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Biomedical subjects

L M King

Publications and source records attributed to L M King.

At least 55 records · Page 3Linked to original sources
PubMed1996

Preictal pseudosleep: a new finding in psychogenic seizures.

BACKGROUND AND OBJECTIVE: The diagnosis of psychogenic seizures (pseudoseizures) may be difficult and usually rests on video-EEG monitoring. We observed that pseudoseizures often arise out of a state that we termed preictal pseudosleep. The objective of this study was to investigate this potential new sign in pseudoseizures. METHODS: We prospectively studied all patients who underwent noninvasive monitoring over a 10-month period. Patients were monitored for a duration of 1 to 19 days (mean 4.9), and were divided into two groups: pseudoseizures and epileptic seizures. Patients with both conditions were excluded. Preictal pseudosleep was defined as a state that resembled normal sleep by behavioral criteria alone (i.e. patient motionless and eyes closed), while EEG showed evidence of wakefulness (alpha rhythm, active EMG, and rapid eye movement). This state had to be sustained for at least 1 minute before clinical onset. RESULTS: Patients had 1 to 25 (mean 7) clinical events recorded. Preictal pseudosleep was seen in 10 of 18 patients with pseudoseizures and in none of 39 patients with epileptic seizures, yielding a sensitivity of 56% and a specificity of 100% for pseudoseizures. CONCLUSION: Because of a high specificity, preictal pseudosleep may be a useful adjunctive finding to support the diagnosis of pseudoseizures.

Adult↗
PubMed1995

Peroxisome proliferation and microsomal enzyme induction by the hypolipidemic CI-924 in rats and mice: relationship to tumorgenicity.

CI-924 (5'5'-[1,1'-biphenyl]-2,5-diylbis(oxy)]bis [2,2-dimethyl-pentanoic acid]), a lipid lowering agent, was previously shown to be hepatotumorigenic in male and female B6C3F1 mice but not in male and female albino Wistar rats. To determine if the difference between the species in tumorigenic response correlated with the extent of peroxisome proliferation or microsomal changes the effects of CI-924 on liver were characterized in rats and mice. CI-924 doses of 0, 25, 75, and 150 mg/kg were administered in the diet for 4 weeks to B6C3F1 mice and albino Wistar rats. Peroxisomal beta-oxidation activity was significantly increased in all groups at doses of 25 mg/kg or higher and was induced up to 25 times in male rats. Peroxisomal carnitine acyltransferase and acyl-CoA oxidase activities were also increased, with the greatest induction observed in male rats. Catalase activity quadrupled in rats and doubled in mice. Serum liver enzyme activities were unchanged with the exception of 5'nucleotidase which was elevated in mice and decreased in male, but not female, rats. Glutathione S-transferase decreased in the males of both species and glutathione peroxidase increased in the mice. Cytochrome P450 4A1 increased in both species at doses of 25 mg/kg or greater and correlated with increased lauric acid hydroxylation. The high degree of peroxisome proliferation in male rats was unexpected in light of the lack of tumorgenicity demonstrated in a previous 2-year study and these results indicate that early peroxisome proliferation alone is not always a good predictor of hepatocarcinogenicity.

Animals↗
PubMed1995

Coronary flow and glucose delivery as determinants of contracture in the ischemic myocardium.

