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Biomedical subjects

R Morgan

Publications and source records attributed to R Morgan.

At least 163 records · Page 9Linked to original sources
PubMed1993

Apolipoprotein (a) concentrations and susceptibility to coronary artery disease in patients with peripheral vascular disease.

OBJECTIVE: To investigate the relation between apolipoprotein(a) concentrations and angiographically defined coronary artery disease in patients with atheromatous peripheral vascular disease. DESIGN: 40 consecutive patients were recruited at the time of admission for peripheral vascular surgery. All underwent clinical assessment and coronary arteriography. Apolipoprotein(a) concentrations were measured by an immunoradiometric assay. SETTING: Tertiary referral centre. SUBJECTS: Patients requiring surgical intervention for large vessel peripheral vascular disease. MAIN OUTCOME MEASURES: Presence or absence and severity and distribution of angiographically defined coronary artery disease. Measurement of circulating contractions of apolipoprotein(a) and other lipid indices. RESULTS: Coronary artery disease was absent in 11 patients (group 1), mild to moderate in 12 (group 2), and severe in 17 (group 3). The distribution of peripheral vascular disease and of standard lipid indices was similar in these three groups of patients. There was a significant difference in apolipoprotein(a) concentrations between the three groups, with concentrations progressively increasing with the severity of coronary artery disease (mean (95% confidence interval): group 1, 112 U/1 (52 to 242); group 2, 214 U/1 (129 to 355); group 3, 537 U/1 (271 to 1064) (analysis of variance p < 0.005). The prevalence of coronary artery disease was increased 7.4 fold in patients with apolipoprotein(a) concentrations that were greater than the cohort median (206 U/1) (p < 0.01). CONCLUSIONS: The results show an association between apolipoprotein(a) concentrations and angiographically defined coronary artery disease in patients with large vessel peripheral vascular disease. The findings imply differences in the pathogenesis of coronary and peripheral atheroma and suggest that the measurement of apolipoprotein(a) may prove a useful additional tool in the risk factor assessment of patients undergoing peripheral vascular surgery.

Aged↗
PubMed1993

Vagus nerve stimulation for complex partial seizures: surgical technique, safety, and efficacy.

Electrical stimulation of the vagus nerve has shown efficacy in controlling seizures in experimental models, and early clinical trials have suggested possible benefit in humans. Eleven patients with complex partial seizures were subjected to implantation of vagus nerve stimulators. Electrode contacts embedded in silicone rubber spirals were placed on the left vagus nerve in the low cervical area. A transcutaneously programmable stimulator module was placed in an infraclavicular subcutaneous pocket and connected to the electrode. One patient required replacement of the system due to electrode fracture. Another patient developed delayed ipsilateral vocal-cord paralysis; the technique was then modified to allow more tolerance for postoperative nerve edema. A third patient showed asymptomatic vocal-cord paresis on immediate postoperative laryngoscopy. Vagus nerve stimulation produces transient vocal-cord dysfunction while the current is on. Nine patients were randomly assigned to receive either high- or low-current stimulation, and seizure frequency was recorded. The high-current stimulation group showed a median reduction in seizure frequency of 27.7% compared to the preimplantation baseline, while the low-current stimulation group showed a median increase of 6.3%. This difference approached statistical significance. The entire population then received maximally tolerable stimulation. The high-current stimulation group showed a further 14.3% reduction, while the low-current stimulation group showed a 25.4% reduction compared to the blinded period. The efficacy of vagus nerve stimulation seemed to depend on stimulus parameters, and a cumulative effect was evident. These results are encouraging, and further study of this modality as an adjunct treatment for epilepsy is warranted.

Adult↗
PubMed1993

Establishment of cell lines from B-cell precursor acute lymphoblastic leukemia.

In an attempt to establish permanent cell lines from children with B-cell precursor acute lymphoblastic leukemia (BCP-ALL), 123 clinical samples from 117 patients were cultured in vitro. Using a method which was successful for the growth of ALL with T-cell phenotype, 3% (2/74) of BCP-ALL samples from patients at diagnosis and 31% (9/29) of BCP-ALL samples from patients at relapse were established as cell lines. However, in most cultures, leukemic cells survived for only a few weeks and the majority of viable cells present after 28 days of culture were esterase-positive mononuclear cells. Based on the hypothesis that mononuclear cells inhibited leukemic cell growth, we evaluated the effect of a monocyte toxin, L-leucine methyl ester (Leu-OMe), on the growth of four frozen BCP-ALL samples. Thawed leukemic cells treated with Leu-OMe, but not untreated control cells, proliferated in three samples and one new cell line was established. Subsequently, when Leu-OMe was added to fresh leukemia cells in culture, leukemic cell lines were grown from 29% (4/14) of samples at diagnosis and 66% (4/6) of relapse samples. Overall, 20 BCP-ALL cell lines were established, all were Epstein-Barr virus (EBV)-negative, and authenticity of each cell line was verified by a direct comparison of the immunophenotype, karyotype, and genotype with the patient's tumor cells. This improved method of cell culture permits a higher success rate of cell line establishment from patients with BCP-ALL thereby aiding in analysis of B-lymphocyte transformation and neoplasia.

