Nail pigmentation associated with zidovudine.
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Acquired Immunodeficiency Syndrome↗
Biomedical subjects
K Nelson
Publications and source records attributed to K Nelson.
Reporting accuracy among mothers of malformed and nonmalformed infants.
The potential for recall bias in case-control studies is a common concern. The authors assessed whether recall bias was present in exposure information reported at postpartum interview by mothers of malformed and nonmalformed infants who delivered at Brigham and Women's Hospital, Boston, during 1984. Accuracy of exposure reporting was measured by comparing interview data with exposure information documented during pregnancy in obstetric records. The authors' measure of recall bias, relative sensitivity (RS), is the ratio of exposure-reporting accuracy for mothers of malformed infants to that of mothers of nonmalformed infants. Relative sensitivity estimates that are greater than 1.0 indicate that mothers of malformed infants are more accurate reporters than mothers of nonmalformed infants. Relative sensitivity was estimated for eight exposure factors: antibiotic or antifungal drug use (RS = 1.2), urinary tract or yeast infection (RS = 2.7), history of infertility (RS = 1.4), use of birth control after conception (RS = 7.6), elective abortion history (RS = 1.1), any over-the-counter drug use (RS = 1.0), spotting or bleeding (RS = 1.2), and nausea or vomiting (RS = 0.8) These data suggest the presence of recall bias for some exposure factors. The authors advise the use of malformed controls to reduce potential recall bias in case-control studies of selected malformations and many etiologic factors.
Abortion, Induced↗
Effects of penbutolol on plasma atrial natriuretic peptide and antidiuretic hormone levels before and after exercise: a double-blind comparison against placebo.
A double-blind crossover trial was carried out in 7 healthy male volunteers to investigate the effects of penbutolol and a placebo on plasma atrial natriuretic peptide (ANP) and antidiuretic hormone (ADH) levels before and after exercise. Each subject underwent several bicycle ergometric exercises lasting 6 min before and after the application of test medications. Ergometric exercises were performed before medication, and at 2, 5, 9 and 24 hours after medication. Blood samples for ANP and ADH levels were drawn before, after 15 min, after 2 hours (immediately after ergometry) and 5, 7, 9, and 24 hours after medication (immediately before ergometry). Urine was collected as follows: -2 to 0, 0 to 2, 2 to 4, 4 to 7, 7 to 14 and 14 to 24 hours after medication, and the volume as well as sodium excretion were documented. Penbutolol caused suppression of the exercise-induced increase in ANP. The 2 to 4 hour fractional sodium excretion was significantly decreased from 12.1 +/- 4.9 mmol/fraction after placebo treatment to 7.8 +/- 3.0 mmol/fraction after penbutolol application (p less than 0.03). There were no differences in the urinary outputs between penbutolol and placebo until 4 hours after medication, but penbutolol caused the total urinary output to increase from 1390 +/- 388 ml/24 hr during placebo treatment to 1725 +/- 549 ml/24 hr (p less than 0.02) due to the last collection fraction. Blood pressure and pulse rate both decreased during exercise after penbutolol. As opposed to the suppressing influence of penbutolol on ANP, ADH plasma levels were increased after exercise.(ABSTRACT TRUNCATED AT 250 WORDS)
Adult↗
Clinical efficacy of Broncho-Vaxom in adult patients with chronic purulent sinusitis--a multi-centric, placebo-controlled, double-blind study.
This study was designed to test the clinical effectiveness of Broncho-Vaxom (an orally applicable bacterial lysate) in a large number of adult patients suffering from chronic purulent sinusitis. Broncho-Vaxom or placebo was administered to 284 patients presenting with chronic purulent sinusitis within the bounds of a multicentric, randomized double-blind study. Patients were clinically examined before admittance to the study and at 1, 2, 3 and 6 months after treatment initiation (one capsule daily for a period of 10 days per month during 3 consecutive months). The sinuses were x-rayed before and at 3 and 6 months after therapy began. Patients assessed the severity of their symptoms on a scale of 0 to 4: 0 = no symptoms, 1 = light symptoms, 2 = moderate symptoms, 3 = severe symptoms, 4 = very severe symptoms. The average severity score for coughing during the course of Broncho-Vaxom therapy decreased in the third month of treatment from 2.34 before treatment to 0.85, compared to placebo before treatment (2.41) and after treatment (1.24). The score decreased further to 0.61 in the sixth month after the initiation of Broncho-Vaxom therapy, with no further decrease as a result of placebo therapy (1.25). Comparable average score courses for expectorations and headache also occurred. In the first month of Broncho-Vaxom therapy, a decrease was already apparent in the severity of the main sinusitis symptom: purulent nasal discharge. The score was 1.55 in the first month of Broncho-Vaxom treatment compared to 1.80 in the placebo group.(ABSTRACT TRUNCATED AT 250 WORDS)
Adjuvants, Immunologic↗
Reduction of hyperlipidemia with 3-sn-polyenyl-phosphatidylcholine in dialysis patients.
