Rest and treadmill exercise first-pass radionuclide ventriculography: Validation of left ventricular ejection fraction measurements

Background

To assess the accuracy of rest and treadmill exercise first-pass radionuclide ventriculographic measurements of left ventricular ejection fraction (LVEF), 40 patients underwent treadmill exercise first-pass and bicycle exercise equilibrium radionuclide ventriculography. To determine the frequency of technically adequate treadmill exercise first-pass studies, an additional 128 consecutive patients undergoing treadmill exercise first-pass procedures during stress^99mTc-labeled sestamibi myocardial perfusion studies were assessed.

Methods and Results

The treadmill exercise first-pass procedure used a multicrystal camera and an²⁴¹Am point source to allow for correction of patient motion. Excellent correlations were observed between resting first-pass and resting equilibrium LVEF (r=0.91; standard error of the estimate=5.6). A high correlation was also observed between treadmill exercise first-pass and bicycle equilibrium exercise LVEF measurements (r=0.85, standard error of the estimate=7.6). Treadmill first-pass LVEF systematically underestimated the bicycle equilibrium LVEF. Intraobserver agreement for rest and exercise first-pass LVEF was high (r values of 0.98 and 0.94, respectively). Of the 168 consecutive treadmill exercise first-pass studies evaluated for technical adequacy, 21 (12.5%) were deemed technically inadequate, with most of the sources of error being avoidable. The frequency of technically adequate studies was as high (87%) in high levels of exercise (Bruce stages 3 and 4) as in lower levels (88%). The findings of this study validate the first-pass treadmill exercise LVEF measurement.

Conclusion

This procedure now provides the option for combining the information of peak treadmill exercise LVEF with measurements of exercise myocardial perfusion from the same injection of radioactivity.     

Prophylactic treatment of patients with esophageal varices: Is it ever indicated?

The prognosis of patients who bleed from esophageal varices is dismal. Prophylactic treatment of the varix or the elevated portal venous pressure offers a possibility of improving the outlook for these patients. However, as only approximately one-third of patients with varices bleed during their lifetime, correct identification of high-risk patients is vital before embarking on prophylaxis. At present, neither European or Japanese selection criteria are perfect in this respect. The documented incidence of initial variceal bleeding varies between 27% and 48%, and most bleeding episodes occur within the first year after varices are diagnosed. Data from six randomized controlled trials comparing prophylactic -blockers with placebo demonstrated a decreased incidence of bleeding in propranolol-treated patients, which in large measure may depend on patient compliance and did not significantly affect survival in all but one study. Early randomized studies of prophylactic sclerotherapy have shown significant reductions in both the incidence of bleeding and mortality, but this promise has not been sustained by subsequent trials, and indeed sclerotherapy was detrimental in two studies. The impressive results in highly selected patients treated in Japan by prophylactic surgery are unlikely to be repeated in a Western setting, involving patient populations that consist predominantly of alcoholic cirrhotics. At present prophylaxis with -blockade seems to offer the best therapeutic option, but the future may lie in the development of new interventional techniques such as tranjugular intrahepatic portosystemic stent shunting (TIPS) or variceal banding, and ultimately with hepatic transplantation.

