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Biomedical subjects

R C Martin

Publications and source records attributed to R C Martin.

At least 19 recordsLinked to original sources

A developmental phonological short-term memory deficit: a case study.

A developmental case of phonological short-term memory deficit was studied in a highly educated subject. The subject, BS, who had obtained a Ph.D. in molecular biology, demonstrated striking deficits on some short-term memory tasks, particularly for auditorily presented nonword lists. With visual presentation and with meaningful words, he often scored at a normal level. The results indicate a deficit in retaining phonological information but an ability to use visual, lexical, and semantic information to boost recall. Despite this phonological short-term memory deficit, BS scored at a normal level on a syntactic comprehension test and on reading of nonwords. He was impaired, however, on repeated list learning, learning of foreign vocabulary, and transcribing dictated materials. The implications of these results for models of short-term memory and the uses of phonological retention in cognitive processing are discussed.

Adult↗

Basosquamous carcinoma: analysis of prognostic factors influencing recurrence.

BACKGROUND: Basosquamous carcinoma is a rare malignancy, with features of both basal cell carcinoma and squamous cell carcinoma. Some authors believe that basosquamous carcinoma merely is a variant of basal cell carcinoma, whereas others have suggested that basosquamous carcinoma may behave more aggressively. To the authors' knowledge the largest published series to date, comprised of 35 cases, was reported >20 years ago. The authors reviewed their recent experience with basosquamous carcinoma to identify prognostic factors influencing recurrence. METHODS: The medical records of all patients with the diagnosis of basosquamous carcinoma treated at the University of Louisville-affiliated hospitals between 1985-1988 were reviewed by a senior pathologist. Prognostic factors were analyzed using Cox regression analysis and the log rank test. RESULTS: Thirty-one cases of basosquamous carcinoma were identified in 28 patients. The median age at diagnosis was 68 years (range, 10-94 years). The median follow-up was 60 months (range, 12-312 months). Seventy-five percent of cases were located on the face, neck, and scalp. One patient had regional lymph node metastasis synchronous with the primary tumor. Patterns of recurrence were: local recurrence only (five patients), local recurrence plus regional lymph nodes (three patients), and pulmonary plus regional lymph nodes (one patient). One patient died of pulmonary metastasis. Significant factors predictive of recurrence (P<0.01) were male gender, positive surgical resection margin, lymphatic invasion, and perineural invasion. Although tumor size was not a statistically significant factor overall (P = 0.076), the 3 patients with lymph node metastases had large tumors (measuring 2 cm, 5 cm, and 5 cm, respectively). CONCLUSIONS: Basosquamous carcinoma is an aggressive epithelial neoplasm with a propensity for local recurrence and potential for distant metastatic spread. This behavior differs substantially from basal cell carcinoma. Complete resection with negative surgical margins is essential. Long term follow-up for the detection of local recurrence and distant metastatic spread is recommended.

Adolescent↗

Limb and hemispatial hypometria.

In a previous study, we demonstrated that unilateral cerebral lesions produce hypometric limb movements of the contralateral arm and hemispatial (i.e., directional) hypometria for movements towards contralateral hemispace. In the present study, we investigated 10 patients with right cerebral lesions and 25 healthy controls using a task to uncouple deficits in sensory perceptual systems and motor-action output systems on directional hypometria. This task required participants, with their eyes closed, to reproduce lateral and medial horizontal displacements (15-27 cm) with each arm. Each participant was seated at a waist high table and had their hand placed at an origin point aligned with the axillary fold on the same side. Their hand was moved by the investigator from the origin point to a target point and brought back to the point of origin (input displacement). The participant was then asked to return their hand to either the same target point or to an equidistant target point in the opposite direction. Healthy dextral participants were significantly more hypometric with their right arm, but patients with right cerebral lesions exhibited an opposite pattern with overall left arm hypometria. In addition, patients were significantly more hypometric for movements when output displacements were toward left hemispace. No effect was found for direction of sensory input. The results suggest that the directional hypometria is predominantly produced by hemispatial output deficits.

