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Is irritable bowel syndrome more likely to be persistent in those with relatives who suffer from gastrointestinal symptoms? A population-based study at three time points.

BACKGROUND: We tested the hypothesis that subjects with relatives who suffered from abdominal pain or bowel dysfunction would be at an increased risk of more persistent irritable bowel syndrome. METHODS: A valid, self-report questionnaire was mailed to an age- and gender-stratified random sample of residents, aged 30-64 years, in Olmsted County, MN, USA, on three occasions over a 4-year period. Persistent irritable bowel syndrome was defined as the presence of irritable bowel syndrome on at least two of the three surveys, and fluctuating irritable bowel syndrome was defined as the presence of irritable bowel syndrome on only one of the surveys. RESULTS: Subjects were less likely to have persistent irritable bowel syndrome over the age of 50 years [odds ratio (OR), 0.20; 95% confidence interval (CI), 0.09, 0.47]. A positive family history was reported by 23%. A family history of gastrointestinal symptoms was independently associated with persistent irritable bowel syndrome (vs. no irritable bowel syndrome: OR, 2.5; 95% CI, 1.3, 4.9) and fluctuating irritable bowel syndrome (vs. no irritable bowel syndrome: OR, 2.4; 95% CI, 1.3, 4.4). However, subjects reporting a positive family history were not more likely to report persistent vs. fluctuating irritable bowel syndrome (OR, 1.2; 95% CI, 0.5, 2.9). The use of non-steroidal anti-inflammatory drugs (OR, 2.3; 95% CI, 1.2, 4.3) and a history of food sensitivity (OR, 3.6; 95% CI, 1.9, 6.9) were the only other predictors of persistent irritable bowel syndrome. CONCLUSIONS: A history of abdominal pain or bowel troubles in first-degree relatives appears to be independently associated with both persistent and fluctuating irritable bowel syndrome.

Adult↗

Persistent cow's milk protein intolerance in infants: the changing faces of the same disease.

BACKGROUND: Recent research has shown that cow's milk protein intolerance (CMPI) often persists beyond 4 years of age. AIMS: To evaluate the clinical and immunological characteristics of a group of infants with persistent CMPI. PATIENTS AND METHODS: Twelve infants (6 m, 6f) with persistent CMPI were followed up from birth until a median age of 5 years. The patients underwent CMP challenge each year to evaluate CMP-tolerance. As controls we followed 26 infants (12 m, 14 f) with CMPI that resolved within 1-2 years. RESULTS: A family history of atopic disease was found in 10/12 patients with persistent CMPI and in 10/26 controls (P<0.01). Clinical presentation changed over time: at onset symptoms were prevalently gastrointestinal, while at the end of the study there was an increased frequency of wheezing and constipation and a higher frequency of delayed reactions to CMP-challenge than at study commencement (9/12 vs 2/12; P<0.007). 11/12 infants with persistent CMPI and 3/26 controls (P<0.0001) presented multiple food intolerance. During the observation period 9/12 infants with persistent CMPI and 2/26 controls showed atopic disease: asthma, rhinitis, eczema (P < 0.0001). CONCLUSIONS: Persistent CMPI forms are characterized by: (a) considerable importance of familial atopic disease; (b) change in CMPI manifestations over time and more prolonged delay between CMP consumption and manifestation of symptoms; (c) very high frequency of multiple food intolerance and allergic diseases.

Animals↗

Risk factors for persistence of bilateral otitis media with effusion.

