Perinatal hemochromatosis: one disease, several diseases or a spectrum?
Explore the source record for details and available documents.
Female↗
SEARCH · PubMed Health
Results for “disease severity”
Explore indexed PubMed citations for clinical trials, systematic reviews and public health research. Read source abstracts and follow each citation to its original PubMed record.
Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.
The splicing machinery is a genetic modifier of disease severity.
Disease severity correlates with the level of correctly spliced RNA transcribed from genes carrying splicing mutations and with the ratio of alternatively spliced isoforms. Hence, a role for splicing regulation as a genetic modifier has been suggested. Here we discuss recent experiments that provide direct evidence that changes in the level of splicing factors modulate the splicing pattern of disease-associated genes. Importantly, modulation of the splicing pattern led to regulation of the protein function and modification of disease severity.
Alternative Splicing↗
Association of HLA-DR and HLA-DQ genes with susceptibility to pulmonary tuberculosis in Koreans: preliminary evidence of associations with drug resistance, disease severity, and disease recurrence.
Only 10% of persons infected with Mycobacterium tuberculosis develop clinical tuberculosis (TB), indicating the existence of host genetic factors regulating disease expression. We investigated the association of human leukocyte antigen (HLA) class II genes with the susceptibility to pulmonary TB in Koreans, with special emphasis on their association with drug resistance, disease severity, and disease recurrence. Human leukocyte antigens (HLA)-DRB1 and -DQB1 gene polymorphisms were analyzed in 160 Korean patients with pulmonary TB and 200 ethnically matched healthy controls. HLA-DRB1*0803 (25.0% vs. 14.5% in controls, OR = 1.97, p = 0.012, corrected p (p(c)) > 0.05) and DQB1*0601 (27.5% vs. 15.5% in controls, OR = 2.07, p = 0.005, p(c) > 0.05) were weakly associated with general susceptibility to TB. DRB1*0803 was significantly associated with drug resistance (30.9% vs. 14.5%, OR = 2.63, p(c) = 0.047) and more advanced lung lesion (29.8% vs. 14.5%, OR = 2.50, p(c) = 0.022). DRB1*0803 showed the strongest association with disease recurrence, especially after curative treatment for the earlier infection (47.4% vs. 14.5%, OR = 5.31, p(c) = 0.00009). DQB1*0601, which is strongly linked to DRB1*0803 in this population showed similar changes in the patients as those of DRB1*0803. It is suggested that DRB1*0803 and DQB1*0601 alleles are associated with disease progression of TB in Koreans, exerting influence on the development of drug resistance, severe disease, and recurrent disease.
Adult↗
Hypokinesia in Parkinson's disease: influence of age, disease severity, and disease duration.
The aim of this cross-sectional study was to compare the role of aging in measures reflecting diurnal activity and immobility in 60 parkinsonian patients with predominant features of hypokinesia and rigidity and 100 healthy subjects aged 50 to 98 years. In the patients, we also studied the relation between disease duration and subjective and objective measures of disease severity. Motor activity was recorded during 5 successive days at home with a wrist-worn activity monitor. For each subject, two mean measures reflecting the diurnal activity level and the relative proportion of activity and immobility were calculated. Diurnal measures of activity revealed in both groups a prominent absolute reduction of activity and an increase of the time spent without movement ("immobility") with advancing age. Parkinsonian patients showed significantly lower values for both motor-activity measures than did the healthy subjects. The rate of the age-related decline of both diurnal activity measures in both groups, however, is comparable. Disease duration showed no relation with subjective and objective measures reflecting disease severity. This study shows that if care is taken to control for disease severity, the rate of the age-related decline of measures reflecting diurnal activity and immobility is similar in both groups. The lack of relation between disease duration and subjective and objective measures of disease severity suggests that the rate of progression of Parkinson's disease can be reliably studied only by means of longitudinal studies.
Activities of Daily Living↗
HLA alleles, IFN-gamma responses to HPV-11 E6, and disease severity in patients with recurrent respiratory papillomatosis.
