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Biomedical subjects

W Lambert

Publications and source records attributed to W Lambert.

At least 37 records · Page 2Linked to original sources

Cultured human trabecular meshwork cells express functional growth factor receptors.

PURPOSE: To compare the mRNA expression of growth factor receptors in cultured human trabecular meshwork (HTM) cells with ex vivo HTM tissues and to determine whether HTM cells generate a physiologic response after exposure to exogenous growth factors. METHODS: The reverse transcription-polymerase chain reaction (RT-PCR) method was used to detect the expression of various growth factor receptor mRNAs using early passaged, cultured HTM cells from donors of several ages. RT-PCR on ex vivo HTM tissues from healthy donors and donors with glaucoma were also used to compare and contrast mRNA expression with cell culture results. After the exogenous administration of growth factors, cell proliferation and extracellular acidification rate studies were used to measure the functional responses of HTM cells to growth factors. RESULTS: Amplification products of the expected size for 15 growth factor receptors were detected in cultured HTM cells and in ex vivo HTM tissues. The administration of exogenous growth factors showed that (a) hepatocyte growth factor (HGF), epidermal growth factor (EGF), insulinlike growth factor (IGF)-1, tumor necrosis factor (TNF) alpha, platelet-derived growth factor (PDGF)-AA, PDGF-BB, PDGF-AB, and basic fibroblast growth factor (FGF-2) stimulated cell proliferation, whereas FGF-1 (acidic), transforming growth factor (TGF) alpha, interleukin (IL)-1alpha, nerve growth factor (NGF), and FGF-7 (keratinocyte growth factor [KGF]) had no significant influence on cell proliferation; (b) TGF-beta isoforms significantly inhibited EGF-stimulated trabecular meshwork cell proliferation; and (c) FGF-1 (acidic), TGF-alpha, EGF, IL-1alpha, IL-1beta, HGF, TNF-alpha, PDGF-AA, and IGF-1 significantly stimulated extracellular acidification, whereas FGF-2 (basic), FGF-7 (KGF), TGF-beta1-beta3 and NGF had no significant influence on extracellular acidification. CONCLUSIONS: These studies show that mRNA for numerous growth factor receptors can be detected in cultured HTM cells and in ex vivo HTM tissues. They also show that many of the receptors are functional, because exogenous growth factor administration elicits a physiologic response. In vivo, these receptors may be activated by growth factors present within the aqueous humor (aquecrine/paracrine) or by growth factors synthesized and released locally by trabecular meshwork cells themselves (autocrine). Specific growth factors acting through high-affinity receptors may be involved in maintaining the normal microenvironment of the HTM and also may be involved in the pathogenesis of primary open-angle glaucoma.

Adolescent↗

Treatment of severe thallium intoxication.

CASE REPORT: We report a successfully treated case of severe thallium intoxication. In spite of very high serum thallium (5,240 micrograms/L), symptomatology was minor and recovery complete. Prussian Blue was administered, diuresis was enhanced by intravenous fluids and a prolonged hemodialysis was started early. High blood flows (300 mL/min) and intravenous potassium chloride supplements, to mobilize thallium from the tissues, resulted in good clearances (96 to 150 mL/min). In order to prevent the well known complications, we recommend aggressive treatment of severe thallium intoxication.

Adult↗

Effect of isotretinoin on endogenous tissue-type plasminogen activator (t-PA) and plasminogen activator inhibitor 1 (PAI-1) in humans.

The effect of isotretinoin on fibrinolysis was investigated in 10 healthy, male volunteers in a randomized, double-blind, crossover-designed study. Isotretinoin (40 mg) was administered in the morning and in the evening for 5 days. t-PA, u-PA and PAI-1 antigen and activity in plasma were measured every morning at 9 a.m. on days 1 to 4 and every 3 hours over 24 hours on day 5. Isotretinoin treatment had no significant stimulatory effect on endogenous t-PA antigen and activity in morning plasma samples nor on their circadian variation. Also, u-PA antigen levels did not change after isotretinoin treatment. Mean PAI-1 antigen and PAI activity in 9 a.m. plasma samples were non-significantly higher during isotretinoin than during placebo treatment. After treatment with isotretinoin a significant rise of fasting triglyceride plasma levels was observed as compared to placebo. The study shows that isotretinoin has no clinically significant effect on endogenous fibrinolysis.

