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Biomedical subjects

A Jackson

Publications and source records attributed to A Jackson.

At least 181 records · Page 10Linked to original sources
PubMed1998

Kennedy's disease: unusual molecular pathologic and clinical features.

Two patients with the Kennedy's disease (KD) mutation have been identified in the Newcastle Brain Tissue Bank. One of these patients had presenile dementia as a prominent clinical feature, previously undescribed in KD. The pathologic substrate underlying the cognitive changes in this patient included neuronal depletion and gliosis in the hippocampus and subcortical gliosis in the prefrontal region. Immunostaining for macrophage markers showed evidence for subtle corticospinal tract pathology in both cases. In contrast to the molecular pathologic features found in ALS, surviving motor neurons in the two KD cases showed no evidence of ubiquitinated inclusions or alterations in neurofilament phosphorylation.

Astrocytes↗
PubMed1998

Effects of repeated withdrawal from chronic ethanol on oral self-administration of ethanol on a progressive ratio schedule.

Male hooded Lister rats were trained using a sucrose-fading technique, to perform an operant lever press response to obtain ethanol. Initial training, using an FR4 schedule in which each reinforcement required four lever presses, included varying the concentration of ethanol in the liquid reinforcer. Changes in reinforcer concentration between 7 and 15% (vol/vol) had little effect on either numbers of lever pressing responses, or reinforcers obtained during the 3h session. Increasing the reinforcer concentration to 20% caused a decline in responding. The effects of varying reinforcer concentration (0-20% ethanol) were also studied in the same animals performing a progressive ratio schedule, in which the number of responses required to obtain a reinforcer was successively increased during the session. In these experiments the point at which rats ceased to respond (breaking point) was taken as a measure of their motivation to obtain ethanol. The function describing the relationship between ethanol concentration and number of responses, and number of reinforcers obtained in a session was an inverted U, with the maximum values occurring at an ethanol concentration of 10%. The value of the breaking point (highest ratio achieved) depended on the criterion used to define cessation of responding, but was between 15 and 22. Rats performing for ethanol showed higher breaking points than when responding for water, but there was no statistically reliable effect of ethanol concentration on the breaking point parameter. The effects of feeding the rats a liquid diet containing ethanol, and its subsequent withdrawal, on progressive ratio responding for 5% ethanol, were studied over four cycles of exposure and withdrawal. Intakes of ethanol of 11 g/kg/day had no effect on the animals' breaking point on the progressive ratio schedule, but withdrawal from the ethanol diet resulted in breaking points significantly higher than those in a control group pair-fed a nutritionally equivalent, ethanol-free diet. Although there was no further effect of repeated exposure and withdrawal on responding during the acute withdrawal phase, baseline levels of responding were elevated in the animals which had received multiple cycles of ethanol diet and withdrawal. These results are discussed in the context of the consequences of sensitization to repeated withdrawal from ethanol in dependent animals and humans.

Administration, Oral↗
PubMed1997

Human bZIP transcription factor gene NRL: structure, genomic sequence, and fine linkage mapping at 14q11.2 and negative mutation analysis in patients with retinal degeneration.

The NRL gene encodes an evolutionarily conserved basic motif-leucine zipper transcription factor that is implicated in regulating the expression of the photoreceptor-specific gene rhodopsin. NRL is expressed in postmitotic neuronal cells and in lens during embryonic development, but exhibits a retina-specific pattern of expression in the adult. To understand regulation of NRL expression and to investigate its possible involvement in retinopathies, we have determined the complete sequence of the human NRL gene, identified a polymorphic (CA)n repeat (identical to D14S64) within the NRL-containing cosmid, and refined its location by linkage analysis. Since a locus for autosomal recessive retinitis pigmentosa (arRP) has been linked to markers at 14q11 and since mutations in rhodopsin can lead to RP, we sequenced genomic PCR products of the NRL gene and of the rhodopsin-Nrl response element from a panel of patients representing independent families with inherited retinal degeneration. The analysis did not reveal any causative mutations in this group of patients. These investigations provide the basis for delineating the DNA sequence elements that regulate NRL expression in distinct neuronal cell types and should assist in the analysis of NRL as a candidate gene for inherited diseases/syndromes affecting visual function.

Adult↗
PubMed1997

The influence of chemical shift artifact on magnetic resonance imaging of the ligamentum flavum at 0.5 tesla.

