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Changes of adult T cell leukemia cell surface antigens at relapse or at exacerbation phase after chemotherapy defined by use of monoclonal antibodies.

Surface phenotypes of leukemic cells from six patients with adult T cell leukemia (ATL) were analyzed by the use of monoclonal antibodies, both at the time of initial diagnosis and at either relapse or exacerbation phase after chemotherapy. Changes of cell surface antigens were observed in four of the six cases. The majority of the leukemic cells of these patients were reactive with anti-Leu-1 and anti-Leu-3a, but unreactive with anti-Leu-2a and MAS 036c monoclonal antibodies at the time of initial diagnosis, indicating that ATL cells are of peripheral inducer/helper T cell origin. In three cases, the Leu-1 antigen disappeared at relapse or at exacerbation phase, and in one of these cases, a small percentage of ATL cells became reactive with MAS 036c, which identifies cortical thymocyte antigen. ATL cells of one other case did not have Leu-1 antigen from the start, but gained Leu-2a antigen at exacerbation phase and became double-labeled cells (Leu-2a+, 3a+), which is known to be a feature of thymocytes. Thus, it appeared that ATL cells sometimes change their surface phenotype to that of an earlier stage of T cell differentiation at relapse or at exacerbation phase. Chronic myelocytic leukemia (CML) cells also usually change to immature cells at blastic crisis involving morphological change. However, this morphological change was not so prominent in the ATL cases studied, except one, in which typical ATL cells with nuclear indentation changed to large immature cells with basophilic cytoplasm at relapse.

Adult↗

[Thiamphenicol versus trimethoprim-sulfamethoxazole in bacterial exacerbations of chronic unspecific respiratory tract diseases. A controlled study].

To document the efficacy of trimethoprim-sulfamethoxazole (TMP-SMZ) in treating bacterial exacerbations of chronic bronchitis, and to evaluate the efficacy of thiamphenicol (TAP), 29 patients with chronic bronchial disease were treated for two separate bacterial exacerbations, once with 0.48 g of TMP and 2.4 g SMZ daily, and once with 1.5 g of TAP daily, for 14 days. Patients were evaluated weekly and different measurements, including graded clinical observations, ventilatory tests, sputum measurements, quantitative bacterial counts and blood studies were performed. Side effects were closely monitored. Of the 29 patients entered, 20 finished the trial and hence 40 exacerbations were evaluated. All graded clinical observations were improved by the antimicrobials, whereas no marked change in the ventilatory tests was seen. Of the sputum measurements the daily volume, purulence, numbers of neutrophils and bronchial epithelial cells decreased, as did the numbers of Haemophilus influenzae and pneumococci. Of the blood studies the red blood cell count fell by more than 20% of the pretreatment value in 2 patients on TAP and 2 on TMP-SMZ. Using the same criterion, the hemoglobin level fell in 4 patients on TAP and in the hemoglobin level fell in 4 patients on TAP and in 2 patients on TAP-SMZ, while the hematocrit fell in 4 patients on TAP and in 1 on TMP-SMZ. However, all these changes were completely reversible. Minor gastrointestinal side effects were observed in 11 patients receiving TAP, compared to 3 patients on TMP-SMZ. 1 patient on the latter drug experienced a rash at the end of therapy. From the viewpoint of overall clinical assessment, 16 patients improved and 4 remained unchanged during therapy with TAP. The corresponding figures for TMP-SMZ were 17 patients improved, 2 the same and 1 worse at the end of therapy. The average relapse time after TAP was 184 days and after TMP-SMZ 180 days. In conclusion, 80% or more of exacerbations were improved by the two drugs. For all the variables measured, no significant differences were statistically detectable between the two antimicrobials, whether given in the sequence TAP first and TMP-SMZ second, or vice versa.

Adult↗

Role of interleukin 1 in antigen-induced exacerbations of murine arthritis.

