Biomedical subjects

S Wilkinson

Publications and source records attributed to S Wilkinson.

At least 73 records · Page 4Linked to original sources

PubMed1997

High-frequency unilateral thalamic stimulation in the treatment of essential and parkinsonian tremor.

Pharmacologic treatment for essential tremor and the tremor of Parkinson's disease is often inadequate. Stereotaxic surgery, such as thalamotomy, can effectively reduce tremors. We performed a multicenter trial of unilateral high-frequency stimulation of the ventral intermedius nucleus of the thalamus in 29 patients with essential tremor and 24 patients with Parkinson's disease, using a blinded assessment at 3 months after surgery to compare clinical rating of tremor with stimulation ON with stimulation OFF and baseline and a 1-year follow-up. Six patients were not implanted because of lack of intraoperative tremor suppression (2 patients), hemorrhage (2 patients), withdrawal of consent (1 patient), and persistent microthalamotomy effect (1 patient). A significant reduction in both essential and parkinsonian tremor occurred contralaterally with stimulation. Patients reported a significant reduction in disability. Measures of function were significantly improved in patients with essential tremor. Complications related to surgery in implanted patients were few. Stimulation was commonly associated with transient paresthesias. Other adverse effects were mild and well tolerated. Efficacy was not reduced at 1 year. Chronic high-frequency stimulation is safe and highly effective in ameliorating essential and parkinsonian tremor.

Aged↗

PubMed1997

Effects of thalamic deep brain stimulation based on tremor type and diagnosis.

It has been suggested that deep brain stimulation (DBS) is less effective in alleviating proximal than distal postural arm tremor reduction is said to be less in essential tremor (ET) than in Parkinson's disease (PD). We analyzed blinded rater's tremor scores and subjects' disability ratings at 3-month follow-up to examine the effects of DBS based on tremor type (rest, kinetic, distal postural, proximal postural) and diagnosis (ET, PD). An independent examiner provided tremor scores using randomized videotaped footage of 19 ET and 10 PD subjects at baseline and at follow-up with DBS "on." Subjects provided self-ratings of disability at baseline and at follow-up. Comparisons of baseline and follow-up tremor scores and disability ratings were made using the Mann-Whitney U and Wilcoxon rank sum W test; correlation analyses were performed using Spearman rank order correlation test. There were significant and essentially equal improvements in tremor scores of test, kinetic, distal postural, and proximal postural tremor at follow-up. Only one subject had no improvement in tremor. Tremor improved significantly and to the same extent in ET and PD subjects in each position except "at rest," which was most improved in PD (p = 0.0003). ET and PD subjects did not differ in the extent of disability improvement. Improved disability correlated only with improved postural tremor scores; proximal postural and distal postural (r = 0.41, p = 0.03; r = 0.47, p = 0.01). DBS is effective in alleviating tremor and disability in both ET and PD. Resting, kinetic, distal postural, and proximal postural tremor can be reduced to an equal degree. However, DBS produces the greatest improvement in disability in association with improved postural tremor in both ET and PD.

Adolescent↗

PubMed1997

An investigation of lower oesophageal redox potentials in gastro-oesophageal reflux patients and healthy volunteers.

Oesophageal electrical properties are thought to be important in the development of gastro-esophageal reflux. This study simultaneously monitored the intraoesophageal pH and redox potentials in 18 patients with gastro-oesophageal reflux symptoms and 15 asymptomatic controls, for a 24 h period. The pH and redox electrodes were positioned 5 cm proximal to the lower oesophageal sphincter, the position of which had been determined by manometry. Since significantly different behaviour was observed during the day and night, the data were divided into periods of waking and sleeping. Data were analysed for acid reflux (pH < 4) and transients in the redox potential-time curve. Both patients and normal subjects showed negative redox transients which were more frequent and pronounced at night than during the day, and which were uncorrelated with acid reflux. The only parameter which was significantly different between normal and refluxing groups was the amount of nocturnal redox activity, which was lower in refluxing subjects than in normals. Some possible hypotheses for these observations, and the origin of the redox species, are discussed.

Adult↗

PubMed1997

Clinicopathologic studies of thymic carcinoids in multiple endocrine neoplasia type 1.

