Experimental glomerulonephritis induced by hydrocarbon exposure: A systematic review

BACKGROUND: Much epidemiological evidence suggests that hydrocarbon exposure may induce glomerulonephritis and worsen its course in many patients. The mechanisms are unknown, however, no specific microscopic pattern has been identified, and it has also been argued that hydrocarbon exposure causes tubular damage mainly. Studying experimental animals may best answer these questions, and as no systematic review of glomerulonephritis produced experimentally by hydrocarbon exposure has been performed previously, I found it relevant to search for and analyse such studies. METHODS: Animal experiments having mimicked human glomerulonephritis by hydrocarbon exposure were sought on Medline and Toxnet RESULTS: Twenty-six experiments using thirteen different hydrocarbons were identified. Several human subtypes were observed including IgA nephritis, mesangial, proliferative and extracapillary glomerulonephritis, focal and focal-segmental sclerosis, minimal change nephropathy, anti-GBM and anti-TBM nephritis, and glomerulonephritis associated with peiarteritis nodosa. Glomerular proteinuria was seen in 10/12 experiments that included urine analyses, and renal failure in 5/8 experiments that included measurements of glomerular function. All experiments resulted in various degrees of tubular damage as well. In most studies, where the animals were examined at different times during or after the exposure, the renal microscopic and functional changes were seen immediately, whereas deposits of complement and immunoglobulins appeared late in the course, if at all. CONCLUSION: These experiments are in accord with epidemiological evidence that hydrocarbon exposure may cause glomerulonephritis and worsen renal function. Probable mechanisms include an induction of autologous antibodies and a disturbance of normal immunological functions. Also, tubular damage may increase postglomerular resistance, resulting in a glomerular deposition of macromolecules. In most models a causal role of glomerular immune complex formation was unlikely, but may rather have been a secondary phenomenon. As most glomerulonephritis subgroups were seen and as some of the hydrocarbons produced more than one subgroup, the microscopic findings in a patient cannot be used as a clue to the causation of his disease. By the same reason, the lack of a specific histological pattern in patients with glomerulonephritis assumed to have been caused by hydrocarbon exposure is not contradictive

Flaws in design, analysis and interpretation of Pfizer's antifungal trials of voriconazole and uncritical subsequent quotations

We have previously described how a series of trials sponsored by Pfizer of its antifungal drug, fluconazole, in cancer patients with neutropenia handicapped the control drug, amphotericin B, by flaws in design and analysis. We describe similar problems in two pivotal trials of Pfizer's new antifungal agent, voriconazole, published in a prestigious journal. In a non-inferiority trial, voriconazole was significantly inferior to liposomal amphothericin B, but the authors concluded that voriconazole was a suitable alternative. The second trial used amphothericin B deoxycholate as comparator, but handicapped the drug by not requiring pre-medication to reduce infusion-related toxicity or substitution with electrolytes and fluid to reduce nephrotoxicity, although the planned duration of treatment was 84 days. Voriconazole was given for 77 days on average, but the comparator for only 10 days, which precludes a meaningful comparison. In a random sample of 50 references to these trials, we found that the unwarranted conclusions were mostly uncritically propagated. It was particularly surprising that relevant criticism raised by the FDA related to the first trial was only quoted once, and that none of the articles noted the obvious flaws in the design of the second trial. We suggest that editors ensure that the abstract reflects fairly on the remainder of the paper, and that journals do not impose any time limit for accepting letters that point out serious weaknesses in a study that have not been noted before

Characteristics Associated with Citation Rate of the Medical Literature

BACKGROUND: The citation rate for articles is viewed as a measure of their importance and impact; however, little is known about what features of articles are associated with higher citation rate. METHODOLOGY/PRINCIPAL FINDINGS: We conducted a cohort study of all original articles, regardless of study methodology, published in the Lancet, JAMA, and New England Journal of Medicine, from October 1, 1999 to March 31, 2000. We identified 328 articles. Two blinded, independent reviewers extracted, in duplicate, nine variables from each article, which were analyzed in both univariable and multivariable linear least-squares regression models for their association with the annual rate of citations received by the article since publication. A two-way interaction between industry funding and an industry-favoring result was tested and found to be significant (p = 0.02). In our adjusted analysis, the presence of industry funding and an industry-favoring result was associated with an increase in annual citation rate of 25.7 (95% confidence interval, 8.5 to 42.8) compared to the absence of both industry funding and industry-favoring results. Higher annual rates of citation were also associated with articles dealing with cardiovascular medicine (13.3 more; 95% confidence interval, 3.9 to 22.3) and oncology (12.6 more; 95% confidence interval, 1.2 to 24.0), articles with group authorship (11.1 more; 95% confidence interval, 2.7 to 19.5), larger sample size and journal of publication. CONCLUSIONS/SIGNIFICANCE: Large trials, with group authorship, industry-funded, with industry-favoring results, in oncology or cardiology were associated with greater subsequent citations

Coal tar creosote abuse by vapour inhalation presenting with renal impairment and neurotoxicity: a case report

A 56 year old aromatherapist presented with advanced renal failure following chronic coal tar creosote vapour inhalation, and a chronic tubulo-interstitial nephritis was identified on renal biopsy. Following dialysis dependence occult inhalation continued, resulting in seizures, ataxia, cognitive impairment and marked generalised cerebral atrophy. We describe for the first time a case of creosote abuse by chronic vapour inhalation, resulting in significant morbidity. Use of the polycyclic aromatic hydrocarbon-containing wood preservative coal tar creosote is restricted by many countries due to concerns over environmental contamination and carcinogenicity. This case demonstrates additional toxicities not previously reported with coal tar creosote, and emphasizes the health risks of polycyclic aromatic hydrocarbon exposure