The mechanism underlying the chronic and intermittent course of rheumatoid arthritis is not elucidated. In the present study, the role of interleukin 1 (IL-1) was investigated in exacerbations of antigen-induced arthritis in mice. A flare-up of smoldering inflammation (weeks 3 to 4 of antigen-induced arthritis) was inducible by injection of a small amount of methylated bovine serum albumin into the hypersensitive knee joint. Immunohistochemistry showed IL-1 expression in the synovial lining layer and in focal areas of the inflamed synovium during the flare-up. IL-1 was also measured in 1-hour culture supernatant of synovial tissue taken during the flare-up by a bioassay. The expression of both immunoreactive and bioactive IL-1 in the hypersensitive joint peaked around 6 hours after antigen (2 micrograms of methylated bovine serum albumin) injection and declined thereafter. Antigen rechallenge induced an acute joint swelling of the arthritic joint but not in the naive joint of the sensitized mouse, yet synovia of both joints produced IL-1 after antigen injection. Remarkably, a single intravenous injection of rabbit anti-IL-1 alpha and -beta antibodies 1 hour before antigen rechallenge neutralized IL-1 in the joint. Anti-IL-1 treatment significantly reduced the antigen-induced joint swelling (30 to 40%) but did not affect the profound influx of polymorphonuclear cells in the onset of the exacerbation. However, a profound relief of the inflammation (synovitis) was obtained by IL-1 blockade on day 4 of the exacerbation. Chondrocyte proteoglycan synthesis was markedly suppressed in the antigen-challenged naive knee joints suggesting that this was a direct IL-1 effect as the inflammation was insignificant. Anti-IL-1 treatment was able to maintain chondrocyte proteoglycan synthesis in the antigen-rechallenged joint, which was highly suppressed in the control group. Furthermore, the enhanced proteoglycan breakdown in the antigen-rechallenged joints was significantly decreased in the anti-IL-1 group. We concluded that IL-1 is an important mediator in exacerbations of murine arthritis, and amelioration of cartilage pathology was obtained with anti-IL-1 antibody treatment.

Animals↗

[Clinical analysis of cases with acute exacerbation of chronic renal failure].

We analyzed the total number of 42 events of acute exacerbation of chronic renal failure (CRF) in 35 patients who were admitted to the Matsuyama Red Cross Hospital Kidney Center between 1985 and 1990. These patients consisted of 16 males and 19 females with a mean age of 59.8 +/- 12.7 years. The most frequent original renal diseases were diabetic nephropathy (DM) and arteriosclerotic nephrosclerosis (NS). The most frequent acute exacerbation factors were dehydration and infection. Four cases died and one case transferred to chronic hemodialysis, but the other 37 events (88%) in 31 cases recovered to normal renal functioning. Tentative dialysis therapy was performed for 12 events, in which the cases with DM as the original disease and infection as the exacerbation factor were responsive to this therapy. In the analysis of long-term prognosis, 7 out of 26 cases died of non-renal diseases, 15 transferred to chronic dialysis therapy and only 4 remained in a CRF state. The intervals between the date of discharge and that of the start of dialysis therapy was shorter in the cases with DM (mean of 5 months) or chronic glomerulonephritis (mean of 7.6 months) than in cases with chronic interstitial nephritis, polycystic kidney disease and NS (mean of 17.7 months). We concluded that even though many of the cases eventually transferred to chronic dialysis therapy, appropriate therapy during the acute exacerbation period could allow recovery to a natural progressive or nonprogressive course in each case.

Acute Kidney Injury↗

Chlamydia pneumoniae infection in acute exacerbations of COPD.

Chlamydia pneumoniae, strain TWAR, is a frequent causative agent of acute respiratory disease. We assessed the incidence and prevalence of Chlamydia pneumoniae infections in COPD. We studied, from January 1990 to May 1991, 142 out-patients with acute purulent exacerbations of chronic obstructive pulmonary disease (COPD) and 114 healthy control subjects. Oropharyngeal swab specimens were collected at each exacerbation and analysed using a high definition monoclonal indirect fluorescent antibody test for Chlamydia pneumoniae identification. Immunoglobulins G and M (IgG and IgM) fractions of antibodies to Chlamydia pneumoniae were studied by microimmunofluorescence test. Prevalence of specific IgG was 63% in COPD, and 46% in controls (Chi-squared test p = 0.007). Moreover, mean titre of IgG was significantly higher in COPD than in controls. Five patients were positive for specific IgM (> or = = 1:16), and one had a fourfold increase of IgG titre; four of these patients had been treated with ciprofloxacin 1 g.day-1 for 10 days, and two with erythromycin, 3 g.day-1 for 14 days, with remission of signs and symptoms of exacerbation. Chlamydia pneumoniae identification was always negative. Our data suggest that Chlamydia pneumoniae infection is a rather frequent event in COPD, since at least 4% of exacerbations may be associated with it.

