Search

Introduction: Parents have an important role ensuring their infants receive oral and medical health care. Their decisions affect the well-being of their children. Methods: This study used data collected from a longitudinal, prospective study with the aim of developing and validating a caries risk assessment tool. The objectives of this study are to ( a ) compare parents’ perceptions of how well they do in taking care of the infants’ teeth and/or gums versus how well they do in taking care of the infants’ medical health and ( b ) determine factors associated with parental perceptions of how well they do in taking care of the infants’ teeth and/or gums. Results: A total of 1323 parent/infant pairs were enrolled in the study at Duke University, Indiana University, and the University of Iowa. Through a survey, 283 (21%) of the parents perceived they did an excellent job of both taking care of both the infant’s oral and medical health, while 861 (65%) perceived the care of their infant’s medical health was better than their care of the teeth and/or gums. In the multivariable model, parents who perceived they provided excellent/very good/good care for the infants’ teeth and/or gums were more likely to brush the infant’s teeth daily, use toothpaste daily, clean inside the infant’s mouth and/or gums daily, and not let the infant have something other than water after brushing and prior to bedtime. Also, those with infants having Medicaid or State Insurance, parents not eating sugary snacks frequently, and parents getting dental checkups at least annually were likely to perceive that they provided excellent/very good/good care for their infant’s teeth and/or gums. Conclusions: Parents who provide good infant oral health care are more likely to perceive they provide good care and more likely to have better personal dental health behaviors. This agrees with previous studies concerning older children.

Objective: To implement a colon cancer screening program for uninsured or underinsured Iowans. Methods: All 1995 uninsured patients or patients with Iowa Care insurance aged 50 to 64 years attending the University of Iowa Clinic or the Iowa City Free Medical Clinic were mailed information about the project. Recruitment also took place in person, by having the clinic receptionist hand subjects a research packet, and through community posters. Individuals with colonic symptoms or who were up to date with screening were ineligible. Eligible subjects received a free fecal immunochemical test (FIT), and those with positive FITs were provided with a colonoscopy at no cost to them. Results: Of 449 individuals who completed eligibility forms (23% of the study population), 297 (66%) were eligible and were provided with an FIT. Two-hundred thirty-five (79%) returned a stool sample, with 49 (21%) testing positive. Thirty of the 49 (61%) individuals had a colonoscopy, and 20 individuals had at least 1 polyp biopsied. Thirteen individuals had at least 1 tubular adenoma; 2 had adenomas more than 1 cm in diameter, with no colon cancers identified. Face-to-face recruitment had the highest rate of returned FITs (72%) compared with handing the subject a research packet (3%) or a mailing only (9%) (Chi-square, P < .001). Conclusion: There was high interest in and compliance with colon cancer screening using a FIT among underinsured individuals. Although the FIT positivity rate was higher than expected, many individuals did not complete recommended follow-up colonoscopies. Population-based strategies for offering FIT could significantly increase colon cancer screening among disadvantaged individuals, but programs will have to develop sustainable mechanisms to include the necessary organization and address substantial costs of providing mass screening, as well as facilitating and providing colonoscopies for those who test positive.