Recurrent respiratory papillomatosis (RRP) remains an immunologic enigma. Human papillomavirus (HPV) types 6 and 11 are the predominant HPV viruses that cause papilloma development. However, it is unclear why only a very small fraction of HPV-exposed individuals develop RRP. We performed high-resolution HLA class I and II genotyping on 70 randomly selected patients (56 Caucasians and 14 African-Americans) with RRP. We report, for the first time, an increased frequency of HLA-DRB1*0102 in Caucasian patients with RRP, suggesting that this allele predisposes individuals to RRP. Additionally, HLA-DRB1*0301, DQB1*0201, and DQB1*0202 alleles were selectively enriched in Caucasians with severe disease, suggesting that these alleles may regulate disease severity. In contrast, HLA-DQB1*0602 was more frequent in controls than in Caucasians with severe disease, suggesting a severity-sparing effect of this allele. Furthermore, both DQB1*0201 and DQB1*0202 were enriched, whereas DQB1*0602 was absent, in African-Americans. Interestingly, HLA-DRB1*0301 and DQB1*0201 correlated with reduced interferon-gamma expression in patients with RRP. Larger studies are needed to identify other class II major histocompatibility complex alleles that may influence disease predisposition, disease severity, or both, especially in African-American patients, to ultimately illuminate the regulatory effects of these alleles in the predisposition and severity of RRP.
Black or African American↗
Dengue viremia titer, antibody response pattern, and virus serotype correlate with disease severity.
Viremia titers in serial plasma samples from 168 children with acute dengue virus infection who were enrolled in a prospective study at 2 hospitals in Thailand were examined to determine the role of virus load in the pathogenesis of dengue hemorrhagic fever (DHF). The infecting virus serotype was identified for 165 patients (DEN-1, 46 patients; DEN-2, 47 patients; DEN-3, 47 patients, DEN-4, 25 patients). Patients with DEN-2 infections experienced more severe disease than those infected with other serotypes. Eighty-one percent of patients experienced a secondary dengue virus infection that was associated with more severe disease. Viremia titers were determined for 41 DEN-1 and 46 DEN-2 patients. Higher peak titers were associated with increased disease severity for the 31 patients with a peak titer identified (mean titer of 107.6 for those with dengue fever vs. 108.5 for patients with DHF, P=.01). Increased dengue disease severity correlated with high viremia titer, secondary dengue virus infection, and DEN-2 virus type.
Adolescent↗
Vardenafil improves erectile function in men with erectile dysfunction irrespective of disease severity and disease classification.
BACKGROUND: Vardenafil (Levitra) is a potent and selective phosphodiesterase 5 (PDE5) inhibitor used in the management of erectile dysfunction (ED). This retrospective subgroup analysis assessed the effectiveness of vardenafil treatment in men with ED of different baseline severity and disease classification. METHODS: Data from two pivotal, randomized, double-blind, placebo-controlled clinical trials enrolling men from the general ED population who received placebo or vardenafil 5 mg, 10 mg, or 20 mg during a 12-week treatment period were retrospectively analysed, stratifying by psychogenic, organic, and mixed ED disease classification as determined by the investigator. Efficacy endpoints included the International Index of Erectile Function (IIEF)-Erectile Function (EF) domain score, per-patient diary response rates to questions on penile insertion [Sexual Encounter Profile (SEP-2)] and maintenance of erection (SEP-3) and rates of positive response to the Global Assessment Question (GAQ). RESULTS: Data from 1,385 men who received at least one dose of study medication and had pre- and post-baseline measures of efficacy available (intent-to-treat population) are presented. At baseline 37-41% of patients had severe ED, 30-34% moderate, 22% mild-to-moderate and 6-8% mild ED. At baseline, 46-51% of patients were considered to have an organic cause for ED, 13-16% psychogenic ED, and 36-38% mixed classification of ED. For all classifications and for mild-to-moderate to severe ED, men treated with 10 or 20 mg of vardenafil showed statistically and clinically significant improvements (P < 0.001) in IIEF-EF scores, diary response rates to the SEP-2 and SEP-3 questions, and GAQ as compared with those given placebo. The greatest improvements relative to placebo were noted in patients with more severe ED. The most common treatment-emergent adverse events were headache, flushing, rhinitis, dyspepsia, and were dose-related, mostly mild to moderate in intensity and consistent with the class. CONCLUSIONS: Vardenafil improves EF in men with ED irrespective of investigator-determined classification and baseline ED severity.
3',5'-Cyclic-GMP Phosphodiesterases↗
Relative disease severity in siblings with myotonic dystrophy.
Myotonic dystrophy is an autosomal dominant disorder in which an early-onset form is characteristically inherited from the mother. We studied 17 affected sibling pairs from 15 families in which two or more affected children were born to mothers with myotonic dystrophy. Later-born affected children suffered more severe disease than their first-born siblings in 13 of 17 sibling pairs. Later-born affected siblings displayed significantly more neonatal feeding difficulties, later age when first sitting alone, later age when first walking alone, and a higher incidence of scoliosis. The overall difference in disease severity between affected siblings increased as the age difference between them increased, suggesting that increasing maternal age is a factor in the relative disease severity of affected children. These findings may have relevance for genetic counseling.
