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Biomedical subjects

M Lambert

Publications and source records attributed to M Lambert.

At least 217 records · Page 12Linked to original sources
PubMed1995

Contrasting effects of tamoxifen and ICI 182 780 on estrogen-induced calbindin-D 9k gene expression in the uterus and in primary culture of myometrial cells.

Antiestrogens have a large range of tissue- and promoter-specific actions, many of which still remain unclear, particularly in the uterus. Thus, we have analyzed the effects of two antiestrogens, tamoxifen (TAM) and ICI 182 780 (ICI) on the uterine estrogen-responsive gene calbindin-D9k (CaBP9k), in the ovariectomized rat uterus, and in primary cultures of myometrial cells. In the ovariectomized rat uterus, estradiol (E2) or E2 plus TAM induced CaBP9k mRNA to the same levels in 6h. Rats given TAM alone had the same mRNA concentration, but maximal induction was obtained later, 12h after injection. ICI alone did not induce CaBP9k gene expression. Rats given E2 plus ICI had low uterine CaBP9k mRNA levels at 6-12h that became undetectable at 24h. Thus ICI has a full antagonistic effect on E2-induced CaBP9k gene. Estradiol receptor (ER) assays showed that TAM had a partial antagonist effect, while ICI had a full antagonist effect on the ER. We also analyzed the effect of TAM and ICI on CaBP9k gene expression in primary cultures of myometrial cells. The effects were similar to those observed in whole uterus. Thus, TAM has mixed effects, being an agonist for CaBP9k gene induction, and an antagonist for ER. ICI antagonizes the effects of E2 on the CaBP9k gene in myometrial cells and in the intact uterus, but in a way that does not involve a decrease in the cellular content of ER. Instead, it interferes with at least one of the events leading to transcriptional activation.

Animals↗
PubMed1995

Correlation of severity and outcome with plasma sterol levels in variants of the Smith-Lemli-Opitz syndrome.

OBJECTIVES: To determine whether type I and the more severe type II variant of Smith-Lemli-Opitz syndrome have the same metabolic defect and to learn which plasma sterol measurements best predict survival. METHODS: Plasma sterols were measured in 33 individuals (24 type I, 9 type II) with a clinical diagnosis of the syndrome. RESULTS: Cholesterol levels were abnormally low (61 +/- 34 mg/dl) in type I subjects, whereas concentrations of the cholesterol precursor 7-dehydrocholesterol and its isomer 8-dehydrocholesterol were elevated 40- to 10,000-fold. Plasma cholesterol levels were significantly lower and total dehydrocholesterol levels higher in type II than in type I. Six children with the type II variant died by 13 weeks with mean plasma cholesterol levels 6.2 +/- 3.1 mg/dl, versus 17 +/- 11 mg/dl in the three surviving children with type II (p < 0.05). No child with a cholesterol level 7 mg/dl or less lived longer than 13 weeks. CONCLUSIONS: Patients with type I and type II variants of Smith-Lemli-Opitz syndrome have markedly reduced activity of the enzyme that converts 7-dehydrocholesterol to cholesterol, but the extent of the block is far more complete in type II. Survival correlates strongly with higher plasma cholesterol concentrations.

Abnormalities, Multiple↗
PubMed1995

[Pulmonary-renal syndrome: diagnostic and therapeutic strategy].

The pulmonary-renal syndrome is defined by the association of alveolar hemorrhage and rapidly progressive glomerulonephritis. Goodpasture syndrome and necrotizing vasculitides are the most frequent causes. New serologic markers are currently more rapidly available (anti-glomerular basement membrane--anti-GBM--and antineutrophil cytoplasmic antibodies -ANCA), allowing clinicians to identify and distinguish these 2 entities, and to hasten the initiation of a pulse therapy, now well standardized, which improves the outcome of patients. However, these 2 serologic markers have limitations so that clinical assessment and renal biopsy remains essential in the diagnosis of pulmonary-renal syndrome. The authors propose an algorithmic approach for those confronted with such a condition.

Anti-Glomerular Basement Membrane Disease↗
PubMed1995

Psychiatric crisis intervention in the general emergency service of a Veterans Affairs hospital.

An after-hours crisis intervention program staffed by psychiatric residents between 5 p.m. and 11:30 p.m. on weekdays was developed in the general emergency room at a Veterans Affairs hospital to reduce inpatient psychiatric admissions. The program offered medication, family interventions, and referrals to outpatient services. In the programs's first year, inpatient admissions during the hours covered by the program decreased by 34 percent, for a net savings of nearly $400,000 in inpatient treatment costs.

