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L J Hirsch

Publications and source records attributed to L J Hirsch.

At least 37 records · Page 2Linked to original sources
PubMed1996

Esophagitis associated with the use of alendronate.

BACKGROUND: Alendronate, an aminobisphosphonate and a selective inhibitor of osteoclast-mediated bone resorption, is used to treat osteoporosis in postmenopausal women and Paget's disease of bone. Aminobiphosphonates can irritate the upper gastrointestinal mucosa. METHODS: We describe three patients who had severe esophagitis shortly after starting to take alendronate and also analyze adverse esophageal effects reported to Merck, the manufacturer, through postmarketing surveillance. RESULTS: As of March 5, 1996, alendronate had been prescribed for an estimated 475,000 patients worldwide, and 1213 reports of adverse effects had been received. A total of 199 patients had adverse effects related to the esophagus; in 51 of these patients (26 percent), including the 3 we describe in case reports, adverse effects were categorized as serious or severe. Thirty-two patients (16 percent) were hospitalized, and two were temporarily disabled. Endoscopic findings generally indicated chemical esophagitis, with erosions or ulcerations and exudative inflammation accompanied by thickening of the esophageal wall. Bleeding was rare, and stomach or duodenal involvement unusual. In patients for whom adequate information was available, esophagitis seemed to be associated with swallowing alendronate with little or no water, lying down during or after ingestion of the tablet, lying down during or after ingestion of the tablet, continuing to take alendronate after the onset of symptoms, and having preexisting esophageal disorders. CONCLUSIONS: Alendronate can cause chemical esophagitis, including severe ulcerations, in some patients. Recommendations to reduce the risk of esophagitis include swallowing alendronate with 180 to 240 ml (6 to 8 oz) of water on arising in the morning, remaining upright for at least 30 minutes after swallowing the tablet and until the first food of the day has been ingested, and discontinuing the drug promptly if esophageal symptoms develop.

Aged↗
PubMed1996

Oral alendronate induces progressive increases in bone mass of the spine, hip, and total body over 3 years in postmenopausal women with osteoporosis.

To determine the effects of long-term daily oral alendronate sodium (ALN) on bone mass in postmenopausal women with osteoporosis, 19 centers enrolled 516 postmenopausal women aged 45-80 years with spine bone mineral density (BMD) at least 2.5 SD below the mean for young premenopausal women in a 3-year, double-blind, placebo-controlled study. Subjects were randomly allocated to one of four treatment groups: placebo; alendronate, 5 or 10 mg/day for 3 years; or alendronate, 20 mg/day for 2 years followed by 5 mg/day for the 3rd year. All patients received 500 mg/day of supplemental calcium to ensure adequate calcium intake. BMD was measured by dual-energy X-ray absorptiometry at several skeletal sites. Nonsignificant mean decreases in BMD of the spine, femoral neck, and trochanter of 0.6, 0.7, and 0.4%, respectively, occurred in the placebo group at 3 years. Relative to placebo-treated patients, spine BMD increased by 5.4%, 7.4%, and 8.4% in the 5, 10, and 20/5 mg ALN groups, respectively. Increases at the femoral neck were 3.5%, 5.5%, and 4.3%, and those at the trochanter were 5.1%, 7.2%, and 7.2%, respectively. Thus, efficacy of 10 and 20/5 mg ALN was similar, whereas the 5 mg dose was less effective. BMD continued to increase over the entire 3-year study duration in the ALN-treated groups and, compared with the other dosage groups, 10 mg ALN produced the largest gains in BMD during the 3rd year. Changes in biochemical markers of bone turnover and mineral homeostasis confirmed the effect of ALN to decrease bone turnover to a new steady-state level. The safety and tolerability of ALN were comparable with those of placebo. In summary, 10 mg daily oral ALN given for 3 years significantly and progressively increases bone mass and is a generally well-tolerated treatment for osteoporosis in postmenopausal women.

Administration, Oral↗
PubMed1995

An overview of the results of clinical trials with alendronate, a promising treatment of osteoporosis in postmenopausal women.

