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Biomedical subjects

M W Jones

Publications and source records attributed to M W Jones.

At least 19 recordsLinked to original sources
PubMed1999

Impaired synaptic plasticity and learning in aged amyloid precursor protein transgenic mice.

We investigated synaptic communication and plasticity in hippocampal slices from mice overexpressing mutated 695-amino-acid human amyloid precursor protein (APP695SWE), which show behavioral and histopathological abnormalities simulating Alzheimer's disease. Although aged APP transgenic mice exhibit normal fast synaptic transmission and short term plasticity, they are severely impaired in in-vitro and in-vivo long-term potentiation (LTP) in both the CA1 and dentate gyrus regions of the hippocampus. The LTP deficit was correlated with impaired performance in a spatial working memory task in aged transgenics. These deficits are accompanied by minimal or no loss of presynaptic or postsynaptic elementary structural elements in the hippocampus, suggesting that impairments in functional synaptic plasticity may underlie some of the cognitive deficits in these mice and, possibly, in Alzheimer's patients.

Aging↗
PubMed1999

Age-related differences in spatial memory: effects of structural and organizational context.

The authors examined effects of structural and organizational spatial context on younger and older adults' memory for an arrangement of dollhouse furniture pieces. For half of the participants, landmark objects (Experiment 1) and a floor plan beneath the array (Experiment 2) served as structural context during study and replacement. Organizational context was varied by grouping items randomly or as 6 rooms in a prototypical house. Two study and replacement trials were given. In Experiment 1, landmark structural cues improved younger adults' performance, whereas both age groups benefited from the floor plan in Experiment 2. In both experiments, positive effects of organizational context and trial occurred. Higher order interactions further revealed that structural and organizational context effects varied in size across trials, suggesting that both age groups used spatial contextual cues more effectively with practice. Implications of these results for current views on cognitive compensation in adulthood are discussed.

Adult↗
PubMed1998

The impact of adjuvant radiotherapy on carcinosarcoma of the uterus.

BACKGROUND: The role of adjuvant radiotherapy in the setting of uterine carcinosarcoma has not been clearly established. METHODS: A retrospective review of 60 patients receiving definitive therapy for carcinosarcoma of the uterus was undertaken at a single institution. Twenty-nine of 60 patients were treated with adjuvant radiotherapy. RESULTS: The addition of radiotherapy significantly reduced the local recurrence rate from 55% (17 patients) to 3% (1 patient). Adjuvant radiotherapy reduced the risk of distant failure and death in patients with disease confined to the uterus but did not impact distant recurrence or survival in stage III patients. Increasing stage and depth of myometrial tumor invasion were negatively associated with overall survival and disease-free survival but had no impact on local recurrence rates. The nuclear grade of the epithelial component was predictive of local recurrence (P = 0.0592), but epithelial architectural grade, grade of stromal component, and stromal versus epithelial predominance did not provide prognostic information. The relative risk of local recurrence of unirradiated patients versus irradiated patients was 17.54 (P = 0.0055) after adjusting for nuclear grade of the epithelial component. CONCLUSIONS: Local failure represents a significant site of failure in the absence of adjuvant radiotherapy. The improvement in local failure rates with the addition of radiotherapy translates into an improvement in distant failure rates and survival only for patients with stage I/II disease. Epithelial nuclear grade, in addition to depth of myometrial invasion and stage, provides important prognostic information. Epithelial architectural grade, stromal grade, type of stromal component (homologous versus heterologous), and predominance of either stromal or epithelial component were not found to be significant prognostic factors.

Aged↗
PubMed1998

Lethal postoperative coronary artery spasm.

