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Biomedical subjects

S Stern

Publications and source records attributed to S Stern.

At least 91 records · Page 5Linked to original sources

Circadian variations in ischemic threshold and their relation to the occurrence of ischemic episodes.

BACKGROUND: The occurrence of ischemic episodes during daily activity has been reported to exhibit a bimodal circadian distribution, yet its relation to the ischemic threshold (heart rate at 1-mm ST segment depression) has not been explored. METHODS AND RESULTS: To determine whether the ischemic threshold during daily activity exhibits a circadian pattern that might relate to the frequency of occurrence of ischemic episodes, we studied the time of occurrence and the heart rate at onset of ischemia in 1,371 ischemic episodes recorded in 41 patients with stable coronary disease, positive exercise testing, and repeated ischemic episodes during ambulatory ECG monitoring (AEM). All patients had 7 days of AEM; 23 were off any anti-ischemic therapy, while 18 were on low dose of beta-blockers. The occurrence of ischemic episodes exhibited the typical bimodal circadian distribution with a prominent peak between 7:00 and 11:00 AM and a second less prominent peak between 6:00 and 9:00 PM. The threshold of myocardial ischemia exhibited a different single-peaked circadian distribution; it was lowest between 1:00 and 3:00 AM and highest between 10 AM and 1 PM. Time series analyses indicated a strong hour-by-hour trend of each of the two circadian distributions, whereas the two series cross-correlated maximally at a lag of zero hours (p < 0.01), indicating a complex interplay between myocardial oxygen demand and supply in determining the occurrence of ischemic episodes during daily activity. The morning increase in the frequency of ischemic episodes could not be attributed to a reduced threshold but rather to an increase in demand. The low threshold at night-time might probably indicate that the mechanism of ischemia during these hours is reduced coronary flow due to increased coronary tone. Secondary analyses for several predefined patients' subsets gave similar results. Patients who received low-dose beta-blockers maintained the bimodal circadian distribution of the occurrence of ischemic episodes, whereas the ischemic threshold exhibited a constant pattern with no circadian changes. CONCLUSIONS: Our results demonstrate that myocardial oxygen demand is a major determinant of daily ischemia, yet changes in the ischemic threshold that probably reflect dynamic changes in coronary tone play also an important role. The relative contribution of increased demand and decreased threshold to the genesis of ischemic episodes during daily activity can be assessed by AEM and may help to optimize medical therapy.

Adrenergic beta-Antagonists↗

Muscle histochemical and biochemical properties in relation to meat quality during selection for increased lean tissue growth rate in pigs.

The relationship between the histochemical and biochemical properties of muscle and the quality of meat during selection to improving the lean tissue growth rate was studied. Pigs (n = 82) from Generations 2 and 4 were randomly sampled in a selection experiment in which the genotype x protein interaction was studied. Comparisons were made of longissimus muscle (LM) and quadriceps femoris (QF) from Generations 2 and 4, and biceps femoris (BF) in the fourth generation from pigs fed a low- or high-protein diet. A higher total growth rate, lean tissue growth rate, and lean percentage were found in pigs fed the high-protein diet than in pigs fed the low-protein diet. Pigs fed the high-protein diet had a higher glycolytic capacity in all muscles than pigs fed the low-protein diet. When the meat quality traits were compared, pigs fed the high-protein diet had a lower intramuscular fat content, higher shear force value, higher protein extractability, lower light reflectance, and somewhat higher water-holding capacity. With selection, pigs became fatter on both diets. In Generation 4, glycolytic and oxidative capacity was somewhat higher in muscle tissue than in Generation 2. Muscle metabolic profile and meat quality traits differed among muscles (LM, BF, QF) but no pronounced differences were found between generations. No marked changes were observed in Type I, IIA, or IIB fibers, either between diets or between generations. The Type IIC fibers could only be identified in Generation 4.

Adipose Tissue↗

Effect of recombinant human manganese superoxide dismutase on radiosensitivity of murine B cell leukemia (BCL1) cells.