Adult↗

The impact of synthesis teaching and parent training with mothers of conduct-disordered children.

A procedure to enhance the impact of parent training with multistressed mother-child dyads was explored with 29 clinic-referred dyads. The procedure, called synthesis teaching, was provided for one randomly selected group of dyads, while the other group was engaged in problem discussions about their children. Both groups received parent training as the principal intervention for the mothers' conduct-disordered children. Results showed that these interventions had no effects on dyads in the clinic setting, but had a progressively more significant effect at home for the synthesis teaching group. That is, mothers in this group showed reductions in their indiscriminate parenting and their children demonstrated behavioral improvements. In contrast, mothers in the control group did not change their behavior and their children did not demonstrate observed behavioral changes. Interpretations of the results center on how synthesis teaching might have produced these effects.

Adult↗

Long-term sequelae of childhood sexual abuse: perceived family environment, psychopathology, and dissociation.

In this study, 105 abused and nonabused women were examined for patterns of adult psychopathology associated with childhood sexual abuse and to test the extent to which these patterns are independent of other pathogenic properties of the family environment. Clinical and nonclinical Ss completed the Family Environment Scale, the Minnesota Multiphasic Personality Inventory (MMPI), the Rorschach, and the Stanford Hypnotic Susceptibility Scale. Greater nonspecific impairment among abused women may be a consequence, at least in part, of pathogenic family structure rather than sexual abuse per se. However, MMPI and Rorschach responses suggest sexual abuse may render victims especially vulnerable to specific disturbances i involving soma and self. Abuse was associated with greater use of dissociation, but covariance analysis revealed this effect to be accounted for by family pathology. There was no evidence that sexual trauma is associated with hypnotizability.

Adaptation, Psychological↗

The distribution of cis- and trans-acitretin in human epidermis.

The concentrations of trans-acitretin and its principal metabolite, cis-acitretin, were measured by h.p.l.c. after single and multiple dosing (50 mg orally for 13 days) in plasma, blister fluid and epidermal samples from four healthy male volunteers. Within-day epidermal concentrations of trans-acitretin exceeded those of the cis-form which were at the limit of assay sensitivity. No accumulation of trans-acitretin was observed in plasma or blister fluid but AUC values for the drug in blister roof cells tended to be higher after multiple dosing.

Acitretin↗

Increased concentrations of endogenous 13-cis- and all-trans-retinoic acids in diffuse idiopathic skeletal hyperostosis, as demonstrated by HPLC.

Endogenous 13-cis- and all-trans-retinoic acids have been quantitated in human serum using a solvent extraction procedure followed by isocratic reversed phase high performance liquid chromatography and UV detection. In healthy adults, after an overnight fasting period, the concentrations of 13-cis- and all-trans-retinoic acids yielded 5.3 +/- 2.43 nmol/l and 11.8 +/- 3.3 nmol/l, respectively (mean +/- SD). The method has been successfully applied to the analysis of both isomers in serum from patients with idiopathic skeletal hyperostosis in whom, the 13-cis- as well as all-trans-retinoic acid levels were raised as compared to the control group.

Adult↗

Fatty acid composition and kinetic behaviour of liver retinyl esters in vitamin A sufficient and deficient rats.

