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Role of IgM antibody to hepatitis B core antigen in the diagnosis of hepatitis B exacerbations.

IgM anti-HBc levels were measured by the IMx Core-M Abbott assay in 939 serum samples in order to define a specific and sensitive cut-off value for diagnosis of chronic hepatitis B. The sera used were obtained from 52 chronic HBV patients and 10 HBV carriers with HCV or HDV co-infections and 155 asymptomatic subjects without evidence of liver disease. A Youden index value of 95.4% with 98% sensitivity and 97.4% specificity was obtained for an IMx Index value of 0.204 as cut-off. A one-year follow-up study with monthly tests has shown that quantitative analysis of IgM anti-HBc can serve as a noninvasive tool for monitoring HBV infection, and provides an accurate diagnosis of hepatitis B exacerbations. Significant elevations of IgM anti-HBc levels were associated with hepatitis B exacerbations in 96.2% of the cases but with none of the ALT flare-ups observed in HCV or HDV infected individuals. These results suggest that quantitative analysis of IgM anti-HBc provides the highest degree of confidence in definition of spontaneous and therapy-induced exacerbations or remissions of hepatitis B.

Adolescent↗

Blood-brain barrier disruption and exacerbation of ischemic brain edema after restoration of blood flow in experimental focal cerebral ischemia.

The mechanism of exacerbation of ischemic brain edema after blood flow restoration was studied in 20 cats under ketamine and alpha-chloralose anesthesia. Regional cerebral blood flow was measured by the hydrogen clearance method, and the left middle cerebral artery (MCA) was occluded for 6 h in group A, and for 3 h with subsequent 3 h recirculation in group B. Severity of brain edema was assessed by specific gravity measurement of tissue samples taken from coronal brain sections at the MCA area, while severity of blood-brain barrier (BBB) disruption was determined by measuring the amount of extravasated serum albumin by using [125I]albumin and tissue-uptake method in the same samples as those used for gravimetry. Structural and ultrastructural change was correlated with the severity of ischemic brain edema and BBB disruption. The results obtained showed that: (i) ischemic brain edema observed in group A was not associated with BBB opening to serum proteins; (ii) ischemic edema in group B was exacerbated significantly after recirculation in correlation with serum protein extravasation in most of the post-ischemic area; (iii) in the severely edematous area, serum protein extravasation reached a plateau and morphological examination at this type of area revealed cell membrane disruption especially of astrocytes, with leakage of intracellular substances. Our study indicated that the increase of extracellular osmotic pressure due to leakage of serum proteins via the disrupted BBB and of intracellular substances via the ischemically injured cell membrane into the extracellular space is the mechanism responsible for edema fluid accumulation in exacerbated ischemic brain edema.

Animals↗

Once daily versus every two week multidose ofloxacin in patients with acute exacerbations of chronic respiratory disease.

Two different oral ofloxacin regimens, daily single-dose treatment with 200 mg (Regimen I) and every two week multidose treatment with 3 x 200 mg/day (Regimen II), were compared to evaluate the efficacy of quinolone regimens in controlling acute exacerbations of chronic respiratory tract infections. Fifty-one patients were evaluated in the study: 28 in Regimen I and 23 in Regimen II. The corrected mean incidence of exacerbation per case during the six months before and during the study was reduced from 2.45 to 0.48 in Regimen I, and from 2.79 to 1.0 in Regimen II. The development of resistant strains was not found to be a problem. We conclude that the long-term administration of new quinolones, especially the daily single-dose regimen with 200 mg of ofloxacin, is useful in controlling acute exacerbations of chronic respiratory tract infections.

Acute Disease↗

Randomized controlled trial of ipratropium bromide and salbutamol versus salbutamol alone in children with acute exacerbation of asthma.

