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Chemoprevention by retinoids of the progression of carcinomas induced in rats by azaserine was evaluated. Wistar/Lewis rats were given 15 weekly injections of azaserine, 10 mg/kg, while fed a chow diet; after the completion of carcinogen treatment, they were fed a chow diet supplemented with four different retinoids at the level of 0.5 to 2 mmol/kg diet for 1 year. The incidence of neoplasms was determined by autopsy and histological study. The incidence of pancreatic carcinoma among a male positive control group (azaserine treated, but not retinoid treated) was 42%. The incidence of pancreatic carcinoma among male rats treated with retinoids was: N-2-hydroxyethylretinamide, 6%; N-4-propionyloxyphenylretinamide, 17%; and retinylidene dimedone, 12%. The incidence in rats fed these three retinoids was significantly (p less than 0.05) below the control group incidence. Thus, these three retinoids appeared to be effective in inhibiting the progression of pancreatic carcinomas in the azaserine-induced model. A similar trend was demonstrated in females, but statistical significance was shown only in rats fed N-2-hydroxyethylretinamide. A fourth retinoid, N-4-carboxyphenylretinamide, was more toxic and less effective in chemoprevention. Since retinoids were fed after exposure to carcinogen, the effect was exerted during the postinitiation phase of carcinogenesis. The ratio of invasive pancreatic carcinomas to localized carcinomas (carcinoma in situ) was clearly higher among non-retinoid-treated rats than among those treated with retinoids. This is consistent with retarded progression in the retinoid-treated groups.
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10,001,201
Phorbol myristate acetate-induced adherence of Walker 256 carcinosarcoma cells.
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10,001,202
Treatment of nonadherent Walker 256 carcinosarcoma cells with phorbol myristate acetate (PMA) causes these cells to become adherent to noncellular foreign surfaces such as nylon fibers and plastic culture dishes and to monolayers of endothelial cells. Increased adherence is first observed after a short lag period (5 to 15 min) and is transient. Other tumor-promoting analogs of PMA also induce this response, while inactive analogs of PMA do not. Simultaneous treatment of the cells with 2-deoxyglucose, colchicine, cytochalasin B, and cycloheximide indicates that the adherence response of the cells is an energy-dependent process that requires an intact cytoskeleton but does not require protein synthesis. Inhibitors of phospholipids and arachidonic acid metabolism including indomethacin, nordihydroguaiaretic acid, and p-bromophenacyl bromide greatly inhibit PMA-induced adherence, but acetylsalicylic acid is much less effective. PMA also increases the rate of attachment to plastic dishes of cells which would normally attach, although slowly, and grow as substrate-attached cells. However, PMA treatment has no effect on the subsequent degree of susceptibility of these cells to release from plastic dishes mediated by proteolytic enzymes. These findings suggest (a) that PMA may be useful in delineating the initial events involved in the adherence of cells to cellular and noncellular surfaces and (b) that PMA may stimulate tumor cell adherence in a manner similar to that of chemotactic peptides may be useful in delineating the events associated with chemotactic factor stimulation of these cells.
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10,001,203
Induction of lymphoma in antigenically stimulated athymic mice.
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10,001,204
Athymic mice infected with pinworms or carrying human tumor xenografts frequently develop a lymphoproliferative disorder which eventually leads to lymphoma. By immunofluorescent analysis of involved tissues, the lymphomas appear to be mixtures of null cells, B-cells, and T-cells. When each lymphoma is established in tissue culture, a predominant cell type grows out. We have now established lymphoma lines of null cells, B-cells, and T-cells. Lymphoma development is preceded by the secretion into the bloodstream of large amounts of murine leukemia virus M.W. 70,000 glycoprotein antigen; however, very little virus is produced. In vivo, the expression of viral envelope antigen appears within a few days after human tumor transplantation and precedes the development of lymphoma by about a month. Cells expressing viral antigens are first seen in the diffuse cortex of lymph nodes and the periarteriolar white sheath of the spleen, the tissue domains in which lymphomas also first appear.
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10,001,205
Influence of convection in the growth medium on oxygen tensions in multicellular tumor spheroids.
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10,001,206
Tumorigenicity of bay-region diol-epoxides and other benzo-ring derivatives of dibenzo(a,h)pyrene and dibenzo(a,i)pyrene on mouse skin and in newborn mice.
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10,001,207
Excessive accumulation of autofluorescent lipofuscin in the liver during hepatocarcinogenesis by methyl clofenapate and other hypolipidemic peroxisome proliferators.
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10,001,208
Inhibitory effects of four isoabrins on the growth of sarcoma 180 cells.
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10,001,209
The four isoabrins were shown to be capable of inhibiting the growth of tumor cells in vivo when one-fifth of their median lethal dose was used. From the in vitro experiments, the doses required for 50% inhibition of protein biosynthesis are 3.2 pg, 45 ng, 32 ng, and 10 ng/ml for abrin-a, -b, -3, and -d, respectively. Except for abrin-b, a good correlation between the inhibitory effects of abrins on the tumor growth and protein biosynthesis was observed. These isoabrins show a moderate inhibitory effect on DNA biosynthesis.
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10,001,210
Differential effect of imidazole antibiotics on untransformed and virus-transformed rat cell lines.
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10,001,211
The imidazole antimycotics clotrimazole and miconazole were tested on untransformed rat cell line 3Y1-B clone 1-6 (3Y1) and six transformed cell lines, which were independently isolated from 3Y1 or 3Y1-B clone 1 after infection with adenovirus 12 (AD-12) or with SV40, to determine their sensitivities to these drugs. The relative plating efficiency of three cell lines (T3, W4, and W5) transformed with AD-12 was reduced to 10(-1( of the initial value by clotrimazole (2 to 4 microgram/ml), whereas that of the parental cell line 3Y1 was reduced to 10(-1) of the initial value by clotrimazole (20 to 25 microgram/ml). By contrast, the differential effect of miconazole on 3Y1 and AD-12-transformed cell lines was found to be a factor of 2. The sensitivity of the SV40-transformed 3Y1 and the AD-12-transformed cell lines. The cellular sensitivity of untransformed 3Y1 cells to clotrimazole was significantly enhanced when exposed to various doses of the unsaturated fatty acid, linoleic acid. The untransformed and transformed cell lines showed sensitivities similar to the cytocidal activity of sterol-binding antimycotics, amphotericin B and filipin.
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10,001,212
Alteration of the survival response of two human colon carcinoma subpopulations to x-irradiation by N,N-dimethylformamide.
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10,001,213
Reproducible growth in tissue culture of retinoblastoma tumor specimens.
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10,001,214
Retinoblastoma is a unique embryonic tumor which frequently arises because of an autosomal dominantly inherited mutation. Study of the genetic changes associated with retinoblastomas requires techniques that allow proliferation of fresh tumor specimens in tissue culture. However, until the present study, there were no reported methods for routinely obtaining in vitro growth of fresh retinoblastoma tumor cells. When placed on selected fibroblast feeder layers, 65% of fresh retinoblastoma specimens grew; but in the absence of fibroblasts, the same specimens died. Individual fibroblast strains from normal donors, retinoblastoma patients, and mice were effective feeder layers. A fibroblast strain that provided good feeder function for one tumor generally supported growth of other tumors also. Direct contact was required between the tumor cells and the fibroblast; conditioned media alone did not support tumor growth and immobilization of tumor cells in semisolid media above fibroblasts failed to give colony growth. Cultured tumor cells injected into the eyes of athymic nude mice formed tumors histologically characteristic of retinoblastomas.
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10,001,215
Reduction of adriamycin toxicity by ascorbate in mice and guinea pigs.
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10,001,216
The effect of ascorbate in reducing Adriamycin toxicity has been examined in mice and guinea pigs. Ascorbate had no effect on the antitumor activity of Adriamycin in mice inoculated with leukemia L1210, but it significantly prolonged the life of mice and guinea pigs treated with Adriamycin. Adriamycin elevated lipid peroxide levels in serum and liver, and ascorbate prevented the elevation. The significant prevention of Adriamycin-induced cardiomyopathy by ascorbate was proved by means of electron microscopy. The earliest alterations of dilation of the sarcoplasmic reticulum and transverse tubular system and the appearance of a large number of cytoplasmic fat droplets, which were seen in cardiac tissue from guinea pigs receiving Adriamycin, were apparently reduced in animals that were treated with ascorbate.
