Occupational and environmental risk factors for idiopathic pulmonary fibrosis: a multicenter case-control study. Collaborating Centers

Occupational exposures were investigated in a multicenter case-control study of clinically and histologically diagnosed idiopathic pulmonary fibrosis (IPF), a chronic diffuse interstitial lung disease of unknown etiology. Results are based on 248 cases, aged 20-75 years, diagnosed at 16 referral centers between January 1989 and July 1993. There were 491 controls ascertained by random digit dialing and matched to cases on sex, age, and geographic region. Data were collected using a standard telephone questionnaire. Occupational factors were based on a detailed history of jobs lasting 6 months or more and job activity, hobby, and specific substance checklists. Several occupational factors, adjusted for age and smoking in conditional multivariate logistic regression analyses, were significantly associated with IPF: farming (odds ratio (OR) = 1.6, 95% confidence interval (CI): 1.0, 2.5); livestock (OR = 2.7, 95% CI: 1.3, 5.5); hairdressing (OR = 4.4, 95% CI: 1.2, 16.3); metal dust (OR = 2.0, 95% CI: 1.0, 4.0); raising birds (OR = 4.7, 95% CI: 1.6, 14.1); stone cutting/polishing (OR = 3.9, 95% CI: 1.2, 12.7); and vegetable dust/animal dust (OR = 4.7, 95% CI: 2.1, 10.4). Interaction was detected between smoking and exposure to livestock (p = 0.06) and farming (p = 0.08). Results confirm previous studies showing increased risk associated with dusty environments.     

Pre and postnatal diagnosis of fetus‐in‐fetu

Differentiation of abdominal masses detected on prenatal ultrasound is difficult and requires careful characterization of the mass and precise localization. Differentiation is required in order to distinguish benign from potentially malignant conditions. We describe a case of fetus‐in‐fetu with pre and postnatal imaging.     

MicroRNA and hepatitis C virus- challenges in investigation and translation: a review of the literature

Investigations into the role of microRNA (miRNA) in hepatitis C virus (HCV) infection, disease pathogenesis and host immune and treatment response have potential to produce innovations in diagnosis, prognosis and therapy. However, investigational challenges remain in generating clinically useful and reproducible results. We review the literature with a primary emphasis on methods and technologies used to construct our current understanding of miRNA and HCV disease. A second emphasis is to understand potential clinical research applications and provide clarification of previous study results. Many miRNA have key roles in viral and immunopathogenesis of HCV infection across multiple tissue compartments. Controversy exists among published studies regarding relative measurements, temporal changes and biological significance of specific miRNA and HCV infection. To reconcile diverging data, additional research into optimal sample processing, in vitro models, techniques for microarray differential expression of miRNAs, practices for sample result normalization, and effect of HCV genotype variation on expression are all necessary. Microarray and miRNA isolation techniques should be selected based on ability to generate reproducible results in the sample type of interest. More direct comparisons of efficacy and reliability of various multiplex microarrays and an improved consensus around miRNA normalization and quantitation are necessary so that data can be compared across studies.     

Depression Change Profiles in Adolescents Treated for Comorbid Depression/Substance Abuse and Profile Membership Predictors

Using data from a randomized trial in which adolescents with depressive and substance use disorders (SUD) received treatments for both disorders in either a sequenced or coordinated manner, we (a) determine the number and nature of depression response profiles through 1-year posttreatment and (b) examine whether 8 previously identified factors predict profile membership. There were 170 adolescents (M age = 16.4 years; 22% female; 28% Hispanic, 61% Non-Hispanic White) with comorbid depressive disorder/SUD randomized to one of three sequences of receiving the Adolescent Coping With Depression Course and Functional Family Therapy for SUD (depression treatment followed by SUD treatment; SUD treatment followed by depression treatment; coordinated treatment). Depression was assessed at 7 points from baseline to 1-year follow-up. A 4-class solution fit the data best, with groups labeled Mildly Depressed Responders (57.1%), Depressed Responders (18.8%), Depressed Non-Responders (12.9%), and Depressed with Recurrence (11.2%). The 4 change profiles differed on indices of all but 1 predictor (age); most differences were driven by lower scores among Mildly Depressed Responders. Profile membership was most strongly predicted by depression severity, cognitive distortions, hopelessness, and global functioning. The strongest predictor of Nonresponse was low family cohesion, whereas Recurrence was associated with hopelessness, suicide attempts, and starting treatment near the end of the school year. Most depressed adolescents experienced a positive response that was maintained. Understanding the most common profiles of depression change during and following treatment and the variables that predict change can help improve treatment outcomes and advance tailoring efforts.     