Adolescent↗

Investigation of executive function change following anterior temporal lobectomy: selective normalization of verbal fluency.

The nociferous cortex hypothesis predicts that electrophysiological normalization to distal extratemporal brain regions following anterior temporal lobectomy (ATL) will result in improvements in executive functioning. The present study examined the effects of seizure laterality and seizure control on executive function change. The authors administered the Wisconsin Card Sorting Test (WCST), Trails B, and the Controlled Oral Word Association Test to 174 temporal lobe epilepsy patients who underwent ATL. No significant changes were found on the WCST or Trails B tests, regardless of surgery side or seizure-free status. However, verbal fluency significantly improved in seizure-free patients. Findings were consistent with the nociferous cortex hypothesis suggesting selective executive function improvement following ATL. These findings are discussed in terms of recent research demonstrating extrahippocampal metabolic normalization following surgery.

Adolescent↗

Conotoxin TVIIA, a novel peptide from the venom of Conus tulipa 1. Isolation, characterization and chemical synthesis.

A novel conotoxin belonging to the 'four-loop' structural class has been isolated from the venom of the piscivorous cone snail Conus tulipa. It was identified using a chemical-directed strategy based largely on mass spectrometric techniques. The new toxin, conotoxin TVIIA, consists of 30 amino-acid residues and contains three disulfide bonds. The amino-acid sequence was determined by Edman analysis as SCSGRDSRCOOVCCMGLMCSRGKCVSIYGE where O = 4-transL-hydroxyproline. Two under-hydroxylated analogues, [Pro10]TVIIA and [Pro10,11]TVIIA, were also identified in the venom of C. tulipa. The sequences of TVIIA and [Pro10]TVIIA were further verified by chemical synthesis and coelution studies with native material. Conotoxin TVIIA has a six cysteine/four-loop structural framework common to many peptides from Conus venoms including the omega-, delta- and kappa-conotoxins. However, TVIIA displays little sequence homology with these well-characterized pharmacological classes of peptides, but displays striking sequence homology with conotoxin GS, a peptide from Conus geographus that blocks skeletal muscle sodium channels. These new toxins and GS share several biochemical features and represent a distinct subgroup of the four-loop conotoxins.

Amino Acid Sequence↗

Practical guidelines for optimal gamma probe detection of sentinel lymph nodes in breast cancer: results of a multi-institutional study. For the University of Louisville Breast Cancer Study Group.

INTRODUCTION: Multiple radioactive lymph nodes are often removed during the course of sentinel lymph node (SLN) biopsy for breast cancer when both blue dye and radioactive colloid injection are used. Some of the less radioactive lymph nodes are second echelon nodes, not true SLNs. The purpose of this analysis was to determine whether harvesting these less radioactive nodes, in addition to the "hottest" SLNs, reduces the false-negative rate. METHODS: Patients were enrolled in this multicenter (121 surgeons) prospective, institutional review board-approved study after informed consent was obtained. Patients with clinical stage T1-2, N0, M0 invasive breast cancer were eligible. This analysis includes all patients who underwent axillary SLN biopsy with the use of an injection of both isosulfan blue dye and radioactive colloid. The protocol specified that all blue nodes and all nodes with 10% or more of the ex vivo count of the hottest node should be removed and designated SLNs. All patients underwent completion level I/II axillary dissection. RESULTS: SLNs were identified in 672 of 758 patients (89%). Of the patients with SLNs identified, 403 patients (60%) had more than 1 SLN removed (mean, 1.96 SLN/patient) and 207 patients (31%) had nodal metastases. The use of filtered or unfiltered technetium sulfur colloid had no impact on the number of SLNs identified. Overall, 33% of histologically positive SLNs had no evidence of blue dye staining. Of those patients with multiple SLNs removed, histologically positive SLNs were found in 130 patients. In 15 of these 130 patients (11.5%), the hottest SLN was negative when a less radioactive node was positive for tumor. If only the hottest node had been removed, the false-negative rate would have been 13.0% versus 5.8% when all nodes with 10% or more of the ex vivo count of the hottest node were removed (P =.01). CONCLUSIONS: These data support the policy that all blue nodes and all nodes with 10% or more of the ex vivo count of the hottest SLN should be harvested for optimal nodal staging.