Otitis media with effusion (OME) is a common, episodic condition in childhood. The subset that has persistent bilateral OME is important to identify so that their management can be targeted. Most guidelines suggest a watchful-waiting period before a decision is made on the appropriateness of surgical intervention. In the UK this usually takes place in a specialist setting (otorhinolaryngology) over a period of 12 weeks. A cohort of children (n = 639), between the ages of 3.25 and 6.75 years with bilateral OME that had no previous ear or throat surgery, was followed up over 12 weeks during the recruitment phase of a multi-centre, randomised controlled study. This allowed multiple factors for persistence to be assessed. The overall spontaneous resolution rate in this cohort was between 26% and 65%, depending on the audiometric cut-off by which a persisting condition was defined. Three significant risk factors-time of year when first seen (July to December); hearing level (>or= 30 dB HL in the better ear); and a route of referral that included prior audiometry--were identified in the multivariate analysis for persistent OME both in isolation and when accompanied by each of three audiometric cut-offs (>or= 15, >or= 20 and >or= 25dB HL). In this age group, parental report of duration of OME, history of acute otitis media, parental smoking and pars tensa retractions were not significant factors for persistence. These risk factors in combination can increase the odds ratio of persistence more than sixfold. However, the proportion persisting is insufficient to bypass a period of watchful waiting, except perhaps in extreme combinations which apply to less than 7% of the cohort.

Acoustic Impedance Tests↗

Immunological background in children with persistent diarrhea in Ghana.

BACKGROUND: Persistent diarrheal diseases have become one of the most serious medical problems in developing countries, but few studies have been conducted to determine the risk factors. In the present study, we investigated the nutritional and immunological background in children with persistent diarrhea in comparison with those with acute diarrhea. METHODS: Children with diarrhea who were brought to the Oral Rehydration Salt Clinic of Princess Marie Louise Children's Hospital in Accra were evaluated from an immunological and nutritional aspect. In the follow-up visit, the cases whose diarrhea stopped within 2 weeks after onset were classified into the acute diarrhea group; those with diarrhea lasting more than 2 weeks were classed in the persistent group. Nutritional and immunological data at the initial visit were compared between these two groups. RESULTS: In general, the diarrhea cases had a tendency to undernutrition and impaired cellular immunity compared with healthy control. Persistent cases had lower values for longer half-life, rapid turn-over proteins. Persistent cases had a higher percentage of CD8+ cells and lower CD4/CD8 ratio. CD25 expression in CD4+ cells stimulated by anti-CD3 antibody was lower in the persistent diarrhea group. CONCLUSION: These results appear to support the hypothesis that more severe nutritional status and impairment of cellular immunity is related to the persistence of diarrhea.

CD4-CD8 Ratio↗

Determinants of persistent atrial fibrillation in patients with DDD pacemaker implantation.

Occurrence of AF in a pacemaker implanted patient is a significant cause of morbidity and mortality. The aim of this study was to prospectively investigate the clinical, echocardiographic, and electrocardiographic determinants of persistent AF in patients with DDD pacemakers. A 101 consecutive patients were followed for an average of 19.8 +/- 11.8 months. Persistent AF was documented in 21 (20.8%) patients and 80 (79.2%) patients were in sinus or physiologically paced rhythm. In patients with persistent AF, previous AF attacks were observed more frequently (P < 0.03) and left atrial dimension was higher (3.5 +/- 0.6 vs 3.0 +/- 0.5 cm, P < 0.001). Average P maximum and P wave dispersion (PWD) values calculated in a 12-lead surface electrocardiogram were also found to be significantly higher in patients with persistent AF (P < 0.001). Cox regression analysis demonstrated that the presence of previous AF attacks (RR 8.95, P < 0.001), increased left atrial dimension (RR 2.1, P < 0.02), P maximum duration 120 ms (RR 6.1, P < 0.001), and PWD 40 ms (RR 12.2, P < 0.001) were associated with an increased risk of persistent AF. Cut-off points were 120 ms for P maximum and 40 ms for PWD. Sensitivity, specificity, and positive and negative predictive values were calculated as 76.2, 82.5, 53.3, and 92.9 for P maximum and as 85.7, 87.5, 64.3, and 95.9 for PWD, respectively. In patients with DDD pacemakers, previous AF attacks, increased left atrial dimension, P maximum value of 120 ms, and a PWD value of 40 ms were associated with a significantly increased risk of persistent AF. These patients must further be managed with other treatment modalities to prevent the development of persistent AF.