The purpose of this overview is to provide a summary of recent data on the clinical safety and efficacy of alendronate sodium, an amino-bisphosphonate that is a potent and specific inhibitor of osteoclast mediated bone resorption, in the treatment of osteoporosis in postmenopausal women. Published data are available from two randomized, placebo-controlled, double-blind clinical trials of 2-year duration in over 470 patients with postmenopausal osteoporosis. The women studied were 4 to 5 years postmenopause, ages 42 to 76, with osteoporosis defined on the basis of low spine bone mineral density (BMD). Percent change in spine BMD was the primary endpoint; hip and total body BMD were secondary outcomes. In the Dose Ranging Study, alendronate 5 and 10 mg/day for 2 years significantly increased lumbar spine BMD by approximately 7.2%, which did not differ from patients receiving higher doses. Total hip BMD increased by 3.6 and 5.3%, respectively, with the 5 and 10 mg doses; 10 mg was significantly more effective than 5 mg. Placebo patients lost 1.2-1.4% BMD at these sites. Total body BMD also significantly increased with alendronate. In the Calcitonin Comparison Study, alendronate 10 and 20 mg/day for 2 years significantly increased spine and hip BMD; 100 IU of intranasal salmon calcitonin did not increase BMD at any site, and did not differ from placebo. Alendronate reduced bone turnover to a new steady state, as assessed by biochemical markers and was well tolerated. Preliminary reports indicate that alendronate progressively increases spine, hip, and total body bone mass for 3 years, with associated significant reductions in vertebral fractures, stature loss, and non-vertebral fractures.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1994

Comparison of hemodynamic responses to pipecuronium and doxacurium in patients undergoing valvular surgery while anesthetized with fentanyl.

Hemodynamic responses to pipecuronium bromide or doxacurium chloride were compared in patients undergoing valvular heart surgery. Thirty ASA class III-IV patients of either sex, mean age 62 +/- 3 years (+/- SD), weight 70 +/- 3 kg, were randomly selected to receive either doxacurium (0.08 mg/kg) or pipecuronium (0.15 mg/kg). Hemodynamic parameters were determined at preinduction, induction, 2 minutes and 6 minutes following administration of the muscle relaxant. Anesthetic induction consisted of midazolam, 0.10 mg/kg, followed by fentanyl, 5 micrograms/kg. Measured or calculated parameters were as follows: mean arterial pressure, heart rate, cardiac index, mean pulmonary artery pressure, systemic vascular resistance index, central venous pressure, pulmonary capillary wedge pressure, stroke volume index, left and right stroke work indices, and pulmonary vascular resistance index. Awake patients who had been randomly assigned to the pipecuronium group had significantly higher pulmonary capillary wedge pressures (22 +/- 2 v 15 +/- 2 mmHg; P < 0.05) and heart rates (86 +/- 3 v 64 +/- 5 beats/min; P < 0.05) than awake patients in the doxacurium group. Following induction, both wedge pressure and heart rate were not significantly different between the two groups. Compared to hemodynamics at induction, there were no clinically significant changes following administration of pipecuronium or doxacurium.

Anesthesia, Intravenous↗
PubMed1994

Urine hydrogen peroxide during adult respiratory distress syndrome in patients with and without sepsis.