Ischemic contracture may be avoided by the provision of glucose under low flow conditions (Owen et al., 1990). However, accumulation of harmful metabolic end products may inhibit glycolytic flux and lessen the benefit of glucose. We assessed whether during increasingly severe flow restriction, provision of glucose might be harmful rather than beneficial, using the Langendorff perfused rat heart. Ischemic contracture (resting tension expressed as percent of preischemic developed pressure) was measured via a left ventricular balloon. Reductions in flow to 0, 0.015, 0.03, 0.06, 0.1, 0.2 or 0.4 ml/min/g wet wt over 60 min were tested. At zero flow, peak contracture was 61.4 +/- 3.5% (+/- S.E.) but fell to 15.6 +/- 6.3% with 0.4 ml/min/g wet wt (P < 0.05) in the presence of 11 mmol/l glucose. Time-to-onset of contracture was significantly delayed by the higher coronary flows. At coronary flows down to zero, the effect of glucose was inconstant or absent, but not harmful. With the residual flow at 0.2 ml/min/g wet wt, a dose response to glucose in ischemia was elicited, using concentrations of 0, 2.5, 5.5, 11 or 22 mmol/l. Maximum protection against ischemic contracture was found with 11 mmol/l glucose. However, once contracture occurred, functional recovery was severely impaired in all cases. Reducing glycogen prior to low flow ischemia (0.2 ml/min/g wet wt) with 11 mmol/l glucose increased peak contracture, and reduced the time-to-onset of contracture. Increased preischemic glycogen had little effect on contracture. Glycolytic flux fell in proportion to the coronary flow. However, there was an increased glucose extraction at lower flows of 0.1 and 0.2 ml/min/g wet wt, suggesting that it is the rate of delivery (i.e. coronary flow) which is the rate limiting step rather than enzyme inhibition by accumulated metabolites. If flow were further reduced, metabolite accumulation would become more important, such that with no flow, this would be the determinant of glycolytic flux rate. In our model, the two requirements for optimal protection from ischemia were (i) provision of glucose (11 mmol/l was optimal) and (ii) an adequate coronary flow to deliver the glucose and remove end product inhibition (greater than 0.06 ml/min/g wet wt).

Animals↗
PubMed1995

Pseudoachondroplasia and multiple epiphyseal dysplasia due to mutations in the cartilage oligomeric matrix protein gene.

Pseudoachondroplasia (PSACH) and multiple epiphyseal dysplasia (MED) are dominantly inherited chondrodysplasias characterized by short stature and early-onset osteoarthrosis. The disease genes in families with PSACH and MED have been localized to an 800 kilobase interval on the short arm of chromosome 19. Recently the gene for cartilage oligomeric matrix protein (COMP) was localized to chromosome 19p13.1. In three patients with these diseases, we identified COMP mutations in a region of the gene that encodes a Ca++ binding motif. Our data demonstrate that PSACH and some forms of MED are allelic and suggest an essential role for Ca++ binding in COMP structure and function.

Achondroplasia↗
PubMed1995

Molecular basis of polymorphism at the esterase-5B locus in Drosophila pseudoobscura.

Sequence variation was studied in a 2.2-kb region encompassing the esterase-5B locus in Drosophila pseudoobscura from two California populations. In these populations, two common electrophoretic classes and many less frequent variants occur, and it was formerly shown by KEITH (1983) that allele frequencies differed from random distribution under an infinite allele model. Nucleotide polymorphisms were determined in 16 sequences representing 14 electrophoretic classes. There was no significant sequence differentiation between populations, and both synonymous and nonsynonymous polymorphisms are distributed homogeneously along the sequence. The data show that the two major electrophoretic classes are heterogeneous at the amino acid level with no diagnostic amino acid(s) distinguishing them. At the nucleotide level, members of one major class are more similar to members of other electrophoretic classes than they are to each other. It appears that random combinations of the neutral amino acid polymorphisms and other undefined physical properties of the proteins generate the different electrophoretic classes and maintain considerable variation at Est-5B.

Amino Acid Sequence↗
PubMed1994

Slipped-strand mispairing in a plastid gene: rpoC2 in grasses (Poaceae).

An exception to the generally conservative nature of plastid gene evolution is the gene coding for the beta" subunit of RNA polymerase, rpoC2. Previous work by others has shown that maize and rice have an insertion in the coding region of rpoC2, relative to spinach and tobacco. To assess the distribution of this extra coding sequence, we surveyed a broad phylogenetic sample comprising 55 species from 17 angiosperm families by using Southern hybridization. The extra coding sequence is restricted to the grasses (Poaceae). DNA sequence analysis of 11 species from all five subfamilies within the grass family demonstrates that the extra sequence in the coding region of rpoC2 is a repetitive array that exhibits more than a twofold increase in nucleotide substitution, as well as a large number of insertion/deletion events, relative to the adjacent flanking sequences. The structure of the array suggests that slipped-strand mispairing causes the repeated motifs and adds to the mechanisms through which the coding sequence of plastid genes are known to evolve. Phylogenetic analyses based on the sequence data from grass species support several relationships previously suggested by morphological work, but they are ambiguous about broad relationships within the family.