Acute Disease↗

Influenza vaccination of children during acute asthma exacerbation and concurrent prednisone therapy.

OBJECTIVES: The influenza vaccination rate is very low among children with moderate to severe asthma. This may be partly because of poor patient motivation and failure to visit clinics for vaccination. Another important factor may be health care providers' deferral of vaccination because of concern about the efficacy and safety of influenza vaccination during asthma exacerbations and concurrent prednisone therapy. We therefore examined the safety and immunogenicity of influenza vaccination during acute asthma exacerbation with concomitant prednisone therapy. SETTING: A pediatric allergy and pulmonology clinic and a pediatric emergency department. DESIGN: Children (n = 109) with a known diagnosis of asthma 6 months to 18 years of age were recruited. All participating patients, 59 without asthma symptoms (no prednisone, control group) and 50 with acute asthma exacerbation requiring prednisone burst therapy (prednisone group) received trivalent subvirion influenza vaccine. Fifteen children in the control group and 12 in the prednisone group received a booster dose according to American Academy of Pediatrics guidelines. Serum antibody titers to influenza A/Beijing/32/92 (H3N2), influenza A/Texas/36/91 (H1N1), and influenza B/Panama/45/90 were measured before and 2 weeks after vaccination. Adverse effects noted within 48 hours after vaccine dose were ascertained during the follow-up visit. RESULTS: The antibody response was analyzed by comparing mean postvaccine titers, the percentage of patients achieving protective antibody levels (> or = 5log2), and the percentage of patients achieving rises in titers of 2log2 or greater. Antibody responses to influenza A/Beijing/32/92 (H3N2) and influenza A/Texas/36/91 (H1N1) in the prednisone-treated and control groups were not different. A significantly better response to the influenza B/Panama/45/90 antigen was seen in the prednisone group for all three parameters. Children who received a booster dose and the subgroup of children with low prevaccination titers (< or = 3log2) showed similar patterns. Adverse effects, including asthma exacerbation, local swelling at the injection site, fever, rash, and headache, were not different in the two groups. CONCLUSIONS: Influenza vaccination can be given safely and effectively to asthmatic children regardless of asthma symptoms or concurrent prednisone therapy when necessary. Vaccination of all moderate to severe asthmatic patients visiting clinics or emergency departments would improve the overall vaccination rate significantly.

Antibodies, Viral↗

A comparison of serum haptoglobin levels between acute exacerbation and clinical remission in asthma.

BACKGROUND: Bronchial asthma is characterized by airway inflammation, which underlies the phenomenon of bronchial hyperresponsiveness. The concentration of serum haptoglobin (Hp), one of the acute phase reactant proteins, has been reported to correlate with bronchial hyperresponsiveness. The extent to which bronchoconstriction or airway inflammation contributes to airflow obstruction of exacerbation is presumed to determine the responsiveness to the initial bronchodilator therapy. OBJECTIVE: To see whether the Hp levels vary with the disease status of asthma, and also to test whether the Hp level at an acute exacerbation (AE) is correlated with the degree of response to initial bronchodilator therapy. METHODS: We measured serum Hp levels in 50 children with asthma at the times of an AE and a clinical remission(CR), and analysed the data according to the response to the initial bronchodilator therapy at AE. RESULTS: The serum concentration of Hp at AE (228.5 +/- 80.8 mg/dl, mean +/- SD) was significantly (P < 0.01) higher than that at CR (152.3 +/- 49.8 mg/dl) in the total study population. The difference of Hp levels between AE and CR was more marked (101.7 +/- 82.2 mg/dl) in the subjects (n = 19) who responded poorly (post-bronchodilator FEV1 < 75% predicted) to the initial bronchodilator therapy at AE than that (61.0 +/- 56.5 mg/dl) of those (n = 31) who responded well (post-bronchodilator FEV1 > or = 75% predicted). The Hp level at AE correlated with the degree of response to initial bronchodilator therapy (r = (-)0.36, P < 0.05), whereas it had no relationship with the severity of exacerbation (r = 0.04, P = 0.79). CONCLUSION: Our results showed that Hp levels may be increased at the time of exacerbation in a given asthma patient. The finding that the elevation of Hp level at AE is more marked in the cases with poor response to initial bronchodilator therapy at AE suggests that the increased Hp level at AE in asthma might reflect the degree of airway inflammation.