Introduction: Intravenous platelet glycoprotein (GP) IIb/IIIa receptor inhibitors have a significant beneficial impact on the outcomes of patients undergoing high-risk coronary interventions and in the stabilization of patients with unstable angina pectoris refractory to conventional medical treatment. The role of long-term treatment with oral platelet GP IIb/IIIa receptor inhibitors in patients with coronary artery disease is unproven. This study examined the dose-response effect on inhibition of platelet aggregation by roxifiban (DMP754), a novel oral platelet GP IIb/IIIa receptor inhibitor, and its safety and tolerability in patients with a history of chronic stable angina pectoris., Methods: Ninety-eight patients were randomized to receive either a placebo or 1 of 8 oral dosages of roxifiban. Twenty-two patients were enrolled in multiple-dose regimens, bringing the total study population to 120. The oral dosages were 0.25, 0.5, 0.75, 1, 1.25, 1.5, 2, or 2.5 mg/day for up to 30 days., Results: Pharmacodynamic response of roxifiban was clearly dose-dependent. Platelet aggregation inhibition in response to 10 micromol/L slope adenosine diphosphate was sustained throughout the study period (up to 1 month). No serious adverse events, including significant major bleeding events, were associated with roxifiban treatment. Minor bleeding was reported in 5% of participants in the placebo group (1 of 21 cases) versus 26% in the study group (26 of 99 cases). Incidence of minor bleeding associated with roxifiban 2 and 2.5 mg/day was significantly (p < or = 0.05) greater than that with placebo. Adverse events, including gastrointestinal disorders, platelet and clotting disorders, and urinary tract disorders, were observed in 1 of 21 cases (5%) in the placebo group and in 12 of 99 cases (12%) in the study group. Reversible thrombocytopenia without other complications developed in two patients., Conclusions: Roxifiban-induced inhibition of platelet aggregation was dose-dependent and sustained throughout the study period: higher drug dosages correlated with higher levels of platelet inhibition and higher incidence of minor bleeding events. No serious adverse events were observed at any dosage. Thus, roxifiban appears to be a potent oral platelet GP IIb/IIIa receptor inhibitor that is clinically well-tolerated and deserves further study as a new treatment strategy in patients with chronic stable angina pectoris.

Thrombocytopenia is a relatively common side effect observed during glycoprotein (GP) IIb/IIIa antagonist therapy. With the oral antagonist roxifiban, we observed thrombocytopenia, defined as 50% reduction of platelets over predose values or below 90 000/microL (9 x 10(10)/L), with a frequency of 2% (8 of 386). Thrombocytopenia occurred either early (days 2 to 4) or delayed (days 11 to 16). No additional cases were observed with up to 6 months of treatment. Retrospective analysis provided evidence for drug-dependent antibodies (DDABs) to GP IIb/IIIa in 5 of 6 subjects, suggestive of an immune etiology of thrombocytopenia. The hypothesis that excluding patients based on positive DDAB reaction would reduce the frequency of thrombocytopenia was tested. Patients were screened for DDABs during the study qualification period and, overall, 3.9% of the patients were excluded based on pre-existing DDAB concentrations above a statistically defined medical decision limit. An additional 2.6% were excluded based on therapy-related antibody production during the first 2 weeks. With antibody testing, 0.2% of patients (2 of 1044) developed immune-mediated thrombocytopenia. One case developed a rapidly increasing antibody concentration and presented with thrombocytopenia despite discontinuation of roxifiban therapy. The second case was related to a false-negative test result. The frequency of thrombocytopenia was statistically significantly reduced from 2% to 0.2% (P =.0007) comparing nonscreened and screened patients. Testing for DDABs can reduce the frequency of thrombocytopenia in patients treated with roxifiban and, by analogy, other GP IIb/IIIa antagonists. Thus, DDAB testing may be employed to increase the safety of GP IIb/IIIa antagonists.

Glycoprotein (GP) IIb/IIIa antagonists are effective therapeutic agents, but elicit thrombocytopenia with a frequency that approaches 2%. Here, we provide evidence that thrombocytopenia in humans treated with the GP IIb/IIIa antagonist roxifiban is immune mediated. Two patients underwent conversion to a highly positive drug-dependent antibody (DDAB) status temporally associated with thrombocytopenia. Despite the continued presence of DDABs, the fall in platelet count was reversed by discontinuation of drug treatment, pointing to the exquisite drug dependency of the immune response. DDABs appear to bind to neoepitopes in GP IIb/IIIa elicited on antagonist binding. This information was used to develop an enzyme-linked immunosorbent assay (ELISA) for DDAB using solid-phase GP IIb/IIIa. A high level of specificity is indicated by the observation that DDAB binding is dependent on the chemical structure of the GP IIb/IIIa antagonist and that only 2% to 5% of human blood donors and 5% of chimpanzees present with pre-existing DDABs. Furthermore, none of 108 nonthrombocytopenic patients from the phase II roxifiban study showed an increase in antibody titer. Absorption of thrombocytopenia plasma with platelets reduced the DDAB ELISA signal, indicating that the test detects physiologically relevant antibodies. Screening patients for pre-existing or increasing DDAB titer during treatment with GP IIb/IIIa antagonists may reduce the incidence of drug-induced thrombocytopenia.

