Procyanidins from the roots of Fragaria vesca: characterization and pharmacological approach.
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Biomedical subjects
Publications and source records attributed to D Gross.
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Three different treatments of regional chemotherapy in colo-rectal malignancies and their results are presented. 1. Prophylactic chemotherapy with 5-FU--via the recanalized umbilical vein in patients without liver metastases (randomized study since 10/1980). 2. Intraportal adjuvant chemotherapy after resection of liver metastases. 3. Intraarterial chemotherapy in patients with unresectable liver metastases. The regional chemotherapy of the liver in colo-rectal diseases seems to increase the survival rate and the quality of life. The Port-A-Cath-system can be used repeatedly, however, there is a certain rate of complications to be expected.
The effect of the leukotriene D4, leukotriene E4 (LTD4/E4) receptor antagonist LY-171883 was studied in endotoxemia. Eighteen awake sheep were divided into three groups. In Group (n = 4) 4 mg/kg LY-171883 was twice injected intravenously. In Group II (n = 9) 1 microgram/kg E. coli endotoxin was administered intravenously. In Group III (n = 5) 4 mg/kg LY-171883 was given 15 min before, and 30 min after endotoxin. Infusion of LY-171883 in Group I did not alter baseline hemodynamic and pulmonary measurements. Infusion of endotoxin in Group II was followed by an initial rise of pulmonary artery pressure (PAP) to 51 torr (P less than 0.001), pulmonary microvascular pressure (Pmv) to 25 torr (P less than 0.005), pulmonary vascular resistance (PVR) to 1,019 dynes sec. cm-5 (P less than 0.001), systemic vascular resistance (SVR) to 2,830 dynes sec. cm-5 (P less than 0.001), plasma thromboxane B2 (TXB2) to 4,971 pg/ml (P less than 0.001), lymph TXB2 to 5,500 pg/ml (P less than 0.001), plasma 6-Keto PGF1 alpha to 1,469 pg/ml (P less than 0.005), and lymph 6-Keto PGF1 alpha to 2,518 pg/ml (P less than 0.005). The cardiac index (CI) fell to 100 ml/min. kg (P less than 0.01), PaO2 to 61 torr (P less than 0.01), and circulating WBC to 2,800 microliter (P less than 0.001). This was followed by a rise in pulmonary lymph flow (QL) to 35 ml/h (P less than 0.01) and lymph protein clearance (L/P.QL) to 23 ml/h (P less than 0.01). Pretreatment with LY-171883 in Group III resulted in rise of PAP to 35 torr (P less than 0.005), PmV to 18 torr (P less than 0.05), PVR to 398 dynes sec. cm-5 (P less than 0.01), SVR to 1,732 dynes sec. cm-5 (P less than 0.05), and CI increased to 170 ml/min.kg (P less than 0.005). L/P.QL, QL, Hgb, WBC, PaO2, PaCO2, Qs/QT, plasma and lymph TXB2, and plasma and lymph 6-Keto PGF1 alpha were not significantly changed by LY-171883. It is concluded that LY-171883 inhibited the smooth muscle effects of endotoxin, namely reduced PAP, Pmv, PVR, and SVR and increased cardiac output. Hypoxemia and increased pulmonary vascular permeability were unaffected by this leukotriene receptor antagonist.
There are currently no measures of maternal confidence specifically for the developmental issues that arise in children between 12 months and 36 months of age. Yet, maternal confidence has been correlated with indices of maternal and child competence. The purpose of this study was to assess the reliability and validity of the Toddler Care Questionnaire (TCQ), a measure of maternal confidence in toddlerhood, for use in clinical and research settings. The data provide strong evidence that the TCQ is a reliable instrument and has validity among middle-class mothers of toddlers. The data are discussed in terms of their clinical significance and directions for future research.
Two patients with pernicious anemia developed gastric carcinoid, one 20 years and the other 1 year after diagnosis of pernicious anemia. One of the patients underwent successful resection of the tumor, while the second, with diffuse gastric carcinoid, was managed conservatively. She is well and asymptomatic 32 months after the diagnosis. We discuss the dilemma in management of gastric carcinoid associated with pernicious anemia.
A 46-year-old woman's antidepressant therapy was changed from doxepin to desipramine because of sedative side effects. Within ten days of initiation of desipramine, a pruritic, morbilliform rash developed. The rash extended despite attempts to continue therapy with a tartrazine-free desipramine as well as antihistamines and prednisone. The rash promptly improved when desipramine was discontinued. Classic drug eruptions are quite uncommon with tricyclic antidepressants. Tartrazine, a common additive in the food and drug industry, is implicated in a number of hypersensitivity reactions. Our report presents an apparent case of desipramine-induced drug rash independent of tartrazine, and discusses the nonassociation of tartrazine.
