Clobetasone butyrate,a new topical corticosteroid: clinical activity and effects on pituitary-adrenal axis function and model of epidermal atrophy.

Clobetasone butyrate is a new corticosteroid, selected for study because of its combination of good activity in the vasoconstriction test and low systemic activity in animals. Formulated as an 0.05% ointment and cream (Molivate) it was clinically effective in patients with eczema, its activity being significantly greater than that of hydrocortisone 1% or fluocortolone 0.2% (Ultradil). Under conditions that predispose to maximal percutaneous absorption clobetasone butyrate ointment had minimal effect on hypothalamic-pituitary-adrenal function. In an animal model of cutaneous atrophy it caused less thinning of the epidermis than steroids other than hydrocortisone. Clobetasone butyrate 0.05% ointment and cream gave every indication of offering clinically effective topical anti-inflammatory activity with a wide margin of safety.     

Abdominal surgical emergencies in the puerperium.

Since surgical emergencies in the puerperium are rare, surgeons and obstetricians amass little experience of them. There may be considerable delay in making a diagnosis, firstly, because the abdominal symptoms are thought to be related to the pregnancy, and, secondly, because the signs are rarely convincing in contrast to the symptoms. Any of the common surgical emergencies may occur in pregnancy and the puerperium and there are some others that appear to be a particullar problem of the puerperium.     

Cu(II) ion interaction with teicoplanin-vancomycin’s analog

Teicoplanin, a member of the “last chance” antibiotic family has a similar structure and the same mechanism of action as parent drug vancomycin, which is proved to be an effective binder of Cu(II) ions. However, the potentiometric and spectroscopic studies (UV-visible, CD, NMR) have shown that the modification of the N-terminal structure of the peptide backbone in teicoplanin affects considerably the binding ability towards Cu(II) ions. While vancomycin forms almost instantly the stable 3 N complex species involving the N-terminal and two amide nitrogen donors, in case of teicoplanin only two nitrogen donors derived from the N-terminal amino group and adjacent peptide bond are coordinated to Cu(II) ion within the whole pH range studied. The major factor influencing the binding mode is most likely the structure of the N-terminus of the peptide unit in the antibiotic ligand.     

The isolation of an antimycin A-resistant human cell line

An antimycin A-resistant derivative of the human cell line, D98, has been obtained by selective mutagenesis with N-methyl-N'-nitro-N-nitrosoguanidine. The derivative, designed MA65, is capable of continuous growth in 15 microM antimycin and the resistant phenotype is stable in the absence of selection. MA65 is not cross-resistant to chloramphenicol or triethyl tin. Crude membrane preparations from MA65 after propagation in medium containing antimycin have normal succinate-cytochrome c oxidoreductase activity and the respiratory activity of whole cells continues in the presence of the drug. The mitochondrially synthesized proteins of D98 and MA65 are similar when compared on sodium dodecyl sulphate (SDS), or isoelectric focusing gels, but there is a reproducible difference in the extent of labelling of one band detected by isoelectric focusing. Genetic analysis is consistent with the existence of a cytoplasmically localized determinant conferring resistance.     

Exposed cranial implants--a salvage operation.

We present our rationale for attempting to cover some exposed cranial implants by tissue transfers. We have tried this in 9 patients, and we have had success in 5.     

The spawning seasons of Caribbean reef fishes

Observations are recorded on the time of spawning of 83 species of Caribbean reef fishes. Details of seasonal variations in the percentage of sexually active fishes are given for 35 species. The majority of species spawn mostly when water temperatures are minimal, in February, March and April. The expected biomass of reef fish eggs in the plankton is about twelve times greater in the above mentioned period than in the period from June to December. Normal recruitment to insular fisheries may be very greatly dependent upon the success of parent stocks spawning elsewhere in the Caribbean and the abundance of recruits to a particular area may be dependent upon the speed and direction of the prevailing currents which carry larvae and juveniles to the insular shelves.     

Mycophenolate mofetil versus azathioprine in kidney transplant recipients on steroid-free,low-dose cyclosporine immunosuppression (ATHENA): A pragmatic randomized trial

BackgroundWe compared protection of mycophenolate mofetil (MMF) and azathioprine (AZA) against acute cellular rejection (ACR) and chronic allograft nephropathy (CAN) in kidney transplant recipients on steroid-free, low-dose cyclosporine (CsA) microemulsion maintenance immunosuppression.Methods and findingsATHENA, a pragmatic, prospective, multicenter trial conducted by 6 Italian transplant centers, compared the outcomes of 233 consenting recipients of a first deceased donor kidney transplant induced with low-dose thymoglobulin and basiliximab and randomized to MMF (750 mg twice/day, n = 119) or AZA (75 to 125 mg/day, n = 114) added-on maintenance low-dose CsA microemulsion and 1-week steroid. In patients without acute clinical or subclinical rejections, CsA dose was progressively halved. Primary endpoint was biopsy-proven CAN. Analysis was by intention to treat.Participants were included between June 2007 and July 2012 and followed up to August 2016. Between-group donor and recipient characteristics, donor/recipient mismatches, and follow-up CsA blood levels were similar. During a median (interquartile range (IQR)) follow-up of 47.7 (44.2 to 48.9) months, 29 of 87 biopsied patients on MMF (33.3%) versus 31 of 88 on AZA (35.2%) developed CAN (hazard ratio (HR) [95% confidence interval (CI)]: 1.147 (0.691 to 1.904, p = 0.595). Twenty and 21 patients on MMF versus 34 and 14 on AZA had clinical [HR (95% CI): 0.58 (0.34 to 1.02); p = 0.057) or biopsy-proven subclinical [HR (95% CI): 1.49 (0.76 to 2.92); p = 0.249] ACR, respectively. Combined events [HR (95% CI): 0.85 (0.56 to 1.29); p = 0.438], patient and graft survival, delayed graft function (DGF), 3-year glomerular filtration rate (GFR) [53.8 (40.6;65.7) versus 49.8 (36.8;62.5) mL/min/1.73 m², p = 0.50], and adverse events (AEs) were not significantly different between groups.Chronicity scores other than CAN predict long-term graft outcome. Study limitations include small sample size and unblinded design.ConclusionsIn this study, we found that in deceased donor kidney transplant recipients on low-dose CsA and no steroids, MMF had no significant benefits over AZA. This finding suggests that AZA, due to its lower costs, could safely replace MMF in combination with minimized immunosuppression.Trial registrationClinicalTrials.gov {"type":"clinical-trial","attrs":{"text":"NCT00494741","term_id":"NCT00494741"}}NCT00494741; EUDRACT 2006-005604-14.

Piero Ruggenenti and co-workers study maintenance immunosuppression in deceased-donor kidney transplantation.