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Biomedical subjects

T Levine

Publications and source records attributed to T Levine.

At least 19 recordsLinked to original sources

Peripheral neuropathies in Waldenström's macroglobulinaemia.

OBJECTIVE: We sought to determine the prevalence, clinical features, and laboratory characteristics of polyneuropathies in Waldenström's macroglobulinaemia (WM), a malignant bone marrow disorder with lymphocytes that produce monoclonal IgM. METHODS: We prospectively studied 119 patients with WM and 58 controls. Medical history was taken, and neurological examinations, electrodiagnostic tests, and serum studies were performed by different examiners who were blinded to results except the diagnosis of WM. RESULTS: Polyneuropathy symptoms, including discomfort and sensory loss in the legs, occurred more frequently (p<0.001) in patients with WM (47%) than in controls (9%). Patients with WM had 35% lower quantitative vibration scores, and more frequent pin loss (3.4 times) and gait disorders (5.5 times) than controls (all p<0.001). Patients with IgM binding to sulphatide (5% of WM) had sensory axon loss; those with IgM binding to myelin associated glycoprotein (MAG) (4% of WM) had sensorimotor axon loss and demyelination. Patients with WM with IgM binding to sulphatide (p<0.005) or MAG (p<0.001) had more severe sensory axon loss than other patients with WM. Demyelination occurred in 4% of patients with WM with no IgM binding to MAG. Age related reductions in vibration sense and sural SNAP amplitudes were similar ( approximately 30%) in WM and controls. CONCLUSIONS: Peripheral nerve symptoms and signs occur more frequently in patients with WM than controls, involve sensory modalities, and are often associated with gait disorders. IgM binding to MAG or sulphatide is associated with a further increase in the frequency and severity of peripheral nerve involvement. Age related changes, similar to those in controls, add to the degree of reduced nerve function in patients with WM.

Aged↗

Immunohistochemical expression of vascular endothelial growth factor and microvessel counting as prognostic indicators in node-negative colorectal cancer.

This manuscript reports a carefully controlled study of patients with Dukes B colorectal cancer (Dukes stage A, n=12 and Dukes stage B, n=44). Immunohistochemistry has been used to demonstrate reactivity for vascular endothelial growth factor (VEGF), and to measure levels of microvessel density (MVD) in order to assess the relationship of tumor angiogenesis with clinical outcome. Immunohistochemistry was performed using antibodies to VEGF and CD34 (for intratumoral vessel identification) and counting was performed at the invasive margin of the tumor. Results showed that for Dukes stage A patients 4/12 died of their disease, none of whose tumor was VEGF positive. In contrast, 2 patients who survived were positive for VEGF cytoplasmically, but neither showed increased tumor MVD. In Dukes B patients 10/44 died, 5 of whose tumor demonstrated VEGF reactivity, both in malignant cells and in tumor vascular endothelium. MVD ranged from 11 to 53 (median 28) for Dukes A cases and from 9 to 69 (median 32.5) for the Dukes B group. Kaplan-Meier plots and log rank test statistics for Dukes B patients demonstrated that VEGF reactivity in cells, and in tumor vascular endothelium was correlated with survival (p=0.047 and p < or = 0.06, respectively). There was a significant relationship between the presence of VEGF reactivity on vascular endothelium and outcome by Fisher's exact test (p=0.018). Similarly, by the same test VEGF positivity was significantly correlated with patient mortality (p=0.032). The presence of endothelial VEGF reactivity correlated with VEGF in malignant cells (p=0.0001) by Mann-Whitney U test and a significant inverse relationship between vessel density and patient survival was demonstrated (p = 0.019). The finding that in Dukes B patients MVD was inversely correlated with mortality supports the hypothesis that a low microvascular count is predicted close to the invasive margin, where VEGF expression is upregulated in response to hypoxia, induced by a lack of a functional vasculature. These data will be used to identify cohorts of patients who have a high risk of relapse and can be selected for adjuvant therapies such as VEGF antibody or antitumor antibody-directed therapy.

Adult↗

Sensory exam with a quantitative tuning fork: rapid, sensitive and predictive of SNAP amplitude.

BACKGROUND: In the standard neurologic examination, outcome measures of sensation testing are typically qualitative and subjective. The authors compared the outcome of vibratory sense evaluation using a quantitative Rydel-Seiffer 64 Hz tuning fork with qualitative vibration testing, and two other features of the neurologic evaluation, deep tendon reflexes and sensory nerve conduction studies. METHODS: The authors studied 184 subjects, including 126 with Waldenström's macroglobulinemia and 58 controls, over the course of a weekend. Standard neurologic examinations and quantitative vibratory testing were performed. Sensory nerve action potentials (SNAP) were tested as a measure of sensory nerve function. Tests were carried out by different examiners who were blinded to the results of other testing and to clinical information other than the diagnosis of Waldenström's macroglobulinemia. RESULTS: Quantitative vibration measurements in all body regions correlated with sural SNAP amplitudes. Quantitative vibration outcomes were more strongly related to sural SNAP results than qualitative evaluations of vibration. Quantitative vibration testing also detected a loss of sensation with increased age in all body regions tested. CONCLUSIONS: Quantitative vibratory evaluation with Rydel-Seiffer tuning fork is rapid, has high inter- and intrarater reliability, and provides measures for evaluating changes in sensory function over time. Examinations with the quantitative tuning fork are also more sensitive and specific than qualitative vibration testing for detecting changes in sensory nerve function. Use of the quantitative tuning fork takes no more time, provides more objective information, and should replace the qualitative vibratory testing method that is now commonly used in the standard neurologic examination.

