Correction to: The effect of beta blocker withdrawal on adenosine myocardial perfusion imaging.

Regrettably the original version of the above article contained errors in Table 2 and wrong values in the text. The corrected table is presented here and the values which have been corrected now appear in bold text. Page 1223 abstract Global MBF showed an increase from 180.2 ± 59.9 to 193.6 ± 60.8 mL minute/100 g (P = .002) after beta blocker withdrawal. Page 1225 Mean systolic and mean diastolic blood pressure during adenosine were nearly identical (P = .77 and P = .79) with and without beta blocker. Mean heart rate and mean RPP during adenosine significantly increased after beta blocker withdrawal by 15.2% ± 17% (P = .001) and 16.2% ± 23% (P = .004), respectively. Page 1226 The data are listed in Table 2, lower third. Global MBF showed a significant increase by 7.4% ± 10% (P = .002) after beta blocker withdrawal. The individual data are depicted in Figure 1. All but three patients had a lower global MBF without beta blocker than with. The segmental MBF values (Figure 2) demonstrated a strong correlation over the entire range of perfusion values. The average effect was a slight perfusion shift of about 1015 mL minute-1/100 g in the range of 100-300 mL minute-1/100 g. The mCR under adenosine declined by 8.1% ± 11% (P = .038) and the normalized RPP by 16.2% ± 21% (P = .004) after betablocker discontinuation. Table 2 Hemodynamic response under adenosine, perfusion, and left-ventricular function.

The effect of beta blocker withdrawal on myocardial SPECT modeled from adenosine 13N-ammonia PET.

AIM: The effect of beta blockers (BB) on myocardial imaging has been studied in several SPECT and PET studies with divergent results concerning perfusion and impact on diagnostic accuracy. The present study evaluated the effect of BB withdrawal on virtual SPECT studies modeled from quantitative PET perfusion scans. PATIENTS, METHODS: Data from 20 CAD patients scheduled for adenosine 13N-ammonia imaging with and without BB were considered. Modeling the uptake characteristics of 99mTc-MIBI, all parametric stress PET polarmaps were transferred to virtual 20-segment SPECT polarmaps. The SPECT studies were categorized with a 5-point score and read to assess the effect of the BB withdrawal on scan result and interpretation. RESULTS: The SPECT analysis revealed a mean score of 6.0 ± 4.7 with, and of 5.9 ± 4.5 without BB (p = 0.84). In 260 (74.9%) segments the scores were equal in both conditions. Without BB a downstaging was recorded in 44 segments (12.7%), an upstaging in 43 segments (12.4%). An essentially different interpretation (shift from medical therapy recommendation to angiography) was recorded in one patient. In six cases the interpretation differed mildly. CONCLUSION: In the majority of patients studied, scan results and interpretation remain unchanged after discontinuation of the BB. Nevertheless, the segmental scan results are not uniformly affected. The recommendation to stop BBs prior to stress testing in order to ensure the highest MBF remains advisable. If temporary BB withdrawal is unfeasible due to contraindications, a tight clinical schedule, or because a patient forgot to withhold the BB, it is appropriate to perform adenosine stress testing according to the results of this study.

Utilization of Minimally Invasive Surgery in Endometrial Cancer Care: A Quality and Cost Disparity.

OBJECTIVE: To describe case mix-adjusted hospital level utilization of minimally invasive surgery for hysterectomy in the treatment of early-stage endometrial cancer. METHODS: In this retrospective cohort study, we analyzed the proportion of patients who had a minimally invasive compared with open hysterectomy for nonmetastatic endometrial cancer using the U.S. Nationwide Inpatient Sample database, 2007-2011. Hospitals were stratified by endometrial cancer case volumes (low=less than 10; medium=11-30; high=greater than 30 cases). Hierarchical logistic regression models were used to evaluate hospital and patient variables associated with minimally invasive utilization, complications, and costs. RESULTS: Overall, 32,560 patients were identified; 33.6% underwent a minimally invasive hysterectomy with an increase of 22.0-50.8% from 2007 to 2011. Low-volume cancer centers demonstrated the lowest minimally invasive utilization rate (23.6%; P<.001). After multivariable adjustment, minimally invasive surgery was less likely to be performed in patients with Medicaid compared with private insurance (adjusted odds ratio [OR] 0.67, 95% confidence interval [CI] 0.62-0.72), black and Hispanic compared with white patients (adjusted OR 0.43, 95% CI 0.41-0.46 for black and 0.77, 95% CI 0.72-0.82 for white patients), and more likely to be performed in high- compared with low-volume hospitals (adjusted OR 4.22, 95% CI 2.15-8.27). Open hysterectomy was associated with a higher risk of surgical site infection (adjusted OR 6.21, 95% CI 5.11-7.54) and venous thromboembolism (adjusted OR 3.65, 95% CI 3.12-4.27). Surgical cases with complications had higher mean hospitalization costs for all hysterectomy procedure types (P<.001). CONCLUSION: Hospital utilization of minimally invasive surgery for the treatment of endometrial cancer varies considerably in the United States, representing a disparity in the quality and cost of surgical care delivered nationwide.

