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Biomedical subjects

F L Sax

Publications and source records attributed to F L Sax.

16 recordsLinked to original sources

Hypertension and renal failure in a patient with tuberous sclerosis.

The cause of hypertension in this patient with tuberous sclerosis appeared to be the result of volume expansion due to renal failure. Renal insufficiency was presumably caused by extensive replacement of renal parenchyma with angiomyolipomas, resulting in compression and distortion of the renal parenchyma. Noninvasive imaging techniques were the most useful for characterizing the extent of the disease. It is clearly important to monitor renal function and blood pressure of patients with tuberous sclerosis as they grow older.

Adult

Left ventricular hypertrophy and impaired diastolic filling in essential hypertension. Diastolic mechanisms for systolic dysfunction during exercise.

Left ventricular ejection fraction is normal at rest but may respond abnormally to exercise in many patients with essential hypertension. To assess the determinants of the abnormal ejection fraction response to exercise, we performed radionuclide angiography at rest and during exercise in 41 hypertensive patients without coronary artery disease. In 22 patients (group 1), the ejection fraction increased more than 5% during exercise; in the other 19 patients (group 2), the ejection fraction either increased by less than 5% or decreased with exercise. Left ventricular diastolic filling was impaired at rest in patients in group 2 compared with group 1, with reduced peak filling rate (2.5 +/- 0.4 vs. 3.1 +/- 0.7 end-diastolic volume/sec; p less than 0.01) and prolonged time to peak filling rate (175 +/- 28 vs. 153 +/- 22 msec; p less than 0.01). Impaired diastolic filling in group 2 was associated with less augmentation in end-diastolic volume during exercise compared with group 1 (p less than 0.01). These observations were not dependent on the threshold value that was arbitrarily chosen to define an abnormal ejection fraction response, as there were significant correlations for the entire group between the magnitude of change in ejection fraction with exercise and both the resting peak filling rate (r = 0.46) and the change in end-diastolic volume with exercise (r = 0.62).(ABSTRACT TRUNCATED AT 250 WORDS)

Cardiomegaly

Calcium-antagonist receptors in the atrial tissue of patients with hypertrophic cardiomyopathy.

Hypertrophic cardiomyopathy is characterized by a nondilated, hypertrophied left ventricle in the absence of any overt cause. A possible role of adrenergic innervation or of cellular calcium regulation is suggested by the presence of hyperdynamic left ventricular function and by the clinical and symptomatic improvement seen in patients treated with beta-receptor antagonists or calcium antagonists. Therefore, we measured the density of calcium-antagonist receptors and beta-adrenoceptors in the atrial myocardium of 16 patients with hypertrophic cardiomyopathy and 19 patients with various other cardiac disorders. For comparison, we also measured the number of voltage-sensitive sodium channels. Calcium-antagonist binding sites, measured as the amount of dihydropyridine bound to atrial tissue, were increased by 33 percent in patients with hypertrophic cardiomyopathy (mean [+/- SD], 397 +/- 104 fmol per milligram of protein in patients with hypertrophic cardiomyopathy, as compared with 299 +/- 108 in patients with other cardiac disorders; P less than 0.01). The densities of saxitoxin-binding sites on voltage-sensitive sodium channels and beta-adrenoceptors were the same in the two groups, although the density of beta-adrenoceptors was higher in atrial samples from patients receiving beta-receptor antagonists (165 +/- 86 fmol per milligram of protein [patients receiving beta-blockers] vs. 85 +/- 60 [patients not receiving beta-blockers]; P less than 0.04). The increase in the number of calcium-antagonist receptors in hypertrophic cardiomyopathy suggests that abnormal calcium fluxes through voltage-sensitive calcium channels may play a pathophysiologic part in the disease.

Adolescent

Implications of plasma levels of catechols in the evaluation of sympathoadrenomedullary function.

This report summarizes new techniques for examining aspects of sympathoadrenomedullary function. Tracer pharmacokinetic methods are more accurate than measurements of antecubital venous norepinephrine (NE) in assessing sympathoneural responsiveness. During mental challenge (playing a video game), patients with essential hypertension had significantly larger increments of NE spillover into arterial blood than did normotensive control subjects, whereas responses of antecubital venous and even arterial NE did not differ significantly between the groups. The rate of neuronal reuptake of endogenous NE can be measured in vivo using plasma levels of NE and of the intraneuronal NE metabolite, dihydroxyphenylglycol (DHPG). Regional production of dihydroxyphenylalanine (DOPA) may reflect catecholamine biosynthesis, and DOPA may be an indirectly acting natriuretic neurohormone. Positron emission tomography after injection of positron-emitting fluorodopamine may allow in vivo, noninvasive assessments of regional sympathetic function.

