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Biomedical subjects

J Allen

Publications and source records attributed to J Allen.

At least 307 records · Page 17Linked to original sources

Plasma protein binding of alpidem in healthy volunteers, in neonates and in liver or renal insufficiency.

The binding of alpidem, a new anxiolytic drug, has been studied in plasma from 6 healthy subjects, 12 patients with renal failure, 12 patients with liver cirrhosis and 12 chronic uraemics maintained on haemodialysis, as well as in 12 serum samples from the placental cord, to represent the situation in the newborn. The unbound fraction was 0.61% (healthy volunteers), 1.31% (newborns), 0.86% (cirrhotic patients), 0.72 (patients with renal failure), 0.70% (before haemodialysis) and 0.79% (after haemodialysis). Binding in the volunteers was significantly different from that in neonates and cirrhotics only. Alpidem became bound to isolated albumin (45 g.l-1) and alpha 1-acid glycoprotein (0.75 g.l-1) to 97.2% and 97.1%, respectively. The bound fraction of the drug in a mixture of two proteins was 99.1%. For alpidem, it appears that alpha 1-acid glycoprotein may balance the effect of any decrease in the albumin concentration.

Adult↗

Overview of alcoholism treatment: settings and approaches.

The alcoholism treatment service delivery system is described in terms of facility characteristics, funding, and demographics of clientele served. A brief discussion of the "Minnesota Model," the most pervasive therapeutic approach to alcoholism in the United States is then offered. The article concludes with a synopsis of key research findings and current public debate issues which may impact the future delivery of treatment services to alcoholics.

Alcoholism↗

Intracervical 17 beta-oestradiol before induction of second-trimester abortion with a prostaglandin E1 analogue.

28 consecutive patients (17.5 weeks pregnant, range 15-21 weeks) referred for therapeutic termination of pregnancy were randomized for pretreatment overnight with either intracervical gel containing 50 mg 17 beta-oestradiol or placebo gel. The induction-abortion time with pessaries containing 16,16-dimethyl-trans-delta 2-prostaglandin E1 methyl ester was significantly reduced in the oestrogen group (median value of 11.5 versus 15 hours). The beneficial effect of oestradiol priming was primarily caused by a reduction of the number of women with high cervical resistance and prolonged induction-abortion time (90 percentiles of 15.5 and 34 hours). Thus, oestrogen pretreatment might reduce the cervical trauma due to the prostaglandins as well as the incidence of cervical incompetence in later pregnancies.

Abortifacient Agents↗

Snap-Gauge band vs multidisciplinary evaluation in impotence assessment.

This study compares the findings of multidisciplinary evaluation to the two-night use of the Snap-Gauge band in 100 impotent men. An organic etiology was diagnosed in 52 percent of those evaluated. The Snap-Gauge band proved accurate as a screening device for organic disease. If no elements were broken over the two-night period, this finding correlated with multisystemic diagnosis of organic etiology in 86 percent of cases. Among the 52 patients in whom an organic etiology was diagnosed, 32 broke no elements for a 62 percent sensitivity. When more than one element was broken, the predictive value as to etiology of the erectile dysfunction diminished.

Erectile Dysfunction↗

Efficacy of aortic balloon valvoplasty: direct measurement of orificial area in a model with pulsatile flow.

The efficacy of balloon valvoplasty of calcific aortic stenosis remains controversial. We studied, therefore, 5 human aortic valves obtained at necropsy in a positive-displacement pulse duplicator which delivered stroke volumes of 40-100 ml with a quasiphysiological waveform of flow. All valves had three leaflets without commissural fusion and were preserved in antibiotic solution before study. Orificial area was planimetered from videotape of opening of the valve and varied with flow in all cases. Valvoplasty with a 20 mm diameter balloon had no effect on the orifice of the normal valve but increased the orifice of 2 mildly calcified valves from 0.70-1.77 cm2 (range) at baseline to 1.06-1.95 cm2. In 2 valves with severe calcification of the leaflets, the orifice was increased from 0.31-0.82 cm2 to 0.73-1.07 cm2. Dual balloon valvoplasty achieved a variable but small further increase in orificial area. No valve showed tears of the leaflets or fracture of calcific deposits after valvoplasty. We conclude that balloon valvoplasty can acutely increase orificial area, independently of any change in stroke volume. In valves without commissural fusion, its mechanism appears to be an increase in the pliability of the leaflets which does not require macroscopic fracture of calcific deposits.

