

Adult↗

Increasing examiner involvement in an objective structured clinical examination by integrating a structured oral examination.

INTRODUCTION: The role of physician examiners in an objective structured clinical examination (OSCE) is relatively passive. In our institution examiners criticized the passive nature of their role. This study evaluates the reliability and viability of adding a structured oral examination to an OSCE. METHOD: Ten 24-minute stations consisted of three parts. Part I: 12 minutes-patient encounter. Part II: 6 minutes-oral presentation covering findings, differential diagnosis, and management plan. Part III: 6 minutes-structural oral examination (SOE), containing 5 predetermined questions. RESULTS: Over 6 consecutive days, 72 graduates were assessed. Overall average score: 72.02 (SD 5.05); reliability 0.84. Part I of the OSCE average score: 69.2 (SD 7.4); reliability 0.69. Part II oral presentation average score 64 (SD 5.8) reliability 0.87. SOE average score 77.7 (SD 6.3); reliability 0.64. Eighty-nine percent of the examiners indicated satisfaction with the new format. CONCLUSIONS: The SOE was a reliable component of an OSCE and contributed to the overall reliability. Examiners reported a higher degree of satisfaction with the examination.

Educational Measurement↗

Proliferating cell nuclear antigen as a marker of cell kinetics in aberrant crypt foci, hyperplastic polyps, adenomas, and adenocarcinomas of the human colon.

BACKGROUND: One of the first steps in multistage colonic carcinogenesis is increased cell proliferation and an upward shift of the proliferation zone of colonic crypts. In the present study, progression in cell kinetics was followed up at all sequential stages of colonic carcinogenesis, starting with aberrant crypt foci (ACF), the earliest putative preneoplastic lesions, hyperplastic and dysplastic polyps, and invasive carcinomas. MATERIALS AND METHODS: Colonic tissue and tumor specimens were prospectively obtained from 65 patients treated at our hospital for adenocarcinoma or malignant polyps. For identification of ACFs, dissected mucosal strips obtained from patients with colorectal cancer were stained with 0.1% methylene blue and scanned under dissecting microscope. Paraffin-embedded ACFs and macroscopic lesions were serially sectioned, deparaffinized, and stained with a monoclonal antiproliferating cell nuclear antigen (PCNA) antibody. The PCNA-labelling index (PCNA-LI), expressed as a ratio of positively stained nuclei to total nuclei counted, was calculated separately for basal, middle, and upper colonic crypt compartments. A comparison of the PCNA-LI was made for each compartment in normal mucosa, and hyperplastic and dysplastic lesions. RESULTS: A stepwise increase in the PCNA-LI was observed during neoplastic progression of colonic lesions. The two most important variables of increased cell proliferation, expressed as PCNA-LI per crypt compartment, were the presence of dysplasia and the size of dysplastic lesions. CONCLUSIONS: In colorectal carcinogenesis, hyperproliferation with upward expansion of proliferative compartment is a characteristic feature at all stages of malignant progression.

Adenocarcinoma↗

Neurofibromatosis of the small intestine mesentery in a child with neurofibromatosis type 1.

The authors present a case of mesenteric neurofibromatosis in a child, which is a rare complication of neurofibromatosis type 1 (NF1). This case is presented to illustrate the clinical features and the radiological appearance of mesenteric neurofibromatosis, which, in the appropriate clinical setting of NF1, are diagnostic. The authors also discuss the long-term complications of this condition, which includes the potential risk of malignant degeneration.

Child↗