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Biomedical subjects

H Graf

Publications and source records attributed to H Graf.

At least 37 records · Page 2Linked to original sources
PubMed1997

[Weight discordance of the second twin: effect on perinatal morbidity and mortality. An 8-year analysis of 213 twin deliveries].

In this retrospective eight-years-study we examine factors to be considered responsible for higher perinatal mortality in twins, especially in twins with discordant body weight. As a main risk factor for this we find vaginal delivery, i.e. from a non-vertex position. Other additional reasons for the higher perinatal mortality of twins are prematurity (less than 34 weeks of gestation) and birthweight lower than 1500 grams. Early hospitalisation has a positive influence on that risk. The perinatal mortality in the second twin (6.7%) is twice as high as in the first twin. The highest perinatal mortality (17.6%), however, is in twins with discordant growth whereas the second twin had a higher birthweight at delivery (15% more than the first twin). In twins with discordant body weight cesarean section gives advantage to the second twin versus vaginal delivery from breech presentation.

Apgar Score↗
PubMed1996

Thyroid hormone activation of transcription is potentiated by activators of cAMP-dependent protein kinase.

We characterized the cross-talk between activators of protein kinase A (PKA) and thyroid hormone (T3) in T3 receptor (TR)-mediated transcription. U937 cells were cotransfected with a plasmid expressing the TR and a reporter plasmid containing a T3 response element (TRE) oriented either as a direct repeat or as a palindrome upstream of the thymidine kinase promoter linked to the chloramphenicol acetyltransferase gene. T3 activated transcription by 10-fold. T3 response was potentiated 2.5-3-fold by activators of PKA, but an activator of protein kinase C or of guanylate kinase was ineffective. In the absence of T3, activators of PKA had no effect on transcription. TR heterodimerization with the retinoid X receptor may facilitate T3/PKA cross-talk because coexpression of the retinoid X receptor potentiated cross-talk. Synergy was not observed in JEG-3, F9, CV-1, HeLa, L929, and HTC cells, indicating that it may require cell-specific factors. Synergy required the DNA- and ligand-binding domains, but not the amino-terminal domain, indicating that T3- and TRE-induced conformational changes on the TR are essential for cross-talk. PKA phosphorylated the TR in vitro, suggesting that, like other nuclear receptors, the TR is a target for PKA. These results imply that PKA cross-talks with T3 at the level of the TRE-bound TR, enhancing its transcriptional activity in a cell-specific manner.

8-Bromo Cyclic Adenosine Monophosphate↗
PubMed1996

Antimetastatic action of the prostacyclin analogue cicaprost in experimental mammary tumors.

In breast cancer, the survival rate strongly depends on the number of lymph nodes involved. A drug with a specific inhibitory activity on lymph node and organ metastases would therefore be a candidate for adjuvant therapy after surgery. Prostacyclin and its stable analogues have been shown to interfere with certain steps of the metastatic cascade and to inhibit the number of lung colonies after i.v.-inoculation of various tumor cell lines. Our data reveal that cicaprost, a metabolically stable and orally active analogue of prostacyclin, has pronounced antimetastatic effects in a series of spontaneously metastasizing rodent tumors. In the SMT 2a and 13762 MTLn3 mammary carcinomas of the rat, cicaprost given daily from the day of tumor implantation strongly inhibits the number of lung metastases as well as lymph node weights without exerting an effect on the primary tumor. Even starting treatment when palpable primary tumors are present gives a pronounced antimetastatic activity. To demonstrate that cicaprost has an effect on metastases already settled in the respective organ, treatment was started after surgical removal of the primary tumor. In the SMT 2a tumor, a strong inhibition of the number of metastases was shown. Interestingly, a perioperative treatment schedule was also effective in both models used. As primary tumor growth in vivo or proliferation in vitro remained unchanged by cicaprost, its mode of action seems to be related to one or more mechanisms of the metastatic process. In tumor cell lines expressing a functional prostacyclin receptor, stimulated tumor cell migration is inhibited and changes of differentiation status are obvious. In conclusion, cicaprost strongly inhibits lymph node and organ metastases of spontaneously metastasizing rodent mammary tumors with a mode of action different from cytostatic or antihormonal drugs.

Animals↗
PubMed1995

Intravenous calcitriol normalizes insulin sensitivity in uremic patients.