Adolescent↗

[Causative role of infections with viruses or atypical pathogens in acute exacerbations of chronic bronchitis less frequent than expected].

OBJECTIVE: To determine the prevalence of viruses and atypical pathogens as causes of acute severe exacerbations of chronic bronchitis. DESIGN: Retrospective. SETTING: University Hospital Utrecht, the Netherlands. METHODS: In 4 studies with 305 patients with severe type-1 exacerbations (increase of dyspnoea, of sputum volume and of sputum purulence) serological tests for viral and atypical pathogens were performed. RESULTS: Positive serology for viral infections was seen in 18 (5.9%) patients and for the atypical pathogens in 12 (3.9%) patients. CONCLUSIONS: Since viruses and atypical pathogens are the cause of the exacerbation in only few cases, clinical signs can be used in decision-making whether or not to prescribe antibiotics in acute exacerbations of chronic bronchitis.

Anti-Bacterial Agents↗

Managing symptoms and exacerbations in pediatric asthma.

International guidelines indicate that the primary goals of asthma treatment are minimizing symptoms and preventing exacerbations. Symptoms last for short periods of time (minutes or hours) and usually disappear either spontaneously or with the use of bronchodilator therapy. Exacerbations last for 1 or more days and need more extensive bronchodilator therapy with the possible addition of a course of oral corticosteroids. Particularly in children, because of their active life style, exercise-induced symptoms may interfere with normal daily life, and nocturnal symptoms may cause severe sleep disturbance. Although the avoidance of triggers that provoke symptoms and exacerbations is advocated in the guidelines, this is not a practical option as it is extremely difficult for asthmatic children to lead a normal life and yet avoid exercise. Long-term use of medication is therefore necessary to achieve the treatment goals. Inhaled corticosteroids have been shown to be the most effective drugs for reducing asthma symptoms and exacerbations. However, most children will not be free of symptoms during corticosteroid therapy and intermittent use of bronchodilator therapy is required. Cessation of inhaled corticosteroid therapy, even after several years of use, is likely to result in a reoccurrence of asthma symptoms. Long-acting beta 2-agonists, such as salmeterol and formoterol, are now available as additional therapy to inhaled corticosteroids in patients who remain symptomatic despite at least a moderate dose of inhaled corticosteroid. Two recent studies in adults revealed addition of salmeterol superior to increasing inhaled corticosteroid dose. So far, no data in children are available, but theoretically it might be attractive to add a long-acting beta 2-agonist to on-going therapy for children who remain symptomatic, especially at nighttime, despite the use of inhaled corticosteroids. There is no place for the use of long-acting beta 2-agonists as monotherapy in pediatric patients.

Adolescent↗

[Precipitating factors in patients with repetitive exacerbation of chronic left heart failure].