BACKGROUND: Coronary artery spasm in the immediate postoperative period after a coronary operation is recognized infrequently. Its severity is variable and manifestations unpredictable. The diagnosis is usually made by an awareness of the possibility and thereafter by exclusion of other causes of myocardial ischemia. An opportunity for a positive diagnosis is rarely available. METHODS: The case reports of 3 patients with similar presentations of ischemic heart disease and with severe manifestations of coronary artery spasm in the postoperative period are presented. RESULTS: All 3 patients were women aged 55 to 60 years. All had single-vessel coronary artery disease involving the left anterior descending artery and underwent a left internal mammary artery bypass graft. Severe manifestations of myocardial ischemia of abrupt onset developed approximately 7 hours postoperatively in each patient. One patient died of severe hemodynamic deterioration from which resuscitation was unsuccessful. Another sustained a large anterior myocardial infarction despite graft patency. The third patient was supported by an intraaortic balloon pump and made a full recovery. CONCLUSIONS: The early diagnosis of coronary artery spasm is achieved by an awareness of the condition. The institution of early appropriate management may prevent its consequences.

Adult↗
PubMed1998

Carcinosarcomas (malignant mixed mullerian tumors) of the female genital tract: comparative molecular analysis of epithelial and mesenchymal components.

Female genital tract carcinosarcomas (FGTCS) are biphasic neoplasms composed of an admixture of malignant epithelial and mesenchymal elements. Histogenesis of FGTCS centers on two theories: (1) simultaneous formation of independent tumors (biclonal theory), (2) multidirectional differentiation of a single neoplasm (monoclonal theory). In an attempt to resolve this histogenetic controversy, we determined the presence, specific genotype, and timing of p53 mutational change in each component of FGTCS using a topographic genotyping (TG) approach. We selected 43 FGTCS from the files of Magee-Womens Hospital, Pittsburgh, and initially immunostained them for p53 protein. Strong p53 immunopositivity was detected in 35 (82%) of 43 tumors. Subsequently, topographic genotyping (TG) was performed on a subset of nine immunopositive tumors with sufficiently distinct malignant components to enable effective sampling. All nine tumors showed point mutations in p53 exons 5 through 8. In each case, the identical point mutational genotype was present in both components. Furthermore, in all nine cases mutations were present with loss of the wild-type allele. P53 gene mutation is a frequent event in progression of FGTCS. Of importance, both p53 mutation and allelic loss occur before the differentiation into separate epithelial and mesenchymal malignant components. These molecular findings strongly support monoclonal, multidirectional histogenesis of FGTCS.

Base Sequence↗
PubMed1998

Topiramate--safety and tolerability.

Topiramate is a new novel drug for the treatment of intractable seizures that is to be used in an adjunctive fashion. A review of the seven double-blind controlled studies was undertaken with special attention paid to safety and tolerability data. The studies were similar in design but used varying doses of the drug. To date there has been no evidence of serious systemic side effects such as rash, hepatotoxicity, cardiotoxicity, serious gastrointestinal toxicity or aplastic anemia. Renal stones were reported in 1.5% of patients with over 80% choosing to remain on the drug because of an improved quality of life. The unique observation of "abnormal thinking" was seen that seemed to be related to high doses and introducing the drug too rapidly. Patients, rather than describing psychomotor slowing, described a phenomenon of slow thoughts, decreased cognition, intermittent difficulty calculating, dulled thinking, blunted mental reactions. Lastly, weight loss appears in approximately 10-20% of patients and is probably related to dulling of appetite. Although increasing doses gave increasing degrees of seizure freedom, it appeared that doses beyond 600 mg/day are often not well tolerated.

Anticonvulsants↗
PubMed1998

Consequences of epilepsy: why do we treat seizures?

Improving health-related quality of life in epileptic patients, rather than simply reducing seizures, has become the principal goal in epilepsy management. Reducing seizure frequency is one of the main factors contributing to improved quality of life. Evidence for and risk of the following potential adverse effects of seizures is reviewed: brain damage from seizures, sudden unexpected death, status epilepticus, kindling, falls or injury and psychosocial consequences. Although the evidence for seizure frequency influencing some of these factors is not clear-cut, as a whole, they offer a strong impetus toward an aggressive approach to controlling recurrent seizures in most cases.

