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Occult lifelong persistence of infectious hepadnavirus and residual liver inflammation in woodchucks convalescent from acute viral hepatitis.

Traces of hepatitis B virus (HBV) genome can persist for years following recovery from hepatitis B. To determine overall duration, molecular characteristics, and pathological implications of this serologically undetectable form of hepadnaviral carriage, we have analyzed the expression of transcriptionally active virus genomes, their infectivity, and examined liver alterations during the natural lifespan of woodchucks convalescent from acute infection with HBV- related woodchuck hepatitis virus (WHV). In this study, we document lifelong persistence of scanty amounts of replicating virus both in the liver and lymphatic system after spontaneous resolution of an episode of experimental hepadnaviral hepatitis. Antibodies to virus nucleocapsid (core) were found to be the most reliable immunovirological marker coexisting with occult infection. In the majority of convalescent woodchucks, serial liver biopsies showed protracted minimal to mild necroinflammation with periods of normal morphology; however, hepatocellular carcinoma (HCC) ultimately developed in 2 of 9 animals studied. Inocula derived from lymphoid cells of convalescent animals induced classical acute hepatitis in virus-naive woodchucks that progressed to chronic hepatitis and HCC in 1 of the animals, demonstrating infectivity and pathogenic competence of the carried virus. Our results reveal that low levels of infectious WHV and residual hepatic inflammation usually continue for life after resolution of hepatitis and that this recovery does not avert HCC development. They also demonstrate that, in addition to the liver, the lymphatic system is the site of the occult lifelong maintenance of replicating hepadnavirus.

Acute Disease↗

Use of convalescent plasma therapy in SARS patients in Hong Kong.

In order to evaluate the efficacy of convalescent plasma therapy in the treatment of patients with severe acute respiratory syndrome (SARS), 80 SARS patients were given convalescent plasma at Prince of Wales Hospital, Hong Kong, between 20 March and 26 May 2003. Good outcome was defined as discharge by day 22 following the onset of SARS symptoms. Poor outcome was defined as death or hospitalization beyond 22 days. A higher day-22 discharge rate was observed among patients who were given convalescent plasma before day 14 of illness (58.3% vs 15.6%; P<0.001) and among those who were PCR positive and seronegative for coronavirus at the time of plasma infusion (66.7% vs 20%; P=0.001).

Blood Component Transfusion↗

The response to an oral glucose load during convalescence from hypoxia in newborn infants.

The ability to tolerate an oral glucose load during convalescence from hypoxia was studied in four term and 11 premature appropriate-for-gestational-age infants by sequential measurements of the changes occurring in blood pH, bicarbonate, plasma lactic acid, and plasma glucose following an oral glucose load. All infants developed metabolic acidosis and lactic acidemia after the oral glucose load. The maximum fall in blood bicarbonate occurred at 30 minutes, and the maximum rise in plasma lactic acid concentration was attained at 60 minutes. The metabolic changes were found to be more severe in infants given the oral glucose load early in their convalescence and in those infants less than 10 days of age. The absorption of glucose was also decreased in these infants, as shown by a reduced rise in blood sugar. These observations indicate that newborn infants, term or premature, tolerate glucose loads poorly during convalescence from hypoxia.

Acidosis↗

Ventilatory changes in convalescent infants positioned in car seats.

Because premature infants have been shown to be at risk for hypoxia and bradycardia when positioned in standard car seats, this study was done to confirm this finding in a larger sample, to investigate convalescent term infants in the neonatal intensive care unit for respiratory compromise in car seats, and to determine the physiologic mechanism or mechanisms responsible. Extensive multichannel polygraph recordings were obtained and pulmonary function tests were performed on 50 convalescent infants from the neonatal intensive care unit before, during, and after placement in a Cosco-Peterson First Ride car seat. Mean total dynamic compliance, total pulmonary resistance, and work of breathing improved in the car seat. Thirty percent of premature infants experienced hypoxia, bradycardia, or both in a car seat; in this group, tidal volume was lower (p = 0.02). In 11 of 16 infants with abnormal findings, oxygen desaturation was temporally related to episodes of short and mixed apnea. No term convalescent infant experienced respiratory difficulty in a car seat regardless of primary diagnosis. We conclude that premature infants may have respiratory compromise of a multifactorial nature when in car seats. Further development of car seats is necessary if such respiratory problems are to be avoided.

