Thermal care of functional dyspepsia based on bicarbonate-sulphate-calcium water: a sequential clinical trial

Drug treatment of functional dyspepsia is often unsatisfactory.We assessed the efficacy of a bicarbonate-sulphate-calcium thermalwater cycle of 12 days, in patients with functional dyspepsia.Patients with functional dyspepsia were sent by their generalpractitioners to 12 days of treatment with thermal water, 200–400ml in the morning, at temperature of 33°C (91.4 F) and wereevaluated on a strict intention to treat basis. Four efficacyendpoints were analyzed as follows: (i) reduction of the globalsymptoms score, (ii) reduction of intensity to a level not interferingwith everyday activities, (iii) specific efficacy on ulcer-likeor dysmotility-like dyspepsia and (iv) esophageal or abdominal-associatedsymptoms. Statistical significance was reached for all threeprimary outcomes after the first 29 consecutive patients. Thermalwater reduced the global symptom score, reduced intensity ofsymptoms to a level not interfering with everyday activity,but was unable to completely suppress all symptoms. A paralleleffect emerged for ulcer-like and dyspepsia-like subgroups.The effect on heartburn and abdominal symptoms was not significant,suggesting a specific effect of the water on the gastric andduodenal wall. The Roma II criteria identify a natural kindof dyspepsia that improves with thermal water. Ulcer-like anddysmotility-like are not therapeutically distinguishable subgroups.Patients with dominant esophageal or abdominal symptoms shouldreceive a different therapy. Sequential methods are very effectivefor the evaluation of traditional care practices and shouldbe considered preliminary and integrative to randomized controlledtrials in this context.     

P53 Gene Mutations in Pituitary Carcinomas

Although p53 overexpression detected by immunohistochemistry has been reported in pituitary adenomas and carcinomas, genetic mutations in the p53 gene have not been previously detected in these tumors. We analyzed a series of eight pituitary adenomas and six pituitary carcinomas by immunohistochemistry, polymerase chain reaction amplification, and sequencing of p53 exon 5 through exon 8 for genetic mutations. Three carcinomas showed more than 20% expression of p53 protein in the tumor cells. One of these tumors with 60% overexpression of p53 protein had a mutation in codon 248, a common “hot spot” for p53 mutation, while the other carcinoma with 90% overexpression of p53 protein had a mutation in codon 135. All adenomas were negative for p53 mutations and had 15% of the cells expressing the p53 protein. Analysis of control tumors including four lung carcinomas with proven p53 mutations also had greater than 85% of the tumor cells overexpressing p53 protein. Two breast carcinoma cell lines with known p53 mutations, MBA-MD 231 and MBA-MD-486, also showed greater than 85% of the tumor cells overexpressing p53. These results show that p53 mutations are present in a subset of pituitary carcinomas and are usually associated with a high percentage of tumor cells overexpressing the p53 protein.     

Nodular fasciitis of the male breast: a case report

A case of nodular fasciitis is reported that involved the breast parenchyma of a 40-year-old man. The differential diagnosis of nodular fasciitis in the male breast mainly includes fibromatosis and myofibroblastoma. However, other benign and malignant spindle cell lesions of the breast, such as pseudoangiomatous stromal hyperplasia and especially spindle cell metaplastic carcinoma and fibrosarcoma, may enter the differential. The classic histomorphologic features and immunohistochemical findings are helpful in arriving at the correct diagnosis. The patient underwent a total excision of the lesion and is free of disease after 14 months. To our knowledge, this is the first reported case of a lesion of this type in the male breast.     

Acute Toxicity of Ammonia,Nitrite and Nitrate to Shrimp <Emphasis Type="Italic">Litopenaeus vannamei</Emphasis> Postlarvae in Low-Salinity Water

Shrimp farming in low salinities waters is an alternative to increasing production, and counteracting disease problems in brackish and marine waters. However, in low-salinity waters, toxicity of nitrogen compounds increases, and there is no available data of its acute toxicity in shrimp postlarvae. This study determined the acute toxicity of ammonia, nitrite and nitrate in Litopenaeus vannamei postlarvae in 1 and 3 g/L salinity, as well as the safety levels. The LC₅₀ confirms that nitrite is more toxic than ammonia and nitrate in low salinity waters, and that its toxicity increases with a decrease in salinity. The safe levels estimated for salinities of 1 and 3 g/L were 0.54 and 0.81 mg/L for total ammonia–N, 0.17 and 0.25 mg/L for NO₂–N, and 5.6 and 21.5 mg/L for NO₃–N, respectively.     

Isolation of Nocardia asiatica from cutaneous ulcers of a human immunodeficiency virus-infected patient in Italy

A strain of Nocardia was isolated from cutaneous ulcers of a human immunodeficiency virus-infected patient in Italy. Comparative 16S rRNA gene sequence analysis revealed that the isolate represented a strain of Nocardia asiatica. Antimicrobial susceptibility testing was essential to guide the clinicians to successfully treat this infection.     

