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R Garcia

Publications and source records attributed to R Garcia.

At least 181 records · Page 10Linked to original sources
PubMed1996

Assessing oral health-related quality of life: findings from the normative aging study.

The contribution of oral health to health-related quality of life (HQOL) has seldom been examined. This study was designed to develop and validate a measure of oral health-related quality of life (OHQOL), examine relations between OHQOL and HQOL, and explore OHQOL's relation to problem-based dental care utilization in a sample of 1,242 older men, using data gathered by a mail survey. Factor analysis of eight oral health items revealed that three items related to the impact of oral conditions on daily functioning defined a factor labeled OHQOL. Factor analysis of the HQOL items and these three OHQOL items showed that OHQOL represents a separate and independent factor. Correlational analyses supported the construct validity of the OHQOL measure: Men with better OHQOL scores reported less dental pain or discomfort, fewer eating problems, and less problem-based dental care utilization. Logistic regression analysis showed that the measures of dental pain and oral discomfort were related positively to utilization, whereas OHQOL was related negatively. These results suggest that OHQOL represents a separate and distinct facet of HQOL that is associated with dental care utilization. Thus they support the validity of the OHQOL construct and suggest its use in future studies of HQOL.

Aged↗
PubMed1996

Changes in synaptic excitability in the lateral septum associated with contextual and auditory fear conditioning in mice.

Synaptic excitability in the lateral septum (LS) was assessed electrophysiologically in freely moving mice either submitted to a painful stimulus (shock) or tested on two forms of conditioned fear: contextual conditioning and auditory cue conditioning. Only the amplitude of the N3 component of the two negative waves (N2 and N3) evoked by fimbrial stimulation displayed significant changes in these tests. Experiment 1 showed that both the painful stimulus and subsequent re-exposure (24 h later) to the conditioning foreground context induced significant and context specific decrease in the N3 amplitude. In Experiment 2, a phasic tone (conditioned stimulus: CS) was paired (paired group) with the footshock (unconditioned stimulus: US) or not (unpaired group) and, 24 h later, animals were re-exposed successively to the auditory cue and to the context. During the auditory cue test, only the paired group displayed significant freezing and this occurred only during presentation of the CS. In this group, however, a significant reduction in the N3 amplitude was only observed immediately after the cessation of the CS. During the context test, the percentage and time-course of freezing across the 10 mm session were similar in each group. However, in the unpaired group the N3 amplitude reduction was significant and outlasted the duration of the freezing behaviour itself. These results show that alterations in LS synaptic excitability may be dissociated from fear-induced freezing behaviour. We suggest that LS synapses are part of a brain circuit that predict if and when the US is going to occur.

Acoustic Stimulation↗
PubMed1996

Differential regulation of renal glomerular and preglomerular vascular angiotensin II receptors.

The activity of the renin-angiotensin system (RAS) can be influenced by sodium intake and angiotensin II (ANG II) infusion. It has been shown that ANG II can regulate the density of its receptors. Therefore, we investigated the regulation of glomerular and preglomerular vascular ANG II receptors by changes in RAS activity. Sprague-Dawley rats were fed a low- or high-sodium diet or were infused with nonpressor or pressor doses of ANG II for 7 days. ANG II receptor characteristics were determined by radioligand binding assays with use of ANG II antagonists losartan and PD-123319. AT1 was the only receptor type found in membrane preparations from all groups. Glomerular ANG II receptor characteristics in all groups were unchanged compared with their controls, whereas vascular receptor density was significantly downregulated by sodium restriction. We conclude that glomerular and preglomerular vascular ANG II receptors are differentially regulated such that AT1 receptors in preglomerular vessels can be regulated by changes in endogenous RAS. ANG II infusion did not induce any modification of either glomerular or vascular AT1 receptors, suggesting a predominant role of the endogenous local renal RAS.

Angiotensin II↗
PubMed1996

Effect of endothelin antagonism on blood pressure and vascular structure in renovascular hypertensive rats.