Airway Resistance↗

Prospective comparison of short-term convalescence: laparoscopic radical prostatectomy versus open radical retropubic prostatectomy.

OBJECTIVES: To evaluate and compare prospectively the convalescence of patients after laparoscopic radical prostatectomy (LRP) and open radical retropubic prostatectomy (RRP) in a standardized clinical care pathway at a single institution by two surgeons of equal experience and training. METHODS: The study included all 60 patients undergoing LRP and RRP by two fellowship-trained surgeons in their first year of practice. The postoperative care of these patients was uniform and standardized. The medical records were reviewed and convalescence data obtained by an independent urologist and physician's assistant. RESULTS: Of the 60 patients, 24 underwent RRP and 36 underwent attempted LRP; 3 patients were converted from LRP to RRP. The differences in mean age, preoperative prostate-specific antigen level, Gleason score, in-hospital morphine equivalent requirement, time to oral intake, and hospital stay were not statistically significant between the LRP and RRP groups. The operating room time was significantly longer (5.8 +/- 1.2 hours versus 2.8 +/- 0.55 hours, P <0.0001) and the estimated blood loss was significantly lower in the LRP group (533 +/- 212 mL versus 1473 +/- 768 mL, P <0.0001) than in the RRP group. Pain medication use at home was significantly less in the LRP group (9 +/- 13 versus 17 +/- 15 oxycodone tablets, P <0.04), as was the time to complete convalescence (30 +/- 18 days versus 47 +/- 21 days, P <0.002). CONCLUSIONS: Although LRP took almost twice as long to complete as RRP in our initial clinical experience, the patients had a similar hospital course. LRP patients required less pain medication after discharge and had a shorter time to complete recovery than did RRP patients. Additional studies are needed to address long-term cancer control, potency, and continence outcomes to determine the precise role of LRP in the treatment of men with clinically localized prostate cancer.

Convalescence↗

Baculovirus expressed 2C of foot-and-mouth disease virus has the potential for differentiating convalescent from vaccinated animals.

Determining whether animals have been infected with foot-and-mouth disease virus or vaccinated is important because infected animals frequently become carriers of the virus, shed it intermittently and thus may be the source of new outbreaks of the disease. We had shown previously that the sera of convalescent animals contain antibodies to 2C, a highly conserved non-structural protein, whereas the sera of vaccinated animals do not. This is explained by observation that 2C is retained on the membranes of cells used for growing the virus for vaccine production. In contrast, the non-structural protein 3D, which is released into the medium, is not removed by centrifugation or filtration during vaccine production and therefore stimulates an immune response in both vaccinated and convalescent cattle. In this study we produced 2C and 3D in insect cells infected with recombinant baculoviruses. As demonstrated by serology and electron microscopy, 2C is also retained on the membranes of the insect cells. Both expressed proteins react with sera of convalescent animals, indicating that they are conformationally similar, but the 2C does not react with sera from vaccinated animals. The baculovirus expressed 2C appears to be a suitable antigen for the development of a reliable diagnostic test.

Animals↗

Evaluation of Th1/Th2 ratio and cytokine production profile during acute exacerbation and convalescence in asthmatic children.

