Effect of conjugated estrogens on platelet function and prostacyclin generation in CRF

In a double-blind, randomized, placebo-controlled cross-over study, we investigated in seven patients with chronic renal failure the effect of conjugated estrogens (0.6 mg/kg/day for 5 days) on template bleeding time and on thromboxane A2 (TxA2), beta-thromboglobulin (beta-TG) and prostacyclin (PGI2) concentrations in blood emerging from the template bleeding time incisions. Administration of conjugated estrogens resulted in a significant shortening of the bleeding time in six out of seven patients with a maximum effect 7 and/or 14 days following treatment. Both TxA2 (measured as thromboxane B2, TxB2) and beta-TG release in bleeding time blood were significantly higher following administration of conjugated estrogens as compared to placebo administration. No difference was seen in endothelial PGI2 (measured as 6-keto-prostaglandin F1 alpha) formation when patients were treated with conjugated estrogens as compared to placebo administration over the 28 day observation period. We conclude that in patients with chronic renal failure, infusion of conjugated estrogens results in a significant shortening of the bleeding time together with an increase in platelet reactivity, as indicated by an increase of TxA2 and beta-TG concentration in the microvasculature. No effect was seen on PGI2 production, thereby excluding a major effect on vascular prostaglandin metabolism.     

Scotopic stimulus/response relations of the B-wave of the electroretinogram

Scotopic b-wave stimulus/response (S/R) functions are abnormal in several human retinal degenerative disorders. However, the mechanisms by which diseases affect the S/R parameters are not yet fully known. Three experiments were done to simulate functional pathologies known to occur in retinal degenerations: 1) attenuated sensitivity of retinal units, 2) loss of rhodopsin, 3) loss of sensitivity with little or no loss of rhodopsin. None of the experimental perturbations of normal function replicated the pattern of S/R abnormalities caused by retinal degenerations. Thus, in the retinal degenerative disorders intrinsic abnormalities of cellular processing must affect the organization of distal retinal function indexed by the b-wave.     

Withdrawal of bromocriptine after long-term therapy for macroprolactinomas; effect on plasma prolactin and tumour size

The present study describes the effect on plasma prolactin values and tumour size of bromocriptine withdrawal in 12 patients who had been treated for macroprolactinomas for a period of 3.5-7 (mean 4.9) years. Pretreatment plasma prolactin values ranged from 12,000 to 210,000 (mean: 66,000) mU/l. Immediately before bromocriptine withdrawal plasma prolactin values were in the normal range (less than 350 mU/l for men; less than 450 mU/l for women). Bromocriptine treatment was associated with tumour reduction in all cases. The following observations were made upon withdrawal of bromocriptine: (1) In 11 patients hyperprolactinaemia redeveloped although plasma prolactin levels remained below 600 mU/l in two of these patients during a follow-up period of 1 year. In the other nine patients bromocriptine treatment was reinstituted after 4-12 weeks. (2) Hyperprolactinaemia was associated with tumour reexpansion in one case and increased density of the tumour in two cases. (3) In one patient plasma prolactin remained undetectable during a follow-up period of 1 year and no tumour re-expansion was found. It is concluded that tumour regrowth is uncommon and of small extent after cessation of long-term bromocriptine treatment for macroprolactinomas.     

Phase II trial of gallium nitrate,amonafide and teniposide in metastatic non-small cell lung cancer

Summary Fifty-five patients with metastatic non-small cell lung cancer (NSCLC) were entered into this phase II randomized study for evaluating three new agents: gallium nitrate, amonafide and teniposide. The patients had to have ECOG performance status 0 or 1, no prior chemotherapy, and adequate hematological, hepatic and renal functions. Forty-seven patients were eligible and evaluable. Fourteen were randomized to receive gallium nitrate, 18 to amonafide and 15 to teniposide. Seventy-four percent of eligible patients were male. The majority of patients (89%) had an ECOG performance status 1. ECOG grade 4 toxicity occurred twice in patients on gallium nitrate, seven times on amonafide and 18 times on teniposide. The cause of death was attributed to amonafide in one patient (from sepsis) and to teniposide in two patients (due to infection and leukopenia). There was no objective response in all the patients entered. The overall survival times ranged from 2 weeks to 156 weeks with a median of 23 weeks. There were no survival differences among the three treatment arms. We conclude that gallium nitrate, amonafide and teniposide are inactive in metastatic NSCLC and do not warrant any further testing in this disease.The contents of this study is solely the responsibility of the authors and does not necessarily represent the official views of the National Cancer Institute.     