Adult↗

Positive thought disorder in a hypothetically psychosis-prone population.

Proverb interpretations of subjects who scored high on the Perceptual Aberration-Magical Ideation Scale (Chapman & Chapman, 1985) were compared with those of low-scoring controls. Responses to 10 familiar and 3 unfamiliar proverbs were scored for Bizarre-idiosyncratic thinking (Marengo, Harrow, Lanin-Kettering, & Wilson, 1986) and literalness (Hertler, Chapman, & Chapman, 1978). A Group by Type of Proverb (familiar versus unfamiliar) interaction was found for bizarre-idiosyncratic scores; (Per-Mags) scored higher than controls on unfamiliar, but not familiar proverbs. The Group X Familiarity interaction for bizarre-idiosyncratic scores indicates that the Per-Mag group displayed a subclinical, positive-thought disorder that is affected by the familiarity of the proverbs.

Adult↗

The increasing incidence of the hemolytic-uremic syndrome in King County, Washington: lack of evidence for ascertainment bias.

The annual incidence of the hemolytic-uremic syndrome was determined for the well-defined population of King County, Washington, between 1971 and 1986, inclusive, to ascertain temporal trends in the epidemiology of this disease. The average annual incidence rose from 0.69 cases per 100,000 children under age 15 years between 1971 and 1975 to 1.77 cases between 1976 and 1980 and 1.74 cases between 1981 and 1986. The mean hematocrits, platelet counts, and blood urea nitrogen and creatinine concentrations on admission were similar in all periods, as were the mean length of hospital stay and the proportions of patients requiring erythrocyte and/or platelet transfusions and dialysis. These results indicate that the increased incidence of hemolytic-uremic syndrome in childhood has been sustained in King County, Washington, and that this increase is not due to ascertainment bias caused by the diagnosis of less severely ill cases. Further investigations are needed to determine whether this increased incidence is being experienced in other populations and to assess strategies for the prevention of microangiopathic sequelae to hemorrhagic colitis.

Adolescent↗

Effect of endogenous vasoconstrictors on maternal intramyometrial and fetal stem villous arteries in pre-eclampsia.

The contractile responses to various endogenous vasoactive agents were investigated in isolated human uteroplacental arteries from normotensive (NT) patients and patients with pre-eclampsia (PE) undergoing caesarian section. Tissue samples were obtained from the uterine incision and from macroscopically normal cotyledons. Vascular ring preparations of intramyometrial and stem villous arteries (length 1.0-1.3 mm, outer diameter 400-600 microns) were dissected and mounted in organ baths and isometric tension was recorded. Concentration-response relationships for vasopressin (VP), oxytocin (OX), angiotensin II (Ang II), noradrenaline (NA), 5-hydroxytryptamine (5-HT), prostaglandin F2 alpha (PGF2 alpha) and prostaglandin E2 (PGE2) were assessed. For each compound, the mean maximum contractile effect (Emax) and the drug concentration producing half-maximal response (EC50) were determined. In intramyometrial arteries from NT and PE patients, VP, Ang II, NA, 5-HT and PGF2 alpha induced contraction while OX and PGE2 produced weak or no responses. Preparations from PE patients showed higher Emax values, while no differences in EC50 were found between the two groups. In fetal stem villous arteries, Ang II, 5-HT, PGF2 alpha and PGE2 induced contractions, while VP, NA and OX produced weak responses. No differences in Emax or EC50 values were found between the fetal vessels of PE and NT patients. No qualitative differences were demonstrated in response to the agents tested between the vessels (fetal and maternal) from NT women at term and PE patients. However, the results may reflect quantitative differences, suggesting increased contractility of maternal uteroplacental arteries from women with PE.

Amines↗

The localization of the bullous pemphigoid and cicatricial pemphigoid antigens: direct and indirect immunofluorescence of suction blisters.

