Antibacterials. synthesis and structure-activity studies of 3-aryl-2-oxooxazolidines. 4. Multiply-substituted aryl derivatives.

The synthesis and structure-activity relationship (SAR) studies of the effect of different polysubstitution patterns in the aromatic ring of 5-(acetamidomethyl)oxazolidinone antibacterials (I) on antibacterial activity are presented. Compounds I were prepared by the six-step synthesis described previously (Gregory, W. A.; et al. J. Med. Chem. [formula: see text] 1989, 32, 1673), electrophilic aromatic substitution reactions of 3-substituted compounds, and functional-group interchange reactions of 3,4-disubstituted compounds. Antibacterial evaluation of compounds I against Staphylococcus aureus and Enterococcus faecalis gave the following results. The 2,4- and 2,5-disubstituted derivatives have weak or no antibacterial activity. Antibacterial activities of 3,4-disubstituted compounds are comparable to those of the 4-monosubstituted analogues for small 3-substituents (smaller than Br), but decline rapidly for larger 3-substituents. 3,4-Annulated derivatives are comparable in activity to their open-chain analogues. 3,5-Disubstituted and 3,4,5- and 2,4,6-trisubstituted derivatives are devoid of antibacterial activity.     

Anesthesia and/or Sedation for Pulsed Dye Laser Therapy

One of the most exciting developments in pediatric dermatology has been the use of the flashlamp-pumped, 585-nm, pulsed dye laser for treatment of vascular birthmarks. In many cases the results are miraculous. The increase in self-esteem and happiness of many children and adolescents has been overwhelming; for some, depression has been lifted, stuttering has ceased, social involvement has increased, and antidepressants have been discontinued. There are many success stories to tell.
Despite the remarkable effects of the pulsed dye laser and the medical and psychosocial indications for its use, the issue of pain control remains significant. We have no perfect outpatient pediatric anesthetic. Most methods carry either some risk or, if not hazardous, often are not very effective for controlling pain. Needless to say, a diversity of opinions exist on how to manage discomfort from this treatment modality. Therefore, we thought it would be useful to share the experiences and opinions of several dermatologists who have extensive experience with the pulsed dye laser.     

The haemodynamic effects of propofol and thiopentone for induction of caesarean section

Forty Chinese women for elective caesarean section received either propofol 2 mg.kg-1 or thiopentone 4 mg.kg-1 for induction of general anaesthesia. Systolic, mean and diastolic arterial pressures and heart rate were recorded non-invasively every minute for ten minutes. Post-induction arterial pressures were similar to pre-induction values with no differences between thiopentone and propofol. Following intubation, the rise in systolic arterial pressure was greater in the thiopentone group, 32.1 mmHg (SD 23.7) compared with the propofol group, 17.4 mmHg (SD 23.8), (P less than 0.05). In the thiopentone group, arterial pressures were slower in returning to baseline values. Heart rate was initially elevated in both groups to the same degree. At caesarean section, induction with propofol causes less variation in arterial pressure than thiopentone. Hypotension is probably prevented by the coincident stimulus of rapid sequence induction. Neonatal Apgar scores were similar between the two groups.     

Inflammatory mediators and the destruction of bone

Bone is remodelled by the coordinated actions of osteoclasts and osteoblasts. Cellular remodelling occurs in discrete packets of bone, and is regulated by local cytokines produced in the environment of the remodelling cells. These cytokines are secreted by immune cells and by bone cells. In addition, some growth regulatory factors are incorporated into the noncollagenous bone matrix and are released in an active form when bone is stimulated to resorb. Complex interactions between these cytokines and their target cells are responsible for the normal delicate balance between bone resorption and bone formation, and disorders of bone loss are due to imbalances between the rates of resorption and formation.     

The emergency physician and patient confidentiality: A review

Confidentiality is a promise rooted in tradition, law andmedical ethics. Emergency physicians treat a variety of patients to whom confidentiality is of vital importance: employees, celebrities, victims of violence or disaster, minors, students, criminals, drug abusers, and patients with STDs. EDs should develop methods of ensuring confidentiality for all patients.³⁴Although confidentiality is an important principle thatshould be respected and guarded, it is not absolute. Various laws mandate disclosure of certain patient information; in addition, an overriding moral duty may occasionally require, a breach of confidentiality. As Beauchamp and Childress noted, “the therapeutic role may sometimes have to yield to ones role as citizen and as protector of the interests of others”.¹⁹ In general, however, circumstances requiring a breach of confidentiality are rare.     

Second-messenger pathways involved in the regulation of survival in germinal-centre B cells and in Burkitt lymphoma lines.

Spontaneous apoptosis in germinal-centre (GC) B cells can be prevented by treatment with anti-immunoglobulin (Ig). By contrast, susceptible group-I Burkitt lymphoma (BL) cells can be driven to apoptosis by anti-Ig. The second-messenger pathways involved in the regulation of apoptosis in GC B lymphocytes and in BL cell lines were studied using pharmacological agonists or inhibitors of intracellular calcium ([Ca2+]i) and protein kinase C (PKC). Anti-Ig was found to mobilize Ca2+ in group-I cells. Pre-incubation with the Ca2+ chelator EGTA partially reduced apoptosis induced by anti-Ig or by Ca2+ ionophore in group-I BL cells. Activation of PKC with phorbol ester reduced such Ca(2+)-driven programmed cell death (PCD) to control levels of apoptosis. Apoptosis in group-I BL cell lines could also be triggered by the kinase inhibitors staurosporine and Ro-31-8220 at concentrations selective for PKC activity. Expression of the bcl-2 protein in BL group-I cells following gene transfer affords protection from apoptosis induced by ionomycin or anti-Ig. In the present study, bcl-2 was additionally found to protect from apoptosis driven by staurosporine. The high levels of spontaneous apoptosis exhibited by normal GC B cells were reduced, but not abrogated, by co-culture with phorbol ester. These results indicate that, in group-I BL cells, imbalance in the phosphoinositide pathway of signalling, in favour of [Ca2+]i and away from PKC, results in apoptosis: constitutive phosphorylation of key proteins by PKC may therefore suppress apoptosis in BL as well as in GC B cells.     

cAMP production via the adenylyl cyclase pathway is reduced in RCS rat RPE.

cAMP production was investigated in retinal pigment epithelium (RPE) cells isolated from normal rats and from rats with an inherited retinal dystrophy (Rdy/p+). In normal RPE cells, 5'-[N-Ethylcarboxamido]-adenosine (A2 receptors) produced a fivefold increase in the level of cyclic adenosine monophosphate (cAMP) over basal levels. However, only a onefold increase in cAMP was observed in dystrophic cells. cAMP production by prostaglandins E1 and E2 (prostaglandin receptors) in dystrophic RPE cells was only 29-38% of the level observed in normal cells. Direct stimulation of adenylyl cyclase by 10 mumol/l forskolin increased cAMP levels in normal RPE cells by 90 fold over basal, but only by sixfold in the dystrophic cells. These data suggest there may be a defect in the adenylyl cyclase signaling pathway in dystrophic RPE cells.