Hyperlipidemia is of particular concern in dialysis patients due to the high incidence of ischemic cardiovascular complications. Two groups of 10 patients with at least one year of dialysis and a residual glomerular filtration rate less than 1 ml/min, serum cholesterol greater than 260 mg/dl, LDL cholesterol greater than 180 mg/dl and triglycerides greater than 200 mg/dl were admitted to the study. The patients received either 3 x 450 mg 3-sn-polyenyl-phosphatidylcholine (PPC) mornings and evenings (2.7 g daily, 6 capsules) or placebo during the double-blind, randomized study. Six weeks treatment was followed by a two-week wash-out phase. Lipid parameters including total cholesterol, triglycerides, HDL and LDL cholesterol were determined 14 days before treatment, at treatment begin, at 2, 4 and 6 weeks during treatment and 14 days after treatment cessation. PPC caused a significant decrease in total cholesterol (-37.8 mg/dl) two weeks after treatment begin (2 p less than 0.001). This decrease remained constant during the duration of treatment. Two weeks after PPC application a decrease in LDL-cholesterol had occurred (-32.0 mg/dl) (2 p less than 0.01) as compared to stable placebo values. Significant PPC induced decreases in triglycerides occurred four (-58.2 mg/dl; 2 p less than 0.001) and six weeks (-43.3 mg/dl; 2 p less than 0.01) after initiation of treatment, as compared to the placebo group (four weeks: +5.7 mg/dl and six weeks: -11.4 mg/dl). Side effects in the PPC group were equivalent to those reported in the placebo group. This study shows that PPC is an effective antihyperlipidemic agent in dialysis patients.
Adult↗
Influence of food intake on the bioavailability of urapidil in healthy volunteers.
The influence of food intake on the pharmacokinetics of a single dose (30 mg) of urapidil in a tablet and a sustained-release capsule form were examined in 12 healthy volunteers in a double crossover trial. Drug administration under fasting conditions requires that a standardized breakfast be eaten, 4 h after drug intake. Drug application with breakfast requires drug intake with the standardized breakfast. Blood was sampled and blood pressure measured before and at 0.25, 0.5, 1, 2, 3, 4, 6, 8, 12, 15, 18, 21, 28 and 32 h after drug administration. Urapidil was determined by HPLC. AUC, Cmax, tmax and t1/2 were calculated. Food intake did not influence the bioavailability of urapidil in tablet form. After the administration of the sustained-release capsule Cmax and tmax were increased while t1/2 was decreased by food intake. Despite these differences, the AUC was not influenced by concomitant food intake with the sustained-release capsule. In the fasting state, the AUC of the sustained-release capsule was 28% lower than that of the tablet. Food intake together with the sustained-release capsule abolished this difference. Since blood pressure decreases in hypertensive patients treated with urapidil are most pronounced in the inclining part of the urapidil-serum concentration curve, maximizing this part of the curve, as is the case with the administration of the sustained-release capsule together with breakfast, should be advantageous. Therefore, the suggestion that the sustained-release capsule be taken with breakfast is of therapeutic significance.
Adult↗
Improved orthostatic dysregulation record after administration of a sustained-release form of urapidil.