Recombinant human manganese superoxide dismutase (SOD) protects cells from oxidative damage and is known to ameliorate post-irradiation damage in mice exposed to whole body or localized chest irradiation. The concept behind the present experiments was to investigate whether it is possible to improve the outcome in leukemia following total body irradiation used as part of the conditioning prior to allogeneic bone marrow transplantation. We determined whether SOD protects leukemic cells from the effects of ionizing irradiation both in vitro and in vivo. Murine B cell leukemia (BCL1) cells, derived from tumor-bearing mice, were irradiated in vitro with or without SOD and injected into BALB/c mice. All mice receiving 10(4) unirradiated BLC1 cells developed leukemia and died within 19-39 days. In vitro exposure of BCL1 cells to 800 cGy or 1600 cGy abolished the potential to induce leukemia by inoculation with 10(4) or 10(6) BCL1 cells, respectively. Addition of SOD in vitro during irradiation increased the resistance of BCL1 cells to ionizing irradiation; all mice receiving 10(6) BCL1 cells previously exposed in vitro to 1200 cGy in the presence of SOD died of leukemia, whereas only 40% of mice receiving a similar inoculum of irradiated BCL1 cells died of leukemia. In contrast, when BCL1-bearing mice were irradiated with 600-800 cGy with or without intravenous injection of SOD (100 mg/kg) 30 minutes prior to irradiation, development of leukemia was unaffected. Residual leukemia cells following therapy were assessed by adoptive transfer of 10(5) spleen cells to secondary BALB/c recipients.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Antibiotic impregnated bone cement in total hip arthroplasty. An in vivo comparison of the elution properties of tobramycin and vancomycin.

A prospective in vivo quantification was performed to measure the elution of tobramycin and vancomycin antibiotics from two commonly used bone cements. Forty patients were divided into four groups: Group I, tobramycin-Simplex; Group II, tobramycin-Palacos-R; Group III, vancomycin-Simplex; and Group IV, vancomycin-Palacos-R. Antibiotic levels were measured from hemovac wound drainage, urine, and serum and compared with control groups who received either intravenous tobramycin or vancomycin. There were no significant differences in daily mean tobramycin levels in hemovac samples between Groups I and II. Tobramycin hemovac levels from Groups I and II were significantly higher than the tobramycin control group. Similarly, no differences were seen in daily mean vancomycin levels of the hemovac samples between Group III and IV; however, the intravenous vancomycin control group had significantly higher levels in the hemovac fluid than Groups III or IV. Tobramycin in the hemovac fluid from Groups I and II was highly bioactive against the control organism. Vancomycin in the hemovac fluid from Groups III and IV had variable bioactivity against the control organism. In 30% of the cases, no vancomycin was detected in the hemovac fluid, and in these cases, the hemovac fluid had no effect on the control organism. Tobramycin elutes to give adequate local tissue levels and releases antibiotic effects when used in an antibiotic bone cement combination. Vancomycin has variable elution properties and is not a predictable additive for the bone cements tested.

Bone Cements↗

[Early recognition of brain death--a contribution to organ explantation].

The criteria for brain death are presented and reference is made to the legally required observation period. To shorten the observation period, the Federal Medical Council (Bundesärztekammer) set out in 1986 possible aids to making decisions. The time at which extensive additional investigations should start makes it necessary to approximately determine the moment of brain death. The tear secretion test presented in this paper could be a further decision aid.

Brain Death↗

Doppler echocardiographic patterns of left ventricular filling in patients early after acute myocardial infarction.