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The importance of "apatite deposition disease" among the arthropathies has been recognized for some years: it is well known that X-ray microanalysis (XRMA) is an efficient method of determining the elemental constitution of microcrystalline deposits obtained from synovial fluids or from tendon washing solutions during examination in scanning electron microscopy. In all 25 patients studied (11 intraarticular and 14 extraarticular samples), alizarine red S staining was positive and XRMA confirmed the diagnosis of apatite deposition by determination of the phosphorus/calcium (P/Ca) ratio in the deposits. In the 25 patients the mean values obtained for the P/Ca ratios were situated between 0.362 and 0.450, with a general mean value of 0.411, i.e. a ratio clearly lower than the P/Ca ratio of pure hydroxyapatite specimens (0.438) measured in identical conditions. This apparent discrepancy seems to be related to the probable presence of carbonated apatites. The study confirmed the presence of apatite microcrystals in intra- and extraarticular location; in the first condition, these were generally found in patients with severe destructive arthrosis, whereas in the second condition the calcifications derived from supraspinatus tendons.
We report the first imaging of the spatial distributions of transmembrane potential changes induced in nonexcitable cells by applied external electric fields. These changes are indicated by the fluorescence intensity of a charge-shift potentiometric dye incorporated in the cell plasma membrane and measured by digital intensified video microscopy.
We employ the intensely fluorescent analogue diI-LDL (Barak, L. S., and W. W. Webb, 1981, J. Cell Biol. 90:595-604) as a counting marker to determine the numbers of LDL-receptor complexes that are contained in clusters on the surfaces of human fibroblasts and human epidermoid carcinoma cells. The application of quantitative digital intensified video optical microscopy allows the measurement of the fluorescence power collected from individual fluorescent spots on a cell with sufficient accuracy that the number of optically unresolved particles producing the fluorescence in the spot can be estimated. We demonstrate that isolated individual diI-LDL particles are detected on the surface of all cells investigated. Analysis of the LDL cluster size distributions on the various cell lines shows clear differences that correlate with efficiency of LDL metabolism. We find that normal fibroblasts (GM3348) have LDL-receptor complex populations dominated by large cluster sizes (greater than 4 LDL), while internalization-deficient J.D. mutant fibroblasts (GM2408A) and epidermoid carcinoma cells (A-431) show predominantly small clusters (1-3 LDL). No evidence for large-scale ordering or "superclustering" of clusters is found.
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41 patients with active rheumatoid arthritis entered a placebo-controlled double-blind randomised study in which 21 received slow intravenous injections (given in fractions over 10 min) of thymopentin (TP-5) 50 mg 3 times a week for 3 consecutive weeks and 20 received placebo in the same way. After 3 weeks of treatment the TP-5 group showed improvement (p less than 0.05 or p less than 0.01) in all but one of the clinical variables tested. There was improvement in the number of joints painful at rest, the number of joints painful on motion, scores for tenderness on pressure and swollen joints, severity of pain on awakening and morning stiffness, and right-hand grip strength; left-hand grip strength remained unchanged. In the placebo group, only morning stiffness improved significantly. The intergroup comparisons showed that thymopentin was significantly better than placebo in reducing tenderness, joint swelling, severity of pain on awakening, and disease activity. 4 weeks after the end of the TP-5 therapy, the improvement was still present although there was a trend towards relapses. No significant modifications occurred in any of the laboratory variables tested and only minor side-effects were experienced by either group.
Forty-one patients with active rheumatoid arthritis entered a controlled double-blind randomized study. Of these patients, 21 received prolonged intravenous injections (10 min) of thymopentin 50 mg three times a week for 3 consecutive weeks, whereas 20 received placebo. Both groups were comparable with regard to clinical parameters. No immunological tests were performed. Analysis of the results after 3 weeks showed that the improvement in the thymopentin group was statistically significant (p less than 0.05 or p less than 0.01) for all clinical parameters, except for the left-hand grip strength. On the other hand, no significant improvement was observed for any parameter, except morning stiffness, in the patients on placebo. The intergroup comparison showed statistically significant differences, favoring thymopentin over placebo treatment, in the Ritchie index, the scores of swollen joints, the assessment of severity of pain, and the scores for changes in the activity of the disease. The present placebo-controlled double blind study thus confirms the positive results generated in a similar open study, i.e., the beneficial therapeutic effect of prolonged intravenous injections of thymopentin in patients with severe rheumatoid arthritis. The drug appears to be safe at the dose regimen used.