Adolescent↗
PubMed1993

Abnormal pituitary-adrenocortical response in early HIV-1 infection.

The corticotropin-adrenocortical response to cold pressor challenge was investigated in a study of human immunodeficiency virus (HIV) infection. Data obtained from 16 HIV-1-positive and 28 HIV-1-negative subjects are presented in this report. After the insertion of a venicatheter and following 30 min of rest, the subjects immersed one of their hands in an ice-water mixture for 2 min, and serial blood samples were obtained for the determination of ACTH and cortisol levels. The results show a significant blunting in the ACTH response and marginally lower levels of cortisol, over all time points, in HIV-1-positive subjects compared to that in HIV-1-negative subjects.

Adrenocorticotropic Hormone↗
PubMed1992

Application of fluorescence in situ hybridization in hematological disorders.

In the present study, chromosome changes in bone marrow (BM) or peripheral blood (PB) cells from 13 patients with malignant hematologic disorders were analyzed by classical cytogenetic techniques (G-banding) and fluorescence in situ hybridization (FISH) procedures using centromere specific probes for chromosomes 1, 6, 7, 8, 9, 12, 18, 13/21, and X, and a DNA probe specific for the long arm of chromosome Y. The cytogenetic data obtained with G-banding were in accord with those obtained by FISH to metaphase chromosomes. Most significantly, FISH to interphase nuclei offered reliable results and in some cases provided important information concerning crucial chromosome anomalies which were not or could not be completely detected by analyzing metaphase chromosomes. Our results indicate that FISH could be clinically valuable in five major areas: 1) marker chromosome identification; 2) identification of trisomy consistent with certain specific hematological neoplasms; 3) clonal evaluation post observation of a single cell with trisomy; 4) clonal evaluation post-sex-mismatched bone marrow transplantation (BMT); and 5) residual disease detection following clinical remission.

Adolescent↗
PubMed1992

Delayed tumor onset in transgenic mice fed a low-folate diet.

BACKGROUND: Transgenic mice carrying the human T-lymphotropic virus type 1 tax1 (transactivator) gene develop peripheral nerve sheath tumors with well-characterized times of onset and tissue involvement. PURPOSE AND METHODS: To evaluate the effect of dietary folic acid on age at tumor onset and on the concentration of folate in tissues and tumors, we bred heterozygous transgenic mice and systematically assigned their offspring at weaning (within litters) to a 2 x 2 x 2 factorial arrangement. The three variables studied were 1) the tax1 gene (presence or absence), 2) gender (male or female), and 3) dietary level of folic acid (0.11 or 11.34 mumol folic acid per kilogram of controlled amino acid-based diet). Blood and tissues were collected from tumor-bearing transgenic mice (prior to cachexia) and from nontransgenic littermates, matched whenever possible for gender and diet. RESULTS: Transgenic mice fed a diet containing 0.11 mumol of folic acid per kilogram developed tumors significantly later (92.8 +/- 6.4 days) than did those fed a diet containing 11.34 mumol of folic acid per kilogram (71.9 +/- 3.9 days). Folate concentrations in tumors of mice fed the low-folate diet were approximately one third those in tumors of mice fed the higher folate diet. Brain folate concentrations in mice fed the low-folate diet were less than one half those in mice fed the higher folate diet. CONCLUSION: Results show that the onset of spontaneous tumors can be delayed by feeding mice the lowest level of folate adequate to meet nutritional requirements for normal growth. IMPLICATION: Transgenic animal models of human disease offer great potential for evaluating the role of micronutrients in human carcinogenesis.

Analysis of Variance↗
PubMed1992

Plasma vitamin B12 level as a potential cofactor in studies of human immunodeficiency virus type 1-related cognitive changes.