To investigate the potential pathogenic role of endothelin in blood pressure elevation and vascular hypertrophy in renovascular hypertensive rats, which present twofold elevations in endothelin-1 mRNA abundance in blood vessels, the response of blood pressure and vascular structure to chronic treatment with the endothelin receptor antagonist bosentan was evaluated. One-kidney, one clip (1K,1C) and two kidney, one clip (2K,1C) Goldblatt hypertensive rats were treated for 2 wk with bosentan (100 mg.kg-1.day-1) in their chow, and systolic blood pressure was measured by the tail-cuff method. Vascular structure was studied in small arteries mounted on a wire myograph. Treatment with bosentan did not result in a significant change in systolic blood pressure or in the structure of small coronary, renal cortical, mesenteric, or femoral arteries in 1K, 1C or in 2K, 1C hypertensive rats. In conclusion, modest (twofold) elevations of endothelin-1 gene expression in blood vessels in renovascular hypertension are not associated with hypotensive responses or regression of vascular hypertrophy during treatment with endothelin antagonists in contrast to what is found in deoxycorticosterone acetate salt hypertensive rats, which exhibit very dramatic increases in endothelin-1 expression (five-to eightfold) and do respond to endothelin antagonism with blood pressure lowering and regression of vascular hypertrophy. These small elevations of vascular endothelin-1 gene expression thus do not appear to indicate the presence of an endothelin component in blood pressure elevation in renovascular hypertension in rats.

Animals↗
PubMed1996

Periodontal disease and cardiovascular disease.

It is our central hypothesis that periodontal diseases, which are chronic Gram-negative infections, represent a previously unrecognized risk factor for atherosclerosis and thromboembolic events. Previous studies have demonstrated an association between periodontal disease severity and risk of coronary heart disease and stroke. We hypothesize that this association may be due to an underlying inflammatory response trait, which places an individual at high risk for developing both periodontal disease and atherosclerosis. We further suggest that periodontal disease, once established, provides a biological burden of endotoxin (lipopolysaccharide) and inflammatory cytokines (especially TxA2, IL-1 beta, PGE2, and TNF-alpha) which serve to initiate and exacerbate atherogenesis and thromboembolic events. A cohort study was conducted using combined data from the Normative Aging Study and the Dental Longitudinal Study sponsored by the United States Department of Veterans Affairs. Mean bone loss scores and worst probing pocket depth scores per tooth were measured on 1,147 men during 1968 to 1971. Information gathered during follow-up examinations showed that 207 men developed coronary heart disease (CHD), 59 died of CHD, and 40 had strokes. Incidence odds ratios adjusted for established cardiovascular risk factors were 1.5, 1.9, and 2.8 for bone loss and total CHD, fatal CHD, and stroke, respectively. Levels of bone loss and cumulative incidence of total CHD and fatal CHD indicated a biologic gradient between severity of exposure and occurrence of disease.

Alveolar Bone Loss↗
PubMed1996

Chronic angiotensin II antagonism with losartan in one-kidney, one clip hypertensive rats: effect on cardiac hypertrophy, urinary sodium and water excretion and the natriuretic system.

OBJECTIVE: To evaluate the effect of 7-day angiotensin II antagonism with losartan, an AT1-receptor antagonist, on systolic blood pressure, renal sodium and water excretion and on the atrial natriuretic factor system in one-kidney, one clip hypertensive rats. METHODS: The one-kidney, one clip hypertensive rats were separated into four groups: untreated (group 1), low-sodium diet (group 2), losartan (20 mg/kg orally, group 3) and low-sodium diet with losartan (group 4). All of the rats were kept in metabolic cages with urinary volume, urinary sodium level and water intake being evaluated daily. Body weight and blood pressure were assessed before treatment and at the end of the observation period. Renal glomerular and papillary atrial natriuretic factor receptors were assessed by radioligand binding experiments. RESULTS: No differences were observed either in body weight or in blood pressure between groups at the outset After 1 week, blood pressure was 184+/-4, 184+/-7, 170+/-5 and 78+/-8 mmHg, in groups 1, 2, 3 and 4, respectively. Group 3 rats failed to gain weight and had high urinary volume. In contrast, group 4 rats lost 15% of their original body weight. Both of the losartan-treated groups presented an apparently reduced cardiac hypertrophy but it was only clear in the low-sodium diet group. Both of the losartan-treated groups had high plasma renin activity. All of the three treated groups showed upregulation of glomerular and no changes in papillary atrial natriuretic factor receptors. Overall, mortality was 18, 27, 0 and 36% in groups 1, 2, 3 and 4, respectively. CONCLUSION: Losartan administration reduces blood pressure in one-kidney, one clip rats only when combined with a low-sodium diet. Both low-sodium diet and angiotensin II antagonism upregulate renal glomerular but not papillary atrial natriuretic factor receptors, suggesting a divergent regulatory mechanism.