STUDY DESIGN: Retrospective clinical magnetic resonance imaging study and prospective magnetic resonance imaging volunteer study of the appearance of the ligamentum flavum. OBJECTIVE: To demonstrate the effect of chemical shift artifact on the apparent thickness of the ligamentum flavum on axial magnetic resonance images. SUMMARY OF BACKGROUND DATA: The ligamentum flavum is a symmetric structure clearly seen on magnetic resonance images. Apparent unilateral thickening may be interpreted as indicating a pathologic process, and the influence of chemical shift artifact on the apparent thickness of the ligamentum flavum has not been emphasized. METHODS: Ligamenta flava thicknesses were measured from axial T1-weighted gradient echo magnetic resonance scans of 12 consecutive patients and various axial sequences in seven volunteers. RESULTS: The ligamentum flavum appeared consistently thicker on the lower side of the readout gradient field. This chemical shift effect could be manipulated by swapping phase and frequency or patient orientation in the magnet. CONCLUSIONS: Caution should be applied in attributing apparent asymmetry of the ligamenta flava to disease; the influence of chemical shift artifact should be considered.

Adolescent↗
PubMed1997

Developmental loss of hypoxic chemosensitivity in rat adrenomedullary chromaffin cells.

1. We investigated whether adrenomedullary chromaffin cells (AMCs) derived from neonatal (postnatal day (P) 1-P2) and juvenile (P13-P20) rats, and maintained in short-term culture (1-3 days), express O2-chemoreceptive properties. 2. In whole-cell recordings, the majority (approximately 70%; n = 47) of neonatal AMCs were sensitive to hypoxia. Under voltage clamp, acute hypoxia (PO2 approximately 40 mmHg) suppressed voltage-dependent K+ current by 25.1 +/- 3.4% (mean +/- S.E.M.; n = 22); under current clamp, acute hypoxia caused a membrane depolarization of 14.1 +/- 1.3 mV (n = 13) from a resting potential of -54.8 +/- 2.8 mV (n = 13), and this was often sufficient to trigger action potentials. 3. Exposure of neonatal AMC cultures to a moderate (PO2 approximately 75 mmHg) or severe (PO2 approximately 35 mmHg) hypoxia for 1 h caused a dose-dependent stimulation (approximately 3 or 6 times normoxia, respectively) of catecholamine (CA) release, mainly adrenaline, determined by HPLC. This induced CA release was abolished by the L-type calcium channel blocker, nifedipine (10 microM). 4. In contrast to the above results in neonates, hypoxia had no significant effects on voltage-dependent K+ current, membrane potential, or CA release in juvenile AMCs. 5. We conclude that rat adrenal chromaffin cells possess a developmentally regulated O2-sensing mechanism, similar to carotid body type I cells.

Adrenal Medulla↗
PubMed1997

Pretransplant exposure to donor HLA-DR antigen in random transfusion units and the development of donor antigen-specific hyporeactivity.

Our previous studies have shown that the in vitro assay of donor antigen-specific hyporeactivity is a useful marker for identifying solid organ transplant recipients (kidney, lung and heart) at low risk for immunologic complications (i.e., late acute rejection episodes and chronic rejection). Donor antigen-specific hyporeactivity is defined as a significantly decreased post- vs. pretransplant proliferative response to donor antigens while response to third-party controls remains unchanged. We analyzed whether exposure to the same HLA-DR antigen pretransplant via random blood transfusion and posttransplant via the transplanted organ influenced the development of hyporeactivity. Thirty previously nontransfused recipients, each receiving two 150 ml pretransplant random blood transfusions, were assessed for hyporeactivity at 1 year posttransplant. Of the 12 recipients with pretransplant exposure to kidney HLA-DR via transfusions, 6 (50%) developed hyporesponsiveness; in contrast, of the 18 recipients who were not preexposed, only 3 (15%) exhibited this form of immunomodulation. Of interest, 2 of the 3 hyporesponsive recipients who were not preexposed, received units containing HLA-DR antigens previously shown to share crossreactive epitopes with the kidney HLA-DR. In conclusion, these results suggest a increased incidence in the development of hyporeactivity in patients receiving pretransplant transfusions which share an HLA-DR antigen with the transplanted kidney.

Blood Transfusion↗
PubMed1997

The effect of intravenous ketorolac given intraoperatively versus postoperatively on outcome from gynecologic abdominal surgery.

