Conformationally constrained congeners of 6-aryl-5-methyl-4,5-dihydro-3(2H)-pyridazinones active on the cardiovascular system: conformational studies by molecular mechanics calculations and 1H NMR spectroscopy

Unsubstituted phenylpyridazinones 1a and 2a and their tricyclic analogues indenopyridazinone 3a, benzocinnolinone 4a, and benzocycloheptapyridazinone 5a were submitted to conformational analysis with Allinger's MM2(85) program in order to better define the relationship between the cardiovascular properties of some derivatives and their preferred conformations. Structures 1-4, giving rise to highly active compounds, were found to exist in a conformation showing a near-planar arrangement of the phenyl and the pyridazinone ring. On the contrary, 5, whose derivatives were inactive, shows two significantly populated conformations both markedly deviated from planarity. 1H NMR analysis of the tricyclic systems 3-5 was in full agreement with the molecular mechanics calculations.     

Quality of life assessment and HIV infection: A review

In the last few years, survival of patients infected with human immunodeficiency virus (HIV) has been improved because of a decreased incidence of some opportunistic complications attributable to prophylactic treatments and antiretroviral drugs. The impact of these agents should also be reflected in the quality of life (QoL) of patients. We have reviewed this topic with an emphasis on different types of measurements such as Q-TWIST, MOS and the Spitzer score which seem to be most appropriate for this patient population. We do not think that a special type of assessment should be designed for HIV-infected persons. It would be less time-consuming to improve already existing validated scores focusing on HIV infection. QoL in intravenous drug users with HIV should be evaluated more often.     

External beam radiotherapy for retinoblastoma: I. Whole eye technique.

A retrospective analysis has been performed of the results of external beam radiotherapy for retinoblastoma using a whole eye technique. Local tumour control has been assessed in a consecutive series of 175 eyes in 142 children all of whom received external beam radiotherapy as the primary treatment for retinoblastoma. Follow up ranged from 2 to 17 years (median 9 years). Tumour control rates have been analysed with respect to the Reese Ellsworth classification and the series includes eyes in groups I to V. Focal salvage therapy was given for persistent, recurrent, or new tumours after radiotherapy. Following whole eye radiotherapy alone, the overall ocular cure rate was 57%, though with salvage therapy 80% of eyes could be preserved.     

Effect of prostaglandin E1 on graft function of kidneys from living related donors

Prostaglandin E₁ (PGE₁) was used in renal transplant recipients with living related donors. The drug was given intravenously from day 1 to day 7 after transplantation at a dose of 40 µg/kg twice a day. A total of 45 patients were studied divided into two groups: 25 patients were treated with PGE₁ (group B) and the remaining 20 patients did not receive the drug (group A). In group B, 24-h creatinine clearance (Ccr) was 66 ± 12.8 ml/min compared with 40.3 ± 13.4 ml/min in group A on the fifth postoperative day (P < 0.05). Urinary levels of N-acetyl-β-d -glucosaminidase (NAG) and serum levels of platelet factor 4 (PF4) in group B were significantly lower than in group A. On the fourth postoperative day, the urinary excretion of thromboxan B₂ (TxB₂) in group A was higher than in group B, but not significantly (5.1 ± 3.0 ng/day and 2.8 ± 1.1 ng/day, respectively). Acute rejection occurred in four patients in group B and in 10 patients (40%) in group A. The percentage of Leu2a-positive lymphocytes in group B was higher than in group A. We conclude that postoperative administration of PGE₁ improves graft function in kidneys from living related donors.     

Inducible beta-lactamases in clinical isolates of non-aeruginosa Pseudomonas.