Base Sequence↗
PubMed1993

Urban violence in Los Angeles in the aftermath of the riots. A perspective from health care professionals, with implications for social reconstruction.

Beginning April 29, 1992, Los Angeles, Calif, was engulfed in a 3-day insurrection reflecting the residents' responses to a legal ruling. Unlike the media-painted picture, this article argues that the enormous outburst of violence and consequential property destruction was not the exclusive domain of the citizens of South-Central Los Angeles and that available data will not support the maintenance of the prevailing uneven distribution of civic and state resources in health care, educational programs, and economic opportunities. What it does support is the proposal for a more equitable allocation of resources among institutions, groups, and peoples, complemented by community empowerment, a more civic-oriented police operation, and a more rational approach to social reconstruction in which all elements of the society are full participants. Finally, the article suggests that augmentation of the present "law and order" approach and the paramilitary police already have proven economically ineffective. Given the dominant role of the medical profession in social and civic life, it is now appropriate for the medical profession to enter the debate on policies of health improvement, violence deterrence, and the general field of social reconstruction.

Health Occupations↗
PubMed1993

The in vitro metabolic activation of the 11-trifluoromethyl analogue of the potent carcinogen 15,16-dihydro-11-methyl-cyclopenta[a]-phenanthren-17-one to mutagens.

A strongly electronegative, bay-region analogue of the potent carcinogen 15,16-dihydro-11-methylcyclopenta[a]phenanthren-17-one, namely 15,16-dihydro-11-trifluoromethylcyclopenta[a]phenanthren-17-one, is mutagenic to Salmonella typhimurium TA100. Also it is metabolized at the 1,2- and 3,4-positions in the A-ring as well as C-15 in the D-ring to give 3,4-dihydroxy-3,4,15,16-tetrahydro-11-trifluoromethyl- cyclopenta[a]phenanthren-17-one as the only mutagenic metabolite. In these respects its behaviour is closely similar to that of the 11-methyl compound, suggesting that the electronic nature of the bay-region substituent is rather less critical than its spatial configuration in influencing metabolism to genotoxic intermediates. It remains to be seen, however, whether the trifluoromethyl compound is also a carcinogen.

Animals↗
PubMed1993

Steroid treatment of radiation-induced choroidopathy.

Irradiation has been an important form of treatment of both ocular and cerebral neoplasms for decades. We report the case of a patient who underwent external beam irradiation to treat an astrocytoma of the left parietotemporal region. Sixteen months later, the patient developed radiation choroidopathy OS. Although not spontaneously resolvable, this case suggests that radiation choroidopathy can be treated successfully by the prompt and repeated application of both local and systemic corticosteroid preparations.

Astrocytoma↗
PubMed1992

An analysis of potential and real cost savings by the addition of ranitidine to total parenteral nutrition solutions.

The results of two analyses that assessed the potential savings and the actual savings derived from the addition of ranitidine to total parenteral nutrition solutions are discussed. A clinical pharmacist determined on a daily basis the number of patients receiving concurrent total parenteral nutrition solutions and intermittent intravenous ranitidine in a critical care unit. The cost of each mode of administration was determined and the savings were calculated to be over +16,000/year. Once the practice of adding ranitidine to total parenteral nutrition solutions became routine, total parenteral nutrition solution orders for April-June 1991 were collected and the number of patient days were counted and the accrued savings were determined to be slightly more than +10,000 each year. Differences are explained by discrepancies in expected and true number of patient days. The authors conclude that there are savings to be realized by adding ranitidine, or any H2 antagonist, to total parenteral nutrition TPN solutions and avoiding intermittent infusions.

Cost Savings↗
PubMed1991

Effect of pH shifts induced by oxygenating crystalloid cardioplegic solutions.