Catechols

Pharmacologic and tracer methods to study sympathetic function in primary hypertension.

Systemically infused tritiated norepinephrine (NE) was used to estimate total body NE spillover into arterial blood during mental challenge (playing a video game) in 18 young (mean age 35 years old) patients with essential hypertension and 20 normotensives of similar age. Arterial NE, epinephrine (E), and total body NE spillover at baseline did not differ between the groups. During the game, total body NE spillover increased significantly in both groups, with the increments related directly to the pressor responses. Mean increments in total body NE spillover, arterial E, and mean arterial pressure were larger in the hypertensives (204 vs 91 ng/min, 33 vs 9 pg/ml, and 16 vs 12 mm Hg). The hypertensives increased total peripheral resistance during the game, whereas the normotensive group did not. Intravenous administration of yohimbine was used to increase NE spillover. Pressor responses to yohimbine were related to responses of arterial NE. The hypertensive group had a larger mean increment in blood pressure and arterial NE than did the normotensive group during yohimbine, due to excessive responses in a subgroup of about 1/3 of the patients. Patients with essential hypertension can have excessive sympathoadrenomedullary responsiveness related to excessive pressor responses, even when sympathoadrenomedullary activity at rest is normal.

Adult

Trade-offs between hospital charges and patient outcomes.

The increasing cost of health care has focused attention on the trade-offs between health care expenditures and patient outcomes. In this study, hospital charges were contrasted with the health status at 1 year of follow-up of 549 patients admitted to a university hospital medical service. The findings related to short-term outcomes were consistent with those of other investigators: large expenditures were associated with patients who died in the hospital, especially those whose death was unexpected. Both 1-year survival and hospital charges were found to correlate with physician estimates of illness severity and prognosis at the time of admission. Patients considered not ill with a favorable prognosis had a mortality rate at 1 year of 3%, comprised 7% of the cohort and generated 2% of total charges. In contrast, patients considered severely ill with an unfavorable prognosis had a mortality rate of 65%, comprised 19% of the cohort and generated 30% of total charges. Nevertheless, 46% of the survivors in this latter group were considered to be functional and only mildly ill at 1 year of follow-up. The imprecision of clinical judgements at the time of admission in predicting long-term outcome argues for aggressive management of acutely hospitalized patients when there is any doubt about their prognosis.

Fees and Charges

Impaired forearm vasodilator reserve in patients with microvascular angina. Evidence of a generalized disorder of vascular function?

In previous work, we described a group of patients with angina-like chest pain and normal coronary arteries. These patients had impaired coronary vasodilator responses to the stress of rapid atrial pacing and to the administration of dipyridamole, a potent vasodilator of coronary arterioles. This abnormality appears to be localized to the prearteriolar microvascular bed. To determine whether these patients have a more generalized abnormality of vasodilator reserve, we used mercury-in-Silastic strain-gauge plethysmography to compare their hyperemic responses to forearm ischemia with those of normal controls. After 10 minutes of ischemia, peak forearm flow was 39.9 +/- 5.0 ml per minute per deciliter in the controls [corrected] and 31.7 +/- 10.5 in the patients [corrected] (21 percent reduction; 95 percent confidence interval, 4 percent to 37 percent). Flow responses were also significantly reduced after three and five minutes of ischemia. Correspondingly, the vascular resistance after ischemia was also consistently higher in the patients with microvascular angina. The degree of vasodilator impairment in the peripheral circulation correlated well with the degree of vasodilator impairment in the coronary circulation (r = 0.74; P less than 0.004). Thus, patients with microvascular angina appear to have an impairment of vasodilator reserve that affects not only their coronary circulation but also their peripheral arterial bed.

Adult

The therapeutic efficacy of critical care units from two perspectives: a traditional cohort approach vs a new case-control methodology.

