Prognostic value of exercise testing soon after myocardial infarction.

The prognostic value of a limited treadmill exercises test performed one day before hospital discharge after acute myocardial infarction was studied in 210 consecutive patients who had no over heart failure and had been free of chest pain for at least four days. No complications occurred. During a one-year follow-up period 28 of 43 patients (65 per cent) who had chest pain during the test reported angina, as compared with 60 of 167 (36 per cent) who had no chest pain during test (P less than 0.001). The one-year mortality rates were 2.1 per cent (three of 146) in patients without changes in the S-T segment during exercise and 27 per cent (17 of 64) in those with depression of the S-T segment (P less than 0.001). Sudden death occurred in one of 146 (0.7 per cent) patients who showed no change in the S-T segment and in 10 of 64 (16 per cent) with depression of the segment (P less than 0.001). Thus, a limited treadmill exercise test performed before hospital discharge after acute myocardial infarction is safe and can predict mortality in the subsequent year.     

Leucine33-proline33 substitution in human platelet glycoprotein IIIa determines HLA-DRw52a (Dw24) association of the immune response against HPA-1a (Zwa/PIA1) and HPA-1b (Zwb/PIA2).

Alloantibody formation against HPA-1a (Zwa/PIA1) has, to date, only been found in HLA-DRw52(a+) (Dw24) individuals. Alloimmunization against the product of the other HPA-1 allele, HPA-1b, is rare. We have been able to evaluate ten cases of HPA-1b alloimmunization in Europe in order to study whether there is an association between HLA phenotype and anti-HPA-1b antibody formation. HLA typing of these patients was performed with particular attention to the DRw52a specificity using specific T-cell clones. No association with DRw52a or any other known HLA phenotype was found. This finding implies that the amino acid substitution leucine33-proline33 in GPIIIa, responsible for HPA-1a/b, is of primary importance for the association of anti-HPA-1a antibody formation with DRw52a. These data show that the amino acid polymorphism affects the presentation of the immunogenic oligopeptides of HPA-1a and -1b in the HLA class-II groove.     

Behavioral and hypnotic treatments for insomnia subtypes

This investigation compared progressive muscle relaxation plus cognitive distraction (PMR/CD), hypothesized to better improve sleep onset, versus sleep restriction and stimulus control (SR/SC), hypothesized to better improve sleep maintenance, versus a flurazepam (Dalmane) positive contrast condition (MED) and a sleep hygiene education minimal treatment control condition (SHE). Participants with chronic insomnia (N = 53), completed 2 baseline weeks of sleep diaries, and were randomly assigned to a treatment group for 2 more weeks. In the second phase, PMR/CD participants were assigned to 2 weeks of PMR/CD + SR/SC + SHE while SHE participants continued SHE. Results indicated that PMR/CD had greater effect upon sleep onset than SR/SC and SHE, SR/SC had greater effect on sleep maintenance than PMR/CD, and MED was better than the other treatments. In the second phase, the treatment package produced modest additional improvements and SHE performed superior to expectations.     

The response to DNA damage induced by 4-nitroquinoline-1-oxide or its 3-methyl derivative in xeroderma pigmentosum fibroblasts belonging to different complementation groups: evidence for different epistasis groups involved in the repair of large adducts in human DNA

The data in this paper show that when the inhibition of growthis measured, xeroderma pigmentosum (XP) complementation groupsA, G and D are very sensitive to 4-nitroquinoline-1-oxide (4NQO),whereas only XP groups G and D are very sensitive to 3-methyl-4NQO(3me4NQO). Cells belonging to XP-C group are not particularlysensitive to either agent. Thus there are different epistasisgroups for the excision repair of DNA adducts induced by theseagents as opposed to the repair of u.v. damage. DNA polymerase is involved in the repair of 4NQO-induced lesions because aphidicolinblocks their repair. XP cells from all the above groups aredefective to some extent in this repair. The degree of repairdefectiveness follows that seen after u.v., with even the XP-Ccell line used having reduced repair (despite the fact thatthe inhibition of growth by 4NQO in this cell line was not markedlydifferent from normal). Aphidicolin did not induce breaks inthe normal or XP cell lines exposed to 3me4NQO, thus the repairof lesions induced by 3me4NQO does not involve DNA polymerase in any of the cell lines. Finally, catalase reduces the alkalinelabile lesions induced by 4NQO, but not 3me4NQO, suggestingthe latter agent does not induce substantial amounts of DNAdamage by the generation of radicals.     

Current Status of the VU MFEL Compton X-Ray Program

The Vanderbilt University medical FEL (free electron laser) Compton x-ray program is close to being operational. The FEL modifications necessary for this new capability are near completion. The transport and detection systems for electron and IR beams have been designed, delivered, and tested. We initially expect to produce 108 x-ray photons per second in the 15- to 20-keV region.     

