Impact of Hepatitis A vaccination with a two-dose schedule in Panama: Results of epidemiological surveillance and time trend analysis

PurposeIn April 2007, Panama introduced Hepatitis A universal vaccination using a two-dose schedule (Havrix^® junior; GSK Vaccines, Belgium). We assessed the impact of this hepatitis A vaccine three years after it was recommended for universal mass vaccination in Panama.Materials and methodsHepatitis A vaccination impact was assessed using two different approaches. The first approach used retrospective data (incidence and number of cases for all age groups), collected from the passive surveillance of the Epidemiologic Surveillance System of the Ministry of Health of hepatitis A and unspecified hepatitis before (2000–2006) and after (2008–2010) introduction of hepatitis A vaccine. The second approach was a prospective hospital-based active surveillance for hepatitis cases conducted in subjects (0–14years) during 2009–2011 at three sentinel hospitals in Panama.ResultsOverall, the annual incidence of hepatitis A and unspecified hepatitis in 2008, 2009 and 2010 were 13.1, 7.9 and 3.7 per 100,000 subjects, lower than the baseline incidence of 51.1 per 100,000 subjects. In comparison to the mean baseline period (2000–2006), there was an 82% mean reduction in the overall hepatitis-related outcomes (hepatitis A and unspecified hepatitis) after vaccine introduction (2008–2010) in all age groups.In the hospital-based surveillance (2009–2011), of the 42 probable viral hepatitis A cases, nine cases were confirmed as acute hepatitis A (8 in 2009, 1 in 2010). Of these confirmed cases, two belonged to the targeted vaccine group (1–4 years) but were not vaccinated.ConclusionsOur study suggests that the introduction of two-dose hepatitis A vaccines in Panama has contributed to the reduction in the incidence of overall hepatitis-related outcomes for all age groups, suggesting herd protection. Additional monitoring is required to document a sustained long-term effect.     

逍遥散调控肝窦内皮窗孔改善大鼠抑郁样行为的机制研究

【目的】探讨逍遥散对大鼠抑郁样行为的作用及其调节机制。【方法】将雄性Wistar大鼠随机分为正常组、模型组、逍遥散组（剂量为19 g·kg－1·d－1）和氟西汀组（剂量为2 mg·kg－1·d－1）。采用慢性不可预测轻度应激（chronic unpredictable mild stress, CUMS）诱导大鼠抑郁样行为,旷场实验观察逍遥散对抑郁样行为的作用, Luminex液相芯片分析系统检测大鼠血清细胞因子,电镜观察大鼠肝窦内皮窗孔数量和大小, Western blot法分别检测肝组织中吲哚胺2,3-双加氧酶（indoleamine 2,3-dioxygenase, IDO）和色氨酸2,3-双加氧酶（tryptophan 2,3-dioxygenaes, TDO）表达。【结果】逍遥散可显著增加大鼠糖水消耗、爬格数和直立数,显著降低血清TNF-α、 IL-6水平,增加窗孔数量与大小,改善肝窦内皮血管化倾向,并降低TDO和IDO的表达（均P＜0.05或P＜0.01)。【结论】逍遥散可显著改善大鼠抑郁样行为,可能与其降低炎症因子、抑制IDO通路、改善肝窦内皮功能作用有关。     

