Ectopic ACTH secretion: a heterogeneous entity

OBJECTIVES: ACTH-secreting non-pituitary tumors are a rare cause of Cushing's disease. We report the clinical course, prognostic aspects and molecular analysis data in three patients for whom the diagnosis was confirmed but who had variable clinical features and laboratory results. CASE REPORTS: Patient n degree 1 had severe hypercorticism which rapidly progressed to death 13 months after diagnosis. In patient n degree 2, signs of hypercorticism severe, leading to death 5 years after discovery of the causal carcinoid tumor. Patient n degree 3 had moderate hypercorticism and has survived for more than 25 years. DISCUSSION: These 3 ectopic tumors are representative examples of a wide range of possible ACTH-secreting ectopic tumors. In highly malignant poorly-differentiated tumors such as small-cell anaplastic carcinomas, ACTH production is aberrant and poorly controlled, and thus not particularly effective. At the other extreme, typical benign bronchial carcinomas have a high degree of neuroendocrine differentiation and secrete ACTH in a well-controlled manner difficult to distinguish from corticotropic adenomas, further exaggerating the diagnostic pitfalls.     

An endogenous sialoprotein and a bacterial B cell superantigen compete in their VH family-specific binding interactions with human Igs

Staphylococcal protein A (SpA), a bacterial membrane protein, and protein Fv (Fv binding protein (pFv)), a human sialoprotein involved in gut-associated immunity, have both recently been shown to have unconventional V(H) family-restricted binding interactions with Igs. To determine whether these Ig binding proteins interact with related structures, we performed a series of comparative binding studies. The results confirmed that both molecules are bound by most V(H)3 IgM, but pFv is also recognized by V(H)3 and V(H)6 Ig that do not interact with SpA. We discovered that pFv and SpA (or a single domain of SpA) can compete for binding to a V(H)3 Ab, which suggests that they can recognize the same (or adjacent) V(H) sites. For both SpA and pFv, binding is less frequent among IgG than IgM. However, V(H)3 IgG more commonly possess Fab-mediated binding activity for pFv than for SpA. Binding studies of denatured Ig suggested that both pFv and SpA interact with conformationally dependent V(H) sites, although in certain cases pFv binding is more permissive than SpA binding. Taken together, these results indicate that the superantigen properties of SpA, a microbial protein, and those of pFv, an endogenous sialoprotein, involve binding interactions with overlapping and at times functionally equivalent sites in the V(H) domain, indicating that self and foreign proteins can employ highly conserved strategies to create superantigens for the Ag receptors of B lymphocytes.     

A new spacer group derived from arylmalonaldehydes for glucuronylated prodrugs

A new glucuronylated prodrug of doxorubicin, potentially useful for ADEPT or PMT cancer chemotherapy, has been prepared from 4-methyl phenyl malonaldehyde. The enol ether spacer, linked via a carbamate to the 3'-amino group of doxorubicin is rapidly cleaved after beta-glucuronidase (E coli) catalyzed hydrolysis at pH 7.2 and 37 degrees C.     

Protection of health care personnel against tuberculosis]

Protection of people who are working in health care against tuberculosis has been evaluated recently in several publications and guidelines. The following aims of guidelines are the reduction of emission from infections patients, limitation of aerosol transmission and protection of personnel and other patients against inhalation of infections particles. Because these protective means cannot abolish risk, a survey of the exposed personnel is mandatory as well as a preventive treatment of those infected.     

Evaluation of the gastrotoxicity of anti-inflammatory drugs: contribution of general registries of digestive endoscopy

The evaluation of the rate of gastroduodenal toxicity of anti inflammatory drugs is a difficult problem. We tried to analyse that question by studying the general endoscopic registers of the Gastro-Enterologic department of the hospital. This retrospective study concerns 2,945 endoscopies performed during the year 1988 and 1992 randomly chosen among the last 5 years. 992 results show injuries suggestive of non steroidal anti inflammatory drugs (NSAID) toxicity, however only in 65 cases the potential role of an anti inflammatory drug is mentioned: 36 men and 29 women, mean age: 50.6 +/- 19.6 years. Concerning the drugs, only the pharmacological classes they belong to are mentioned except for Aspirin. Acetyl salicylate acid 7 cases, NSAIDS 36 and Steroids 22. In the drug group 63% of injuries are located to the stomach (ulcers 13%, gastritis 50%), 37% to the duodenum (19% ulcers, 18% duodenitis). Compared to the groups with the same kind of injuries, but without any mention of drugs, there are no statistical difference in the proportion of ulcers. Aging and sex are not influent in our results on the genesis of drug induced ulcers. These results must be discussed because a lot of datas are missing in the registers and so the number of patients taking drugs is probably underestimated. This means that unless a prospective study is held with someone enquiring for all the risk factors, the study of the general endoscopic registers is not a good way to estimate gastrointestinal damages due to drugs.