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Biomedical subjects

S M Shapiro

Publications and source records attributed to S M Shapiro.

At least 37 records · Page 2Linked to original sources
PubMed1995

Bilirubin induces a calcium-dependent inhibition of multifunctional Ca2+/calmodulin-dependent kinase II activity in vitro.

Excessive bilirubin levels in newborn infants result in long-term neurologic deficits that remain after bilirubin levels return to normal. Much of the observed neurologic deficits can be attributed to bilirubin-induced, delayed neuronal cell death. Inhibition of calcium/calmodulin-dependent kinase II (CaM kinase II) activity that precedes cell death is observed in conditions such as seizure activity, stroke, and glutamate excitotoxicity. Because neonatal bilirubin exposure results in neuronal loss in developing brain systems, we tested whether bilirubin exposure would induce an immediate inhibition of CaM activity, in vitro. P-81 filtration assay of basal and calcium-stimulated kinase activity was performed under standard kinase assay conditions. Bilirubin and/or albumin was added to the reaction vessels to determine the effect of these agents on kinase activity. Bilirubin exposure resulted in a concentration-dependent inhibition of CaM kinase II activity (IC50 = 16.78 microM). At concentrations above 50 microM, bilirubin exposure resulted in a 71 +/- 8% (mean +/- SD) inhibition of kinase activity (p < 0.001, t test, n = 10). Bilirubin exposure did not result in kinase inhibition if excessive bilirubin was removed by albumin binding before stimulation of kinase activity (106.9 +/- 9.6% control activity, n = 5). However, removal of bilirubin by binding with albumin after calcium addition did not restore kinase activity. (36.1 +/- 3.8% control activity, n = 5). Thus, once inhibition was observed, the activity could not be restored by addition of albumin. The data suggest that bilirubin exposure resulted in a calcium-dependent inhibition of CaM kinase II activity that, once induced, was not reversible by removing bilirubin by the addition of albumin. Because inhibition of CaM kinase II activity has been correlated with delayed neuronal cell death in many neuropathologic conditions, bilirubin-induced inhibition of this enzyme may be a cellular mechanism by which bilirubin exposure results in delayed neuronal cell death in developing brain.

Animals↗
PubMed1994

Evaluation of new clinical criteria for the diagnosis of infective endocarditis.

PURPOSE: The clinical diagnosis of infective endocarditis (IE) can be difficult. A new diagnostic schema for IE (the Duke criteria) has been proposed, utilizing clinical, microbiologic, and echocardiographic data. We evaluated the Duke criteria in a cohort of prospectively enrolled patients suspected of having IE and compared the diagnostic efficiency of these criteria with the previously published criteria of von Reyn. PATIENTS: Sixty-three febrile patients with suspected IE at a non-referral, municipal hospital were evaluated. All patients had the following parameters defined: the presence and nature of underlying heart disease; recent abuse of intravenous drugs; peripheral stigmata of IE; blood culture results; findings on two-dimensional transthoracic and transesophageal echocardiography (TTE, TEE); and the results of open heart surgery. RESULTS: Twelve of 63 patients underwent open heart surgery, at which time IE was pathologically confirmed in 10 patients and excluded in 2 patients. All 10 patients with pathologically confirmed IE were classified as "clinically definite" by Duke criteria, whereas 5 of 10 were rejected by von Reyn criteria (p < 0.05). Among the remaining 51 patients suspected of IE and evaluated by both von Reyn and Duke clinical criteria, significantly more cases were classified as "definite" IE by Duke criteria than by von Reyn criteria (p < 10(-5)). Similarly, significantly fewer cases were rejected as IE by the Duke criteria as compared with the von Reyn criteria (p < 10(-6). Duke criteria were also significantly better at diagnosing IE than von Reyn criteria in the following clinical settings: suspected right-sided IE (p < 0.01); suspected left-sided IE (p = 0.014); suspected culture-negative IE (p < 10(-2); and IE complicating Staphylococcus aureus or viridans streptococcal bacteremias (p < 10(-5); p < 0.05, respectively). Among 30 cases defined as clinically definite by the Duke criteria, the presence of blood culture positivity and echocardiographically defined vegetations was important in this classification of 77% and 57% of cases, respectively. Among the 17 patients in the clinically definite category with vegetative endocarditis observed by echocardiography, 7 (41%) had vegetations defined only by TEE. CONCLUSION: The Duke criteria are superior to the von Reyn criteria for the clinical diagnosis of IE, predominantly reflecting use of two-dimensional echocardiographic demonstration of valvular vegetations in the Duke schema.