Adult↗
Prognosis with mechanical ventilation: the influence of disease, severity of disease, age, and chronic health status on survival from an acute illness.
This report presents a model for relating readily available clinical and physiologic measurements to prognosis from mechanical ventilation. Using data from 571 acutely ill, ventilated patients admitted to the intensive care units of 12 hospitals, it illustrates the relationship between the disease, the initiating respiratory failure, the acute severity of the disease, and the patient's age and chronic health status and the patient's probability of survival. The results indicate that, of the 296 deaths among the 571 ventilated patients, 142 (48%) could be identified on the day of ICU admission to be at a 75% or greater risk of hospital death; 49 of these patients were estimated to have a 90% or greater risk of death. After 3 days of ICU treatment, estimates for hospital mortality increased to 97% (39 patients). We believe that such estimates, when available from a larger number of patients and combined with additional information on the patient's desires, expectations, preillness quality of life, and prognosis for long-term survival, can be helpful in decisions to withhold and withdraw mechanical ventilation.
Acute Disease↗
Severe disease in children with trachoma is associated with persistent Chlamydia trachomatis infection.
The immediate study objective was to determine if variable disease severity in children with trachoma could be attributable in part to host variation in the ability to clear Chlamydia trachomatis infection. Identification of sibling cohorts with these variant phenotypes would be useful for immunogenetic studies. A weekly survey for 3 months in a trachoma-hyperendemic village using detection of chlamydial DNA and grading of disease severity indicated that 62% (33/53) of children had at least one infection episode. Of those, 64% (21/33) who were persistently infected had both significantly higher mean chlamydial DNA loads and more severe trachoma than did sporadically infected children. Of importance, duration of infection differed between siblings in 60% (6/10) of families. The results suggest that chlamydial load and duration of infection determine the chronic nature of severe disease in trachoma and that host variable efficiency for chlamydial clearance between siblings is in part determined by host variation.
Adenoviruses, Human↗
Factors associated with prolonged symptoms and severe disease due to Clostridium difficile.
OBJECTIVE: toxigenic Clostridium difficile is responsible for a spectrum of disease severity ranging from mild diarrhoea to fulminant colitis. This study attempts to determine the proportion of patients in each category of severity and evaluate the risk factors for a more prolonged and complicated course. DESIGN: prospective cohort study. SETTING: university teaching hospital. SUBJECTS: all patients with symptomatic C. difficile infection during 4 months of an outbreak (January-April 1995); n=73; median age 74 years (range 17-91). MEASUREMENTS: incidence of C. difficile-associated disease (CDAD); severity of disease; percentage of patients in each category of severity; risk factors for severe disease/prolonged symptoms (univariate and multivariable analyses). RESULTS: the incidence of CDAD was 0.93%. Of the cases identified, 18 (24.7%) had mild, self-limiting disease; 26 (35.6%) had moderately severe disease; 23 (31.5%) had prolonged symptoms and six (8.2%) had a complicated course. Although CDAD was more common in older patients (P < 0.001), increasing age was not a risk factor for severity. Significant risk factors for severe CDAD included low Barthel and abbreviated mental test scores (P < 0.01, P < 0.001 respectively) and recent endoscopy (P=0.03). Logistic regression analysis revealed the following independent predictors of severe CDAD: endoscopy [odds ratios (OR) 4.0, P=0.03] and cognitive impairment (OR 11.0, P < 0.01). A trend towards significance was noted for nasogastric tube insertion (OR 3.1, P=0.08). Complications of infection included dehydration, malnutrition and faecal incontinence (which was statistically significantly associated with more severe disease; P < 0.01). CONCLUSION: risk factors for severity of CDAD include functional disability, cognitive impairment, and recent endoscopy. Anticipation of severe CDAD may limit morbidity and mortality.
Adolescent↗
Correlation of angiographic abnormalities with disease manifestations and disease severity in polyarteritis nodosa.
We evaluated angiograms of 26 patients with polyarteritis nodosa (PAN) as well as the associated clinical and laboratory features. All patients had visceral angiograms and either biopsy or angiographic proof of PAN. Severe disease was defined as central nervous system PAN, renal failure requiring dialysis, gangrene of fingers or toes, cardiomyopathy, bowel infarction, hepatic failure, or hepatic infarction. The presence of aneurysms was associated with severe hypertension, hepatitis B surface antigenemia and clinically severe disease. Angiography may therefore identify a subset of patients with more severe involvement and may be of value in management decisions.
Adolescent↗
Protection against severe disease is conferred by DERAA-bearing HLA-DRB1 alleles among HLA-DQ3 and HLA-DQ5 positive rheumatoid arthritis patients.