The therapeutic efficacy of critical care units-whether they do more good than harm and for whom--has not been established, except for patients who are admitted for life-sustaining interventions, such as mechanical support of ventilation. However, most patients are admitted for observation, and to facilitate intervention if deterioration occurs or complications develop. The objective of this study was to determine whether direct admission to critical care units reduced mortality rates. The population under study consisted of all 604 patients admitted to the medical service during a one month period. At the time of admission, the responsible residents rated patients as to how sick and stable they were. These ratings of illness severity and stability have been shown to be the most significant predictors of in-hospital mortality and morbidity, respectively; they were employed to stratify the patients prognostically. The first analysis utilized the entire cohort of 604 patients. After patients who would have been ineligible for entry into a trial were removed, direct admission to the unit was associated with a reduced mortality in only one group of patients: the unstable, moderately ill (p less than 0.05). "Unstable, severely ill" patients had high mortality rates when admitted to the floor or units, and stable patients (mildly or moderately ill) did equally well when admitted to either location. A further analysis revealed a possible explanation for these findings. Among the unstable, moderately ill patients, the rate of deterioration of pre-existing problems was significantly lower among patients directly admitted to the unit (p less than 0.05), whereas the rate of new complications did not differ.(ABSTRACT TRUNCATED AT 250 WORDS)

Critical Care

Morbidity during hospitalization: can we predict it?

Physicians use the concept of stability to estimate the likelihood that a patient will deteriorate during a hospitalization. To determine whether physicians can accurately predict a patient's risk of morbidity, 603 patients admitted to the medical service during a one month period were rated prospectively as to how stable they were. Overall, 15% of patients had deterioration of already compromised systems, while 17% had new complications, such as sepsis. Eight percent of patients had both. Twelve percent of stable patients experienced morbidity; 39% of the somewhat unstable and 61% of the most unstable. When all of the demographic and clinical variables were taken into account including the reason for admission and comorbid diseases, the residents' estimates of the patient's stability was the most significant predictor of morbidity (p less than 0.001). The judgment that a patient was stable had an 87% negative predictive accuracy, while the judgment unstable had a 46% positive predictive accuracy.

Aged

Medical patients at high risk for catastrophic deterioration.

The objective of this study was to develop criteria to demarcate patients at risk for catastrophic deterioration (arrest or major decompensation) and those likely to require intensive care. From an inception cohort of patients admitted to the medical service, 544 patients were evaluated prospectively for severity of illness and stability by the admitting residents; the course of patients was reviewed blindly by observers. Patients admitted with acute dyspnea, particularly those with chronic pulmonary disease, were at a significantly greater (p less than .01) risk of arrest. All but one of the other arrests occurred in patients who were rated unstable on admission and who had further deterioration of pre-existing problems in the hospital (p less than .0001). The deterioration rates were highest among patients rated as unstable, particularly in patients with comorbid disease. Patients who are unstable on admission or who begin to deteriorate due to comorbid disease or the condition leading to admission, should be considered at extremely high risk for subsequent arrest and should be admitted to critical care units for early observation.

Critical Care

Utilization of critical care units. A prospective study of physician triage and patient outcome.

To identify patients likely to be admitted to a critical care unit as well as those at high risk of deterioration, we studied all patients admitted to the medical service. Cardiac patients had a high likelihood of unit admission even if they were rated as not ill and stable, whereas ill and unstable noncardiac patients went to the floor. Stable cardiac or noncardiac patients who were not severely ill had very low deterioration and mortality, but unstable, severely ill patients with cardiac or noncardiac reasons for admission had high deterioration rates. If the goal is to admit patients at highest risk, the optimal strategy is to admit unstable, severely ill, and moribund patients in both the cardiac and noncardiac groups. By doing this, it is possible to decrease unit admission of patients likely to do well, increase the admission of patients likely to do poorly, while decreasing the number of patients admitted.

Cardiovascular Diseases

Resuscitation: how do we decide? A prospective study of physicians' preferences and the clinical course of hospitalized patients.

Physicians have to address the question of the measures to be employed in the event that a patient's condition deteriorates after admission to the hospital. To identify the information that physicians use in making such decisions, all 604 patients admitted to the medical service during a one-month period were studied. The patient's age and residents' estimates of the patient's long-term prognosis and ability to function were the three primary factors that correlated with intervention preferences. When illness severity, the reason for admission, comorbidity, and poor function were taken into account, mortality and morbidity rates did not differ between patients for whom full vs not-full intervention was favored. Apart from differential rates of admission to critical care units, there were no important differences in the care, course, or mortality of patients for whom less than full intervention was initially favored. Suggestions that physicians should discuss resuscitation with all or most patients who may die are unrealistic. A more prudent strategy is to discuss the issue with patients whose hospital course is marked by a steady deterioration.