Adult↗
PubMed1994

Transesophageal echocardiography in diagnosis of infective endocarditis.

STUDY OBJECTIVE: To determine whether transesophageal echocardiography (TEE) was superior to transthoracic echocardiography (TTE) in defining valvular vegetations and diagnosing clinical infective endocarditis (IE) in patients suspected of having this infection. PATIENTS AND METHODS: Between April 1989 and May 1991, 64 febrile patients with clinical and/or microbiologic risk factors for IE were prospectively enrolled. Patients underwent both TEE and TTE, which were interpreted in a blinded fashion as to the patient's clinical status. Clinical criteria for the diagnosis of IE were compared with TEE and TTE findings to delineate the ability of the two echocardiographic techniques to define valvular vegetations and to establish the clinical diagnosis of vegetative IE. RESULTS: Thirty-four valves had typical valvular vegetations demonstrated by either TEE or TTE. Transesophageal echocardiography was more sensitive than TTE in identifying valvular vegetations (33/34 vs 23/34 instances, respectively; p = 0.004). Also, TEE was better at identifying smaller vegetations (< 1 cm) than TTE; 12 patients with such vegetations were identified by TEE as compared with only 5 of 12 identified by TTE (p = 0.02). Of the 64 patients enrolled, 30 (47 percent) were classified as having "definite" or "probable" IE by modified von Reyn criteria. Among these 30 patients, TEE was significantly more sensitive than TTE at documenting vegetative valvular lesions (26/30 [87 percent] vs 18/30 [60 percent], respectively) (p < 0.01). Both TEE and TTE were highly specific (91 percent) in delineating valvular vegetations in this patient population; two of the three false-positive TEE studies for valvular vegetations occurred in patients with a history of IE. All nine periannular complications of IE were identified by TEE, as compared with only two being defined by TTE (p = 0.001). CONCLUSIONS: Transesophageal echocardiography is significantly more sensitive than TTE and highly specific in both confirming the clinical diagnosis of IE, as well as in identifying valvular vegetations in patients at risk for this infection. Our data also support the concept that TEE is the echocardiographic method of choice for defining small vegetations and periannular complications in IE.

Abscess↗
PubMed1994

Atrial-esophageal fistula shown by transthoracic echocardiogram.

Nontraumatic atrial-esophageal fistula is a catastrophic problem usually diagnosed postmortem and almost invariably fatal. We report the first case of a patient in whom the diagnosis of atrial-esophageal fistula was made from a transthoracic echocardiography antemortem. Echocardiography showed multiple microbubbles in the left atrium and ventricle emanating from the posterior aspect of the left atrium adjacent to the pulmonary veins. The literature is reviewed and the significance of the case and the echocardiogram is discussed.

Echocardiography↗
PubMed1993

Influence of cardiac motion on Doppler measurements using in vitro and in vivo models.

OBJECTIVES: Using both in vitro and in vivo techniques, we investigated the extent to which cardiac motion alters Doppler-measured blood flow velocity and thus potentially can alter the calculation of valve areas or pressure gradients. BACKGROUND: Blood flow velocity measured by Doppler ultrasound represents the net motion of the blood relative to the transducer. It is widely assumed that the measured velocity represents the actual flow. It has been demonstrated that cardiac motion generates regularly occurring low velocity Doppler signals that are commonly treated as artifact. METHODS: We used an in vitro model that allowed us to measure and independently control the flow of a liquid through a chamber and the motion of the chamber relative to the Doppler beam. A cornstarch-water slurry was driven by a pulsatile pump through tubing to simulate the blood flow within the heart, and the tubing was cyclically moved by a piston to simulate the heart motion. We also measured cardiac motion using M-mode and two-dimensional echocardiography and compared the results with the Doppler signal derived from cardiac motion in subjects without cardiac disease. RESULTS: In the in vitro model, alteration in the motion of the tubing resulted in apparent changes in the measured maximal velocity of the fluid. The Doppler spectrum of the combined motion of the tubing and the fluid was the algebraic sum of their Doppler signals. In human subjects, the maximal slope of the M-mode tracing of the aortic annular motion and the peak Doppler signal due to cardiac motion were compared and were highly correlated. CONCLUSIONS: Cardiac motion alters the Doppler signal derived from blood flow. This effect can be demonstrated in vitro and in vivo.

