PubMed Health⌕ Search

Biomedical subjects

D E Clarke

Publications and source records attributed to D E Clarke.

At least 19 recordsLinked to original sources
PubMed2003

Synthesis, pharmacology and pharmacokinetics of 3-(4-aryl-piperazin-1-ylalkyl)-uracils as uroselective alpha1A-antagonists.

Predominance in the urethra and prostate of the alpha(1A)-adrenoceptor subtype, which is believed to be the receptor mediating noradrenaline induced smooth muscle contraction in these tissues, led to the preparation of alpha(1A)-selective antagonists to be tested as uroselective compounds for the treatment of benign prostatic hyperplasia. Thus, a number of selective alpha(1A)-adrenoceptor antagonists were synthesized and assayed in vitro for potency and selectivity. Dog pharmacokinetic parameters of 12 (RO700004) and its metabolite 40 (RO1104253) were established. The relative selectivity of intravenously administered 12, 40 and standard prazosin to inhibit hypogastric nerve stimulation-induced increases in intraurethral prostatic pressure versus phenylephrine-induced increases in diastolic blood pressure in anesthetized dogs was 76, 71 and 0.6, respectively.

Administration, Oral↗
PubMed2001

Effect of methoxamine on maximum urethral pressure in women with genuine stress incontinence: a placebo-controlled, double-blind crossover study.

The aim of the study was to evaluate the potential role for a selective alpha1-adrenoceptor agonist in the treatment of urinary stress incontinence. A randomised, double-blind, placebo-controlled, crossover study design was employed. Half log incremental doses of intravenous methoxamine or placebo (saline) were administered to a group of women with genuine stress incontinence while measuring maximum urethral pressure (MUP), blood pressure, heart rate, and symptomatic side effects. Methoxamine evoked non-significant increases in MUP and diastolic blood pressure but caused a significant rise in systolic blood pressure and significant fall in heart rate at maximum dosage. Systemic side effects including piloerection, headache, and cold extremities were experienced in all subjects. The results indicate that the clinical usefulness of direct, peripherally acting sub-type-selective alpha1-adrenoceptor agonists in the medical treatment of stress incontinence may be limited by associated piloerection and cardiovascular side effects.

Adrenergic alpha-Agonists↗
PubMed2001

Vital pulp therapy for complicated crown fracture of permanent canine teeth in dogs: a three-year retrospective study.

A 36-month retrospective study compared the results of vital pulp therapy based on the duration of pulp exposure for complicated crown fracture of 97 permanent canine teeth in 76 dogs. Postoperative oral and radiographic examinations were performed at 3, 12, and 36-months following treatment. Based on the 36-month postoperative examinations 88.2%, 41.4 %, and 23.5% of teeth were vital when treated within 48-hours, 1-week, and 3-weeks of pulp exposure, respectively. There was a significant difference in the incidence of tooth vitality between groups. The duration of pulp exposure following complicated crown fracture influenced the success of vital pulp therapy. Vital pulp therapy should be performed as soon as possible following traumatic pulp exposure.

Animals↗
PubMed2001

Clinical and microbiological effects of oral zinc ascorbate gel in cats.

The clinical and microbiological effects of zinc ascorbate gel applied orally in cats were evaluated during a 42-day study period. Cats were divided randomly into two equal groups, with the treatment group (18 cats) receiving zinc ascorbate gel and the control group (18 cats) receiving a placebo (0.9% sterile saline). Clinical parameters evaluated biweekly included halitosis, plaque, calculus, and gingivitis. Aerobic and anaerobic bacterial cultures were obtained from cats in the treatment group at Days 0 and 42. There was a significant decrease in plaque, gingivitis, and anaerobic periodontal pathogens in treatment group cats. Halitosis and calculus scores were not significantly different in treatment group compared with control group cats. The results of this study suggest that zinc ascorbate gel used as an oral antiseptic improves feline oral health, and may be most effective in decreasing bacterial growth, plaque formation, and gingivitis when applied following a professional teeth cleaning procedure.

Administration, Topical↗
PubMed2001

Effects of the nuclear factor-kappaB inhibitors 2-hydroxy-4-trifluoromethylbenzoic acid and aspirin on micturition in rats with normal and inflamed bladder.