Biopsy↗

Visual confrontation naming and hippocampal function: A neural network study using quantitative (1)H magnetic resonance spectroscopy.

Prior research on the relationship between visual confrontation naming and hippocampal function has been inconclusive. The present study examined this relationship using quantitative (1)H magnetic resonance spectroscopy ((1)H-MRS) to operationalize the function of the left and right hippocampi. The 60-item Boston Naming Test (BNT) was used to measure naming. Our sample included 46 patients with medically intractable, focal mesial temporal lobe epilepsy who had been screened for all pathology other than mesial temporal sclerosis. Statistics included Pearson correlations and neural network analysis (multilayer perceptron and radial basis function). Baseline BNT performance correlated significantly with left (1)H-MRS hippocampal ratios. Thirty-six per cent of the variance in baseline BNT performance was explained by a neural network model using left and right (1)H-MRS ratios(creatine/N-acetylaspartate) as input. This was elevated to 49% when input from the right hippocampus was lesioned mathematically. In a second model, left (1)H-MRS hippocampal ratios were modelled using measures of semantic and episodic memory as input (including the BNT). Explained variance in left (1)H-MRS hippocampal ratios fell from 60.8 to 3.6% when input from BNT and another semantic memory measure was degraded mathematically. These results provide evidence that the speech-dominant hippocampus is a significant component of the overall neuroanatomical network of visual confrontation naming. Clinical and theoretical implications are explored.

Adult↗

Wisconsin Card Sorting performance in patients with temporal lobe epilepsy: clinical and neuroanatomical correlates.

PURPOSE: A sizable proportion of patients with temporal lobe epilepsy (TLE) display impairments on tests of executive function. Previous studies have suggested several factors that may explain such performance, including the presence of hippocampal sclerosis, electrophysiological disruption to extratemporal regions, and early age of seizure onset. However, no clear determinants have been found that consistently explain such executive dysfunction. The present study investigated the contribution of several clinical variables and temporal lobe neuroanatomic features to performance on the Wisconsin Card Sorting Test (WCST) in a series of patients with TLE. METHODS: Eighty-nine patients with lateralized TLE (47 left, 42 right) were examined. Seventy-two patients from this series underwent anterior temporal lobectomy (ATL). Regression analysis was used to examine the effects of age, education, age at seizure onset, seizure duration, seizure laterality, history of secondary generalized seizures, and MRI-based volumes of the right and left hippocampi on preoperative WCST performance (number of categories completed, perseverative errors). Further univariate analyses examined whether the presence of bilateral hippocampal sclerosis, mesial temporal lobe abnormalities beyond the hippocampus, or temporal neocortical abnormalities affected preoperative WCST performance. In addition, we examined whether becoming seizure free after ATL affected change in WCST performance. RESULTS: Overall regression analysis was not significant. However, an examination of individual partial correlations revealed that patients with a history of secondary generalized seizures performed more poorly on the preoperative WCST than did patients without such history. In addition, patients who were seizure free after ATL did not exhibit better WCST outcome than patients who did not become seizure free. The presence of bilateral hippocampal sclerosis, extrahippocampal mesial temporal atrophy, or temporal neocortical lesions did not affect WCST performance. CONCLUSIONS: These results indicate that the presence of temporal lobe structural abnormalities do not significantly affect executive function as measured by the WCST. The present study does suggests that the critical determinants of WCST performance in patients with TLE lie outside the temporal lobe and likely relate to metabolic disruption to frontostriatal neural network systems.

Adult↗

Initial neck exploration for untreated hyperparathyroidism.