Accidental Falls↗
PubMed1998

Management of the woman with gestational diabetes mellitus.

The management of gestational diabetes mellitus focuses on the woman's physical, psychosocial, and educational needs. Education is the basis for ensuring the best possible outcome for the mother and infant, and the nurse is an integral part of the educational process. The woman must acquire new knowledge and skills regarding diet, blood glucose monitoring, insulin therapy, and exercise. An individualized approach to treatment includes sensitivity to the woman's cultural background and learning ability. Compliance with the treatment plan can be enhanced by rapport between the woman and health care providers.

Adult↗
PubMed1997

Adjuvant radiation for vulvar carcinoma: improved local control.

PURPOSE: Local recurrence is a significant problem following primary surgery for advanced vulva carcinoma. The objectives of this study were to evaluate the impact of adjuvant vulvar radiation on local control in high risk patients and the impact of local recurrence on overall survival. METHODS AND MATERIALS: From 1980-1994, 62 patients with invasive vulva carcinoma and either positive or close (less 8 mm) margins of excision were retrospectively studied. Thirty-one patients were treated with adjuvant radiation therapy to the vulva and 31 patients were observed after surgery. Kaplan-Meier estimates and the Cox proportional hazard regression model were used to evaluate the effect of adjuvant radiation therapy on local recurrence and overall survival. Independent prognostic factors for local recurrence and survival were also assessed. RESULTS: Local recurrence occurred in 58% of observed patients and 16% in patients treated with adjuvant radiation therapy. Adjuvant radiation therapy significantly reduced local recurrence rates in both the close margin and positive margin groups (p = 0.036, p = 0.0048). On both univariate and multivariate analysis adjuvant radiation and margins of excision were significant prognostic predictors for local control. Significant determinants of actuarial survival included International Federation of Gynecologists and Obstetricians (FIGO) stage, percentage of pathologically positive inguinal nodes and margins of excision. The positive margin observed group had a significantly poorer actuarial 5 year survival than the other groups (p = 0.0016) and adjuvant radiation significantly improved survival for this group. The 2 year actuarial survival after developing local recurrence was 25%. Local recurrence was a significant predictor for death from vulva carcinoma (risk ratio 3.54). CONCLUSION: Local recurrence is a common occurrence in high risk patients. In this study adjuvant radiation therapy significantly reduced local recurrence rates and may improve overall survival in certain subgroups. As salvage rates after developing local recurrence are poor adjuvant vulvar radiation should be considered for patients at risk after primary surgery.

Adult↗
PubMed1997

Epilepsy and driving: a survey of Canadian neurologists.

BACKGROUND: A seizure is the most common cause of loss of driving privileges for medical reasons but there is variability in how physicians and the authorities who regulate driving approach this issue. METHODS: A questionnaire regarding epilepsy and driving was sent to all adult neurologists in Canada (n = 494). RESULTS: Of 289 (59%) neurologists responding, 50% usually report patients with seizures to the department of motor vehicles compared to only 4% for stroke/TIA, 26% for dementia and 8% for other neurologic disorders (p < 0.0001). In the five provinces with mandatory reporting laws, seizures were reported most of the time by 84% compared to only 19% in the five provinces with discretionary reporting (p < 0.0001). Nationwide, 44% agreed with mandatory reporting but this also differed in provinces with and without mandatory reporting legislation (63% vs. 37%, p < 0.0001). Only 49% agreed with the current recommendation of at least one year seizure free interval before resuming driving. CONCLUSIONS: Seizures are disproportionately reported compared to other neurological conditions. Many neurologists disagree with the recommended Canadian standards for duration of driving restriction after seizures. Variability in the attitude and practice of neurologists in regard to reporting of seizures is confirmed.

Adult↗
PubMed1997

The origin and molecular characterization of adenoid basal carcinoma of the uterine cervix.