The location of in vivo bound immunoreactants was studied in 37 patients with subepidermal blistering diseases by direct immunofluorescence (IMF) on suction blisters taken from uninvolved forearm skin. The patients studied included 18 with bullous pemphigoid (BP), nine with cicatricial pemphigoid (CP), three with acquired epidermolysis bullosa (EBA) and 7 hybrid cases. The patterns of IMF in the suction blisters were: BP, epidermal 1, dermal 1, combined 4, negative 12; CP, epidermal 1, dermal 2, negative 6; EBA, dermal 2, negative 1; and 'hybrid' patients, epidermal 3, negative 4. The different patterns of suction blister staining could not be correlated with the clinical features of the patients in respect of mucous membrane involvement, scars or milia or a history of skin fragility. Both BP and CP are probably heterogeneous in respect of their antigen specificity, and the two diseases cannot reliably be distinguished by the patterns of direct IMF on suction blisters. In addition, some individual patients with BP have more than one target antigen as indicated by a combined pattern of suction blister fluorescence. The lack of correlation between the pattern of suction blister fluorescence and the clinical features suggests that factors other than antigen specificity determine the clinical expression of subepidermal blistering diseases.

Adult↗

Mechanics of the respiratory system during high frequency ventilation.

No rational approach has evolved for selecting operating conditions for clinical application of high-frequency ventilation (HFV). To this end, we divide our discussion of HFV into considerations of mechanics versus transport, and treat the latter as a constraint. After describing some of the phenomena that influence distending pressure (and its distribution) expressed across pulmonary tissues, we address the pressure costs per unit ventilation and the factors that influence them. This narrowly defined approach leads to some fundamental strategies, compromises, and dilemmas. In particular, consideration of the mechanical interaction of the lung and chest wall leads to a paradox, and points out that the influence of the chest wall upon phasic regional lung distension is not well understood.

Animals↗

Bacteroides loeschei PK1295 cells express two distinct adhesins simultaneously.

Bacteroides loeschei synthesizes two distinct adhesins that mediate its coaggregation with Streptococcus sanguis 34 and Actinomyces israeli PK14. Streptococcal adhesin-specific and actinomyces adhesin-specific monoclonal antibodies were used to prepare antibody-coated 5- or 10-nm gold particles. These were used in immunoelectron microscopic studies to establish that essentially all bacteroides cells in a population express both adhesins. In general, the two sizes of gold particles representing each type of adhesin appeared to be spatially separated on neighboring fimbriae of B. loeschei. Deposition of antibody-coated gold particles, representing both types of adhesin, at or near the same fimbria was observed less frequently.

Antibodies, Monoclonal↗

Effects of indomethacin on human placental stem villous arteries.

Ring preparations of human stem villous arteries were prepared by microtechnique from placentae born after normal-term vaginal delivery. Isometric tension was recorded in organ baths. Indomethacin 10(-8)-10(-5) M left responses to K+ depolarization and contractions produced by prostaglandin F2 alpha (PGF2 alpha) unaffected, while indomethacin 10(-4) M slightly decreased K+-induced contractions and inhibited responses to PGF2 alpha. In contrast, nitrendipine 10(-9)-10(-6) M markedly decreased responses to K+ while nitrendipine 10(-8)-10(-6) M inhibited PGF2 alpha-induced responses. Relaxant responses to vasointestinal polypeptide 10(-8)-10(-7)M were left unaffected by pretreatment with indomethacin 5 X 10(-5) M. Indomethacin affects contractile activation in human stem villous arteries only in high concentrations, and the effects differ in profile from those of calcium entry blockers like nitrendipine. The results do not leave evidence for increased placental arterial tone during indomethacin treatment in pregnancy.

Arteries↗

Poikilothermia in a 68-year-old female. A risk factor for accidental hypothermia, or hyperthermia.

A 68-year-old woman presented in wintertime in a cold climate with ataxia and numbness in her legs and was found to be profoundly hypothermic in hospital. No endocrine or neurological cause for hypothermia could be distinguished. Physiological investigation, including a sympathetic release test, exposure to gradually increasing environmental temperatures and prolonged exposure to a high temperature suggested she was at that time regulating her core temperature around a set value which was several degrees lower than normal. Metabolic rate was 42 per cent below the value predicted from standard tables. Further measurements over a one-month period in a warm climate suggested a poikilothermic temperature control mechanism, with a possible risk of environmental hyperthermia. No pathological basis for this disorder has yet been identified, but it is suggested that a small localized hypothalamic vascular event has occurred.