Adolescent↗
PubMed1993

Intrinsic positive end-expiratory pressure in ambulatory patients with airways obstruction.

In patients with severe expiratory airflow limitation, dynamic hyperinflation often occurs when inspiratory efforts are initiated at a thoracic volume above the relaxation point of the respiratory system. The result is intrinsic positive end-expiratory alveolar pressure (PEEPi). To determine whether PEEPi occurs in ambulatory patients, we measured alveolar pressure (Palv) noninvasively during tidal breathing in 8 normal subjects, 15 asthmatic subjects, and 19 patients with COPD, using a body plethysmographic technique that includes computerized corrections for nonlinear pneumotachometer output and for plethysmograph leakage. In all 8 normal subjects, 9 asthmatic subjects, and 3 COPD patients, Palv descended smoothly to zero at end expiration. In contrast, among each of the remaining 22 patients, there was an abrupt change in slope of the Palv tracing near end expiration, identifying the onset of the next inspiratory effort and indicating the presence of PEEPi, ranging from 0.2 to 9.5 cm H2O. PEEPi was significantly correlated with FRC (% of predicted); PEEPi = (0.040 x %FRC) - 3.65, r = 0.73, p < 0.001, and with the reciprocal of FEV1 (% of predicted), PEEPi = (138/%FEV1) - 1.34, r = 0.69, p < 0.001. PEEPi could be elicited in normal subjects by severe expiratory resistive loading but not by the increased expiratory muscle activity occurring during an MVV maneuver. We conclude that PEEPi is common in patients with airways obstruction, even without overt ventilatory failure, and that its severity is generally in proportion to the severity of the hyperinflation and the airways obstruction.

Adult↗
PubMed1993

Reversible brainstem auditory evoked potential abnormalities in jaundiced Gunn rats given sulfonamide.

Neurologic and audiologic sequelae produced by bilirubin toxicity are preventable by appropriately timed therapeutic intervention. To understand the timing and reversibility of the neural dysfunction that follows exposure to bilirubin, we recorded brainstem auditory evoked potentials (BAEP) in the Gunn rat model of bilirubin encephalopathy. Abnormal BAEP occur in jaundiced Gunn rats after injection of sulfadimethoxine (sulfa) 100 mg/kg intraperitoneally, which displaces bilirubin from blood albumin binding sites and promotes the net transfer of bilirubin into brain tissue. Reversal of BAEP abnormalities with injection of human serum albumin (HSA) 2 g/kg intraperitoneally was studied in 17- to 20-d-old jaundiced Gunn rats. One animal from each of 14 litters was randomly assigned to one of the following treatment groups: 1) sulfa alone, 2) sulfa + HSA at 2 h, 3) sulfa + HSA at 8 h, or 4) saline alone. BAEP were recorded in each rat before and 0.1, 4, 8, 24, and 48 h after injection of sulfa or saline. BAEP I-II interwave intervals increased in all sulfa groups (p < 10(-9) to 0.27 ms (21%) above baseline at 8 h for the two sulfa groups not receiving treatment before that time (p = 0.0002), but increased less for the sulfa group given HSA at 2 h compared with untreated animals (p = 0.02). Partial recovery of function occurred at 24 and 48 h for both HSA-treated groups compared with their 8-h values (p = 0.001), and there was increased mortality at 24 h for the sulfa group not treated with HSA (p < 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1992

Effects of exercise test results on physician perceptions of coronary artery disease probability using a threshold analysis.