BACKGROUND: Th2-type cytokines, such as IL-4 and IL-5, are generally believed to play an important role in the pathogenesis of allergic asthma. In contrast, Th1-type cytokine, especially interferon (IFN)-gamma, is thought to have a downregulatory effect on Th2 immune response cells. Thus, the imbalance of Th1 and Th2 cells may be a key factor in relation to disease severity. OBJECTIVE: The aim of this study is to examine the changes in the Th1/Th2 ratios and cytokine production profiles of asthmatic children at acute attacks and convalescent stages. METHODS: Twelve asthmatic patients were included in this study. The percentages of IFN-gamma- or IL-4-producing cells were determined with a flow-cytometric method of intracellular protein detection. Fresh whole blood obtained from normal controls and patients at two stages was stimulated with brefeldin A, phorbol myristate acetate, and ionomycin for 4 hours. Cells were fixed and stained intracellularly with fluorescein isothiocyanate- or phycoerythrin-conjugated antibody specific to each cytokine in combination with anti-CD4. ELISA assays were applied to measure cytokine concentrations of supernatant from peripheral blood mononuclear cells (PBMC) activated with phorbol myristate acetate and ionomycin for 24 hours. RESULTS: Among CD4+ cells, the percentage of IL-4+ cells decreased significantly from 8.18 +/- 4.77% at acute attacks to 4.18 +/- 1.26% (P < .020) at convalescence. The percentage of IFN-gamma+ cells also decreased from 13.49 +/- 4.21% to 9.03 +/- 5.42% (P < .052). The Th1/Th2 ratios of patients at the two stages were similar, and both were lower than the normal controls. Significantly higher IL-5 and lower IFN-gamma production were detected from activated PBMC of asthmatic patients than normal controls. CONCLUSIONS: The decrease of IFN-gamma+ and IL-4+ cells detected at the single-cell level may explain the potential mechanism of convalescence from acute asthma attacks. High Th1/Th2 ratio and low IL-5 production from the PBMC of normal controls support the idea of a biased Th2 immune response in asthmatic patients.

Acute Disease↗

Surveillance of transcriptomes in basic military trainees with normal, febrile respiratory illness, and convalescent phenotypes.

Gene expression profiles permit analysis of host immune response at the transcriptome level. We used the Pax gene Blood RNA (PAX) System and Affymetrix microarrays (HG-U133A&B) to survey profiles in basic military trainees and to classify them as healthy, febrile respiratory illness (FRI) without adenovirus, FRI with adenovirus, and convalescent from FRI with adenovirus. We assessed quality metrics of RNA processing for microarrays. Class prediction analysis discovered nested sets of transcripts that could categorize the phenotypes with optimized accuracy of 99% (nonfebrile vs febrile, P<0.0005), 87% (healthy vs convalescent, P=0.001), and 91% (febrile without vs with adenovirus, P<0.0005). The discovered set for classification of nonfebrile vs febrile patients consisted of 40 transcripts with functions related to interferon induced genes, complement cascades, and TNF and IL1 signaling. The set of seven transcripts for distinguishing healthy vs convalescent individuals included those associated with ribosomal structure, humoral immunity, and cell adhesion. The set of 10 transcripts for distinguishing FRI without vs with adenovirus had functions related to interferon induced genes, IL1 receptor accessory protein, and cell interactions. These results are the first in vivo demonstration of classification of infectious diseases via host signature transcripts and move us towards using the transcriptome in bio-surveillance.

Adenovirus Infections, Human↗

Risk of subsequent cardiac events in stable convalescing patients after first non-Q-wave and Q-wave myocardial infarction: the limited role of non-invasive testing. The Multicenter Myocardial Ischemia Research Group.

BACKGROUND: Patients recovering from myocardial infarction are frequently evaluated by non-invasive tests for evidence of myocardial ischemia before returning to work or full activity. The purpose of this study was to evaluate the prognostic significance of clinical and non-invasive ischemic test variables assessed in 549 stable, convalescing patients (median 2 months) after their first Q-wave (n = 363) and non-Q-wave (n = 186) myocardial infarction. METHODS: The ischemic tests performed were resting ECG, exercise ECG, ambulatory ECG, and stress thallium scintigraphy. RESULTS: Cardiac events (unstable angina requiring hospitalization, non-fatal reinfarction, or death from cardiac causes) were observed during a mean 23-month follow-up in 57 patients (15.7%) with Q-wave and in 31 of patients (16.7%) with non-Q-wave infarction. In a step-wise Cox regression model, the only significant independent predictors of subsequent cardiac events (P < 0.001) were post-infarction angina and insulin-dependent diabetes mellitus. The type of infarction did not make a significant contribution to the risk of cardiac events (P = 0.29). However, an interaction between infarct type and post-infarction angina was of borderline significance (P = 0.065), with angina associated with more cardiac events in patients with non-Q-wave than in those with Q-wave infarction. None of the ischemic tests contributed significantly to the Cox model in predicting cardiac events in either infarct type. CONCLUSION: Stable convalescing patients who have recovered from first Q-wave and non-Q-wave myocardial infarction have similar long-term prognoses. The occurrence of post-infarction angina is associated with increased risk of cardiac events in patients with both infarct types, with more marked effect in non-Q-wave than Q-wave infarctions. Ischemia detected by non-invasive tests performed in the convalescing phase after myocardial infarction was not prognostically useful in either infarct type.