OBJECTIVE: To evaluate effect of addition of ipratropium to salbutamol delivered by metered dose inhaler and spacer in the beginning of treatment of mild to moderate exacerbation of asthma. METHODS: Children between 5 to 15 years of age with mild to moderate exacerbation of asthma were randomized to receive either a combination of ipratropium bromide and salbutamol or salbutamol alone administered by metered dose inhaler and spacer. The effects on clinical asthma score and spirometric parameters were compared. RESULTS: A total of 60 children were randomized in the study. The baseline characteristics of two groups were comparable. Children getting combination of salbutamol and ipratropium showed significantly greater improvement in percent-predicted PEFR and FEF25-75% than children receiving salbutamol alone. CONCLUSION: There was beneficial effect of addition of ipratropium to salbutamol administered by MDI with spacer at the beginning of therapy for mild to moderate acute exacerbation of asthma in children.

Adolescent↗

Comparison of terbutaline and salbutamol inhalation in children with mild or moderate acute exacerbation of asthma.

OBJECTIVE: To compare the clinical efficacy and side effects of terbutaline and salbutamol administered by metered dose inhaler and holding chamber in the mild to moderate acute exacerbations of asthma in children. METHODS: The study subjects were children in the age group of 5- 15 years who presented with a mild or moderate acute exacerbation of asthma. Baseline assessment included clinical parameters and spirometry. The children were then randomized to receive salbutamol or terbutaline. Three puffs each of either 100 mcg salbutamol or 250 mcg of terbutaline were administered using 750 ml holding chamber with valve. Thirty minutes after drug administration, the children were reevaluated for clinical parameters and spirometry. RESULTS: Of the total 60 subjects studied, 31 were administered terbutaline and 29 salbutamol. The baseline spirometric parameters were comparable. After drug administration, all the studied variables showed significant improvement within each group. However, there were no statistically significant differences when the two groups were compared with each other. There was no significant difference in the side effects between two groups. CONCLUSION: Terbutaline and salbutamol, when administered by MDI with holding chamber, are equally efficacious in children with mild or moderate acute exacerbation of asthma.

Administration, Inhalation↗

[Antibiotic therapy for exacerbation].

Bacterial infections are involved in approximately 50% of acute exacerbations of chronic bronchitis (AECB). Pneumococci, Haemophilus influenzae and Moraxella catarrhalis are the main pathogens. Studies using quantitative cultures and molecular typing suggest a causal relationship between bacterial infection and exacerbation. Furthermore, an association between infection and bronchial inflammation has been demonstrated. In contrast to steroid therapy and non-invasive ventilation, the benefits of antibiotic treatment are not well established. Current guidelines recommend antimicrobial therapy for AECB in type I exacerbations, for patients needing ventilatory support and for patients with cardiac comorbidity. Bacterial eradication is able to prolong the infection free interval.

Anti-Bacterial Agents↗

Short-term effects of expiration under positive pressure in patients with acute exacerbation of chronic obstructive pulmonary disease and mild acidosis requiring non-invasive positive pressure ventilation.

OBJECTIVE: To investigate the feasibility and the efficacy of expiration under positive pressure (PEP mask) as a chest physiotherapy in patients with exacerbation of chronic obstructive pulmonary disease (COPD) and acute hypercapnic respiratory failure (AHRF) requiring non-invasive positive pressure ventilation (NIPPV). DESIGN: A prospective, randomised, controlled study. SETTING: A respiratory intensive care unit. PATIENTS AND INTERVENTIONS: Twenty-seven patients with large amounts of bronchial secretions on clinical examination due to exacerbation of COPD and mild acidosis were randomly divided into two groups. Group A (13 patients) received PEP mask plus assisted coughing. The controls (group B, 14 patients) received assisted coughing alone. OUTCOME MEASURES: The primary end point was to compare total sputum wet weight and to assess the feasibility of the PEP mask. Secondary outcomes were: (a) the time required for weaning patients from NIPPV, (b) treatment failure expressed as mortality within 2 months after discharge from the respiratory intensive care unit (RICU) or the need for endotracheal intubation (ETI). RESULTS: The amount of sputum production at the end of physiotherapy was significantly ( p<0.01) higher in group A (9.6+/-3.9 g) compared with group B (4.7+/-2.5 g). The total length of weaning time was significantly lower in group A (4.9+/-0.8 days) versus group B (7.0+/-0.7 days), p<0.01. Mortality and ETI were not significantly different in the two groups of patients (0 versus 1 and 0 versus 1, respectively). CONCLUSIONS: Expiration under positive pressure was effective in acutely removing secretions in patients with exacerbation of COPD and mild acidosis requiring NIPPV. In conclusion, we suggest that this chest physiotherapy technique represents a useful therapeutic option for such patients and it should often be performed in addition to NIPPV.