Diastolic function is routinely assessed using Doppler-derived left ventricular (LV) filling patterns. Ratios between peak flow velocities during early filling and atrial contraction (E/A) of less than 1 are considered pathologic and diagnostic of impaired relaxation. Myocardial stiffness can normalize the E/A ratio, and thus, in some clinical settings, a normal E/A ratio may identify patients with high filling pressures. LV filling patterns were studied with Doppler echocardiography in 15 healthy subjects and 38 patients with recent acute myocardial infarction. The results were correlated with clinical and hemodynamic variables. E/A ratio less than 1 was found in 14 patients (37%) and in only 1 control subject; E/A ratio greater than 2 found in 5 patients (13%) and in only 1 control subject; 19 patients (50%) had an apparently normal E/A ratio. No correlation was found between LV filling pattern and ejection fraction or presence of diabetes or arterial hypertension. LV end-diastolic pressures were low to normal in patients with an E/A ratio less than 1 and were usually greater than 15 mm Hg in those with normal or abnormally increased (greater than 2) E/A ratios. Thus, an apparently normal E/A ratio in patients after myocardial infarction may identify those with more severe LV diastolic dysfunction and increased LV filling pressure.

Cardiac Catheterization↗

Improved outcome with early blood administration in a near-fatal model of porcine hemorrhagic shock.

Current recommendations for the preoperative management of hemorrhagic shock include the initial infusion of 2 L of isotonic crystalloid regardless of the severity of hemorrhage. While this approach may be adequate for patients who experience only mild to moderate hemorrhagic insults, it has never been tested in a clinically relevant model of severe life-threatening hemorrhage. The authors used a porcine model of rapidly fatal hemorrhage with a reproducible and relevant physiologic end-point, the absence of vital signs, to test the hypothesis that even brief delays in blood replacement may result in higher mortality rates and worsen hemodynamic and metabolic responses to hemorrhage. Twenty-four immature swine (11-17 kg) were bled continuously at a decelerating rate until the following criteria were met: (1) respiratory arrest, (2) a pulse pressure of 0 and, (3) a slowing of cardiac electrical activity of 15% or more. Resuscitation was begun 1 minute later. The animals were randomly assigned to one of three resuscitation regimens. Group A (n = 8) received shed blood at a rate of 3 mL/kg/min for 10 minutes followed by normal saline (NS) at a rate of 3 mL/kg/min for 10 minutes. Group B (n = 8) received NS at a rate of 3 mL/kg/min for 10 minutes followed by shed blood at a rate of 3 mL/kg/min for 10 minutes. Group C, controls, (n = 8) received NS at a rate of 3 mL/kg/min for 20 minutes. Animals were observed for 30 minutes after resuscitation or until death. Mortality was 25%, 37.5%, and 100% for groups A, B, and C, respectively (P < .05 for group C versus group A or B).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Effect of benazepril on myocardial ischaemia in patients with chronic stable angina pectoris.

The anti-ischaemic properties of benazepril, a non-sulfhydryl inhibitor of angiotensin-converting enzyme, were assessed in 20 patients with chronic stable angina pectoris, by repeated exercise tests and repeated 72-h ambulatory electrocardiographic monitoring. The study was a double-blind, placebo-controlled cross-over; 11 patients received benazepril 10 mg b.i.d. and nine received 20 mg b.i.d. All patients had a positive treadmill stress test and at least three ischaemic episodes during 24 h of ambulatory electrocardiographic monitoring. Benazepril at a dose of 10 mg b.i.d. did not improve the exercise duration, the time taken to reach 1 mm ST depression. Similar findings were observed during treatment with 20 mg b.i.d. Benazepril at a dose of 10 mg b.i.d. was ineffective in improving ischaemic parameters during daily activities. However, among the nine patients who received 20 mg b.i.d. the number of ischaemic episodes was reduced from 142 to 103, and the total duration of ischaemic was reduced from 1099 to 531 min. The number of weekly anginal attacks was reduced from 58 to 33, and the weekly sublingual nitroglycerin tablets consumption was reduced from 31 to 14. When the two doses (10 mg and 20 mg) were combined (N = 20), the number of ischaemic episodes was reduced from 314 to 260 (P = 0.074), and the duration of ischaemic was reduced from 3453 to 2514 min (P = 0.072).

Aged↗

Improved outcome with hypotensive resuscitation of uncontrolled hemorrhagic shock in a swine model.