Effects of intravenously administered propranolol on wall motion abnormalities

Although propranolol is frequently utilized as therapy for angina pectoris in patients with previous myocardial infarction, its effects on wall motion abnormalities in such patients have not been adequately defined. Accordingly, using external wall motion video tracking, we studied 18 patients with previous myocardial infarction and wall motion disorders and 5 normal subjects before and after administration of propranolol, 5 mg intravenously. Systolic time intervals, heart rate and left heart size (measured by the distance between the mid-line and left heart border in an X-ray film triggered at end-diastole after a standard inspiration) were also measured before and after administration of propranolol. In each instance propranolol produced a reduction in the amplitude and velocity of wall motion in areas of normal movement, hypokinesis and paradox, resulting in decreased outward bulging. In the normal subjects, the amplitude and velocity of wall motion also decreased. In the patients with previous myocardial infarction, propranolol increased the ratio of the preejection period to the left ventricular ejection time from a mean of 0.377 ± 0.03 (standard error of the mean) to 0.409 ± 0.03 (P <0.001); decreased heart rate by an average of 7.5 beats/min (P <0.001); and increased the distance from the mid-line to the left heart border from 94.3 ± 2.6 to 97.3 ± 2.6 mm (P <0.001). Similar changes occurred in the 5 normal subjects. We conclude that doses of propranolol sufficient to increase the ratio of the preejection period to left ventricular ejection time, decrease heart rate and increase heart size do not exaggerate preexisting paradoxical wall motion or accentuate latent areas of paradox in patients with previous myocardial infarction.     

Radionuclide analysis of peak filling rate, filling fraction, and time to peak filling rate. Response to supine bicycle exercise in normal subjects and patients with coronary disease

Using gated equilibrium radionuclide angiography, variables of diastolic filling were analyzed at rest and during supine bicycle exercise in normal subjects (Group 1, n = 18), coronary patients with normal resting ejection fractions (Group 2, n = 26), and coronary patients with reduced resting ejection fractions (Group 3, n = 8). Indexes analyzed were peak filling rate and filling fraction during the first third of diastole. At rest, the peak filling rate was significantly lower in coronary patients than in normal subjects (3.18 +/- 0.82 end-diastolic volume [EDV]/s in Group 1 versus 2.41 +/- 0.66 EDV/s in Group 2, p less than 0.005; and 1.34 +/- 0.26 EDV/s in Group 3, p less than 0.001 versus Group 1). These differences persisted at peak exercise. Coronary patients also had significantly lower filling fractions at rest and during exercise than did normal control subjects. The time from end-systole to peak filling rate was longer at rest in patients in Group 2 (203 +/- 52 ms) than in subjects in Group 1 (172 +/- 50 ms, p less than 0.025). This remained true when the time to peak filling was normalized by the R-R interval. Although the exercise time to peak filling was longer in coronary patients in both Groups 2 and 3 than in Group 1, these differences were not apparent when the interval was normalized by the R-R interval. Thus, abnormalities in peak filling rate and filling fraction exist in patients with coronary disease both at rest and during exercise, but large overlaps exist between normal and coronary patients. Caution is advised in comparing the timing of events during diastole because apparent group differences may be related in part to rest or exercise heart rate.     

Sensitivity and specificity of nuclear phase analysis versus ejection fraction in coronary artery disease

Phase standard deviation (SD) and skew characteristics of the first Fourier harmonic of equilibrium radionuclide volume curves were examined and compared during rest and during supine bicycle exercise with ejection fraction (EF) changes and the development of ischemia in 17 control subjects and in 2 groups of patients (n = 57) with coronary artery disease (CAD). Group I comprised 37 patients with CAD; IA was a subgroup of 20 patients with previous myocardial infarction (MI) and IB a subgroup of 17 patients with CAD without MI (all with coronary stenosis greater than 75% diameter narrowing). Group II comprised 20 patients with CAD who had undergone coronary bypass surgery. In the Group I subjects, phase SD was the most sensitive indicator of CAD at rest (Group I, 56%; Group IA, 70%, and Group IB, 29%), and the EF was the most sensitive indicator at submaximal (Group I, 78%; Group IA, 86%, and Group IB, 64%) and maximal exercise (Group I, 70%; Group IA, 93%, and Group IB, 53%). When phase SD and skewness were combined with EF changes, little increase in sensitivity occurred in Group I (rest 61%, submaximal exercise 88% and maximal exercise 76%). The results from Group II subgroups were qualitatively similar to those observed with Group I subgroups. These data reveal a marginally improved sensitivity for detection of CAD during supine bicycle radionuclide ventriculography when phase measurements were added to changes in global EF values.     