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Resumen El pronóstico de los pacientes que sangran como consecuencia de várices esofágicas es sombró. El tratamiento profiláctico de las várices o de la elevada presión portal ofrece una posibilidad de mejorar el futuro de estos pacientes.Sin embargo, como apenas aproximadamente un tercio de los pacientes con várices sangran en el curso de su vida, la correcta identificación de los casos de alto riesgo es de vital importancia antes de embarcarse en tratamiento profiláctico.En la actualidad ni los criterios de selección europeos ni los japoneses pueden considerarse como perfectos a este respecto. La frecuencia del sangrado varicoso inicial oscila entre 27% y 48%, y la mayoría de los episodios hemorrágicos ocurren dentro del primer año después de establecido el diagnóstico de las várices. Los resultados de seis (6) ensayos clinicos randomizados en que compararon los beta-bloqueadores con placebeo demuestran una disminución en la incidencia de sangrado en los pacientes tratados con propranolol, lo cual en gran parte depende de la obediencia del paciente, pero afectó en forma significativa la sobrevida, excepto en uno de los estudios.Anteriores estudios randomizados sobre escleroterapia profiláctica han demostrado reducciones significativas tanto en la incidencia de sangrado como en la mortalidad, pero ésto no ha sido reproducido en ensayos clínicos subsiguientes, y en realidad la escleroterapia pareció ser nociva en dos estudios. Los impresionantes resultados en pacientes altamente seleccionados logrados en el Japón con la cirugía profiláctica muy probablemente no lograrán ser reproducidos en Occidente, donde las poblaciones de pacientes están conformadas predominantemente por cirróticos alcohólicos. En el momento actual la profilaxis con beta-bloqueadores parece ser la mejor opción terapéutica, pero el futuro puede bien ser el desarrollo de nuevas técnicas intervencionistas tales como shunts transyugulares intrahepáticos (TIPS) o la ligadura endoscópica de las várices y, por último, el trasplante de hígado.

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Résumé Le pronostic des patients ayant saigné de varices oesophagiennes est médiocre. Le traitement prophylactique des varices ou d'une hypertension portale permet une amélioration potentielle du pronostic de ces patients. Cependant, comme seulement un tiers des patients avec des varices saignent pendant leur vie, l'identification correcte des patients à risque élevé est capitale avant d'envisager une politique prophylactique généralisée. Actuellement, ni les critères européens ni les critères japonais ne sont suffisants pour déterminer cette population à risque. L'incidence d'hémorragie par rupture des varices initiale va de 27% à 48% dans la littérature et la plupart des hémorragies se produisent pendant la première année après le diagnostic de varices oesophagiennes. Les résultats provenant de six études comparant les béta bloqueurs à un placebo ont démontré une baisse de l'incidence de l'hémorragie chez les patients traités par le propranol. Ce résultat peut certes être attribué à une différence de coopération parmi les patients: la survie n'est pas différente d'une étude à l'autre sauf une. Les études randomisées de sclérothérapie prophylactique ont démontré une réduction significative dans l'incidence d'hémorragie et de la mortalité, mais cet espoir n'a pas été retrouvé par les essais suivants et la sclérothérapie a été néfaste dans deux de ces essais. Il est peu probable que les résultats impressionnants recueillis au Japon puissent être reproduits en Occident où la population est composée en grand majorité par des cirrhotiques d'origine alcoolique. Actuellement, la prophylaxie par béta-bloqueurs semble être le meilleur des traitements mais à l'avenir, la meilleure option thérapeutique pourrait être le shunt intrahépatique transjugulaire ou le wrapping périoesophagien et ultérieurement la transplantation hépatique.

     

The Influence of Obesity on the Self-Reported Health Status of Chamorros and other Residents of Guam