The incidence of antimicrobial resistance and expression of imipenem-inducible beta-lactamase were examined in 22 strains of non-aeruginosa Pseudomonas isolated from clinical specimens. The percentage of strains resistant to form one to eight antibiotics was 45. The most active antibiotics against all strains were norfloxacin, ciprofloxacin and imipenem. Eighteen out of the 22 strains were positive for beta-lactamase in a spectrophotometric assay using nitrocefin as substrate. A low inducible beta-lactamase specific activity (0.001-0.999 nmoles nitrocefin hydrolyzed/min/mg protein) was found in twelve strains whereas six strains had a relatively high specific activity (3.5-159.8 nmoles nitrocefin hydrolyzed/min/mg protein). Five strains representing different Pseudomonas spp. and showing high beta-lactamase activity were studied further. Crude enzymes from two species (Pseudomonas mendocina, Pseudomonas acidovorans) hydrolyzed cefazolin at a higher rate than penicillin and ampicillin. All enzymes from the five species were inhibited by cloxacillin and p-chloromercuribenzoate (1 mM), but were insensitive to inhibition by clavulanic acid, ethylenediamine acetic acid (EDTA) at the same concentration. The isoelectric point and molecular weight of the main beta-lactamase band from the 5 species were 6.5-6.8 and 47,000 respectively.     

Ausfallhonorar wegen Nichterscheinens zu einem Exklusiv-Termin

Abstrakt 1. Nimmt ein Patient einen ihm von seinem (Zahn-)Arzt einger?umten Exklusiv-Termin nicht wahr, obwohl er auf dessen Eigenschaft ausdrücklich hingewiesen wurde, so hat er dem (Zahn-)Arzt den Behandlungsausfall abzüglich eines angemessenen Eigenanteils des (Zahn-)Arztes zu ersetzen. 2. Die Ersatzpflicht tritt auch dann ein, wenn der Patient den Termin nicht in der in dem Behandlungsvertrag vorgesehenen Frist absagt. Eine hierfür seitens des (Zahn-)Arztes bestimmte Frist von zwei Tagen vor Behandlungsbeginn stellt sich für den Patienten grunds?tzlich auch nicht als unangemessene Benachteiligung i.S. des § 307 BGB dar. 3. Ein Anspruch des Arztes entf?llt auch bei nur mündlicher Vereinbarung nicht unter dem Gesichtspunkt des § 4 Abs. 5b BMV-Z, denn diese Vorschrift ist teleologisch dahin zu reduzieren, dass nur zahn?rztliche Honoraransprüche aus erfolgten Behandlungen schriftlich vereinbart werden müssen. Soweit es jedoch um einen vertraglichen Anspruch wegen einer Leistungsst?rung geht, vermag das Schriftformerfordernis des § 4 Abs. 5b BMV-Z grunds?tzlich nicht einzugreifen. (Leits?tze des Bearbeiters)     

Role of IL-2 in rat fetal thymocyte development

Early during rat thymus ontogeny, an important proportion of thymocytes expresses IL-2R and contains IL-2 mRNA. To investigate the role of the IL-2-IL-2R complex in rat T cell maturation, we supplied either recombinant rat IL-2 or blocking anti-CD25 mAb to rat fetal thymus organ cultures (FTOC) under several experimental conditions. The IL-2 treatment initially stimulated the growth of thymocytes and, as a result, induced T cell differentiation, but the continuous addition of IL-2 to rat FTOC, as well as the anti-CD25 administration, resulted in cell number decrease and inhibition of thymocyte maturation. These results indicate that immature rat thymocytes bear functional high- affinity IL-2R and that IL-2 promotes T cell differentiation as a consequence of its capacity to stimulate cell proliferation. Modifications in TCR alpha beta repertoire and increased numbers of NKR- P1+ cells, largely NK cells, were also observed in IL-2-treated FTOC. Furthermore, IL-2-responsiveness of different thymocyte subsets changed throughout thymic ontogeny. Immature CD4-CD8-cells responded to IL-2 in two stages, early in thymus development and around birth, in correlation with the maturation of two distinct waves of thymic cell progenitors. Mature CD8+ thymocytes maximally responded to IL-2 around birth, supporting a role for IL-2 in the increased proliferation of mature thymocytes observed in vivo in the perinatal period. Taken together, these findings support a role for IL-2 in rat T cell development.