BACKGROUND: The lung injury in adult respiratory distress syndrome (ARDS) has been associated with increased expiratory hydrogen peroxide (H2O2) concentrations. Furthermore, patients with sepsis and ARDS are reported to have greater serum scavenging of H2O2 than patients with ARDS only. We hypothesized that the systemic presence of H2O2 would be detectable in the urine of these two groups of patients and that, in the case of ARDS sepsis, the relative contribution of each disease to the production this analyte would be discernible. Accordingly, we used an in vitro radioisotope assay to follow the weekly course of urine H2O2 levels in ARDS patients with and without sepsis, and in samples from control non-ARDS patients with sepsis with indwelling urinary catheters and in samples provided by healthy volunteers. METHODS: Thirty patients with ARDS were included in the study: 23 had sepsis and 7 were sepsis free. An indwelling catheter was used to collect urine from each patient over a 24-h period, first within 48 h of ICU admission and then every seventh day over the course of their illness. Urine H2O2 was measured by competitive decarboxylation of 1-14C-alpha-ketoglutaric acid by H2O2. Urine samples were provided by 20 healthy volunteers while, in 10 non-ARDS patients with sepsis, urine was collected over one 24-h period following a 5-day minimum with an indwelling urinary catheter. RESULTS: Urine H2O2 concentration in healthy control subjects (88 +/- 4 mumol/L) and non-ARDS patients with urinary catheters (96 +/- 5 mumol/L) was not significantly different. During the first 48 h in the ICU, urine H2O2 in patients with ARDS only (295 +/- 29 mumol/L) was significantly lower (p < 0.05) than patients with ARDS and sepsis (380 +/- 13 mumol/L); however, the lung injury scores of these two groups did not differ. Furthermore, within the first 48 h, the urine H2O2 of the patients with ARDS and sepsis who did not survive (427 +/- 19 mumol/L; n = 7) was significantly higher than that in patients who survived sepsis (352 +/- 14 mumol/L; n = 15). Thereafter, the lung injury scores and urine H2O2 levels of the nonsurvivor ARDS-sepsis group remained significantly higher compared with the other two groups. At lung injury scores of 3 and 2, regardless of days in ICU, the patients with ARDS only had significantly lower urine H2O2 (266 +/- 30 mumol/L and 167 +/- 24 mumol/L, respectively) compared with the survivor ARDS-sepsis group (376 +/- 19 mumol/L and 250 +/- mumol/L). When the patients with ARDS (both ARDS only and with sepsis) recovered, their urine H2O2 concentration did not differ from the control groups (healthy donors and patients without ARDS). CONCLUSION: Lung injury scores did not differentiate patients with ARDS and sepsis from patients with ARDS only during the first 10 days in the ICU; however, urine H2O2 levels were significantly greater in the patients with ARDS and sepsis. Moreover, despite no initial difference in lung injury, patients who did not survive ARDS and sepsis had consistently greater urine H2O2 concentration than patients who survived sepsis. The urine H2O2 level in the ARDS-only group was about 70 percent of the level in the survivor ARDS and sepsis group, suggesting that ARDS alone is the major contributor to the H2O2 oxidant processes during combined ARDS and sepsis. Furthermore, these studies demonstrate that urine H2O2 may be a useful analyte to differentiate the severity of oxidant processes in patients with ARDS and sepsis albeit the prognosis appears to be survival or nonsurvival.

Adolescent↗
PubMed1994

Measurement of right ventricular volume in human explanted hearts using ultrafast cine computed tomography.

The quantitative measurement of right ventricular (RV) volume has been attempted by a number of methods, including nuclear magnetic resonance imaging, contrast angiography, echocardiography, and radionuclide angiography. All of these methods have limitations. Ultrafast cine computed tomographic (CT) scan is a new technology that may have an important role in on-line ventricular volume measurements. Twelve human explanted hearts, fixed in formalin, were subjected to ultrafast cine CT scans to estimate RV volume. The volumes derived from the CT scans were compared with actual fluid volumes needed to fill the RV volume measurements. All measurements were conducted independently by two observers. Actual RV volumes in the 12 hearts ranged from 29.8 ml to 174.6 ml. A strongly significant correlation between actual volume and CT volume was seen (r = 0.99). Agreement between observers was also seen to be highly significant (r = 0.992). Limitations to accurate in vivo assessment due to bolus injection of contrast medium might include alterations in ventricular pressure change. Similarly, differentiation of the endocardial border with contrast may not be as sharp as that with an air-tissue interface. This study demonstrates that RV volumes can be reliably determined by ultrafast cine CT scans in explanted hearts. On-line systolic and diastolic volumes and thus stroke volume, ejection fraction, etc, can be accurately defined independent of cardiac orientation. This technique offers opportunities to study ventricular function under various conditions.

Cardiac Volume↗
PubMed1993

Coronary angiographic changes with lovastatin therapy. The Monitored Atherosclerosis Regression Study (MARS).