The incremental diagnostic value of exercise electrocardiographic testing compared with clinical data alone in the diagnosis of coronary artery disease (CAD) was found to be of limited value in a previous study. That study used a computer algorithm for diagnosing disease. Thus, the strict use of the results apply only to computerized disease diagnosis rather than physicians' diagnoses. The aim of the present study was to determine whether exercise test data improve a physician's ability to detect the presence or absence of CAD and 3-vessel or left main CAD, and whether the data effect the decision to perform angiography. The study sample comprised a data base of 312 patients whose clinical data, exercise test results and coronary anatomy were known. Individual cases were presented to 8 cardiologists with and without exercise data. The cardiologists provided estimates of disease probability and were asked whether they would request coronary angiography. Receiver-operating characteristic curves and goodness-of-fit analysis showed better discrimination and calibration of the estimates for the presence of CAD and 3-vessel/left main CAD after exercise test results were known. Individualized probability thresholds for deciding whether to request angiography were determined for each physician. Forty-three percent of patients crossed greater than or equal to 1 threshold, with 64% of the crossings in the correct direction. For estimating the presence of any CAD, 84% of crossings from below to above a threshold were correct, whereas only 36% from above to below were correct. For 3-vessel/left main CAD, 36% of crossings from below to above a threshold were correct, whereas 88% from above to below were correct.(ABSTRACT TRUNCATED AT 250 WORDS)

Coronary Angiography↗
PubMed1992

Quantitative stress echocardiography.

Dramatic improvements in our ability to treat coronary artery disease have created the need to develop sensitive and specific noninvasive tests for diagnosing and assessing the severity of ischemic disease. The purpose of this review is to examine stress echocardiography and, in particular, quantitative stress echocardiography in this context. Methodology and technical aspects of performing and interpreting stress echocardiography are discussed, including the type of exercise performed, imaging and recording techniques, and methods for on-line and off-line analysis. Qualitative, semiquantitative, and quantitative approaches are compared and contrasted. In assessing quantitative stress echocardiography, the role of global measurements of left ventricular function including ejection fraction, peak systolic pressure to end-systolic volume index ratio, as well as regional measurements including wall-motion analysis and wall stress, are discussed. Pertinent literature using quantitative approaches is reviewed including those comparing quantitative stress echocardiography with other noninvasive modalities. Future directions for study are also addressed. We concluded that quantitative stress echocardiography has excellent sensitivity and specificity for diagnosing ischemic heart disease. It was useful in localizing lesions, defining multivessel disease, and predicting patients with poor prognosis postmyocardial infarction. Its reproducibility makes it a valuable technique in following patients noninvasively over time.

Coronary Disease↗
PubMed1991

Brainstem auditory evoked potentials correlate with morphological changes in Gunn rat pups.

The relationship of brainstem structure and function in bilirubin encephalopathy is incompletely understood. The present experiments compare quantitative measures of brainstem structures with brainstem auditory evoked potentials (BAEPs) in infant jaundiced (jj) and nonjaundiced (Nj) Gunn rats. Ten jj's from 4 litters were injected with sulfadimethoxine at 11-12 days of age to raise their brain bilirubin concentration. Littermate controls were jj's given saline, and Nj's given sulfadimethoxine or saline. At 15-17 days of age BAEPs were recorded, and rats were prepared for histological examination, as was reported in the previous paper (Conlee and Shapiro, 1991). Significant differences between groups were seen for BAEP wave I latency (P = 0.002). I-II interwave interval (P = 0.001), and amplitudes of waves I, II, III, and IV (each P less than 0.0005) due to increased latencies and decreased amplitudes in the jj-sulfa group. Animals with the most severe BAEP abnormalities had the most severe histological abnormalities. Cochlear nucleus volume had a positive linear correlation with the amplitude of BAEP waves I, II, and IV, and an inverse correlation with wave I latency and I-II interwave interval (P less than or equal to 0.001). The highest correlations were BAEP I-II interwave interval and amplitude of waves I and II with cochlear nucleus volume (r = -0.78, 0.71 and 0.70, respectively, P less than 0.0005).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1991

Morphological changes in the cochlear nucleus and nucleus of the trapezoid body in Gunn rat pups.

