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Postprandial blood pressure changes during hemodialysis.

The effect of eating on BP during hemodialysis was examined in nine nondiabetic end-stage renal disease (ESRD) patients. A standard meal was given during 62 of 125 dialysis treatments in a prospectively controlled study. Diastolic (P = 0.01) and mean (P = 0.03) BPs fell significantly faster in the 45-minute postprandial period in the fed treatments compared with equivalent times in the fasting treatments. In this period, symptomatic hypotension occurred 13 times in five patients fed during dialysis compared with two episodes in one patient while fasting (P less than 0.05). Consumption of meals during hemodialysis should be avoided in patients at risk for hypotension during treatment.

Adult↗

The effect of red cell transfusion on hemodialysis-related hypotension.

Blood pressures of 25 stable end-stage renal disease patients with chronic anemia (mean hemoglobin 5.9 g/dL) who had received 2 units of packed red cells during hemodialysis were studied. Three treatments preceding and three following the transfusion dialysis were compared. Twenty-eight hypotensive episodes preceded and 12 followed transfusion (P = .02). Intravenous sodium chloride used for hypotension declined from a mean of 20.4 to 10.2 mEq per dialysis (P = .01). The rate of decline in mean arterial pressure during dialysis was significantly slower following transfusion (P less than .01). Mean postdialysis weight fell from 62.0 kg before transfusion to 61.5 kg following transfusion (P less than .001). Thus, red cell transfusion raises intradialytic pressure and reduces the frequency of intradialytic hypotension.

Adult↗

Magnesium sulfate in the treatment of refractory ventricular fibrillation in the prehospital setting.

OBJECTIVE: To determine if magnesium sulfate (MgSO(4)) improves outcome in cardiac arrest patients initially in ventricular fibrillation (VF). METHODS: Randomized, prospective, double blind, placebo-controlled, multicenter prehospital trial using 2 g of MgSO(4). Eligible patients were non-traumatic cardiac arrest patients (> or =18 years of age) presenting in VF. The protocol included those patients refractory to three electroshocks. Epinephrine and either 2 g of MgSO(4) or placebo (normal saline) were then administered. The primary outcome variable was return of spontaneous circulation (ROSC) in the field and a perfusing pulse on arrival at the ED. Secondary endpoints included admission to the hospital (ADMT) and hospital discharge (DISC). IRB approval was obtained at all participating centers. RESULTS: Total 116 patients (58 MgSO(4), 58 placebo) were enrolled during the period from 4/1992 to 10/96 with 109 available. There were no significant differences between the groups in baseline characteristics and times to cardio pulmonary resuscitation (CPR), advanced life support (ALS), and first defibrillation, except for time to study drug administration. There was no significant differences in ROSC (placebo, 18.5%, and MgSO(4), 25.5%, P=0.38), ADMT (placebo rate=16.7%, MgSO(4)=16.4%, P=1.0) or DISC (placebo rate=3.7%, MgSO(4)=3.6%, P=1.0). CONCLUSIONS: We failed to demonstrate that the administration of 2 g of MgSO(4) to prehospital cardiac arrest patients presenting in VF improves short or long term survival.

Adolescent↗

Structure and juvenile hormone-mediated regulation of the HMG-CoA reductase gene from the Jeffrey pine beetle, Dendroctonus jeffreyi.

In several pine bark beetle species, juvenile hormone (JH) III regulated 3-hydroxy-3-methylglutaryl coenzyme A reductase (HMG-R) gene expression has an important role in monoterpenoid pheromone production in males. We investigated the structure and regulated expression of the HMG-R gene (HMG-R) in the Jeffrey pine beetle, Dendroctonus jeffreyi. cDNA and genomic sequences were recovered using a combination of library screening and PCR. The transcribed portion of the gene spans 9.8 kb and is interrupted by 13 introns. When compared to vertebrate HMG-Rs, the distribution of intron sites suggests a functional role for those in the 5' untranslated region and membrane anchor domains. Northern blots show that topically applied JH III stimulates HMG-R expression up to 30-fold in male D. jeffreyi, compared to untreated insects, in both a dose- and time-dependent manner. There was no increase in expression levels in similarly treated female insects. The expression pattern is consistent with the production of monoterpenoid pheromone components in male D. jeffreyi, and suggests the utility of the system as a new tool for studying the mechanism of JH action.

5' Untranslated Regions↗

Human locognosic acuity on the arm varies with explicit and implicit manipulations of attention: implications for interpreting elevated tactile acuity on an amputation stump.