Angiotensin Receptor Antagonists↗
PubMed1996

Comparison of fluorine-18-FDG PET and technetium-99m-MIBI SPECT in evaluation of musculoskeletal sarcomas.

UNLABELLED: We compared the diagnostic accuracy of [18F]FDG PET and 99mTc-MIBI SPECT in musculoskeletal sarcomas. METHODS: Forty-eight patients with clinically suspected recurrent or residual musculoskeletal sarcomas were examined with both FDG-PET and MIBI-SPECT within 2 wk of each study (one follow-up study in nine patients and we follow-up studies in one patient). Imaging findings were visually inspected with grading scales in conjunction with CT and/or MRI, and count-density ratios of lesion-to-contralateral area and standard uptake values (SUVs) of FDG and MIBI in lesions were also generated. The results were correlated with histologic findings (in 51 studies) and/or long-term follow-up evaluations. RESULTS: The diagnostic sensitivities and specificities were 98% and 90% using FDG, and 81.6% and 80% using MIBI, respectively, with statistical significance in the sensitivity. The tumors were demonstrated better in FDG studies, which produced higher visual grades (2.1 versus 1.6), and the tumors showed increasing SUVs with time (from 6.3 to 7.3). Four of nine patients with positive FDG but negative MIBI scans failed to respond to multidrug therapy. CONCLUSION: FDG-PET and MIBI-SPECT are useful in differentiating active sarcomas from post-treatment changes and in evaluating therapeutic response. MIBI-SPECT and FDG-PET findings should be interpreted in con junction with CT and/or MRI. FDG-PET shows statistically significant higher sensitivity than MIBI-SPECT. A positive FDG but negative MIBI scan might suggest a multidrug resistance.

Adult↗
PubMed1995

Characterization of endothelin receptor subtypes in isolated rat renal preglomerular microvessels.

Endothelin (ET) increases renal vascular resistance by constriction of post- and preglomerular vessels in the rat. However, ET receptor subtypes in renal microvessels have not been clearly defined. Radioligand binding experiments were performed in isolated arcuate and interlobular arteries as well as branching afferent arterioles to characterize 125I-ET-1 binding sites. Competitive inhibition assays were performed with ET-1, ET-2, ET-3, sarafotoxin 6b (S6b), BQ-123 (a preferential ETA receptor antagonist) and 4-Ala-ET-1 (a preferential ETB receptor agonist). Saturation data revealed a single class of high affinity binding sites with a kd of 0.31 +/- 0.03 nM and a Bmax of 1336 +/- 181 fmol/mg protein. Competitive inhibition of 125I-ET-1 binding showed that all assayed compounds displaced 125I-ET-1 in a dose-related manner. ET-1 displaced 100% of 125I-ET-1 binding, displaying monophasic curves with Bmax and kd values of 1369 +/- 170 fmol/mg protein and 0.35 +/- 0.04 nM, respectively. ET-2's displacement curves were similar to those of ET-1. ET-3 and S6b inhibited 100% of 125I-ET-1 binding in a biphasic manner, suggesting these peptides bind both high and low affinity sites. BQ-123 displaced about 50% of 125I-ET-1 in a monophasic manner, indicating a single high affinity binding site. 4-Ala-ET-1 displaced 125I-ET-1 in a clearly biphasic manner with an almost equal proportion of high and low affinity binding sites. Our results suggest that both ETA and ETB receptors are expressed in rat renal preglomerular vessels in almost equal proportions. However, the characteristics of competitive inhibition of 125I-ET-1 binding by several agents cannot be fully explained by a two-receptor model.

Animals↗
PubMed1995

Inertial, substratal and landmark cue control of hippocampal CA1 place cell activity.

