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Biomedical subjects

L Cohen

Publications and source records attributed to L Cohen.

At least 37 records · Page 2Linked to original sources

Intraoperative mapping of the cortical areas involved in multiplication and subtraction: an electrostimulation study in a patient with a left parietal glioma.

OBJECTIVES: Advances in neuroimaging studies have recently improved the understanding of the functional anatomy of the calculation processes, having in particular underlined the central role of the angular gyrus (AG). In this study, the authors applied this knowledge to the surgical resection of a glioma invading the left AG, by localising and sparing the cortical areas involved in two different components of calculation (multiplication and subtraction), using direct electrical stimulations. METHODS: A calculation mapping was performed in a patient without deficit except a slightly impaired performance for serial arithmetic subtraction, during the resection under local anaesthesia of a left parieto-occipital glioma invading the dominant AG. After somatosensory and language mappings, cortical areas involved in single digit multiplications and subtractions of seven were mapped using the method of electrostimulation, before glioma removal. RESULTS: Distinct sites specifically involved in multiplication or subtraction were detected within the left AG, with a precise spatial distribution and overlapping. All the eloquent (somatosensory, language, and calculation) areas were surgically spared. Postoperatively, the patient had a transient complete deficit for arithmetic subtraction, without either multiplication or language disturbance. The tumour removal was complete. CONCLUSIONS: These findings suggest: firstly, the usefulness of an intraoperative calculation mapping during the removal of a lesion involving the left dominant AG, to avoid permanent postoperative deficit of arithmetic processes while optimising the quality of tumour resection; secondly, the possible existence of a well ordered and dynamic anatomo-functional organisation for different components of calculation within the left AG.

Adult↗

Pseudoascites.

Explore the source record for details and available documents.

Ascites↗

Liquid chromatography-tandem mass spectrometric quantitation of cyclophosphamide and its hydroxy metabolite in plasma and tissue for determination of tissue distribution.

Cyclophosphamide (CP) and its metabolite, hydroxycyclophosphamide (OH-CP) have been quantitated in mouse plasma and tissue by derivatization combined with liquid chromatography-tandem mass spectrometry (LC-MS-MS). The derivatization was conducted immediately upon sample collection, to trap the OH-CP metabolite intermediate prior to further conversion to phosphoramide mustard or other reaction products. This simple and straightforward derivatization procedure, combined with sample extraction via protein precipitation, allowed quantitation of CP and the oxime derivative of OH-CP in plasma for concentrations ranging from approximately 12.5-3333 ng/ml, and in spleen tissue for concentrations of 1,250-50,000 ng/g. The short cycle time (2.5 min) of the LC-MS-MS method allowed high throughput analysis with minimal matrix interference. Mouse plasma levels were quantitated for doses of 40, 65 and 120 mg/kg; spleen concentrations were determined for mice dosed at 120 mg/kg. The CP and oxime plasma levels correlated well with dose amounts. The CP levels in the spleen and plasma were similar while the oxime levels in the spleen were significantly lower than the plasma.

Animals↗

Noradrenergic modulation of human cortex excitability by the presynaptic alpha(2)-antagonist yohimbine.

The objective of this study was to determine if yohimbine, a central norepinephrine enhancing drug, increases cortico-motoneuronal excitability in intact humans. Transcranial magnetic stimulation was used to assess excitability of the motor system reflected in the parameters motor threshold, recruitment curve, intracortical inhibition and intracortical facilitation before and after oral administration of 20 and 40 mg yohimbine. Oral intake of 40 but not 20 mg yohimbine increased slope and plateau of the recruitment curve and intracortical facilitation. Motor threshold and intracortical inhibition remained unchanged. The data show that pharmacological enhancement of central norepinephrine in humans is effective to increase the cortico-motoneuronal excitability. Since cortical excitability is closely linked to neuroplasticity, this observation might be of possible relevance for strategies to enhance rehabilitative processes after cortical lesions by pairing noradrenergic drugs with motor training.

Adrenergic alpha-Antagonists↗

The association between treatment-specific optimism and depressive symptomatology in patients enrolled in a Phase I cancer clinical trial.

BACKGROUND: Previous research has found that cancer patients often overestimate the likelihood that they will achieve a positive response in Phase I trials. However, maintaining optimistic expectations may help patients cope with a poor prognosis and uncertain outcome. The authors prospectively examined the association between treatment-specific optimism and mental health among patients participating in a Phase I/b trial. METHODS: Twenty-four patients with metastatic renal cell carcinoma and 22 patients with metastatic melanoma completed an assessment battery at the beginning of treatment and 3 weeks later, on the final day of treatment. Patients completed measures of treatment-specific optimism (e.g., beliefs regarding the treatment working), depressive symptomatology, mood disturbance, and overall distress. RESULTS: The majority of patients believed that the treatment would either cure them (87%) or stop cancer progression (85%). Regression analyses revealed that the level of treatment-specific optimism (e.g., "The treatment I am receiving may cure me") was associated negatively with baseline measures of depressive symptoms (P < 0.006), mood disturbance (P < 0.001), and symptoms of distress (P < 0.0001) after controlling for age, number of metastases, and time since diagnosis. Patients with symptoms of clinical depression at baseline reported significantly lower levels of treatment-specific optimism than patients without symptoms (P < 0.03). Treatment-specific optimism also was associated negatively with symptoms of depression at the end of treatment (P < 0.003), controlling for symptoms of depression at the beginning of treatment. CONCLUSIONS: The results of the current study suggest that high levels of treatment-specific optimism are associated with better mental health outcomes at both the beginning and end of treatment.