Recent animal studies have shown that aggressive saline infusion may produce significant mortality in models of moderately severe (20-30 mL/kg) uncontrolled hemorrhage. The postulated mechanism is an increase in hemorrhage that accompanies restoration of normal blood pressure. Although aggressive saline infusion and restoration of blood pressure appear indicated when hemorrhage is potentially lethal (40-45 mL/kg), we hypothesized that the attempt to restore blood pressure with aggressive saline infusion would not improve survival. This study used a swine model of severe uncontrolled hemorrhagic shock to compare the effects of resuscitation to mean pressures of 40 and 80 mm Hg. Twenty-four immature swine, each with a surgical steel aortotomy wire in place, were bled rapidly from a femoral artery catheter to a mean arterial pressure (MAP) of 30 mm Hg. The aortotomy wire was then pulled, producing a 4-mm aortic tear and free intraperitoneal hemorrhage. When the pulse pressure decreased to 5 mm Hg, saline infusion was begun at 6 mL/kg/minute and continued as needed to maintain the following endpoints: group I (MAP = 40 mm Hg), group II (MAP = 80 mm Hg), and group III (no resuscitation). After a maximum saline infusion of 90 mL/kg, the infusate was changed to shed blood at 2 mL/kg/minute. Data were compared using analysis of variance and Fisher's exact test. One-hour survival was 87.5%, 37.5%, and 12.5% for groups I, II, and III, respectively. Intraperitoneal hemorrhage for the three groups was 8.2 mL/kg, 39.9 mL/kg, and 6.7 mL/kg. The amount of saline infused was 55.8 mL/kg in group I and 90 mL/kg in group II.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Quantification of walking exercise required for improvement of dipyridamole thallium-201 image quality.

Dipyridamole 201Tl imaging is an accepted diagnostic procedure for the evaluation of patients unable to perform adequate treadmill exercise, but is limited by high infradiaphragmatic activity. While recent studies have shown that the addition of exercise reduces this activity, the amount of exercise needed to effect such an improvement is uncertain. To prospectively evaluate the amount of walking exercise required to produce improvement in image quality, 120 patients were randomized to either a control group receiving dipyridamole alone, or to dipyridamole supplemented with one of four exercise protocols. Ratios of heart-to-liver and heart-to-adjacent infradiaphragmatic activity were generated from anterior images acquired immediately following the test. Heart-to-total infradiaphragmatic activity was also graded semiquantitatively. Results showed improved target-to-background ratios as well as semiquantitative assessment of image quality for dipyridamole supplemented with exercise as compared to dipyridamole alone. No difference was seen between walking in place and Bruce treadmill exercise at Stage 0 or 0.5. A trend towards higher values was seen with Bruce Stage 1 exercise supplementation, but this did not reach statistical significance. No significant complications occurred during the study. We conclude that 3 min of walking exercise is a safe and effective means of improving the quality of dipyridamole 201Tl images.

Adult↗

[Obstetrical peridural anesthesia with bupivacaine and buprenorphine. A randomized double-blind study in comparison with untreated controls].