The effect of beta blocker withdrawal on adenosine myocardial perfusion imaging.

BACKGROUND: The effect of beta blockers on myocardial blood flow (MBF) under vasodilators has been studied in several SPECT and PET myocardial perfusion imaging (MPI) studies with divergent results. The present study evaluated the effect of a beta blocker withdrawal on quantitative adenosine MBF and on MPI results. METHODS: Twenty patients with beta blockers and CAD history were studied with quantitative adenosine N-13 ammonia PET. The first study was performed under complete medication and the second after beta blocker withdrawal. The PET studies were independently read with respect to MPI result and clinical decision making. RESULTS: Global MBF showed an increase from 180.2 ± 59.9 to 193.6 ± 60.8 mL·minute(-1)/100 g (P = .02) after beta blocker withdrawal. The segmental perfusion values were closely correlated (R(2) = 0.82) over the entire range of perfusion values. An essentially different interpretation after beta blocker discontinuation was found in two cases (10%). CONCLUSION: A beta blocker withdrawal induces an increase in adenosine MBF. In the majority of cases, MPI interpretation and decision making are independent of beta blocker intake. If a temporary beta blocker withdrawal before MPI is not possible or was not realized by the patient, it is appropriate to perform adenosine stress testing without loss of the essential MPI result.

Myocardial sympathetic innervation in diabetic patients with symptomatic coronary artery disease.

AIM: In non-diabetic patients, sympathetic innervation can be preserved even if there is major impairment of myocardial blood supply. Matters may be more complex in diabetic patients because denervation can be caused by cardiac autonomic neuropathy (CAN) or by ischemic injury. Our aim was to determine whether restrictions in myocardial blood supply have a pronounced influence on sympathetic innervation in diabetics and if this effect can be differentiated from CAN. PATIENTS, METHODS: We analyzed 20 diabetics with advanced coronary artery disease (CAD) and without known CAN. We determined quantitative myocardial blood flow using (13)N-ammonia-PET, myocardial viability with (18)F-FDG, and cardiac innervation with (11)C-HED. We investigated the relationship between regional HED retention, blood flow, and coronary flow reserve (CFR). Attenuated heart rate response to adenosine was taken as indicator for CAN (HR ratio). RESULTS: There was minor correlation of segmental stress flow and HED retention (r(2)=0.063, p<0.0001). Correlation improved when stress flow as well as HED retention were normalized to the individual maximum (r(2)=0.162, p<0.0001). In nine patients, a HR ratio <1.2 implicated subclinical CAN. Duration of diabetic disease or glycaemic control (HbA1c) did not correlate with mean HED retention in the viable segments, but with its variation coefficient. CONCLUSIONS: As in non-diabetic patients, a slight correlation exists between CFR and sympathetic innervation. The sensitivity of sympathetic nerves to reductions in CFR does not seem to be increased as compared to the results reported for non-diabetics. Besides impaired blood supply, long duration of diabetic disease and bad glycaemic control also seem to impair sympathetic innervation provoking higher heterogeneity.

Effects of Na(+) on the predominant K(+) channel in the tonoplast of Chara: decrease of conductance by blocks in 100 nanosecond range and induction of oligo- or poly-subconductance gating modes.

We present three mechanisms by which Na(+) inhibits the open channel currents of the predominant K(+) channel in the tonoplast of Chara corallina: (i) Fast block, i.e., short (100 ns range) interruptions of the open channel current which are determined by open channel noise analysis, (ii): Oligo-subconductance mode, i.e., a gating mode which occurs preferentially in the presence of Na(+); this mode comprises a discrete number (here 3) of open states with smaller conductances than normal, and (iii): Polysubconductance mode, i.e., a gating mode with a nondiscrete, large number (>30) of states with smaller conductances than the main open channel conductance. This novel mode has also been observed only in the presence of Na(+).