This study represents the experience of the Department of Surgery at the University of Louisville over a 21-year interval. Many aspects of surgical management of hyperparathyroidism have changed over the last 2 decades; controversies regarding the extent of exploration and the value of preoperative localization studies remain unresolved. One hundred ninety-three patients underwent neck exploration for hyperparathyroidism from 1976 to 1997. Data were collected from four University of Louisville-affiliated hospitals by independent evaluators. One hundred sixty patients with untreated hyperparathyroidism underwent neck exploration. Preoperative localization was carried out in 52 per cent (83 of 160). The exact location of the abnormal gland was indicated in 55 per cent (46 of 83), and the correct side of the neck was identified in 74 per cent (61 of 83). Technetium sestamibi scan was most reliable and identified the abnormality in 83 per cent (24 of 29). The average operative time with preoperative localization was 118 minutes compared with 137 minutes without preoperative localization. Intraoperative methylene blue was used in 42 of 160 neck explorations. Average operative time with methylene blue was 102 minutes compared with 124 minutes without methylene blue. Thirty-seven per cent (59 of 160) of patients underwent unilateral neck exploration. Sixty-three per cent (101 of 160) underwent bilateral exploration. Successful exploration was conducted in 98 per cent of the unilateral group and 91 per cent of the bilateral group. Postoperative local complications were essentially the same in both groups (3%), whereas temporary hypocalcemia occurred in 24 per cent (24 of 101) of the bilateral group compared with 3 per cent (2 of 59) of the unilateral group. We conclude that neck exploration for hyperparathyroidism is a highly successful, safe treatment with no mortality and minimal morbidity. Preoperative localization studies modestly reduced the duration of surgery without improving outcome.

Adolescent↗

Cognitive correlates of 1H MRSI-detected hippocampal abnormalities in temporal lobe epilepsy.

OBJECTIVES: To examine associations between 1H magnetic resonance spectroscopic imaging (1H MRSI)-detected hippocampal creatine to N-acetylaspartate (Cr/NAA) ratios and neuropsychological measures sensitive to mesial temporal lobe function. BACKGROUND: The measurement of 1H MRSI-detected hippocampal metabolites has proved effective in determining extent and lateralization of neuronal damage. However, relationships between 1H MRSI-detected hippocampal metabolic abnormalities and specific areas of cognitive functioning have received limited attention compared to other studies using MRI volumetry or cerebral blood flow techniques. METHODS: We analyzed right and left hippocampal Cr/NAA ratios in 46 adult mesial temporal lobe epilepsy patients (32 left, 14 right) by 1H MRSI at high magnetic field (4.1 T). We examined the relationship between the right and left Cr/NAA hippocampal ratios to measures of verbal and visual memory, intelligence, attention, visuoperception, and confrontation naming. RESULTS: Measures of episodic verbal memory (n = 33) and visual confrontation naming (n = 46) were selectively associated with left hippocampal metabolic function (p<0.004), whereas neuronal function of the right hippocampal region was strongly associated with performance on a measure of facial recognition (n = 46; p<0.02). CONCLUSIONS: This study shows that specific areas of cognitive function are related to hippocampal neuronal metabolic abnormalities as detected by spectroscopic imaging. The current study indicates that 1H MRSI offers a complimentary technique to structural imaging studies in the study of mesial temporal lobe epilepsy and may enhance understanding of the role of hippocampal function in complex cognitive systems.

Adult↗

Subjective versus objective memory change after temporal lobe epilepsy surgery.

OBJECTIVE: To examine subjective versus objective memory change after anterior temporal lobectomy (ATL). METHODS: A prospective, controlled study. Controls included 39 unoperated patients with intractable temporal lobe epilepsy (TLE) who were administered a series of cognitive and health-related quality of life measures at baseline and at 12-month follow-up intervals. The surgery sample included 65 patients with intractable, focal TLE who had undergone either a right or left ATL. These patients were tested preoperatively and at 6-month follow-up intervals. Subjective and objective memory change was quantified using a newly developed methodology to control for practice effect and regression to the mean. RESULTS: Measures of subjective and objective memory change were not significantly related in the surgery sample. Prevalence of significant subjective memory decline 1 year after surgery ranged from 3 to 7%, whereas prevalence of significant objective memory decline ranged from 26 to 55%. Postoperative levels of emotional distress significantly predicted self-reported memory decline 1 year after ATL. Postoperative medication side effect and seizure outcome were also related significantly to subjective memory change in patients who had undergone left ATL. CONCLUSIONS: Subjective and objective memory change after temporal lobectomy are not related. Complaints of significant memory decline after ATL are infrequent and may serve as a marker for depression or other mood disorder rather than organically based memory decline.