Thymic carcinoid is part of the multiple endocrine neoplasia type 1 (MEN1) syndrome occurring predominantly in male patients who were heavy smokers, presenting most commonly in middle age. In contrast with metastatic midgut carcinoids, MEN1-related thymic carcinoid is not associated with carcinoid syndrome, nor is it associated with Cushing syndrome, in contrast with sporadic thymic carcinoids. Local invasion and metastasis are common. Prognosis is poor because of late detection, lack of effective treatment, and the aggressive nature of the tumor. All patients with thymic carcinoids should be investigated for MEN1, including thorough clinical evaluation and family studies. Anterior mediastinal lesions in MEN1 male patients should be considered thymic carcinoids until proven otherwise. All male MEN1 patients and asymptomatic gene carriers should be warned of the risk of thymic carcinoids and the possible link to smoking. Computed tomography (CT) of the chest is recommended on first screening for MEN1 in male patients more than 25 years of age, followed by yearly chest X-rays and chest CT every 3 years. Prophylactic thymectomy should be carried out during subtotal or total parathyroidectomy on MEN1 patients.

Adult↗

PubMed1997

Analysis of pallidotomy lesion positions using three-dimensional reconstruction of pallidal lesions, the basal ganglia, and the optic tract.

OBJECTIVE: To assess the position of radiofrequency pallidotomy lesions placed using microelectrode stimulation and cellular recordings in relation to a stereotactically defined starting point. Radiofrequency lesion locations were also evaluated in relation to the putamen, posterior limb of the internal capsule, and optic tract. METHODS: Magnetic resonance images obtained from 23 patients with Parkinson's disease who underwent pallidotomy at the University of Kansas Medical Center were analyzed. Using computerized techniques, lesion positions in relation to the midcommissural point and a hypothetical starting point were determined. Data segmentation and three-dimensional reconstruction of pallidal lesions, the internal capsule, and the optic tract allowed assessment of lesion position in relation to internal anatomy. Clinical outcome of pallidotomy was assessed using both the Unified Parkinson's Disease Rating Scale and the Dementia Rating Scale. RESULTS: Pallidal lesions were usually placed anterior and dorsal to the stereotactically defined starting point. The position of pallidal lesions in the men were observed, in four trials, to be significantly more dorsal than the lesions in the women. The outer zone of the lesion was usually adjacent to the internal capsule and the putamen and relatively close to the optic tract. The inner zone of the lesion was usually several millimeters removed from anatomic boundaries of the putamen, internal capsule, and optic tract. Patients achieved favorable outcomes, with reduced dyskinesias and "off" time and improvement of their Parkinsonian symptoms, as evidenced by clinical assessment, the Unified Parkinson's Disease Rating Scale, and the Dementia Rating Scale. CONCLUSION: Microelectrode stimulation and cellular recordings usually led to a final pallidotomy lesion position that deviated from the stereotactically defined starting point. The pallidotomy lesions in the men were observed to be more dorsal than the lesions in the women. Clinical outcomes were not correlated with either lesion location relative to the starting point or distances between the pallidal lesion and the putamen, internal capsule, or optic tract. Kinesthetically responsive cells may be localized generally more anterior and dorsal to the starting point (within the globus pallidus) and may be grouped variably from patient to patient in relation to other basal ganglia structures. Although the primary lesion site is most likely within the sensorimotor region of the globus pallidus internus, the more dorsal locations of responsive cell groups may indicate that some lesion sites may be localized within the globus pallidus externus.

Aged↗

PubMed1997

High-frequency stimulation of the globus pallidus for the treatment of Parkinson's disease.

Long-term treatment of Parkinson's disease (PD) with levodopa is complicated by the development of motor fluctuations and dyskinesias. Posteroventral pallidotomy can improve tremor, bradykinesia, rigidity, and dyskinesias in PD. We performed chronic stimulation of the globus pallidus (CSGP) to duplicate the positive results of pallidotomy with reduced risk of permanent neurologic deficit in patients with advanced PD. The lead for CSGP was stereotactically implanted with the aid of microelectrode recordings in the globus pallidus pars interna. An electrical pulse generator was implanted in the subclavicular region. Stimulation settings were adjusted by computer. Five PD patients (four men, one woman) with disabling symptoms were enrolled. Three of the patients had bilateral implants. At 3 months following the last implant, four patients rated themselves as markedly improved, and one patient was moderately improved. The amount of time in the "on" state increased from 21% at baseline to 65% at 3-month follow-up (p < 0.05). There was a significant improvement in all subscales of the UPDRS (p < 0.05). One patient had an asymptomatic intracranial bleed, one patient had transient hemiparesis during surgery with stimulation, and one patient required surgical repositioning of the lead. Adverse effects caused by stimulation were minimal. CSGP is a safe and effective procedure in PD patients with motor fluctuations and dyskinesias.

Aged↗

PubMed1996

Lie as narrative truth in abused adopted adolescents.