Objectives: This study explored the association between the initiation of hormone replacement therapy (HRT) and early cardiac events (<1 year) in women with a recent myocardial infarction (MI)., Background: Observational studies have linked postmenopausal hormone use with a reduced risk of death from heart disease. However, a recent randomized trial of HRT found no long-term benefit, primarily due to an increase in cardiac events in the first year., Methods: The Coumadin Aspirin Reinfarction Study (CARS) database contains information on HRT use and menopausal status for women with a recent MI. We classified the 1,857 postmenopausal women in CARS as prior/current HRT users if they took HRT before enrollment, new users if they began HRT during the study period or never users. We assessed the incidence of cardiac events (death, MI, unstable angina [UA]) during follow-up., Results: In our cohort, 28% (n = 524) used HRT at some point. Of these, 21% (n = 111) began HRT after their MI. New users had a higher incidence of death/MI/UA (41% vs. 28%, p = 0.001) during follow-up than never users, largely due to a higher incidence of UA (39% vs. 20%, p = 0.001). After adjustment, new users still had a significantly higher risk of death/MI/UA than never users during follow-up (relative risk [RR] = 1.44 [1.05-1.99]). Prior/current users had no excess risk of the composite end point after adjustment. Users of estrogen/progestin had a lower incidence of death/MI/UA during follow-up than users of estrogen only (RR = 0.56 [0.37-0.85])., Conclusions: Postmenopausal women who initiated HRT after a recent MI had an increased risk of cardiac events largely due to excess UA during follow-up.

Neuropeptide Y (NPY) has been shown to potentiate the response of the isolated rabbit ear artery to field stimulation, provided that the vascular endothelium is intact. This report describes efforts to elucidate the mechanism by which NPY produces this effect. The response of the perfused rabbit ear artery to brief intermittent field stimulation was significantly enhanced by NPY (100 nmol/L). The administration of indomethacin (10 mumol/L) to inhibit cyclooxygenase did not affect the ability of NPY to potentiate neurogenic vasoconstriction. Blockade of calcium channels with nifedipine (1 mumol/L) produced a partial attenuation of the NPY effect. Our studies therefore suggest that an arachidonic acid metabolite is not involved in NPY induced potentiation of vascular neuroeffector transmission in the rabbit ear artery. On the other hand, the translocation of extracellular calcium may play a role in this process.

We studied the possibility of multiple neuropeptide Y (NPY) receptor subtypes. NPY-stimulated Ca2+ mobilization in human erythroleukemia (HEL) cells was used to screen a number of NPY analogues. The potencies of three of these analogues [peptide YY (PYY), [D-Tyr-36]NPY, and NPY-(18-36)] were compared with that of NPY in the following model systems: Ca2+ mobilization and inhibition of adenosine 3',5'-cyclic monophosphate accumulation in HEL cells, potentiation of vasoconstriction in the isolated rabbit ear artery, reduction of cutaneous microvascular perfusion in the rat digit, and inhibition of [3H]serotonin release in rat brain. In each of the five models, PYY was a full agonist that exhibited a similar or slightly higher potency than NPY, whereas [D-Tyr-36]NPY and NPY-(18-36) were partial agonists with lower potencies: NPY-(18-36) had a lower potency and efficacy than [D-Tyr-36]NPY in HEL cells and the rabbit ear artery, but was more effective than [D-Tyr-36]NPY for constricting cutaneous microvasculature and inhibiting serotonin release. Because of its weak partial agonism, we also tested NPY-(18-36) as an antagonist of NPY-stimulated Ca2+ mobilization in HEL cells. NPY-(18-36) shifted the NPY concentration-response curve to the right with a KB affinity value of 297 nM. In summary, [D-Tyr-36]NPY and NPY-(18-36) are partial agonists, the relative potency of which varies between systems. These data demonstrate the presence of multiple NPY receptor subtypes. We propose a modified classification scheme of NPY receptor subtypes.

