To determine if intravenous cyclophosphamide (IV-C) causes an excess of cervical dysplasia and/or cancer in systemic lupus erythematosus (SLE) patients, a retrospective review was conducted. Patients with SLE who received IV-C between 1988-98 (study group) were compared with a group of SLE patients who had not received IV-C (control group). Of the 79 IV-C-treated SLE patients identified, we excluded 18 because of absence of pertinent data. We found 10 cases of cervical dysplasia in the remaining 61 patients, compared to 2 in 49 non-exposed patients (P<0.04). Comparison of the two groups revealed no difference in: mean years of disease duration, months of follow-up and age. The non-exposed patients were more likely to be on estrogen and hydroxychloroquine but less often on steroids and azathioprine. The study group with and without dysplasia were assessed; we found no difference in the mean, or total IV-C dose, smoking and estrogen use. There was a significant decrease in time to dysplasia in those, given IV-C, with previous dysplasia compared to those without. These preliminary data suggests that IV-C causes an increased number of abnormal Papanicolaou (Pap) smears in SLE patients, particularly those with previous dysplasia.

SUMMARY. We compared alterations of pulmonary hemodynamics with the plasma concentrations of thromboxane B2, 6-keto-PGF la , and PGF20 following intravenous Escherichia coli endotoxin infusion (1 /ig/kg) in three groups of awake sheep. Group 1 served as controls. The animals in group 2 were rendered leukopenic (<1000 WBC/mm 3 ) by nitrogen mustard treatment. Group 3 received ibuprofen (12 mg/kg) one hour before endotoxin. After endotoxin infusion, the pulmonary artery pressure (PAP) and pulmonary vascular resistance (PVR) increased markedly in groups 1 and 2; however, in group 2, the increases of PAP and PVR were half those of group 1. In group 3, only minimal increases of PAP and PVR were measured. In groups 1 and 2, the rise of PAP correlated with an increased plasma TxB2 concentration at 30 minutes after endotoxin (group 1-from 0.5 ± 0.04 to 16 ± 3 ng/ml; group 2-from 0.32 ± 0.1 to 5.6 ± 1.2 ng/ml). The peak plasma concentrations of TXB2 were significantly less in group 2 than in group 1. In the sheep in both groups 1 and 2, 20 minutes after endotoxin infusion, consistent pulmonary artery to aortic increases of TxB2 were measured (group 1 A3.7 ± 1.1 ng/ml and group 2 A3.1 ± 0.7 ng/ml). In group 3, plasma TxB2 increased slightly to 240 ± 80 pg/ml. Plasma concentrations of 6-keto-PGFi,, increased in group 1 from 0.06 ± 0.01 to 0.59 ± 0.12 ng/ml and in group 2 from 0.06 ± 0.01 to 0.58 ± 0.12 ng/ml. In group 3 sheep, plasma concentrations of 6-keto-PGF ]o remained below the detection limit of the radioimmunoassay. TxA2 is a likely mediator of endotoxin-induced pulmonary hypertension and is generated in large quantities by cells in the lung. Circulating leukocytes contribute substantially to the peak plasma concentrations of thromboxane following endotoxin infusion. (Circ Res 50:688-694, 1982)

To investigate the effects of isometric tension development on myocardial protein metabolism, 14 C-phenylalanine incorporation into protein was studied in the isolated rabbit right ventricular papillary muscle. Amino acid incorporation was linear for 6 hours in resting muscles and was totally inhibited by ICHM cycloheximide and ICHM puromycin. Phenylalanine incorporation into total protein was unaltered by 90 minutes of isometric tension development at peak tension at stimulation rates of 30, 50, or 100/min. Significant increases were noted in muscles stimulated at 50 and 100/min for 180 minutes (P < 0.01). Electrical stimulation, in the absence of isometric tension development, was not responsible for this effect. Passive stretch also appeared to stimulate incorporation, although to a lesser degree than did active tension development. The specific activities of the intracellular phenylalanine pools were identical in control and stimulated muscles. Alpha-aminoisobutyric acid was used to evaluate the effect of tension development on myocardial amino acid transport. Enhanced transport was noted in muscles stimulated isometrically at 30, 50, or 100/min at peak tension. The increased transport ratios could not be solely attributed to active tension development since passive stretch resulted in comparable changes. This study indicates that both passive stretch and tension development are important in regulating myocardial protein synthesis. KEY WORDSpassive stretch mechanochemical coupling alpha-aminoisobutyric acid phenylalanine cardiac work• The heart will hypertrophy when it is exposed to a sustained increase in mechanical work (1-3). This is a positive adaptation which permits the myocardium to meet increased work demands, albeit with a probable decrease in efficiency (4, 5). Alterations in protein and nucleic acid metabolism have been described in many investigations

A B S T R A C T Cyclooxygenase inhibitors prevent the pulmonary vasomotor changes in response to low-dose endotoxin. We, therefore, explored the role of two highly vasoactive prostanoids, thromboxane A2, a vasoconstrictor, and prostacyclin, a vasodilator, in the transient pulmonary vasoconstriction and subsequent loss of alveolar hypoxis vasoconstriction (AHPV) that follows endotoxin. AHPV was tested in the dog with a double-lumened endotracheal tube allowing ventilation of one lung with nitrogen as a hypoxic challenge while the other lung was ventilated with oxygen to maintain systemic oxygenation. Relative distribution of perfusion to the two lungs was assessed with intravenous 133Xe and external scintillation detectors. The stable metabolites of thromboxane and prostacyclin, i.e., thromboxane B2 and 6-keto-prostaglandin F1,a were measured in plasma with radioimmunoassay. 15 ,ug/kg i.v. ofendotoxin induced no rise in pulmonary vascular resistance (PVR), but prevented AHPV so that the initial 33% (±2 SEM) decrease in perfusion to the hypoxic lung became only a 2% (± 1) decrease. Circulating levels of thromboxane and prostacyclin concurrently rose (P < 0.01) from nondetectable levels to 380 pg/ml (±40) and 360 pg/ml (±130). 150 ,g/kg of endotoxin induced a transient rise in PVR from 4.09 to 9.00 mm Hg/liter per min in association (r = 0.89, P < 0.01) with a sharp rise in thromboxane levels to 4,460 pg/ml (± 1,350) whereas prostacyclin levels were elevated less markedly to 550 pg/ml (+400). Prostaglandin F2<,X another vasoconstrictor, was not elevated. 30 min after endotoxin when PVR was again base line and AHPV lost, thromboxane fell significantly (P < 0.01) to 2,200 pg/ml (± 1,100) whereas prostacyclin remained elevated at 360 pg/ml (±135), a level similar to that seen when 15 ,g/kg of endotoxin induced Dr. Peterson is an Established Investigator ofthe American Heart Association.