The efficacy and safety of urapidil has been demonstrated in a long-term treatment. However, a relatively good record of side effects has been marred by reports of orthostatic dysregulation. This study was designed to examine the blood pressure lowering effect, tolerability and pharmacokinetics of a sustained-release formulation of urapidil. Twelve patients received either 60 mg of sustained-release urapidil (Ebrantil 60) or 50 mg urapidil for experimental reference as a fast-release tablet in single or multiple doses in a randomized, double-blind fashion. To ensure the double blind-character of the study, the tablets were encapsulated. Blood samples for the determination of urapidil (HPLC) were drawn before and at 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10 and 12 h post application. Blood pressure was measured at 0.5, 1.5, 3, 8, 10 and 12 h post application. An orthostatic test was performed before and at 1, 2, 4 and 6 h post application. Twelve h after the first application, patients received a second capsule or encapsulated tablet and continued medication for two days. On day four, the same procedure as on day one was repeated, except that patients received no evening medication and blood samples and blood pressure were measured at 24, 28 and 32 h post application on the fifth day. The Cmax of sustained-release urapidil was 44% lower than for the single tablet dose and 37% lower after multiple dosing. The peak-trough fluctuation of the steady-state serum concentrations was 29% lower for the sustained-release capsule (138 +/- 45%) compared to the tablet (195 +/- 83%).(ABSTRACT TRUNCATED AT 250 WORDS)
Adult↗
Multiplicity dependence of the transverse-momentum spectrum for centrally produced hadrons in antiproton-proton collisions at sqrt s =1.8 TeV.
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Journal Article↗
Magnesium pyridoxal 5-phosphate glutamate reduces hyperlipidaemia in patients with chronic renal insufficiency.
Chronic renal insufficiency is often accompanied by hyperlipidaemia and subsequent coronary heart disease. Two groups of 15 patients with serum creatinine greater than 2 mg/100 ml and serum cholesterol less than 250 mg/100 ml were given 3 x 50 mg magnesium pyridoxal 5-phosphate glutamate (MPPG) or placebo for 12 weeks in a double-blind, randomised study. Total cholesterol in the MPPG group (282.4 mg.100 ml-1) was lower than in the placebo group (354.3 mg.100 ml-1) after 12 weeks of treatment. Triglycerides in the MPPG group were 265.1 mg.100 ml-1 compared to 361.9 mg.100 ml-1. After 12 weeks on MPPG the LDL/HDL ratio of 3.56 was lower than in the placebo group-6.83. Side effects in the MPPG group were similar to those in the placebo group. Thus, MPPG was an effective antihyperlipidaemic agent in patients with renal insufficiency.
Adult↗
The role of alpha-adrenoceptor blockade in the antihypertensive effects of fenoldopam in humans.
Fenoldopam, a dopamine-1 receptor agonist, has been reported to exhibit alpha-adrenoceptor-blocking actions in intact and isolated animal preparations. To determine whether alpha-adrenoceptor blockade contributes to its antihypertensive properties in humans, the effects of fenoldopam on the pressor responses to norepinephrine and angiotensin II were compared in eight normal volunteers. Fenoldopam (0.5 micrograms/kg/min) shifted the dose-response curves for both agonists to the right (p less than 0.05). Dose ratios for an increase in mean blood pressure of 10 mm Hg were 3.3 +/- 0.9 for norepinephrine and 3.2 +/- 0.6 for angiotensin II (p not significant). Consequently, fenoldopam is not a selective alpha-adrenoceptor antagonist at therapeutic concentrations in humans.
Adrenergic alpha-Antagonists↗
Clinical pharmacokinetics of urapidil.
Urapidil is a selective alpha 1-adrenoceptor antagonist with central antihypertensive action which is increasingly used in the treatment of hypertension. Urapidil is readily absorbed, is subject to moderate first-pass metabolism and is eliminated primarily as metabolites of much lower antihypertensive activity than the parent drug. The influences of age, renal and hepatic disease on the disposition of urapidil are reviewed. Studies on the relationship between pharmacodynamics and pharmacokinetics show that the optimum use of urapidil in clinical practice depends on an understanding of the pharmacokinetic properties of the drug.
Adult↗
Comparison of the effects of dopamine and fenoldopam, a selective dopamine-1 agonist, on parathyroid hormone release in man.