Destruction of WiDr multicellular tumor spheroids with the novel thymidylate synthase inhibitor 1843U89 at physiological thymidine concentrations

The activity of a novel thymidylate synthase inhibitor, 1843U89, against WiDr human colon carcinoma multicellular tumor spheroids was investigated. Continuous exposure of the spheroids to 3 nM 1843U89 for 10 days resulted in spheroid disruption, whereas 100 nM methotrexate (MTX) was required for similar effects. Short-term treatment experiments demonstrated that a 3-day exposure to 100 nM 1843U89 caused spheroid disruption 9 days after drug removal. A 4-day exposure to 10 nM 1843U89 caused spheroid disruption 8 days after drug removal. In contrast, treatment with 10 or 100 nM 1843U89 for 6–48 h or treatment with 1 nM 1843U89 for up to 5 days caused only growth delay. Continuous exposure of spheroids to 30 nM 1843U89 in the presence of 0.05–0.3 M thymidine was as effective in causing spheroid disruption as treatment in the absence of thymidine, but treatment in the presence of 0.7–3.0 M thymidine caused partial reversal of spheroid disruption. The results of these experiments suggest that 1843U89 should have potent solid tumor activity in humans but should be less effective in mice due to differences in circulating thymidine levels (0.1 vs 1 M, respectively).     

Breast Biopsies with ABBI(R): Experience with 183 Attempted Biopsies

When first introduced, the advanced breast biopsy instrumentation (ABBI^®) system seemed to have many advantages as a diagnostic procedure. Problems have arisen, however, both in terms of patient unsuitability and mechanical failure. In addition, there has been uncertainty as to whether the complete lesion removal it afforded could be considered definitive treatment in malignant cases. Incision margins were looked at to investigate that possibility. Of the 183 patients we saw in our first year of experience with ABBI, 48 (26%) were rejected for being poor candidates for it. In the remaining 132 biopsies there were 31 (23%) technical difficulties. All told, 14 malignancies were discovered, all of which appeared to have pathology-free incision margins radiologically. However, 13 of these 14 (93%) proved on pathologic examination to have residual malignancy. ▪     

Repeated injections of a ciliary neurotrophic factor analogue leading to long-term photoreceptor survival in hereditary retinal degeneration

PURPOSE: To determine whether ciliary neurotrophic factor (CNTF) or brain-derived neurotrophic factor (BDNF) treatment leads to long-term photoreceptor survival in hereditary retinal degeneration. METHODS: An autosomal dominant feline model of rod-cone dystrophy was used throughout the study with two normal animals. In the first experiment, intravitreal injections of a human CNTF analogue (Axokine; Regeneron Pharmaceuticals, Tarrytown, NY) were administered to one eye of each animal (n = 10) beginning on postnatal day 10 and were repeated every 4 weeks. Clinical and histopathologic examinations were performed at 5.5, 9.5, and 13.5 weeks. In the second experiment, animals (n = 17) were randomly assigned to receive intravitreal injections of either Axokine (at half the initial dose), human BDNF, or the vehicle for Axokine to one eye at 5.5 weeks. The same therapy was repeated every 4 weeks in each group. Clinical and histopathologic examinations were performed at 9.5, 13.5, and 17.5 weeks. Photoreceptor survival was assessed by cell counting. Apoptotic cells were identified by morphology and a modified TdT-dUTP terminal nick-end labeling (TUNEL) technique. In the third experiment, two normal animals were treated with Axokine as in the first experiment. Glial fibrillary acidic protein ((GFAP) immunohistochemistry was performed to assess glial cell reaction. RESULTS: In the first two experiments, Axokine significantly prolonged photoreceptor survival (P < 0.01) and reduced the presence of apoptotic cells (P < 0.05) and TUNEL-positive cells (P < 0.05). In the second experiment, results in the the BDNF- and sham-injected eyes were not significantly different from those in the untreated eyes. Minimal posterior subcapsular cataract and mild retinal folds were found in all Axokine-treated eyes in both dystrophic and normal animals. These complications were milder in the second experiment when injections were started later and at a reduced dose. GFAP immunolabeling was also increased in all Axokine-treated eyes. CONCLUSIONS: Axokine, but not BDNF, delays photoreceptor loss in this hereditary retinal degeneration. Repeated injections maintain the protective effect.     

Growth hormone receptor expression in the Dunning R 3327 prostatic carcinoma of the rat.

The Dunning R3327 rat carcinoma is an important model for human prostate adenocarcinoma. In the present study this tumor was further characterized by immunohistochemical demonstration of receptors for growth hormone (GH-R). Weak GH-R immunoreactivity was present in the secretory epithelial cells of the tumor acini. Large epithelial cells which were localized at the periphery of the acini and large cells in the stroma, which are probably derived from the epithelium ("Large neoplastic epithelial cells"), displayed a strong staining with one of the monoclonal antibodies (Mab 263) to GH-R. The presence of GH-R receptors in proliferating prostatic tumor cells supports the concept that GH reacts directly on prostate target tissue to facilitate tumor cell growth.