Recent studies suggest that secondary hyperparathyroidism and/or vitamin D deficiency are responsible for the insulin resistance in chronic renal failure. We investigated the effect of a 12-week intravenous treatment with 1,25 dihydroxycholecalciferol on glucose metabolism in 10 hemodialysis patients compared with 10 healthy control subjects by the frequently-sampled intravenous glucose tolerance test, analyzed with the minimal model technique. Compared to control subjects, the uremic patients featured elevated levels of parathyroid hormone (432 +/- 60 vs. 41 +/- 4 ng/liter, P < 0.001), insulin resistance (insulin sensitivity index, SI: 4.9 +/- 0.8 vs. 9.5 +/- 0.9 min-1/(microU/ml), P < 0.002), increased posthepatic insulin delivery (6.48 +/- 2.48 vs. 2.73 +/- 3.14 nmol/liter in 4 hr, P < 0.001) and a reduced C-peptide fractional clearance (0.033 +/- 0.004 vs. 0.085 +/- 0.009 min-1, P < 0.0002). Following treatment with 1,25 dihydroxycholecalciferol, the parathyroid hormone levels decreased significantly to 237 +/- 30 ng/liter (P < 0.05), the insulin sensitivity index (SI: 9.6 +/- 2.2, P < 0.05) reached a value similar to that of control subjects, and posthepatic insulin delivery decreased to 4.63 +/- 0.83 nmol/liter in 4 hr (P < 0.01), while all the other parameters remained unchanged. In summary, uremic patients with secondary hyperparathyroidism were found to be severely insulin resistant and hyperinsulinemic. Intravenous vitamin D treatment led to a significant reduction of parathyroid hormone levels and to a complete normalization of insulin sensitivity in the hemodialysis patients. Thus, intravenous 1,25 dihydroxycholecalciferol improves insulin resistance in uremic patients, acting per se or by reducing secondary hyperparathyroidism.

Adult↗
PubMed1995

Reliability of single and double probing attachment level measurements.

Clarification of the reliability associated with probing attachment level measurements and with diagnostic rules derived from them is necessary to examine the potential of these measurements as reliable markers of the disease process and as an outcome measure in clinical treatment studies. The purpose of the present study was to describe and compare the longitudinal reliability of single and double probing attachment level measurable by estimating false positive and false negative rates. In 20 systemically healthy adults with untreated advanced adult periodontitis, probing attachment levels and probing depth were measured at 6 sites in all teeth at the start of the study, and every 30 days thereafter for 11 months. Attachment levels were double measured, using acrylic onlays providing reference points and an electronic pressure sensitive probe. Attachment loss from baseline of 2.5 mm or more was used to accept dynamic attachment loss. The statistical methods for the cross-sectional analysis included mean absolute differences between double measurements and cross-correlations. Longitudinal analyses, expressing estimates of diagnostic error rates were made using maximum likelihood methods. 5 measurement protocols were compared. The results showed that the mean absolute difference between replicate measurements was 0.095 mm in bicuspids and 0.107 mm in molars. The mean absolute differences decreased over time from 0. 128 mm in visit 3 to 0.08 mm in visit 7. Correlation coefficients for replicate measurements were higher than 0.98. In general, false positive rates were markedly lower (< or = 0.02) than false negative rates (< or = 0.31). The relative sample size required to obtain comparable statistical power, was minimized in premolars when using the first of 2 measurements or the mean of 2 measurements, and in molars when using the first of 2 measurements. The methodology used in the present study provides guidelines for designing clinical studies which maintain statistical power by balancing off examiner reliability and sample size.

Acrylic Resins↗
PubMed1995

Influence of hemodialysis on plasma concentration-time profiles of mefloquine in two patients with end-stage renal disease: a prophylactic drug monitoring study.

Prophylactic drug monitoring of mefloquine and its carboxylic acid metabolite were studied in two patients with end-stage renal disease undergoing long-term hemodialysis treatment. The patients, short-term travellers to areas where malaria is endemic, took 250 mg of mefloquine (Lariam) once weekly for 2 weeks before and during their 3-week stay abroad and for one week after their return. Pre- and postdialysis blood samples were drawn before their departure and after their return. The concentration-time profiles of mefloquine and its metabolite in plasma samples taken before and after the 3- to 4-h dialysis sessions were similar. Mefloquine and its metabolite could not be detected in the dialysate. These findings show that mefloquine and its metabolite are not, or are very poorly, removed by hemodialysis. Concentrations in plasma and accumulation kinetics were similar to those reported for healthy volunteers and were associated with high prophylactic efficacy against malaria. No special dosage adjustments have to be made in patients undergoing hemodialysis treatment to achieve concentrations in plasma similar to those in healthy volunteers. The prophylactic dose of mefloquine could be given before, during, or after the hemodialysis session.

Africa, Eastern↗
PubMed1995

Short-term effects of phase I therapy on crevicular cell populations.