Studies of cognitive function in subjects with human immunodeficiency virus type 1 (HIV-1) infection who remain relatively asymptomatic (ie, Centers for Disease Control stages II and III) have provided widely variable estimates of cognitive impairment. In view of the finding that approximately 25% of asymptomatic HIV-1-infected subjects demonstrate either marginal or overt vitamin B12 deficiency, we have investigated plasma vitamin B12 status as a potential cofactor in studies of HIV-1-related cognitive impairment. When cognition was assessed in asymptomatic (Centers for Disease Control stages II and III) HIV-1-infected participants taking into consideration vitamin B12 status, those subjects with low plasma vitamin B12 levels (less than 180 pmol/L) performed more poorly than did those with normal (greater than or equal to 180 pmol/L) vitamin B12 status on specific measures of information processing speed and visuospatial problem-solving skills. These findings suggest that concurrent vitamin B12 deficiency may be a cofactor in subtle cognitive changes observed in the asymptomatic stages of HIV-1 infection. These differences in prevalence of low plasma vitamin B12 levels may help to explain differences among studies in the proportion of HIV-1-infected subjects showing cognitive impairment.

Adult↗
PubMed1992

An aberrant plastid ribosomal RNA gene cluster in the root parasite Conopholis americana.

The plastid ribisomal RNA (rRNA) operon of the achlorophyllous root parasite Conopholis americana was completely sequenced. Full-length rRNA genes are retained in the gene cluster, but significant divergence has occurred in the 16S, 23S and 5S genes. Both the 16S-23S intergenic spacer and the 4.5S-5S intergenic spacer have suffered substantial deletions, including the two tRNA genes typically found in prokaryotic and plastid 16S-23S spacers.

Base Composition↗
PubMed1992

Loss of transfer RNA genes from the plastid 16S-23S ribosomal RNA gene spacer in a parasitic plant.

The plastid 16S-23S intergenic spacer region in Conopholis americana, a totally heterotrophic angiosperm in the family Orobanchaceae, has undergone large deletions, including the entire tRNA(Ile) gene and all but small remnants of the tRNA(Ala) gene. The length of the region is less than 20% of that of other land plants which have been investigated, making it the smallest 16S-23S intergenic spacer reported thus far for any land plant. The remaining sequences in the spacer are 90.1% identical to tobacco, indicating that, while the region is well conserved at the sequence level, it is evolving rapidly by deletion. Experiments using the polymerase chain reaction and hybridization to DNA gel blots have failed to reveal either of the two missing tRNA genes elsewhere in the Conopholis cell.

Base Sequence↗
PubMed1992

Phase II trial of 5-fluorouracil, high-dose leucovorin calcium, and dipyridamole in advanced prostate cancer.

To examine the effect of altering intracellular folate pools on the efficacy of 5-fluorouracil (FUra) in the treatment of advanced prostate cancer, we performed a phase II trial of FUra (300-370 mg m-2 day-1 x 5 as an i.v. bolus) combined with high-dose folinic acid (500 mg m-2 day-1 x 5.5 days by continuous i.v. infusion) and dipyridamole (75 mg p.o. every 6 h x 5.5 days) administered on a 28-day schedule in patients with stage D2 disease. A group of 13 patients have been treated. The median age was 68 years (range 48-78 years); the performance status ranged from 50% to 90%. Among 12 evaluable patients, there were no objective responders; the median time to progression was 1.9 months. Median survival after entry on this trial was 8.6 months. Treatment with FUra, high-dose folinic acid and dipyridamole was well tolerated. Only one episode each of grade 3 leukopenia, granulocytopenia, and thrombocytopenia was observed. These results suggest that, despite previous trials demonstrating activity for FUra in stage D2 prostate cancer, this disease may be relatively resistant to fluoropyrimidines and, thus, less amenable to biochemical modulation with high-dose folinic acid and dipyridamole.

Aged↗
PubMed1992

Insulin receptor and insulin-responsive glucose transporter (GLUT 4) mutations and polymorphisms in a Welsh type 2 (non-insulin-dependent) diabetic population.

