Effect of hydrochlorothiazide 25 mg/day on essential hypertension.
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Adult↗
Biomedical subjects
R L Williams
Publications and source records attributed to R L Williams.
Endothelioma cells expressing the polyoma middle T oncogene induce hemangiomas by host cell recruitment.
Mouse endothelioma cells expressing the polyoma middle T oncogene induced hemangiomas in a variety of species such as mice, rats, chicks, and quails. In embryos and newborn mice the hemangiomas expanded within 10-18 hr of injection, disrupting the vasculature and causing the death of the animal. In contrast, the hemangiomas formed a stable structure reminiscent of benign human hemangiomas in adult mice within 5 days. Analysis of the cells comprising the hemangioma revealed that over 95% of the endothelial cells were host derived. No induction of host cell proliferation was detected, and no endothelial mitogens were secreted by the endothelioma cells in vitro. The maintenance of the hemangioma appeared to require the continuous presence of endothelioma cells. The results indicate that these endothelioma cells act as a potent stimulating agent in the rapid formation of hemangiomas by recruiting nonproliferating host endothelial cells.
Animals↗
Health status of children in self-care.
Are children in self-care more obese, do they miss more school days, and do they make more visits to the school health office than children not in self-care? We undertook a cross-sectional survey of students in ten public elementary schools in Tucson over a two-year period in an attempt to answer these questions. The sample included 503 fifth-grade students, 137 in self-care and 366 not in self-care. Demographic information and data on school absences were obtained from school records. Physical examinations were performed at school. Obesity was assessed using the body mass index calculation, in which body mass index = (body weight in kilograms)/(height in meters). Every visit to the school health office during the 1985-1986 and 1986-1987 school years was recorded for each child. There were no differences in age between those in the self-care and adult-care groups. Boys were more likely to be in self-care, as were non-Hispanic children. There were no differences in weight, body mass index, school days missed, or visits to the school health office between children in self-care and those in adult care. Our findings suggest that, by the criteria used in this study, 11-year-old children in self-care do not suffer more ill health than their counterparts in adult care.
Absenteeism↗
The spatial resolution of protein adsorption on surfaces of heterogeneous metallic biomaterials.
This study was designed to examine the heterogeneity of the adsorption of proteins onto metallic materials. The materials studied included pure Ag, Au, and Ti and sintered Ag 10% Ti and Ag 10% Ta. The distribution of the protein adsorption was studied using I-125 labeled albumin detected by microautoradiography. The surface morphology of the specimens was examined in the scanning electron microscope prior to exposure to the protein solution. A heterogeneous distribution in albumin adsorption was observed over the Ag surface. Similar regions were observed over parts of the mixed metal specimens, but superimposed on this pattern were distinct regions of very low protein adsorption which appeared to correlate closely with the regions of Ti or Ta observed in the scanning electron microscope. A uniform distribution of adsorbed albumin was observed on the Au and Ti, with Au giving a much denser microautoradiograph than Ti. This work demonstrates that variations in the protein adsorption to heterogeneous materials can be observed on a microscopic scale.
Adsorption↗
The prevalence of periodic limb movements during sleep in men with erectile dysfunction.
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Adult↗
Professional qualifications.
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Expert Testimony↗
Erectile dysfunction in hypertensive men: sleep-related erections, penile blood flow and musculovascular events.
To explore how hypertension affects penile erection, we studied erectile hemodynamics during nocturnal penile tumescence in 3 groups of middle-aged men: hypertensive patients with and without erectile dysfunction, and normotensive controls without erectile problems. The hypertensive patients were not taking antihypertensive medication. Evaluations included standard monitoring of penile circumference change as well as noninvasive monitoring of penile segmental pulsatile blood flow and activity in the bulbocavernosus-ischiocavernosus muscles. Variables differed in how they discriminated among groups. Median amplitude of penile blood flow during rapid eye movement sleep differed significantly among all 3 study groups: controls had the highest amplitudes, patients without erectile problems had lower values and patients with erectile complaints had the lowest values. By contrast, standard measures of nocturnal penile tumescence (that is based on penile circumference change during sleep) only distinguished the patients with erectile problems from the 2 other groups. Density of musculovascular event clusters during rapid eye movement sleep (nearly simultaneous muscle activity burst, blood flow burst and circumference pulsation) distinguished the 2 groups of hypertensive men from controls. The sensitivity of the blood flow measure to changes in the hypertensive men without erectile complaints may indicate that the measure can reveal subclinical signs of developing vasculogenic erectile dysfunction.