Convalescence↗

Killing of Escherichia coli in the peritoneal cavity of convalescent mice; role of specific and non-specific immune mechanisms.

Mice surviving a sublethal E. coli O18:K1 infection possess a greatly increased resistance to a subsequent lethal E. coli O18:K1 peritonitis. A similar increase in resistance can also be achieved by LPS pretreatment. The early course of the infection in the convalescent mice at day 1 was identical to that in LPS-pretreated mice. At this time, the convalescent mice were also able to restrict the growth of the heterologous E. coli O78(ColV) strain, suggesting that non-specific phagocyte activation was responsible for the increased destruction of the bacteria. At day 4, the kinetics of infection in convalescent mice were identical to those in mice passively immunised with specific anti-K1 capsule antiserum. A rapid decline in the numbers of viable homologous, but not heterologous, bacteria took place in the peritoneal cavity suggesting effective antibody-mediated opsonisation followed by phagocytosis and killing of the bacteria.

Animals↗

Evaluation of renal tubular functions in convalescent phase of hemorrhagic fever with renal syndrome.

To evaluate renal tubular functions and to investigate the causative factors of urinary-concentrating defects in the late stage of hemorrhagic fever with renal syndrome (HFRS), 11 HFRS patients in the convalescent phase were studied and compared with 8 acute renal failure (ARF) patients in convalescence (disease controls) and 9 healthy adults preparing for kidney donation (normal controls, NC). Minimal urine osmolality induced by water loading was higher (p < 0.05) in HFRS (89.5 +/- 22.1 mosm/kg) and ARF patients (84.8 +/- 14.7 mosm/ kg) than in NC (47.8 +/- 4.6 mosm/kg), but the solute-free water clearance of HFRS patients (9.0 +/- 1.3%), measured at maximal diuresis, was not different from that of ARF patients (6.7 +/- 1.2%) or NC (10.5 +/- 1.4%). After 12-hour water deprivation + vasopressin stimulation, HFRS had lower urine osmolality (433.7 +/- 31.1 versus 850.0 +/- 35.1 mosm/kg; p < 0.05), urine-to-plasma osmolality ratio (1.47 +/- 0.11 versus 2.91 +/- 0.11; p < 0.05), and solute-free water reabsorption (0.53 +/- 0.07 versus 0.91 +/- 0.12%; p < 0.05) than NC. As compared with ARF patients (1.09 +/- 0.16%) or NC (1.49 +/- 0.16%), HFRS patients (0.43 +/- 0.20%) had lower solute-free water reabsorption measured at maximal antidiuresis induced by water deprivation + vasopressin stimulation + hypertonic saline infusion (p < 0.05). In HFRS, the plasma vasopressin level and plasma vasopressin/osmolality ratio increased from 3.9 +/- 0.8 to 6.1 +/- 1.1 pg/ml and from 0.013 +/- 0.003 to 0.020 +/- 0.004 pg/ml/mosm/kg after 12-hour water deprivation, respectively (p < 0.01). However, neither basal nor stimulated values of the plasma vasopressin level or plasma vasopressin/osmolality ratio was different among the 3 groups. HFRS patients were not different from ARF patients or NC in lithium clearance, urinary-acidifying capacity, and fractional excretions of sodium, potassium and bicarbonate. We conclude that in the convalescent phase of HFRS, the urinary-acidifying ability is not disturbed, the urinary-diluting defect is mild, and the urinary-concentrating capacity is obviously impaired. This study suggests that the most important factor contributing to the urinary-concentrating defect in HFRS is the reduced collecting duct responsiveness to vasopressin.