Comorbidity↗
PubMed1995

Serum interleukin 10 titers in systemic lupus erythematosus reflect disease activity.

We investigated whether serum titers of interleukin 10 (IL-10), a cytokine known to shift lymphocyte responses towards humoral immunity, reflect disease activity in systemic lupus erythematosus (SLE). Sera from 72 SLE patients, 25 RA patients and 30 healthy controls were tested for IL-10 by ELISA. Low titers of IL-10 were detected in the serum of 37.5% of SLE patients and in 24% of RA patients but in only 3% of healthy controls. Interestingly, serum IL-10 titers in SLE patients were positively correlated with the SLE Disease Activity Index (SLEDAI) and with anti-DNA antibody titers, but negatively with complement fraction C3 levels. These results indicate that serum IL-10 values reflect SLE disease activity and suggest that overexpression of IL-10 might play a pathogenic role in severe lupus disease.

Adolescent↗
PubMed1995

Medical aspects of ketone body metabolism.

Ketone bodies are produced in the liver, mainly from the oxidation of fatty acids, and are exported to peripheral tissues for use as an energy source. They are particularly important for the brain, which has no other substantial non-glucose-derived energy source. The 2 main ketone bodies are 3-hydroxybutyrate (3HB) and acetoacetate (AcAc). Biochemically, abnormalities of ketone body metabolism can present in 3 fashions: ketosis, hypoketotic hypoglycemia, and abnormalities of the 3HB/AcAc ratio. Normally, the presence of ketosis implies 2 things: that lipid energy metabolism has been activated and that the entire pathway of lipid degradation is intact. In rare patients, ketosis reflects an inability to utilize ketone bodies. Ketosis is normal during fasting, after prolonged exercise, and when a high-fat diet is consumed. During the neonatal period, infancy and pregnancy, times at which lipid energy metabolism is particularly active, ketosis develops readily. Pathologic causes of ketosis include diabetes, ketotic hypoglycemia of childhood, corticosteroid or growth hormone deficiency, intoxication with alcohol or salicylates, and several inborn errors of metabolism. The absence of ketosis in a patient with hypoglycemia is abnormal and suggests the diagnosis of either hyperinsulinism or an inborn error of fat energy metabolism. An abnormal elevation of the 3HB/AcAc ratio usually implies a non-oxidized state of the hepatocyte mitochondrial matrix resulting from hypoxia-ischemia or other causes. We summarize the differential diagnosis of abnormalities of ketone body metabolism, as well as pertinent recent advances in research.

3-Hydroxybutyric Acid↗
PubMed1995

Familial hypercholesterolemia: molecular, biochemical, and clinical characterization of a French-Canadian pediatric population.

BACKGROUND: Familial hypercholesterolemia (FH) is a dominantly-inherited disorder attributable to a defect in the low-density lipoprotein (LDL) receptor gene. Five mutations at this locus have been identified in French-Canadians. In children, it may be difficult to clinically distinguish FH from other forms of polygenic or monogenic hyperlipidemia. Therefore, our objectives were to define the molecular basis of our subjects' hypercholesterolemia, to characterize their biochemical phenotype in relation to the underlying molecular defect, and to assess their response to chronic dietary therapy. METHODS: We studied 88 unrelated French-Canadian children with a persistent increase in LDL cholesterol and a parental history of hyperlipidemia. Baseline and end-of-diet lipid and apolipoprotein levels were measured. Mutational analysis at the LDL receptor gene locus was performed. RESULTS: Heterozygosity for the common French-Canadian LDL receptor gene > 10-kb deletion was found in 57% of subjects (group 1), 14% carried one of the other four previously characterized LDL receptor gene mutations (group 2), and none of the five molecular defects tested was detected in 29% (group 3). Total cholesterol, LDL cholesterol, and apolipoprotein B baseline levels were similar among these three groups but significantly higher than in control subjects. However, there was wide interindividual variability even among those carrying the same mutation. Significantly lower baseline levels of high-density lipoprotein cholesterol and apolipoprotein A1 were found in group 1 compared with group 3 and the controls. The response to diet was similar among the three groups with an average reduction in the mean level of total cholesterol of 4.4%. CONCLUSIONS: The frequency of proven FH heterozygotes (71%) was remarkable in the pediatric population studied. Our data suggest that, in children, a persistent primary increase in LDL cholesterol associated with a parental history of hyperlipidemia is a good predictor of an underlying monogenic disorder as opposed to a polygenic disorder, at least in French-Canadians. Only molecular analysis allowed us to unequivocally define the cause of our patients' hypercholesterolemia. Most children with familial hyperlipidemia did not reach desirable plasma lipid levels solely under diet therapy.