Epidural anaesthesia with local anaesthetics has become a standard method of pain relief during labour. In recent years, spinal opiates, alone and in combination with local anaesthetics, have also been tried with varying degrees of success. Buprenorphine, a potent lipophilic opiate with long duration of action, has been used in several trials for caesarean section [3, 4, 6], but not yet in spontaneous labour. The aim of the present investigation was to evaluate epidural anaesthesia with bupivacaine alone and with bupivacaine+buprenorphine in comparison with no anaesthetic treatment in control parturients. METHODS. A total of 80 healthy women during labour at full term (age 18-38 years, weight 54-107 kg) were studied to evaluate the influence of 0.3 mg buprenorphine (group BB) vs placebo (group B) added to an initial dose of 15 ml plain bupivacaine 0.33% for lumbar catheter epidural anaesthesia. Plain bupivacaine 0.25% (10 ml) without any opiate admixture was used for reinjections. The control group was made up of 48 untreated parturients. After every injection, blood pressure, heart rate and respiratory rate were measured repeatedly, as were time intervals between injections, extent of blockade, duration of labour, actual and retrospective visual analogue pain score, and side effects such as pruritus, shivering or nausea and emesis. Maternal capillary blood gases were analysed three times during labour, and Apgar scores and venous and arterial umbilical blood gas analyses were obtained immediately after delivery. RESULTS. Admixture of buprenorphine 0.3 mg significantly increased the time interval between the first and second epidural doses (B: 162 +/- 47 vs BB: 224 +/- 64 min; mean, SD; Table 2) and significantly reduced the incidence of shivering (Table 9). The incidence of instrumental delivery was comparable in all groups (bupivacaine 32.5%, bupivacaine+buprenorphine 27.5%, control 21%; n.s.). No clinically relevant differences were observed between the epidural patients in onset and duration of the block (Fig. 1), analgesic efficacy (Fig. 2), duration of spontaneous labour (BB: 8.6 +/- 3.1 h, B: 8.5 +/- 2.9 h; n.s.) and vital functions of mothers and newborns. Although some statistically significant differences between the three groups were found in some parameters of the blood gas analyses (Table 7), the clinical condition of the newborns was always acceptable; Apgar scores were not significantly different. DISCUSSION AND CONCLUSIONS. The addition of buprenorphine to bupivacaine resulted in some advantages to the mother (reduced incidence of shivering) and the anaesthetist (time lapse before first reinjection was necessary) without jeopardizing the situation of the baby. Compared with untreated control parturients, retrospective pain scores during epidural anaesthesia with bupivacaine (with or without buprenorphine) were significantly lower. No clinically relevant disadvantages of epidural anaesthesia were observed. More studies are required to evaluate whether buprenorphine admixture allows a dose reduction of bupivacaine and could then claim clearer advantages than were found in the present investigation.

Adult↗

Complementary role of ambulatory electrocardiographic monitoring and exercise testing in evaluation of myocardial ischemia.

For detection of myocardial ischemia, exercise testing is a better tool than AEM and therefore should be preferred procedure for this purpose. In patients who exhibit ischemic changes on exercise testing, the presence of ischemic changes on AEM carries significant prognostic information beyond the results of exercise testing; therefore, it is recommended that this test be performed in those who have ischemic changes on exercise at a moderate or low workload. AEM together with exercise testing can be used to assess efficacy of anti-ischemic drugs, can help to define the underlying mechanism of ischemia during daily life, and in certain groups of patients, like those with unstable angina, peripheral vascular disease, or after cerebrovascular events, it can replace exercise testing as a method for detecting ischemic changes.

Coronary Disease↗

The prognostic significance of glial fibrillary acidic protein staining in medulloblastoma.

Histologic and immunohistochemical properties of 53 medulloblastomas were analyzed with regard to clinical features and survival rate. No correlation was found between survival rate and histologic features of the tumor, such as desmoplastic reaction, number of mitoses, hemorrhages, necrosis, endothelial proliferation, glomerular arrangement, calcifications, rosettes, or oligodendroglial cells. However 82% of the patients with positive glial fibrillary acidic protein (GFAP) staining in numerous tumor cells survived more than 5 years; only 30% survived that long if their tumor cells were GFAP negative (P = 0.0093). This significant difference was not related to the mode of therapeutic protocol used. The authors suggest that GFAP staining may be a useful prognostic tool in medulloblastoma.

Adolescent↗

Usefulness of severity of myocardial ischemia on exercise testing in predicting the severity of myocardial ischemia during daily activities.

