Renal failure due to mesangiocapillary glomerulonephritis in pregnancy: use of plasma exchange therapy.

A 20-year-old female became pregnant 4 years after diagnosis of type I mesangiocapillary glomerulonephritis. Despite normal serum creatinine at conception renal function deteriorated during pregnancy. The use of plasmapheresis and albumin substitution as well as antihypertensive therapy enabled the continuation of the pregnancy from 27 weeks' gestation until a healthy infant could be delivered at 33 weeks. However, an abrupt decline in function at delivery did not reverse and the patient remains dialysis dependent. We conclude that plasma exchange therapy with albumin substitution may be of benefit in women with mesangiocapillary glomerulonephritis when renal function has deteriorated in pregnancy. Stabilization of renal function can allow continuation of the pregnancy until greater fetal maturity makes the delivery of a healthy infant more likely. Although plasma exchange is an experimental therapy, in our hands it appears safe for the fetus and maternal complications were limited to minor vascular access problems. The best prognostic marker in this case was the severity of the most recent renal biopsy rather than the level of renal function or hypertension at the start of pregnancy. This contrasts with most reported cases of pregnancy and primary glomerular disease where irreversible deterioration of renal function was uncommon when renal function at the start of pregnancy was only mildly impaired and hypertension well controlled.

Inflammatory bowel disease presenting in pregnancy.

A case of inflammatory bowel disease (IBD) presenting in pregnancy is described. Despite previous reports of severe fulminating disease in this type of patient, this woman did well with an uncomplicated course; she responded to standard medical therapy and there were no fetal complications. IBD should not be a contraindication to pregnancy unless the disease is poorly controlled. Pregnancy does not increase the risk of relapse of IBD, but should this occur it is more likely in the first trimester or in the postpartum period. Treatment of IBD in pregnancy should be much the same as in the nonpregnant woman. Corticosteroids and sulphasalazine are safe in pregnancy and are the mainstays of medical treatment. Surgery should proceed for the usual indications of toxic megacolon and perforation. In the group requiring surgery fetal mortality is considerable but the maternal outcome is improving. Patients presenting with IBD in pregnancy may have more severe disease but recent reports suggest that the outcome for mother and infant in this group is improving.

The antioxidant responsive element. Activation by oxidative stress and identification of the DNA consensus sequence required for functional activity.

We have characterized further the antioxidant responsive element (ARE) identified in the 5'-flanking region of the rat glutathione S-transferase Ya subunit gene and the NAD(P)H:quinone reductase gene by mutational and deletion analyses. Our data suggest that the sequence, 5'-puGTGACNNNGC-3' 3'-pyCACTGNNNCG-5' where N is any nucleotide, represents the core sequence of the ARE required for transcriptional activation by phenolic antioxidants and metabolizable planar aromatic compounds (e.g. beta-naphthoflavone and 3-methylcholanthrene). We also have found that the ARE is responsive to hydrogen peroxide and phenolic antioxidants that undergo redox cycling. These latter data suggest that the ARE is responsive to reactive oxygen species and thus may represent part of a signal transduction pathway that allow eukaryotic cells to sense and respond to oxidative stress.

Delirium in an elderly woman possibly associated with administration of misoprostol.

Misoprostol has been associated with adverse reactions, including gastrointestinal symptoms, gynecologic problems, and headache. Changes in mental status, however, have not been reported. We present a case in which an 89-year-old woman in a long-term care facility became confused after the initiation of misoprostol therapy. The patient's change in mental status was first reported nine days after the initiation of therapy. Her delirium significantly improved after misoprostol was discontinued and her mental status returned to normal within a week. Because no other factors related to this patient changed significantly, the delirium experienced by this patient possibly resulted from misoprostol therapy.

Isolation and characterization of the rat glutathione S-transferase Yb1 subunit gene.

We have isolated and characterized a rat liver glutathione S-transferase Yb1 subunit gene. DNA sequence analysis of the Yb1 subunit gene indicates that it comprises eight exons separated by seven introns and spans approximately 5.0 kb. The transcription initiation site has been mapped by primer extension experiments. Transcription begins at a guanine residue 29 nucleotides downstream from a "TATA" sequence. The DNA sequences of all exons and some introns share significant sequence identity with the corresponding exons and introns in the Yb2 subunit gene characterized by Tu and co-workers [J. Biol. Chem. 263, 11389-11395 (1988)]. The isolation and characterization of the glutathione S-transferase Yb1 gene will allow for a detailed analysis of regulatory elements required for transcriptional regulation of this gene.