Adult↗

Intracellular measurement of prostaglandin E2: effect of anti-inflammatory drugs on cyclooxygenase activity and prostanoid expression.

Cyclooxygenase (COX) converts arachidonic acid to prostaglandin (PG) H2, which is further metabolized to various prostaglandins, prostacyclin and thromboxane A2. COX exists in at least two different isoforms. COX-1 is constitutively expressed, whereas COX-2 is induced by proinflammatory stimuli. Prostaglandin E2 is a major metabolite of COX activation. In order to compare the activity of target ligands and COX inhibitors on PGE2 synthesis and release, the responsiveness of several cell lines to the calcium ionophore A23187, bacterial lipopolysaccharide (LPS), nonsteroidal anti-inflammatory drugs (NSAIDs), and the glucocorticoid, dexamethasone, were investigated. For intracellular measurements, the culture supernatant was aspirated, and the cells were thoroughly washed and lysed with dodecyltrimethylammonium bromide. Intracellular and secreted PGE2 were measured with an enzyme immunoassay. A23187 and LPS increased intracellular PGE2 in a dose-dependent manner. Kinetic experiments with A23187-stimulated mouse 3T3 fibroblast cells revealed a distinct biphasic response in COX activity. In the presence of NSAIDs or dexamethasone, there was a dose-dependent inhibition in intracellular PGE2 with A23187-stimulated 3T3 cells. Inhibitory studies demonstrated an apparent increased sensitivity of COX activity to the action of inhibitors when measuring intracellular PGE2 compared with using cell culture supernatants. Indeed, intracellular PGE2 levels were comprehensively reduced in the presence of low concentrations of inhibitor. The utilization of cell culture lysates and, in particular, measurement of intracellular PGE2 should prove useful for identifying new COX inhibitors.

3T3 Cells↗

Isolation of a cytokinin gene, ZOG1, encoding zeatin O-glucosyltransferase from Phaseolus lunatus.

Zeatin is the most active and ubiquitous of the naturally occurring cytokinins. The O-glucoside of zeatin, found in all plants examined, is considered to be important in cytokinin transport, storage, and protection against cytokinin oxidases. The enzyme UDPglucose:zeatin O-glucosyltransferase (EC 2.4.1.203) was previously isolated from Phaseolus lunatus seeds. Immunoscreening of an expression library with monospecific antibody resulted in the isolation of a cDNA encoding the enzyme. The recombinant protein efficiently converts labeled zeatin to O-glucosylzeatin and has properties similar to the native enzyme. The cDNA of 1.5 kb contains an ORF encoding a 51. 4-kDa polypeptide of 459 amino acids. The sequence is unique based on a BLAST search of data bases. The genomic sequence, isolated with PCR using specific primers based on the cDNA sequence, does not contain introns. The cloning of this gene provides the tools for further study of the regulation of cytokinin metabolism and analysis of the precise role of O-glucosylzeatin in plant development.

Amino Acid Sequence↗

The relation of phoneme discrimination, lexical access, and short-term memory: A case study and interactive activation account.

A brain-damaged patient (AP) is reported who had a strong tendency to identify nonwords as words on auditory lexical decision and to lexicalize nonwords in repetition, yet who showed a normal ability to perceive individual phonemes. It was initially hypothesized that these findings could be accounted for in terms of disrupted lexical phonological representations. This hypothesis was rejected on the basis of an interactive activation model of word recognition which revealed that modifications at the lexical level did not mimic the patient's pattern of results. Instead, it was found that increasing the rate of decay of activation at the phoneme level produced output that was consistent with the phoneme discrimination, lexical decision, and repetition results. This hypothesis of increased phoneme level decay led to the prediction that speech discrimination would decline with increased interstimulus interval and that short-term memory performance would be impaired. Both predictions were confirmed. The results of this study provide support for an interactive activation model of word recognition with feedback from the lexical to the phonemic level and for a close connection between the processes involved in word recognition and short-term memory.