Aged↗

Results of grid keratotomy, superficial keratectomy and debridement for the management of persistent corneal erosions in 92 dogs.

Ninety-two cases of persistent corneal erosions in dogs were analyzed for breed, gender, age and which eye was affected. The results of the treatment of 92 persistent corneal erosions in dogs by superficial keratectomy (SK), grid keratotomy (GK), or debridement with a sterile dry cotton swab are presented. These techniques gave better rates of healing than have been previously reported. All cases of persistent corneal erosions healed in this study. However, it must be noted that three cases treated with debridement only failed to heal after several treatments and were eventually treated with SK. After one procedure 80 out of 92 (87%) had healed. After one procedure, 63% of cases treated with debridement healed, 100% of cases treated with SK healed, and 85% of cases treated with GK healed. At the first postoperative visit, 88% (21/24 cases) of ulcers treated by SK had healed, and 75% (39/52 cases) of ulcers treated by GK had healed. Only 25% of the persistent corneal erosions had healed at the first visit after debridement. All 24 cases of persistent corneal erosions treated with SK healed after one treatment in a mean +/- SD of 9.3 +/- 3.9 days (median of 7 days). Fifty-two cases were managed with GK; 44 (83%) of these healed with one procedure and eight cases required a second GK procedure to resolve. A mean +/- SD of 13.4 +/- 5.1 days (median of 11.5 days) following GK was required for the persistent corneal erosions to heal. Nineteen cases were initially managed by debridement with a dry cotton swab under local anesthesia. Sixteen out of these 19 debridement cases healed (giving an overall healing rate of 84%) in a mean +/- SD time of 23.4 +/- 11.1 days (median 21.5). There were three cases that did not heal with debridement. These cases were debrided at 10-20 day intervals for 30-60 days, and were then treated with SK. Two of these cases healed within 7 days, the other case required 18 days to heal. Sixty-three per cent of persistent corneal erosions treated with debridement healed after one procedure; however, only four out of 19 cases (21%) were healed at the first revisit. Complications were rare: corneal edema occurred in two cases following multiple GK, and excessive granulation tissue in one case was managed with a SK. There was the occurrence of an ulcer adjacent to the surgery site in four cases, two cases following GK and two cases following SK.

Journal Article↗

Electron microscopic evidence of persistent chlamydial infection following treatment.

Chlamydia trachomatis infections of the female and male genital tracts are often asymptomatic and, thus, tend to become persistent. In the persistent state the typical Chlamydia life cycle is arrested and standard antibiotic regimens do not always eradicate this infection. We sought to relate treatment failures in men and women with persistent chlamydial genital tract infections to electron microscopic evidence of chlamydial persistence and with atypical morphological forms of the organism. Of 16 patients with chlamydial persistence following azithromycin treatment, morphological variants of this organism were observed by electron microscopy from one endocervical sample and one male urethral sample. We document the presence of intracellular inclusions containing only reticulate bodies, extracellular monomembrane and polymembrane phagosomes containing elementary bodies and reticulate bodies with abnormal outer membranes in the process of dividing extracellularly. These observations parallel previous in vitro studies of chlamydial persistence under adverse conditions. This capacity of C. trachomatis to undergo atypical morphological alterations in vivo may contribute to its persistence and relative resistance to antibiotics.

Azithromycin↗

Factors associated with back pain symptoms in pregnancy and the persistence of pain 2 years after pregnancy.