Investigation of insulin resistance during diabetic ketoacidosis: role of counterregulatory substances and effect of insulin therapy.

It has been generally accepted that insulin resistance (IR) exists in diabetic subjects during episodes of ketoacidosis (DKA). However, little experimental data exist regarding this question. We have studied IR in nine untreated diabetic subjects (mean age 20 yr) both during their initial episode of DKA and after 2–7 wk of insulin therapy. The experimental protocol consisted of a 150-min intravenous infusion of glucose (6 mg/kg/min) and insulin (80 mU/min). Under these conditions steady-state plasma glucose (SSPG) and insulin (SSPI) levels were reached by 90 min and maintained for the duration of the study. Since all subjects achieved similar SSPI and all received the same glucose load, the SSPG could be used as a measure of an individual's IR. In addition, steady-state plasma levels of glucagon, cortisol, growth hormone, and free fatty acids were measured in an attempt to gain insight into their roles in the maintenance of IR during DKA. Although mean (± SE) SSPI levels were the same during both study periods (93 ± 4 versus 92 ± 4 μU/ml), there was a marked difference between the initial and posttherapy SSPG levels for the nine subjects 342 ± 32 versus 104 ± 16 mg/100 ml,p < .001). Mean steady-state plasma levels of growth hormone, corticol, and free fatty acids were significantly higher during the initial studies, but only cortisol and free fatty acid levels correlated significantly with their corresponding SSPG levels. Steady-state plasma glucagon levels were the same during both study periods, and individual levels did not correlate with associated SSPG levels. These studies demonstrate that significant IR was present in these subjects during DKA as compared to the posttherapy period. Furthermore, the results suggest that while increased plasma concentrations of cortisol and free fatty acids may be involved in the maintenance of IR during DKA, elevated levels of plasma growth hormone and glucagon are not necessary for this phenomenon.     

Intravenous and oral prenalterol in congestive heart failure. Effects on systemic and coronary hemodynamics and myocardial catecholamine balance

Systemic and coronary hemodynamic effects of prenalterol, a beta-1 receptor agonist, were determined in patients with chronic congestive heart failure, initially after intravenous administration (10 patients) and then after oral administration (eight patients). Cardiac index increased by 33 percent and 30 percent after intravenous and oral prenalterol, respectively. The increase in stroke volume index and stroke work index and decrease in pulmonary capillary wedge pressure and systemic vascular resistance were not significant. Myocardial oxygen consumption and coronary sinus blood flow increased in the majority of patients, although these changes were not statistically significant. There were no significant changes in transmyocardial norepinephrine or epinephrine balance. The systemic and coronary hemodynamic effects of both intravenous and oral prenalterol were similar. Major side effects included sudden death (two patients) and hypotension and bradycardia (three patients) during oral prenalterol treatment. It is concluded that improved left ventricular function following both intravenous and oral prenalterol may be associated with increased myocardial oxygen consumption, and serious adverse effects may occur during prenalterol therapy.     

Inorganic phosphate treatment of nephrolithiasis

We report the results of long-term inorganic phosphate therapy in 47 patients suffering from recurrent calcium-containing urinary calculi. Forty-five patients had hypercalciuria before treatment. Phosphate therapy had no effect on urinary calcium excretion or stone passage but did appear to reduce the need for lithotomy. The stone passage-removal rate in the 5 years before therapy was 1.3 per patient per year and fell to 0.8 in the years of treatment (mean 5.5 years). The lithotomy rate fell from 0.12 per patient per year to 0.04 with treatment (p < 0.01). Patients who were free of stones at the start of the therapy fared best. Significant decreases in serum alkaline phosphatase were noted in many patients, possibly a sign of healing subclinical osteomalacia.