Adult↗

Breaking bad news about cancer: patients' preferences for communication.

PURPOSE: The goal of this study was to assess patients' preferences regarding the way in which physicians deliver news about their cancer diagnosis and management. PATIENTS AND METHODS: A sample of 351 patients with a variety of cancers completed a measure assessing their preferences for how they would like to be told news about their cancer. Patients rated characteristics of the context and content of the conversation as well as physician characteristics. RESULTS: Factor analysis indicated that patients' preferences for how they would like to be told news regarding their cancer can be grouped into the following three categories: (1) content (what and how much information is told); (2) facilitation (setting and context variables); and (3) support (emotional support during the interaction). Women (P =.02) and patients with higher education (P =.05) had significantly higher scores on the Content scale, women (P =.02) had higher scores on the Support scale, and younger patients (P =.001) and those with more education (P =.02) had higher scores on the Message Facilitation scale. Medical variables were not associated with patients' ratings of the importance of the three subscales. CONCLUSION: Patients rated items addressing the message content as most important, though the supportive and facilitative dimensions were also rated highly. Understanding what is important to patients when told news about their cancer provides valuable information that may help refine how this challenging task is best performed.

Adult↗

Risk of endometrial carcinoma associated with BRCA mutation.

OBJECTIVE: Inherited mutations in the BRCA1 or BRCA2 genes are associated with a greatly increased lifetime risk of breast and ovarian cancers and a modestly increased risk of several other cancer types. Several case reports of endometrial carcinoma in women with a BRCA mutation have led to speculation regarding the effect of these genes on the risk of endometrial cancer. The purpose of this study was to test the hypothesis that germline mutation of a BRCA gene is associated with an increased risk of endometrial carcinoma. METHODS: A retrospective cohort of 199 consecutive Ashkenazi Jewish patients with endometrial carcinoma was identified from a 12-year period at this institution. All were genotyped for the three BRCA founder mutations (185delAG and 5382insC in BRCA1 and 6174delT in BRCA2) that exist in this population, and the case frequency was compared to the known population frequency of these mutations. Additionally, endometrial carcinomas occurring in patients with BRCA mutations were assessed for somatic loss of the wild-type BRCA allele. RESULTS: Germline BRCA mutations were identified in 3 (1 in BRCA1 and two in BRCA2) of 199 (1.5%) patients, compared to a frequency of 2.0% in this population generally. A relative risk of endometrial carcinoma associated with BRCA mutation, as estimated by the odds ratio, was calculated as 0.75 (95% CI = 0.24--2.34; P = 0.6). Loss of the wild-type BRCA allele was observed in two of three tumors associated with a BRCA mutation. CONCLUSIONS: For individuals with a germline BRCA mutation, the lifetime risk of endometrial carcinoma is not increased.

Aged↗

Role of the human motor cortex in rapid motor learning.

Recent studies suggest that the human primary motor cortex (M1) is involved in motor learning, but the nature of that involvement is not clear. Here, learning-related changes in M1 excitability were studied with transcranial magnetic stimulation (TMS) while na subjects practiced either a ballistic or a ramp pinch task to the 0.5-Hz beat of a metronome. Subjects rapidly learned to optimize ballistic contractions as indicated by a significant increase in peak pinch acceleration and peak force after the 60-min practice epoch. The increase in force and acceleration was associated with an increase in motor evoked potential (MEP) amplitude in a muscle involved in the training (flexor policis brevis) but not in a muscle unrelated to the task (abductor digiti minimi). MEPs returned to their baseline amplitude after subjects had acquired the new skill, whereas no practice-induced changes in MEP amplitude were observed after subjects had overlearned the task, or after practicing slow ramp pinches. Since the changes in MEP amplitude were observed only after TMS of M1 but not after direct stimulation of the corticospinal tract, these findings indicate task- and effector-specific involvement of human M1 in rapid motor learning.

Adolescent↗

Pericardial reinforcement after partial atrial resection in idiopathic enlargement of the right atrium.

A 2-year-old boy in whom idiopathic enlargement of the right atrium was diagnosed in utero by fetal echocardiography underwent surgical intervention because of progression of right atrial dilatation. During operation, the lateral right atrial wall was externally reinforced after partial resection by approximating and fixing the neighboring autologous pericardium around the external circumference of the right atrium. This technique is a useful means of preventing recurrence of dilatation in histologically abnormal right atrial tissue that predisposes the patient to possible reintervention.

