https://www.thelancet.com/pdfs/journals/lancet/PIIS0140-6736(05)71144-2.pdf

Shiga-toxin-producing Escherichia coli and haemolytic uraemic syndrome

Antibiotic resistance is one of the greatest challenges of the twenty-first century. However, the increasing understanding of bacterial pathogenesis and intercellular communication has revealed many potential strategies to develop novel drugs to treat bacteria-mediated disease. Interference with bacterial virulence and/or cell-to-cell signalling pathways is an especially compelling approach, as it is thought to apply less selective pressure for the development of bacterial resistance than traditional strategies, which are aimed at killing bacteria or preventing their growth. Here, we discuss the mechanisms of bacterial virulence and present promising anti-virulence strategies and compounds for the future treatment of bacterial infections.

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Anti-virulence strategies to combat bacteria-mediated disease

Nineteen patients whose bone marrow smears showed histiocytic hyperplasia with prominent hemophagocytosis were found to have a clinicopathologic syndrome associated with active viral infection. High fever, constitutional symptoms, liver function, and coagulation abnormalities and peripheral blood cytopenias were characteristic findings. Hepatosplenomegaly, lymphadenopathy, bilateral pulmonary infiltrates, and skin rash were often present. Fourteen of the patients were immunosuppressed. Active infection by herpes group viruses was documented in 14 patients and by adenovirus in 1. The bone marrow of most patients also showed decreased granulopoiesis and erythropoiesis with normal to increased numbers of megakaryocytes. Treatment generally consisted of supportive therapy and withdrawal of immunosuppressive drugs. Thirteen patients recovered. Lymph node biopsy and autopsy material showed generalized histiocytic hyperplasia with hemophagocytosis. The relationship of this disorder to familial hemophagocytic reticulosis, familial erythrophagocytic lymphohistiocytosis, histiocytic medullary reticulosis, and malignant histiocytosis is discussed. Immunosuppressive and cytotoxic therapy may be contraindicated in the treatment of this virus-associated syndrome.

Virus-associated hemophagocytic syndrome: a benign histiocytic proliferation distinct from malignant histiocytosis.

https://www.scielo.br/pdf/bjm/v47s1/1517-8382-bjm-47-s1-0003.pdf

Diarrheagenic Escherichia coli.

The objective of this review is to highlight the importance of cattle in human disease due to Shiga toxin-producing Escherichia coli (STEC) and to discuss features of STEC that are important in human disease. Healthy dairy and beef cattle are a major reservoir of a diverse group of STEC that infects humans through contamination of food and water, as well as through direct contact. Infection of humans by STEC may result in combinations of watery diarrhea, bloody diarrhea, and hemolytic uremic syndrome. Systems of serotyping, subtyping, and virulence typing of STEC are used to aid in epidemiology, diagnosis, and pathogenesis studies. Severe disease and outbreaks of disease are most commonly due to serotype O157:H7, which, like most other highly pathogenic STEC, colonize the large intestine by means of a characteristic attaching and effacing lesion. This lesion is induced by a bacterial type III secretion system that injects effector proteins into the intestinal epithelial cell, resulting in profound changes in the architecture and metabolism of the host cell and intimate adherence of the bacteria. Severe disease in the form of bloody diarrhea and the hemolytic uremic syndrome is attributable to Shiga toxin (Stx), which exists as 2 major types, Stx1 and Stx2. The stx genes are encoded on temperate bacteriophages in the chromosome of the bacteria, and production and release of the toxin are highly dependent on induction of the phages. Regulation of the genes involved in induction of the attaching and effacing lesion, and production of Stx is complex. In addition to these genes that are clearly implicated in virulence, there are several putative virulence factors. A major public health goal is to prevent STEC-induced disease in humans. Studies aimed at understanding factors that affect carriage and shedding of STEC by cattle and factors that contribute to development of disease in humans are considered to be important in achieving this objective.

Shiga toxin-producing Escherichia coli: An overview

How blind is the double-blind?: an assessment in a lithium-prophylaxis study

Rapid cycling manic depressive patients

In order to test the hypothesis that bipolar (manic-depressive) patients may be distinguished on the basis of family history, the authors have investigated two matched samples of 30 patients each, distinguished by the presence or absence of a family history for manic-depressive illness. Among the variables studied are socio-economic and civil status, clinical features of illness and hospitalization patterns. Family history is associated with onset of illness and with other key features of the course of illness. Models are presented which may explain these results.

Manic-Depressive Illness: A Comparative Study of Patients With and Without a Family History

IT has been generally recognized that sodium and potassium ions are essential to neural conduction and to the normal functioning of the nervous system. The role of lithium in nerve conduction is less understood. It does reduce manic hyperactivity and elation2–5, however; thus its therapeutic use in the manic phase of manic depressive psychosis. A substance capable of producing similar improvements in the depressive phase remains to be discovered.

R. R. Fieve

Papers

How blind is the double-blind?: an assessment in a lithium-prophylaxis study

Rapid cycling manic depressive patients

Manic-Depressive Illness: A Comparative Study of Patients With and Without a Family History

Rubidium: a Potential Modifier of Affect and Behaviour

Statistical predictions of suicide in depressives.