Aged↗

Ten-year study of pediatric drownings and near-drownings in King County, Washington: lessons in injury prevention.

The factors associated with submersion events among less than 20-year-old persons that occurred in King County from 1974 to 1983 were studied to focus prevention efforts. Near-drowning (n = 103) and drowning (n = 96) victims were identified from medical examiners' reports, paramedics' reports, and hospital discharge registers. Annual incidence was 5.5; the mortality rate was 2.6 per 100,000 children. Although preschool-aged children had the largest incidence (12.8), followed by older adolescents (4.9), adolescents had the largest case fatality rate, 77%. Lake and river victims had the largest incidence, mortality, and case fatality rate; swimming pools, the smallest case fatality rate (25%). A total of 89% of all victims had absent or no supervision; victims supervised by lifeguards had a 42% case fatality rate. Prior seizures were part of the history of 7.5% of all victims; 25% of fatal submersions by adolescents were associated with alcohol. Bathtub submersions were associated with child abuse in three of 16 preschool-aged children and epilepsy in four of five older children. Certain age groups and sites combined had the greatest incidence: preschool-aged children in swimming pools, infants in bathtubs, teenagers in lakes and rivers. Incidence decreased in public and semipublic pools coincident with fencing regulations. These findings suggest prevention strategies: extending fencing requirements to private pools, discouraging alcohol consumption during water sports, changing bathing practices of epileptics, and improving lifeguard efficacy.

Adolescent↗

Pleistocene dates for the human occupation of New Ireland, northern Melanesia.

Pleistocene dates from three cave sites indicate the human capacity to colonise across two oceanic straits to the east of a former Tasmania-Australia-New Guinea continent by 33 kyr BP. The sites demonstrate exploitation of costal marine and lowland tropical forest resources. They extend Pleistocene occupation into island Melanesia and demonstrate that the large islands of northern Melanesia have an antiquity of human occupation of the same order as the adjacent Greater Australian continent.

Animals↗

Regulation of pH and HCO3 in brain and CSF of the developing mammalian central nervous system.

Acute (2-h) metabolic acidosis or alkalosis was induced in immature rats to ascertain the ability of their incompletely-developed CNS to regulate pH when challenged with perturbations in blood [H] and [HCO3]. Brain and cisternal CSF pH were determined from steady-state distribution of [14C]dimethadione, a weak organic acid. By 1 week post partum, there was a remarkable stability of pH in the cerebral cortex of animals subjected to arterial pH extremes of 7.1 and 7.5. However, CSF pH in 1-week-old animals rendered alkalotic remained 0.07-0.08 units above control due to lack of a compensatory increase in pCO2, and to a blood-CSF barrier apparently more permeable to HCO3. As arterial HCO3, i.e. [HCO3]art, was varied from about 10 to 30 mmol/l, the infants maintained [HCO3]csf only half as effectively as adults, i.e. delta [HCO3]art was 0.4 and 0.2 at 1 and greater than 4 weeks, respectively. Throughout postnatal ontogenesis, [HCO3]csf was more resistant to alteration by metabolic acidosis than by alkalosis. Overall, the results indicate that immature rats challenged with systemic acid-base loads are less capable than adults in regulating CSF pH, but they are able to maintain brain pH.

Acidosis↗

Determination of the beta-blocker betaxolol and labelled analogues by gas chromatography/mass spectrometry with selected ion monitoring of the alpha-cleavage fragment (m/z 72).

Low concentrations of betaxolol in blood plasma and physiological buffers were determined by selected ion monitoring of the intense m/z 72 fragment [CH2 = NH-CH(CH3)2]+ formed by electron impact ionization of the O-trimethylsilyl derivative. At a mass spectrometric resolution of 3000, fewer potentially interfering peaks were seen than at low resolution. There remained a chemical interference, corresponding to 100 pg/sample, which arose during treatment of the samples. This method is more sensitive than previous ones, but it is restricted to situations where the specificity can be controlled. When the m/z 72 fragment was mass-shifted by using betaxolol appropriately labelled with deuterium or 13C, both the interference and the baseline noise were greatly reduced; concentrations of labelled betaxolol as low as 10-20 pg/sample can be determined with little difficulty.

Adrenergic beta-Antagonists↗