Hemodynamics↗
Pharmacists recovering from alcohol and other drug addictions: an interview study.
An interview study of 86 pharmacists recovering from alcohol or other drug addiction was conducted to describe their experiences during development of and recovery from the addiction. Patterned after similar studies of other recovering health-care professionals, the study permitted comparisons with these other groups. Many felt inadequately prepared to recognize or deal with warning signs of problems of addiction in themselves or others. Forty-four had been arrested; 45 had experienced unemployment because of drinking or other drug use; 16 lost their licenses. Eighteen reported suicide attempts, 13 by drug overdose. Most reported experiences that are regarded as late-stage events, although 50 had never been subject to board action because of their drinking and other drug use. The use of chemicals interfered with the pharmacists' lives long before they were consciously worried about it. For 18, recovery occurred through the assistance of mutual-help groups alone; others had a variety of treatment experiences. Fewer pharmacists reported addiction to only alcohol than did other health-care professionals. Very few reported addiction to parenteral drugs, a significant deviation from the other groups studied. Pharmacists differed from other groups also in that they were extra scrupulous in reporting acts of dishonesty associated with their addiction, which may make their behavior appear worse than that of the other groups when the opposite may be the case. The profession must begin to answer questions about how recovering pharmacists should be treated, and what the role of professional groups in their recovery is.
Adult↗
The pharmacokinetics and pharmacodynamics of diltiazem and its metabolites in healthy adults after a single oral dose.
A potential complicating factor in the characterization of the pharmacokinetics and pharmacodynamics of diltiazem after an oral dose in the presence of two metabolites, N-demethyldiltiazem and desacetyldiltiazem, in plasma. Both N-demethyldiltiazem and desacetylditiazem have been shown to have pharmacologic activity in animal tissues. It is therefore possible that these metabolites contribute to the pharmacologic effect of diltiazem, but this possibility has not been explored. The purpose of this study was to investigate the pharmacokinetics and pharmacodynamics of diltiazem, N-demethyldiltiazem, and desacetyldiltiazem. Particular attention was paid to the effect of diltiazem on atrioventricular conduction. Six healthy men received a 120 mg oral dose of diltiazem. Concentrations of diltiazem, N-demethyldiltiazem, and desacetyldiltiazem in plasma and urine were measured by a sensitive HPLC method. Measures of pharmacologic response (heart rate, blood pressure, and PR interval) were obtained at each blood sampling time. Mean (+/- SD) peak plasma concentrations of diltiazem, N-demethyldiltiazem, and desacetyldiltiazem were 174.3 +/- 72.7, 42.6 +/- 10.0, and 14.9 +/- 3.3 ng/ml, respectively. The apparent half-lives of diltiazem, N-demethyldiltiazem, and desacetyldiltiazem were 6.5 +/- 1.4 hours, 9.4 +/- 2.2 hours, and 18 +/- 6.2 hours, respectively. Both N-demethyldiltiazem and diltiazem were eliminated by net secretion, whereas the renal clearance of desacetyldiltiazem did not exceed clearance by filtration. Both N-demethyldiltiazem and desacetyldiltiazem are bound to plasma proteins, with unbound fractions of 0.323 +/- 0.035 and 0.230 +/- 0.021. These values are similar to the unbound fraction of diltiazem (0.254 +/- 0.027). No significant effect of diltiazem on blood pressure or heart rate was noted. However, a prolongation of the PR interval was observed in all six subjects. Furthermore, an apparent clockwise hysteresis in the concentration-effect relationship was found in four of the six subjects. These findings suggest that some form of acute tolerance to the electrophysiologic effect of diltiazem develops, but the results of pharmacodynamic modeling suggest that this is not caused by the antagonistic effects the metabolites.
Administration, Oral↗
The pharmacokinetics of the enantiomers of atenolol.