Acidosis↗

Acute effects of non-invasive ventilatory support on functional mitral regurgitation in patients with exacerbation of congestive heart failure.

OBJECTIVE: The purpose of this study was to evaluate the acute effects of continuous positive airway pressure (CPAP) and bi-level airway pressure (BiPAP) on functional mitral regurgitation (MR) in patients with acute exacerbation of severe chronic congestive heart failure (CHF). DESIGN: A cross-over study. SETTING: A cardiopulmonary intensive care unit. PATIENTS AND INTERVENTIONS: Ten male patients affected by an acute exacerbation of congestive heart failure and hemodynamically significant MR were submitted to an echocardiograph color Doppler ultrasound evaluation during CPAP and BiPAP non-invasive ventilation. We analyzed left ventricle ejection fraction, area of MR and deceleration time (Dec-t). OUTCOME MEASURES: The primary end point was to evaluate whether CPAP and BiPAP were effective in reducing functional MR. RESULTS: After 30 min, the area of MR decreased from 10.0+/-2.7 to 8.0+/-2.9 cm(2) with CPAP and from 9.9+/-2.6 to 8.6+/-2.6 cm(2) with BiPAP ( p<0.01); Dec-t increased from 120.9+/-12.7 to 136.0+/-8.7 ms after CPAP and from 120.5+/-11.4 to 134.2+/-13.6 ms after BiPAP ( p<0.01). CONCLUSION: In patients with exacerbation of severe CHF and functional MR, both modalities of non-invasive ventilation (CPAP and BiPAP) significantly improved ejection fraction and were equally effective in reducing MR.

Aged↗

Virus infection in exacerbations of chronic obstructive pulmonary disease requiring ventilation.

OBJECTIVES: We aimed to characterise and quantify the incidence of common infectious agents in acute exacerbations of chronic obstructive pulmonary disease (COPD) requiring ventilation, with a focus on respiratory viruses. DESIGN: An epidemiological study conducted over 3 years. SETTING: A 12-bed intensive care unit (ICU). PARTICIPANTS: ICU patients over 45 years of age with a primary diagnosis of COPD exacerbation requiring non-invasive ventilation (NIV) or ventilation via endotracheal tube (ETT). MATERIALS AND METHODS: Nasopharyngeal aspirates (NPA) and posterior pharyngeal swabs (PS) were tested for viruses with immunofluorescence assay (IFA), virus culture (VC) and polymerase chain reaction (PCR). Paired virus and atypical pneumonia serology assays were taken. Blood, sputum and endotracheal aspirates were cultured for bacteria. RESULTS: 107 episodes in 105 patients were recorded. Twenty-three (21%) died within 28[Symbol: see text]days. A probable infectious aetiology was found in 69 patient episodes (64%). A virus was identified in 46 cases (43%), being the sole organism in 35 cases (33%) and part of a mixed infection in 11 cases (10%). A probable bacterial aetiology was found in 25 cases (23%). There was no statistically significant difference in clinical characteristics or outcomes between the group with virus infections and that without. CONCLUSION: Forty-six (43%) of the patients with COPD exacerbation requiring mechanical ventilation had a probable viral pathogen. Prodromal, clinical and outcome parameters did not distinguish virus from non-virus illness. PCR was the most sensitive whilst virus culture was the least of virus assays.

Aged↗

Functional involvement of central nervous system in acute exacerbation of chronic obstructive pulmonary disease A preliminary transcranial magnetic stimulation study.