Child, Preschool↗

Cerebral mechanisms of word masking and unconscious repetition priming.

We used functional magnetic resonance imaging (fMRI) and event-related potentials (ERPs) to visualize the cerebral processing of unseen masked words. Within the areas associated with conscious reading, masked words activated left extrastriate, fusiform and precentral areas. Furthermore, masked words reduced the amount of activation evoked by a subsequent conscious presentation of the same word. In the left fusiform gyrus, this repetition suppression phenomenon was independent of whether the prime and target shared the same case, indicating that case-independent information about letter strings was extracted unconsciously. In comparison to an unmasked situation, however, the activation evoked by masked words was drastically reduced and was undetectable in prefrontal and parietal areas, correlating with participants' inability to report the masked words.

Adult↗

ANCA-associated vasculitis in Greek siblings with chronic exposure to silica.

We present the case of two siblings with similar environmental exposure to silica. Both of them developed perinuclear antineutrophil cytoplasmic antibody (p-ANCA)-associated vasculitis with pulmonary-renal syndrome. p-ANCAs were present with antimyeloperoxidase specificity on capture enzyme-linked immunosorbent assay. Treatment with corticosteroids and cyclophosphamide resulted in resolution of the clinical picture. Chronic exposure to silica is the leading environmental factor associated with ANCA-positive vasculitis. Several clusters of systemic vasculitis have been described. Positive and negative human leukocyte antigens (HLA) have been reported in systemic vasculitis. Affected brothers in our case shared one parental HLA haplotype. To the best of our knowledge, this is the first report of a family cluster of silica-induced, ANCA-associated systemic vasculitis with members sharing some of their HLA antigens.

Adult↗

Characterization of recombinant hepatitis A virus genomes containing exogenous sequences at the 2A/2B junction.

Hepatitis A virus (HAV) differs from other members of the family Picornaviridae in that the cleavage of the polyprotein at the 2A/2B junction, commonly considered to be the primary polyprotein cleavage by analogy with other picornaviruses, is mediated by 3C(pro), the only proteinase encoded by the virus. However, it has never been formally demonstrated that the 2A/2B junction is the site of primary cleavage, and the actual function of the 2A sequence, which lacks homology with sequence of other picornaviruses, remains unknown. To determine whether 2A functions in cis as a precursor with the nonstructural proteins, we constructed dicistronic HAV genomes in which a heterologous picornaviral internal ribosome entry site was inserted at the 2A/2B junction. Transfection of permissive FRhK-4 cells with these dicistronic RNAs failed to result in the rescue of infectious virus, indicating a possible cis replication function spanning the 2A/2B junction. However, infectious virus was recovered from recombinant HAV genomes containing exogenous protein-coding sequences inserted in-frame at the 2A/2B junction and flanked by consensus 3C(pro) cleavage sites. The replication of these recombinants was less efficient than that of the parent virus but was variable and not dependent upon the length of the inserted sequence. An HAV recombinant containing a 420-nt insertion encoding the bleomycin resistance protein Zeo was stable for up to five passages in cell culture. Inserted sequences were deleted from replicating viruses, but this did not result from homologous recombination at the flanking 3C(pro) cleavage sites, since the 5' and 3' segments of the inserted sequence were retained in the deletion mutants. These results indicate that the HAV polyprotein can tolerate an insertion at the 2A/2B junction and that the 2A polypeptide does not function in cis as a 2AB precursor. Recombinant HAV genomes containing foreign protein-coding sequences inserted at the 2A/2B junction are novel and potentially useful protein expression vectors.

Animals↗

Reliability and validity of three-dimensional fetal brain volumes.

OBJECTIVE: To determine the intraobserver and interobserver variability in calculating three-dimensional fetal brain volumes and to examine the relationship between these volumes and biparietal diameter and head circumference measurements and estimated gestational age. METHODS: Eighty-five subjects between 16 and 40 completed weeks' gestation participated in the Institutional Review Board-approved study. Fetal head images were obtained axially and stored on a magnetic optical disk. The fetal brain volumes were calculated in triplicate by each of 2 observers using 8 to 10 coronal cuts. The coefficient of variation was determined for both physicians. Pearson correlations and linear regression were used to evaluate the relationship between three-dimensional head volume and standard biparietal diameter and head circumference measurements and estimated gestational age. RESULTS: The coefficients of variation were low for both investigators, at 2.04% and 2.44%. The correlations between fetal brain volumes and biparietal diameter, head circumference, and estimated gestational age were all highly significant (P < .001). The linear regression of brain volumes with estimated gestational age was also highly significant (P < .001). CONCLUSIONS: Three-dimensional fetal brain volume measurements had excellent intraobserver and interobserver reliability. The volumes correlated very well with standard biparietal diameter and head circumference measurements. These volumes can also be used to determine estimated gestational age.

Brain↗