OBJECTIVE: To assess the effects of lipid-lowering therapy with lovastatin on coronary angiographic findings in patients with coronary artery disease and to compare the findings with those of two lipid-lowering angiographic trials using similar end points. DESIGN: Randomized, double-blind, placebo-controlled, multicenter coronary angiographic trial. SETTING: Community- and university-based cardiac catheterization laboratories. PARTICIPANTS: A total of 270 patients, 37 to 67 years old, with total cholesterol ranging from 4.92 to 7.64 mmol/L (190 to 295 mg/dL) and angiographically defined coronary artery disease. INTERVENTION: A cholesterol-lowering diet and either lovastatin, 80 mg/day, or placebo. OUTCOME: Per-patient change in percent diameter stenosis as determined by quantitative coronary angiography (primary end point). Global change score, based on the consensus of blinded expert readers regarding angiographic change (secondary endpoint). RESULTS: Lovastatin lowered total cholesterol level by 32%, low-density lipoprotein cholesterol by 38%, and the apolipoprotein B by 26% and raised the high-density lipoprotein cholesterol by 8.5% (P < 0.001). Average percent diameter stenosis increased 2.2% in placebo recipients and 1.6% in lovastatin recipients (P > 0.20). For lesions 50% or greater, average percent diameter stenosis increased 0.9% in placebo recipients and decreased 4.1% in lovastatin recipients (P = 0.005). The mean global change score was +0.9 (indicating progression) in the placebo group and +0.4 in the lovastatin group (P = 0.002); 13 placebo recipients and 28 lovastatin recipients had global change scores indicating regression (P < 0.02). CONCLUSION: Treatment with lovastatin plus diet slows the rate of progression and increases the frequency of regression in coronary artery lesions (by global change score), especially in more severe lesions (by quantitative angiography). This is the third lipid-lowering trial to show a benefit using the global change score, an end point predictive of clinical coronary events. Differences between two of these trials, using quantitative coronary angiographic end points, may have theoretical bearing on the mechanisms by which lipid-lowering therapy operates at the level of the arterial wall.

Adult↗
PubMed1993

Effects of fentanyl on coronary blood flow distribution and myocardial oxygen consumption in the dog.

Little data exist on the effects of fentanyl on coronary blood flow (CBF), myocardial oxygen balance, and the regional distribution of blood flow. These studies were designed to determine whether fentanyl had any intrinsic effects on myocardial oxygen consumption (MVO2) and blood flow distribution. In anesthetized dogs, fentanyl was administered in a dose of 50 micrograms/kg and various measurements were made at 5 and 20 minutes. After hemodynamic recovery from the fentanyl, the animals were treated with atropine to block the known vagomimetic effect of fentanyl and challenged with acetylcholine (3.5 micrograms/kg); then fentanyl (50 micrograms/kg) was again administered and measurements made at 5 and 20 minutes. In the untreated dogs at 5 minutes post-fentanyl, heart rate (HR) decreased 30% and at 20 minutes decreased 29%. Treatment with atropine essentially eliminated HR changes at both time periods. Mean arterial pressure (MAP) fell by 20% and 22% at 5 minutes and 20 minutes, respectively, in the untreated group, but when atropine was administered, MAP was observed to be intermediate between baseline and the untreated animals. Left ventricular MVO2 at 5 minutes in the untreated group was modestly but not significantly reduced. However, at 20 minutes post-fentanyl, MVO2 decreased significantly. MVO2 was essentially unchanged after atropine. Regional CBF (measured by radiolabelled microspheres) was unchanged at 5 minutes, but all layers exhibited significant reductions at 20 minutes. In the atropine group, only the LV epicardial area appeared to show decreases in flow.(ABSTRACT TRUNCATED AT 250 WORDS)

Anesthesia, Inhalation↗
PubMed1993

Hemodilution with oxyhemoglobin. Mechanism of oxygen delivery and its superaugmentation with a nitric oxide donor (sodium nitroprusside).