PURPOSE: We examined the effects of intravenous administration of the 2 nuclear factor-kappaB inhibitors aspirin and 2-hydroxy-4-trifluoromethylbenzoic acid (HTB) on bladder filling and voiding in anesthetized and conscious rats. MATERIALS AND METHODS: Disappearance of isovolumic bladder contractions after intravenous administration of different doses of aspirin and HTB in anesthetized, transurethrally catheterized rats was evaluated. Cystometry was performed in conscious rats during bladder infusion with saline or diluted acetic acid as well as in those with cyclophosphamide induced cystitis. Changes in bladder capacity and voiding pressure were evaluated after intravenous administration of test compounds. RESULTS: Aspirin induced a dose dependent disappearance of isovolumic bladder contractions in anesthetized rats with an extrapolated dose of 2.1 mg./kg. inducing 10 minutes of bladder quiescence. HTB was practically inactive, inducing a dose independent block of 3 to 4 minutes after intravenous administration of 1 to 10 mg./kg. In conscious rats with a bladder infused with saline aspirin was poorly active on bladder capacity, inducing a 20% increase 60 minutes after intravenous administration of 30 and 100 mg./kg. In rats with a bladder infused with acetic acid aspirin was much more active when injected at the initiation of inflammation and after 1 hour of irritant infusion. In this latter situation aspirin increased bladder capacity up to 60% after intravenous administration of 30 and 100 mg./kg. Similar results were obtained in rats with cyclophosphamide induced cystitis in which the bladder was infused with saline. In these cystometrography models 30 mg./kg. HTB intravenously was completely inactive. CONCLUSIONS: The results show that HTB is devoid of significant effects on the micturition reflex in the absence or presence of bladder inflammation, suggesting that acute inhibition of nuclear factor-kappaB does not influence bladder urodynamics in rats. In contrast, aspirin, which is a cyclooxygenase and nuclear factor-kappaB inhibitor, was always effective, indicating the important role of cyclooxygenase enzymes.

Animals↗
PubMed2000

Perspectives of women living with schizophrenia.

OBJECTIVE: The study investigated the perceptions of women with schizophrenia or schizoaffective disorder about their illness in the context of their life stages and corresponding health needs. This paper reports narratively and through direct quotations what the women's daily lives are like. METHODS: Five focus groups totaling 28 women who identified themselves as having schizophrenia or schizoaffective disorder and who were living in the community met to discuss their health-related needs, ranging from parenting and reproductive health to relationships and getting older. Verbatim transcripts were analyzed inductively, and data were coded and organized around key themes. RESULTS: This group of women led marginalized, deprived lives in the face of multiple losses, social stigma, limited interpersonal contacts, and poverty. Perceived rejection and criticism were commonplace. The women felt that the health care system focused on their illness and that they had become invisible as women. Nevertheless, they conveyed a persistent sense of wanting life to improve and hoping that it could. CONCLUSIONS: The quality of a woman's life can be seriously impaired by illness or its treatment. Health care providers can help improve the lives of women with severe mental illness by focusing on how options and alternatives are presented, by exploring the impact of illness and treatment on a woman's day-to-day life, and by determining the appropriate structure of the therapeutic relationship.

Adult↗
PubMed2000

Evaluation of a networked self-testing program.

The use of a computerized, multiple-choice test bank to present practice and assessment tests on a network was evaluated with 46 men and 119 women from a first-year class in psychology. A correlation of .65 (p < .001) between scores on a traditional paper-and-pencil test and scores on a computerized test provided some validity for the computerized assessment. Regression analysis showed that ability (previous academic performance) and motivation (number of practice tests taken) accounted for 73% of the explained variance in computerized test scores. Sex differences did not enter the regression equation significantly.

Adolescent↗
PubMed1999

Human cloned alpha1A-adrenoceptor isoforms display alpha1L-adrenoceptor pharmacology in functional studies.