A number of studies have demonstrated that lipophilic beta-adrenoceptor blocking agents, eliminated almost exclusively by hepatic metabolism, are stereoselectively metabolized in human beings. Previous studies in our laboratory have demonstrated that pindolol, a beta-adrenoceptor blocking agent of intermediate lipophilicity that is eliminated by both hepatic metabolism and renal excretion, is eliminated stereoselectively in the kidney. In the present study we examined the pharmacokinetics of the enantiomers of atenolol, a hydrophilic cardioselective beta-adrenoceptor blocking agent that is eliminated almost exclusively by the kidney. A single 100 mg oral dose of racemic atenolol was administered to six healthy adult men. Concentrations of d- and l-atenolol in plasma and urine were measured by a stereospecific HPLC analytic procedure. In each subject the peak concentration of d-atenolol was greater than the peak concentration of l-atenolol (mean +/- SD of 420 +/- 81 ng/ml vs 366 +/- 61 ng/ml; p less than 0.05). The peak concentration of both enantiomers was reached at the same time in each subject (between 2 and 3 hours). The renal clearances of d- and l-atenolol were not significantly different (109.7 +/- 33.5 ml/min vs 112.5 +/- 36.7 ml/min), probably because the major route of renal elimination is glomerular filtration. The half-lives of d- and l-atenolol were not significantly different (mean +/- SD of 4.6 +/- 1.1 hours vs 5.2 +/- 0.9 hours). However, both the AUC and the amount excreted unchanged in the urine in 24 hours Ae [0-24]) were significantly greater for d-atenolol than for l-atenolol (p less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)
Adult↗
The effect of probenecid on the renal elimination of cimetidine.
It is generally assumed that the systems involved in the transport of organic cations and organic anions in the renal proximal tubule are substrate selective (i.e., organic anions do not inhibit organic cation transport and vice versa). However, recent data obtained in vitro have suggested that the organic anion probenecid inhibits the renal transport of the organic cation cimetidine. We addressed the question of whether this interaction is biologically relevant in human beings. The study involved a two-treatment, randomized crossover design. Six healthy male subjects were given an intravenous infusion of 300 mg cimetidine alone as one treatment and, as the other treatment, received multiple oral doses of probenecid before receiving the cimetidine infusion. The renal clearance of cimetidine and inulin was determined in each period. There were no significant differences between treatments in cimetidine plasma concentrations, apparent volume of distribution, systemic clearance, half-life, amount of drug excreted unchanged in the urine, or nonrenal clearance. Probenecid significantly decreased the renal clearance of cimetidine by decreasing both the filtration clearance and the net secretory clearance. These effects were most evident in the first 1/2 to 1 hour after cimetidine administration, when probenecid levels in plasma and renal tissue would have been the highest. Because there was no effect of probenecid on cimetidine plasma concentrations, this interaction is not clinically relevant to the therapeutic use of these two compounds. However, the study demonstrates that renal interactions between organic cations and organic anions can occur in human beings. The mechanism of this interaction and the implications to other drug combinations are being explored.
Adult↗
LIF: a molecule with divergent actions on myeloid leukaemic cells and embryonic stem cells.
We have previously characterized, purified and cloned a novel murine and human regulator [leukaemia inhibitory factor, LIF] which induces the differentiation of certain murine and human myeloid leukaemic cells. Recently we have shown that there are specific LIF receptors on murine embryonic stem [ES] and embryonal carcinoma [EC] cells and that purified recombinant LIF can substitute for feeder cells and crude sources of differentiation inhibiting activity [DIA] [such as BRL-cell-conditioned medium] in the maintenance of ES cells in a pluripotential state in vitro. Furthermore, ES cells maintained in culture in recombinant LIF for a prolonged period can give rise to germline chimaeric mice. Thus, based on a number of biochemical and biological similarities, it is likely that LIF and DIA are the same molecule. The identification of LIF as a molecule, necessary and sufficient for the maintenance of ES cells in culture, should have a profound impact on the use of these cells for genetic manipulations.
Amino Acid Sequence↗
Hypertension, erectile dysfunction, and occult sleep apnea.
Sleep-related respiratory pattern was evaluated in 175 hypertensive and 110 normotensive men, none of whom reported difficulties in initiating or maintaining sleep. Patients were grouped according to sexual status (complaint of erectile problems), hypertension treatment status (treated or untreated), and blood pressure (diastolic less than 90 or greater than or equal to 90). The prevalence of sleep apnea, apnea index, duration of the longest episode of apnea, and penile rigidity were tabulated. The group with elevated blood pressure, persistent even with antihypertensive drug therapy, had the most sleep apnea. The treated hypertensive men with controlled blood pressure had significantly less apnea than those whose blood pressure remained high. Untreated hypertensive groups, however, did not differ from normotensive groups with respect to apnea. Evidence of abnormal sleep-related respiratory activity was found in both hypertensive and normotensive groups with erectile problems. Interestingly, penile rigidity was significantly lower for hypertensive men with erectile complaints than for normotensive men with erectile complaints. There was also a small, but significant, negative correlation between apnea index and penile rigidity among men with erectile complaints. These results indicate that sexual status is an important consideration in the diagnosis of hypertension and sleep apnea. Moreover, these data suggest an interrelationship among hypertension, erectile dysfunction, and sleep apnea.