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10,001,217
Tamoxifen and metabolites in MCF7 cells: correlation between binding to estrogen receptor and inhibition of cell growth.
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10,001,218
The binding of [3H]tamoxifen ([3H]Tam), a nonsteroidal antiestrogen, and of 4-[3H]hydroxytamoxifen ([3H]OH-Tam), a metabolite accumulated in vivo in target cell nuclei, was characterized in soluble extracts of human breast cancer MCF7 cells growing in a medium depleted in estrogens. Saturation analysis indicated a much higher affinity for OH-Tam (Kd = 0.15 nM) than for Tam (Kd = 4.8 nM). The binding of [3H]Tam and [3H]estradiol was competitive and mutually exclusive, and the binding site concentration (0.16 to 0.47 pmol/mg total protein) was similar for both ligands, strongly suggesting that antiestrogens were binding to the estrogen receptor (ER) in these cells. The ability of Tam and of some of its metabolites or derivatives to prevent the MCF7 cell growth was found to be correlated with their affinity for ER as determined by direct interaction or by binding competition with [3H]estradiol on the uterine and MCF7 cytosol ER. OH-Tam was the highest-affinity compound and was 100-fold more active than Tam. The inhibitions observed were actually due to Tam and OH-Tam, respectively, since we did not detect any significant metabolism of these two labeled compounds by the MCF7 cells. N-desmethyltamoxifen, the other Tam metabolites found in high concentration in human plasma, was as effective as Tam while cis-tamoxifen appeared less effective. Compound E, which has no lateral chain, was the only tested compound having a good affinity for ER and a poor efficiency in preventing cell growth. These results support the hypothesis that antiestrogens control the growth of breast cancer by acting directly on the ER located in cancer cells.
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10,001,219
Effect of beta-glucuronidase inhibitor on azoxymethane-induced colonic carcinogenesis in rats.
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10,001,220
In this study of the role of microfloral beta-glucuronidase in colonic carcinogenesis, the effect of beta-glucuronidase inhibitor was evaluated. Starting at 5 weeks of age, male Donryu rats were fed either a semisynthetic diet or the same diet containing 0.1% beta-glucuronidase inhibitor as N-cyclohexyl-5-O-acetyl-2,4-O-p-methoxybenzylidene) -D-glucaro-1-amide-6,3-lactone (C-GAL). All animals were given s.c. injections of 7.4 mg azoxymethane (AOM) per kg body weight once a week for 11 weeks and followed for an additional 20 weeks. Most animals receiving the colonic carcinogen developed tumors in the colon, and a few also developed tumors in the small intestine. However, the number of tumors in the large intestine of the rats given C-GAL at the same time as AOM was significantly lower than in the control rats, especially in the proximal half of the colon, but those given C-GAL after AOM treatment had almost the same number of colon tumors as did the controls. It is concluded that, since bacterial beta-glucuronidase activity in the feces of rats given 0.1% C-GAL was significantly inhibited, intestinal microfloral beta-glucuronidase may play an important role in colonic carcinogenesis caused by AOM.
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10,001,221
Surface marker identification of small cleaved follicular center cell lymphomas with a highly favorable prognosis.
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10,001,222
Between 1976 and 1980, 143 cases of non-Hodgkin's lymphoma have been prospectively analyzed for correlations between surface marker phenotype, histomorphology, and prognosis. This study analyzed 44 adults with tumors classified by Lukes-Collins criteria as small cleaved follicular center cell lymphomas. Two surface marker phenotypic subsets were membrane immunoglobulin, immunoglobulin D (IgD), or a receptor for the third component of the complement system (C'3) (Group I = IgD+ and/or C'3+, group II = IgD-C'3-). Eleven of the 44 patients have died with a projected median survival of 58 months. Four patients in Group I have died with a median survival of 58 months while seven patients in Group II have died with a median survival of 30 months. The difference in the survival curves for the two subgroups is statistically significant (p = 0.01). An analysis of variables such as stage, age, sex, and sites of involvement revealed no differences between the two groups. When classified histologically, the two groups were morphologically indistinguishable and had similar distributions of nodular (follicular) and diffuse variants. Of interest, five patients in Group I were judged to require no initial therapy whereas none in Group II remained untreated initially. The expression of the second heavy chain delta and/or a receptor for C'3 appears to define a subgroup of small cleaved follicular center cell lymphomas with an indolent course and an excellent prognosis.
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10,001,223
Phase I clinical trial of 9,10-anthracene dicarboxaldehyde (Bisantrene) administered in a five-day schedule.
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10,001,224
Bisantrene is a substituted anthracene derivative which preclinically demonstrated a spectrum of activity similar to that of doxorubicin but without associated cardiotoxicity. A Phase I evaluation of the drug has been performed using daily i.v. administrations for 5 days. Sixty courses of treatment were administered to 23 patients at doses from 2.5 to 90 mg/sq m/day. Courses were repeated at 4-week intervals. Dose-limiting toxicities were leukopenia and local cutaneous reactions. The leukopenia was dose related, noncumulative, and of brief duration. Local reactions occurred in 14 of 37 courses administered at doses greater than 60 mg/sq m and in 13 patients resulted in clinical cellulitis of the infused extremity. Gastrointestinal side effects were mild. No alopecia or cardiotoxicity was observed. Two mixed responses were obtained in patients with hypernephromas. Using a daily schedule for 5 days, approximately 40% more drug can be delivered per course than by single-day i.v. administration. However, with this schedule, local cutaneous reactions may prove additionally dose limiting. Phase II studies of Bisantrene in a daily i.v. schedule for 5 days are planned at a dose of 80 mg/sq m/day to be repeated every 4 weeks.
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10,001,225
Effect of estrogen and progesterone on cellular replication of human breast tumors.
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10,001,226
A total of 54 infiltrating carcinomas of the breast were studied for estrogen receptor concentration in the tumor cytosol and thymidine-labeling indexes. The results showed that there was no significant difference in the level of thymidine-labeling index between 22 primary and 32 metastatic breast cancers. No significant association between the levels of thymidine-labeling index and the presence or absence of estrogen receptors was observed. The effect of "physiological" doses of estrogen and progesterone on cell proliferative activity was studied by the level of thymidine-labeling indexes in the tumor cells in 10 patients with multiple skin and s.c. metastases. Tumor biopsies were performed for labeling indexes both before and after hormonal treatment. The results showed that physiological doses of estrogen and progesterone induced a significant rise in thymidine-labeling index within 3 days after hormonal treatment in seven of the 10 tumors. Of the seven tumors that showed a rise in thymidine-labeling index, three were estrogen receptor positive and four were estrogen receptor negative. Of the three nonresponsive tumors, one was estrogen receptor positive and two were estrogen receptor negative. The study suggests that estrogen and progesterone can induce cell replication in both estrogen receptor-positive and -negative tumors.
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10,001,227
Relationship between natural killer cell activity and histological features of lymphocyte infiltration and partial regression of the primary tumor in melanoma patients.
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10,001,228
A group of 194 melanoma patients with Stage I melanoma was studied in an attempt to correlate histological features of prognostic importance in malignant melanoma with the level of natural killer cell (NK) activity in blood mononuclear cells. Histological features examined were lymphocytic infiltrate of the tumor base, lymphocyte infiltration at the tumor margin, and evidence of partial regression in the tumor. NK activity against melanoma cells and non-melanoma cells was studied in the same patients before and after surgical removal of melanoma. Patients with high NK activity against melanoma and Chang cells had less lymphocyte infiltrate at the base of the tumor irrespective of its thickness than did those with low NK activity. Patients with low NK activity and thin tumors had more lymphocyte infiltration at the base of the tumor than did those with high NK activity. Similar results were obtained in certain subsets of cases with respect to lymphocytic infiltration at the tumor margins and to the presence of partial regression. Although the nature of the association between these histological features and NK activity in blood is unknown, it is suggested that previously unexplained associations between histological features and prognosis may be accounted for by their association with NK activity. If this proves to be correct, measurement of NK activity may be an important additional prognostic factor in patients with melanoma.
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10,001,229
Membrane glycopeptides from chemically transformed cells: comparison between mesenchymal and epithelial cell lines derived from dimethylnitrosamine-treated rat kidney.