BACKGROUND: Hemodilution (HD) with oxyhemoglobin colloid (oxyHb) provides a greater arterial oxygen content (CaO2) than HD with conventional colloids; however, oxygen delivery (DO2) is essentially the same, because, in contrast to conventional HD, cardiac output (CO) is not augmented. This study seeks to elucidate the mechanism that limits CO during oxyHb-HD and to test whether infusion of a nitric oxide (NO) donor would augment DO2, because oxyHb is known to inactivate in vitro endothelial-derived NO. METHODS: Anesthetized dogs were isovolemically hemodiluted with 10% oxyHb, 8% albumin, or 10% methemoglobin (weak NO inactivator) to 20% hematocrit. After HD, sodium nitroprusside (SNP) was titrated intravenously until decreases (> 10 mmHg) in mean aortic pressure (Pao) indicated the presence of exogenous NO. Systemic hemodynamics and regional blood flows (microsphere method) were measured. RESULTS: Albumin-HD and metHb-HD produced typical HD-mediated responses: increased CO (63-65%), slight decreases (13-15%) in DO2, decreases in systemic vascular resistance (SVR) proportional to the decreases (49-52%) in blood viscosity of all three groups, and increased regional blood flows (RBF). Responses to oxyHb-HD were atypical: CO and its determinants were not changed, DO2 decreased (23%) proportional to CaO2, and SVR and most RBF were not changed except for a net redistribution of CO to myocardium and skeletal muscle. In albumin-HD or metHb-HD, SNP (2-5 micrograms.kg-1.min-1) induced comparable decreases in mean Pao (29-37%) and SVR (39-41%); however, CO, RBF, and DO2 were not affected. In oxyHb-HD, exceptionally large doses of SNP (54 +/- 5 micrograms.kg-1.min-1) decreased mean Pao only 19 +/- 1%; however, CO increased 78 +/- 5% and decreases (61 +/- 3%) in SVR were slightly greater than viscosity reductions. Other determinants of CO were not affected. Most RBF increased proportional to CO; there was, however, preferential distribution to myocardium and skeletal muscle. Consequently, the augmented CO, and CaO2 of oxyHb-HD, produced large increases in DO2, 77 +/- 5% from HD alone and 43 +/- 3% from prehemodilution values. CONCLUSIONS: This study indicates that the limited CO and DO2 of oxyHb-HD resulted from opposing changes in two determinants of flow, i.e., reduced blood viscosity and increased arterial resistance (vasoconstriction). The vasoconstriction was not evident with metHb-HD and was reversed by the SNP infusion, indicating that oxyHb inactivated in vivo endothelial-derived NO. The ability of the NO donor (SNP) to facilitate large viscosity-mediated increases in DO2 during oxyHb-HD is an important finding that could potentially render oxyHb colloids more useful than conventional colloids, particularly for the individual with a compromised circulation who would benefit from an increased oxygen supply.

Animals↗
PubMed1993

Separation of myocardial versus peripheral effects of calcium administration in normocalcemic and hypocalcemic states using pressure-volume (conductance) relationships.

This study used left ventricular pressure-volume (conductance) relationships to separate the effects of calcium administration on myocardial performance and peripheral vasoconstriction in normocalcemic and hypocalcemic states. Hypocalcemia was produced in anesthetized dogs with intravenous citrate-phosphate-dextrose until serum [Ca2+] was approximately 0.7 mmol/L. Calcium (CaCl2) bolus (5 mg/kg) was administered during normocalcemia (n = 6) and hypocalcemia (n = 6), and data were collected at 1, 5 and 10 min after CaCl2 administration. During normocalcemia, CaCl2 administration increased [Ca2+] 19% at 1 min and was accompanied by a 47% (P < 0.05) decrease in left ventricular contractility (i.e., end-systolic elastance or E(lves)) and a 13% (P < 0.05) increase in systemic vascular resistance. At 5 and 10 min, serum [Ca2+] and the hemodynamic variables began to return to the baseline values. During hypocalcemia, E(lves) decreased 25% (P < 0.05), but after CaCl2 bolus, it increased to baseline levels and remained there during the 10-min period. Hypocalcemia and the CaCl2 bolus did not significantly affect SVR. In conclusion, these studies suggest that the indications for the use of calcium should depend on the initial serum level of ionized calcium.

Animals↗
PubMed1992

The Monitored Atherosclerosis Regression Study (MARS). Design, methods and baseline results.