Immune responses to AAV in clinical trials

Recent findings in a clinical trial in which an adeno-associated virus (AAV) vector expressing coagulation factor IX (F.IX) was introduced into the liver of hemophilia B subjects highlighted a new issue previously not identified in animal studies. Upon AAV gene transfer to liver, two subjects enrolled in this trial developed transient elevation of liver enzymes, likely as a consequence of immune rejection of transduced hepatocytes mediated by AAV capsid-specific CD8(+) T cells. Studies in healthy donors showed that humans carry a population of antigen-specific memory CD8(+) T cells probably arising from wild-type AAV infections. The hypothesis formulated here is that these cells expanded upon re-exposure to capsid, i.e. upon AAV-2 hepatic gene transfer, and cleared AAV epitope-bearing transduced hepatocytes. Other hypotheses have been formulated which include specific receptor-binding properties of AAV-2 capsid, presence of capsid-expressing DNA in AAV vector preparations, and expression of alternative reading frames from the transgene. Absence of a valid animal model has prevented an in-depth mechanistic study of the phenomenon. Several possible solutions to the problem are discussed, including the administration of a short-term anti-T cell immunosuppression regimen concomitant with gene transfer. While more studies will be necessary to further define mechanisms and risks associated with capsid-specific immune responses in humans, monitoring of these responses in clinical trials will be essential to achieving the goal of long-term therapeutic gene transfer in humans.     

From normal to clonal B cells: Chronic lymphocytic leukemia (CLL) at the crossroad between neoplasia and autoimmunity

Chronic lymphocytic leukemia (CLL) is a B-cell malignancy endowed with a number of features that recall autoimmune disorders, including the CD5 expression and the development of autoimmune manifestations restricted to self antigens expressed by hematopoietic cells. Several evidences strongly support the possibility that an antigenic stimulation through the B-cell receptor (BCR) is involved in the selection and possibly also the expansion of the malignant clone. Though all evidences suggest specific Ag recognition and possibly stimulation at different time-points, the nature of the Ag(s) is still unknown. It appears likely that CLL cells derive from a pool of auto/polyreactive CD5(+) B cells. Hence CLL appears to be a B-cell malignancy triggered or facilitated in its development and evolution by an auto-Ag. The crucial issues have become to what extent this deleterious binding capacity is central to the natural history of the disease and how it relates to the malignant transformation of the cell.     

Epithelial–mesenchymal transition (EMT) of renal tubular cells in canine glomerulonephritis

Tubulo-interstitial fibrosis in dogs may result from primary injury to the interstitium or develop secondary to other renal diseases. As in human renal pathology, tubular epithelial cells (TEC) are believed to actively participate in the mechanisms of renal fibrosis. In this study, we examined the changes in the tubular epithelial component in two specific canine diseases. Immunohistochemistry showed the expression of the epithelial marker cytokeratin, the smooth muscle marker α-SMA, the mesenchymal marker vimentin and PCNA in 20 dogs with membranous glomerulonephritis and membrano-proliferative glomerulonephritis. Results showed that the loss of the epithelial marker in TEC was directly correlated to the grade of tubulo-interstitial disease present and independent of the type of glomerulonephritis. Varying degrees of vimentin positivity were detected in tubular epithelium in areas of inflammation, and low numbers of scattered α-SMA-positive cells were also observed. Immunohistochemistry showed that epithelial tubular cells lose their cytokeratin staining characteristics and transdifferentiate into cells exhibiting key mesenchymal immunophenotypic feature of vimentin-positive staining in both diseases investigated. The integrity of the tubular basement membrane is likely to be fundamental in maintaining the epithelial phenotype of TEC. Animal models provide opportunities for investigating the pathogenesis of renal fibrosis in humans.     

Preventing harm from high-alert medications

BACKGROUND: One of the 12 interventions that the Institute for Healthcare Improvement (IHI) recommends for its 5 Million Lives Campaign is "Prevent Harm from High-Alert Medications . . . starting with a focus on anticoagulants, sedatives, narcotics, and insulin." EXECUTING SYSTEM-LEVEL CHANGES: Three essential elements are needed to execute system-level changes in an organization: will, ideas, and execution. Will is developed by examining the status quo in an organization and agreeing that it is no longer acceptable. Ideas-changes that will make the system safer-can be found in the literature and in the experience of other hospitals and are the basis for the recommended general interventions to reduce errors and harm associated with high-alert medications. Execution, the process of making those changes real, requires commitment from senior leaders and clinical leaders, along with the organizational capacity to improve. The steps in the medication system are so interrelated that a change in one area will affect others' ability to complete their work. In addition, senior leadership and clinical leadership must visibly support the effort, connecting the reduction in high-alert medication-related harm to the overall hospital goal of harm reduction is essential. CONCLUSION: The campaign's goal is to achieve a 50% reduction in harm related to high-alert medications. Employing strategies such as standardization and simplification will provide the foundation for improved medication safety.