In Experiment 1, normal subjects' ability to localize tactile stimuli (locognosia) delivered to the upper arm was significantly higher when they were instructed explicitly to direct their attention selectively to that segment than when they were instructed explicitly to distribute their attention across the whole arm. This elevation of acuity was eliminated when subjects' attentional resources were divided by superimposition of an effortful, secondary task during stimulation. In Experiment 2, in the absence of explicit attentional instruction, subjects' locognosic acuity on one of three arm segments was significantly higher when stimulation of that segment was 2.5 times more probable than that of stimulation of the other two segments. We surmise that the attentional mechanisms responsible for such modulations of locognosic acuity in normal subjects may contribute to the elevated sensory acuity observed on the stumps of amputees.

Adolescent↗

Tachykinins may modify spontaneous epileptiform activity in the rat entorhinal cortex in vitro by activating GABAergic inhibition.

The effects of substance P and related tachykinins on intrinsic membrane properties and synaptic responses of neurons in cortical slices were determined. Substance P had no detectable effect on membrane properties of principal neurons in layer II or V of the rat medial entorhinal cortex or on neurons in either layer of the anterior cingulate cortex. Specific agonists at the neurokinin1-receptor were also without effect as were agonists at both neurokinin1- and neurokinin3-receptors. Substance P hyperpolarized a small number of principal neurons. These responses were weak and desensitized with repeated applications. Similar effects were seen with other neurokinin1-receptor agonists. Excitatory synaptic potentials mediated by either alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionate- or N-methyl-D-aspartate-receptors in principal neurons of the entorhinal cortex were unaffected by substance P. Responses of entorhinal neurons to iontophoretically applied glutamate and N-methyl-D-aspartate were also unaffected. Inhibitory synaptic potentials mediated by either GABA(A)- or GABA(B)-receptors in entorhinal neurons were slightly but consistently enhanced by substance P. Neurons identified as interneurons on the basis of their firing characteristics were consistently depolarized by substance P. These responses also desensitized with repeated applications. Spontaneous epileptiform discharges evoked in entorhinal cortex by perfusion with a GABA(A)-receptor antagonist (bicuculline), were reduced in frequency and, sometimes, in duration by substance P. This effect was mimicked by other neurokinin1-receptor agonists and blocked by neurokinin1-receptor antagonists. It was also mimicked by neurokinin A but not by a specific neurokinin1-receptor agonist. The reduction in frequency of discharges was also mimicked by a GABA(B)-receptor agonist, L-baclofen, and blocked by the GABA(B)-receptor antagonist, CGP55845A. Neurokinin B, and a specific neurokinin1-receptor agonist (senktide), increased the frequency and (sometimes) duration of epileptiform discharges. Substance P could also increase frequency but this usually succeeded or preceded a decrease in frequency. The effect of neurokinin B was reduced by a metabotropic glutamate receptor antagonist. Substance P appears to have little direct effect on principal neurons of the entorhinal cortex but may hyperpolarize them indirectly by activating interneurons and releasing GABA. This indirect inhibition may be responsible for the ability of substance P to reduce the frequency of epileptiform discharges in the entorhinal cortex and may suggest that neurokinin1-receptor agonists have potential as anticonvulsant drugs.

Animals↗

Multiple modes of inner hair cell stimulation.

Most current theories of cochlear mechanics assume that the pattern of cochlear partition vibration is simple, similar to that of a bending beam. Recent evidence suggests, however, that the vibration of the organ of Corti can be complex and that multiple vibrational modes may play an important role in cochlear transduction. Inner hair cell (IHC) and auditory nerve responses to pure tones can exhibit large phase shifts and complex response waveforms with increasing stimulus level. In contrast, the comparable basilar membrane (BM) responses are much less complex, exhibiting only small phase shifts and relatively sinusoidal waveforms. To reconcile the differences observed between the published BM data and the IHC data, we have recorded receptor potentials from IHCs and compared these waveform data to the output of two computational models: a traditional linear model where IHC excitation depends only on BM displacement and a new model that assumes that outer hair cell (OHC) force production provides the major mechanical input to the IHC along with two additional mechanical components. Comparisons of the output of the two models with the experimental data show that the new model is capable of reproducing the very complex voltage responses of the IHC recorded in vivo whereas the traditional model performed poorly.