STUDY OBJECTIVES: To examine the effect of timing of an intravenous (i.v.) dose (intraoperative vs. postoperative) of ketorolac tromethamine on pain scores and overall outcome after total abdominal hysterectomy (TAH) and myomectomy. DESIGN: Prospective, randomized, placebo-controlled study. PATIENTS: 248 ASA physical status I and II adult female patients scheduled for elective hysterectomy or myomectomy. INTERVENTIONS: General anesthesia was administered that consisted of thiopental sodium for induction, enflurane or isoflurane in nitrous oxide-oxygen for maintenance, and small doses of fentanyl and midazolam. Patients were randomized into three groups to receive toradol/placebo on a dosing schedule of dose 1 given one-half hour prior to expected end of surgery, dose 2 given on awakening in the postanesthesia care unit, and doses 3, 4, and 5 given at 6, 12, and 18 hours, respectively, after dose 2; Group 1 patients received placebo (saline) for dose 1, ketorolac 60 mg i.v. for dose 2, and ketorolac 30 mg i.v. for doses 3, 4, and 5. Group 2 patients received ketorolac 60 mg i.v. for dose 1, placebo for dose 2, and ketorolac 30 mg i.v. for doses 3, 4, and 5. Group 3 patients received placebo for all doses. All patients were given i.v. morphine PCA postoperatively, and morphine usages, visual analog pain intensity (VAS) scores, as well as adverse events and median times to recovery milestones were recorded. MEASUREMENTS AND MAIN RESULTS: VAS scores (mean) before dose 2 were significantly lower in Group 2 than Group 1, as were at-rest evaluations at 15 minutes and one hour. Group 2 patients also had decreased morphine requirements as compared to placebo. Both ketorolac groups (Groups 1 and 2) had significantly higher values for patient and observer overall ratings, case of nursing care, and tolerability as compared to placebo (Group 3). There were no significant differences among groups in adverse events or median times to recovery milestones. CONCLUSIONS: Although it is possible to demonstrate an improvement in early postoperative pain scores with intraoperative ketorolac and better overall ratings of ketorolac both intraoperatively and postoperatively as compared with placebo, the lack of clinically significant differences in analgesic efficacy in the two active study groups indicates the need for a careful consideration by the clinician of the risks versus benefits involved in the administration of antiplatelet medication in the perioperative period.

Adult↗
PubMed1997

1997 IPA/Bayer Research Awards in Psychogeriatrics. Subcortical hyperintensities in late-life depression: acute response to treatment and neuropsychological impairment.

Subcortical hyperintensities are easily visualized areas of signal abnormality that are seen on T2-weighted magnetic resonance imaging (MRI). Characteristically they occur in the white matter of the brain and are more common in elderly people. In depression, little is known of the clinical significance of subcortical hyperintensities or their contribution to the prognosis. Fifty-eight consecutive patients with DSM-III-R depression and an age range of 65 to 85 years were prospectively collected from an old-age psychiatry service. Response to treatment was assessed with a clinical global outcome measure. A neuropsychology battery was completed on all patients after treatment. Forty-four patients completed MRI scanning. The scans were scored using a regional rating system for hyperintensities. Forty-eight percent of patients had a favorable response to treatment on the clinical global outcome scale. Poor outcome was associated with female sex (p = .07), poor physical health (p = .040), diabetes (p = .018), psychosis (p = .026), and an early age at onset of first episode of depression (p = .036). Even after adjustment for confounding effects, there were significant neuropsychological associations with the regional hyperintensities. Distribution in the periventricular area correlated with delayed recall after distraction (p = .025), and punctate lesions in the basal ganglia correlated with impaired category production (p = .020). Pontine reticular formation hyperintensities were related to impaired psychomotor speed (p = .04). Location in the frontal deep-white matter (p = .024), basal ganglia (p = .03), and pontine reticular formation (p = .02) was associated with a poor acute response to treatment. However, the response to treatment was not related to total cerebral white-matter hyperintensity load. A logistic regression equation included all the significant prognostic features and found four independent predictors of poor outcome: More than five punctate lesions of the basal ganglia, diabetes, lower mean arterial pressure, and hyperintensity of the pontine reticular formation significantly predicted outcome. These four factors correctly predicted 95.6% of patients with a poor outcome and 85.7% with a favorable outcome. In late-life depression, subcortical hyperintensities are common. Lesions in the cerebral white matter are predominantly associated with memory disturbance, and those in deeper infratentorial areas, with psychomotor slowing and executive deficits. Total white-matter load has no prognostic value, and although some subcortical regions are associated with poor response, individually they have little specificity. However, a combination of involvement in three areas (basal ganglia, pons, and frontal lobe) is clinically relevant and predicts outcome with great accuracy (91%). Patients with lesions in the basal ganglia and deep white matter had an especially poor response to pharmacotherapy.

Aged↗
PubMed1997

Dopaminergic properties of cultured rat carotid body chemoreceptors grown in normoxic and hypoxic environments.