OBJECTIVE: The Monitored Atherosclerosis Regression Study (MARS) was designed to evaluate the effect of cholesterol lowering by monotherapy with an HMG-CoA reductase inhibitor on progression/regression of atherosclerosis in subjects with angiographically documented coronary artery disease. The purpose of this paper is to present the design, methods, and baseline results of MARS. DESIGN: MARS is a prospective, randomized, double-blind, placebo-controlled trial with baseline, 2-year, and 4-year coronary angiography as well as carotid, brachial, and popliteal ultrasonography. SETTING: Outpatient clinics at the University of Southern California School of Medicine and the University of Wisconsin School of Medicine. SUBJECTS: Two hundred seventy participants of both sexes were recruited directly from the cardiac catheterization laboratory or by chart review of patients having undergone cardiac catheterization in the past. Subjects were considered eligible if they had angiographically demonstrable atherosclerosis in 2 or more coronary artery segments, unaltered by angioplasty, with at least 1 lesion > or = 50% but < 100% diameter stenosis (%S). The inclusion range for total cholesterol (TC) was between 190 and 295 mg/dL. Exclusion factors were: triglycerides > or = 500 mg/dL; premenopausal females; uncontrolled hypertension; diabetes mellitus; untreated thyroid disease; liver dysfunction; renal insufficiency; congestive heart failure; major arrhythmia; left ventricular conduction defects; or any life-threatening disease. INTERVENTION: Subjects were placed on a low-fat, low-cholesterol diet and either 40 mg b.i.d. lovastatin (Mevacor) or placebo. Randomization was stratified by sex, smoking status, and TC. MAIN OUTCOME MEASURES: Per-subject average change in %S as determined by quantitative coronary angiography (QCA) is the primary angiographic endpoint. Secondary endpoints are: categorical analyses of the proportion of subjects with progression; human panel reading of coronary angiograms; and change in minimum lumen diameter (MLD) in mm by QCA. Carotid, brachial, and popliteal ultrasonography is also being performed. RESULTS: The subjects randomized into MARS are 91.5% male with an age range of 37 to 67 years (mean age 57.9 years). For the cohort, baseline lipids are (mean +/- SD): TC, 231 +/- 24 mg/dL; low-density lipoprotein cholesterol (LDL-C) by ultracentrifugation, 153 +/- 24 mg/dL; LDL-C, by calculation, 157 +/- 23 mg/dL; high-density lipoprotein cholesterol (HDL-C), 43 +/- 10 mg/dL; and triglycerides, 160 +/- 73 mg/dL. There were no significant differences between treatment groups in baseline lipid levels or baseline angiographic characteristics. CONCLUSIONS: MARS baseline data show adequacy of randomization with comparability of lovastatin and placebo groups in demographic, lipid, and angiographic characteristics.

Adult↗
PubMed1992

Background and methods for the lovastatin restenosis trial after percutaneous transluminal coronary angioplasty. The Lovastatin Restenosis Trial Study Group.

Restenosis remains a critical limitation of percutaneous transluminal coronary angioplasty (PTCA). Recent experimental and clinical data have suggested that lovastatin, an hydroxymethylglutaryl coenzyme A reductase inhibitor, may reduce the rate of restenosis through reduction of low density-lipoprotein (LDL) cholesterol or possibly by direct effects. Lovastatin may therefore produce favorable alterations in endothelial healing, resulting in a decreased smooth muscle cell proliferative response to injury after angioplasty. Emory University, in conjunction with Merck Research Laboratories, has initiated a 10-center double-blinded, placebo-controlled, randomized trial to assess the effect of both pretreatment and aggressive lipid lowering with lovastatin in reducing the rate of restenosis. Lovastatin achieves approximately 75% of its effect on LDL cholesterol by 1 week. Thus, patients scheduled for PTCA are randomly assigned pretreatment with lovastatin, 40 mg twice daily, or placebo 7 to 10 days before PTCA. Therapy is continued for 6 months, at which time repeat coronary arteriography is performed. A detailed safety algorithm was designed, with patients receiving lovastatin and matching placebo back-titrated on a 1:1 basis for LDL cholesterol less than 50 mg/dl. The power is a 90%, alpha = 0.05, 2-tailed test to reduce restenosis from 30 to 15%. The sample size is 360 patients in the 2 arms; allowing for a 10% dropout rate, approximately 400 patients will be randomized. Patients with successful PTCA, less than 50% residual diameter stenosis and greater than or equal to 20% diameter stenosis reduction are analyzed for restenosis at 4 to 6 months by quantitative coronary arteriography.(ABSTRACT TRUNCATED AT 250 WORDS)

Angioplasty, Balloon, Coronary↗
PubMed1992

Lack of increased cardiac output during hemoglobin hemodilution can be reversed with sodium nitroprusside.