Although neuropeptide Y is not a potent vasoconstrictor in many vascular beds, nanomolar concentrations of this peptide can potentiate the response of isolated blood vessels to sympathetic stimulation or exogenous vasoconstrictors. Potentiation of the response to field stimulation was observed in superfused ring segments of rabbit ear artery or canine saphenous vein, provided that the endothelium was not mechanically damaged. The ability of neuropeptide Y to potentiate the constrictor response to noradrenaline in the ear artery was also dependent on the presence of an intact endothelium. The release of an endothelial-derived vasoconstrictor substance, as yet unidentified, by neuropeptide Y may explain its ability to potentiate the responses to both nerve stimulation and a variety of exogenous vasoconstrictors.

The effect of neuropeptide Y on the contractile response to field stimulation was examined in isolated blood vessels. Exogenous neuropeptide Y at a concentration of 100 nmol/l significantly potentiated the response to field stimulation in rabbit ear artery and canine saphenous vein. Administration of neuropeptide Y antiserum to tissues not previously exposed to neuropeptide Y significantly reduced the response to field stimulation; greater effects were observed in the rabbit ear artery than in the canine saphenous vein. Furthermore, this antiserum depressed the response to field stimulation in caudal arteries from spontaneously hypertensive rats (SHR), but not in those from normotensive Wistar-Kyoto rats (WKY). The depression by the anti-neuropeptide Y antibody did not appear to be produced by a non-specific mechanism, since antiserum against either thyrotrophin-releasing factor or platelet-derived growth factor did not affect the response to field stimulation. It is concluded that endogenous neuropeptide Y can contribute to the vascular contractile response to field stimulation, and that this contribution may be enhanced in hypertensive animals.

A series of alpha adrenoceptor antagonists, including both reference compounds and the novel benzazepine antagonists, SK&F 86466 (6-chloro-2,3,4,5-tetrahydro-3-methyl-1H-3-benzazepine) and two of its 9-substituted derivatives, SK&F 101253 and SK&F 104078, were tested in vitro for affinity at central and peripheral alpha adrenoceptor subtypes. Peripheral alpha-1 adrenoceptor antagonist potency of these agents, as assessed by the receptor dissociation constant (KB) against norepinephrine-induced contraction in the rabbit aorta, correlated with the Ki value for inhibition of [3H]prazosin binding to central alpha-1 adrenoceptors in rat brain homogenates. Central alpha-2 adrenoceptor affinity, measured as the Ki for inhibition of [3H]rauwolscine binding to rat brain homogenates, correlated well with antagonist activity at peripheral postjunctional alpha-2 adrenoceptors as reflected by the KB against B-HT 920-induced contraction in canine saphenous vein. The 9-substituted benzazepines, SK&F 101253 and SK&F 104078, produce preferential blockade of postjunctional vs. prejunctional alpha-2 adrenoceptors in peripheral models. The high affinity of SK&F 104078 for postjunctional alpha-2 adrenoceptors in the canine saphenous vein was confirmed by its ability to inhibit [3H]rauwolscine binding to postjunctional alpha-2 adrenoceptors in this tissue. The observation that the Ki values for these antagonists against [3H] rauwolscine binding correlate with their KB values at the postjunctional alpha-2 adrenoceptors, rather than those at the prejunctional neuroinhibitory alpha-2 adrenoceptor, suggests a pharmacologic similarity between the postjunctional vascular alpha-2 adrenoceptors and the central [3H]rauwolscine binding site.(ABSTRACT TRUNCATED AT 250 WORDS)