Adolescent↗
PubMed1995

Nucleotide pool imbalances in the livers of patients with urea cycle disorders associated with increased levels of orotic aciduria.

Liver samples obtained at autopsy from patients with ornithine transcarbamylase (OTC) deficiency, a urea cycle disorder that is associated with high levels of orotic acid biosynthesis and excretion were analysed for nucleotide pools. As a control, liver samples from patients with a deficiency of mitochondrial carbamyl phosphate synthetase (CPS-I) which is not associated with increased levels of orotic acidurias were also analysed. The results show that liver tissue from OTC deficiency patients exhibited an increased ratio of uridine nucleotides to adenosine nucleotides, while in CPS-I deficiency patients, no such increase was noted. This study indicates that genetic disorders that are associated with increased loads of orotic acid exhibit abnormally high ratios of uridine to adenosine nucleotides in the liver. This type of imbalance is analogous to that seen in the liver of rats and mice exposed to an orotic acid supplemented or an arginine-deficient diet under liver tumor promoting conditions. It is likely that an imbalance in nucleotide pools may have a significant role in the pathophysiology associated with these disorders.

Adenine Nucleotides↗
PubMed1994

Autosomal dominant polycystic kidney disease in the fetus.

We report on 3 cases with a fetal presentation of autosomal dominant polycystic kidney disease (ADPKD), which illustrate the variable expression of ADPKD during fetal life. Fetus 1 was diagnosed at 20 weeks of gestation by ultrasonography; a molecular prenatal diagnosis was performed at 10 weeks on fetus 2, a sib of fetus 1; and ADPKD was an incidental finding in fetus 3 who was aborted at 16 weeks for anencephaly. All pregnancies were terminated and pathologic studies of the fetal kidneys were performed. From these cases and a review of the literature, we draw the following conclusions: (1) so far, all fetal ADPKD kidneys that have been histologically studied have shown cystic dilatations; 28/32 of these fetuses had ultrasonographic manifestations of the disease and/or had sibs with an early-onset form of it; (2) these cysts can be found in newly formed nephrons (fetus 2), predominantly in the more mature nephrons of the deep cortex (fetus 1) or more sparsely distributed in the cortex (fetus 3); these different patterns may reflect different rates of progression of the disease; (3) in contrast to the histologic findings in adult kidneys, glomeruli seem to be predominantly affected in fetal ADPKD; (4) severe fetal expression of ADPKD seems to cluster in some families; and (5) so far, all DNA analyses performed in families with subjects presenting during the fetal or neonatal period have been consistent with linkage to the PKD1 locus.

Adult↗
PubMed1994

LYC1 is the structural gene for lysine N-6-acetyl transferase in yeast.

In the yeast Yarrowia lipolytica, the LYC1 locus controls the first step of the lysine degradation pathway which is catalyzed by lysine N-6-acetyl transferase (LAT). This gene was cloned by complementation of the lyc1-100 mutation. Its position in the cloned insert was determined by conversion mapping and by complementation. The LYC1 gene encodes a 391 amino-acid polypeptide which has no homolog in protein databases. The required upstream region extends over 960 bp. When placed under the control of the GAL10 promoter in Saccharomyces cerevisiae, LYC1 drives the expression of lysine acetyl transferase activity, thus providing strong evidence that it is the structural gene encoding this enzyme.

Acetyltransferases↗
PubMed1994

EEG seizure duration monitoring of ECT.

The use of electroencephalographical monitoring in convulsive therapy has gained widespread acceptance in the United States where devices with this capability are readily available. In other countries, clinical monitoring alone is more common. Discrepancies between electroencephalographic and clinical observation (such as the "cuff method" described below) have been known to exist. Duration guidelines have evolved based on concerns about decreased effectiveness of very short seizures and neurotoxicity of overly long seizures. While these guidelines need further research to verify the assumptions they are based on, they have been recommended for use in clinical decision making. Currently available guidelines do not indicate how to manage disparate results when two measurement methods are used simultaneously. The authors examine the controversy and report the frequency of discrepancies across several guidelines.

