Intraluminal cyclosporine A reduces capsular thickness around silicone implants in rats

One theory of the cause of connective tissue capsule formation around silicone mammary prostheses is based on an immunological interaction. In an in vitro pilot study, it is shown that intraluminal cyclosporine A, a potent T-lymphocyte-specific immunosuppressive agent, can diffuse slowly through the outer shell of a standard double-lumen silicone breast implant. Round silicone tissue expanders containing 50 mg of cyclosporine A were implanted subcutaneously in 10 rats. Ten animals served as controls. Evaluation was performed after three months. A significant decrease in collagen capsular thickness of 21.6 +/- 5.4 microns (mean +/- standard deviation was measured histomorphometrically in the treated group compared with 39.6 +/- 8.6 microns in the control group (p less than 0.001).     

Clinical and immunological results of corneal allograft rejection

Of 111 episodes of graft rejection in 66 patients, 62 responded to therapy with graft clearing (responders); 49 did not (non-responders). Both groups were of similar age, sex, and etiology; both had a similar rate of glaucoma and a similar rate of previous grafting. In responders the graft reaction was shorter in duration (2.2 vs. 5.6 wks. p less than 0.005), and it was necessary to increase the number of glaucoma medications more often in non-responders compared to responders (41% vs. 19%, p less than 0.02). The interval from surgery to reaction was similar in responders and non-responders (18.2 vs. 13.3 mos., p greater than 0.1). An epithelial rejection line was present in 11% of responders, but was not present in non-responders (p less than 0.05). Lymphocytotoxic antibody development correlated with rejection in 16 of 64 episodes. Patients who responded to treatment were more frequently asymptomatic (p less than 0.05) or were treated earlier following the onset of symptoms compared to non-responders (p less than 0.0001).     

Evolution of a form of pure alexia without agraphia in a child sustaining occipital lobe infarction at 21/2 years

The progress of cognitive visual dysfunction over an 8-year period of a child who sustained bilateral occipital-lobe infarctions at the age of 21/2 years is described. She survived with normal intelligence and went on to attend mainstream school. She manifested many features of cognitive visual impairment and, in particular, developed a form of pure alexia without agraphia. She achieved some letter-by-letter reading but no sight vocabulary development, including to her own name. She learned to write imaginatively employing phonetically true spelling but cannot read what she has written. Her progress and the difficulties encountered during the management of her condition are discussed in this first case report of the evolution of pure alexia without agraphia in childhood. The features of this syndrome in the developing child who has never developed the capacity to read are contrasted with that seen in affected adults.     

New Potent Azomethine Prodrugs of the Histamine H3-Receptor Agonist (R)-α-Methylhistamine Containing a Heteroarylphenyl Partial Structure

The therapeutic value of histamine H₃-receptor ligands is under current investigation. On the basis of recently described diaryl imine prodrugs of the histamine H₃-receptor agonist (R)-α-methyl-histamine ( 1 ) a series of new azomethine prodrugs containing five- and six-membered heterocycles were synthesized and tested for their in vitro hydrolysis rates and in vitro activity after oral application. It was found that electron-deficient six-membered heterocycles drastically destabilized the imine double bond so that these prodrugs decomposed unsuitably fast. On the contrary, prodrugs containing five-membered heterocycles appeared to be highly effective for the CNS delivery of 1 , and a remarkable correlation between chemical structure and pharmacokinetic profile was observed. Particularly (R)-4-fluoro-2-[[N-[1-(1H-imidazol-4-yl)-2-propyl]imino](1H-pyrrol-2-yl)methyl]phenol ( 8c ), the 2-furanyl analogue 8d , and its 3-furanyl isomer 8e proved to be equipotent to the most potent of recently described halogenated diaryl imine prodrugs of 1. However, in contrast to any other azomethine prodrug, 8c exhibited an incomparably long lasting delivery of 1 in the CNS and can thus be regarded as a ‘retard’ prodrug. Assuming that a therapeutic indication of histamine H₃-receptor agonists will soon be established, these highly potent heteroarylphenyl azomethine prodrugs, which already serve as valuable pharmacological tools, may also become potential drugs in clinical use.     