We used transcranial magnetic stimulation to evaluate cortical excitability in acute exacerbations of chronic obstructive pulmonary disease (COPD). Patients affected by COPD were studied during acute exacerbation that required hospital admission and 3-4 months after oxygen therapy. Their data were compared with those of age-matched healthy controls. Intracortical inhibition and cortical silent period duration were significantly reduced in patients during acute exacerbation of COPD. These findings could reflect impairment of GABAergic cortical circuits during hypoxia.

Aged↗

Pancreatic and bile duct obstruction exacerbates rat caerulein-induced pancreatitis: a new experimental model of acute hemorrhagic pancreatitis.

BACKGROUND: Pancreatic duct obstruction induces edematous but not hemorrhagic pancreatitis even when combined with maximal secretory stimulation. The aim of the present study was to test the hypothesis that pancreatic and bile duct obstruction exacerbates edematous pancreatitis induced by supramaximal secretory stimulation by caerulein. METHODS: In in vivo studies using rats, biliopancreatic duct ligation was combined with supramaximal stimulation of caerulein, and pancreatic histology, serum amylase level, pancreatic edema, and intrapancreatic trypsin activation were evaluated. In in vitro studies, the pancreatic acini were isolated from the rats with biliopancreatic duct ligation, and amylase secretion, intracellular trypsin activation, and acinar cell fragility were evaluated. RESULTS: Biliopancreatic duct ligation exacerbated caerulein-induced pancreatitis from edematous to hemorrhagic only when the obstruction preceded caerulein administration. The amylase secretion from the acini was inhibited, and intracellular trypsin activation and the acinar cell fragility on the supramaximal stimulation with cholecystokinin in vitro were enhanced by the preceding in vivo biliopancreatic duct obstruction. CONCLUSIONS: Preceding biliopancreatic duct obstruction exacerbates caerulein-induced pancreatitis. Enhancement of intracellular trypsin activation is possibly involved in this mechanism.

Amylases↗

Postpartum acute exacerbation of chronic hepatitis C with complete response to interferon-alpha.

We describe a patient with chronic hepatitis C who had severe postpartum acute exacerbation of the disease, with marked aminotransferase elevations and jaundice. The viral genotype was 2a, and the patient had a low viral load. Neither superinfection with another hepatotropic virus nor autoantibodies were evident. Markedly increased serum concentrations of T-helper (Th) 1-type cytokines and cytokine receptors, including interleukin (IL)-8, tumor necrosis factor (TNF)-alpha, soluble TNF receptor (sTNFR)-p55, sTNFR-p75, and soluble Fas antigen (sFas), as well as that of the Th 2-type cytokine, IL-10, were present. Complete biochemical and virologic response was achieved with interferon (IFN)-alpha treatment, which decreased cytokine elevations while favoring Th 1 dominance. Acute exacerbation of hepatitis C may occur when cellular immune responses are activated, as in late pregnancy and in the postpartum period. Treating such acute exacerbations immediately with IFN may be highly efficacious.

Adult↗

Serological evidence of acute infection with the Chlamydia-like microorganism Simkania negevensis (Z) in acute exacerbation of chronic obstructive pulmonary disease.

The aims of this study were twofold: (i) to test for possible associations between serological evidence of acute Simkania negevensis (Sn) infection and acute exacerbation of chronic obstructive pulmonary disease and (ii) to examine the prevalence of past infections with Sn in patients with chronic obstructive pulmonary disease. In 120 patients (63%) there was serological evidence of past infection with Sn, which was not significantly different from the rate in a control population. In five hospitalizations serological evidence existed of acute infection with Sn around the time of the exacerbation of chronic obstructive pulmonary disease. In four of these cases, there was serological evidence of acute infection with at least one other respiratory pathogen. It is concluded that Sn can be associated serologically with exacerbation of chronic obstructive pulmonary disease, in most cases together with other respiratory pathogens. The implications of these findings should be investigated further.

Acute Disease↗

Randomised double-blind comparison of oral gatifloxacin and co-amoxiclav for acute exacerbation of chronic Bronchitis.