Dopamine has been reported to transiently increase parathyroid hormone (PTH) secretion in man; however, the mechanism is unclear. To test the hypothesis that selective dopamine-1 receptor (DA1) stimulation increases PTH secretion, we compared the effects of fenoldopam, a novel selective DA1 receptor agonist, as well as dopamine on serum PTH secretion and total serum calcium concentration in seven normal human subjects. Dopamine was infused at 1 and 3 micrograms/kg/min, each for 10 minutes, and 5 micrograms/kg/min for 25 min. Fenoldopam was infused at 0.1 and 0.3 micrograms/kg/min, each for 10 min. and thereafter at 0.5 micrograms/kg/min for 25 min. The infusions were given at least 1 week apart. Blood samples for PTH, calcium and dopamine or fenoldopam concentrations were drawn prior to and at the 25th minute of each drug infusion. PTH concentrations increased in all subjects at the 25th minute of dopamine but not fenoldopam infusion. Serum calcium was not significantly affected. The plasma concentrations of both dopamine (83.6 +/- 7.1 ng/ml) and fenoldopam (13.0 +/- 3.4 ng/ml) were in the range known to cause equivalent DA1 receptor stimulation. Since dopamine but not fenoldopam increased PTH secretion in man, we conclude that selective DA1 receptor stimulation alone does not increase PTH release and the effects of dopamine must be mediated through some other mechanism.
Adolescent↗
Estrogens and antiestrogens mediate contrasting transitions in estrogen receptor conformation which determine chromatin access: a review and synthesis of recent observations.
Our perspective is that the mechanisms separating the action of estrogen agonists and antagonists involve contrasting transitions in receptor conformation which determine receptor access to different chromatin regions. Although we have suggested that size related exclusion of receptor may provide one manner for determining chromatin access (Pavlik et al., 1985), additional mechanisms may also be involved. The most recent evidence from several laboratories supports this perspective and indicates that estrogen receptors associated with antiestrogens are competent with respect to activation and response elicitation. Thus, we believe that an important course for future effort will be to define chromatin interactions that are limited to estrogen receptors complexed with either agonist or antagonist.
Animals↗
Characterization of specific HLA-DQ alpha allospecificities by genomic, biochemical, and serologic analysis.
Bgl II restriction endonuclease digestion of genomic DNA from lymphoblastoid cell lines homozygous for HLA DR and DQ serological specificities, followed by hybridization with a DQ alpha cDNA probe, identified a genomic polymorphism characterized by two reciprocal patterns, one associated with DR 3, 5 and 8 and the other with DR 1, 2, 4, 7, and 9. The former pattern corresponded precisely to the reactivity of monoclonal antibody SFR20-DQ alpha 5, shown by Western blotting to react with isolated alpha-chains, but not with beta-chains. Additional variants of the DQ alpha genes were identified by using a locus-specific oligonucleotide probe for the DQ alpha gene, indicating differences among the DQ alpha 5-negative set of alleles. This analysis defines a set of DQ alpha allelic markers that are distinct from the well-established DQ serologic specificities DQw1, 2, 3 or "blank." Although most DQ alpha 5+ cells carry the DRw52 specificity associated with the DR beta 2 gene, analysis of DQ alpha polymorphisms on DR5, DQw1; DR8, DQw1; and DRw13, DQw1 cells verified that this DQ alpha family of alleles was not invariably linked to the DR beta 2 locus.
Epitopes↗
Effect of age on circulating immunoreactive and bioactive parathyroid hormone levels in women.
Although levels of serum immunoreactive parathyroid hormone (iPTH) increase with age in women, this could be caused by retention of non-biologically active PTH fragments by the aging kidney. In 102 normal women, aged 30 to 89 yr, serum iPTH increased with age by 58% (r = 0.33, p less than 0.001) with antiserum GP-1M (which has midmolecule specificity) and 43% (r = 0.32, p less than 0.001) with antiserum CH-12M (which may have whole molecule specificity); urinary cAMP/GFR excretion increased by 29% (r = 0.22, p less than 0.05). The results of these assays were validated by comparison with serum levels of biologically active PTH (BioPTH) in immunoextracts of serum followed by renal adenylate cyclase assay in a selected subgroup of 25 of the women. Serum BioPTH correlated with serum iPTH assessed by antiserum GP-1M (r = 0.48, p less than 0.05) and antiserum CH-12M (r = 0.48, p less than 0.05) but not with urinary cAMP. The data are consistent with an increase of parathyroid function with aging: clearly, we do not find decreased parathyroid function as would be expected if age-related bone loss was not mediated, in part, by PTH.
Adult↗
Pharmacodynamics and pharmacokinetics of urapidil in hypertensive patients: a crossover study comparing infusion with an infusion-capsule combination.
