Coronary artery bypass surgery during pregnancy.

A 32-year-old woman, in the 22nd week of pregnancy, underwent emergency coronary artery bypass grafting to the left anterior descending artery (LAD). She had suffered an acute myocardial infarction 10 days previously, and continued to suffer from intractable angina pectoris afterwards. Cardiac catheterization revealed spontaneous dissection of the LAD. The left internal mammary artery was used to bypass the LAD, and the operation was performed on a beating heart without the use of cardiopulmonary bypass. The patient's recovery was uneventful, and ultrasound examination and pulse monitoring of the fetus were both normal. She subsequently gave birth to a healthy term baby. To our knowledge this is the second report of coronary artery bypass surgery performed successfully in a pregnant woman. We believe the unique surgical approach avoided the risk of cardiopulmonary bypass to the fetus and placenta.

Tumoricidal and immunomodulatory activities of drugs and implications for therapy of mice bearing a late stage MOPC-315 plasmacytoma.

The effectiveness of a relatively low dose of cyclophosphamide (15 mg/kg CY), melphalan (2.5 mg/kg L-PAM) or the monofunctional form of CY (150 mg/kg MoCY) for the cure of mice bearing a large primary s.c. MOPC-315 tumor and extensive metastases has been shown to be dependent on the cooperation of the drugs' tumoricidal activity with T-cell-dependent antitumor immunity, the latter facilitated by the drug's immunomodulatory activity. Here, we have compared the curative effectiveness of three additional drugs: methyl nitrosourea (MNU), hydroxyurea (OH-urea) and bis-chloroethyl nitrosourea (BCNU). Among these drugs, only a relatively low dose of BCNU (15-20 mg/kg) was effective in curing most mice (85%) bearing a large, late stage tumor. A higher dose of BCNU (40 mg/kg, LD10) was much less effective. After an optimal dose of BCNU, the proliferative capacity of the tumor cells 24 h after therapy was reduced by greater than 97%. However, viable tumorigenic cells were still present in the primary tumor and enhanced T-cell-dependent antitumor immunity was necessary for their eradication. The cured mice were resistant to tumor rechallenge. When a low curative dose of L-PAM was followed by OH-urea, the therapeutic effectiveness was not affected, but when this dose of L-PAM was followed by a high nontoxic dose of MNU (100-150 mg/kg), the therapeutic effectiveness was diminished even though MNU was highly tumoricidal (i.e. greater than 99% inhibition of proliferative activity). Thus, BCNU appears to be similar to CY, L-PAM and MoCY in its mechanism of MOPC-315 tumor eradication. The alkylating activity of CY, L-PAM, MoCY and BCNU appears to be critical for their combined tumoricidal and immunomodulatory effects. Since BCNU is the simplest of these four drugs with respect to metabolic pathway, a further study with BCNU and related constructs may shed some light on the biochemical mechanisms of their mode of action. At least one reason for the ineffectiveness of OH-urea or MNU at either low or nontoxic high doses was poor tumoricidal or immunomodulatory activity, respectively. Thus, it seems important to consider both the tumoricidal and immunomodulatory activities of drugs when developing regimens for effective chemotherapy.

The effect of changes in arterial CO2 tension on plasma lidocaine concentration.

The authors studied the effect of changes in arterial carbon dioxide tension on plasma lidocaine concentrations during a constant lidocaine infusion in eight healthy volunteers. With a PaCO2 of 41.4 +/- 0.9 mmHg (mean +/- SE), total plasma lidocaine concentrations were 3.97 +/- 0.20 microgram X ml-1. There was no significant change associated with hypercarbia (PaCO2 = 55.7 +/- 1.5 mmHg, lidocaine = 3.93 +/- 0.18 microgram X ml-1) or hypocarbia (PaCO2 = 19.5 +/- 1.4 mmHg, lidocaine = 4.29 +/- 0.25 microgram X ml-1), despite the known effects of changes in CO2 tension on hepatic blood flow and lidocaine protein binding. During hypercarbia, plasma lidocaine binding decreases while total plasma lidocaine remains essentially constant; therefore, increased CO2 tensions could cause toxicity if total lidocaine concentrations were in the high therapeutic range (5 micrograms X ml-1). Four subjects experienced transient symptoms of mild lidocaine toxicity during acute increases in carbon dioxide tension.

Evaluation of the Ohmeda 3700 pulse oximeter: steady-state and transient response characteristics.

The authors determined the accuracy of the Ohmeda 3700 (version J) pulse oximeter in healthy volunteers rendered hypoxic (SaO2 from 60-98%) by breathing mixtures of O2 in N2. When equipped with an ear probe, the pulse oximeter reading (y) reliably predicted arterial saturation (x) under steady-state conditions (y = 1.05x - 4.66, r = 0.98) as well as when oxygen saturation was rapidly decreasing (y = 1.05x - 6.38, r = 0.96). Conversely, when equipped with a finger probe, the oximeter tended to significantly underestimate steady-state arterial saturation (y = 1.21x - 19.1, r = 0.98, P less than 0.001). In response to this information, the manufacturer modified the oximeter's software (version XJ1), resulting in improved agreement between oximeter readings and arterial values (y = 0.96x + 4.59, r = 0.99). Despite the close correlation between steady-state oximeter readings and arterial saturation, the 99% prediction limits for both the ear and finger probes (version XJ1) were +/- 8%. Finger probe readings did not reliably reflect radial arterial oxygenation during rapid desaturation (y = 0.55x + 45.2, r = 0.78). This may be related to the time required to "arterialize" the blood in the finger; during acute resaturation, we found that the ear- to finger-probe delay was 24.0 +/- 2.3 s (means +/- SE, P less than 0.001).