BACKGROUND: Factors associated with back pain symptoms in pregnancy and the persistence of pain 2 years after pregnancy. AIMS: To determine the prevalence of back pain during pregnancy and to delineate the factors associated with the development and persistence of such symptoms 2 years after delivery. MATERIALS AND METHODS: Prospective observational cohort. Consecutive patients in a low-risk obstetric population with singleton pregnancies were surveyed for back pain symptoms during pregnancy in the early postpartum period by a structured questionnaire. Data from this survey were then correlated with the details of labor and pregnancy outcome, as well as epidemiological, occupation and work data. A follow-up questionnaire survey was administered 24 months after delivery to the group who reported back pain symptoms in the first survey. The absence/presence of persistent symptoms at 24 months was correlated with the characteristics of their pregnancy, as well as their daily life activities at the time of the survey. RESULTS: A total 326 patients with complete data were recruited. Two hundred and fifty (76.6%) reported one or more significant episodes of back pain during their pregnancy. Significantly more patients with presence of pain in pregnancy had history of previous back pain episodes when not pregnant (48% vs. 19.7%, p < 0.001), as well as during previous pregnancies (66% vs. 40%, p < 0.025), or in the postpartum period (40% vs. 6.6%, p < 0.001). There was no significant difference between those with or without pain in their pregnancy outcome. Complete data on 189 of the 250 study patients (75.6%) were available for analysis at 24 months after delivery. The incidence of persistent back pain symptoms was 21.1% (n = 40). Those with persistent pain were older, had significantly earlier onset of pain symptoms in the index pregnancy compared with those without pain at 24 months, and they also had their worse symptoms at an earlier gestation during the index pregnancy. Moreover, those with persistent pain had a higher weight gain at 24 months compared with their preindex pregnancy weight (6.8 kg, SD3.0) compared with those without further pain (4.0 kg, SD2.8) (p < 0.01), as well as less weight loss compared with their early postpartum weight (8.1 kg, SD4.8 vs. 1.1.5 kg, SD5.6) (p < 0.01). CONCLUSION: The main factors associated with development of back pain were previous episodes of back pain while non-pregnant or pregnant. The occurrence of back pain during pregnancy did not affect the pregnancy outcome. The main risk factors associated with persistent back pain at 24 months appeared to be the onset of severe pain at an early gestation in the index pregnancy, as well as the inability to reduce weight to their pre-pregnant level.

Adult↗

Infectivity, persistence and serological response of nine Trichinella genotypes in rats.

Domestic and sylvatic Trichinella genotypes were evaluated for infectivity, muscle larvae persistence, and host antibody responses in rats. Groups of rats were inoculated with T. spiralis, T. nativa, T. britovi, three genotypes of T. pseudospiralis (from USSR, USA, and Australia), T. murrelli, Trichinella T6, and T. nelsoni, respectively. The muscle larvae intensity (larvae per gram), total larval burden (lpg x rat weight), and the antibody levels were determined at necropsy 5, 10, 20, and 40 weeks post inoculation. All Trichinella genotypes were established in the rats, but infectivity and persistence differed significantly: T. spiralis established and persisted in high numbers, the three T. pseudospiralis genotypes were also highly infective but differed significantly in persistence, T. britovi and T. nativa had limited infectivity and persistence, Trichinella T6 had low infectivity and very low persistence, and T. murrelli and T. nelsoni were almost non-infective. Except for T. spiralis, initial total muscle larval burdens declined significantly for other genotypes during the experiment. A high initial serological response was detected for all genotypes, but the antibody levels decreased rapidly in relation to decreasing larval burdens. After 20 w.p.i. the antibody levels remained high only in T. spiralis and T. pseudospiralis infected rats. The high infectivity and persistence of T. pseudospiralis in rats, suggests that in addition to T. spiralis, this species might be of significant importance in the domestic cycle of trichinellosis.

Animals↗

Signal-averaged P-wave ECG discriminates between persistent and paroxysmal atrial fibrillation.