Transient and permanent fusion of vesicles in Zea mays coleoptile protoplasts measured in the cell-attached configuration.

Exocytosis in protoplasts from Zea mays L. coleoptiles was studied using patch-clamp techniques. Fusion of individual vesicles with the plasma membrane was monitored as a step increase of the membrane capacitance (Cm). Vesicle fusion was observed as (i) An irreversible step increase in Cm. (ii) Occasionally, irreversible Cm steps were preceded by transient changes in Cm, suggesting that the electrical connection between the vesicle with the plasma membrane opens and closes reversibly before full connection is achieved. (iii) Most frequently, however, stepwise transient changes in Cm did not lead to an irreversible Cm step. Within one patch of membrane capacitance steps due to transient and irreversible fusions were of similar amplitude. This suggests that the exocytosis events do not result from the fusion of vesicles with different sizes but are due to kinetically different states in a fusion process of the same vesicle type. The dwell time histogram of the transient fusion events peaked at about 100 msec. Fusion can be described with a circular three-state model for the fusion process of two fused states and one nonfused state. It predicts that energy input is required to drive the system into a prevailing direction.

Acupuncture in alcoholism treatment: a randomized out-patient study.

Seventy-two alcoholics were treated with acupuncture to the ear in a randomized single-blind controlled design over 10 weeks. Orthodox points and incorrect points 3-5 mm from orthodox points were used. No initial differences were found regarding social characteristics, the responses to the Swedish version of the Alcohol Use Inventory and the Three-dimensional Personality Questionnaire, indicating a successful randomization. There were non-significant tendencies towards gender differential response after acupuncture treatment (P = 0.07). There was no difference in the number of drinking days or level of craving between treatment and control patients. Among females, those in the treatment group reported reduction of anxiety after 1 month, more often than those in the control group (P < 0.05). Response to acupuncture was not related to personality or drinking pattern. Patients' experience of needle placement was similar in the study and control groups. The effects of acupuncture were less pronounced than those previously reported.

Improvement in coronary flow reserve determined by positron emission tomography after 6 months of cholesterol-lowering therapy in patients with early stages of coronary atherosclerosis.

BACKGROUND: Early stages of coronary atherosclerosis are characterized by a mainly functional impairment of coronary vasodilator capacity under the impact of such risk factors as hypercholesterolemia. The goal of this study was to determine whether 6-month cholesterol-lowering therapy improves coronary flow reserve in patients with angina, reduced flow reserve despite minimally diseased coronary vessels or even normal angiogram, and mild to moderately elevated LDL levels on average. METHODS AND RESULTS: We noninvasively investigated 23 consecutive patients (18 men, 5 women; mean age, 56+/-7.6 years) with a mean LDL level of 165+/-34 mg/dL at baseline by PET for myocardial blood flow measurement with [13N]ammonia at rest and under dipyridamole stress (0.56 mg/kg) before and after lipid-lowering therapy with simvastatin for 6 months. Between baseline and the 6-month follow-up, total cholesterol concentration fell from 241+/-44 to 168+/-34 mg/dL, and the LDL level decreased from 165+/-34 to 95+/-26 mg/dL (P<0.001). Overall, coronary flow reserve increased from 2.2+/-0.6 to 2.64+/-0.6 (P<0.01). Maximal coronary flow increased significantly from 182+/-36 to 238+/-58 mL/minx100 g (P<0.001) at follow-up. Minimum coronary resistance declined significantly from 0. 51+/-0.12 to 0.40+/-0.14 mm Hg. mL-1. minx100 g (P<0.001). Concomitantly, a regression of anginal symptoms was observed in most patients. CONCLUSIONS: Our results suggest that cholesterol-lowering therapy with simvastatin may improve overall coronary vasodilator capacity assessed noninvasively by PET in patients with mild to moderate hypercholesterolemia. Consequently, intensive lipid-lowering therapy is considered a vasoprotective treatment for selected patients in very early stages of coronary atherosclerosis with the potential of preventing further disease progression.

[Improved coronary vasodilator capacity by drug lipid lowering therapy in patients in the early stage of coronary atherosclerosis with reduced coronary reserves and moderate LDL hypercholesteremia]. / Verbesserung der koronaren Vasodilatationskapazität durch medikamentöse Lipidsenkung bei Patienten im Frühstadium der koronaren Atherosklerose mit eingeschränkter Koronarreserve und mässiggradiger LDL-Hypercholesterinämie.