The recombinant alpha1A-adrenoceptor displays a distinct pharmacological profile ('classical alpha1A-adrenoceptor') in homogenate binding assays, but displays the properties of the so-called alpha1L-adrenoceptor in functional studies in whole cells at 37 degrees C. As three splice variants of the human alpha1A-adrenoceptor have been described previously (alpha1A-1, alpha1A-2 and alpha1A-3), we have compared their functional pharmacological profiles, when expressed stably in Chinese hamster ovary (CHO-K1) cells (antagonist inhibition of noradrenaline-stimulated [3H]inositol phosphates accumulation). A fourth, novel isoform (alpha1A-4) has also been studied: alpha1A-4 mRNA predominates in several human tissues including prostate, liver, heart and bladder. In homogenate binding studies, all four isoforms displayed essentially identical affinity profiles, with prazosin (1-(4-amino-6,7-dimethoxy-2-quinazolinyl)-4-(2-furoyl)piperazine), tamsulosin (5-[2-[[2-(2-ethoxyphenoxy)ethyl]-amino]propyl]-2-methoxybenzen esulfonamide), RS-17053 (N-[2-(2-cyclopropylmethoxyphenoxy)ethyl]-5-chloro-alpha,alphad imethyl-1H-indole-3-ethanamine hydrochloride), WB 4101 ((2,6-dimethoxyphenoxyethyl)aminomethyl-1,4-benzodioxane hydrochloride) and 5-Me-urapidil (5-methyl-6[[3-[4-(2-methoxyphenyl)-1-piperazinyl]propyl]amino]-1,3-d imethyuracil) all displaying subnanomolar affinities. In functional studies, noradrenaline accelerated [3H]inositol phosphates production with potencies (p[A]50) of between 5.8 and 6.6. The affinities of prazosin, RS-17053, WB 4101 and 5-Me-urapidil, at antagonizing responses to noradrenaline, were reduced by approximately 10-fold (cf. binding data), while those for tamsulosin and indoramin (N-[1-[2-(1H-indol-3-yl)ethyl]-4-piperidinyl]benzamide) remained constant or increased, consistent with the previously described alpha1L-adrenoceptor. Thus, all four human recombinant alpha1A-adrenoceptor isoforms display the pharmacology of the alpha1L-adrenoceptor when studied in functional assays, consistent with the hypothesis that the putative alpha1L-adrenoceptor represents a functional phenotype of the alpha1A-adrenoceptor.

Adrenergic alpha-Agonists↗
PubMed1999

In vitro alpha1-adrenoceptor pharmacology of Ro 70-0004 and RS-100329, novel alpha1A-adrenoceptor selective antagonists.

It has been hypothesized that in patients with benign prostatic hyperplasia, selective antagonism of the alpha1A-adrenoceptor-mediated contraction of lower urinary tract tissues may, via a selective relief of outlet obstruction, lead to an improvement in symptoms. The present study describes the alpha1-adrenoceptor (alpha1-AR) subtype selectivities of two novel alpha1-AR antagonists, Ro 70-0004 (aka RS-100975) and a structurally-related compound RS-100329, and compares them with those of prazosin and tamsulosin. Radioligand binding and second-messenger studies in intact CHO-K1 cells expressing human cloned alpha1A-, alpha1B- and alpha1D-AR showed nanomolar affinity and significant alpha1A-AR subtype selectivity for both Ro 70-0004 (pKi 8.9: 60 and 50 fold selectivity) and RS-100329 (pKi 9.6: 126 and 50 fold selectivity) over the alpha1B- and alpha1D-AR subtypes respectively. In contrast, prazosin and tamsulosin showed little subtype selectivity. Noradrenaline-induced contractions of human lower urinary tract (LUT) tissues or rabbit bladder neck were competitively antagonized by Ro 70-0004 (pA2 8.8 and 8.9), RS-100329 (pA2 9.2 and 9.2), tamsulosin (pA2 10.4 and 9.8) and prazosin (pA2 8.7 and 8.3 respectively). Affinity estimates for tamsulosin and prazosin in antagonizing alpha1-AR-mediated contractions of human renal artery (HRA) and rat aorta (RA) were similar to those observed in LUT tissues, whereas Ro 70-0004 and RS-100329 were approximately 100 fold less potent (pA2 values of 6.8/6.8 and 7.3/7.9 in HRA/RA respectively). The alpha1A-AR subtype selectivity of Ro 70-0004 and RS-100329, demonstrated in both cloned and native systems, should allow for an evaluation of the clinical utility of a 'uroselective' agent for the treatment of symptoms associated with benign prostatic hyperplasia.

Adrenergic alpha-1 Receptor Antagonists↗
PubMed1999

The crystalline components of dental calculus in the domestic cat.

Feline dental calculus was found to consist of carbonate-containing hydroxyapatite, Ca10(PO4)3(CO3)3(OH)2. Other forms of calcium phosphates consistently present in human calculus, and calcium carbonates found in horse, dog, and miniature pig calculus were not present. Calculus composition was performed using wet chemical method, x-ray diffraction, spectrographic analysis, and infrared spectrophotometric analysis. All samples showed traces of amorphous material, including magnesium and ammonium, but were negative for uric acid, cysteine, and oxalate.