To determine the relation between myocardial ischemic indexes on exercise testing and on ambulatory Holter recording, 60 patients with stable coronary artery disease who exhibited an ischemic response to both testing procedures were studied. All patients performed a Bruce protocol exercise test and underwent 24-hour Holter recording within 2 weeks without antianginal medications. Mean exercise duration was 7.4 +/- 2.8 minutes, mean heart rate at 1-mm ST depression was 118 +/- 20 beats/min and mean maximal ST depression during exercise was 2.2 +/- 1 mm. During Holter recording the average number of ischemic episodes was 4.7 +/- 2.6 per patient, mean duration of daily ischemia was 62 +/- 54 minutes, mean maximal ST depression was 3.2 +/- 1.3 mm and average heart rate at 1-mm ST depression was 93 +/- 17 beats/min. Overall, the correlations between ischemic indexes on both testing procedures were very weak (mean r2 = 0.054). The only exercise variable that had a significant correlation (p less than 0.05) with all Holter variables was heart rate at 1-mm ST depression, yet it correlated very weakly (0.064 less than or equal to r2 less than or equal to 0.125) with most Holter covariates and had a better correlation (r2 = 0.256) only with average heart rate at 1-mm ST depression during Holter. Thus, ischemic indexes on exercise testing cannot accurately predict ischemic indexes on ambulatory Holter recording in patients with stable coronary artery disease who exhibit ischemic changes on both tests.(ABSTRACT TRUNCATED AT 250 WORDS)

Coronary Disease↗

Fatal pulmonary venoocclusive disease secondary to a generalized venulopathy: a new syndrome presenting with facial swelling and pericardial tamponade.

We describe a patient who developed fatal pulmonary artery hypertension secondary to diffuse venulitis. This otherwise healthy young woman first presented with generalized venulopathy, with chemosis, facial swelling, pleural effusions, and pericardial tamponade. The symptoms partially responded to steroid therapy, but over a 2-year course, a rapidly progressive and fatal venoocclusive disease developed. No other primary condition was diagnosed, and at autopsy, the patient had striking venulitis throughout, including the pulmonary bed. We believe that this is a unique case of pulmonary hypertension resulting from a generalized venulopathy.

Adult↗

Terminology of torsades de pointes.

Marked prolongation of the QT interval may be associated with life-threatening ventricular tachycardia. The ventricular tachycardia has a polymorphous appearance and is usually induced by antiarrhythmic drugs. This peculiar type of ventricular tachycardia was termed by Desserstenne torsades de pointes because of its twisting ORS axis. The main reason to give this entity a special name that differentiates it from other types of ventricular tachycardia is the unique therapeutic approach to its treatment. Torsades de pointes can be suppressed by interventions that shorten the QT interval by increasing the heart rate, such as ventricular or atrial pacing, isoproterenol infusion, or atropine. Recently intravenous magnesium was also shown to be extremely effective. If torsades de pointes is treated as a conventional ventricular tachycardia by drugs that may further prolong the QT interval, it may lead to fatal results. To draw the attention of physicians to this unusual form of ventricular tachycardia, we suggest that the term torsades de pointes be kept. This specific diagnosis will hopefully guide the treating physician in selecting the appropriate mode of therapy.

Animals↗

The herpes simplex virus trans-activator VP16 recognizes the Oct-1 homeo domain: evidence for a homeo domain recognition subdomain.

The homeo domain of the Oct-1 transcription factor directs formation of a multiprotein-DNA complex containing Oct-1, the herpes simplex virus (HSV) trans-activator VP16, and a second host cell factor (HCF). This VP16-induced complex alters the regulatory activity of Oct-1, in part, by associating it with the potent VP16 acidic transcriptional activation domain. Here, we show that in the absence of HCF, VP16 can recognize specifically the Oct-1 homeo domain. A region of VP16 near the acidic activation domain appears to be involved exclusively in homeo domain recognition because a 4-amino-acid insertion within this region only affects the ability of VP16 to interact with Oct-1, leaving its DNA- and HCF-binding activities unchanged. A 33-amino-acid peptide containing this region complexes with the Oct-1 POU domain bound to DNA, suggesting that this VP16 region contains an autonomous homeo domain recognition subdomain.

Amino Acid Sequence↗