Five cases of adenoid basal carcinoma (ABC) of the uterine cervix were examined for the presence of p53 tumor suppressor gene, K-ras-2 oncogene, and human papillomavirus (HPV). A topographic genotyping approach was used to search for point mutations in K-ras-2 (exon 1 and 2) and p53 (exons 5 to 8) in archival formalin-fixed tissue blocks. Minute target sites were selected from polymerase chain reaction (PCR) amplified and directly sequenced tissue sections. Tissue sections were additionally subjected to immunohistochemical staining for p53 and WAF-1 protein. Because wild type p53 induces WAF-1 gene expression, immunohistochemical staining for WAF-1 protein using monoclonal antibodies may serve as an indirect means to test for p53 mutational damage. Mutational genotype was compared to histopathologic features and immunohistochemical staining. To study the role of HPV, L1 region consensus primers were used to amplify topographic samples, followed by HPV genotyping by direct sequencing and comparison to known viral strains. ABC was found to contain HPV in all cases, proven by genotyping to be HPV type 16 in each case. The virus showed no evidence of genomic variation from prototype HPV type 16 in the L1 segment examined. No K-ras-2 point mutations were identified. p53 immunopositivity was present in all tumors, being weak and focal in 4 and strong and diffuse in 1. WAF-1 immunostaining was positive in two tumors showing weak focal p53 immunopositivity. The single strong and diffuse p53 immunopositive tumor was negative for WAF-1 and was shown to contain a missense p53 point mutation (exon 7-codon 248 tryptophan). In conclusion, ABC is characterized by the presence of HPV type 16. K-ras-2 point mutation appears to play no role in the development of this tumor. p53 gene alterations are common including wild type hyperexpression (weak focal p53 immunopositivity, WAF-1 positivity, no mutational change) and p53 point mutational damage.

Adult↗
PubMed1997

Prognostic value of p53 and K-ras-2 topographic genotyping in endometrial carcinoma: a clinicopathologic and molecular comparison.

The predictive value of p53 and K-ras-2 mutational genotyping in determining tumor aggressiveness and survival in patients with endometrial carcinoma (EC) was retrospectively evaluated using a molecular genotyping approach on fixative treated tissue specimens. Two groups of patients with EC were selected based upon length of survival. Group A consisted of 14 patients that died within 3 years of initial diagnosis and treatment (mean survival of 1.1 years). Group B consisted of 18 patients that survived beyond 3 years (mean survival of 4.7 years). Clinicopathologic features including clinical stage, histologic type, and combined nuclear and architectural grade of each tumor were statistically analyzed with respect to oncogene/tumor suppressor gene alterations. The majority of carcinomas in group A were serous (57%), stage III or IV (93%), and high combined grade (93%). Group B consisted mostly of endometrioid (89%) and low-grade carcinomas (83%); 56.1% were stage III or IV. K-ras-2 point alterations were found in 2 (14%) and 4 (22%) patients from group A and B respectively; the spectrum of K-ras-2 genotypes was similar in both groups. p53 gene mutations were identified in 9 (64%) and 1 (6%) patient from group A and B respectively. p53 staining in group A tended to be of strong intensity and diffuse distribution, being associated with the presence of point mutations, mainly in exon 8. Only a single group B tumor exhibited point mutational change. The presence of p53 mutations strongly correlated with short survival (p <0.05) but the finding of K-ras-2 alterations did not. p53 genotyping has potential prognostic value in EC and can be used along with histopathologic type and histologic grade to identify subsets of more aggressive tumors and to guide the treatment.

Adenocarcinoma↗
PubMed1995

Reactive microglia in hippocampal sclerosis associated with human temporal lobe epilepsy.

An immunoperoxidase method was used to demonstrate expression of HLA-DR (a Class II major histocompatibility antigen) as an indicator of microglial activation in cases of hippocampal sclerosis derived from temporal lobectomy for intractable seizures. HLA-DR-immunoreactive microglia were increased approximately 11-fold in CA1 and 3-fold in CA3, compared to control autopsy hippocampus. The numbers of HLA-DR-immunoreactive perivascular cells were also significantly increased in hippocampal sclerosis cases (9-, 7- and 6-fold increases in CA1, CA3 and CA2, respectively). Since animal studies have found microglial activation to be an acute or subacute response to injury, the results presented here suggest that, contrary to the classical conception of human hippocampal sclerosis as an inert scar, neuronal injury continues to occur as a result of ongoing seizure activity.