Animals↗
PubMed1998

Molecular cloning, genomic characterization and expression of novel human alpha1A-adrenoceptor isoforms.

We have isolated and characterized from human prostate novel splice variants of the human alpha1A-adrenoceptor, several of which generate truncated products and one isoform, alpha(1A-4), which has the identical splice site as the three previously described isoforms. Long-PCR on human genomic DNA showed that the alpha(1A-4) exon is located between those encoding the alpha(1A-1) and alpha(1A-3) variants. CHO-K1 cells stably expressing alpha(1A-4) showed ligand binding properties similar to those of the other functional isoforms as well as agonist-stimulated inositol phosphate accumulation. Quantitative PCR analyses revealed that alpha(1A-4) is the most abundant isoform expressed in the prostate with high levels also detected in liver and heart.

Adrenergic alpha-Antagonists↗
PubMed1998

Alpha1L-adrenoceptor mediation of smooth muscle contraction in rabbit bladder neck: a model for lower urinary tract tissues of man.

1. The alpha1-adrenoceptor population mediating contractile responses to noradrenaline (NA) in smooth muscles of the bladder neck from rabbit (RBN) has been characterized by use of quantitative receptor pharmacology. 2. Experiments with several 'key' alpha1-adrenoceptor antagonists of varying subtype selectivities (RS-17053, BMY 7378, indoramin, 5-methylurapidil, prazosin, REC 15/2739, SNAP 5089, terazosin, WB 4101, tamsulosin, (+)-cyclazosin and RS-100329) were conducted. Schild regression analyses yielded affinity (mean pKb) estimates of 7.1, 6.2, 8.6, 8.6, 8.4, 9.3, 7.0, 7.4, 8.9, 10.0, 7.1 and 9.3, respectively, although deviations from unit Schild regression slope question the robustness of data for RS-17053 and SNAP 5089. 3. The nature of antagonism by these agents and the profile of affinity determinations generated together suggest that a single alpha1-adrenoceptor subtype mediates contractile responses of RBN to NA. Additional studies with phenylephrine indicated also an agonist-independence of this profile. Pharmacologically, this profile was reminiscent of that described as 'alpha1L'-adrenoceptor, which has been shown to mediate contractions of several tissues including lower urinary tract (LUT) tissues of man. Furthermore, a similarity was noticed between the 'alpha1L'-adrenoceptor described here in RBN and the rabbit and human cloned alpha1a-adrenoceptor (based on data from both whole cell radioligand binding at 37 degrees C and [3H]-inositol phosphates accumulation assays), characterizations of which have been published elsewhere. 4. In conclusion, the RBN appears to provide a predictive pharmacological assay for the study of NA-induced smooth muscle contraction in LUT tissues of man.

Adrenergic alpha-1 Receptor Antagonists↗
PubMed1998

Relationship between diet, dental calculus and periodontal disease in domestic and feral cats in Australia.

OBJECTIVE: To compare the dental calculus scores and prevalence of periodontal disease in domestic cats eating commercially available canned and dry foods with those in feral cats consuming a diet consisting of small mammals, birds, reptiles and insects. ANIMALS: Twenty-nine feral cats and 20 domestic cats were included in the study. PROCEDURE: A dental chart and dental calculus scores were recorded using the maxillary canine, maxillary third and fourth premolar, mandibular canine, mandibular fourth premolar and first molar teeth on both sides. Periodontal disease was recorded using gingival recession, increased periodontal pocket formation, radiographic alveolar bone loss, osteomyelitis, furcation and root exposure, and the presence of calculus as indicators. RESULTS: Dental calculus scores were significantly higher in domestic cats than in feral cats. There was no statistical difference in the prevalence of periodontal disease between the two groups. CONCLUSIONS: It can be inferred that diet may play a role in the accumulation of calculus, but a diet based on live prey does not protect cats against periodontal disease.

Animal Feed↗
PubMed1998

Inpatient group psychotherapy: the role of the staff nurse.

Inpatient groups are inherently different from outpatient groups and require modification in approach. Patients' needs, staff interests and expertise, and the needs of the health care system are major driving forces in the development of inpatient groups. A co-therapy model helps to achieve a balance between skills and abilities of the therapist.

Hospitalization↗