The precipitating factors of repetitive exacerbation were investigated in 110 consecutive patients with chronic left heart failure admitted due to acute exacerbation more than twice to the medical emergency ward of National Cardiovascular Center from January, 1992 to December, 1996. The controls were 189 consecutive patients with chronic left heart failure admitted to the ward due to acute exacerbation only once during the same period. Excessive intake of water or sodium, overwork and infection were common precipitating factors in the first decompensation of left heart failure, but the former two factors became less common with repeated admission. Patient mistakes such as excessive intake of water or sodium, overwork and noncompliance with medications, and new onset arrhythmias were common precipitating factors in patients (n = 13) admitted to the ward more than four times. Infection was a common precipitating factor (63%) in patients with a time interval between readmission and the last discharge of longer than 2 years. Despite repeated admission, infection was a common precipitating factor in patients with valvular heart disease (n = 31), patient mistakes were common in heart disease with left ventricular hypertrophy (n = 20), and infection and new onset arrhythmias were common in dilated cardiomyopathy (n = 28) and old myocardial infarction (n = 31). Patient mistakes and new onset arrhythmias were the common factors that led to repetitive exacerbation of left heart failure, and precipitating factors were characterized by the etiology of left heart failure.

Aged↗

Phagocytic synovial lining cells regulate acute and chronic joint inflammation after antigenic exacerbation of smouldering experimental murine arthritis.

OBJECTIVE: To investigate the in vivo role of phagocytic synovial lining cells in inflammation after exacerbation of smouldering murine antigen induced arthritis. METHODS: Phagocytic synovial lining cells were selectively depleted, by intraarticular injection of clodronate laden liposomes, 2 weeks after induction of modified bovine serum albumin induced arthritis. Exacerbation of arthritis was induced at Week 3, intravenously or locally into the knee joint. Arthritis was evaluated by 99mTc uptake measurements or in hematoxylin and eosin stained sections. Retention of radiolabeled antigen was evaluated by external measurement of radioactivity or autoradiography. Chemotactic factor production and interleukin 1 (IL-1) protein level were detected in washout samples of arthritic joints by transwell chemotactic assay and NOB.EL-4 bioassay or immunolocalization, respectively. RESULTS: One day after induction of flare, swelling measured by 99mTc uptake was similar in control and lining depleted knee joints. Histological examination of control reactivated knee joints revealed infiltrate in both superficial and deep synovial layers, while florid exudate occurred in the joint cavity. In lining depleted reactivated knee joints infiltrate was significantly decreased, found mainly in the deep synovial layer around the blood vessels, whereas exudate was significantly lower. No difference was found in the topography of the synovial infiltrate for antigen given intraarticularly versus intravenously. Antigen removal was slowed in lining depleted joints and autoradiographs showed antigen persistence mainly in the joint cavity and the synovial layer. Reduced influx of inflammatory cells was correlated to decreased production of chemotactic factors. Level of IL-1 was lower in washouts and was mainly detected in macrophages in the deep layer, as shown by immunolocalization. In controls, more IL-1 was detected in the lining and subsynovial layer. At Day 7 after exacerbation no synovitis was found in the synovial lining cell depleted arthritic joint, whereas florid synovitis persisted in the arthritic control joint. CONCLUSION: Phagocytic synovial lining cells are involved in acute and chronic inflammation after exacerbation of hyperreactive joints with antigen given either directly into the knee joint or intravenously.

Acute Disease↗

Airways microbial flora in COPD patients in stable clinical conditions and during exacerbations: a bronchoscopic investigation.

Patients affected with chronic obstructive pulmonary disease (COPD) undergo frequent exacerbations of their illness characterized by increased cough and expectoration. The precise aetiology of these episodes often remains unknown. In the absence of clinical or radiographic signs of pneumonia, bacterial or viral cultures of sputum usually provide little useful information. Thus, we performed fibreoptic bronchoscopy using a protected specimen brush (PSB) to obtain uncontaminated secretions for culture from 56 patients with COPD, 16 with stable clinical conditions and 40 affected with exacerbations of the disease. The aim of our study was to evaluate bronchial microbial flora by quantitative aerobic and anaerobic culture of each specimen. Twenty five subjects (45%), 4 (16%) in stable state and 21 (84%) with COPD exacerbations, had specimens which gave rise to significant bacterial growth (> 10(3) colony forming units.mL-1). The predominant bacteria were Streptococcus pneumoniae (in 10 cases) and alpha-haemolytic streptococci (in 6 cases); other bacteria found were coagulase-negative staphylococci and Branhamella catarralis in (2 cases each), and Proteus mirabilis, Haemophilus influenzae, Pseudomonas aeruginosa, Aerococcus viridans and Chromobacterium violaceum (each in a single case only). Although significant bacterial growth was more frequently found in patients with chronic obstructive pulmonary disease exacerbations and in those with a higher degree of bronchial inflammation, the differences between the two groups of patients were not statistically significant. Nevertheless, the results obtained in our study confirm the validity of and the need for reliable sampling methods (like the protected specimen brush) to demonstrate significant bacterial colonization of the airways in chronic obstructive pulmonary disease patients.