The purpose of the present study was to use a novel intracrevicular lavage technique to evaluate short-term effects of phase I therapy on crevicular cell populations. Nineteen patients with untreated advanced adult periodontitis were selected for phase I therapy. One side of the dentition was treated with ultrasonic curets (U), the other side with manual curets (M). Nine months before (-9), immediately prior to (0), and 1 month after treatment (+1) gingival index (GI), plaque index (PI), bleeding index (BI), bleeding on probing (BOP), probing depth (PD), and probing attachment levels (PAL) were measured at all sites in the dentition. Crevicular lavages were obtained from 3 to 4 selected sites per patient at the same time points. Crevicular leukocytes were vital stained with ethydium bromide-fluorescein-diacetate (EB-FDA). The total number of cells and the percentage of vital cells (%) were calculated for each sample. Clinical and lavage parameters obtained from the selected sites were compared between U and M sites, and between pre- and post-treatment values. The results showed that without treatment PAL remained at the same level at both pretreatment time points -9 and -0 (control). At 1 month after treatment there were statistically significant reductions in GI, PI, BOP, and PD (P < 0.001 for each comparison), and a statistically significant gain in PAL from 4.9 to 4.1 mm (P = 0.014). The total number of leukocytes per sample was similar at both pretreatment time points, but numerically reduced at 1 month after treatment. The percent of vital leukocytes was above 74% at both pretreatment time points (control). After treatment these values were below 70%. This reduction was statistically significant (P < 0.002). These results suggest that periodontal phase I therapy leads to shifts in crevicular cell populations.

Adult↗
PubMed1994

Bromelain protease F9 reduces the CD44 mediated adhesion of human peripheral blood lymphocytes to human umbilical vein endothelial cells.

The thiol protease bromelain has been shown to remove T-cell CD44 molecules from lymphocytes and to affect T-cell activation. We investigated the effect of a highly purified bromelain protease F9 (F9) on the adhesion of peripheral blood lymphocytes (PBL) to human umbilical vein endothelial cells (HUVEC). Preincubation of the lymphocytes with F9 reduced the adherence to about 20% of unstimulated and to about 30% of phorbol-dibutyrate (P(Bu)2) stimulated lymphocytes. Using flow cytometry, both crude bromelain and protease F9 reduced the expression of CD44, but not of LFA-1, on PBL. F9 was about 10 times more active than crude bromelain; at 2.5 micrograms/ml of F9 about 97% inhibition of CD44 expression was found. A mAb against CD44 was tested and found to block the F9-induced decrease in PBL-binding to HUVEC. The results indicate that F9 selectively decreases the CD44 mediated binding of PBL to HUVEC.

Antibodies, Monoclonal↗
PubMed1994

[Effect of rapeseed in beef cattle feeding on fatty acid composition, vitamin E content and oxidative stability of body fat].

Four groups of five fattening bulls each consumed a concentrate--wheat straw-diet (2.5:1) supplemented with either 0, 7, 14 or 21% ground rape seed for 350 days. Rape seed contained 427 g crude fat (ether extract) and 127 mg vitamin E per kg dry matter. The supplementation with rapeseed increased the fat concentrations in the rations from 25 to 50, 75 and 100 g, and of vitamin E from 11 to 19, 26 and 34 mg per kg dry matter. All bulls were slaughtered with about 560 kg body weight. Fatty acid composition of depot fat and of the fat of musc. long. dorsi were determined by gas liquid chromatography. Vitamin E concentrations in blood, depot fat and muscle were determined by HPLC. Oxidative stability of depot fat was measured as induction time by means of rancimat-test. Rape seed supplementation decreased C16-fatty acids and increased C18-fatty acids in depot and muscle fat. Muscle fat contained significantly more mono and poly unsaturated fatty acids (40.2 and 7.4%) than depot fat (33.5 and 2.0%, respectively). Rape seed supplementation enhanced significantly the vitamin E-concentrations in all body samples. In depot fat vit. E increased from 4.5 to 7.3, 8.5 and 14.9 micrograms/g. Induction time increased from 10.9 to 18.5, 16.1 and 19.5 h, when 0, 7, 14 or 21% rapeseed were added.

Adipose Tissue↗
PubMed1994

Increased levels of circulating islet amyloid polypeptide in patients with chronic renal failure have no effect on insulin secretion.