Acute Kidney Injury↗

Plasma homocysteine concentrations in the acute and convalescent periods of atherothrombotic stroke.

BACKGROUND AND PURPOSE: Homocysteine is a proposed causal risk factor for atherosclerosis, but this remains controversial. We measured fasting plasma homocysteine concentrations immediately after atherothrombotic stroke and in the convalescent period to investigate this controversy. METHODS: One hundred six patients (59 men and 47 women, mean age 57.2 [25 to 70] and 56.5 [26 to 69] years, respectively) were recruited within 24 hours of admission, and 82 patients were resampled at least 3 months later. Fasting total plasma homocysteine (tHcy) concentrations were measured by high-performance liquid chromatography. RESULTS: Median tHcy in the acute phase of stroke was not significantly higher than in matched control subjects (men 9.2 [range 4.4 to 22.8] versus 8.7 [4.9 to 20] micromol/L, P:=0.09, Mann-Whitney U: test; women 8.1 [4.8 to 32.3] versus 7.6 [3.3 to 14.4] micromol/L, P:=0.58). Median plasma concentrations increased significantly in the convalescent period (from 8.5 [4.8 to 19.2] to 10.1 [4.3 to 31.5] micromol/L, P:<0.001, Wilcoxon signed rank test) and were then significantly higher than in control subjects in both men and women (P:=0.03 and 0.05, respectively, Mann-Whitney U: test). This did not appear to be explained by alteration in the known covariates red-cell folate, serum B(12), or creatinine concentrations. CONCLUSIONS: Homocysteine concentrations are not elevated after recent atherothrombotic stroke but rise in the convalescent period. These data do not support the hypothesis that raised plasma homocysteine concentrations predate atherothrombotic stroke. Instead, they offer an explanation for the discrepancies between prospective and retrospective studies and suggest that elevated tHcy levels may be caused by the disease process itself.

Acute Disease↗

Maternal feeding behavior and child acceptance of food during diarrhea, convalescence, and health in the central Sierra of Peru.

Feeding patterns by mothers and child acceptance of food were measured in a Peruvian village to determine changes on days when children had diarrhea as compared to days of convalescence and health. Morbidity surveillance identified 40 children, aged 4-36 months, with diarrhea. Children were followed using twelve-hour in-home structured observations during two to four days each of diarrhea, convalescence, and health. Using scales of maternal encouragement to eat and child acceptance of food and cumulative logistic regression analyses, maternal encouragement to eat decreased significantly during convalescence compared to diarrheal days (OR: 0.54, 90% CI: 0.35, 0.82) and health compared to diarrhea (OR: 0.65, 90% CI: 0.46, 0.93). In contrast, child acceptance of food increased during health compared to diarrhea (OR: 1.55, 90% CI: 1.02, 2.35). Results illustrate the importance of carefully examining the behavioral aspects of nutritional intake. Decreases in intake during diarrhea are due to anorexia and not withdrawal of food by mothers. In response to reductions in child appetite during illness, mothers are more likely to encourage children to eat, while they tend to become more passive feeders after the diarrhea has stopped. Program efforts should focus on messages to feed children more actively especially after diarrhea episodes, when appetite levels increase.

Adult↗

[Hepatobiliary alternations in leptospirosis convalescents].

AIM: To study hepatic function in leptospirosis convalescents. MATERIALS AND METHODS: Clinical laboratory and device examinations were performed in 121 leptospirosis convalescents. RESULTS: The majority of the examinees retained biochemical signs of cholestatic, mesenchymal-inflammatory and moderate cytolytic syndromes secondary to hepatic impairment. Ultrasound and radionuclide investigations detected biliary disorders and secondary chronic hepatitis in many of leptospirosis convalescents. CONCLUSION: It is shown that leptospirosis rehabilitation must be targeted. Reasons of development of chronic hepatic and biliary lesions in population of the north Caucus and Kuban in the absence of viral hepatitis markers are suggested.

Adult↗

[Thoracic high resolution CT findings of 100 SARS patients in convalescent period].