Action Potentials↗

Epithelial-myoepithelial carcinoma of the parotid gland: a case report and review of the cytological and histological features.

Epithelial-myoepithelial carcinoma (EMC) is a rare biphasic tumour of the salivary glands typically arising in the parotid. Fine needle aspiration cytology is widely used in the initial investigation of salivary gland swellings and whilst the cytological features of this tumour have been described they are not well recognized. This report describes the clinicopathological features of a case of epithelial-myoepithelial carcinoma of the parotid gland and highlights the importance of awareness of this tumour in the differential diagnosis of biphasic tumours on fine needle aspiration cytology.

Biopsy, Needle↗

Sexual motives, gender, and sexual behavior.

The roles of gender and the sexual motives of Love, Pleasure, Conformity, Recognition, Dominance, and Submission in numerous usual and unusual sexual behaviors were investigated. In a survey of 191 college undergraduates it was found that Love, Pleasure, Conformity, and Recognition motives, often in interaction with gender, were all important predictors of sexual behavior. Gender was the best predictor of initiating usual sexual behavior, whereas the Love motive was the best predictor of actually engaging in usual sexual behavior. Pleasure and Recognition in interaction with gender were the best predictors of engaging in unusual sexual behavior. None of the sexual motives predicted initiating unusual sexual behavior. Findings suggest that a variety of sexual motives may underlie sexual behavior.

Adolescent↗

Effect of labor analgesia on breastfeeding success.

BACKGROUND: The effect of labor analgesia on breastfeeding success is not well defined. Some authors have hypothesized that labor analgesia may affect lactation success. The purpose of this observational study was to determine if intrapartum analgesia influenced breastfeeding success at 6 weeks postpartum in a setting that strongly supported breastfeeding. METHODS: Healthy women with uncomplicated term pregnancies who planned to breastfeed consented to a telephone interview. We recorded demographic data, labor induction status, delivery mode, and analgesic medications. At between 6 and 8 weeks postpartum, patients were asked to describe breastfeeding use, problems encountered, solutions derived, sources of support and information, and satisfaction. We created a logistic regression model using intrapartum analgesia information and controlling for demographic factors previously correlated with lactation success. RESULTS: We enrolled 189 women, contacted 177 women postpartum, and obtained complete data on 171 women. Of these, 59 percent received epidural analgesia, 72 percent breastfed fully, and 20 percent breastfed partially (> 50% of infant nutrition) at 6 weeks postpartum. After controlling for demographics and labor outcome, we could not demonstrate a correlation between breastfeeding success at 6 to 8 weeks and labor analgesia. CONCLUSIONS: In a hospital that strongly promotes breastfeeding, epidural labor analgesia with local anesthetics and opioids does not impede breastfeeding success. We recommend that hospitals that find decreased lactation success in parturients receiving epidural analgesia reexamine their postdelivery care policies.

Adult↗

A role for giantin in docking COPI vesicles to Golgi membranes.

We have previously shown that p115, a vesicle docking protein, binds to two proteins (p130 and p400) in detergent extracts of Golgi membranes. p130 was identified as GM130, a Golgi matrix protein, and was shown to act as a membrane receptor for p115. p400 has now been identified as giantin, a Golgi membrane protein with most of its mass projecting into the cytoplasm. Giantin is found on COPI vesicles and pretreatment with antibodies inhibits both the binding of p115 and the docking of these vesicles with Golgi membranes. In contrast, GM130 is depleted from COPI vesicles and inhibition of the GM130 on Golgi membranes, using either antibodies or an NH2-terminal GM130 peptide, inhibits p115 binding and vesicle docking. Together these results suggest that COPI vesicles are docked by giantin on the COPI vesicles and GM130 on Golgi membranes with p115 providing a bridge.

Animals↗

Ancient schwannoma masquerading as parotid pleomorphic adenoma.

Pleomorphic adenoma of the parotid gland is common. We report a typical case of a parotid gland swelling which clinically, radiologically and cytologically represented a pleomorphic adenoma. Only following surgical excision and histological examination however, was the true diagnosis of ancient schwannoma made. Benign peripheral nerve sheath tumours should always be considered in the differential diagnosis of parotid gland tumours.