Rat liver NAD(P)H: Quinone reductase. Regulation of quinone reductase gene expression by planar aromatic compounds and determination of the exon structure of the quinone reductase structural gene.

We have determined the effect of beta-naphthoflavone and the azo dye, sudan III, on the level of quinone reductase mRNA in a responsive rat hepatoma cell line. Our data indicate that both of these planar aromatic compounds produce a 4-5-fold elevation in quinone reductase mRNA. The induction of quinone reductase mRNA can be blocked by cycloheximide, suggesting a requirement for ongoing protein synthesis in the induction process. We have determined the exon structure of the quinone reductase structural gene. The gene is separated into six exons by five introns. A "TATA" box is located 29 base pairs upstream from the transcription initiation site. A "CCAAT" sequence is found at position -129, and an inverted "GC" box is located at position -78. Quinone reductase promoter-chlor-amphenicol acetyltransferase fusion genes containing different lengths of the 5'-flanking region were transfected into rat and human hepatoma cells. Treatment of the transfected cells with beta-naphthoflavone or sudan III resulted in a 4-5-fold elevation in chloramphenicol acetyltransferase activity. These data suggest the presence of a cis-acting regulatory element(s) in the 5'-flanking region of the quinone reductase structural gene which regulates inducible expression.

Erythromycin-induced digoxin toxicity.

The potential interaction between certain antibiotics and digoxin has been discussed in the literature; however, few cases of actual erythromycin-induced digoxin toxicity have been reported. We present a case in which an 86-year-old woman who was taking digoxin 0.25 mg/d developed probably digoxin toxicity after the administration of erythromycin for the treatment of otitis media and streptococcal pharyngitis. Her digoxin concentration increased from a trough of 1.9 to 5.1 nmol/L six days after the erythromycin was started. Digoxin was discontinued and restarted approximately six weeks later when the patient's atrial fibrillation and congestive heart failure recurred. Her digoxin dose at this time was 0.125 mg/d and resulted in steady-state concentrations of 1.2, 1.4, and 1.2 nmol/L over the next year. Erythromycin inhibition of Eubacterium lentum, which converts digoxin into digoxin-reduction products in the gut, is the proposed mechanism of this interaction.

Lack of theophylline assay interference from pentoxifylline and its metabolites.

Pentoxifylline, a hemorheologic agent, and its metabolites are structurally similar to theophylline and other xanthines; therefore, they have the potential to interfere with serum assays for theophylline. Any false elevation of theophylline serum concentrations could have a significant impact on drug therapy decisions. Serum was obtained from six elderly subjects who had been taking 400 mg of pentoxifylline three times daily for at least six months. A serum assay using the TDx fluorescence polarization immunoassay failed to detect any measurable amount of theophylline. Normal doses of pentoxifylline and the resulting metabolites do not appear to interfere with the TDx method of serum assay for theophylline.

Drug sensitivity in older adults: the role of physiologic and pharmacokinetic factors.

Age-related changes in physiology and pharmacokinetics (how drugs are used in the body) lead to increased drug sensitivity and potentially harmful drug effects. This report addresses the heightened sensitivity to drug effects seen in older adults. The first section of the report presents three examples of physiologic decline: a) decreased plasma protein binding affects drug distribution, b) declining liver function affects drug metabolism, and c) impaired kidney function delays drug elimination. The next section illustrates by example the risks associated with altered physiology: a) decline in plasma protein binding may result in an intensified effect of the drug Phenytoin, b) altered liver function increases the sedative effects of Diazepam, and c) declining kidney function results in accumulation of the drug Gentamicin, where toxic effects include kidney failure and deafness. The last section is a discussion of some broad considerations for geriatric pharmacology. Adverse drug reactions can largely be avoided by carefully weighing the needs and clinical status of older persons on an individual basis both prior to and throughout the course of a given drug therapy.

A board searches for a CEO.

The board of directors of Mercy Hospital, Urbana, IL, recently chose to conduct its own search for a new CEO. Research on other self-directed searchers, delineation of the hospital's needs, and development of criteria for the CEO led to the screening of candidates. Both the board and the new CEO believe that the selection method--a time- and energy-consuming one--contributed greatly to the current mutual satisfaction.