Two case examples of abused adopted adolescents are discussed to highlight tension within the treatment relationship when the therapist is expected to accept without question a clearly unbelievable story. These examples illustrate how the lies of such youths can function as narrative truth. The unbelievable tales that emerge in the therapeutic work effectively alter the adolescents' perceptions about the perplexing loss of continuity, both internal and external, that occurred when they were removed from their homes. Characters in the stories represent fragmented self- and object-representations as victim, abuser, rescuer, and passive onlooker. Counterparts to the patient as victim, abuser, rescuer, and passive onlooker can be recognized in the therapist's subjective responses. If the therapist can use countertransference to inform an understanding of the treatment process, an appreciation emerges that the truth of the lie is in its impact. Decisions about how to intervene can then be crafted. The second separation-individuation intrinsic to adolescent development is understood to provide a ripe opportunity for this working-through process.

Adolescent↗

PubMed1996

The prevalence of MEN-1 in Tasmania.

BACKGROUND: An extensive programme was undertaken to trace and screen four known families in Tasmania with multiple endocrine neoplasia type 1 (MEN-1). METHODS: Written and personal contact was made with family members over the age of 20 years recommending a review by family practitioners for the purpose of recording their medical history and collecting a blood sample. Those suspected of MEN-1 were referred to our Department for further investigation. RESULTS: In January 1993, the total number of individuals alive and known to be affected by MEN-1 was 107, giving a prevalence of MEN-1 disease in Tasmania of 23/100 000. The estimated prevalence of MEN-1 trait in Tasmania (including affected cases and those considered at 50% risk of possessing the trait) is 45/100 000. CONCLUSION: The prevalence of MEN-1 has never previously been determined accurately. The prevalence of MEN-1 in Tasmania is at the upper end of the possible range and would justify the allocation of resources for screening programmes equal to those available for the detection of several less prevalent genetic diseases.

Adolescent↗

PubMed1996

P53 tumour suppressor gene expression in hyperparathyroidism.

BACKGROUND: Mutations of the p53 tumour suppressor gene lead to the loss of control of normal cellular proliferation and differentiation and have been shown to be associated with the development of malignancy. METHOD: Archival paraffin resection specimens from 86 cases of hyperparathyroidism treated surgically using the rabbit polyclonal CMI antibody were investigated to detect p53 immunoreactivity in these sections. RESULTS: Eighteen of the 86 sections examined (21%) showed nuclear immunoreactivity. No correlation was detected between tumour histology and p53 immunoreactivity (P = 0.45), nor was there any correlation between tumour clonality and immunoreactivity (P = 0.54). Multiple endocrine neoplasia type 1 (MEN 1) status did not correlate with p53 immunoreactivity. A significant correlation between p53 immunoreactivity and preparathyroidectomy calcium levels of > 1.5 mmol/L was detected (P < 0.005) although no correlation was noted between p53 immunoreactivity and higher levels of preparathyroidectomy intact parathyroid hormone (PTH) levels. CONCLUSION: A relationship is postulated between abnormal serum calcium regulation and p53 mutation in hypercalcaemic states associated with hyperparathyroidism.

Calcium↗

PubMed1996

Bodily integrity and the sale of human organs.

Existing arguments against paid organ donation are examined and found to be unconvincing. It is argued that the real reason why organ sale is generally thought to be wrong is that (a) bodily integrity is highly valued and (b) the removal of healthy organs constitutes a violation of this integrity. Both sale and (free) donation involve a violation of bodily integrity. In the case of the latter, though, the disvalue of the violation is typically outweighed by the presence of other goods: chiefly, the extreme altruism involved in the giving. There is usually no such outweighing feature in the case of the former. Given this, the idea that we value bodily integrity can help to account for the perceived moral difference between sale and free donation.

Altruism↗

PubMed1996

Deep brain stimulation for essential tremor.

We examined the effects and safety of deep brain stimulation (DBS) as a treatment for essential tremor (ET). Ten ET patients with disabling medication-refractory tremor underwent stereotactic implantation of a DBS lead in the left Vim thalamic nucleus and completed a 6-month follow-up. The Clinical Tremor Rating Scale and disability assessments were performed at baseline, 1-, 3-, and 6-month follow-up. There were significant improvements in dressing, drinking, eating, bathing, and handwriting as reported by the subjects. Tremor severity, writing, pouring, and spiral and line drawing were significantly improved as rated by the examiner. Improvements persisted through the 6-month follow-up period. Although global disability significantly lessened in the group as a whole, one subject with hand-finger tremor accentuated by writing had no change in disability status. In this 6-month open-label study, DBS was effective and safe in reducing tremor and functional disability in ET.