Atrial fibrillation (Afib) has been associated with abnormal signal-averaged P wave (SAPW) parameters but whether SAPW is associated with the time course of these arrhythmias (persistent vs. paroxysmal, frequent vs. rare episodes) remains unknown. This article assesses the significance of SAPW duration in distinguishing patients with paroxysmal from those with persistent Afib. SAPW electrocardiogram was performed with a "double triggering" software system for acquisition and analysis of data. SAPW total duration (TD), X, Y, and Z leads magnitudes and vector signal magnitudes were measured offline. Optimal cutoff value between control and patient groups was determined by using a receiver operator characteristic curve. Data were analyzed to compare controls with patients groups and between patient groups according to time course of the arrhythmic history. Fifteen age-matched patients without a history of Afib and 55 patients with a history of Afib (33 with paroxysmal and 22 with persistent arrhythmia) were studied off antiarrhythmic drugs. Patients with history of persistent arrhythmia were studied within 2 days after electrical cardioversion to sinus rhythm. SAPW TD was the only parameter consistently associated with Afib. SAPW TD was 98 +/- 6 ms (mean +/- SD) in the control group, 127 +/- 19 ms in the pooled patients group (P =.0001); 122 +/- 20 ms for paroxysmal and 133 +/- 17 ms for the persistent Afib group (P =.04). Analysis of other SAPW parameters were not statistically significant. SAPW duration is a simple method to identify patients with history of Afib. A significantly longer SAPW TD characterizes patients with a history of persistent as opposed to paroxysmal Afib. Prolongation of SAPW TD possibly reflects more advanced electrophysiological changes, creating a more stable substrate that leads to persistence of the arrhythmia.

Algorithms↗

Precut papillotomy versus persistence in difficult biliary cannulation: a prospective randomized trial.

BACKGROUND AND STUDY AIMS: Failed biliary cannulation occurs in up to 10% of patients undergoing ERCP. There is some controversy as to the safety and efficacy of using precut techniques to achieve biliary cannulation in difficult cases. To date, no randomized trial has compared the success and complication rates of precut with the rates for persistence when biliary cannulation is difficult. The aim of this study was to compare the success rates and complication rates of precut with the success rates and complication rates of persistence in cases of difficult biliary cannulation. PATIENTS AND METHODS: Patients without prior sphincterotomy who required biliary cannulation were screened. A "difficult biliary cannulation" was arbitrarily defined as failed cannulation after 12 minutes. These patients were then randomized to continue treatment by needle-knife cut over the roof of the papilla or by persistence with a non-wire-guided, single-lumen papillotome. "Primary" success was defined as deep cannulation within 15 minutes of randomization. Primary and final success rates and complication rates within 30 days after ERCP were compared. RESULTS: Over a 38-month period a total of 642 patients were screened. Patients in whom biliary cannulation was successful within a time period of 12 minutes or less formed the reference group (n = 580). The remainder of the patients were randomly assigned to the "precut" arm (n = 32) or to the "persistence" arm (n = 30). Primary success rates and complication rates were similar in the precut and persistence arms (75% and 4% respectively for the precut arm vs. 73% and 9% for the persistence arm). The final successful cannulation rate in the entire group of 642 patients was 99.5%. CONCLUSIONS: In experienced hands, precut papillotomy and persistence in cannulation are equally effective in cases of difficult cannulation, with a similar complication rate.

Abdominal Pain↗

Expression of human telomerase reverse transcriptase, the catalytic subunit of telomerase, is associated with the development of persistent disease in complete hydatidiform moles.