Antihypertensive Agents↗
A comparison of the influence of famotidine and cimetidine on phenytoin elimination and hepatic blood flow.
The H2-receptor antagonist cimetidine has been reported to decrease the hepatic clearance of numerous drugs by inhibiting cytochrome P-450 metabolism, decreasing liver blood flow or both. In this open-label, randomized crossover study we determined whether therapeutic doses of famotidine, a newer H2-receptor antagonist, has similar effects. Ten healthy subjects received single doses of both phenytoin 100 mg orally and indocyanine green intravenously without other treatment, and then again during treatment with famotidine or cimetidine. After a drug-free period, this sequence was repeated with the alternate H2-receptor antagonist. Cimetidine decreased the plasma clearance of phenytoin by 16% +/- 14% (mean +/- s.d.), but was not found to have a significant influence on phenytoin volume of distribution or terminal elimination rate constant nor on blood clearance of indocyanine green. Famotidine was not found to alter either phenytoin or indocyanine green kinetics.
Cimetidine↗
The pleiotropic actions of leukemia inhibitory factor.
Leukemia inhibitory factor (LIF) is a glycoprotein regulator that induces the differentiation and suppresses the clonogenicity of M1 myeloid leukemic cells. M1 cells require only a brief exposure to LIF to become irreversibly committed to differentiation. In combination with granulocyte colony-stimulating factor or granulocyte-macrophage colony-stimulating factor, LIF is also able to suppress HL-60 and U937 cell proliferation. Normal monocytes and macrophages have LIF receptors, but the function of LIF on such cells is unclear. Recently it was discovered that LIF also acts on embryonic stem (ES) cells, where its continuous presence is required to prevent ES cell differentiation.
Animals↗
The use of token economies with individuals who have developmental disabilities.
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Activities of Daily Living↗
Anencephalic infants: life expectancy and organ donation.
Between 1978 and 1982, 205 anencephalic infants weighing more than 2,500 g were born alive in California. Although typically none were offered significant support, almost 9% lived more than one week. It seems reasonable to assume that modern intensive care would have increased survival times dramatically. In fact, preliminary data from centers specializing in neonatal organ transplantation demonstrate that seven to 14 days of ventilatory support can be accomplished for anencephalic infants without occurrence of brainstem death. Given these data and medical information that clearly establishes anencephalic infants as a "special case" of children who have not suffered brain death but could reasonably be used as organ donors, we believe that parents who wish to do so should be allowed to continue ventilatory support for their anencephalic children for whatever period of time is necessary to find organ recipients and arrange for organ donation. Arbitrary cutoff points for intensive care and artificial criteria for brain death should not be necessary to allow the use of anencephalic infants as organ donors. We believe that current laws should be changed to permit this scenario.
Anencephaly↗
Tumour induction in fetal brain transplants exposed to the viral oncogenes polyoma middle T and v-src.
Using a neural transplantation model, we have studied the effect of polyoma virus middle T antigen and of the viral src oncogene on the developing rat brain. For this purpose, single-cell suspensions of fetal rat brain were prepared on day 14 of gestation (E14), infected with a replication-defective retroviral vector which carries the middle T oncogene driven by an internal thymidine kinase promoter, and stereotaxically injected into the caudoputamen of adult host rats. With mock-infected donor cells, the transplants developed into an organotypically differentiated population of neurons, astrocytes, oligodendrocytes and other central nervous system cell types and expressed marker proteins of mature neuroectodermal cells, including neuron-specific enolase, synaptophysin, neurofilament protein, glial fibrillary acidic protein and S-100 protein. A high percentage of rats carrying transplants infected with the middle T-encoding vector died within two to six weeks from massive haemorrhage into the transplant. Upon microscopic examination, gross abnormalities of the microvasculature were seen, with formation of large blood-filled spaces lined by a thin layer of proliferating endothelial cells. This effect of middle T was apparently cell type-specific, since the differentiation of neuroectodermal cells within the graft proceeded in a regular fashion. In order to assess further the cell-specificity of the oncogene, analogous experiments were carried out with a retroviral construct in which the middle T cDNA had been replaced by the viral src gene (v-src). Transplants infected with the v-src vector developed astrocytomas, but no vascular abnormalities.(ABSTRACT TRUNCATED AT 250 WORDS)
Animals↗