To investigate a possible connection between EDRF or nitric oxide (NO) and the unchanged cardiac output (CO) during hemoglobin-hemodilution we infused nitroprusside (NP) in eight Hb-diluted dogs (Hct approximately 20%). Normal hypotensive doses of NP were not effective and supranormal doses (133.0 micrograms/kg/min) were needed to induce even a modest decrease in mean AoP (approximately 25 mmHg). With these NP doses, cardiac output increased 177%, diastolic AoP (afterload) decreased 30%, while systolic AoP and LVEDP (preload) were unchanged. Heart rate, LV contractility (pressure-volume function) and blood volume were not changed throughout the study. Normally, NP alone decreases both preload and afterload resulting in unchanged CO. In the Hb + NP dogs, CO increased because only afterload decreased suggesting a selective effect of Hb on venous and arterial smooth muscle relaxation. In hemodilution with nonhemoglobin colloids, CO increases primarily because the diluted blood offers less viscous resistance to ventricular ejection. It appears that in order for cardiac output to increases in the presence of Hb, some decrease in arteriolar resistance is needed, presumably to unmask the effects of reduced viscosity. These results suggest the unchanged CO during Hb-dilution is related to a selective effect of Hb on venous and arteriolar nitric oxide (EDRF) function.

Animals↗
PubMed1991

Comparison of bitemporal and unitemporal epilepsy defined by depth electroencephalography.

Of 166 consecutive patients studied with depth electroencephalography (EEG), 87 had seizures arising from one temporal lobe and 23 had seizures arising independently from each temporal lobe. We retrospectively reviewed and compared those patients with unitemporal and those with bitemporal seizures. There was no statistically significant differences between the two groups in terms of age at onset of seizures, duration of epilepsy, localization of scalp EEG abnormalities, surgical results, or pathological findings. The bitemporal group, however, had significantly fewer patients with a history of febrile seizures (p less than 0.025). Two patients with bitemporal seizures were later found to have extratemporal lesions, and one an extrahippocampal temporal lesion, on magnetic resonance scans; one patient's extratemporal lesion was resected and all habitual seizures stopped. These findings suggest that a single pathophysiological process accounts for unitemporal and some bitemporal epilepsy, but that independent onset of seizures from each temporal lobe detected by depth EEG may also indicate extratemporal foci.

Adolescent↗
PubMed1991

Temporal lobectomy in patients with bitemporal epilepsy defined by depth electroencephalography.

Patient selection for temporal lobectomy was reviewed for 23 patients with seizures that arose independently from each temporal lobe as detected by depth electroencephalography (EEG). Although neuropsychological testing, interictal EEG findings, imaging studies, and subclinical seizures were also considered, all patients offered temporal lobectomy had (1) at least 50% of the clinical seizures originating from the lobe to be resected, (2) adequate contralateral memory on testing with amobarbital, and (3) no clear evidence of an extratemporal focus. Eleven patients underwent temporal lobectomy. Pathological findings were considered positive in all nine specimens reviewed. Nine patients had no seizures, one had greater than 75% reduction in seizure frequency, and 1 had 50 to 75% reduction. Pathological features and clinical outcome were similar in the 6 patients with fewer than 80% and the 5 patients with at least 80% of seizures originating from the resected lobe. Thus, having fewer than 80% of seizures originate from one temporal lobe should not be an absolute contraindication for temporal lobectomy.

Adolescent↗
PubMed1991

Studies of central nervous system disorders with single photon emission computed tomography and positron emission tomography: evolution over the past 2 decades.

Single photon emission computed tomography (SPECT) was introduced in the 1960s to detect breakdowns in the blood-brain barrier and was replaced by x-ray computed tomography in the mid-1970s. The development of the deoxyglucose (DG) technique to measure regional cerebral glucose metabolism by employing either autoradiography, using 14CDG, or positron emission tomography (PET), using 18FDG, added a major dimension to the investigation of brain function. In the late 1970s and early 1980s, the FDG-PET technique was widely used to examine a variety of neuropsychiatric disorders. It soon became apparent that functional imaging was more sensitive than anatomic imaging in detecting abnormalities of the brain related to aging, dementia, tumors, seizures, cerebral vascular accidents, and psychiatric problems. Because of its complexity and the cost involved, PET was used in a limited number of centers in the United States. However, the success of PET resulted in the resurgence of interest in SPECT as an alternative technology after almost a decade. This became possible because of the synthesis of iodine 123- and technetium 99m-labeled radiopharmaceuticals to determine regional cerebral blood flow. Since blood flow and metabolism are coupled in most pathological states, patterns of abnormality noted on SPECT were similar to those seen on PET in many disorders. Since the introduction of high resolution SPECT imaging instruments, the role of SPECT has been further enhanced. The successful synthesis of both positron and single emitting radioligands to image dopamine and other receptors has started a new era in neurosciences and will have a far-reaching impact on the day-to-day practice of neuropsychiatry.

Adult↗