PURPOSE OF THE PAPER. We report on an analysis of the relationship of obesity to self-assessments of physical health for a probability sample of Guam's indigenous (Chamorro) and resident populations. Further, we examine whether Guam's populations fit a Western model, in terms of viewing obesity as an unhealthy condition. As background for our analysis, we review the literature on (1) the relationship between obesity and chronic noninfectious diseases; (2) social and behavioral associations of obesity; and (3) the reliability of self-assessed physical health and measures of obesity. METHODS. The data analyzed were taken from a Behavioral Risk Factor Survery (BRFS) conducted on Guam in 1991. We employed various standard univariate (chi-square analysis, ANOVA) and multivariate (OLS regression and logisitic regression analusis) statistical procedures in exploring our data and testing hypotheses on the correlates and associations of self-reported health and obesity. PRINCIPAL FINDINGS. Controlling for ethnicity, age, gender, marital and socioeconomic status, we found that obesity and being Chamorro was associated significantly with low assessments of physical health and that income was a signifcant predictor of higher self-assessments. A small sample of Micronesians, with a slightly greater level of obesity than the Chamorros, did not show the same tendency towards lower self-evaluation of their health. This probably reflects their lesser degree of internalizaition of Western ideas about obesity, appearance and health. When controlling for self-assessments of physical health, obesity was also shown to be related significantly with dieting by Chamorro women but was not a significant predictor of their increased participation in physical exercise. Young males were significantly more likely to report participation in physical exercise regardless of their weight or ethnicity. CONCLUSIONS. We hypothesize that historical (acculturative) changes to the diet and life ways of Chamorros, together with a likely genetic predisposition to store fat, has led to the relatively high levels of obesity seen on Guam today. Because of internalization of Western ideals about obesity and appearance, and increased community awareness of the health perils of obesity, Chamorros are at a public health crossroads. Effective health interventions must reckon with powerful genetic and cultural cross-currents. RELEVANCE TO ASIAN PACIFIC ISLANDER AMERICAN POPULATIONS. Colleagues are encouraged to examine the effects of ethnicity and acculturation on the health attitudes, behaviors, and status of other Pacific Islander and Asian populations. The creation of such a comparative data base will service APIA health interventions. KEY WORDS. Guam, Chamorros, Asian Pacific Islander Americans, survey, obesity, self-evaluated health status, socioeconomic status, cross-cultural comparisons.     

Effects of two stressors on behaviour in the elevated X-maze: preliminary investigation of their interaction with 8-OH-DPAT

Effects of water deprivation and restraint were compared in the rat elevated X-maze. Water deprivation for 12–48 h increased corticosterone and had a duration-dependent anxiolytic effect in the elevated X-maze, increasing the ratio of open/total arm entries (OTR) and the proportion of time spent on the open arms (% time) without affecting total entries. Brain 5HIAA/5HT was increased only after 24 or 48 h deprivation. Restraint for 15 min also increased plasma corticosterone and brain 5HIAA/5HT but had no effect on behaviour in the elevated X-maze when rats were tested immediately afterwards. However, 1 h restraint was anxiogenic in the elevated X-maze immediately after release, reducing OTR and % time, but with a less consistent reduction in total entries; reductions in OTR and % time were still present 24 h later. The 5HT_1A agonist 8-hydroxy-2-(di-n-propylamino) tetralin (8-OH-DPAT) (0.1–0.2 mg/kg), administered 10 min before testing in the elevated X-maze, had anxiogenic actions in non-stressed rats. The effect of 0.1 mg/kg 8-OH-DPAT was not significantly altered by 24 or 48 h water deprivation but was abolished by restraint for 1 h immediately beforehand, despite the anxiogenic effect of restraint alone. Similar mutual antagonism of 8-OH-DPAT and restraint occurred when the dose of 8-OH-DPAT was increased to 0.2 mg/kg. Twenty-four hours after restraint, restrained rats which had received 8-OH-DPAT (0.1–0.2 mg/kg) still did not show any significant anxiogenic effect compared with non-restrained vehicle treated controls. Restraint-induced deficits in elevated X-maze exploration may prove a useful model with which to study the pharmacology of depression-related anxiety. However, the effects of the stressors examined, and their interaction with 8-OH-DPAT in the elevated X-maze, appear to depend on the nature of the stressor.     

Pre-irradiation chemotherapy in children with high-grade astrocytoma: Tumor response to two cycles of the ‘8-drugs-in-1-day’ regimen