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10,001,230
Radiation-induced mammary carcinogenesis in virgin, pregnant, lactating, and postlactating rats.
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10,001,231
Comparative metabolism of 2,6-dimethylnitrosomorpholine in rats, hamsters, and guinea pigs.
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10,001,232
The metabolism of N-[3,5-3H]nitroso-2,6-dimethylmorpholine (NDMM) was studied in female Sprague-Dawley rats. Syrian golden hamsters, and guinea pigs. NDMM induces tumors in the esophagus in rats, pancreatic cancer in hamsters, and hemangioendothelial tumors of the liver in guinea pigs. An intragastric dose of NDMM (2 mg, 2 muCi/animal) was rapidly distributed throughout the tissues of both the rat and hamster, with no apparent accumulation of radioactivity in any one tissue. At low dose levels, NDMM was metabolized rapidly by both species. The hamster appeared to metabolize the compound faster than did the rat or guinea pig. At appreciable amount of radioactivity was excreted in the urine in all three species after 8 hr: approximately 54% in the hamster, 39% in the rat; and 30% in the guinea pig. During the first 24 hr, only a small percentage of the radioactivity excreted by the hamster, rat, and guinea pig was NDMM (0.8, 2, and 0.5%, respectively). High-pressure liquid chromatography analysis of urine collected 24 hr after administration revealed 12 metabolites. Although the urinary metabolites appeared to be similar in all three species, one large difference was the presence of a major urinary metabolite in hamster urine, which was absent or present in only small quantities in the rat and guinea pig. The guinea pig urine also had relatively more radioactivity present in one major fraction than did the hamster or rat.
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10,001,233
Comparison of the in vitro metabolism of N-nitrosohexamethyleneimine by rat liver and lung microsomal fractions.
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10,001,234
The in vitro metabolism of N-nitrosohexamethyleneimine by lung and liver microsomes and cytosol from uninduced male Fischer rats is described. Metabolites produced by both organs appeared to be identical. The liver subcellular fractions had a lower Km (0.6 mM) than did lung fractions (3 mM) and metabolized 2.5 to 5 times as much nitrosamine per mg protein. Our results, together with those from our earlier studies, indicate that, as the size of the carbon ring increases from nitrosopyrolidine to nitrosohexamethyleneimine, lung microsomes had an increased affinity for the cyclic nitrosamines; they was only a small effect with liver enzymes. Ths suggests that microsomal enzymes that metabolize cyclic nitrosamines in rat livers and lungs are not the same. The first stable alpha-hydroxylation product, 6-hydroxyhexanal, was not detected in reactions involving microsomes alone. Apparently, this compound is rapidly converted to 1,6-hexanediol by liver or lung microsomes. The presence of cytosol was needed for the full conversion of these metabolites to xi-hydroxycaproate and maximal alpha-hydroxylation activity. xi-Aminocaproate was always found in direct proportion to the hydroxyacid, suggesting that both acids arise from the same alpha-hydroxylation event by different breakdown mechanisms. beta- and gamma-hydroxynitrosohexamethyleneimine were not metabolized significantly by rat liver enzymes and thus, in this species, may be "detoxification products" of N-nitrosohexamethyleneimine.
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10,001,235
Effect of regenerative hyperplasia on the urinary bladder: carcinogenicity of sodium saccharin and N-[4-(5-nitro-2-furyl)-2-thiazolyl]formamide.
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10,001,236
Different activities of unscheduled DNA synthesis in human melanoma and bone marrow cells.
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10,001,237
Unscheduled DNA synthesis (UDS) indicated by melphalan was studied in freshly collected tumor cells from human melanoma metastases. Comparative studies were done on human bone marrow blast cells. Significant levels of UDS comparable with those in myeloblasts were found in only two of eight melanoma cell populations. This difference between melanoma and blast cells was not related to different cellular uptake of melphalan. When UDS was induced by ultraviolet irradiation, significant levels of UDS were found in all melanoma and blast cell populations studied. Also, in a human melanoma cell line, high levels of UDS were found after exposure to ultraviolet irradiation, while treatment with melphalan did not result in detectable levels of UDS. Possible explanations for the divergent results of UDS in melphalan-exposed melanoma cells are discussed.
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10,001,238
Effect of 1,2-dimethylhydrazine and diethylnitrosamine on cell replication and unscheduled DNA synthesis in target and nontarget cell populations in rat liver following chronic administration.
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10,001,239
Differentiation of rat myocytes in single cell cultures with and without proliferating nonmyocardial cells. Cross-striations, ultrastructure, and chronotropic response to isoproterenol.
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10,001,240
Effects of capsaicin and bradykinin on afferent fibers with ending in skeletal muscle.
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10,001,241
Capsaicin, injected into the arterial supply of the skinned hindlimb of dogs, evokes reflex increases in cardiovascular function. Moreover, the cardiovascular reflexes evoked by capsaicin are very similar to those evoked by static exercise. The afferent fibers initiating these reflex increases have not been identified electrophysiologically, although their endings are believed to be located in skeletal muscle. We have, therefore, attempted to determine which afferent fibers are stimulated by capsaicin. In anesthetized dogs, we recorded impulses from afferent fibers with endings in either the gastrocnemius or gracilis muscles and injected capsaicin (10-30 microgram/kg) into the abdominal aorta. Capsaicin stimulated 24 of 34 group IV (C fiber) endings, but only 5 of 19 group III (A delta fiber) endings. By contrast, bradykinin (0.5-1.5 microgram/kg) stimulated 17 of 33 group IV endings and 9 of 19 group III endings. Impulse activity for the 24 group IV afferents stimulated by capsaicin increased from 0.7 +/- 0.1 to a peak of 9.3 +/- 1.4 imp/sec. Firing started 6 +/- 1 seconds after injection and remained above control levels for 24 +/- 5 seconds. Capsaicin had no significant effect on the firing rate of 30 group I and II muscle afferents. Our results suggest that group IV muscle afferents are primarily responsible for causing the reflex increases in cardiovascular function evoked by injecting capsaicin into the arterial supply of the skinned hindlimb of dogs. Moreover, capsaicin is likely to be a useful pharmacological tool with which to determine the reflex autonomic effects caused by stimulation of group IV muscle afferents.
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0.10133419930934906, 0.04586797207593918, -0.042993731796741486, 0.05103123188018799, -0.01204659417271614, 0.08392356336116791, 0.008083523251116276, -0.0005773218581452966, -0.03347167745232582, -0.0863782986998558, 0.06609901785850525, 0.017169084399938583, -0.04786605387926102, 0.030832264572381973, -0.0772714614868164, 0.02559112198650837, -0.013456723652780056, 0.047244902700185776, -0.024025771766901016, -0.05661115422844887, -0.040184371173381805, 0.01499272882938385, 0.1116408035159111, 0.014990664087235928, 0.08074361830949783, 0.09250311553478241, -0.03523479402065277, -0.06800012290477753, 0.0038075526244938374, 0.05185902491211891, -0.04216406121850014, 0.006099493242800236, -0.059021107852458954, -0.04952091723680496, -0.028651997447013855, 0.0941978320479393, -0.0302647165954113, 0.05891724303364754, -0.04802333936095238, -0.014814299531280994, 0.041382890194654465, -0.04028536006808281, 0.11816773563623428, 0.052585989236831665, 0.006511731073260307, 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0.007845038548111916, 0.09724787622690201, -0.00666067935526371, 0.01777712069451809, 0.04499445855617523, -4.888259752533486e-8, -0.022511441260576248, 0.07226654142141342, -0.020719418302178383, 0.06842875480651855, -0.025834163650870323, 0.06302640587091446, -0.05033427104353905, -0.03218649700284004, -0.046481046825647354, -0.10258830338716507, 0.021885961294174194, 0.08347669243812561, 0.04504258930683136, 0.012392202392220497, 0.03535296767950058, 0.007059028372168541, 0.00623752037063241, 0.05843089520931244, 0.015688134357333183, -0.0026650752406567335, -0.027934962883591652, -0.05926233157515526, -0.035572223365306854, -0.04800519719719887, 0.014390313997864723, -0.10313596576452255, -0.07222803682088852, 0.045076847076416016, -0.0845179632306099, -0.018889395520091057, 0.09283957630395889, -0.016442248597741127, -0.025648828595876694, -0.056364383548498154, -0.040915749967098236, 0.06294935196638107, 0.004894502926617861, -0.025086481124162674, -0.08184734731912613, 0.03258827328681946, -0.016744034364819527, -0.012129236944019794, -0.08246823400259018, 0.0018364433199167252, -0.029668401926755905, -0.03773880749940872, 0.08508583158254623, -0.0006909380899742246, 0.010524150915443897, 0.046098724007606506, -0.04859375208616257, 0.006808908190578222, -0.021352028474211693, 0.015414539724588394, -0.02083868347108364, -0.030753374099731445, -0.05760497972369194, -0.0312623456120491, 0.03820039704442024, -0.02769295498728752, -0.001308004604652524, 0.009125332348048687, -0.022862868383526802, -0.03224516659975052 ]
10,001,242
"Electrical activity from the sinus node region in conscious dogs".