Aged↗

PubMed1996

Can we be both women and analysts?

The authors, candidates at a psychoanalytic institute that has not had a woman training analyst for more than 20 years, have a unique vantage point from which to examine the woman's development as an adult female and as a psychoanalyst. Our group has engaged in a series of discussions asking: Can we be both women and analysts? Comparing and contrasting our experiences with feedback from colleagues across the United States and abroad, we had to accept that our unique situation could not be a foil for the training dilemmas facing women. Our insights into the challenges involved with training, expression of sexuality, family ties, formation of an analytic identity, creative contributions to the field, and career progression have caused us to arrive at some sobering observations and hard-hitting questions which we present here. We hope that as we describe our discussions about the woman analyst's experience an active dialogue will arise within the reader's mind, and subsequently with colleagues.

Adult↗

PubMed1995

Changes in the blood group Wright antigens are associated with a mutation at amino acid 658 in human erythrocyte band 3: a site of interaction between band 3 and glycophorin A under certain conditions.

The Wright (Wr) blood group antigens, Wra and Wrb, have been suggested to be determined by alleles of the same gene. The Wrb antigen appears to involve both red blood cell (RBC) band 3 and glycophorin A (GPA). We have examined the cDNA sequences of the band 3 and GPA of one of the two known Wr(a+b-) individuals. We show that this individual is homozygous for the mutation Glu658-->Lys in band 3, but has normal GPA. Putative heterozygotes with Wr(a+b+) RBCs have both Glu and Lys at residue 658 of band 3, whereas the common Wr(a-b+) RBC phenotype only have band 3 with Glu658. The Wra and Wrb antigens are determined by the amino acid at residue 658 of band 3 and are antithetical. Examination of the amino acid sequence and Wrb antigen expression of GPA-related hybrid glycophorins suggests that Arg61 of GPA interacts with Glu658 of band 3 to form the Wrb antigen. We suggest that the interaction is stabilized by the presence of anti-Wrb antibodies and that this site of association between GPA and band 3 may be responsible for the previously reported ability of anti-GPA antibodies to decrease the deformability of RBCs.

Alleles↗

PubMed1995

Inactivation of retinoblastoma gene in malignant parathyroid growths: a candidate genetic trigger?

The molecular basis for parathyroid carcinoma remains undetermined. Parathyroid carcinoma potentially remains curable by early en bloc resection. This requires a reliable diagnostic tool as histological features alone are insufficient to distinguish parathyroid carcinoma from its benign counterpart, parathyroid adenoma. A variety of human cancers arise from the inactivation of the retinoblastoma (RB) gene, a tumour-suppressor gene on chromosome 13q14. We investigated the role of this gene in parathyroid growths by using a mouse monoclonal antibody to detect RB gene expression immunohistochemically. Two of the three parathyroid carcinomas in this study showed evidence of RB gene inactivation compared with one of 11 benign parathyroid entities. Three normal parathyroid glands stained showed strong evidence of RB gene expression in all three glands. The relationship between RB gene inactivation and parathyroid malignancy, however, was not statistically significant.

Animals↗

PubMed1995

Immunohistochemical detection of p53 and the recurrence of rectal adenocarcinoma.

The relationship between immunohistochemical detection of the p53 tumour-suppressor gene and recurrence of disease in 66 cases of rectal adenocarcinoma treated at the Royal Hobart Hospital, Hobart, Tasmania, between 1984 and 1992 was investigated. Fifty-five per cent (n = 36) of patients demonstrated p53 nuclear immunoreactivity consistent with the presence of the stabilized protein derivative of a mutation at the p53 gene locus. No correlation between p53 immunoreactivity and tumour site, differentiation and stage was noted. An overall recurrence rate of 64% (n = 42) was noted. Multivariate analysis confirmed the absence of p53 immunoreactivity and anatomical site of tumour below 7 cm from the anal verge to be significant predictors of tumour recurrence (P < 0.001). A review of the current literature on p53 suggests caution in using the immunohistochemical detection of p53 to predict the clinical outcome in cases of rectal adenocarcinoma because of discordant results between studies.

Adenocarcinoma↗

PubMed1995

Bcl-2 protein expression in normal human bone marrow precursors and in acute myelogenous leukemia.