OBJECTIVE: This study was undertaken to determine the putative role of telomerase activity and human telomerase reverse transcriptase (hTERT) expression in the development of persistent disease in patients with a diagnosis of complete hydatidiform mole. The ribonucleoprotein telomerase has been shown to have a major role in the process of cellular immortality and carcinogenesis. The reactivation of this enzyme that occurs in the development of malignancies appears to be limited by the regulation of its catalytic subunit hTERT. Compared with their somatic counterparts, most human malignancies demonstrate telomerase activity, and this activity is dependent on the cellular presence of hTERT. The role of telomerase in the pathogenesis of complete hydatidiform moles is not clearly understood. Moreover, the role of hTERT in trophoblastic disease, as well as in the development of persistent trophoblastic disease, has yet to be elucidated. STUDY DESIGN: Telomerase activity and hTERT expression were analyzed in the initial uterine evacuation specimen of 54 complete hydatidiform moles by use of the telomeric repeat amplification protocol assay and reverse transcription-polymerase chain reaction methods. The results were compared and then correlated with the development of persistent trophoblastic disease. RESULTS: Among the 54 patients who were examined with a diagnosis of complete hydatidiform mole, persistent trophoblastic disease requiring postevacuation chemotherapy developed in 6. In the remaining 48 patients, spontaneous remission of the disease occurred after uterine evacuation. Both telomerase activity and hTERT expression were detected in all 6 cases of persistent disease on the initial molar tissue sampled. Among the 48 nonpersistent moles, telomerase activity was detected in 29 (60%) and hTERT expression was demonstrated in 26 (54%). The detection of hTERT expression was significantly associated with the presence of persistent disease (P =.035). Moreover, the absence of hTERT expression in molar tissue obtained from uterine evacuation demonstrated a 100% negative predictability in determining cases of complete mole that were nonpersistent. CONCLUSIONS: Compared with telomerase activity, the expression of hTERT is significantly associated with the development of persistent disease in complete hydatidiform moles. The absence of hTERT expression in the initial tissue sample from complete moles may have potential clinical value in determining patients who will eventually undergo spontaneous remission after uterine evacuation.

Adolescent↗

The art of survival during viral persistence.

Central nervous system infection by the neurotropic JHM strain of mouse hepatitis virus (JHMV) results in chronic demyelination characterized by viral persistence in the absence of infectious virus. CD8(+) T cells inhibit acute viral replication via cell type-specific effector mechanisms. Perforin-mediated cytolysis controls virus in microglia/macrophages and astrocytes, whereas interferon (IFN)-gamma regulates viral replication in oligodendroglia. JHMV infection of antibody-deficient mice confirmed a primary role of cellular immunity and a redundant role for humoral immunity during acute infection. However, infectious virus reactivates in antibody-deficient mice following viral clearance. This observation suggests that virus-specific T cells in the central nervous system are unable to control viral persistence. Reactivation in antibody-deficient mice is not associated with increased T-cell infiltration, but is prevented via transfer of neutralizing antibody. A vital role for humoral immunity during persistence is supported by the accumulation and retention of virus-specific antibody secreting cells following clearance of infectious virus. Thus, cell-mediated immune responses control acute infection, whereas humoral immunity maintains viral persistence. Therefore, although the central nervous system provides an environment for prolonged retention of both T cells and plasma cells, plasma cells are critical in maintaining persistent virus at undetectable levels. The low turnover of virus, T cells, and B cells constitute a unifying feature of persistent infection, illustrating the dichotomy between distinct immune effectors in regulating acute and persistent central nervous system infection.

Animals↗

Studies on persistent infections of tissue cultures. I. General aspects of the system.