Aged↗

Exacerbation of cold restraint-induced gastric ulcer by GABA in mice.

AIM: To study the effect of GABA on cold restraint-induced gastric ulcer (CRGU) and its mechanism. METHODS: CRGU was produced in adult male mice at 1 degree C in cold room under restraint for 1 h. The ulcer index indicated the severity of gastric mucosa lesion. Gastric mucin was determined with alcian blue dye. RESULTS: GABA 2 mumol (i.c.v.) accelerated CRGU, Bicuculline (Bic) 0.2 mumol (i.c.v.) did not affect CRGU, whereas Baclofen (Bac) 4 mumol (i.c.v.) exacerbated CRGU. Bic did not modify the exacerbation of CRGU by GABA and Bac. Atropine (Atr) 0.2 mg.kg-1 (s.c.) and Phentolamine (Phen) 2.5 mg.kg-1 inhibited CRGU, and abolished the exacerbation of CRGU by GABA. Cold restraint (CR) decreased the amount of the gastric mucin, but GABA 2 mumol had no effect on CR gastric mucin. CONCLUSION: While GABA-B receptor in brain was activated, exogenous GABA exacerbated CRGU via vagal and sympathetic nerves, bearing no relation to decrease of the gastric mucin or weakening of the gastric mucosal barrier.

Adrenergic alpha-Antagonists↗

Subacute cutaneous lupus erythematosus induced or exacerbated by terbinafine: a report of 5 cases.

BACKGROUND: Subacute cutaneous lupus erythematosus is a nonscarring, non-atrophy-producing photosensitive cutaneous disorder. Half of the patients have 4 or more of the criteria for classification as systemic lupus erythematosus. In some patients, drugs induce or exacerbate the cutaneous disease. OBSERVATION: We describe 5 patients who had either an exacerbation or a new onset of subacute cutaneous lupus erythematosus while taking terbinafine for presumed onychomycosis. CONCLUSION: In general, terbinafine is a safe drug, but perhaps patients with known lupus erythematosus or photosensitivity are predisposed to drug-induced or drug-exacerbated disease.

Adult↗

Asthma in adventure travelers: a prospective study evaluating the occurrence and risk factors for acute exacerbations.

BACKGROUND: Exacerbation of asthma during travel to remote regions may lead to devastating consequences. The course of asthma in travelers and the risk factors for disease exacerbation during travel have not been studied. METHODS: We screened 5835 consecutive travelers and identified 203 patients with asthma. Before travel, all enrollees were assessed for presumed risk factors for asthma exacerbation by means of an interview and an exercise test combined with spirometry. After travel, data regarding travel characteristics and asthma severity were recorded by means of a structured telephone interview. RESULTS: The 203 enrollees visited 56 countries for a median duration of 13 weeks, 147 were engaged in high-altitude trekking, and 88 had asthma attacks. Among these, 40 reported worsening asthma during travel, 32 experienced the worst asthma attack ever, and 11 reported a life-threatening asthma attack. Two independent risk factors for attacks during travel were identified: frequent use (> or = 3 times weekly) of inhaled bronchodilators before travel (relative risk [RR], 3.35; 95% confidence interval [CI], 1.75-6.39) and participation in intensive physical exertion during treks (RR, 2.04; 95% CI, 1.04-3.98). When both risk factors were present, the RR for asthma attacks increased to 5.52 (95% CI, 2.81-10.84). CONCLUSIONS: Asthma frequently worsens during travel and should not be ignored as a potentially life-threatening condition requiring pretravel consideration. Asthmatic travelers who frequently use inhaled bronchodilators before travel or participate in intensive trekking during travel are at increased risk to develop asthma attacks. Therapy should be intensified to achieve better disease control; intensive trekking should be discouraged.