Hippocampal 'place cells' discharge when a rat occupies a location that is fixed in relation to environmental landmarks. A principal goal of this study was to determine whether hippocampal place cell activity could be influenced by inertial cues. Water-deprived rats were trained in a square-walled open field in a dark room. The behavioral task required alternating visits to water reservoirs in the centre and in the four corners of the arena. The rat and arena were rotated in total darkness through +/-90, 180 or 270 degrees C. The next water reward was then presented in the corner at the same position relative to the outside room as before the rotation. A cue card was later illuminated in this corner as a visual cue for the extra-arena (room) reference frame. Fifteen out of 97 recorded hippocampal CA1 complex spike cells had spatially selective discharges in non-central parts of the arena. After arena rotations, the firing fields of three units shifted between corners of the arena to maintain a fixed orientation relative to the room. This indicates that the hippocampus updated its representation of the position and heading direction of the rat using vestibular-derived inputs concerning rotation angle. Other spatially selective discharges were guided to landmark cues (cue card or position of the reward: two units) or arena-locked 'substratal' cues (eight units). In six cells, place cell activity suddenly ceased or appeared following rotations. These results provide evidence for contributions of inertial as well as substratal and landmark information to hippocampal spatial representations.

Animals↗
PubMed1995

Pharmacological and biochemical profiles of unique neurotensin 8-13 analogs exhibiting species selectivity, stereoselectivity, and superagonism.

Recently, the rat neurotensin receptor and the two human neurotensin receptor clones (differing by one amino acid residue) have been isolated. We present results with 33 newly synthesized neurotensin analogs. We have evaluated their binding potency at the three neurotensin receptor clones by determining equilibrium dissociation constants and coupling to phosphatidylinositol turnover. Our work focused on position 8 and 9 substitutions as well as position 11 of the neurotensin hexamer NT8-13. The results presented include: 1) the development of a compound that is species selective, with a binding potency at the rat receptor that is 20-fold more potent than at the human receptor; 2) the development of a pair of stereoselective compounds with the L-isomer exhibiting 190-700-fold more potency than the D-isomer; and 3) the development of an agonist that has a Kd of 0.3 and 0.2 nM at the human and rat neurotensin receptor, respectively, ranking it as among the most potent tested. Also, we present the first evidence that 1) the effect of pi electrons at position 11 (L-Tyr) are important for binding to the neurotensin receptor, and 2) the length of the side chain on position 9 (L-Arg) changes binding potency.

Amino Acid Sequence↗
PubMed1995

Phase I/II study of intravitreal cidofovir for the treatment of cytomegalovirus retinitis in patients with the acquired immunodeficiency syndrome.

PURPOSE: In this study we evaluated the safety and efficacy of the nucleoside phosphonate analogue intravitreal cidofovir to treat cytomegalovirus retinitis in humans. METHODS: We conducted a phase I/II unmasked consecutive case series in a single-center institutional referral practice. Eligible patients with the acquired immunodeficiency syndrome had active cytomegalovirus retinitis in at least one eye, despite adequate intravenous therapy with ganciclovir or foscarnet, were intolerant to intravenous therapy, were noncompliant with intravenous therapy, or refused intravenous therapy. In a preliminary safety study (Group 1), ten eyes of nine patients received 14 injections of cidofovir while being treated concurrently with intravenous ganciclovir. In a dose-escalating efficacy study (Group 2), eight eyes of seven patients received 11 injections of cidofovir as sole treatment for cytomegalovirus retinitis. The primary outcome was time to retinitis progression. RESULTS: In the Group 1 eyes receiving 20 micrograms of cidofovir, the median time to retinitis progression was between 49 and 92 days (mean, 78 days). In Group 2 eyes treated with 20 micrograms cidofovir, the median time to retinitis progression was 64 days (mean, 63 days). Hypotony occurred in the two eyes treated with a 100-micrograms dose of cidofovir and in one of three eyes receiving a 40-micrograms dose. No adverse effects resulted from the remaining 20 cidofovir injections. CONCLUSIONS: Cidofovir (also known as HPMPC) appears to be safe and effective for the local treatment of cytomegalovirus retinitis, providing a long duration of antiviral effect. These preliminary results indicate that additional studies should be performed to investigate more fully this promising medication.

AIDS-Related Opportunistic Infections↗
PubMed1995

Cardiac endothelin-1 content and receptor subtype in spontaneously hypertensive rats.