Oxygenation of a bicarbonate-containing crystalloid cardioplegic solution alters the partial pressure of both oxygen (O2) and carbon dioxide (CO2). Therefore, oxygenating St. Thomas' Hospital II plus glucose (11 mmol/L) cardioplegic solution with 95% O2 + 5% CO2 induces a pH shift to 7.0 (10 degrees C) as opposed to pH 9.3 with 100% O2. In an isolated working rat heart model, we show that pH 7.0 (10 degrees C) improves mechanical postischemic recovery in the absence or presence of O2. However, in the absence of O2, pH 7.0 appears to inhibit glycolysis and diminish the stability of cellular membranes. The provision of O2 independently improved mechanical recovery and at pH 7.0, improved the preservation of the sarcolemma. Increasing the O2 content by including a perfluorocarbon (FC-43) in the oxygenated St. Thomas' plus glucose cardioplegia is not additionally beneficial. St. Thomas' Hospital plus glucose cardioplegic solution should be oxygenated, but with 95% O2 + 5% CO2 and not 100% O2.

Animals↗
PubMed1991

St. Thomas' Hospital cardioplegic solution. Beneficial effect of glucose and multidose reinfusions of cardioplegic solution.

The intention of this study was to determine whether glucose is beneficial in a cardioplegic solution when the end products of metabolism produced during the ischemic period are intermittently removed. The experimental model used was the isolated working rat heart, with a 3-hour hypothermic 10 degrees C cardioplegic arrest period. Cardioplegic solutions tested were the St. Thomas' Hospital No. 2 and a modified Krebs-Henseleit cardioplegic solution. Glucose (11 mmol/L) was beneficial when multidose cardioplegia was administered every 30 minutes. Including glucose in Krebs-Henseleit cardioplegic solution improved postischemic recovery of aortic output from 57.0% +/- 1.8% to 65.8% +/- 2.2%; p less than 0.025. The addition of glucose to St. Thomas' Hospital No. 2 cardioplegic solution improved aortic output from 74.6% +/- 1.9% to 87.4% +/- 1.9%; p less than 0.005. Furthermore, a dose-response curve showed that a glucose concentration of 20 mmol/L gave no better recovery than 0 mmol/L, and glucose in St. Thomas Hospital No. 2 cardioplegic solution was beneficial only in the range of 7 to 11 mmol/L. In addition, we showed that multidose cardioplegia was beneficial independent of glucose. Multidose St. Thomas' Hospital No. 2 cardioplegia, as opposed to single-dose cardioplegia, improved aortic output recovery from 57.4% +/- 5.2% to 74.6% +/- 1.9%; p less than 0.025, and with St. Thomas' Hospital No. 2 cardioplegic solution plus glucose (11 mmol/L) aortic output recovery improved from 65.9% +/- 2.9% to 87.4% +/- 1.9%; p less than 0.005. Hence, at least in this screening model, the St. Thomas' Hospital cardioplegic solution should contain glucose in the range of 7 mmol/L to 11 mmol/L, provided multidose cardioplegia is given. We cautiously suggest extrapolation to the human heart, on the basis of supporting clinical arguments that appear general enough to apply to both rat and human metabolisms.

Animals↗
PubMed1991

Effect of oxygenation and consequent pH changes on the efficacy of St. Thomas' Hospital cardioplegic solution.