Quantitative and qualitative enzyme studies of Hodgkin's disease-derived cell lines

Any extensive analysis of Hodgkin (H) and Reed-Sternberg (RS) cells is limited by the scarcity of available material and by the common contamination with "by-stander" cells. The establishment of Hodgkin's disease-derived cell lines provides the opportunity to undertake studies in which large numbers of cells are required, as these cell lines are by definition monoclonal populations with unlimited cell growth. In this study, we analyzed the enzyme profiles of eight Hodgkin's disease cell lines (Co, Ho, Fox, HDLM-2, KM-H2, L428, L540, and L591) whereby cellular alpha-naphthyl acetate esterases, acid phosphatases, and dipeptidylpeptidase IV were examined quantitatively or qualitatively by IEF or chromatographic techniques. The results indicate that all of the H-RS cell lines examined had enzymatic features typical for lymphoid cells and, in particular, a monocyte/histiocyte origin of the cell lines could be excluded. Extrapolation of the available immunological, molecular biological, and enzymological evidence gained in vitro on cultured representatives of H-RS cells suggests a lymphoid origin for in vivo H-RS cells.     

Glutathione mutagenesis in Salmonella typhimurium is a {gamma}-glutamyltranspeptidase-enhanced process involving active oxygen species

Reduced glutathione (GSH) is mutagenic in Salmonella in thepresence of -glutamyltranspeptidase (GGT), with the highestresponse obtained in strain TA102. Reduced cysteinylglycine,one of the products of GGT metabolism of GSH, is mutagenic inthe absence of GGT. In strain TA102, GSH mutagenesis was dependenton molecular oxygen, enhanced by iron, inhibited by EDTA, desferrioxaminemesylate, mannitol, butylated hydroxyanisole, peroxidase andcatalase, but not by superoxide dismutase. Binding of GSH orits GGT-dependent metabolites to DNA in vitro was not detected.This is consistent with a model of an indirect mechanism ofmutagenesis, i.e. cleavage of GSH by GGT, followed by facileauto-oxidation of the resulting cysteinylglycine, with the productionof free radicals which lead to the (pen)ultimate mutagen, H₂O₂.     

Use of end-tidalPco 2 and transcutaneousPco 2 as noninvasive measurement of arterialPco 2 in extubated patients recovering from general anesthesia

This study was designed to assess the accuracy of end-tidalPco ₂ and transcutaneousPco ₂ as measurements of arterialPco ₂ in extubated, spontaneously breathing patients recovering from general anesthesia. In 30 patients, measurement of arterial transcutaneous, and end-tidalPco ₂ were taken simultaneously with body temperature approximately every 15 minutes over a 2-hour period. ArterialPco ₂ values were corrected for body temperature. Values for Paco ₂ were compared with those forPetCO₂ and Psco ₂ by linear regression analysis and by calculation of bias ± precision. Thirty-six percent of the capnogram tracings obtained did not develop a plateau phase. We found poor correlation between end-tidal and arterialPco ₂ regardless of the shape of the capnogram tracing, as well as poor correlation between transcutaneous and arterialPco ₂. Although the measurements of bias and precision of noninvasivePco ₂ monitors in this population are comparable to studies in other populations, we advise caution in relying on the routine use ofPetCO₂ or Psco ₂ for the noninvasive assessment of respiratory depression in extubated, spontaneously breathing patients recovering from general anesthesia.     

Schizophrenic patients' attitudes to therapists using behavioral and holistic-humanistic techniques

In a preliminary study of patients' perceptions of therapists' styles, 18 subjects with diagnoses of schizophrenia were randomly assigned either to social skills training or holistic health therapy. Four therapists conducted each treatment session in pairs, rotating between treatment conditions daily. At the end of 10 weeks of treatment, patients were able to discriminate among therapists on three interactional styles-"understanding," "independence-encouraging," and "and "critical-hostile"-and were able to differentiate between behavioral and holistic health treatments on "authoritarian" attitudes.