IgA nephropathy in a laboratory worker that progressed to end-stage renal disease: a case report

BACKGROUND: IgA nephropathy (IgAN) is the most common form of glomerulonephritis, a principal cause of end-stage renal disease (ESRD) worldwide. The mechanisms of onset and progression of IgAN have not been fully revealed, and epidemiologic studies have yielded diverging opinions as to the role of occupational exposure to organic solvents in the initiation or worsening of IgAN. As the authors encountered a laboratory worker with IgAN that progressed to ESRD, we present a case report of IgAN progression due to dichloromethane exposure along with a review of literature. CASE PRESENTATION: A 41-year-old male laboratory worker began to experience gross painless hematuria after two years of occupational exposure to toluene. Although clinical follow-up was initiated under the impression of IgAN based on clinical findings, the patient continued to work for four more years in the same laboratory, during which he was in charge of laboratory analysis with direct exposure to a high concentration of dichloromethane without proper protective equipment. During that time, his renal function rapidly worsened and finally progressed to ESRD 10 years after the first clinical symptoms. The result of exposure assessment through reenactment of his work exceeded the occupational exposure limit for dichloromethane to a considerable degree. CONCLUSIONS: The causal association between occupational solvent exposure and IgAN is still unclear; therefore, this case report could be used as a basis to support the relevance of occupational solvent exposure to IgAN and/or its progression. Early intervention as well as close monitoring of laboratory workers exposed to various organic solvents is important to prevent or delay the progression of glomerulonephritis to ESRD in the occupational setting

Are benefits and harms in mammography screening given equal attention in scientific articles? A cross-sectional study

<p>Abstract</p> <p>Background</p> <p>The CONSORT statement specifies the need for a balanced presentation of both benefits and harms of medical interventions in trial reports. However, invitations to screening and newspaper articles often emphasize benefits and downplay or omit harms, and it is known that scientific articles can be influenced by conflicts of interest. We wanted to determine if a similar imbalance occurs in scientific articles on mammography screening and if it is related to author affiliation.</p> <p>Methods</p> <p>We searched PubMed in April 2005 for articles on mammography screening that mentioned a benefit or a harm and that were published in 2004 in English. Data extraction was performed by three independent investigators, two unblinded and one blinded for article contents, and author names and affiliation, as appropriate. The extracted data were compared and discrepancies resolved by two investigators in a combined analysis. We defined three groups of authors: (1) authors in specialties unrelated to mammography screening, (2) authors in screening-affiliated specialties (radiology or breast cancer surgery) who were not working with screening, or authors funded by cancer charities, and (3) authors (at least one) working directly with mammography screening programmes. We used a data extraction sheet with 17 items described as important benefits and harms in the 2002 WHO/IARC-report on breast cancer screening.</p> <p>Results</p> <p>We identified 854 articles, and 143 were eligible for the study. Most were original research. Benefits were mentioned more often than harms (96% vs 62%, P < 0.001). Fifty-five (38%) articles mentioned only benefits, whereas seven (5%) mentioned only harms (P < 0.001). Overdiagnosis was mentioned in 35 articles (24%), but was more often downplayed or rejected in articles that had authors working with screening, (6/15; 40%) compared with authors affiliated by specialty or funding (1/6; 17%), or authors unrelated with screening (1/14; 7%) (P = 0.03). Benefits in terms of reduced breast cancer mortality were mentioned in 109 (76%) articles, and was more often provided as a relative risk reduction than an absolute risk reduction, where quantified (45 articles (31%) versus 6 articles (3%) (P < 0.001)).</p> <p>Conclusion</p> <p>Scientific articles tend to emphasize the major benefits of mammography screening over its major harms. This imbalance is related to the authors' affiliation.</p

Regulating STING in health and disease.

The presence of cytosolic double-stranded DNA molecules can trigger multiple innate immune signalling pathways which converge on the activation of an ER-resident innate immune adaptor named "STimulator of INterferon Genes (STING)". STING has been found to mediate type I interferon response downstream of cyclic dinucleotides and a number of DNA and RNA inducing signalling pathway. In addition to its physiological function, a rapidly increasing body of literature highlights the role for STING in human disease where variants of the STING proteins, as well as dysregulated STING signalling, have been implicated in a number of inflammatory diseases. This review will summarise the recent structural and functional findings of STING, and discuss how STING research has promoted the development of novel therapeutic approaches and experimental tools to improve treatment of tumour and autoimmune diseases

The "Statinth" wonder of the world: a panacea for all illnesses or a bubble about to burst

After the introduction of statins in the market as effective lipid lowering agents, they were shown to have effects other than lipid lowering. These actions were collectively referred to as 'pleiotropic actions of statins.' Pleiotropism of statins formed the basis for evaluating statins for several indications other than lipid lowering. Evidence both in favour and against is available for several of these indications. The current review attempts to critically summarise the available data for each of these indications

Reporting bias in medical research - a narrative review

Reporting bias represents a major problem in the assessment of health care interventions. Several prominent cases have been described in the literature, for example, in the reporting of trials of antidepressants, Class I anti-arrhythmic drugs, and selective COX-2 inhibitors. The aim of this narrative review is to gain an overview of reporting bias in the medical literature, focussing on publication bias and selective outcome reporting. We explore whether these types of bias have been shown in areas beyond the well-known cases noted above, in order to gain an impression of how widespread the problem is. For this purpose, we screened relevant articles on reporting bias that had previously been obtained by the German Institute for Quality and Efficiency in Health Care in the context of its health technology assessment reports and other research work, together with the reference lists of these articles