We examined the ultrastructure of somatostatin-containing pancreatic D-cells in the rat in order to shed light on the function and mode of action of somatostatin in the pancreas. D-cells were first identified by indirect immunocytochemistry with the peroxidase-antiperoxidase technique on semithin (1-micron) sections of 2% glutaraldehyde-1.7% paraformaldehyde-fixed tissue from the tail of the pancreas. Fine ultrastructure of the positively identified D-cells was examined in adjacent sections (0.08 micron) by electron microscopy. D-cells characteristically exhibited long cytoplasmic projections that extended to capillaries. Each cell was divided arbitrarily into three zones of roughly equal size, nuclear, central, and capillary, and distribution of secretory granules into each zone was quantified. In unstimulated cells, secretory granules were dispersed throughout the D-cell. In sections obtained from rats stimulated to secrete somatostatin by infusion of 20 mM glucose-5 mM theophylline-20 mM L-arginine HCl, 75 +/- 4% of the D-cell granules was polarized to the capillary end of the cell, while only 54 +/- 2% was is this region in unstimulated rats (P less than 0.05). These studies suggest that pancreatic somatostatin is released into islet capillaries.
We investigated the effects of high-frequency chest wall compression (HFCWC) on peripheral and tracheal mucus clearance in anesthetized spontaneously breathing dogs. HFCWC was achieved by oscillating the pressure in a thoracic cuff with a piston pump. Regional lung retention of a technetium-99m sulfur colloid aerosol was monitored with a gamma camera. A peripheral mucus clearance index (PMCI) was defined for each region of interest. The tracheal mucus clearance rate (TMCR) was determined by bronchoscopic visualization of marker particle transport. Phase I: In seven dogs, 30 min of HFCWC at 13 Hz with peak cuff pressure (Pcuff) 100-120 cmH2O was found to significantly enhance PMCI in regions immediately under the cuff. (delta PMCI = 24.4 +/- 4.6 in the basal peripheral region.) Phase II: Because of subpleural hemorrhage in phase I, the effect of HFCWC on TMCR at various Pcuff levels was studied in five dogs. The enhancement of TMCR by HFCWC reached a plateau level at Pcuff = 50 cmH2O. Phase III: HFCWC at 13 Hz with Pcuff = 50-60 cmH2O was found to significantly enhance PMCI in five dogs without the consequence of hemorrhage. Correlations were found between the enhancement of PMCI and TMCR by HFCWC. These results demonstrate that HFCWC is effective in enhancing both peripheral and central mucus clearance in dogs and safe when moderate pressures are applied.
We examined the possibility that somatostatin, a tetradecapeptide distributed in the gut and the central nervous system, may influence food intake and behavior in rats. Although intravenously infused somatostatin did not alter food intake in 8 hour fasted rats, intracerebroventricularly infused somatostatin resulted in a biphasic response, first increasing then decreasing food intake. We also observed that the effects of somatostatin vary depending upon whether animals are fed or fasted. In fed rats, food intake was decreased, while in fasted rats food intake was increased. These results suggest that somatostatin can act in the central nervous system to stimulate appetite; but that other factors, possibly related to gut motility or clearance, may inhibit further feeding once the stomach is full.
IFN-gamma is known to induce expression of Ia antigens on a variety of cell types. In the present study, this activity of IFN-gamma has been analyzed with a panel of 36 melanoma cell lines, normal melanocytes, and 97 cell lines representing a range of other differentiation lineages. 55% of the melanoma cell lines express Ia antigens in a constitutive manner without IFN-gamma induction. Of the 16 Ia-melanoma lines, 13 could be induced to express Ia antigens by IFN-gamma, whereas three were noninducible. Melanocytes, which do not normally express Ia antigens, are converted to Ia expression by IFN-gamma. Ia antigens expressed constitutively or after IFN-gamma induction were identified with antibodies detecting monomorphic and allomorphic products of DR and DC loci. IFN-gamma appeared to be unique in its ability to induce Ia expression on melanoma and melanocytes; 14 other agents (including IFN-alpha and IFN-beta) known to influence growth or differentiation did not have Ia-inducing activity. Equally striking is the restriction of antigenic changes following IFN-gamma induction to HLA-associated products; of the 38 systems of cell surface antigens examined, only HLA-A,B,C, beta 2m, and Ia antigens were affected. A variety of other Ia- cell types were shown to be Ia-inducible by IFN-gamma; these included established lines of breast, colon, pancreas, bladder, kidney, ovary, and brain cancers, and cultures of normal fibroblasts, kidney epithelia, and epidermal keratinocytes. In contrast, three tumor types, teratocarcinoma, choriocarcinoma, and neuroblastoma, were not inducible for Ia expression, even though IFN-gamma could induce expression of HLA-A,B,C products. The broad representation of Ia antigens on most somatic cell types expressed either constitutively or after IFN-gamma can be viewed in an immunological context (antigen presentation/immune regulatory signals) or could indicate that Ia products have functions other than those related to immune reactions.