Inoculation of the MCN and Lung-To lines of human cells in continuous culture with Newcastle disease (NDV), mumps, or 6-6 viruses led to slight cytopathic effects (CPE) if the multiplicity of infection exceeded one. On second passage or with smaller initial inocula no CPE became apparent. The viruses multiplied, however, as determined by titrations in HeLa cultures or chick embryos. Indeed, persistently infected sublines of MCN and Lung-To were readily established without resort to special manipulations and some of these have been carried now for over 18 months on the same media and schedules as the uninfected parent strains. The viruses were found to be associated mainly with the cells and only 1, or at most 10 per cent of it was detectable in the media. The titers obtained were always low in relation to the available cell population. Reduction or even omission of the horse serum component in the media or ultraviolet irradiation of the cultures did not increase the yield of virus, and CPE became apparent only when similarly treated, uninfected cultures were, likewise, affected by the manipulations. The persistently infected cultures differed from their uninfected counterparts in that they exhibited (a) decreased cellular growth rates and ultimate yields; (b) increased aerobic glycolysis; and (c) a high degree of resistance to cytopathogenic viruses, influenza A (PR8), herpes simplex and, especially vesicular stomatitis (VSV) viruses. Prolonged treatment of persistently infected cultures by addition of specific antiviral immune sera to the media reduced significantly the amount of virus present and the degree of resistance to VSV. However, upon removal of the sera after as many as 187 days of treatment the viruses reappeared in all but one instance. The cured culture, on reinfection, became again persistently infected. No evidence was obtained to indicate genetic inhomogeneity of the cell populations. Of 50 cloned MCN lines none was destroyed by NDV and all became persistently infected. None were initially resistant to VSV but all after establishment of persistent NBV infection. All 39 cloned lines derived from MCN(NDV) cultures in the presence of anti-NDV serum, were free of virus and susceptible to VSV, and all acquired persistent infections and with it resistance to VSV following inoculation of NDV. NDV maintained in MCN cultures differed from the parent, chick embryo-adapted strain with respect to its plaque morphology. Whereas the former yielded only plaques on monolayers of chick embryo fibroblasts which were of pin-point size and hazy, those obtained with the latter were rarely of this type and mostly large and clear. This apparent selection of virus particles did not alter significantly their behavior with respect to cytopathogenicity for uninfected MCN cultures.

Animals↗

Liver biopsy findings for HIV-infected patients with chronic hepatitis C and persistently normal levels of alanine aminotransferase.

BACKGROUND: Severe liver fibrosis is common in patients coinfected with human immunodeficiency virus (HIV) and hepatitis C virus (HCV) who have a high alanine aminotransferase (ALT) level. However, little is known about the frequency, liver biopsy findings, and significance of a persistently normal ALT level in coinfected patients. METHODS: We analyzed clinical data and histological findings for 256 patients coinfected with HIV and HCV, 24 (9.4%) of whom had an ALT level within the normal range on > or =2 separate occasions within a 6-month period. RESULTS: The proportion of patients demonstrating advanced stages of fibrosis (F3 and F4) was 78 (33.7%) of 232 patients in the high ALT level group, compared with 0 (0%) of 24 patients in the persistently normal ALT level group (P<.001). Among patients with persistently normal ALT levels, 23 (96%) had any grade of fibrosis, and 7 (29%) had stage F2 of fibrosis. No differences were found between both groups with respect to age, sex, HIV transmission category, Centers for Disease Control and Prevention clinical category, CD4+ cell count (both nadir and baseline values), type of antiretroviral therapy, years since onset of HCV infection, alcohol use, or HCV load. However, the proportion of patients infected with HCV genotype 3 was significantly higher among patients with high ALT levels than in patients with persistently normal ALT levels (61 [26.9%] of 232 patients vs. 1 [4.2%] of 24 patients; P=.04). CONCLUSIONS: Histological abnormalities are significantly milder in patients coinfected with HIV and HCV who have persistently normal ALT levels than those found in patients with high ALT levels. However, a subgroup of patients with persistently normal ALT levels may have significant cases of fibrosis. Liver biopsy may be recommendable in patients coinfected with HIV and HCV who have persistently normal ALT levels, to determine the extent of liver fibrosis and, consequently, to assess suitability for treatment.

Adult↗

Onset and persistence of depression in older people--results from a 2-year community follow-up study.