The effect of age on presynaptic alpha 2 adrenoceptor-mediated regulation of norepinephrine (NE) release was studied in hearts isolated from male Fischer 344 rats 6-, 12- and 24-months of age. Cocaine (10(-6)M) and metanephrine (10(-5)M) were added to the perfusion fluid separately and in combination to block neuronal and extraneuronal uptake mechanisms, respectively. The amount of NE overflow in the effluent was significantly lower with increasing age at any given frequency of nerve stimulation. Metanephrine increased NE overflow in heart preparations of 12- and 24-month-old animals only. Yohimbine, a selective alpha 2 adrenoceptor antagonist at concentrations of 10(-6)M and 3 x 10(-6)M significantly increased the amount of NE overflow only in the perfusion effluent of hearts isolated from 6-month-old animals. These results suggest that extraneuronal uptake mechanisms increase with age and that presynaptic alpha 2 adrenoceptor-mediated autoregulation of NE decreases with age. The findings could account, at least in part, for the decrease in adrenergic control of the heart shown to occur with age.

Although neuropeptide Y (NPY) is not a potent vasoconstrictor in many vascular beds, nanomolar concentrations of this peptide can potentiate the response of isolated blood vessels to sympathetic stimulation or exogenous vasoconstrictors. In the isolated perfused rabbit ear artery, NPY produces a concentration-related potentiation of the response to field stimulation. The potency of NPY in inducing potentiation of nerve-mediated vasoconstriction was not dependent on whether the NPY was administered intra- or extraluminally. In these perfused vessels the endothelium was intact. Similar potentiation of the response to field stimulation is also observed in superfused ring segments of rabbit ear artery, provided that the endothelium was not damaged mechanically. The response to field stimulation in the rabbit ear artery is mediated by the alpha-1 adrenoceptor; in contrast, stimulation induced contraction in the canine saphenous vein results from the activation of vascular alpha-2-adrenoceptors. Despite this difference, the effect of NPY in ring segments of canine saphenous vein was similar to that observed in the ear artery. NPY also produced an endothelium-dependent potentiation of the constrictor response to exogenous norepinephrine in superfused segments of both ear artery and saphenous vein. Although the NPY-induced potentiation of stimulation-induced vasoconstriction was not inhibited by indomethacin, suggesting that an arachidonic acid metabolite is not involved, the release of another endothelial-derived vasoconstrictor substance, as yet unidentified, by NPY may explain its ability to potentiate the responses to both nerve stimulation and a variety of exogenous vasoconstrictors.

The effect of age on the capacity of the right cardiac sympathetic nerve to release norepinephrine (NE) into perfusion effluent (NE overflow) was studied in hearts isolated from male Fischer 344 rats at 6, 12 and 24 months of age. The hearts were perfused through an aortic cannula with Krebs-Ringer solution and the cardiac sympathetic nerve was stimulated electrically with supra-maximal voltage at frequencies of stimulation that produced 20%, 50% or 80% of maximal NE overflow at each age. The content of NE in the perfusion effluent was measured by electro-chemical detection after alumina extraction and high-performance liquid chromatography separation. The NE overflow was significantly lower in hearts of 12- and 24-month-old animals compared to hearts from 6-month-old animals at each frequency of stimulation. In addition the frequency of stimulation necessary to produce 50% or 80% of maximal NE overflow was significantly greater in heart preparations from both 12- and 24-month-old animals compared to preparations from 6-month-old animals. Perfusion with cocaine (10(-6) M) significantly increased the quantity of NE in the effluent after nerve stimulation only in hearts from 12- and 24-month-old animals. Nevertheless, NE overflow remained significantly lower than that observed in hearts of 6-month-old animals. The results suggest that the capacity of the cardiac sympathetic nerve to release NE is diminished in 12- and 24-month-old animals. Furthermore, in these age groups an increase in neuronal uptake appears to reduce further the quantity of NE made available to the heart. These changes seem to occur by middle age and persist to senescence.