Electroconvulsive Therapy↗
PubMed1994

Intravenous access in the critically ill trauma patient: a multicentered, prospective, randomized trial of saphenous cutdown and percutaneous femoral access.

STUDY OBJECTIVE: To compare the speed of IV access and the rate of infusion for saphenous venous cutdown and percutaneous femoral catheterization. DESIGN: Prospective, randomized, multicentered trial. Patient enrollment occurred from September 1990 through September 1991. SETTING: Patients were enrolled at three urban Level I trauma centers. TYPE OF PARTICIPANTS: Seventy-eight critically ill trauma patients. INTERVENTIONS: Participants were randomized to one of two groups: saphenous cutdown or percutaneous femoral line. After successful cannulation of the vein, 1 L of crystalloid was infused by gravity. RESULTS: The mean procedure time for the cutdown group was 5.63 +/- 2.58 minutes compared with 3.18 +/- 1.19 minutes for the femoral line group (P < .0001). The mean infusion time for the cutdown group was 6.65 +/- 4.29 minutes compared with 4.56 +/- 2.47 minutes for the femoral line group (P < .03). The mean overall time for the cutdown group was 11.76 +/- 4.81 minutes compared with 7.67 +/- 2.78 minutes for the femoral line group (P < .0002). CONCLUSION: Percutaneous femoral catheterization can be performed more rapidly than saphenous cutdown in the critically ill trauma patient with a palpable femoral pulse and allows for more rapid fluid administration. We support the use of a percutaneous femoral line as an acceptable alternative to saphenous venous cutdown in the initial resuscitation of trauma patients.

Adult↗
PubMed1994

Thyroid dysfunction in HIV infection.

During infection with HIV, overt clinical or biochemical thyroid dysfunctions are rare. When present, thyroid failure generally results from the destruction of the thyroid gland by opportunistic infections such as Pneumocystis carinii, or tumoural processes such as KS. Less frequently, hypothalamic-pituitary failure due to central nervous system infections is involved. Some cases of thyroiditis with thyrotoxicosis or hypothyroidism due to Pneumocystis carinii have also been reported. Subtle alterations of thyroid function tests are more common in HIV infection and are sometimes already detectable in the early phase of the disease. Contrary to what is observed in severe non-thyroidal illnesses, the low T3 syndrome and the sick euthyroid syndrome are less marked; these changes are mainly present in the final stage of the disease, when anorexia and weight loss occur, and indicate a poor outcome. Unique abnormalities of thyroid function indices have also been recently documented. A progressive elevation in serum TBG--but not in other binding proteins such as CBG and SHBG--accompanying the decline of the CD4 lymphocyte count, and associated with a concomitant increase in the serum T4 value, has been reported. An unusual prolonged maintenance of normal T3 levels with a paradoxical decrease in serum rT3 values has also been recognized. Finally, a hypothyroid-like regulation of the pituitary-thyroid axis, possibly directed to limit hypermetabolism in HIV infection, has been observed. The recognition of these particular thyroid profiles is of clinical importance as serum TBG appears to be a specific marker of the progression of HIV infection and serum T3 a reliable prognostic indicator for AIDS.

HIV Infections↗
PubMed1994

[An unusual cause of chronic diarrhea: lymphocytic colitis].

We report a case of lymphocytic colitis in a 74-year-old woman presenting with watery diarrhea since 1 year and in whom previous extensive investigations were normal. The diagnosis could be made on the basis of typical pathological pattern in colonic biopsies. The outcome was favourable with salazopyrine therapy. The clinical, histological and pathophysiological aspects of lymphocytic colitis are discussed.

Aged↗
PubMed1994

Validity of Euroqol--a generic health status instrument--in patients with rheumatoid arthritis. Economic and Health Outcomes Research Group.

The main aim of this pilot study was to test the 'construct' validity of Euroqol, a new generic health status instrument which consists of a questionnaire and visual analogue scale. Its ability to measure both current health status and change in health status was assessed in 55 patients with RA. The Euroqol questionnaire and visual analogue scales showed significant and clinically relevant correlations with other condition-specific instruments measuring loss of function, joint pain, joint tenderness and mood; change in these symptoms as measured by the condition-specific instruments was also predictive of change in Euroqol scores. Either component of the Euroqol instrument provide an index of current clinical status and these data provide preliminary evidence for the 'construct' validity of Euroqol in RA. Further work is needed to evaluate more fully the sensitivity of Euroqol to change over time.

Adolescent↗