Mechanisms underlying bilirubin encephalopathy and hearing loss remain poorly understood, including the way bilirubin enters the nervous system and how bilirubin accumulates in circumscribed regions of the brain. The present experiments examined the auditory brainstem in heterozygous (Nj) and homozygous (jj) Gunn rats at an age when serum bilirubin levels were highest, and after brain bilirubin concentration was artificially raised by sulfadimethoxine administration. In four litters of 11-12 days old Gunn rats, Nj and jj littermates received a single intraperitoneal injection of sulfadimethoxine (100 mg/kg) or a comparable volume of saline. At 16-17 days of age, brainstem auditory evoked potentials were recorded to assess the severity of bilirubin toxicity in the Nj and jj animals. Following the recordings, each animal was perfusion-fixed and frozen sections of the brainstem were cut in the transverse plane from medullary through mesencephalic levels. Sections were mounted on slides, stained with thionin and coded to avoid observer bias. Quantitative analysis revealed no differences between saline and sulfa-treated Nj rats for cochlear nucleus volume, or for cell size in the cochlear nucleus or superior olive. In the sulfa-treated jj rats, cochlear nucleus volume, and cross-sectional areas of spherical cells in the anteroventral cochlear nucleus and principal cells in the nucleus of the trapezoid body, were all significantly smaller than in the combined groups of Nj animals. The affected areas in the cochlear nucleus and superior olive are innervated by large axosomatic end-bulbs of Held or calyceal endings, and were associated with bilirubin staining of glia in the most severely jaundiced jj sulfa-treated rats.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1991

Binaural effects in brainstem auditory evoked potentials of jaundiced Gunn rats.

Bilirubin toxicity causes encephalopathy associated with lesions of the central auditory nervous system. Abnormal brainstem auditory evoked potentials (BAEPs) in jaundiced Gunn rats made acutely bilirubin toxic suggest abnormal input into the superior olivary complex, which might result in abnormal binaural interaction. Binaural difference waves (BDWs), obtained by subtracting the sum of two monaural BAEPs from a binaural BAEP, were obtained in 16- to 20-day-old jaundiced Gunn rats before and after injection of sulfadimethoxine, which produces bilirubin neurotoxicity by promoting net transfer of bilirubin out of the circulation into brain tissue. Reliable BDWs were recorded with onset 4.5 ms after the stimulus, followed by a large, often bimodal, positive peak occurring at about 6 ms. Following injection of sulfadimethoxine to produce bilirubin neurotoxicity, there was loss of BDW amplitude (21% +/- 14% of baseline, P less than 0.0001) and increase in latency (0.62 +/- 0.42 ms, P = 0.03) in bilirubin-toxic jaundiced rats compared to baseline, but no significant changes in nonjaundiced controls treated similarly. This documents abnormal BDWs in acute bilirubin encephalopathy suggesting that abnormalities of functions dependent on binaural processing of auditory information may be found as neurologic sequelae to bilirubin toxicity. BAEP BDWs may be a sensitive method for detecting neurophysiological abnormalities due to bilirubin toxicity.

Animals↗
PubMed1991

An evaluation of the accuracy of Assess and MiniWright peak flowmeters.

With the advent of small inexpensive peak flowmeters, the at-home monitoring of peak flow rates has become an invaluable aid in the treatment of asthmatic patients. In this study, we evaluated the performance of the MiniWright and Assess peak flowmeters for accuracy and reproducibility. Measurements were made at varying peak flow rates and compared with those obtained simultaneously by a calibrated pneumotachograph. When this segment of the study was completed, the peak flow devices were subjected to 200 uses and were then retested. Four MiniWright peak flowmeters that had been extensively used in our clinic were tested as well. The Assess peak flowmeter was more accurate than the MiniWright at low flow rates (less than 300 L/min), while the MiniWright meter was more accurate at high flow rates (greater than 400 L/min). We also found that the accuracy of the MiniWright meter deteriorated after 200 uses and worsened further after extensive use, while the Assess meter retained its accuracy after 200 uses.

Evaluation Studies as Topic↗