Using dissociated carotid body (CB) cultures prepared from neonatal (postnatal days 5-7; P7) or juvenile (postnatal day 19-20; P20) rats, we compared catecholaminergic properties and mechanisms of O2 sensing in glomus cells grown in normoxic (Nox; 20% O2) and chronically hypoxic (CHox; 6% O2) environments for up to 2 weeks. In Nox cultures, basal dopamine (DA) release, determined by HPLC and normalized to the number of tyrosine hydroxylase-positive glomus cells present, was similar for P7 and P20 cultures (approximately 0.3 pmol/1,000 cells/15 min) and was unaffected by culture duration (2 vs. 12 days). Acute hypoxia (5 and 10% O2) caused a dose-dependent stimulation (6x and 3x basal, respectively) in DA release, that was inhibited by nifedipine (10 microM). DA release was also stimulated by high extracellular K+ (30 mM) and iberiotoxin (200 nM), a selective blocker of PO2-regulated, Ca-dependent K+ channel in glomus cells. The stimulatory effect of iberiotoxin was similar to 5% O2 in P20 cultures, but substantially less (about one-half) in P7 cultures. In contrast, in CHox cultures, basal DA release was substantially elevated, approximately 8x Nox levels, although this did not correlate with significant differences in stores. Further, whereas acute hypoxia (5% O2) and high K+ also stimulated DA release in CHox cultures (approximately 2x and approximately 3x basal), iberiotoxin (200 nM) did not. Thus, after chronic hypoxia in vitro, there is an enhanced basal catecholamine release and an apparent down-regulation of functional Ca-dependent K+ channels in CB chemoreceptors. These cellular adaptations may relate to changes in CB chemosensitivity during chronic hypoxemia.

Animals↗
PubMed1997

Phase I-II study of gamma interferon and 5-fluorouracil for patients with metastatic renal cell carcinoma

We have completed a phase I/II trial to evaluate the toxicity and efficacy of the combination of gamma interferon and 5-fluorouracil in metastatic renal cell carcinoma. Gamma interferon was administered at a weekly dose of 100 micrograms. 5-fluorouracil was given as a 5 day continuous infusion days 1-5 of each 21 day cycle. In the phase I portion of the trial, the gamma interferon dose was held constant, while the 5-fluorouracil was escalated from 500 to 800 mg/m2/day. Serum neopterin and beta 2 microglobulin were measured prior to and 48 hours after each dose of gamma interferon for the first six weeks of treatment. Dose limiting toxicity was not encountered in the phase I part of the trial; therefore the phase II study was initiated at the 800 mg/m2/day dose of 5-fluorouracil. No responses were seen among 34 patients treated on the phase II trial. Forty-six percent of patients experienced disease stabilization and the remainder progressed through treatment. In the phase I trial, increments in neopterin and beta 2 microglobulin levels differed significantly between patients treated with lower and higher doses of 5-fluorouracil. We conclude that the addition of 5-fluorouracil to gamma interferon does not appear to enhance the cytokines clinical activity. Incremental increases in macrophage activation markers with escalating 5-fluorouracil doses suggests a role for 5-fluorouracil beyond its usual proposed cytotoxic activity and warrants further investigation into potential immunologic effects of this drug.

Journal Article↗
PubMed1997

A five-year experience with fragile X testing. Setting laboratory standards of practice and a cost-effective protocol.

During the years 1990-1994, our center tested 652 patients, with a broad range of referral indications, for fragile X syndrome using either cytogenetic analysis alone (Protocol 1) or more recently, a combination of DNA analysis and routine karyotyping (protocol 2). The overall positive rate for fragile X was 3.1% with an incidence of other chromosomal abnormalities (OCAs) of 3.2%. Breakdown of cases using each testing protocol along with percent positives is: [table: see text] Use of Protocol 2 yielded only definitive fragile X results, while more than half of the "positives" using Protocol 1 were equivocal. Historically this has been problematic for both the laboratory and physician since interpretation is often dependent on an equally equivocal clinical picture. Protocol 2 eliminates these diagnostic dilemmas without compromising detection of other chromosomal abnormalities, the incidence of which appears to be unaffected by testing method used. The overall incidence of OCA of 3.2% underscores the value of routine karyotyping in this referral group and likely reflects the phenotypic variability of fragile X and its clinical overlap with other chromosomal abnormalities. We believe that a fragile X testing protocol combining routine karyotyping with definitive molecular technology represents the most cost-effective diagnostic approach to this clinically challenging patient population.

Clinical Laboratory Techniques↗
PubMed1997

Carcinoma of the sigmoid colon presenting as a scrotal swelling.

A case of adenocarcinoma of the sigmoid colon, presenting as a testicular mass, is described. At sigmoid colectomy widespread metastases were found and only palliative care could be offered thereafter. The incidence and age of such a presentation and manner of spread of the occult primary are discussed.

Adenocarcinoma↗
PubMed1997

Reassessing Oregon's Death With Dignity Act.

In 1994 the state of Oregon made people all over the country sit up and take notice when its citizens voted to enact the Death with Dignity Act. This year, after the Supreme Court of the United States declined to address the Act's constitutionality, citizens will again address the issue, deciding whether terminally ill patients will be able to ask their physicians to help them die.

Hospices↗