Adolescent↗
PubMed1995

Statistical prediction of the optimal site for thalamotomy in parkinsonian tremor.

Stereotactic lesions in the thalamus for treatment of parkinsonian tremor are often made at the location where neurons fire at approximately tremor frequency (tremor cells). Some of these cells show a large amount of activity at tremor frequency and are significantly correlated with electromyographic activity (EMG) during tremor. Our analysis of cellular location identifies a cluster of neurons showing activity characterized both by concentration of power at tremor frequency and by significant correlation with EMG. In a retrospective analysis of results in 15 patients, lesions placed within 2 mm of the center of this cluster were uniformly effective in relieving tremor. Therefore, a small lesion targeting this cluster is effective in treatment of parkinsonian tremor.

Brain Mapping↗
PubMed1995

Interactions between metabotropic and ionotropic glutamate receptor agonists in the rat spinal cord in vivo.

Microelectrophoretic application of the non-selective metabotropic glutamate receptor (mGluR) agonist (1S,3R)-1-aminocyclopentane-1,3-dicarboxylic acid [(1S,3R)-ACPD] and the group I selective mGluR agonist (RS)-3,5-dihydroxyphenylglycine [(RS)-3,5-DHPG] potentiated the responses of rat spinal neurones to the cyclically-ejected ionotropic excitatory amino acid (EAA) agonists NMDA, AMPA and kainate in vivo. Potentiation was not selective between the three ionotropic responses and was paralleled by an enhancement of background activity in spontaneously active cells. "Correcting" spike count data for this increase in background activity showed that the EAA responses were not potentiated beyond the apparent enhancement of cell excitability. Neither mGluR agonist produced potentiation when NMDA/AMPA cycling was superimposed on background discharge held constant with kainate. It is concluded that potentiation produced by both (1S,3R)-ACPD and (RS)-3,5-DHPG is secondary to an enhancement of cell excitability rather than being due to a specific interaction with ionotropic EAA receptors. The mechanism of excitability enhancement cannot be determined by extracellular recording, but group I mGluRs are most likely to be responsible.

Action Potentials↗
PubMed1995

Adenosarcoma of the uterine cervix: a clinicopathological study of 12 cases.

The clinical and pathologic features of 12 cervical adenosarcomas from the files of the Armed Forces Institute of Pathology are described. The patients ranged in age from 13 to 67 years (mean 37). The majority (58%) presented with abnormal bleeding. All tumors were located in the cervix and consisted of soft, tan, polypoid or papillary masses ranging in size from 1.5 to 4.5 cm. Microscopically, they showed a biphasic pattern with mesenchymal and epithelial components. There was a characteristic stromal condensation below the epithelial surface and around glandular structures. The cytologic atypia of stromal cells was 1+ in three, 2+ in five, and 3+ in four. The mitotic activity ranged from four to 28 (mean 7.0) mitotic figures per 10 high-power fields. One neoplasm contained cartilage and one striated muscle. Myometrial invasion was present in three. Treatment consisted of hysterectomy in nine patients and excisional biopsy in three. Two patients received radiotherapy; one before surgery and the other after hysterectomy. Two were treated with chemotherapy. Follow-up ranged from 9 months to 18.8 years. Nine patients were alive and well with no evidence of recurrent tumor at postoperative intervals of 0.8-18.8 years. One patient died 1 year after diagnosis with intraabdominal metastasis. One developed a recurrent tumor. This study demonstrates a favorable prognosis for patients with cervical adenosarcoma. Similar to patients with uterine adenosarcoma, prognosis is mostly affected by the presence of deep myometrial invasion.

Adenosarcoma↗