Weanling rats were fed vitamin A deficient diets (-A) or diets supplemented with vitamin A (+A) (4.4 mg retinol equivalents/kg diet) for a period of 7 or 6 wk, respectively. In liver tissues of these two groups of animals both the subcellular localization as well as the fatty acid composition of the retinyl esters was studied. During vitamin A supplementation or deprivation, the kinetics of the different ester forms were investigated. Results indicate that the subcellular localization of all retinyl esters is similar and dependent on age. Two pools exist, ie one consisting of the nuclear/cell debris and mitochondrial-lysosomal fractions and the other containing the microsomal and cytosol fractions. HPLC analysis showed retinyl palmitate as the predominating (80%) form of the various retinyl esters. By supplementation clearly two kinetic behaviours can be demonstrated: one being a relatively stable storage of the palmitate and stearate, increasing with time and the second one being a more labile pattern for the ester forms with other saturated and unsaturated fatty acids. By vitamin A depletion all retinyl esters are affected indicating that the ester forms other than palmitate and stearate are also storage forms of vitamin A.

Animals↗

Plasma concentrations of vitamin K1 and PIVKA-II in bottle-fed and breast-fed infants with and without vitamin K prophylaxis at birth.

Plasma vitamin K1 and proteins induced by vitamin K absence (PIVKA) were assayed simultaneously 1-4 days and 29-35 days after delivery in three groups of infants: breast-fed not receiving vitamin K at birth (n = 12), bottle-fed without vitamin K administration at birth (n = 7) and breast-fed receiving 1 mg vitamin K1 administered by intramuscular injection at birth (n = 13). The bottle-fed infants had a significantly higher vitamin K1 plasma level than breast-fed infants who did not receive vitamin K1 at birth. Extremely high levels of vitamin K were obtained 1-4 days after intramuscular administration. At the age of 1 month, breast-fed infants had the same plasma vitamin K1 concentration whether or not they had received vitamin K1 supplements. Decarboxy prothrombin (PIVKA-II) a reliable indicator of biochemical vitamin K deficiency, was found in 5 out of 12 breast-fed and in 2 out of 6 bottle-fed infants who had not received supplemental vitamin K1 after birth. In a separate study, we followed up to 90 days after birth a larger group if infants. PIVKA-II was found with significantly greater frequency in breast-fed infants receiving no vitamin K than in breast-fed infants receiving 1 mg vitamin K intramuscularly at birth, or in bottle-fed infants without extra vitamin K1. These data form a strong argument for routine vitamin K prophylaxis after birth for all breast-fed infants. The optimum dose and manner of administration require further study.

Biomarkers↗

A fatal case of trazodone and dothiepin poisoning: toxicological findings.

A fatal case of trazodone and dothiepin self-poisoning is presented. A multi-technique approach (EMIT, TLC, HPLC/DAD, and GC/MS) allowed the unequivocal identification of trazodone and dothiepin as toxicologically relevant substances. Both compounds were quantitatively determined in a number of postmortem samples. Blood and urinary trazodone concentrations (28.7 and 90.5 micrograms/mL, respectively) and dothiepin concentrations (2.1 and 9.7 micrograms/mL, respectively) were far above therapeutic concentrations (i.e., 1.5 and 0.05 microgram/mL for trazodone and dothiepin, respectively, in blood) and were clearly the cause of death in this particular case. These data confirm the high toxicity and the high mortality rate in trazodone intoxications, especially when co-ingestion of other substances is involved.

Adult↗

Analysis of zopiclone (Imovane) in postmortem specimens by GC-MS and HPLC with diode-array detection.

A 26-year-old black female was found dead at home. Her mouth was covered with a fluid containing chalky particles. Empty strips of Imovane (zopiclone) and an empty bottle of Fortal (pentazocine) were also found. No urine was available at autopsy. Screening of postmortem blood and stomach contents with enzyme-multiplied immunoassay technique (EMIT) detected only caffeine. Further screening using routine high-performance liquid chromatography (HPLC) with diode-array detection and gas chromatography (GC) with mass spectrometric detection revealed the presence of large amounts of pentazocine in the blood and stomach contents. In the HPLC chromatogram, a second peak that was only partially resolved from the solvent front was observed. Thin-layer chromatography demonstrated the presence of zopiclone, but optimized HPLC and GC conditions had to be used for proper identification and quantitation. This case illustrates the fact that zopiclone can be easily overlooked during routine forensic screening.

Adult↗