Age Factors

Assessing illness severity: does clinical judgment work?

Accurate classification of clinical severity is important for interpreting casemix in clinical studies and for stratifying patients for clinical trials. To evaluate whether clinical judgment might be an effective method of estimating severity, all 604 patients admitted to the medical service in a one month period were rated at the time of admission by the responsible resident as to how sick they were. Within the 13 comorbid disease groups, and within the 15 basic categories of reason for admission, the physicians' severity ratings were the most significant predictor of in-hospital mortality. Death rates rose from 0% in those rated as not ill, to 2% in the mildly ill, to 6% in the moderately ill, to 23% in the severely ill, and to 58% in those rated as moribund (p less than 0.001). Sickness ratings also predicted time to death: mildly ill patients died after prolonged hospitalizations, while the moribund died shortly after admission. The patients' age, sex, race, the number of comorbid diseases or problems did not predict mortality. Patients with serious comorbidity (metastases, AIDS, or cirrhosis) had a higher mortality rate than other patients (p less than 0.001); however, the severity ratings predicted outcomes within this group (p less than 0.001) as well as among those without such serious comorbidity (p less than 0.001). Patients who were admitted with acute neurologic (p less than 0.05) or acute cardiovascular (p less than 0.01) events did have an independently worse prognosis. In conclusion, physicians' estimates or sickness provided an accurate estimate of illness severity, with mortality rates that essentially tripled from one stratum to the next. Clinical judgment may suffice to classify the clinical severity of patients at the time of enrollment in prospective trials and can provide a useful method of controlling for casemix.

Acute Disease

Cognitive impairment. Can it predict the course of hospitalized patients?

All patients admitted to three medical services at the New York Hospital during a one-month period were screened with Folstein's Mini-Mental State Examination. The prevalence of cognitive impairment was 19.8% (23 of 116). Cognitively "impaired" patients, ie, those with a Folstein score less than 24, were older, sicker, and less physiologically stable than the cognitively "intact." The in-hospital mortality (17 versus 5%) and morbidity (39 versus 18%) rates were higher for the cognitively "impaired" patients; these differences could be explained by the greater severity of illness, instability, and comorbidity found in these patients. Cognitively "impaired" patients were particularly susceptible to respiratory complications. Cognitively "impaired" patients had longer lengths of hospital stay, spent more time in hospital awaiting placement, and were more likely to be discharged to a nursing home or require home assistance than their cognitively "intact" counterparts. Three-month mortality rates were also higher for the cognitively "impaired" patients (30 versus 15%). These findings suggest that cognitive impairment on admission may be regarded as a marker for patients with poorer prognoses.

Aged

Plasma norepinephrine pharmacokinetics during mental challenge.

We simultaneously infused tracer-labeled norepinephrine (NE) and isoproterenol (ISO) intravenously into 14 subjects to measure forearm and total body NE pharmacokinetics at rest and in response to mental challenge (video game or cognitive task). Mental challenge was associated with significantly increased heart rate (24%), systolic blood pressure (13%), cardiac output (impedance cardiography, 9%), forearm blood flow (38%), and the rate of release of endogenous NE into arterial blood (total body NE spillover, 29%), but not with changes in cardiac output (r = 0.68) and systolic blood pressure (r = 0.60), whereas those of antecubital venous NE were not. Forearm extraction of NE was related inversely to forearm blood flow both at rest (r = -0.80) and during mental challenge (r = -0.81), and total body clearance of NE was positively related to cardiac output at rest (r = 0.78) and during mental challenge (r = 0.54). The results indicate that mental challenge is associated with generally increased sympathetically-mediated NE release that determines the hemodynamic responses. Because of regional changes in sympathetic activity and blood flow during psychological stress, changes in antecubital venous NE and even arterial NE may not reflect accurately sympathetic nerve activity. Measurement of total body and regional NE pharmacokinetics avoids these difficulties.

Adrenocorticotropic Hormone