Antimicrobial therapy can have a significant impact in the treatment of acute infectious exacerbations in patients with chronic bronchitis, in whom repeated episodes are common. The aim of this randomised, double-blind, double-dummy, parallel group study was to compare the efficacy and safety of oral gatifloxacin (200 and 400 mg once daily) administered for 5 days with co-amoxiclav (500 mg amoxicillin/125 mg clavulanic acid t.i.d.) administered for 10 days in 414 adult patients with acute exacerbation of chronic bronchitis. Overall clinical response rates (cure plus improvement) were 86.2%, 79.4% and 81.7% in the gatifloxacin 200 mg, gatifloxacin 400 mg and co-amoxiclav groups, respectively, and the equivalence hypothesis used for statistical analysis showed equivalent efficacy for both gatifloxacin 200 and 400 mg compared to co-amoxiclav. The same was true for rates of bacterial response, with eradication or presumed eradication of causative pathogens achieved in 87.5%, 87.3% and 79.1% of cases in the gatifloxacin 200 mg, gatifloxacin 400 mg and co-amoxiclav groups, respectively. All treatments were well tolerated, with the nature and frequency of treatment-related adverse events similar in all groups. The results of the study show that gatifloxacin is a safe and effective agent for the treatment of patients with chronic bronchitis experiencing an acute infectious exacerbation.

Administration, Oral↗

APOM-associated inflammation and apoptosis in stroke-exacerbated myocardial infarction: implications for brain-heart interactions.

Brain-heart syndrome (BHS) describes cardiac dysfunction secondary to central nervous system injury, with acute ischemic stroke (AIS) serving as a critical driver that exacerbates myocardial infarction (MI). This study aimed to elucidate the role of Apolipoprotein M (APOM) in stroke-aggravated MI and to explore its underlying systemic and molecular mechanisms. Clinical data were analyzed to evaluate the correlation between stroke and MI. A combined mouse model of middle cerebral artery occlusion (MCAO) and MI was established to assess neurological and cardiac injury. Quantitative proteomics and Weighted Gene Co-expression Network Analysis (WGCNA) were employed to screen key differentially expressed proteins. The role of APOM in myocardial injury was validated using APOM-knockout (KO) mice. Furthermore, nuclear-cytoplasmic fractionation, immunofluorescence, and Western blot were performed to investigate its effects on the Saa1 and NF-&#x3ba;B signaling, NLRP3-related inflammatory signaling pathway, and lipid metabolism pathways. Clinical analysis indicated that stroke is a significant risk factor for MI (OR&#x2009;=&#x2009;4.5). In the mouse model, MCAO significantly exacerbated post-MI electrocardiographic abnormalities, myocardial inflammatory response, while elevating circulating levels of cTnT and IL-1&#x3b2;. Proteomics identified a significant downregulation of APOM in the heart, brain, and serum post-stroke, a trend consistent with observations in AIS patients. Further experiments revealed that APOM deficiency markedly worsened cardiac conduction disturbances, histological damage, and inflammatory responses in MI mice. Mechanistically, the loss of APOM upregulates the acute-phase protein Saa1, triggers NF-&#x3ba;B phosphorylation and nuclear translocation, and enhances inflammatory signaling related to inflammasomes, while simultaneously mediating cytokine release from cardiomyocytes. Concurrently, APOM deficiency led to a significant decrease in sphingosine-1-phosphate (S1P) and also caused myocardial lipid droplet accumulation and metabolite changes. Additionally, the loss of APOM increased the expression of D-dimer and fibrinogen family proteins. Our findings suggest that APOM is a potential cardioprotective agent post-AIS. Downregulation of APOM may exacerbate myocardial injury after MI by elevating Saa1 expression, activating the NF-&#x3ba;B pathway and the inflammasome-mediated signaling, and inducing lipid metabolic disorders and coagulation-associated alterations. APOM may represent a potential therapeutic target for the intervention of brain-heart syndrome.

Animals↗

Differentiating acute hepatitis B from the first episode of symptomatic exacerbation of chronic hepatitis B.