Experimental studies in transgenic mice have suggested that HLA-DQ predisposes to rheumatoid arthritis (RA), but could also modulate disease severity by presenting peptides derived from self-DR molecules. In particular, a short amino acid sequence, (70)DERAA(74), in the third hypervariable region of HLA-DRB1 confers protection for the disease, while particular HLA-DQ [DQB1*0501/DQA1*01 (DQ5) and DQB1*03/DQA1*03 (DQ3)] molecules predispose to the disease. We have therefore analyzed the allelic distribution of HLA-DRB1, DQA1, and DQB1 and the presence of rheumatoid factor and nodules among 199 German RA patients and 196 healthy controls. Our results show that HLA-DQB1*03/DQA1*03 (or DRB1*04) predisposes to RA more than HLA-DQB1*0501/DQA1*01 (i.e., DRB1*01 and DRB1*10). Homozygosity for DQ3 confers the strongest genetic risk for RA (OR = 19.79 compared to OR = 10.05 for two doses of shared epitope (SE) positive HLA-DRB1 alleles). Furthermore, patients carrying both predisposing DQ and (70)DERAA(74)-positive HLA-DRB1 alleles are more often rheumatoid factor (RF) negative than patients carrying predisposing DQ alleles alone. Only one out of 14 patients (7%) with a protective combination (DQ3/(70)DERAA(74) and DQ5/(70)DERAA(74)) had rheumatoid nodules compared to 67 out of 144 patients (46.5%) with predisposing DQ alleles alone (OR = 0.12, 95% CI: 0.02-0.72, p = 0.004). These results demonstrate a protective role of (70)DERAA(74)-positive DRB1 alleles against disease severity among RA patients.
Alleles↗
Functional status in depressed patients: the relationship to disease severity and disease resolution.
BACKGROUND: We set out to measure the impact of depression and its clinical resolution on patients' functional status. METHOD: The Work and Social Disability Scale (WSDS), a five-category investigator-rated scale measuring patient functional status, was completed at baseline and study discontinuation in a 56-day, open, uncontrolled study evaluating the safety of a sustained release (SR) formulation of bupropion in 3167 patients at 105 sites. To be included in the study, patients had to be 18 years or older, have a diagnosis of depression, and be considered appropriate for treatment with bupropion SR. The proportion of patients in each WSDS category, for those patients taking more than 7 days of bupropion SR (N = 2915), was assessed at screen and study discontinuation. The percentage of patients with improved WSDS scores at 56 days was also measured for all patients and correlated with patient and treatment characteristics. RESULTS: Of the patients entering the trial, 61.8% were markedly or severely impaired in their work or social activities, and only 5.4% were mildly or not impaired. At study discontinuation, more than 54% of patients were judged by the investigator to have very much or much improvement in their clinical symptoms. Results on the WSDS correlated with the clinical improvements; only 22.3% were markedly or severely impaired; and 50.0% were mildly or not impaired at study discontinuation. In addition, 63.9% of patients had less work or social disability at the end of the trial than at study entry. Functional status improved more in patients who had not previously been treated for the episode, had more severe depression at study entry, and had a higher dose and duration of treatment with bupropion SR. CONCLUSION: The results show that depression results in significant impairment in patients' functional status. Functional status improved in patients treated with bupropion SR for up to 56 days. This improvement was highly correlated with improvement in clinical symptoms and was related to patient characteristics at study entry as well as to treatment patterns during the study.
Adolescent↗
[Celiac disease--a severe disease].
Celiac disease (Celiacal sprue = gluten-sensitive enteropathy = netropic sprue) is the all-life genetically determined autoimmune disease with permanent intolerance to gluten, which damages the intestinal mucous membrane and alterates the immune system. The atrophy and typical inflammatory changes of mucous membrane results in malabsorption with diarrhea, general weakness, anemia and weight loss. The clinical picture of celiac disease is considerably heterologous. Only 20-30% of patients suffer from active-classical form of the disease. Non-diagnosed, inactive forms of the disease form 70-80% of cases of celiac disease in adult individuals. The therapy is based on diet without gluten. Application of the diet usually results in clinical improvement and signs of the disease are diminished. The relapse of celiac disease occurs after a gluten load. Celiac disease and dermatitis Duhring are considered to be two equal forms how gluten enteropathy becomes manifest. Celiac disease is often associated with other autoimmune diseases (e.g. insulin-dependent diabetes mellitus, autoimmune thyreoiditis). Untreated celiac disease still represents a serious medical risk, since it is an important precancerosis. Introduction of highly sensitive methods for the determination of antibodies against endomysium and tissue transglutaminase significantly extended possibilities of diagnosis and screening for celiac disease. It became obvious that the real incidence of celiac disease including the non-diagnosed forms of the disease in the European population is greater than 1:200 to 1:250.