Adenoma, Pleomorphic↗

The relationship of histology to genotype in chronic HCV infection.

The histological description of chronic hepatitis is undergoing considerable change at present. It has become important to define chronic hepatitis aetiologically and then define levels of necro-inflammatory change (grade) and fibrosis (stage). The aim of this study was to compare the ability of different histological scoring systems to detect differences in the pathological changes associated with infection with the different HCV genotypes that are known to have different natural histories. The histological appearances of liver biopsies from 29 HCV infected patients were compared by the Knodell histological activity index (HAI), modified histological activity index and the Scheuer histological scoring system. HCV genotyping was performed for each patient by sequence analysis of the 5' non-coding region. The histological appearances from HCV 1 infected patients showed a tendency towards more active necro-inflammatory changes when compared with those from HCV 2 or 3 infected patients. The levels of fibrosis were similar for all genotypes. The modified HAI and Scheuer scoring systems detected differences, not revealed by the Knodell system, in the types of inflammatory pathology produced by the different genotypes of HCV. In particular these scoring systems noted significant differences in the component scores of inflammation, in addition to the total inflammatory scores. In conclusion, the recently introduced scoring systems were able to detect differences in liver pathology produced by infection of similar duration with different viral genotypes. As genotype is considered an important determinant of disease progression and response to anti-viral therapy, it is likely that those scoring systems correlating with genotype will yield more useful histological information than those that do not.

Adult↗

Histological verification of computerised carotid plaque characterisation.

The correlation between the computerised measurement of carotid plaque echogenicity on high resolution ultrasound imaging and plaque histology was studied in 52 patients undergoing carotid endarterectomy. Thirteen plaques were from asymptomatic patients, 15 were associated with amaurosis fugax, 10 with transient ischaemic attacks and 14 with stroke. Longitudinal images of the anterior and posterior component of each plaque were obtained by ATL Ultramark-4 Duplex scanner and were transferred to a computer. Using an image analysis program the median of the overall grey scale content of each plaque component was evaluated and used as a measure of echogenicity. Following carotid endarterectomy each plaque specimen was divided into anterior and posterior component and then fixed, oriented, sectioned and stained in the longitudinal plane corresponding to the ultrasound image. Plaque histology sections were then examined by computer morphometric analysis and the percentage surface areas of fibrous tissue, lipid deposits and haemorrhage were calculated. This was then correlated with the grey scale median for each plaque component. Plaques with a high lipid and haemorrhage content as established histologically had a low grey scale median (Spearman correlation r=-0.351, p<0.05) and those with a high fibrous content had a high grey scale median (r=0.411, p<0.001). This study has shown that computerised measurement of carotid plaque echogenicity correlates well with histology and could be used to predict plaque composition, thus identifying high risk plaques with high lipid and haemorrhage content.

Carotid Arteries↗

Mitotic disassembly of the mammalian Golgi apparatus.

A cell-free system that mimics mitotic fragmentation of Golgi stacks has provided a working model for the disassembly process. Two distinct pathways, one COP-dependent and one COP-independent, act on Golgi stacks to give rise to two types of end products: transport vesicles and larger, more heterogeneous vesicles and tubules. We suggest that both mitotic end products result from enhanced fission of Golgi membranes under conditions where membrane fusion is generally inhibited.

Journal Article↗

Ethmoidal myofibroblastoma.

Myofibroblastoma is an uncommon mesenchymal tumour characterized by spindle cells exhibiting the ultrastructural and immunohistochemical features of myofibroblasts. We report a case of a myofibroblastoma occurring in the ethmoid sinus, which to our knowledge is the first case reported in the literature. The clinical presentation, diagnosis, histology, and management of this lesion is discussed with a review of the relevant literature.

Actins↗

Selection of a subset of mRNAs from combinatorial 3' untranslated region libraries using neuronal RNA-binding protein Hel-N1.

Hel-N1, a human RNA-binding protein, shares significant homology with Drosophila protein ELAV, which is essential for fly neuronal development. Hel-N1 has been shown to bind in vitro to 3' untranslated regions of mRNAs encoding c-myc, c-fos, granulocyte/macrophage colony-stimulating factor, and transcriptional repressor, Id. We report that Hel-N1 and a related form, Hel-N2, are expressed in human medulloblastoma cells, but their ratio differs significantly from that in adult brain and fetal brain. Selection of RNA targets from randomized combinatorial libraries yielded (A+U)-rich consensus sequences for both Hel-N1 and Hel-N2. As a means to identify cellular RNA targets for these proteins, we devised combinatorial shape libraries representing naturally derived 3' untranslated regions and were able to select a structurally related subset of transcripts that bound to Hel-N1. Approximately 10% of the proteins encoded by these subset mRNAs were identifiable in the data bases and most are implicated in cell growth regulation. This approach provides a means to gain access to novel genes expressed in various cell types by partitioning mRNAs containing common sequence elements using RNA-binding proteins.

Base Sequence↗