Acoustic Stimulation↗

A saccular origin of frequency tuning in myogenic vestibular evoked potentials?: implications for human responses to loud sounds.

Previous research has indicated that an early component of click-evoked myogenic potentials in the sternocleidomastoid muscle is vestibularly mediated, since it can be obtained in subjects with loss of cochlear function, but is absent in subjects with loss of vestibular function (Colebatch et al., 1994). We report here the results of an experiment to investigate whether this response shows any tuning properties. In a sample of 11 subjects, we obtained acoustically evoked EMG from the sternocleidomastoid muscle in response to 110 dB SPL 10 ms tone pips with frequencies of 100 Hz, 200 Hz, 400 Hz, 800 Hz, 1600 Hz and 3200 Hz. The results of this experiment indicate that this response does indeed have a well-defined frequency tuning which may be modelled as a resonance with a maximum response at frequencies between 300-350 Hz. The possible saccular origin of the tuning response and the consequences that this may have in human responses to loud sounds is discussed. Also discussed are the consequences of particular electrode arrangements in relation to the innervation and anatomy of sternocleidomastoid.

Acoustic Stimulation↗

Evaluation of the clinical usefulness of C. difficile toxin testing in hospitalized patients with diarrhea.

Although numerous studies have evaluated the sensitivity and specificity of different assays for Clostridium difficile toxin, none has evaluated how physicians utilize these tests or respond to test results. Therefore, we assessed patient characteristics, clinical findings, and physician responses to positive and negative assay results at two university-affiliated hospitals, one of which used a cell cytotoxicity assay to test for C. difficile toxin and the other of which used an enzyme immunoassay. Two hundred one patient samples at Hospital A and 199 samples at Hospital B were assessed. Positive toxin assays were more frequent at Hospital A than at Hospital B (p < 0.001), at least in part due to the fact that patients tested at Hospital A were more likely to have fever (p < 0.001), an abnormal abdominal exam (p < 0.001), an abnormal leukocyte count (p < 0.001), and a history of prior antibiotic use (p < 0.001). Empiric therapy for C. difficile before results of the toxin assay was more common (p < 0.001) at Hospital A (83/201, 41. 3%) than at Hospital B (25/199, 12.5%). Once empiric therapy was started, most physicians continued therapy despite negative test results (Hospital A, 76%; Hospital B, 69%). Patients who were treated empirically were more likely than patients not treated empirically to have positive toxin assay results and to have fever (p < 0.001), an abnormal abdominal exam (p = 0.003), or an abnormal leukocyte count (p < 0.05). Physicians seldom ordered repeat toxin assays (Hospital A, 14%; Hospital B, 10%) if the initial assay result was negative. In logistic regression analysis, predictors of a positive toxin assay were prior antibiotic therapy, an abnormal abdominal exam, residence at Hospital A, and age >/= 60 years. Predictors of empiric therapy were residence at Hospital A and prior antibiotic therapy. Because physicians electing to empirically treat inpatients with diarrhea rarely alter therapy based on C. difficile toxin assay results, a more cost-effective management strategy may be not to obtain a toxin assay at all in such situations. Testing should be limited to patients who have received antibiotics within the prior month and who have significant diarrhea and/or abdominal pain.

Bacterial Toxins↗

The treatment of diastolic heart failure.

Recommendations for the treatment of diastolic heart failure must be based on theoretical issues. Evidence-based outcomes from clinical trials are not available at this time, but there is an increasing mandate for more focused studies for this clinical disorder. Meaningful outcomes require delineation of patient populations, including identification of underlying disease and comorbid cardiovascular disorders. Until such information is available, we must rely on an understanding of the natural history of associated disorders, extrapolation of treatment strategies that are successful for systolic heart failure management, and use of pharmacologic agents that empirically target the observed hemodynamic abnormalities of diastolic heart failure.

Animals↗

Evaluation of a long-acting converting enzyme inhibitor (enalapril) for the treatment of chronic congestive heart failure.