Identification and characterization of prostaglandin-binding components in rat ileum.

A specific prostaglandin E2 (PGE2) binding component was identified in the membrane fractions of rat ileum. Two ligands, 3H-PGE2 and 14C-PGE2, competed for the binding sites in crude homogenates of ileum during competition experiments, demonstrating the presence of a limited number of binding sites. There was enhancement in the specific 3H-PGE2 binding to particulate fractions over control when endogenous prostaglandin synthesis was blocked by the administration of indomethacin to rats prior to sacrifice. The specific prostaglandin-binding protein was purified by a combination of [NH4]2SO4 fractionation and Sephacryl S-200 column chromatographic techniques, and shown to be active after these biochemical steps.

Glucocorticoids and lactation. In vitro metabolism of glucocorticoids by rat mammary glands.

In view of: 1. the extensive in vitro 21-acylation of [3H]corticosterone by rat mammary glands, especially during lactation; 2. the accumulation of 21-acyl [3H]corticosterone as the predominant form of the hormone in the alveolar nuclear fraction with which it is strongly associated; 3. the results of a systematic study of the influence of acylation per se of corticosterone and dexamethasone on their binding affinities for specific glucocorticoid-binding proteins; and 4. the extensive metabolic acylation, similarly, of adrenocortical hormones other than corticosterone, it is suggested that the acylation of glucocorticoid by the mammary gland may serve to modulate the biological action of the hormone on this target organ, and indirectly influence the flow of glucocorticoid from plasma to milk.

The levels of corticosterone-binding proteins in rat milk and coincidental serum, and the dissociation rates of the corticosterone.protein complexes.

The corticosterone-binding protein present in rat whey was further characterized by determining, with the aid of a dextran-coated charcoal procedure, the apparent rate of dissociation of the corticosterone.protein complex. The half-time values for the dissociation of the corticosterone.protein complexes in rat whey and serum were compared and found to be identical, i.e. 23 min at 0 C, when the measurements were made over a period of 40 min. The possible presence in small amounts of a corticosterone.protein complex in whey with the much slower dissociation rate characteristic of mammary glucocorticoid receptor could not be detected even when the dissociation was followed over a much longer period. The charcoal adsorption method also provided independent estimates of the molar concentrations of the corticosterone-binding proteins in rat serum and whey. The mean concentration of corticosterone-binding protein in whey was found to be 15% of that in coincidental serum during early lactation. The serum levels of corticosterone-binding protein decline markedly at parturition and then rise from day 2 to day 6 of lactation in rats with small litters. The results of this and a previous study suggest that the corticosterone-binding protein in whey is probably derived from that in serum. The mode of transport of the corticosterone-binding protein from the bloodstream across the mammary epithelium into milk as well as the concentrations of the corticosterone-binding proteins in serum and whey may be factors influencing the uptake of the glucocorticoid by its target cells.

Isolation and characterization of four peptide hydrolases from the brush border of rat intestinal mucosa.

Peptide hydrolases (EC 3.4.-.-) were solubilized from purified brush borders of rat intestinal mucosa by papain digestion. Three peptide hydrolases, I, II, and III, with different substrate specificities were isolated by means of DEAE-cellulose chromatography and preparative acrylamide gel electrophoresis. On repeat preparative acrylamide gel electrophoresis under slightly different conditions, enzyme II was resolved into two proteins, IIa and IIb, with vary similar, possibly identical, substrate specificities. Efforts to discover additional brush border peptide hydrolases revealed none. Studies using more than 50 substrates showed that enzyme I was most active against Met-Met, Met-Ala, and Met-Phe while enzyme II was most active against Phe-Gly, Phe-Ser, and Leu-Gly-Gly, and enzyme III most rapidly hydrolyzed Gly-Leu, Leu-Gly, and Met-Gly. Efforts to discover substrates which are highly discriminating for each enzyme were partly successful. Thus, a number of substrates including leucine amide, leucyl-beta-naphthylamide and Phe-Asp were hydrolyzed almost exclusively (95% or more) by enzyme II while Gly-Leu was similarly specific for enzyme III. No substrate highly discriminating for enzyme I was discovered. Ion-exchange chromatography resulted in increases in specific activity of 10- and 120-fold for enzymes II and III, respectively. By sequential use of ion-exchange chromatography and preparative acrylamide gel electrophoresis, each of the three enzymes was partially purified to the point that they were free of contaminating disaccharidases and enzymes I and II gave single dense bands on analytical acrylamide gel electrophoresis while enzyme III gave a single dense band plus one additional faint protein band. Under appropriate conditions, analytical gel electrophoresis also resolved enzyme II into two bands with enzyme activity. The three enzymes were isolated from intestinal brush borders of germ-free rats indicating that none of the enzymes is of bacterial origin. With Phe-Gly as substrate, pH optima for enzymes I, II, and III were 8.0, 8.0, and 8.5, respectively. Molecular weights determined by gel filtration were 283 000, 284 000, and 134 000, respectively. Studies of activation by metal ions and inhibition by metal ion chelators suggested that the activity of each of the enzymes is dependent on a relatively tightly bound metal cofactor. Peptide hydrolases of the intestinal mucosa play an essential role in protein digestion. The studies presented here help to clarify the total number and substrate specificities of these enzymes in the rat brush border.