BACKGROUND: An abnormal coronary flow reserve represents an early marker of impaired blood flow regulation in the natural history of coronary atherosclerosis under the impact of risk factors such as hypercholesterolemia. Our clinical investigation was aimed at assessing noninvasively the integrative coronary flow response to dipyridamole stress in 18 consecutive patients with microvascular angina, only moderately elevated LDL-cholesterol levels (168 +/- 33 mg/dl), and reduced vasodilator capacity despite normal (n = 9) or slightly abnormal (n = 9) coronary arteriograms (minimal disease with luminal irregularities and/or diameter reduction < or = 30%) before and after 6-month lipid-lowering therapy (simvastatin). METHODS: Regional and averaged myocardial blood flow were measured at rest and after dipyridamole induced vasodilation (0.56 mg/kg) using dynamic positron emission tomography (PET) and N-13 ammonia as flow tracer related to a 3-compartment kinetic model. Baseline data (mean +/- SD): 13 males, 5 females; mean age: 56 +/- 8 years; basal coronary flow: 90 +/- 22 ml/min x 100 g; after lipid intervention: 93 +/- 18 ml/min x 100 g (n.s.). Total cholesterol: 246 +/- 45 mg/dl. RESULTS AFTER 6-MONTH LIPID INTERVENTION: Total cholesterol decreased to 170 +/- 36 mg/dl (p < 0.001); mean LDL level: 97 +/- 26 mg/dl (p < 0.001). Coronary dilator capacity increased, assessed in terms of minimal coronary resistance: 0.38 +/- 0.08 vs 0.49 +/- 0.09 units at baseline (p < 0.01), myocardial blood flow under dipyridamole: 232 +/- 43 vs 186 +/- 37 ml/min x 100 g at baseline (p < 0.01), and instantaneous flow ratio: 2.6 +/- 0.7 vs 2.2 +/- 0.6 (p = 0.06). Concomitantly, a considerable regression of angina was noticed in the majority of patients. CONCLUSIONS: An improvement of the non-invasively determined integrative dipyridamole induced coronary vasodilator capacity may be achieved after 6 months by intensive lipid lowering at a very early stage of coronary atherosclerosis. Consequently, aggressive cholesterol-lowering therapy represents an antiischemic and antianginal approach suggesting, at least in part, functional reversal and probably prevention of further disease progression.

Improvement of coronary vasodilatation capacity through single LDL apheresis.

A concomitant phenomenon of hypercholesterolemia is reduced coronary vasodilatation capacity due to disturbed endothelial function. Endothelial function can be partially or completely normalized by reducing cholesterol levels through drug therapy, but it is still unclear how rapidly this desired effect is achieved. An interval of between weeks and months has been presumed. LDL apheresis (LDL-A) is capable of achieving a high-degree LDL cholesterol reduction within hours. With positron emission tomography (PET), carried out immediately before and after LDL-A, changes in coronary reserve due to this abrupt LDL cholesterol reduction could be measured both quantitatively and non-invasively. In nine patients (six women, three men) with documented coronary artery disease and hypercholesterolemia, PET was carried out immediately before and 18-20 h after LDL-A. A reduction in LDL cholesterol (from 194 +/- 38 to 81 +/- 20 mg/dl), facilitated significant improvement in myocardial blood flow (MBF) (173 +/- 63 versus 226 +/- 79 ml/min per 100 g) after pharmacologic recruitment of coronary flow capacity (dipyridamole stress), coronary flow reserve (CFR) (1.91 +/- 0.68 versus 2.48 +/- 0.68) and minimum coronary resistance (MCR) (0.61 +/- 0.18 versus 0.43 +/- 0.16 mmHg/100 g per min per ml) within 24 h. Plasma viscosity was reduced slightly, by 6.6%. Probably for the first time, a 30% improvement in coronary vasodilatation capacity could be demonstrated quantitatively and non-invasively by PET after a single LDL-A within 24 h.

Cytotoxicity of linoleic acid diols to renal proximal tubular cells.