Acute Disease↗

Corticosteroid therapy for patients with acute exacerbations of chronic obstructive pulmonary disease: a systematic review.

OBJECTIVE: To determine whether systemic corticosteroids are of benefit to patients with acute exacerbations of chronic obstructive pulmonary disease (COPD). METHODS: An English-language search of MEDLINE (1966 to February 2002) and the Cochrane Library and a bibliographic review was performed to identify published clinical trials of systemic corticosteroid administration in acute exacerbations of COPD. All relevant English-language, randomized, placebo-controlled clinical trials were considered. Trials investigating the adverse effects of systemic steroids were also retrieved. Studies were assigned a quality rating according to explicit criteria. Clinically relevant end points, such as treatment failure and duration of hospital stay, were considered preferentially. To compare outcomes across all qualifying studies, we considered the difference in spirometric measures between treatment and placebo groups. Potential confounding factors and bias relating to patient selection, treatment protocols, and outcome measurement were considered independently for each study. RESULTS: Among the 8 studies that met all criteria, 5 found that significant improvement in forced expiratory volume in 1 second (>20%) was associated with steroid administration. Two studies found improvement in clinically relevant outcomes. One published study and 2 study abstracts did not find significant improvement in spirometric measures with corticosteroid administration. CONCLUSION: Short courses of systemic corticosteroids in acute exacerbations of COPD have been shown to improve spirometric outcomes (good-quality evidence) and clinical outcomes (good-quality evidence).

Acute Disease↗

Cerebrospinal myelin basic protein in multiple sclerosis. Identification of two groups of patients with acute exacerbation.

The myelin basic protein concentration in the cerebrospinal fluid (CSF) of 125 patients with multiple sclerosis was measured using a radioimmunoassay technique with a detection level of 200 pg/mL and was correlated with the clinical course of the disease. Myelin basic protein was detected in the CSF of some patients with an active progressive form of the disease and in the CSF obtained during exacerbations with the presence of signs or symptoms not previously experienced by the patient (26 of 29 cases were positive during the period of maximal symptoms). Myelin basic protein was not detected in any patient with an inactive or slowly progressive form of the disease, nor in any patient during exacerbations with only recurrence of old signs or symptoms. These results are consistent with the hypothesis that the two clinical forms of exacerbation defined above may be associated respectively with the absence or presence of an acute demyelination.

Humans↗

Exacerbation rates and adherence to disease type in a prospectively followed-up population with multiple sclerosis. Implications for clinical trials.

Two hundred fifty-four patients with definite multiple sclerosis were followed up prospectively for 1 to 5 years (mean, 2.6 years). None of the patients received immunosuppressive medication. Yearly exacerbation rates and each patient's adherence to initial disease type were determined. Disease type was defined at entry and prospectively each subsequent year as stable, relapsing remitting stable, relapsing remitting progressive, or chronic progressive. Exacerbation rates determined prospectively did not decline significantly during 3 years of follow-up, even if patients were stratified by disease duration. Adherence to the initially assigned disease type was highly variable. When followed up for 2 years, 30% of patients with chronic progressive disease had conditions become stable, 32% of patients with stable disease had conditions become chronic progressive, 20% of patients with relapsing remitting disease had conditions become stable, and 20% of patients with relapsing remitting disease had conditions become chronic progressive. Patients with stable or relapsing remitting stable disease switched to one of the progressive categories as frequently (44%) as patients with progressive disease stabilized (46%). Progression of disease measured by changes in Kurtzke Expanded Disability Status Scores did not differ between the different disease types. The results challenge dogma regarding the natural history of exacerbation rates and the assumption that we can reliably assign patients to a specific disease type. The findings have important implications for understanding the natural history of multiple sclerosis and designing clinical trials.

Clinical Trials as Topic↗