BACKGROUND: baseline physical health, disability and social support have been shown to predict depression onset, but findings for persistence are inconsistent. For onset and persistence of depression, the effect of changes in these risk factors over time is unclear. OBJECTIVE: to use baseline factors and change in factors over time to predict onset and persistence of depression over a 2-year period. METHODS: a prospective cohort study with index assessment and 2-year follow-up of patients initially aged > or =65 years registered with two South London practices (n = 1,164). Depression was defined by a score >5/15 on the 15-item Geriatric Depression Scale. Associations between risk factors and onset and persistence of depression were analysed using multiple logistic regression. RESULTS: the incidence of depression was 8.4%, while depression persisted amongst 61.2% of those depressed at baseline. Comparing onset and persistence suggested some common predictors: greater baseline depression score; and follow-up measures of poor general health and compromised social support. There was some evidence that pain and worsening disability were more important for depression onset. In contrast, low baseline belief in powerful others (health locus of control measure) predicted persistence only. CONCLUSION: focusing on older people with increasing disability, pain, physical ill-health and compromised social support should help in both the prevention and recognition of onset of later-life depression. In older people with depression, those with the highest symptom scores and low belief in powerful others at baseline were more likely to develop chronic symptoms and could be targeted for more intensive treatment and support.

Age of Onset↗

T-13910 DNA variant associated with lactase persistence interacts with Oct-1 and stimulates lactase promoter activity in vitro.

Two phenotypes exist in the human population with regard to expression of lactase in adults. Lactase non-persistence (adult-type hypolactasia and lactose intolerance) is characterized by a decline in the expression of lactase-phlorizin hydrolase (LPH) after weaning. In contrast, lactase-persistent individuals have a high LPH throughout their lifespan. Lactase persistence and non-persistence are associated with a T/C polymorphism at position -13,910 upstream the lactase gene. A nuclear factor binds more strongly to the T-13,910 variant associated with lactase persistence than the C-13,910 variant associated with lactase non-persistence. Oct-1 and glyceraldehyde-3-phosphate dehydrogenase were co-purified by DNA affinity purification using the sequence of the T-13,910 variant. Supershift analyses show that Oct-1 binds directly to the T-13,910 variant, and we suggest that GAPDH is co-purified due to interactions with Oct-1. Expression of Oct-1 stimulates reporter gene expression from the T and the C-13,910 variant/LPH promoter constructs only when it is co-expressed with HNF1alpha. Binding sites for other intestinal transcription factors (GATA-6, HNF4alpha, Fox and Cdx-2) were identified in the region of the -13,910 T/C polymorphism. Three of these sites are required for the enhancer activity of the -13,910 region. The data suggest that the binding of Oct-1 to the T-13,910 variant directs increased lactase promoter activity and this might provide an explanation for the lactase persistence phenotype in the human population.

Binding Sites↗

Persistent diarrhoea in a rural area of Bangladesh: a community-based longitudinal study.

As part of a health impact evaluation of a water supply and sanitation project in a rural area of Bangladesh, diarrhoeal morbidity was recorded in children 0-4 years of age using weekly recall in household interviews, during the period March 1984 to December 1987. During the baseline year, 1984, the incidence rate of all diarrhoea episodes (3.8 episodes per child per year), and those defined as persistent, duration greater than 14 days (0.6 episodes per child per year), showed a similar age distribution, peaking in the 12-23 month age group. Sixteen per cent of all episodes were classified as persistent, and this proportion was greatest in the 0-5 month age group (25%). Children suffering at least one episode of persistent diarrhoea in 1984 also experienced a higher incidence of acute diarrhoea (less than = 14 days duration) than those suffering acute diarrhoea only (4.2 versus 3.7 episodes per child per year). Persistent diarrhoea showed a similar seasonal pattern to that of all episodes. Rates of abdominal pain, isolation of Shigella spp and a diagnosis of dysentery were significantly higher in persistent episodes than in acute episodes. Closer follow-up of children during 1986 and 1987, through the recording of all periods of absence of the child from the home, showed that overall diarrhoea incidence rates were little affected when absence was taken into account, but that the incidence of persistent diarrhoea and the proportion of episodes classified as persistent were significantly reduced. The implications of this methodological problem are discussed.

Acute Disease↗