To elucidate the metabolism of islet amyloid polypeptide (IAPP) with respect to a possible renal elimination we investigated IAPP levels in 20 lean, nondiabetic patients with renal failure maintained on chronic hemodialysis (HD) and in 20 healthy controls. The basal levels of IAPP were significantly higher in uremic patients than in controls (15.1 +/- 3.2 vs. 3.2 +/- 0.2 pM, P < 0.001) suggesting renal excretion of IAPP. To investigate the impact of chronically elevated levels of endogenous IAPP on insulin secretion and insulin sensitivity, a frequently sampled intravenous glucose tolerance test (FSIGT) was performed in a subset of patients on hemodialysis and in age-matched healthy controls (C) and obese patients with normal (NGT) and with impaired glucose tolerance (IGT). Insulin sensitivity index (SI) was 8.7 +/- 1.5 in C (P < 0.05 vs. NGT, P < 0.01 vs. IGT), 5.4 +/- 0.9 in HD (P < 0.05 vs. IGT), 3.1 +/- 1.0 in NGT, and 2.0 +/- 0.5 in IGT. First phase insulin secretion was increased in patients on HD compared with those of several control groups. The results of this study therefore indicate a renal route of metabolism of IAPP. Increased endogenous circulating IAPP levels over a long period of time do not lead to a decrease in insulin release in patients on HD and do not cause the insulin resistance commonly seen in obesity and diabetes. Increased levels of circulating IAPP therefore are not likely to be a pathogenetic factor in the development of non-insulin-dependent diabetes mellitus (NIDDM).

Adult↗
PubMed1994

Ion exchange resins for the purification of monoclonal antibodies from animal cell culture.

We have compared various ion exchangers for monoclonal antibody (MAb) purification using different starting materials such as ascitic fluid and cell culture supernatant. Twelve cation and anion exchange resins were tested so far. Purification of MAbs with regard to the starting material is described. In well-defined conditions of adsorption (20 mM MES buffer, pH 6.50), one purification step based on cation-exchange chromatography is generally sufficient to achieve at least 90% purity of the MAb, even when produced by animal cell culture. Cation-exchange supports exhibit higher capacity for MAbs compared to anion exchangers. Among the cation exchangers tested, we have selected the cross-linked matrix S Sepharose FF for its large specificity and capacity for MAbs. Considering these key parameters and also the good mechanical resistance of the S Sepharose FF, we describe how, by varying the flow rate, sample concentration, and size of the column, the productivity may be improved in a monoclonal antibody purification process. Finally, a general 'gram scale' purification protocol of MAbs produced by animal cell cultures is proposed. This protocol, based on economical adsorption conditions and three steps of elution (100 mM, 200 mM and 1 M NaCl), allows the recovery of highly purified MAbs.

Animals↗
PubMed1994

[Reaction of the anterior eye segment to preventive Credé treatment].

A controversily carried discussion concerning the prophylaxis according to Credé is in process. Reviewer decline the Credé-prophylaxis. The high rate of side effects (Argentum conjunctivitis) interdicts with applications of Argentum nitricum. In a blind study we examined the reaction of the ophthalmic front-region in the first 5 days after delivery in 40 neonates with and without Credé-prophylaxis with Argentum nitricum. We found no significant differences in the frequency of pathological chances in the palpebra, conjunctiva bulbi et tarsi and cornea between the two groups. In the group of children, who had not been given Credé-prophylaxis there was the same frequency of palpebral edema and conjunctival hyperemia. Until there is no general screening for gonorrhea in the late pregnancy and because of lack of a better method as the prophylaxis according to Credé we can recommend the Credé-prophylaxis with argentum nitricum as an undangerous and save method for preventing gonoblennorrhea of neonates.

Anterior Eye Segment↗
PubMed1994

[Blood pressure values in normal pregnancy].

In two studies independent from each other we examined the behaviour of arterial blood pressure in normal pregnancy. Study 1 was performed in exactly defined external conditions, study 2 in normal antenatal clinic. Especially in study 1 a distinct reduction of blood pressure could be proved. Towards the end of pregnancy there is a raise of blood pressure. Blood pressure is dependent on the position of the body. Havdarized examination conditions have to be claimed with respect to reproducibility and comparability of the values.

Adult↗
PubMed1994

[The clinical value of plasma fibronectin in pregnancy].

We have measured plasmatic fibronectin in 23 normotensive pregnant women during pregnancy (overall 161 values). On the average 6 samples from every woman have been taken. Plasmatic fibronectin rose continuously from 313 +/- 76 mg/l in the first trimester to 416 +/- 194 mg/l in the third trimester. Normal pregnant women (n = 173, 358 +/- 140 mg/l) were compared with pregnant patients with preeclampsia (n = 37), woman with chronic hypertension in pregnancy (n = 25) and normotensive pregnant patients with intrauterine growth retardation (IUGR, n = 5). In the group with chronic hypertension (466 +/- 119 mg/l) there was no significant difference to the normal group, but we found a significant (p < 0.01) different value of fibronectin (748 +/- 195 mg/l) in the group of patients with preeclampsia. A tendency to higher fibronectin values was also noticed in the group with IUGR (739 +/- 212 mg/l). Because of the low number of patients this difference was not statistically significant. We conclude, that plasmatic fibronectin is an important, but not absolutely specific screening parameter for estimation of the endothelial injury in hypertensive disorders of pregnancy. We believe, that fibronectin is one the best parameters to forecast a preeclampsia.

Adult↗