In countries with intermediate or high endemicity for chronic hepatitis B virus (HBV) infection, exacerbations of chronic hepatitis B (CHB) are common. We studied the clinical, biochemical, and virologic characteristics of patients first presenting clinically with features of acute icteric hepatitis B, to identify features that might differentiate between acute viral hepatitis B (AVHB) from first episode of exacerbation of chronic hepatitis (ECHB). We retrospectively analyzed 79 patients (mean age 35.4 +/- 14 years; M:F = 60:19) who first presented clinically as AVHB, within 4 weeks of onset of symptoms. Patients who on follow-up cleared HBsAg and/or did not develop any clinical, radiologic, or histologic evidence of chronic liver disease (CLD) were categorized as AVHB (group 1). Patients who had persistence of HBsAg and developed clinical, biochemical, radiologic, or histologic evidence of chronic liver disease were categorized as ECHB (group 2). Forty-nine patients were in group 1 and 30 in group 2. The 2 groups were comparable with respect to prodrome, onset of jaundice, serum bilirubin, ALT, prothrombin time prolongation, serum albumin, and A/G ratio. Among group 1 patients, 78% had IgM anti-HBc positive in titers > 1:1000; in group 2, there were negative or positive in titers < 1:1000 in 70% patients (P < .001). Forty-seven of 49 (95.9%) patients in group 1 had HBV-DNA levels < 0.5 pg/mL, whereas 26 of 30 (86.73%) patients in group 2 had levels > 0.5 pg/mL (P < or = .001). Quantitative HBV DNA and IgM anti-HBc titers at initial presentation can differentiate patients with a true episode of acute hepatitis B from patients with first episode of symptomatic exacerbation of chronic hepatitis B. Clinical and biochemical features do not help in differentiating the two.

Acute Disease↗

Sputum and blood eosinophils during corticosteroid treatment of acute exacerbations of asthma.

Eleven patients with chronic bronchial asthma were studied during a noninfectious exacerbation. Each patient received 80 mg of prednisone daily for three days. Spirometric values, total blood eosinophil counts, and 24-hour quantitation of sputum eosinophils were studied. Three patients had total blood eosinophil counts of less than 250 at the time of presentation. Statistical comparisons with findings on Day 0 showed significant improvements for the one-second forced expiratory volume, total blood eosinophil count, and sputum eosinophil number. On Day 7, the one-second forced expiratory volume maintained a statistically significant difference from that on Day 0, but the total blood eosinophil count did not. Analysis of correlation coefficients showed significant relation between the total blood eosinophil count and one-second forced expiratory volume, the sputum eosinophil count and one-second forced expiratory volume, and the sputum eosinophil and total blood eosinophil counts. The conclusions are (1) blood eosinophilia is not an invariable feature of acute exacerbations of asthma; (2) numbers of blood and sputum eosinophils reflect the response of an acute exacerbation of asthma to corticosteroids; (3) sputum eosinophils may be more meaningful for monitoring the stable postcorticosteroid state; (4) there is no support for the belief that eosinophils disappear from the sputum of asthmatic patients with clinically effective doses of corticosteroids.

Acute Disease↗

Comparison of ciprofloxacin with ampicillin in acute infectious exacerbations of chronic bronchitis. A double-blind crossover study.

Two separate acute bacterial exacerbations of chronic bronchitis and/or asthma were treated in 22 patients in a double-blind crossover study. One course of treatment consisted of 750 mg of ciprofloxacin twice daily and the other of 500 mg of ampicillin four times a day; each drug was given for 14 days. Patients were observed initially, every three to four days during therapy, and weekly during the post-therapy period. Observations that were recorded included graded chest symptoms and physical findings, vital signs, hematologic parameters, and objective sputum measurements (daily volume, purulence, differential quantitative cytology, bacterial counts, and physical properties). Both antibiotic regimens were effective in resolving these acute bacterial exacerbations. Paired t test analysis revealed that ciprofloxacin is as clinically effective as ampicillin in the treatment of acute bacterial exacerbations in chronic bronchial disease, and appears to be superior in clearing bacterial pathogens from the sputum.

Adult↗