OBJECTIVE: To study thoracic high resolution CT findings of severe acute respiratory syndrome (SARS) patients in convalescent period and the relationship between the features with laboratory and pulmonary function results. METHODS: All the 100 SARS patients who had been discharged from hospital for about 2 months underwent thoracic high resolution CT examinations. Among them, 65 also had laboratory results and 91 underwent examinations of pulmonary function. RESULTS: Forty-nine SARS patients (49.0%, 49/100) in convalescent period still had abnormal findings in CT examination. And ground-glass opacification (95.9%, 47/49) and reticular opacification (59.2%, 29/49) were common. There was no significant difference in the level of lymphocytes and CD4 cells among groups divided according to severity of CT findings (P > 0.01). Diffusing capacity for carbon monoxide (DLco%) of level 2 and 3 were statistically lower than that of level 0 (P < 0.01). CONCLUSIONS: The features of CT findings of SARS patients in convalescent period are not the same as those of patients in period of apparent manifestation. The high resolution CT can reflect pulmonary diffusing function to some degree.

Adolescent↗

[Assessment of pulmonary function in SARS patients during the convalescent period].

OBJECTIVE: To investigate the pulmonary function in severe acute respiratory syndrome (SARS) patients during the convalescent period. METHODS: Followup 89 outpatients of SARS. The follow-up study included interview, physical examination, and pulmonary function test. RESULTS: The interval between hospital discharge and functional assessment was 1.75 +/- 0.53 months (0.5-3.4 months). Mild to moderate abnormalities in pulmonary function were found in 48 patients (53.9%). Diffusion capacity for carbon monoxide (DLco) was impaired in 38 patients (42.7%); in 7 patients (7.9%), lung function was restrictive defect combined DLco impairment; Other patterns of impairment were revealed in 3 patient. Dyspnea during acute phase and CT during the convalescent period were found to have significant influences on DLco and total lung capacity (TLC). CONCLUSIONS: Diffusing capacity impairment as well as restrictive defect persist in convalescence SARS.

Adolescent↗

[Study on the RNA of severe acute respiratory syndrome (SARS) associated coronavirus in the blood and excretion of convalescent patients with SARS].

OBJECTIVE: To examine the RNA of severe acute respiratory syndrome-associated coronavirus (SARS-CoV) in the blood and excretion of convalescent patient with SARS for prevention and treatment of the disease. METHODS: A total of 276 samples, including plasma, urine, feces and sputum, obtained from 23 convalescent patients with SARS were studied at 3 time-points at least 21 days after the onset of symptoms. RNA was extracted and nested reverse transcription-polymerase chain reaction (RT-PCR) was carried out using SARS-CoV specific primers. RESULTS: Among the 276 samples, SARS-CoV RNA was detected in 6 cases (38.8%) by nested RT-PCR. The positive rates of SARS-CoV RNA was 5.8% in feces and 2.9% in sputum samples but SARS-CoV RNA was not detectable in plasma and urine of all the cases. CONCLUSION: The existence of SARS-CoV RNA in the excretion of some convalescent patients with SARS showed that the excretion from these patients should be carefully treated whilthe re-transmission of SARS by which, should be further studied.

Adolescent↗

Antigenic glycopolypeptides HA1 and HA2 of influenza virus haemagglutinin. III. Reactivity with human convalescent sera.

The immune reactivity to both haemagglutinin glycopolypeptides HA1 and HA2 [prepared from bromelain-released haemagglutinin of influenza virus A/Dunedin/4/73 (H3N2)], was demonstrated by both gel double immundiffusion and radioimmunoassay in human convalescent sera obtained after natural infection during influenza epidemics in 1974/75 and 1976/77. In gel double immunodiffusion, the precipitin line(s) corresponding to glycopolypeptide HA1 were always more distinct than precipin line(s) corresponding to glycopolypeptide HA2. In radioimmunoassay, human convalescent sera revealed higher titres for binding of 125-I-labelled HA2 than for 125-I-labelled HA1. Characterization of human convalescent sera was completed by haemagglutination-inhibition test.

Antibodies, Viral↗