Adenoid cystic carcinoma: DNA as a prognostic indicator

A retrospective study was performed on 20 patients with adenoid cystic carcinomas of major salivary glands to see if DNA. patterns correlated with their prognoses. Fourteen tumors were found to be DNA. diploid; 6 were DNA aneuploid. Histologically, all DNA-aneu-ploid tumors had solid components, compared with only 5 of the DNA-diploid tumors. All of the DNA-aneuploid tumors recurred, in contrast to only 2 of the DNA-diploid tumors; the difference was highly significant (P<0.001). All of the patients with no recurrences had DNA-diploid tumors. In our study, DNA measurements of adenoid cystic carcinomas gave statistically significant information about prognosis and correlated to histological grading. We propose that evaluation of DNA content may be performed before planning the treatment of adenoid cystic carcinomas.     

Application of a 3D volume 19FMR imaging protocol for mapping oxygen tension (pO2) in perfluorocarbons at low field

A limited flip angle gradient-echo 3D volume acquisition imaging protocol for mapping partial pressure of oxygen (pO₂) in perfluorocarbon compounds (PFCs) at low field (0.14 T) is presented. The pO₂ measurement method is based on the paramagnetic effect of dissolved molecular oxygen (O₂) which reduces the PFC ¹⁹F T_1? Specific objectives related to imaging of PFCs through use of the protocol include improved image signal-to-noise characteristics and elimination of ¹⁹F chemical shift artifacts. A parametric Wiener deconvolution filtering algorithm is used for suppression of ¹⁹F chemical shift artifacts. Application of the protocol is illustrated in a series of calculated pO₂ maps of a gas equilibrated, multi-chamber phantom containing perfluorotributylamine (FC-43). The utility of the protocol is demonstrated in vivo through images of a commercially available perfluorocarbon based blood substitute emulsion containing FC-43 sequestered in the liver and spleen of a rat.     

Ascending Aortic Extension for Right Pulmonary Artery Stenosis Associated With Ventricular-to-Pulmonary Artery Conduit Replacement

A bstract Background : Ventricular-to-pulmonary artery conduits in growing patients with congenital heart disease will require replacement from time to time due to somatic growth, neointimal hyperplasia, and pulmonary artery stenosis. The purpose of this article is to review our experience with ascending aortic extension for significant long-segment pulmonary artery stenosis in patients undergoing reoperation for right ventricular-to-pulmonary artery conduit replacement. Methods : From 1989 to 1997, 8 patients had aortic transection, right pulmonary artery augmentation arterioplasty, and aortic interposition graft (Hemashield in 7 and Gore-tex in 1) in association with right ventricular-to-pulmonary artery conduit replacement in 7 patients and completion Fontan operation in 1 patient. Aortic cross-clamp time was 90 ± 34 minutes, and the cardiopulmonary bypass time was 205 ± 37 minutes. Results : All patients survived. In those 7 patients who had conduit replacement, the RV/LV ratio declined from 0.78 ± 0.15 to 0.45 ±; 0.05 postoperatively (P < 0.05). Average length of stay was 8.9 ± 7.2 days. Follow-up range is 18 months to 8 years (mean 4 years). Two complications included cardiac transplantation for pre-existing poor left ventricular function and accelerated conduit stenosis leading to conduit re-replacement. Conclusion : Ascending aortic extension facilitates long-segment pulmonary artery augmentation arterioplasty and enlarges the retroaortic space, preventing future compression restenosis.