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10,001,243
Hyperemic response of the coronary circulation to brief diastolic occlusion in the conscious dog.
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10,001,244
This study was undertaken to determine whether coronary blood flow can be regulated in response to coronary arterial occlusions briefer than a single diastole. The possible involvement of metabolic vs. myogenic mechanisms in such regulation was investigated. Eleven conscious dogs with experimentally produced complete heart block, chronically implanted electromagnetic flow probes, and pneumatic occluders on the left circumflex coronary artery were studied. Diastolic coronary occlusions lasting 100 to 400 msec were performed at paced heart rates of 40, 60, and 120 beats/min. At a heart rate of 60 beats/min, a 200-msec occlusion was sufficiently long to produce a significant reactive hyperemic response; 400-mec occlusions resulted in larger responses, while 100-msec occlusions did not generate a discernible response. The onset of reactive hyperemia was delayed from the end of the occlusion until the first post-occlusion systole. The length of this delay could be altered by changing the heart rate or occlusion duration, but no significant response was detected before the first post-occlusion systole. This characteristic of the data is more consistent with a metabolic than with a myogenic mechanism. If the response is metabolic, the data demonstrate that autoregulation of coronary flow by such a mechanism is very rapid, occurring during the first systole in which a flow deficit is detected by the myocardium.
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10,001,245
Coronary vasodilation after a single ventricular extra-activation in the conscious dog.
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10,001,246
This study was undertaken to determine if coronary blood flow can be regulated in response to a transient increase in cardiac metabolic demand. Eight conscious dogs with experimentally produced complete heart block, a chronically implanted electromagnetic flow probe on the left circumflex coronary artery, and fluid-filled catheters for measurement of left ventricular and aortic pressures were studied. At a paced heart rate of 60 beats/min, a single ventricular extra-stimulus was introduced with a delay of 150-200 msec from the preceding R-wave. The extra-stimulus produced a ventricular extra-activation, but not a discrete mechanical extra-systole. The ensuing beats exhibited systolic potentiation, manifest by a 50 +/- 8% increase from control in maximum left ventricular dp/dt in the first potentiated beat, presumably accompanied by increased myocardial oxygen demand. In the diastole immediately following the first potentiated systole, the coronary vascular resistance index (mean aortic pressure/mean coronary flow in that diastole) fell significantly from control by 12 +/- 2%. The results indicate that a transient increase in cardiac metabolic demand is followed immediately by a compensatory coronary vasodilation that occurs within the same cardiac cycle.
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10,001,247
A dynamic electrical record of the pathway of human His bundle activation from surface mapping.
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10,001,248
Body surface potential maps of human His bundle activity have been difficult to product for two reasons: (1) The peak surface potentials are often less than 5 muv, and (2) the simultaneous atrial repolarization potentials frequently exceed 100 muv. We have therefore amplified surface signals 25 times the standard gain of 1000, and then removed by cross-correlation the static pattern of atrial repolarization for serial 1-msec maps of the P-R segment in five normal men. A consistent finding emerged: a positive anterior chest peak appeared 40 msec before QRS onset, and then-within 10 msec-spread out into a long, low transverse mound before disappearing in 5 more msec. The map data were analytically converted to serial electrical sources: the center of electrical activity moved first slightly down, then directly forward, before retracing its path and disappearing. The retrace and accompanying surface spread-out strongly suggests diverging dipolar sources. Thus the data fit a simple heart source which moves anteriorly and then breaks into two (right and left)-as expected from activation of the bundle of His and its bifurcation into left and right bundle branches.
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10,001,249
Left ventricular energetics. Heat loss and temperature distribution of canine myocardium.
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10,001,250
The sum of total left ventricular heat loss and left ventricular mean total external power was compared with the product of oxygen consumption and its energy equivalent. Myocardial blood flow, measured with 15 +/- 3 micrometers radioactive microspheres, was multiplied by the transcoronary arteriovenous temperature difference and by oxygen content difference to obtain coronary heat loss and oxygen consumption, respectively. Since only part of the heat is carried away by the coronary system a thermodilution technique was used to obtain the ratio between the heat removed by the coronary system and the external heat loss. A correction was made for the endothermic reactions of hemoglobin deoxygenation and carbon dioxide reactions with blood. Left ventricular oxygen consumption corresponded to 2.26 +/- 0.66 W/100 g, and for the sum of total left, ventricular heat loss and external power, 2.09 +/- 0.51 W/100 g was found (n = 14). In a second series, the measured transmyocardial temperature distribution was compared with the calculated temperature distribution, assuming that heat production in the myocardium is uniform and that heat is lost by coronary flow and diffusion. When thoracic and luminal myocardial surface temperatures were about equal, blood flow was found to be about the same in the various layers of the heart, whereas myocardial temperature was found to be highest near the middle of the wall (0.36 +/ 0.07 degrees C warmer than luminal temperature (n = 6). When thoracic surface temperature was increased or decreased (by + 1.56 +/- 0.99 degrees and -1.10 +/- 0.59 degrees C, respectively), consistent changes were seen for the temperature distribution in the myocardium, but not for the local flow (endo/epi ratio: 1.06 +/- 0.29 and 0.96 +/- 0.21, respectively). These data suggest that myocardial blood flow is independent of tissue temperature.
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10,001,251
The effects of peripheral impedance and inotropic state on the power output of the left ventricle in dogs.
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10,001,252
The power output of the left ventricle as measured by the product of the Fourier components of aortic pressure and aortic flow is linked by definition to the arterial impedance facing the heart as measured by the quotient of these components. Consequently, the use of power measurements to assess ventricular performance can be ambiguous when accompanied by afterload changes. The heart is considered to function normally between two extremes, a constant flow pump, and a constant constant pressure pump, and two power limits are defined from these. The power limits describe the extent to which impedance changes can affect the power delivered by the left ventricle. Measured power changes that are found to lie outside the two limits can be unambiguously ascribed to changes in inotropic state. The results from preliminary dog experiments designed to test this method are reported. Cardiac sympathetic stimulation and isoprenaline infusion were used to provide a pure inotropic stimulus and a mixture of inotropic and afterload changes, respectively. The technique was able to detect inotropic changes in the heart even in the presence of simultaneous changes in afterload. Eight conventional indices of cardiac performance were monitored for comparison. The extent of their afterload dependence may not be as easily quantified.
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10,001,253
Mechanical interactions between four heart chambers with and without the pericardium in canine hearts.
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10,001,254
By using excised postmortem hearts obtained from 15 mongrel dogs with the pericardium intact, we investigated mechanical interactions between the four heart chambers from the standpoint of ventricular pressure-volume relationships. The interactions investigated were those between (1) the atrium and the ventricle, (2) the right ventricle and left ventricles, (3) the atrium and one ventricle vs. the other ventricle, and finally (4) the left and right atrium and the right ventricle vs. the left ventricle. For these purposes, we inserted compliant balloons into the four heart chambers without injuring the pericardium, i.e., we incised the base of the atria which was not covered with the pericardium. We obtained the right and/or left ventricular pressure-volume relationships under a constant pressure in three other heart chambers by changing the height of the reservoir connected to each balloon. As a result, both ventricular pressure-volume relationships were hardly affected by an increase in the atrial pressure ranging from 5 to 30 cm H2O with the pericardium removed, although the ventricle became less compliant due to an increase of the same magnitude of the opposite ventricular pressure. On the other hand, the effect of an increase in atrial pressure was distinct with the pericardium intact. Also, all mechanical interactions were enhanced dramatically with the intact pericardium. Thus, the pericardium plays an important role in these mechanical interactions, especially when the filling pressures of all heart chambers increase simultaneously. Clinically, these findings may be important to understanding ventricular functions as related to various heart disease-especially acute heart failure.