The expression of bcl-2 protein that is involved in preventing apoptosis in hemopoietic and other cells was evaluated by quantitative flow cytometry in various subpopulations in the normal fetal bone marrow (FBM) and in different types of acute myelogenous leukemias (AML). In the FBM the highest bcl-2 levels (mean antibody binding capacity 51 x 10(3) molecules/cell) were found in CD34+ intermediate sized blasts and myeloblasts, while a CD34+ subset of CD10+ lymphoblasts had low bcl-2 content (8-10 x 10(3) molecules/cell) and the CD34-, CD10+ lymphoblasts were, as expected from previous studies, bcl-2- (< 5 x 10(3) molecules/cell). Variable levels of bcl-2 (5.1-222 x 10(3)) were found in 43 tested cases of AML. The bcl-2 levels decrease with granulocytic and monocytic differentiation and, accordingly, cases of AML with M1 and M2 features showed significantly higher mean bcl-2 levels than the leukemias with promyelocytic (M3) or myelo-monocytic (M4/M5) features. Nevertheless, in seven cases of AML the bcl-2 levels were higher than seen in the normal FBM cells and none of these patients remain in remission after 2 years. Furthermore, in several AML cases intraclonal heterogeneity was observed. The undifferentiated smaller blasts with Class-IIdim display had higher bcl-2 content than the more differentiated larger blasts with more granular side scatter and Class-bright expression. In the same subsets of AML blasts the proliferative S-G2-M fractions showed a reciprocal correlation to bcl-2 content. Thus the higher bcl-2 levels may give a survival advantage and confer some degree of drug resistance to the least differentiated blast populations. The multi-parameter analysis described in this paper, including a combined bcl-2 and cytokinetic analysis of phenotypically defined subgroups of AML blasts, may detect early population shifts during relapse and also guide combination drug therapy.

Antigens, CD↗

PubMed1994

Receptor interactions of the position 4 side chains of angiotensin II analogues: importance of aromatic ring quadrupole.

A triad of interacting groups (TyrOH-His-O2C) in angiotensin II (ANG II) has been postulated to create the tyrosinate anion pharmacophore (tyanophore) responsible for receptor activation/triggering (Biochim. Biophys. Acta 1991, 1065, 21). In the present study we investigated the effects on bioactivity of substituting the Tyr4 residue in [Sar1]ANG II with other anionic or electronegative amino acids, and with a number of aromatic amino acids lacking a hydroxyl group. [Sar1 Nva(delta-OH)4]ANG II, [Sar1 Nva(delta-OCH3)4]ANG II, [Sar1 Met4]ANG II, [Sar1 Gln4]ANG II, [Sar1 Glu4]ANG II and [Sar1 DL-Alg]ANG II had agonist activities in the rat isolated uterus assay of 4, 3, 19, 10, < 0.1 and < 0.1%, respectively, of that of ANG II. [Sar1 Nal4]ANG II, [Sar1 Pal4]ANG II, [Sar1 DL-Phg(4'-F)4]ANG II, [Sar1 Phe(4'-F)4]ANG II, [Sar1 Phe(F5)4]ANG II and [Sar1 His4]ANG II had agonist activities of 4.5, 7, < 0.1, 0.2, 1 and 0.6%, respectively. All peptides investigated were devoid of measurable antagonist activity except [Sar1 Phe(4'-F)4ANG II (pA2 = 7.7). These findings illustrate that anionic or electronegative aliphatic side chains replacing tyrosinate at position 4 can partially activate the angiotensin receptor. For ANG II analogues containing an aromatic amino acid other than Tyr at position 4, ligand binding and agonist activity are not dependent on the electronegativity or dipole moment of the aromatic ring, or on the ability of the 4' ring substituent to accept a proton.(ABSTRACT TRUNCATED AT 250 WORDS)

Amino Acid Sequence↗

PubMed1994

Abnormalities in p53 and DNA content in transitional cell carcinoma of the bladder.

OBJECTIVE: To determine if transitional cell tumours of the bladder which contain mutations in the p53 gene have alterations in their DNA content. MATERIALS AND METHODS: In 33 transitional cell tumours of the bladder, DNA content was determined by flow cytometry and compared with expression of mutant p53 as assessed by immuno-histochemistry. RESULTS: Abnormal DNA content was associated with increased staining for p53 (P < 0.05), high tumour stage (P < 0.001) and increased histological grade (P < 0.01). Although positive staining for p53 was frequently associated with abnormal DNA content, a significant number of non-diploid tumours stained negatively for mutant p53. CONCLUSION: These data demonstrate that increased staining for p53 is associated with abnormalities in DNA content suggesting that mutation of the p53 gene is associated with an increased rate of chromosomal abnormalities and an increased rate of cell proliferation.

Carcinoma, Transitional Cell↗