The pharmacokinetics and haemodynamic effects of infused urapidil and an infusion-capsule combination were followed to study the correlation between the serum urapidil level and the blood pressure. Prior to urapidil administration, basal blood pressure and heart rate were measured for 16 h in 12 male hypertensive patients. Six patients received infusions lasting for 4 h of urapidil 10, 2.5 and 5 mg/h. Six patients were infused with urapidil 10 mg/h for 4 h and 2 h after the end of the infusion each took a 60-mg capsule. After a 5 day washout period the procedures were crossed over. A maximum serum urapidil level of 625 +/- 232 ng/ml was achieved at the end of the 10 mg/h infusion, when the fall in blood pressure was 37/21 mmHg. During the 2.5 and 5 mg/h infusions the serum urapidil level was 330 and 420 ng/ml, respectively, and the corresponding decreases in blood pressure were 28/16 mmHg and 31/8 mmHg. Although the urapidil concentration 1 hour after beginning the infusion was only 184 +/- 89 ng/ml a near maximal blood pressure decrease had already occurred 33 +/- 9/20 +/- 8 mmHg, whereas, 1 h after the end of the infusion the reduction in blood pressure was only 10 +/- 12/3 +/- 8 mm, with a urapidil concentration of 358 +/- 120 ng/ml. During the plateau phases of both the infusion and infusion-capsule treatments the falls in blood pressure followed the serum urapidil levels. Only in the initial rising and final falling phases of the treatments were the pharmacodynamics and pharmacokinetics of urapidil not correlated.
Blood Pressure↗
Risk of transmitting the human immunodeficiency virus, cytomegalovirus, and hepatitis B virus to health care workers exposed to patients with AIDS and AIDS-related conditions.
This prospective cohort study was designed to evaluate the risk of occupational transmission of human immunodeficiency virus (HIV), hepatitis B virus (HBV), and cytomegalovirus (CMV) to health care workers with intensive exposure to HIV-infected patients. Seventy-five percent of the 270 subjects had been exposed to patients with AIDS and AIDS-related conditions (ARC) for at least one year before enrollment, 18% worked in specialized AIDS units, and 35% sustained a total of 342 accidental parenteral exposures to HIV-infected body fluids. At the time of enrollment, none had antibody to HIV, and none of the 175 subjects retested 10 months later had acquired antibody. No evidence of increased risk of acquiring CMV or HBV was obtained. These results indicate that health care workers are at minimal risk for HIV, CMV, and HBV transmission from occupational exposure to patients with AIDS or ARC, even when intensively exposed for prolonged periods of time.
AIDS-Related Complex↗
Extensive in situ activation of nuclear estrogen receptors after exposure of murine uteri to [3H]estradiol or [3H]4-hydroxytamoxifen.
Estrogen receptor activation has been examined in murine uteri by characterizing binding to ATP-Sepharose. Determinations were performed under conditions in which specific binding to estrogen receptors was demonstrated by both agonist and antagonist without participation by nonreceptor antiestrogen-binding components. Cell-free activation of estrogen receptors in cytosol was more effectively promoted by [3H]estradiol estradiol than by [3H]4-hydroxytamoxifen or [3H]tamoxifen aziridine. However, when in situ activation was examined after intact uteri were exposed to [3H]estradiol or [3H]4-hydroxytamoxifen, virtually all extracted nuclear receptors demonstrated activated binding to ATP-Sepharose within 20 min of hormone exposure. Profiles of nuclear receptor activation were remarkably similar after exposure to either agonist or antagonist. Estrogen receptors in cytosol prepared after exposing intact uteri to 3H-labeled ligands were characterized by much less ability to bind to ATP-Sepharose than nuclear receptors. After uteri were exposed to [3H]estradiol, the activated receptor fraction in the cytosol progressively increased in contrast to preparations obtained after uteri were exposed to [3H]4-hydroxytamoxifen, which demonstrated a constant level of activation. Thus, even when activation has occurred within the intact uterus, agonists and antagonists may be characterized by different apparent levels of receptor activation in the cytosol fraction. These differences in the cytosol, however, are considerably overshadowed by the extensive activation occurring within the nuclear fraction, which we have observed to be similar with agonist and antagonist. Since estrogen receptors appear to act within chromatin, and cytosol receptors may be produced by receptor redistribution during preparation, we interpret these observations to indicate that in situ receptor activation is very similar after exposure to either agonist or antagonist. Consequently, antagonism does not appear to be associated with antiestrogens that impede receptor activation within intact murine uteri.
Animals↗