Celiac Disease↗
Alterations in the composition of the supramucosal defense barrier in relation to disease severity of ulcerative colitis.
Mucin glycoproteins and trefoil peptides play an important role in protection and repair of the gastrointestinal epithelium. This study investigates alterations in mucin and trefoil peptide gene expression and product localization in ulcerative colitis (UC). Product localization and message expression of mucin MUC1 to 6 and trefoil peptide TFF1 to 3 genes was analyzed in rectosigmoid tissue from a cohort of patients with active UC and compared with that of normal colorectal mucosa. MUC1 expression was upregulated in severe UC at the site of rupture of crypt abscesses. Reduction in MUC2 expression occurred in UC adjacent to ulceration. No alteration in MUC3 or MUC4 gene expression was detectable in UC compared with normal colorectal mucosa. No ectopic expression of MUC5AC, MUC5B, or MUC6 was identified in UC. Ectopic TFF1 expression was identified in tissues eliciting histological features of severe disease. Decreased TFF3 localization was demonstrated in UC tissues, but no TFF2 expression was detected in any colorectal specimens. Subtle alterations in composition of the supramucosal defense barrier exist in UC and vary in relation to clinical severity of disease. There is upregulation in mucin MUC1 at crypt abscesses and neo-expression of TFF1 trefoil peptide in severe disease.
Adult↗
Quality of life in cystic fibrosis: the impact of gender, general health perceptions and disease severity.
BACKGROUND: Disease progression in cystic fibrosis (CF) is marked by deterioration across a number of physiological systems. In addition, there is evidence that females have a worse prognosis than males. The current work assesses the impact of both these factors on health related quality of life (HRQoL). METHODS: Two hundred and twenty-three adolescents and adults completed the cystic fibrosis quality of life (CFQoL) questionnaire with a further 185 approached and not responding by non-completion of the questionnaire. The CFQoL is divided into nine domains: physical, social, treatment, chest symptoms, emotional functioning, concerns for the future, relationships, body image, and career. Measurement of objective clinical status included, body mass index (BMI), and percentage of predicted forced expiratory volume in one second (FEV1). General health perceptions (GHP) were also measured. RESULTS: Patients were sub-divided by gender and disease severity (mild > 70% FEV1, moderate 40-69% and severe < 40%). Factorial analysis of variance indicated significant main effects for FEV1 (F = 587.98, P < or = 0.001) and BMI (F = 17.29, P < or = 0.001) as a function of disease severity. Post hoc tests revealed significant two-group differences for FEV1 and BMI between disease severity groups. No differences were observed for gender across FEV1 or BMI. Differences emerged across most CFQoL domains for disease severity, with the exception of concerns for the future, which was consistently low throughout. Gender differences emerged for chest symptoms, emotional functioning, concerns for the future, body image and career. With the exception of body image, females exhibited poorer HRQoL. Pearson correlations indicated that females' perception of health was more closely related to clinical status than males. CONCLUSIONS: Disease severity has an impact on HRQoL in adolescents and adults with CF. Some differences emerged between males and females, with females generally reporting poorer HRQoL. Evidence indicated that males and females perceived their health status differently, with females having a more accurate perception of objective clinical health status.
Adaptation, Psychological↗
3849+10 kb C-->T mutation and disease severity in cystic fibrosis.
50% of patients with cystic fibrosis (CF) are homozygous for the delta F508 mutation, but the remainder have at least one of many other less common mutations. The 3849 + 10 kb C-->T splice mutation seems to be associated with less severe disease. We report ten CF patients who are hemizygous for this mutation. Three male patients do not have azoospermia (sperm counts 12, 53, and 198 x 10(6)/mL). Another boy died before CF was diagnosed; his genital tract appeared normal at necropsy. All patients had clinically sufficient exocrine pancreatic function. Pulmonary disease was delayed in onset in most of these patients (range < 1 to 16; median 9 years), but then became severe in some, progressing to death (in two) and need for transplantation in one. Sweat chloride concentration was abnormal (80 mmol/L) in one patient but in others was in the intermediate range (45-65 mmol/L). There was substantial variation in pulmonary disease severity within sibships. These observations suggest some dissociation in genetically determined severity between different organs. There was some evidence among these patients of a tendency for disease of the genital tract to become progressively more severe. Perhaps sperm banking should be offered to male patients. We speculate that some normal CF transmembrane conductance regulator is made in patients with this splice abnormality.
Adolescent↗