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10,001,255
Assessment of jeopardized myocardium in patients with one-vessel disease.
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10,001,256
Blood flow reductions in stenosed canine coronary arteries: vasospasm or platelet aggregation?
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-0.05006127804517746, -0.02940816432237625, 0.01290043443441391, 0.03701218217611313, 0.03254316747188568, 0.10798463970422745, -0.009622468613088131, 0.0012410796480253339, -0.05355880782008171, -0.09233193099498749, 0.04094109684228897, 0.007420926820486784, -0.004977438598871231, -0.05389689654111862, -0.06096111610531807, 0.0018585195066407323, -0.04680478572845459, 0.07924243062734604, -0.009860251098871231, 0.025294700637459755, 0.0016783636528998613, 0.06087286025285721, -0.007228822447359562 ]
10,001,257
In 67 dogs with a 60-80% coronary stenosis produced by an external constricting plastic ring, blood flow measured with an electromagnetic flowmeter showed cyclical flow reductions of varying magnitude and duration, and then an abrupt return to control flow. In 45 dogs, heparin did not prevent these flow reductions, but ibuprofen (Motrin) or indomethacin abolished them. With incremental doses of each of these drugs, the cyclical flow reduction and the platelet function in vitro were diminished proportionately. In 10 more dogs, during low flow, pinching or poking the narrowed vessel suddenly restored normal flow. Topical application of papaverine and nitroglycerin proximal to the stenosis did not abolish the cyclic flow reduction, although a transient fall in systemic pressure indicated that they had been absorbed. Seven dogs had the constricting cylinder and flow probe chronically implanted for 4-6 weeks. A single oral dose of aspirin, 20 mg/kg, abolished their cyclic flow reductions for 2-4 days. In five dogs with 70% stenosis in the circumflex coronary artery, coronary arteriography was performed before coronary flow reduction and when coronary blood flow was low. This showed that there was a considerable additional reduction in the size of the mechanically constricted lumen during spontaneous flow reduction. In one dog, a nonopacified mass was dislodged from the area of constriction in 67 msec and this restored the lumen to its control diameter. Similar rapid clearing was filmed in two more dogs. In no case was vasospasm observed. These results suggest that obstruction from platelets aggregated in the narrowed lumen caused the cyclic flow reductions.
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10,001,258
Determinants of arrhythmic death due to coronary spasm: effect of preexisting coronary artery stenosis on the incidence of reperfusion arrhythmia.
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10,001,259
Coronary spasm can occur in the presence or absence of coronary artery disease. We therefore determined the effect of preexisting coronary stenosis on the incidence of ventricular fibrillation during reperfusion after circumflex artery (CFX) occlusion. Twenty dogs underwent a 30-minute open-chest CFX occlusion. During reperfusion, CFX blood flow was restricted by a partial occluder. In dogs that survived reperfusion, peak CFX flow was 91 +/- 44% of baseline (mean +/- SD) compared with 163 +/- 68% in dogs that died of ventricular fibrillation (p less than 0.02). In another 17 dogs, the left anterior descending coronary artery was gradually occluded by an ameroid constrictor. After 17-39 days, the CFX was acutely occluded for 30 minutes and then reperfused. Collateral flow to the CFX, measured by microspheres, was 27.6 +/- 28.3 ml/min . 100 g-1 in dogs that died of reperfusion ventricular fibrillation, compared with 64.4 +/- 27.2 ml/min . 100 g-1 in surviving dogs (p less than 0.02). Thus, the risk of reperfusion ventricular fibrillation is greater in dogs with normal coronary arteries than in dogs with a flow-limiting partial stenosis of the artery undergoing transient occlusion, or chronic stenosis of a second coronary artery inducing collateralization to the artery subsequently undergoing transient occlusion. These results suggest that the risk of ventricular fibrillation during release of coronary spasm may be greater in patients without than in those with coronary artery disease.
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10,001,260
Exercise testing in patients with variant angina: results, correlation with clinical and angiographic features and prognostic significance.
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10,001,261
Eighty-two patients with variant angina underwent a treadmill exercise test using 14 ECG leads, and 67 also underwent exercise thallium-201 scans. The test induced ST elevation in 25 patients (30%), ST depression in 21 (26%) and no ST-segment abnormality in 36 (44%). ST elevation during exercise occurred in the same ECG leads as during spontaneous attacks at rest, and was always associated with a large perfusion defect on the exercise thallium scan. In contrast, exercise-induced ST depression often did not occur in the leads that exhibited ST elevation during episodes at rest. The ST-segment response to exercise did not accurately predict coronary anatomy: Coronary stenoses greater than or equal to 70% were present in 14 of 25 patients (56%) with ST elevation, in 13 of 21 (62%) with ST depression and in 14 of 36 (39%) with no ST-segment abnormality (NS). However, the degree of disease activity did correlate with the result of the exercise test: ST elevation occurred during exercise in 11 of 14 patients who had an average of more than two spontaneous attacks per day, in 12 of 24 who had between two attacks per day and two per week, and in only two of 31 who had fewer than two attacks per week (p less than 0.005). St elevation during exercise was reproducible in five of five patients retested during an active phase of their disease, but not in three of three patients who had been angina-free for at least 1 month before the repeat test. Twelve patients wih exercise-induced ST elevation were retested during treatment with calcium antagonist drugs; in 10 of 12, ST elevation did not occur with the second test. During a mean follow-up of 20.3 +/- 14.5 months, death or myocardial infarction occurred in three of the 25 patients with ST elevation during exercise, none of 21 with ST depression and two of 36 with no ST abnormality. We conclude that in variant angina patients, the results of an exercise test correlate well with the degree of disease activity but not with coronary anatomy, and do not define a high-risk subgroup.
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10,001,262
Postinfarction angina caused by coronary arterial spasm.
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10,001,263
Recurrent ST-segment elevations in leads where new Q waves developed were repeatedly recorded in six patients during a recovery phase of acute myocardial infarction. Such ST-segment elevations were transient, occurred with or without chest pain, and returned to control levels. No enzymatic changes signifying recurrent myocardial necrosis were found after each episode. Selective coronary cineangiography in one patient demonstrated a mild segmental stenosis in the coronary artery perfusing the infarcted area; this artery became completely occluded after administration of i.v. ergonovine. Administration of calcium antagonists effectively reduced the frequency of postinfarction angina and ST-segment elevations. The clinical features suggest that the postinfarction angina in these patients is produced by coronary arterial spasm and that coronary arterial spasm may cause severe life-threatening dysrhythmias.
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10,001,264
Relationship of blood pressure in 20-39-year-old men to subsequent blood pressure and incidence of hypertension over a 30-year observation period.
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-0.029746457934379578, -0.07702946662902832, -0.00433848612010479, 0.031451690942049026, -2.6901615157726155e-8, -0.0048210034146904945, 0.046105507761240005, -0.00420346250757575, -0.004884605295956135, -0.040878403931856155, -0.0024291081354022026, -0.012696757912635803, 0.10359872132539749, 0.024877414107322693, -0.01228333543986082, -0.005801148246973753, 0.0112588070333004, 0.09627071768045425, -0.027702797204256058, -0.034328196197748184, -0.06150767579674721, 0.07633963972330093, 0.0008593667298555374, 0.01911020837724209, 0.0060819899663329124, 0.17807388305664062, -0.036688677966594696, 0.032448552548885345, 0.04832978919148445, 0.040349118411540985, -0.026160258799791336, 0.05099961906671524, -0.047589436173439026, 0.0014499466633424163, 0.013265423476696014, 0.08174565434455872, 0.00514267897233367, -0.012132915668189526, -0.06556819379329681, 0.06307677179574966, -0.038148269057273865, -0.04467913508415222, 0.05850764736533165, 0.019404267892241478, 0.011276144534349442, 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10,001,265
The objective of this investigation was to determine the relationship of blood pressure (BP) in young men, ages 20-39 years, to their subsequent BP from the perspective of BP tracking, position in BP distribution and later evidence of hypertensive BP values. Since 1948, the Manitoba Study group has followed 3983 men, 90% of whom were 20-39 years old at entry. BP in persons not prescribed antihypertensive medications was examined at 5-year intervals during the 30-year observation period to 1978. To adjust for age, BP was examined within 5-year age groups at entry. The correlations between entry and subsequent BP at the same length of follow-up were greater for systolic than diastolic BP and increased with older ages. The correlation decreased wtih every 5-year examination after entry for all ages. Men whose BP was below the mean at entry were less likely to have a BP greater than 1 standard deviation (SD) above the mean at any of the examinations. Men with an entry BP greater than 1 SD above the mean were more likely to have BP greater than 1 SD above the mean later, but the relationship decreased considerably after 20 years, especially in 20-24-year age group. The results were similar for the probability of hypertension values (systolic BP greater than or equal to 140 or 150 mm Hg, diastolic BP greater than or equal to 90 or 95 mm Hg) at later examinations. Thus, BP in later life can be predicted from BP at ages 20-39 years and can identify groups at high or low risk for hypertension.