Converting enzyme inhibition of the renin-angiotensin system has proved a valuable therapeutic approach in patients with severe chronic congestive heart failure. In the present study, a new long-acting converting enzyme inhibitor (enalapril) was evaluated with acute single dose testing (10, 20 or 40 mg) in nine patients with severe chronic congestive heart failure. Four hours after administration, there was a significant reduction of systemic vascular resistance (-19%) and pulmonary wedge pressure (-19%); in addition, there were related increases of cardiac index (+16%) and stroke index (+19%) (probability [p] less than or equal to 0.05 for all changes). This was associated with an increase of plasma renin activity (9 +/- 3 to 35 +/- 11 ng/ml per hour) and a decrease of plasma aldosterone (19 +/- 4 to 9 +/- 2 ng/100 ml) (p less than 0.02 for both). With long-term therapy (1 month), there was improvement of exercise tolerance time and lessening of symptoms based on the New York Heart Association classification. Hemodynamic improvement was maintained in most, but not all, patients. There was no orthostatic hypotension during head-up tilt and hemodynamic values in the upright position were associated with normalization of intracardiac pressures. Long-term converting enzyme inhibition was indicated by a persistent increase of plasma renin activity (16 +/- 2 ng/ml per hour) and a decrease of plasma aldosterone (8 +/- 3 ng/100 ml). In addition, relative angiotensin II receptor occupancy was decreased as judged by the pharmacodynamic response to infusion of the angiotensin II analog saralasin. In conclusion, the long-acting converting enzyme inhibitor, enalapril, was effective in patients with chronic congestive heart failure; however, additional studies will be necessary to further delineate the optimal dose range and identify those patients who are most likely to respond to the drug.

Administration, Oral↗

Milrinone in congestive heart failure: acute and chronic hemodynamic and clinical evaluation.

Acute and chronic hemodynamic and clinical responses to milrinone, a new oral inotrope-vasodilator agent, were evaluated prospectively in 37 patients with severe congestive heart failure. The majority of patients (n = 31) had not responded to prior vasodilator therapy, with a substantial number (n = 8) requiring intravenous inotropic support at the time of initial study. All patients showed acute hemodynamic improvement with oral milrinone, and an optimal maintenance dose was chosen for each patient during dose-ranging studies (average dose 48 mg/day). Milrinone was discontinued before follow-up hemodynamic study in 12 patients (because of worsening congestive heart failure in 6 patients, sudden death in 3 patients, arrhythmia in 1 patient and refusal by 2 patients). Hemodynamic effects of milrinone both acutely and after chronic therapy (average 37 days) were compared in the remaining 25 patients. Acutely, mean cardiac index increased from 1.9 +/- 0.5 to 2.5 +/- 0.5 liters/min per m2 (p less than 0.001), and mean pulmonary capillary wedge pressure decreased from 28 +/- 9 to 18 +/- 8 mm Hg (p less than 0.001). When oral milrinone was readministered after chronic therapy, mean cardiac index increased from 1.9 +/- 0.5 to 2.5 +/- 1.7 liters/min per m2 (p less than 0.001), and pulmonary capillary wedge pressure decreased from 27 +/- 8 to 20 +/- 8 mm Hg (p less than 0.001) at 1 hour. New York Heart Association functional class improved in 18 of the 25 patients treated over a long-term period (mean 5.5 +/- 2.3 months).(ABSTRACT TRUNCATED AT 250 WORDS)

Actuarial Analysis↗

Systemic and pulmonary hemodynamic responses to nicardipine during graded ergometric exercise in patients with moderate to severe essential hypertension.

In 10 patients with moderate to severe hypertension, the hemodynamic effects of ergometric exercise and nicardipine, a dihydropyridine calcium channel antagonist, were characterized under basal conditions and after 1 week of therapy. The responses of plasma renin activity and catecholamines were also assessed. Nicardipine induced significant reductions of systolic, diastolic and mean blood pressure under conditions of rest and peak exercise (p less than 0.001), mediated by reversal of vasoconstriction (p less than 0.001). Overall, cardiac index and stroke volume index responses were not significantly altered by nicardipine. Although rest pulmonary wedge pressure was unchanged (6 +/- 3 to 5 +/- 4 mm Hg), peak exercise pulmonary wedge pressure decreased from 24 +/- 22 to 7 +/- 5 mm Hg (p less than 0.001) with nicardipine therapy. This effect of nicardipine on pulmonary wedge pressure was present across all work loads studied, and was accompanied by reduction of peak exercise pulmonary artery pressure from 43 +/- 10 to 25 +/- 7 mm Hg (p less than 0.001). Oxygen consumption was unchanged, associated with reduction of arteriovenous oxygen difference (p less than 0.02). Both plasma renin activity (p less than 0.05) and norepinephrine (p less than 0.005) were significantly increased with nicardipine therapy. Thus, nicardipine produced significant blood pressure reduction by reversal of vasoconstriction in patients with essential hypertension. The preservation of cardiac output, with markedly reduced pulmonary wedge pressure, indicated that nicardipine improved ventricular performance in response to reversal of vasoconstriction.

