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Biomedical subjects

M Hartmann

Publications and source records attributed to M Hartmann.

At least 37 records · Page 2Linked to original sources

Lack of pharmacokinetic interaction as an equivalence problem.

The demonstration that concomitant administration of drug B does not affect the pharmacokinetics of drug A can be adequately handled as an equivalence problem. Administration of drug A alone serves as reference and simultaneous administration of drugs A and B as test situation. The range of clinically acceptable variation in the pharmacokinetic characteristics of drug A defines the equivalence range. This will usually correspond to the bioequivalence range accepted for the comparison of different formulations of drug A. Equivalence, i.e. lack of pharmacokinetic interaction, is concluded if the 90%-confidence interval for the ratio (difference) of the expected medians for test and reference is entirely within the equivalence range. This decision procedure ensures that the consumer risk of incorrectly concluding "lack of interaction" is limited to 5%. Moreover, the producer risk of incorrectly concluding "interaction" can be controlled by appropriate sample sizes.

Drug Interactions

[Ocular changes in Alport's syndrome].

In a group of 17 patients with Alport's syndrome changes on the ocular fundus were detected in 35.3% without influence on the central visual acuity. At the same time a statistically significant reduction of sensitivity to contrast was proved. ERG examination revealed statistically significant changes in the a and b wave as regards steepness and in the b wave also as regards amplitude.

Adolescent

Correlation between retinoblastoma gene expression and differentiation in human testicular tumors.

Inactivation of the retinoblastoma gene (RB gene) is associated with the development of several human malignancies including retinoblastomas, some osteo- and soft tissue sarcomas, small cell lung cancer, and possibly breast and bladder cancers. To our knowledge, this gene has not been evaluated in human germ-cell malignancies. In this study 67 primary testicular germ-cell tumors and 4 testicular non-germ-cell malignancies were examined to determine the prevalence and nature of RB gene alterations. Decreased expression of RB gene mRNA was found in all testicular germ-cell tumors (both seminomas and nonseminomas) examined. The RB protein could not be detected by immunohistochemical analysis in the undifferentiated cells of any germ-cell tumors whereas the differentiated malignant cells present in 14/15 teratocarcinomas expressed the protein. No gross alterations of the RB gene were found at DNA level in any of the examined specimens. This and the presence of the RB protein in the more differentiated tumor cells of teratocarcinomas suggest that changes in transcript levels rather than mutation(s) of the gene may be responsible for the absent or decreased RB expression in human germ-cell tumors. To date studies on the mechanism of RB regulation have demonstrated that it occurs at the protein level by phosphorylation of the p105 gene product. The findings presented here indicate that additional regulation might occur at the transcript level.

Blotting, Southern

Expression of the hst-1 and c-kit protooncogenes in human testicular germ cell tumors.

Seventy testicular germ cell tumors were analyzed at the DNA and RNA levels for the c-kit, hst-1, and int-2 oncogenes using Northern and Southern blot analyses, respectively. There were significant differences in oncogene expression between seminomas and nonseminomas with c-kit being expressed in 24 of 30 (80%) seminomas but in only 3 of 40 (7%) nonseminomatous tumors (P = 0.0001, chi 2 test) and hst-1 being expressed in 24 of 38 (63%) nonseminomas but only 1 of 24 (4%) of seminomas (P = 0.0001, chi 2 test), demonstrating an inverse relationship in the expression pattern of these 2 oncogenes in human testicular germ cell tumors. A significant association between tumor stage and hst-1 expression in the nonseminoma group was found (P = 0.0002, chi 2 test). No gross alterations in the c-kit, hst-1, and int-2 loci were found at the DNA level and no int-2 mRNA expression was detected in any of the germ cell tumors examined.

Blotting, Southern

Protein phosphorylation in intact coronary endothelial cells by bradykinin.

In cultured coronary endothelial cells obtained from guinea pig hearts, bradykinin (10(-6) M) stimulated the 32Pi-incorporation into 5 substrate proteins with molecular weights corresponding to 27, 32, 60, 86 and 100 kDa. The time course of phosphorylation of the 60, 86 and 100 kDa proteins was rapid (within 30 s), but transient (max. within 1-2 min.), while the 32Pi incorporation into the 27 and 32 kDa protein was delayed but increased within 10 minutes. Ca+(+)-ionophore A 23187 (10(-5) M) and 12-O-tetradecanoylphorbol-13-acetate (TPA) (10(-5) M) both mimicked the effects of the bradykinin induced phosphorylation pattern. While A 23187 enhanced the phosphorylation of the 27, 60 and 100 kDa substrates, TPA increased the 32Pi-incorporation into the 32 and 86 kDa proteins. Furthermore the time course of protein phosphorylation elicited by A 23187 and TPA showed marked similarities to those obtained with bradykinin. Our findings are consistent with the view, that stimulation of coronary endothelial bradykinin-receptors activates both Ca+(+)-dependent protein kinases and protein kinase C.

Animals

Peritonitis caused by Trichomonas--a preliminary case report.

Trichomonas infections of the abdominal cavity are uncommon and case histories have not been published previously. A patient to whom reference is made this paper developed a combined immunodeficiency syndrome and portal hypertension with ascites on the basis of a cirrhosis of the liver. This seems to have been the precondition for a peritonitis caused by a Trichomonas species.

Ascites

Tissue oxygenation in hemorrhagic shock measured as transcutaneous oxygen tension, subcutaneous oxygen tension, and gastrointestinal intramucosal pH in pigs.