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10,001,266
Coronary artery disease mortality in relatives of hypertriglyceridemic school children: the Muscatine study.
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0.004802868235856295, 0.034524884074926376, 0.03158235177397728, -0.06811484694480896, -0.006903443019837141, -0.006471827160567045, 0.07296165078878403, 0.05063957720994949, 0.014765414409339428, 0.03824649378657341, -0.08310084044933319, -0.06961517781019211, -0.06232207268476486, -0.042878251522779465, -0.03727603703737259, 0.01654239371418953, -0.043553102761507034, -0.024113263934850693, 0.14265474677085876, -0.008571725338697433, 0.03570698946714401, 0.047441266477108 ]
10,001,267
From 2655 healthy school children participating in the 1973 and 1975 Muscatine Coronary Risk Factor School surveys, two groups of index cases were selected for a detailed family study of coronary mortality: a group with fasting triglyceride levels greater than the ninetieth percentile on both surveys (n = 75) and a group with triglyceride levels less than the tenth percentile on both surveys (n = 47). Coronary mortality in adult (age 30 years or older) first- and second-degree relatives was not different between the two groups. When the families of the high-triglyceride group was further subdivided based on the cholesterol percentile of the index child, greater coronary mortality was observed in the relatives of index cases with high cholesterol (higher than the seventy-fifth percentile). This study suggests that family members of children with elevated triglyceride and low cholesterol levels do not have excess coronary mortality.
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10,001,268
Tellurium-123m-labeled-9-telluraheptadecanoic acid: a possible cardiac imaging agent.
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10,001,269
Factors that affect the reproducibility of measurements of left ventricular function from first-pass radionuclide ventriculograms.
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10,001,270
To examine which factors affect the reproducibility of ejection fraction (EF), pulmonary transit time (PTT) and segmental wall motion assessed from first-pass radionuclide angiograms (FPRA), 32 patients who had FPRA were randomized for site of injection of isotope (right or left arm) and projection (right or left anterior oblique [RAO or LAO]). The quality of injected bolus was measured from the full width at half maximum (FWHM) of the bolus time-activity curve in the superior vena cava. All patients had two sequential studies on each of two consecutive days, and each study was analyzed independently by two observers. For EF, inter- and intraobserver correlations ranged from 0.94-0.98. EF was higher in the RAO than the LAO projection (mean 47.4% vs 40.3%, p less than 0.001), but neither injection site nor bolus FWHM affected the results. For PTT, interobserver correlations ranged from 0.75-0.93 and intraobserver correlations from 0.61-0.85. Variability in PTT was large, and inter- and intraobserver variabilities were directly related to bolus FWHM (mean 0.60 +/- 0.21 second for interobserver differences in PTT of less than 2.0 seconds, mean 1.55 +/- 0.86 seconds for interobserver differences in PTT of greater than 2 seconds [p less than 0.005]). Differences in FWHM between sequential studies were 0.28 +/- 0.29 second when intraobserver differences in PTT were less than 2 seconds and 1.04 +/- 0.67 seconds when differences in PTT were greater than 2.0 seconds (p less than 0.005). Variations in PTT were not related to differences in projection or injection site. Wall motion was highly reproducible for both projections. In the RAO projection, one of 116 anterior segments (0.9%), one of 116 apical segments (0.9%), and four of 116 inferior segments (3%) were judged normal from one observer's images and abnormal from another. In the LAO view, discrepancies occurred in one of 126 septal segments (0.8%), two of 126 apical segments (1.6%) and four of 126 posterolateral segments (3%). This study shows that EF and wall motion are highly reproducible in any projection, but the choice of projection significantly affects the values for EF from FPRA. PTT measurements are less reliable, highly bolus dependent, and their use in clinical practice depends on quality control of the bolus of injected radionuclide.
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10,001,271
Immediate diagnosis of acute myocardial infarction by two-dimensional echocardiography.
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-0.040477436035871506, 0.017634151503443718, -2.2308224600919857e-8, -0.10195015370845795, -0.15773321688175201, -0.008183837868273258, -0.08074446022510529, -0.09753473103046417, -0.04713136702775955, 0.006905247922986746, -0.003176677506417036, -0.018560506403446198, -0.016679778695106506, -0.00850914791226387, -0.02820451371371746, -0.023140400648117065, -0.09396234154701233, 0.04015852138400078, -0.05587024614214897, -0.05429708585143089, -0.031122175976634026, -0.01815642975270748, -0.019792838022112846, 0.05638067051768303, 0.10413386672735214, 0.03093961626291275, -0.05275871977210045, -0.050263989716768265, 0.015931326895952225, -0.020719001069664955, -0.07071537524461746, 0.016305673867464066, -0.002551083220168948, -0.020531369373202324, 0.029559584334492683, 0.03978552669286728, 0.021646179258823395, 0.11627081781625748, -0.04764137044548988, -0.06007219851016998, 0.05456554889678955, -0.0286403838545084, -0.07127608358860016, -0.007146352902054787, 0.011683925054967403, 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10,001,272
To define the role of portable two-dimensional echocardiography (2-D echo) in the immediate diagnosis of acute chest pain syndrome, 80 consecutive patients were studied. Adequate 2-D echo studies were obtained in 65 (81%). Thirty-three patients had clinical evidence of transmural or nontransmural acute myocardial infarction (AMI), 18 of whom had nondiagnostic initial ECGs. Thirty-two did not have a clinical AMI. Thirty-one of the 33 (94%) patients with clinical AMI had regional wall motion abnormalities on the initial 2-D echo; the other two had uncomplicated nontransmural AMIs, diagnosed only by ECG in one and by ECG and moderate elevation of CK-MB isoenzyme in the other. Twenty-seven of the 32 patients without clinical AMI had normal regional wall motion on the initial 2-D echo and none had a complication (severe arrhythmia, recurrent pain, heart failure or death) during the hospital course. Conversely, 10 of the 36 patients with initial 2-D echo regional wall motion abnormalities had a complication (p less than 0.05). Thus, in patients with acute chest pain syndrome, an initial 2-D echo that shows no regional wall motion abnormality suggests that such patients will not develop an AMI or clinical complication during the hospital course. An initial 2-D echo with regional wall motion abnormality identifies a high-risk group of patients who are likely to have AMI and important cardiac complications and may, therefore, benefit from admission to an intensive care unit.
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10,001,273
Right atrial pacing soon after myocardial infarction.
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10,001,274
Esophageal pacing: a diagnostic and therapeutic tool.
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10,001,275
Evaluation of a QRS scoring system for estimating myocardial infarct size. I. Specificity and observer agreement.
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10,001,276
We evaluated a simplified version of a previously developed QRS scoring system for estimating infarct size using observations of Q- and R-wave durations and R/Q and R/S amplitude ratios in the standard 12-lead ECG. Groups of subjects with a minimal likelihood of having myocardial infarcts and minimal likelihood of having common noninfarction sources of QRS modification were studied to establish the specificity of each of the 37 criteria. Only two criteria required modification to achieve 95% specificity. These 37 criteria form the basis of a 29-point QRS scoring system. A 98% specificity was achieved when a score of more than 2 points was required to identify a myocardial infarct. Fifty patients were studied to determine the intra- and interobserver agreement with this scoring system. Each criterion achieved at least 91% intra- and interobserver agreement. These impressive levels of specificity and observer agreement must be matched by high sensitivity of the scoring system and a good correlation between the point score and infarct size in patients with proven infarcts if the point score is to be useful for detecting and sizing infarcts. Sensitivity and correlation between point score and infarct size are evaluated in later studies in this series. The standard ECG is inexpensive and can be obtained repetitively and noninvasively; its QRS complex may be an important means of estimating the size, presence and location of myocardial infarcts.