The hypothesis tested is that shifts in pH, induced when a cardioplegic solution is oxygenated, can be detrimental. We added either 100% nitrogen, 95% nitrogen and 5% carbon dioxide, 100% oxygen, or 95% oxygen and 5% carbon dioxide to the cardioplegic solution (St. Thomas' Hospital No. 2 plus glucose 11 mmol/L), and determined postischemic recovery of isolated rat hearts after 3 hours of 10 degrees C cardioplegic protected ischemia. Hearts were arrested and reinfused every 30 minutes throughout the ischemic period with cardioplegic solution. When 5% carbon dioxide was added to nitrogen, the pH of the cardioplegic solution decreased from 9.1 (100% nitrogen) to 7.0 (95% nitrogen: 5% carbon dioxide), a change associated with improved postischemic functional recovery. Aortic output improved from 52.3% +/- 2.7% to 63.9% +/- 2.8%, p less than 0.05, and cardiac output from 60.8% +/- 3.6% to 75.4% +/- 3.3%, p less than 0.01. This improvement was associated with diminished efflux of lactate during ischemia but increased postischemic release of lactate dehydrogenase. When nitrogen was replaced with oxygen, the addition of 5% carbon dioxide resulted in a similar decrease of pH, which again was associated with improved postischemic functional recovery. Aortic output improved from 66.3% +/- 2.8% (100% oxygen) to 88.9% +/- 3.7% (95% oxygen: 5% carbon dioxide), p less than 0.005, and cardiac output from 75.3% +/- 4.1% to 88.9% +/- 2.4%, p less than 0.01. The efflux of lactate during ischemia and the postischemic release of lactate dehydrogenase were similar in both groups. Furthermore, provision of additional oxygen with perfluorocarbons in an electrolyte solution identical to the St. Thomas' Hospital plus glucose solution and oxygenated with 95% oxygen: 5% carbon dioxide conferred no extra protection. In conclusion, the St. Thomas' Hospital No. 2 plus glucose cardioplegic solution should be oxygenated but with 95% oxygen: 5% carbon dioxide and not 100% oxygen because of the additive effect of a relatively "acidotic" pH.

Animals↗
PubMed1990

Genotypic variation within asexual lineages of Taraxacum officinale.

Restriction site variation in DNA that encodes rRNA (rDNA) was surveyed among 714 offspring within 31 lineages (26 genotypes) of obligate asexually reproducing Taraxacum officinale (dandelions). Although clonal offspring are expected, plants with nonparental rDNA were produced from two parents that were themselves siblings (same genotype). The variation is best characterized by the loss of an EcoRI restriction site that maps to the spacer region in the parental rDNA and is most likely involved in amplification of rare or unique rDNA repeats. In one family, 41 surveyed offspring lacked the EcoRI site. In the other family, only 1 of 26 offspring lost the EcoRI site. Other classes of DNA surveyed, chloroplast DNA and the alcohol dehydrogenase 2 gene (Adh2), showed no variation. However, offspring with nonparental rDNA also had nonparental alcohol dehydrogenase 1 (Adh1) restriction fragments. Because somatic mutations in plants can be incorporated into reproductive tissue, we propose that somatic events affecting at least both multicopy rDNA and DNA homologous to the maize Adh1 gene occurred at different developmental times in the two families. An event early in development would result in all variant offspring; an event late in development would result in a single variant offspring. These results support the view that mutation (in the broad sense) influences the level of genotypic variation in asexual organisms, which may facilitate adaptive evolution of asexual species.

Alcohol Dehydrogenase↗
PubMed1988

Circadian temperature rhythm blunting and sleep composition.

The sleep patterns of nine male subjects were studied on four consecutive nights comprising two baseline nights, one night on which environmental temperature was elevated from 21 degrees C to 30 degrees C one hour after lights out, and a recovery night. There was a suppression of stage 4 sleep during the initial three hours of sleep on the hot night. A significant increase in stage 4 sleep with a decrease in stage 2 sleep occurred during the first three hours of the recovery sleep. There was a shortening in sleep onset latency and an increase in sleep efficiency on the recovery night. There were no changes in REM latency or REM sleep time. Rectal temperature rose after the increase in ambient temperature on the hot night. These results indicate that elevations in environmental temperature during sleep affect sleep patterns in a manner opposite to elevations of body temperature occurring prior to sleep onset. The curtailing of the usual circadian temperature drop during the first few hours of sleep reduces slow-wave sleep during this period. These findings have implications for those conditions with both altered sleep and altered temperature rhythms, for example, depression.

Adult↗
PubMed1987

Pulmonary tuberculosis in corticosteroid-treated asthmatics.

In a population with a high prevalence of tuberculosis, no statistically significant risk of developing pulmonary tuberculosis could be attributed to the long-term use of systemic corticosteroid therapy in a group of asthmatic men. A trend towards an increased risk of tuberculosis was noted but the extent of the attributable risk was too small to justify routine treatment with isoniazid. There is certainly no justification for withholding necessary corticosteroid therapy in black subjects with asthma.

Adrenal Cortex Hormones↗