SummaryPurpose This study was undertaken to evaluate the radiographie response to two cycles of chemotherapy prior to irradiation in newly diagnosed children with high-grade astrocytomas.Patients and methods. One hundred and thirty children less than 21 years of age with newly-diagnosed highgrade astrocytoma were treated with the eight-drugs-in-one-day chemotherapy regimen as part of a phase III multi-institutional Childrens Cancer Group (CCG) trial. Computerized Tomographic (CT) or Magnetic Resonance Image (MRI) scans, obtained after two cycles of chemotherapy had been administered, were compared with post-operative scans to determine treatment response. Scans were evaluated by institutional radiologists, and were reviewed centrally by a single neuroradiologist.Results Of 79 patients with evaluable post-operative residual tumor on CT or MRI scans, 26 (33%) were determined on institutional evaluation to have had an objective response. However, central review of scans documented responses on only 14/79 (18%). A significantly higher response rate on central review was observed for those children 36 months of age or less at study entry than for older children (33% v 11%; p < 0.001). However, a higher disease progression rate was also observed for those children 36 months of age or less than for older children (21% v 2.6%; p < 0.001).Conclusion In this study, the largest yet reported in newly-diagnosed children with high-grade astrocytomas, the chemotherapy regimen has activity in younger children. The differences in response rates reported by institutional and central review highlight the difficulties inherent in assessing response to brain tumor therapy. However, the study does demonstrate the consistent ability of radiologists to identify disease progression within the institutional and central reviews.     

Anti-CD3 and anti-cd16 monoclonal-antibody in-vitro enhancement of NK activity in pbl from gastrointestinal-tract cancer-patients

Natural killer (NK) cell cytotoxicity was assessed using peripheral blood mononuclear cells from 103 healthy volunteers and 51 cancer patients. Peripheral blood cells were assessed by flow cytometry, and cytotoxicity in a standard 4-hour Cr-51-release assay using K562 cells as targets. Anti-CD3 and anti-CD16 mAb significantly enhanced cytoxicity in vitro. NK cell numbers correlated with levels of cytotoxicity. Patients with liver metastases had significantly more CD3+ lymphocytes coexpressing NK markers than patients without liver involvement. These CD3+ NK cells may also mediate cytotoxicity. Enhancement of cellular cytotoxicity by anti-CD3 and anti-CD16 may be of use in cancer immunotherapy protocols.     

Treatment of systemic and renal-limited vasculitic disorders with pooled human intravenous immune globulin

Idiopathic crescentic glomerulonephritis is characterized by an absence of immunohistological evidence of immune deposits, often with evidence of segmental glomerular necrosis. Such pauciimmune crescentic glomerulonephritis is the most common renal manifestation seen in patients with Wegener's granulomatosis, polyarteritis nodosa, and glomerulonephritis associated with other systemic vasculitic disorders (i.e., Churg-Strauss syndrome). Recently, the idiopathic crescentic glomerulonephritides, either in renal-limited form or in association with other systemic vasculitic disorders, were found to have in common a serologic marker, antineutrophil cytoplasmic autoantibodies. These cytoplasmic and perinuclear antineutrophil cytoplasmic autoantibodies are specific for constituents of neutrophil primary granules and monocyte lysosomes. As serologic markers for vasculitic disorders, they are also felt to be directly involved in the pathogenesis of necrotizing vascular injury.In vitro, both perinuclear and cytoplasmic antineutrophil cytoplasmic autoantibodies are capable of causing cytokineprimed neutrophils to undergo degranulation and respiratory burst, releasing toxic oxygen species and lytic enzymes. Antiidiotype antibodies which inhibit antineutrophil cytoplasmic autoantibodiesin vitro, in a V region-dependent manner, are found in pooled humanγ-globulin preparations. Intravenous immune globulin infusionsin vivo have produced dramatic improvements in the necrotizing vascular injury produced by antineutrophil cytoplasmic autoantibodies, and a rapid reduction in these autoantibody levels is seen post-intravenous immune globulin infusion in most patients. The proposed mechanisms of action of intravenous immune globulin in vasculitic disorders include Fc-dependent mechanisms, and F(ab′)₂-dependent mechanisms are likely important. Intravenous immune globulin infusions appear to have an important place in the management of the necrotizing vascular injury. Blinded, randomized, placebo-controlled trials will be necessary to establish definitively intravenous immune globulin as a therapeutic option in vasculitic disorders.     