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10,001,277
Acceleration of the ventricular response during atrial fibrillation in the Wolff-Parkinson-White syndrome after verapamil.
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10,001,278
We examined the electrophysiologic effects of verapamil in eight patients with the Wolff-Parkinson-White syndrome. Verapamil shortened the antegrade effective refractory period of the accessory pathway in three patients and abbreviated the shortest cycle length with 1:1 conduction over the accessory pathway in two patients. More significantly, verapamil decreased the shortest RR interval between preexcited ventricular complexes during atrial fibrillation (279 +/- 20 msec vs 236 +/- 18 msec, mean +/- SEM; p less than 0.01). After verapamil, two patients required cardioversion for hemodynamic deterioration after acceleration of the ventricular response during atrial fibrillation. In the four patients with predominantly preexcited ventricular complexes during atrial fibrillation the ventricular rate accelerated after verapamil, whereas in patients with predominantly normal ventricular complexes, the average ventricular rate decreased or did not change after verapamil. Verapamil may result in significant acceleration of ventricular response during atrial fibrillation in the Wolff-Parkinson-White syndrome. The safety of verapamil in individual patients with the Wolff-Parkinson-White syndrome should be established by electrophysiologic testing before its use.
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10,001,279
Procainamide and retrograde atrioventricular nodal conduction in man.
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10,001,280
Recent studies that show a depressant effect of procainamide (PA) on retrograde conduction in patients with atrioventricular (AV) nodal reentrant tachycardia (RT) have suggested possible incorporation of AV nodal bypass tracts. Electrophysiologic effects of i.v. PA, 10 mg/kg, on retrograde AV nodal conduction were examined in 13 patients without RT, demonstrable AV nodal refractory period curves, or accessory pathways. Ventriculoatrial (VA) conduction was recorded before and after PA using intracardiac electrograms, incremental ventricular pacing and extrastimulation. With incremental pacing during the control, VA block occurred at a mean cycle length (CL) of 364.6 +/- 87.9 msec. After PA, VA conduction was abolished in five of 13 patients due to onset of retrograde block in the AV node; in seven of 13, VA block occurred at a longer paced CL after PA (344.2 +/- 51.2 msec vs 477.1 +/- 93.2 msec). In one patient, PA did not affect VA conduction. PA invariably produced prolongation in the VA interval at comparable CL of pacing. With ventricular premature stimulation, the retrograde H2A2 intervals during the control period were short (less than 50 msec) in seven of 13, intermediate (60-100 msec) in three of 13 and long (greater than 100 msec) in three of 13 cases. PA either abolished H2A2 conduction (H2 but no A2) or prolonged the H2A2 intervals by 5-20 msec in most cases in this series. The data suggest that i.v. PA almost uniformly depresses retrograde AV nodal conduction in the intact human heart. This depressant response to PA is not indicative of presence of partial or complete AV nodal bypass tracts.
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10,001,281
Pirmenol, a new antiarrhythmic agent: initial study of efficacy, safety and pharmacokinetics.
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-0.03515153005719185, 0.0712338238954544, -0.0025073476135730743, -2.4332750925282198e-8, 0.024452444165945053, -0.029985226690769196, 0.012743700295686722, -0.009441397152841091, -0.039120592176914215, -0.03885786235332489, -0.007907035760581493, -0.009191439487040043, -0.0695878341794014, 0.006388477049767971, 0.01115585956722498, 0.006793129723519087, 0.050857413560152054, 0.013630833476781845, -0.013175412081182003, 0.03811553493142128, -0.006202249322086573, 0.06297697871923447, 0.07764086127281189, 0.023313477635383606, -0.03780045732855797, -0.03582325205206871, -0.0286148339509964, -0.05076691135764122, -0.0021473506931215525, 0.019473562017083168, 0.035645101219415665, 0.013750186190009117, -0.006142315920442343, -0.048469699919223785, -0.003521583741530776, 0.003954373300075531, 0.0180200282484293, 0.09934554249048233, 0.009167686104774475, 0.045346904546022415, -0.010328342206776142, -0.013156693428754807, -0.010617195628583431, 0.08670944720506668, -0.04192327335476875, 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10,001,282
Pirmenol (CI-845), a new antiarrhythmic drug, was studied for the first time in humans to establish a minimum effective i.v. dose in 10 patients with chronic, stable premature ventricular complexes (PVCs) and to evaluate toxicity and pharmacokinetics. Infusions of 70-150 mg were associated with a 90% or greater reduction in PVCs nine of the 12 times they were administered to six patients. Peak plasma concentrations were 1.0-3.8 micrograms/ml at the end of these infusions. At the same time, small but significant increases in diastolic blood pressure (4 mm Hg) and QTc interval (0.01 second) were seen, but both values were within the normal range. Pirmenol was associated with no change in heart rate, systolic blood pressure, PR interval or QRS duration, renal, hepatic or hematologic function, or symptoms. Blood, plasma and free drug concentrations declined biexponentially after cessation of a 150-mg infusion (n = 4), with a terminal half-life of 7-9.4 hours. The therapeutic response, lack of toxicity, and relatively long half-life indicate that pirmenol is a promising antiarrhythmic agent.
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-0.10110969841480255, -0.03815518319606781, 0.009491310454905033, 0.05849401280283928, -0.03360174968838692, 0.029240787029266357, -0.023371638730168343, 0.06817079335451126, 0.024681182578206062, 0.017838237807154655, 0.09890120476484299, 0.04621495306491852, -0.07493717968463898, -0.055062342435121536, 0.07151307165622711, -0.04833503067493439, -0.0008244074415415525, 0.0032501097302883863, -0.07096106559038162, -0.019116071984171867, -0.045211851596832275, -0.0006392463692463934, -0.00685052340850234 ]
10,001,283
Sequelae of the initial attack of acute rheumatic fever in children from north India. A prospective 5-year follow-up study.
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10,001,284
We determined the outcome of acute rheumatic fever in 85 children from North India who had received regular antistreptococcal prophylaxis after their first attack. By the end of the 5-year follow-up, 33 patients had rheumatic heart disease. Mitral insufficiency, the most common valvular lesion, appeared in 91% of the patients, whereas mitral stenosis developed in only 18%. Initial carditis, congestive heart failure, cardiomegaly or moderate-to-severe mitral insufficiency significantly increased the risk of rheumatic heart disease (p less than 0.001). The recurrence rate of acute rheumatic fever in children who received continuous prophylaxis was 0.006 per patient-year. Most recurrence (92%) mimicked the first attack and produced further cardiac damage in five patients with carditis and in one patient with chorea. Cardiac status during the first attack of rheumatic fever and the continuity of prophylaxis were the major determinants of outcome. Statistical comparisons disclosed that with continuous prophylaxis, the prevalence rate, evolution and clinical spectrum of the sequelae of acute rheumatic fever in children from India do not differ significantly from those in the West.
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10,001,285
Overestimation of pediatric cardiac output by thermal indicator loss.
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10,001,286
The accurate measurement of pediatric cardiac output by thermodilution requires that the quantity of cold indicator introduced into the central circulation be known. This study defines an important source of error in the correction factor for the amount of heat gained by small volumes of cold injectate during passage through pediatric catheter systems. This error may result in significant overestimation of cardiac output (as much as 59%) when blood at body temperature is withdrawn into the injection lumen of the pediatric catheter before the injection.
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10,001,287
Right ventricular dysplasia: a report of 24 adult cases.
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10,001,288
Right ventricular dysplasia is characterized by an abnormality in the development of part of the right ventricular musculature. Patients with right ventricular dysplasia may present with ventricular tachycardia, supraventricular arrhythmias, right-heart failure or asymptomatic cardiomegaly. Twenty-two adult patients with right ventricular dysplasia who had recurrent ventricular tachycardia were seen during a 7-year period. The male/female ratio was 2.7:1. The mean age at the time of hospitalization was 39 years. All but one of the patients had ventricular tachycardia of a left bundle branch block configuration. With few exceptions, the T waves were inverted over the right precordial leads. The heart was usually enlarged and the pulmonary vasculature was usually normal. In six patients who had two-dimensional echocardiograms, all showed increased right ventricular diastolic dimensions. All patients had right ventricular angiography; the diagnosis of right ventricular dysplasia was substantiated during surgery in 12 patients and at autopsy in another. Two other patients who did not have arrhythmias had right ventricular dysplasia diagnosed by right- and left-heart angiography. Our unique experience, when combined with a literature review of 34 adult cases, permits a composite clinical profile of this condition in the adult.