Adult↗

Age-related differences in diagnoses within the elderly population.

The most common diagnoses of elderly patients in the emergency department (ED) were compared among three age subgroups: 65 to 74, 75 to 84, and 85 and older. The computerized billing records for patient visits to 10 northern New Jersey hospital EDs for the years 1985 to 1991 were retrospectively analyzed. The most frequently occurring ICD-9-CM codes for elderly patients were compared among the three age subgroups. Elderly persons comprised 174, 146 (14% of the total) patient visits. The 176,146 patient visits were assigned 259,440 ICD-9-CM codes. The most common ICD-9-CM codes for medical diagnoses included chest pain, cardiac dysrhythmias, congestive heart failure, syncope, abdominal pain, and dyspnea. Fractures, particularly of the lower limb and upper limb; contusions; open wounds, particularly of the head, neck, and trunk; and falls were among the most common trauma diagnoses. The proportions in the three age subgroups of each diagnosis were statistically significantly different, except for cardiac arrest and contusions of the trunk and of multiple sites. The diagnoses with clinically significant higher relative risks in older age subgroups were atrial fibrillation, congestive heart failure, syncope, hypovolemia/dehydration, gastrointestinal hemorrhage, dyspnea, pneumonia, pulmonary edema, cerebrovascular accident, septicemia, urinary tract infection, fractures, and open wounds of the head, neck, trunk, particularly the scalp, and falls. Clinically significant lower relative risks were found in older age subgroups for chest pain, acute myocardial infarction, hypertension, angina, chronic airway obstruction not elsewhere classified, epistaxis, contusions of the upper limb, and open wounds of the finger.

Age Factors↗

The effect of long-term methylprednisolone treatment on the femoral head in growing pigs.

The effect of long term steroid treatment on coagulation, intraosseous pressure (IOP), femoral head (FH) blood flow, and histology in the normal organism was investigated in this study in growing pigs. From 24 growing female Danish Landrace pigs from 12 litters, 12 animals daily received 100 mg methylprednisolone orally for three months. Their 12 sister pigs served as controls without steroid treatment. Prothrombin time, activated partial thromboplastin time (aPTT), fibrinogen, and antithrombin III levels were recorded in jugular venous blood. Blood flow of the hip regions was measured by means of the radioactive microsphere technique. Metaphyseal and epiphyseal IOP of the left or right proximal femur were measured. Histomorphometry of the left or right FH epiphysis was performed. Major growth inhibition was found in the corticosteroid (CS) treated group. In CS pigs, aPTT was shortened to 50% compared to control pigs. Plasma fibrinogen was higher in the CS animals. Total FH blood flow was not different while regional blood flow in the cranial subregion of the FH epiphysis was higher in the CS group. Metaphyseal and epiphyseal IOP of the proximal femur were not different in the CS animals. Histomorphometrically, cancellous bone volume (23 +/- 1% vs. 34 +/- 2%; p < 0.001) and bone turnover (10 +/- 2% vs. 55 +/- 8%; p < 0.001) of the FH epiphysis was lowerin the CS than in the control group. The FH epiphysis of the CS animals invariably showed an irregular cartilage-bone interface with cartilaginous projections into the subchondral bone mainly in its cranial part. In normal growing pigs, long term high dose CS treatment has induced a hypercoagulable state of plasma via the intrinsic pathway of coagulation, cartilaginous projections into FH subchondral bone, FH osteopenia, and reduced bone turnover. Long-term steroid treatment did not produce FH necrosis or FH IOP alterations in the immature pig model.

Animals↗

Structural and functional magnetic resonance imaging of autism.

Magnetic resonance imaging (MRI) of brain structures and function is uniquely suited to characterize the range of neuroanatomical and physiological changes that characterize the autism phenotype as it develops over time. In this review, we examine the scientific literature in MRI as applied to autism and related areas, over approximately the last decade, discussing findings which have emerged, methodological stumbling blocks which have been identified, and potential future directions. Structural MRI studies have recently begun to elucidate the neurodevelopmental underpinnings and brain-behavior relationships in autism while fMRI studies, building on the wealth of data in normal individuals, are beginning to characterize the underlying neuropsychological deficits of the disorder. Together, these two methods combine to contribute to a better understanding of the neural basis and brain phenotype of this disorder.

Autistic Disorder↗