"Early-peak" carbon monoxide production in certain erythropoietic disorders

The "early-labeled" peak (ELP) of 14CO excretion following injection of glycine-2-14C was used to study erythropoiesis in a patient with sideroblastic anemia and in four subjects with myeloproliferative disorders. The ELP was greatly enlarged in all patients, as compared with a normal volunteer. The contour of the peaks from the hematologically abnormal subjects suggested the presence of increased erythroid heme degradation. In the patient with sideroblastic anemia, all hours of the early peak were significantly reduced after transfusion. This was interpreted to mean that even the earliest or "nonerythroid" phase of the peak is influenced by erythropoietic activity, at least under conditions of erythropoietic stress.     

Childhood urinary tract infection in primary care: a prospective observational study of prevalence,diagnosis, treatment,and recovery

BackgroundThe prevalence of targeted and serendipitous treatment for, and associated recovery from, urinary tract infection (UTI) in pre-school children is unknown.AimTo determine the frequency and suspicion of UTI in children who are acutely ill, along with details of antibiotic prescribing, its appropriateness, and whether that appropriateness impacted on symptom improvement and recovery.MethodSystematic urine sampling from children aged <5years presenting in primary care with acute illness with culture in NHS laboratories.ResultsOf 6079 children’s urine samples, 339 (5.6%) met laboratory criteria for UTI and 162 (47.9%) were prescribed antibiotics at the initial consultation. In total, 576/7101 (8.1%) children were suspected of having a UTI prior to urine sampling, including 107 of the 338 with a UTI (clinician sensitivity 31.7%). Children with a laboratory-diagnosed UTI were more likely to be prescribed antibiotics when UTI was clinically suspected than when it was not (86.0% versus 30.3%, P<0.001). Of 231 children with unsuspected UTI, 70 (30.3%) received serendipitous antibiotics (that is, antibiotics prescribed for a different reason). Overall, 176 (52.1%) children with confirmed UTI did not receive any initial antibiotic. Organism sensitivity to the prescribed antibiotic was higher when UTI was suspected than when treated serendipitously (77.1% versus 26.0%; P<0.001). Children with UTI prescribed appropriate antibiotics at the initial consultation improved a little sooner than those with a UTI who were not prescribed appropriate antibiotics initially (3.5 days versus 4.0 days; P = 0.005).ConclusionOver half of children with UTI on culture were not prescribed antibiotics at first presentation. Serendipitous UTI treatment was relatively common, but often inappropriate to the organism’s sensitivity. Methods for improved targeting of antibiotic treatment in children who are acutely unwell are urgently needed.     

Recombinant human interleukin-11 stimulates multilineage hematopoietic recovery in mice after a myelosuppressive regimen of sublethal irradiation and carboplatin

Interleukin-11 (IL-11) is a novel multifunctional hematopoietic cytokine capable of stimulating cells of the myeloid, lymphoid, erythroid, and megakaryocytic lineages in vitro. We have tested the pleiotropic properties of this cytokine on the hematopoietic recovery of mice after a combined regimen of sublethal irradiation and carboplatin administration. This regimen results in severe myelosuppression, characterized by a prolonged period of thrombocytopenia and severe anemia. Administration of recombinant human IL-11 (rhIL-11; 250 micrograms/kg/d) had multilineage effects on bone marrow and spleen hematopoietic activity, increasing the number of megakaryocyte, erythroid, granulocyte, and macrophage progenitors compared with the vehicle-treated controls. This was reflected in the peripheral circulation by a reduction of both the platelet and hematocrit nadirs and a significantly reduced period of thrombocytopenia and anemia in the rhIL-11-treated mice. The results from this study support the broad spectrum of biologic activities that have been attributed to rhIL-11 in vitro and suggest that this cytokine may be an effective agent in the treatment of myelosuppression associated with cancer chemotherapy and bone marrow transplantation.