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10,001,289
Late survival and symptoms after repair of tetralogy of Fallot.
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10,001,290
The long-term results of 414 patients who underwent repair of tetralogy of Fallot between 1967 and 1977 were studied and correlated with the results of others. There were nine late deaths (8-year actuarial survival 95.8%). Six of the deaths wee directly related to the malformation or its treatment. Eight patients (2.4%) required reoperation. Ten patients (4.8%) had arrhythmic symptoms. Eight (3.1%) had congestive heart failure that required treatment. The risk factors associated with late events of all types, including death, were: older age at repair, a high mean ratio of peak systolic right-to-left ventricular pressures (PLV/RV) immediately after repair, and the presence of a Potts anastomosis. Neither a transannular patch nor a previous Blalock-Taussig or Waterson anastomosis was an incremental risk factor. Bacterial endocarditis was not observed. Three hundred seven patients underwent repair primarily or after a single Blalock-Taussig or Waterston shunt and had a PRV/LV of 0.85 or less after repair. Among these selected patients, the actuarial survival was 98.1%, which is still lower than that for the general population (p = 0.12), and freedom from events was 95.9%. Late after repair, PRV/LV was lower by 6 +/- 28% (+/- SD) than PRV/LV immediately after repair (p = 0.03) in the 33 restudied patients with such data. The higher the PRV/LV immediately after repair, the greater the percent reduction.
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10,001,291
Comparison of synthetic and natural glucosylceramides as substrate for glucosylceramidase assay.
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10,001,292
Commercially available [3H]glucosylceramide is derived from spleen tissue of patients with Gaucher's disease. When such tritiated glucosylceramide was diluted with unlabelled glucosylceramide from different sources and used as the substrate for assays of glucosylceramidase, the apparent activities obtained differed drastically. When diluted with synthetic N-stearoyl- or N-lignoceroyl-glucosyldihydrosphingosine, the release of [3H]glucose was 4-5 times greater than when diluted with unlabelled glucosylceramide from Gaucher spleen, with either brain or fibroblast homogenate as the enzyme source. The Ki values of the synthetic substrates were 15-30 times greater than the Km for the natural mixture, indicating much lower affinity of the synthetic substrates for the enzyme. Although the reason for the reduction in affinity could not be identified, caution is required when the commercial [3H]glucosylceramide is to be diluted with unlabelled glucosylceramide.
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10,001,293
Determination of phosphatidylglycerol in amniotic fluid by a simple one-dimensional thin-layer chromatography method.
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10,001,294
Phosphatidylglycerol (PG) in amniotic fluid is the second important component of lung surfactant phospholipids and may be clinically useful in assessing fetal lung maturity in utero. Although methods for PG determination are available, there are shortcomings in clinical application. We developed an alternative reliable one-dimensional thin-layer chromatography(TLC) method for separating and quantitating PG in amniotic fluid. A mini-TLC plate (8 X 10 cm) was prepared from silica gel H containing 5% ammonium sulfate. The plate was first developed in tetrahydrofuron/dimethoxymethane/methanol/2N ammonium hydroxide (30.0:20.6:5.6:3.0 v/v) and then in chloroform/methanol (60.9, v/v) in the same direction. PG was clearly separated from other phospholipids and neutral lipids, even when large amounts of other phospholipids were present on the TLC plate. The density of the charred PG was directly proportional to the amount of PG up to 8 nmol. The content of PG in nmol in the specimen can be quantitated by comparing with a standard PG. Up to 10% of blood serum or 3% meconium showed no detectable PG, nor did these substances affect PG quantitation in amniotic fluid. This method is sensitive and accurate. It is also time-saving and economical.
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10,001,295
Phospholipid enhances triglyceride quantitation using an enzyme kit methods.
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10,001,296
Covalent linkage of antisera to microparticulate cellulose using 1,1'-carbonyldiimidazole: a rapid, practical method with potential use in solid-phase immunoassay.
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10,001,297
Determination of human serum placental alkaline phosphatase, using theophylline inhibition.
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-0.026169156655669212, 0.01996377296745777, -0.06523991376161575, 0.016160856932401657, 0.03627731651067734, 0.09273853898048401, 0.03537454083561897, 0.08057618141174316, 0.08409327268600464, 0.11334381252527237, -0.04551133140921593, 0.021899709478020668, -0.03887563943862915, -0.00850942824035883, 0.04785040393471718, -0.015831349417567253, 0.06495271623134613, 0.07405992597341537, 0.008370929397642612, -0.09333653748035431, -0.04917038232088089, -0.03714867681264877, 0.0520375594496727, 0.07550077885389328, 0.028325609862804413, -0.04984666779637337, 0.034719400107860565, -0.03717485070228577, 0.033484384417533875, -0.039706312119960785, 0.0910457894206047, -0.0444161519408226, -0.05469377338886261, 0.04170757159590721, 0.048048779368400574, -0.035110000520944595, -0.009260268881917, 0.035762492567300797, -0.03027573972940445, -0.013811537995934486, -0.03161473572254181, 0.07861766964197159, -0.010756745003163815, -0.07307221740484238, 0.10783432424068451, 0.00244660465978086, 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-0.0026459498330950737, 0.03756813332438469, -2.2079843731148685e-8, 0.10784351080656052, -0.08617445826530457, 0.030285295099020004, -0.0016704740701243281, -0.07485772669315338, -0.09055741876363754, 0.02501155063509941, -0.015274417586624622, -0.03814128413796425, -0.011265215463936329, -0.05673559010028839, -0.01947571337223053, -0.06014474853873253, 0.018360106274485588, -0.014361044391989708, 0.032075680792331696, -0.013958310708403587, 0.07557522505521774, -0.013484027236700058, -0.019560381770133972, 0.04459125176072121, 0.035144008696079254, -0.06413647532463074, -0.005678545217961073, -0.01176399551331997, 0.030384492129087448, 0.026072362437844276, 0.032841697335243225, -0.0223124697804451, -0.023496100679039955, 0.11145898699760437, -0.018152961507439613, -0.007341158110648394, -0.03110392764210701, 0.018448131158947945, 0.02584294229745865, -0.03129987791180611, 0.07530886679887772, -0.04862503334879875, 0.032795246690511703, -0.06514296680688858, -0.014647775329649448, -0.0045713866129517555, 0.006121662445366383, 0.07126577198505402, -0.05579127371311188, 0.04651612043380737, 0.010964476503431797, 0.013972023501992226, -0.007000320125371218, 0.03925906494259834, -0.07808614522218704, -0.043692294508218765, -0.03914012014865875, -0.052560944110155106, -0.016107358038425446, 0.0023404608946293592, -0.14782127737998962, -0.12610718607902527, -0.004572812933474779, 0.01830035261809826, 0.022721225395798683, 0.1623716950416565, -0.016063189134001732 ]
10,001,298
Comparison of the polypeptide composition of cystic fibrosis plasma with normal plasma by high resolution electrophoresis.
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10,001,299
Cystic fibrosis and normal plasma proteins were compared by the method of high resolution two-dimensional electrophoresis in polyacrylamide gels. For the first dimension, samples were treated with urea and dithiothreitol and then subjected to isoelectric focusing in pH gradients of 3.5-10.0 or 5.0-8.0. The second dimension involved sodium dodecyl sulfate electrophoresis into gels of 10-20% polyacrylamide gradients. In one "blind" experiment, an attempt to segregate 12 plasma samples into six cystic fibrosis and six normals based on the polypeptide patterns was unsuccessful. Experiments using known cystic fibrotic and normal plasma samples (three further samples of each), depleted of albumin prior to electrophoresis, also failed to confirm the presence of cystic fibrosis related proteins or peptides. We have not been able to substantiate, by electrophoretic means, changes of sialic acid content of any plasma glycoprotein which might be expected to occur, for example, as a result of the postulated altered sialyltransferase activity in cystic fibrosis liver.
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