Is the IV obstructed or infiltrated? A simple clinical test

Objective. The objective of our study was to determine if clinical observation of pressure-flow relationships (PFR) can differentiate between partial external obstruction (obstruction) and infiltration as a cause of poor performance of gravity-fed infusions.Methods. A total of 24 patients with functional intravenous cannulae in situ had obstruction simulated by the application of a tourniquet proximal to the cannula. The change in flow (F) for a discrete change in pressure (P) was determined in each case by counting drop rates at two different elevations of the fluid reservoir level, 10 cm apart. The same process was repeated in 15 patients in whom the cannula was in an extra vascular location (infiltration). Three sizes of cannula—16-gauge, 18-gauge, and 20-gauge—were examined, with equal distribution of sizes in each group. The effect on flow rates of inflating a blood pressure (BP) cuff proximally on the cannulated limb was assessed. The ratio P/F is the total resistance of the infusion system, and by subtracting known values for resistance of infusion tubing and cannula, the venous or tissue resistance was calculated.Results. There was a statistically significant difference between the change in flow for obstructed compared with infiltrated cannulae for the same change in pressure for each cannula size. The mean venous resistance was 23 mm Hg/L/hr, while that of tissue was 280 mm Hg/L/hr, with no overlap between groups. There was no effect on flow rate with blood pressure cuff inflation in the infiltrated group whereas flow progressively fell in the obstructed group.Conclusions. Clinical observation of PFRs in poorly functioning gravity-fed IV infusions can assist in detecting infiltration as a cause. Inflation of a blood pressure cuff will further impair flow where the cannula is intravascular, but will have no effect in an extravascular location.     

The Influence of Dirithromycin on the Pharmacokinetics of Cyclosporine in Healthy Subjects and in Renal Transplant Patients

The effect of a standard regimen of the investigational macrolide antibiotic, dirithromycin, on the single-dose kinetics of orally administered cyclosporine (CSA) was investigated in healthy young males and on the steady-state disposition kinetics of cyclosporine in a panel of renal transplant patients. Eight male volunteers participated after giving informed consent. CSA was administered in three single doses (15 mg kg(minus sign1) p.o. each) in each of three phases: (1) prior to a 14-day regimen of dirithromycin; (2) at the end of a 14-day regimen of dirithromycin (500 mg p.o. qAM); and (3) 2 weeks after the last dose of a 14-day regimen of dirithromycin. Pharmacokinetic parameters of CSA were estimated, and the differences among treatments were assessed by analysis of variation. No significant differences among treatment (phase) means were detected (p < 0.05). We conclude that a typical 14-day regimen of dirithromycin failed to alter the disposition kinetics of CSA when taken orally healthy young adult males. The effect of a standard regimen of dirithromycin on the steady-state disposition kinetics of orally administered CSA was investigated in a panel of 15 stable renal transplant patients. Pharmacokinetic parameters for CSA were evaluated prior to, during, and 2 weeks after discontinuing a 14-day (500 mg day(minus sign1)) oral regimen of dirithromycin. Dirithromycin elicited small but significant changes in the following parameters: C(av) was increased by 16% during dirithromycin treatment, and the changes in normalized C(av) were comparable. Likewise, C(SS,min) and normalized C(SS,min) were increased by 19% and 20%, respectively, during dirithromycin treatment. CSA oral clearance, CL/F(SS), decreased by 17% during dirithromycin treatment. C(SS,max) and normalized C(SS,max) were increased by 13% and 17%, respectively, during dirithromycin treatment but were not significantly different from those either before or after dirithromycin. The magnitude of the pharmacokinetic changes for CSA during dirithromycin treatment (<15% in normal subjects and 15--20% in renal transplant patients) when considered in the context of the therapeutic range of cyclosporine concentrations was relatively small, and not likely to warrant special attention to the dosing of CSA in such patients beyond routine whole-blood CSA and serum creatinine monitoring.