Endothelin-1 (ET-1), a newly discovered peptide with potent vasoconstrictor and growth-promoting effects, has been implicated in high blood pressure and cardiac hypertrophy in the spontaneously hypertensive rat (SHR). In the present study, we measured plasma ET-1 levels and tissue ET-1 concentrations in the four cardiac chambers of 17- to 18-week-old SHR and their normotensive controls. Wistar Kyoto (WKY) rats. SHR had slightly but significantly higher plasma ET-1 levels than WKY. The ventricles had the highest ET-1 content and the atria in both strains had the highest ET-1 concentrations. ET receptor subtypes were analysed by radiogand binding with ET-1, BQ-123 and IRL 1620 in crude membrane preparations of the four cardiac chambers. No differences in receptor subtype densities or affinities were apparent between the two strains. ET(A) represented 75 to 85% of both ET receptors. Competition analysis revealed that in both strains left ventricular tissue had lower receptor densities and higher affinities than the atria. These results suggest that ET-1 and its receptor although contributing in the maintenance of high blood pressure may not be an important factor during stable cardiac hypertrophy in adult SHR. The differential distribution of ET-1 content and receptor densities favoring the atria in both strains suggest that this peptide may have a different physiological role in the atria from that in the ventricles.

Animals↗
PubMed1995

Localization of atrial natriuretic factor receptors in the mesenteric arterial bed. Comparison with angiotensin II and endothelin receptors.

Although receptors for atrial natriuretic factor (ANF) and angiotensin II (Ang II) have been reported in rat mesenteric arteries, both peptides induce weak biological responses. Endothelin-1 (ET-1) evokes a potent vasoconstriction in the mesenteric artery. To identify the tissue localization of ANF, Ang II, and ET-1 receptors, radioligand binding experiments with 125I-ANF, 125I-[Sar1,Ile8]Ang II, and 125I-ET-1 were performed in defatted mesenteric arteries and in the surrounding adipose tissue. 125I-ANF binding assays in adipose tissue showed a single class of high-affinity binding sites (Bmax, 420 +/- 16 fmol/mg protein; Kd, 343 +/- 16 pmol/L). In vascular membranes, most 125I-ANF binding was nonspecific. The majority of receptors present in adipose tissue recognized ANF, C-type natriuretic peptide (CNP), and des-[Gln18,Ser19,Gly20,Leu21,Gly22]ANF-(4- 23) (C-ANF) with close affinities, with C-ANF competing for > 98% of the binding sites. In adipocytes, ANF and CNP stimulated cGMP generation. cGMP production by mesenteric arteries was stimulated by sodium nitroprusside but not by ANF or CNP. Autoradiographic localization of 125I-ANF and 125I-ET-1 showed that in the case of ANF, most specific binding occurred in adipocytes, whereas for ET-1, specific binding was present in both adipose tissue and mesenteric arteries. Cross-linking of 125I-ANF followed by SDS-PAGE revealed two receptor species of 130 and 70 kD in adipose membranes and none in vascular tissue. Both were completely displaced by ANF, CNP, and C-ANF. 125I-[Sar1,Ile8]Ang II binding assays in adipose tissue exhibited a single class of binding sites (Bmax, 211 +/- 4 fmol/mg protein; Kd, 520 +/- 10 pmol/L.(ABSTRACT TRUNCATED AT 250 WORDS)

Adipose Tissue↗
PubMed1995

Effect of component fixation method on osteolysis in total knee arthroplasty.

Eighty-three total knee arthroplasties done at a single university hospital were reviewed specifically to examine the presence of lysis. Components that were radiographically loose were excluded. The incidence of lysis varied significantly with the method of component fixation. The highest incidence of lysis (30%) was seen when the tibial component was fixed with cement and screws and the femoral component was implanted without cement. When the tibial component was fixed with cement and screws and the femoral components was cemented, the incidence of lysis was 13% (2 of 13). When the femoral component was press fit and the tibia was cemented without screws, the incidence of lysis was 10% (1 of 10). When the femoral and tibial components were cemented and no screws were used, the incidence of lysis was 0 (0 of 12). Using screws with cement to fix the tibial component was associated with a high incidence of lysis and cannot be recommended. A press fit femoral component also may contribute to the incidence of lysis.

Aged↗