Monoepoxides of linoleic acid (leukotoxin and isoleukotoxin) have been associated with a variety of pathophysiological diseases in humans including multiple organ failure. They also have been shown to be toxic when injected into experimental animals. Because leukotoxin and isoleukotoxin are excellent substrates for epoxide hydrolases, we tested the hypothesis that the diol metabolites are less toxic than the parent monoepoxides using the rabbit renal proximal tubule (RPT) suspension model. An equimolar mixture of the positional isomers of the methyl esters of leukotoxin and isoleukotoxin did not cause cell death to RPT cells at concentrations up to 1 mm using lactate dehydrogenase release as the endpoint. The corresponding diols, however, caused cell death in a time- and concentration-dependent manner beginning at 4 hr and reaching 42% cell death in 6 hr at 1 mm. Cell death was not due to oxidative stress since malondialdehyde content did not increase and the iron chelator deferoxamine and the antioxidant N,N'-diphenyl-1, 4-phenylenediamine were not cytoprotective. In contrast, cell death was associated with mitochondrial dysfunction with respiration decreasing 54% prior to the onset of cell death. Secondary to the mitochondrial dysfunction, the diols completely inhibited active Na+ transport within 30 min of addition. These results suggest that the in vivo toxicity and pathophysiology previously attributed to the monoepoxides of linoleic acid may be due to the diol metabolites.

On the need for standardization in panic disorder treatment research: survey of the literature, 1980-1992.

A retrospective literature survey (1980-1992) was conducted to chronicle the development of panic disorder treatment research. Based on a National Institute of Mental Health conference on assessment standardization in this area (Shear and Maser, 1994), the results and implications of the survey are presented in terms of eight domains of measurement recommended as essential for high quality research.

The clinical spectrum of so-called "minor" depressions.

Reviewing the recent literature on the overlapping spectrum of neurotic depressive and dysthymic conditions--unofficially referred to as "minor," "atypical" or "characterologic" depressives--the authors conclude that significant symptomatologic admixtures with anxiety disorders do not represent the prototypical features of these disorders as defined in DSM-III-R. It is long-standing anhedonia on an intermittent or chronic basis which appears to characterize the trait illness of dysthymia. The emerging data on dysthymia suggest that it begins early in life, is often complicated by major depressions, and pursues a chronic--often pernicious--course. The development of hypomanic switches during the prospective course of some of these patients further suggests some kinship to bipolar disorder. Although traditionally conceived as being largely "psychogenic," familial data and selected biologic indices--especially in the area of sleep--and thymoleptic responsiveness impart some credibility to the role of biologic factors in the origin of these disorders. Given the high prevalence of dysthymic conditions in clinical practice, new research strategies on their causes are needed as a precondition for more rational treatment approaches.

International use and attitudes toward DSM-III and DSM-III-R: growing consensus in psychiatric classification.

A survey of the uses and attitudes of 146 mental health professionals, primarily psychiatrists and psychologists, in 42 countries (not including the United States) toward the 3rd edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM-III) and its revision (DSM-III-R; American Psychiatric Association, 1980,1987) is reported. The results revealed wide-spread endorsement of the multiaxial system, theoretical neutrality, descriptive symptom criteria forming discrete categories, and the placement of personality disorders on a separate axis. We report that the DSM-III and DSM-III-R are more widely used around the world than the International Classification of Diseases for teaching, research, and clinical practice. Opinions about various dimensions of the DSM's usefulness and shortcomings are presented.

Orbitotonography, the dynamic assessment of orbital tension: 2. Results in patients with orbital disease.

Dynamic orbitotonography was done in 17 patients with Graves' disease, 25 patients with orbital tumours and 15 healthy subjects. The mean orbital pressure for both patient groups was significantly different from that for the healthy subjects at each time interval (p less than 0.001). Healthy patients may be differentiated from those with orbital disease with a good degree of reliability with this technique. As well, the technique may provide information about the location of disease within the orbit.

Conjunctival transplantation. Autologous and homologous grafts.

Autologous conjunctival transplants have been used successfully for restoration of damaged ocular surfaces. Homologous (allogeneic) conjunctival grafts have been explored less systematically. We developed a nonhuman primate model for comparison of autologous and homologous conjunctival transplantation in order to assess the clinical viability and immunopathologic characteristics of these grafts. Autologous or homologous grafts were performed in nine adult rhesus monkeys. Both autologous and homologous grafts were compared for clinical viability and immunopathologic change. Clinical results suggest that, although homologous grafts incited a greater inflammatory and scarring response, there was minimal graft shrinkage and a normal surface epithelium. Immunopathologic studies using laminin, bullous pemphigoid antigen, and fibronectin indicate that, despite the increased inflammatory response seen in homografts, the epithelial surface is normal. With our increasing ability to modulate the immune response, conjunctival homografts may play a role in restoration of the ocular surface.