Aphasia↗

MRI extrahippocampal volumes and visual memory: correlations independent of MRI hippocampal volumes in temporal lobe epilepsy patients.

Limbic system atrophy and memory dysfunction are common in patients with temporal lobe epilepsy (TLE). However, the relationship between extrahippocampal limbic structures and memory functioning within TLE has received little attention. The present study examined associations of MRI volumetric measurements of the mammillary body, fornix, amygdala, and hippocampus to measures of episodic verbal and visual memory. The Logical Memory and Visual Reproduction subtests from the Wechsler Memory Scale were administered to 47 unilateral TLE patients (25 right, 22 left). Normalized right and left MRI volumes were determined for each patient by cursor tracing 1.5 mm slices from 3D-MRI. Significant associations were found between left hippocampal volume and the immediate, delayed, and percent retention scores of the Logical Memory Test; between the left mammillary body volume and the Logical Memory Test delayed and percent retention scores; immediate Visual Reproduction performance was significantly related to the right and left amygdala volumes, and right mammillary body volume; only the right amygdala and right mammillary body volume were associated with the delayed Visual Reproduction trial. However, neither right nor left hippocampal volumes were related to visual memory performance. Multiple limbic system structural volumes were independently associated with verbal and nonverbal memory performance. Results suggest that visual memory, as measured by the Visual Reproduction Test, may be uniquely associated with extrahippocampal volumes in patients with TLE.

Adult↗

Semantic and phonological codes interact in single word production.

The relationship between semantic-syntactic and phonological levels in speaking was investigated using a picture naming procedure with simultaneously presented visual or auditory distractor words. Previous results with auditory distractors have been used to support the independent stage model (e.g., H. Schriefers, A. S. Meyer, & W. J. M. Levelt, 1990), whereas results with visual distractors have been used to support an interactive view (e.g., P.A. Starreveld & W. La Heij, 1996b). Experiment 1 demonstrated that with auditory distractors, semantic effects preceded phonological effects, whereas the reverse pattern held for visual distractors. Experiment 2 indicated that the results for visual distractors followed the auditory pattern when distractor presentation time was limited. Experiment 3 demonstrated an interaction between phonological and semantic relatedness of distractors for auditory presentation, supporting an interactive account of lexical access in speaking.

Acoustic Stimulation↗

A gene encoding the cytokinin enzyme zeatin O-xylosyltransferase of Phaseolus vulgaris.

Zeatin is the most active and ubiquitous form of the naturally occurring cytokinins. Glycosyl conjugates of zeatin are found in many plant tissues and are considered important for storage and protection against degradative enzymes. Two enzymes catalyzing the formation of O-glycosyl derivatives of zeatin have been characterized, O-glucosyltransferase and O-xylosyltransferase, occurring in seeds of lima bean (Phaseolus lunatus) and bean (Phaseolus vulgaris), respectively. Recently, the ZOG1 gene (zeatin O-glucosyltansferase) was isolated from P. lunatis (). Based on the ZOG1 sequence, the ZOX1 gene (zeatin O-xylosyltransferase) was cloned from P. vulgaris. ZOX1 contains an open reading frame of 1362 bp that codes for a 454-amino acid peptide of 51 kD. The recombinant protein has properties identical to the native enzyme: it catalyzes O-xylosylzeatin formation with UDP-Xyl as a glycosyl donor but does not recognize UDP-Glucose as a substrate. The ZOX1 and ZOG1 genes exhibit 93% identity at the nucleotide level and 90% similarity at the amino acid level. Neither gene contains introns. These zeatin-specific genes and their promoters will be useful for studies of the regulation of active versus storage forms of cytokinins. Comparison of sequences encoding similar enzymes with distinct substrate specificity may lead to identification of epitopes specific to cytokinin and glycosyl donor molecules.

Base Sequence↗