We have recently examined the exons encoding the insulin receptor tyrosine kinase domain and GLUT 4 in 30 subjects with Type 2 (non-insulin-dependent) diabetes mellitus using a molecular scanning approach. The variant sequences Val-Met985 and Lys-Glu1068 of the insulin receptor and Val-Ile383 of GLUT 4 were each separately found in three different diabetic subjects. In a study of a Welsh population, the GLUT 4(383) variant was found in three of 160 diabetic and none of the 80 control subjects. In this study, the same group of Welsh Type 2 diabetic and control subjects was analysed using allele-specific oligonucleotide hybridisation, single nucleotide primer extension and allele-specific restriction digestion to ascertain the frequency of the two insulin receptor mutations. The Val-Met985 mutation was found in none of the 160 Welsh Caucasian Type 2 diabetic subjects and two of 80 control subjects. The Lys-Glu1068 mutation removes a Sty 1 site and digestion of amplified exon 18 with Sty 1 confirmed the presence of the mutation in the heterozygous state in the original subject. None of the Welsh diabetic or control subjects had the Glu1068 mutation. The discovery of a very common silent polymorphism at codon 130 of GLUT 4 allowed examination of the association of this locus with Type 2 diabetes using allele-specific oligonucleotide hybridisation in a subset of the Welsh subjects.(ABSTRACT TRUNCATED AT 250 WORDS)

Alleles↗
PubMed1992

Cytogenetic biclonality in malignant hematologic disorders.

Generally, malignant hematologic disorders have been believed to be of monoclonal origin. However, cytogenetically unrelated clones have been reported in some disorders including one case of acute leukemia (AL), one of acute lymphoblastic leukemia (ALL), one of acute myeloblastic leukemia (AMMoL), and five of myelodysplastic syndromes (MDS). The most frequent chromosome abnormality was trisomy 8 (75%), followed by trisomy 21 (37.5%, including tetrasomy 21) and trisomy 11 (25%). Two patients showed both trisomy 8 and 11, one also had trisomy 21 (triclonal). One patient showed two cytogenetically distinctive clones in which one was 47,XY,+8, related to myeloid cells, and the other had a del(6q) and del(9p), suggesting lymphoid cells. One patient we report and 5 from the literature had two unrelated clones with trisomy 8 and deletion of the long arm of chromosome 5 (5q-); all had MDS. Review of our records showed that 11 patients with both trisomy 8 and 5q- in the same abnormal karyotype (not biclonal) had AL, i.e., 10 of acute nonlymphocytic leukemia (ANNL) and one of chronic myelogenous leukemia (CML) in blastic crisis. These findings suggest that cytogenetically unrelated clones may indicate hematopoietic biclonality.

Acute Disease↗
PubMed1992

Predominance of chromosome 5 deletions in myeloid neoplasia associated with solid tumors managed by surgical excision.

To assess potential differences in genetic predisposition to myeloid neoplasia, we evaluated the karyotypes and reviewed results of cytogenetic studies on bone marrow specimens from six patients with myelodysplastic syndrome, or acute myeloid leukemia, and a history of solid tumor managed solely by surgical resection. Structural or numerical deletions of chromosome 5 were identified in each of four patients with abnormal marrow karyotypes. Constitutional karyotypes were normal in two patients studied with clonal marrow chromosome abnormalities. Review of previously reported cases of myeloid neoplasia following resection of solid tumors disclosed a preponderance of chromosome 5 deletions. Predisposition to specific chromosome loss may influence genetic expression of disease in solid tumor patients developing hematologic malignancy.

Acute Disease↗
PubMed1992

Cytogenetic and FISH studies of abnormal X chromosomes in a patient with ANLL.

We report a case of idic(X)(q13),r(X)(p22q13), and del(X)(:p11-->cen-->q11:) in a 71-year-old female patient with de novo acute nonlymphocytic leukemia (ANLL), FAB-M4. The abnormal X chromosomes of this patient were identified cytogenetically by G-banding technique and were further confirmed by fluorescence in situ hybridization (FISH) using an alpha-satellite probe to chromosome X centromere. The features of this are compared with other cases reported in the literature.

Aged↗
PubMed1992

Critical loads and steady-state chemistry for streams in the state of Maryland.

The critical loads to streams, steady-state stream chemistry and catchment chemical weathering rate in 73 catchments has been determined in the state of Maryland, USA. It was calculated with the PROFILE model from chemical limits for biological indicators, soil mineralogy, soil texture, annual average temperature, average soil moisture, net long-term uptake of base cations and nitrogen to the vegetation, annual precipitation and runoff and deposition of sulphur and nitrogen precursors of acid deposition. The results show a full range of critical loads from very low values in the sensitive catchments of western Maryland and the Coastal Plain on the Chesapeake Bay, to insensitive catchments in the Fredrick Valley and Ridge and the Piedmont plain. The critical loads will be used as an input to an integrated regional assessment of the quantitative sensitivity of streams to acid rain, and the assessment of regional stream alkalinity response to different abatement strategies. The mapping of steady-state stream chemistry indicates that streams in Maryland are still acidfying under the present deposition load. Land-use seems to play an important role in maintaining neutral pH in many of the streams of Maryland.

Journal Article↗