BACKGROUND AND METHODS: Tissue oxygenation, measured in peripheral tissue as transcutaneous PO2 (PtCO2) and subcutaneous PO2, was compared with the oxygenation in GI mucosa, which was measured as intramucosal wall pH (pHi), during experimental hemorrhagic shock and resuscitation in pigs. The pigs were hemorrhaged stepwise to a BP of 80 and 45 mm Hg, followed by retransfusion. PtCO2 was measured in the groin and subcutaneous PO2 was measured in the hip region. Intraluminal PCO2 was measured in the stomach, in the small intestine, and the sigmoid colon using silicone catheters. A simultaneous determination of arterial blood HCO3 concentration allowed pHi to be calculated using Henderson-Hasselbalch equation. Cardiac output was determined by thermodilution, and oxygen delivery (DO2) was calculated. RESULTS: Early indications of shock were decreases in PtCO2 and intestinal pHi (p less than .01). All measured variables decreased at the second step of bleeding. PtCO2 and subcutaneous PO2 was correlated to DO2 through the entire experiment (r2 = .25 and .49, respectively). Also, the pHi of the small intestine and the sigmoid colon correlated with DO2 (r2 = .36 and .25, respectively). PtCO2 and subcutaneous PO2 correlated with pHi in the small intestine and sigmoid colon. CONCLUSIONS: PtCO2 and pHi in the small intestine and sigmoid colon were the variables that most rapidly indicated blood volume loss. Subcutaneous PO2 and PtCO2, and small intestine and sigmoid colon pHi were correlated to total body oxygen transport. Peripheral tissue perfusion followed intestinal perfusion to some extent.

Animals

Carcinoma-in-situ cells in cultured human seminiferous tubules.

For the first time, early germ-cell derived tumour cells were studied in an in-vitro system of cultured seminiferous tubules. The intratubular tumour cells not only survived in culture for 7 days but were also able to multiply. Dividing tumour cells were identified in semi-thin sections and electron micrographs by morphological criteria. Additionally, mitotic activity was demonstrated by [3H]thymidine histo-autoradiography. There are numerous reports on cell lines established from solid non-seminomas, but up to now no references to seminoma cell lines or cultures of intratubular tumour cells are available. The culture of seminiferous tubules offers a tool in making carcinoma-in-situ cells accessible for experimental work.

Autoradiography

Insulin and glucose do not affect the glycogen content in isolated and cultured trophoblast cells of human term placenta.

The influence of insulin and glucose on the glycogen content of isolated trophoblast cells was measured for the first time. The cells were obtained by tryptic digestion of villous tissue from term placentae of 15 healthy women, further purified on a Percoll gradient and enriched by employing a monoclonal anti HLA class-I antibody. The cells stained intensively with PKK1 and exhibited the structural and phenotypical characteristics of intermediate and syncytiotrophoblasts. The mean glycogen content of cells cultured in Dulbecco's Modified Eagle's Medium with 5.5 mM glucose was 17.7 +/- 3.2 micrograms/mg protein, remained constant from days 1-4, and was unaltered by higher glucose concentrations (17 and 28 mM) in the medium. Between 2-5 h after a medium change, the cells contained 50% more glycogen than at the time of replacement. Short term (0-5 h) as well as long term incubations (24 h) with both pathological (10(-8) M) and physiological (10(-9) M) concentrations of insulin had no effect, with respect to either the rate of increase in glycogen or the maximum level. We conclude that the glycogen content of isolated syncytiotrophoblasts in vitro is invariant to extracellular glucose concentrations and is not regulated by insulin. This suggests that cells other than syncytiotrophoblasts and their immediate precursors account for the reported alterations of glycogen content in normal human term placenta in vitro under hyperglycemic or hyperinsulinemic conditions.

Cells, Cultured

[Visual acuity and color sensitivity in retinal detachment].

In patients with unilateral detachment of the retina after successful operation (buckling 3x, cerclage 3x, combined operation 4x), the visual acuity was assessed on Snellen optotypes or Landolt's ring chart. Optotype charts with rings were made according to recommendations of the commission for vision of the American Academy of Sciences. Snellen's visual acuity of healthy and affected eyes was 6/9-6/6. In all patients moreover sensitivity to contrast was examined assessed by means of a VISTESCH testing table. It was revealed that sensitivity for contrast in all operated eyes is significantly lower than in healthy eyes and that the threshold visual acuity and steepness of lines is significantly lower.

Color Perception

[Beta-HCG positive seminoma--incidence with special reference to tumor marker concentration in testicular venous blood].

The treatment of so-called "marker-positive" pure seminoma is still a controversial subject. We report on 32 cases of seminoma treated within 2 years. In these we measured beta-HCG and AFP in a cubital vein and in the spermatic cord veins. While 78% of the patients affected had elevated beta-HCG levels in the spermatic cord, in only 25% elevated beta-HCG levels were found in a cubital vein. This shows the markedly higher sensitivity of marker evaluation in spermatic cord veins. Furthermore, we conclude that seminoma generally produces beta-HCG and that therefore no change of the usual principles of therapy is required.

Adult

[SEP monitoring during clonidine therapy of alcohol delirium].

In 12 patients with developing alcohol withdrawal syndrome after abdomino-thoracic surgical procedures who were treated with Clonidine, short latency somatosensory evoked potentials were recorded. Clonidine leads to a good sedation, anxiolysis and moderated the psychotic symptoms. However, there was no significant correlation between the Clonidine medication and the SEP results over the time of drug administration concerning the primary cortical response N20 and the following N20/P25 wave. Therefore, the short-latency SEP-recording cannot provide a reliable monitoring of the good sedative effect of Clonidine in alcoholic withdrawal. The SEP responses after Clonidine are like those of morphine and are thought to have a similar central mode of action.

Alcohol Withdrawal Delirium

[Detection of proviral HIV DNA with polymerase chain reaction in the epidermis].

The infection of cells of the epidermis with HIV can still not be taken as proved, since the demonstration of HIV in Langerhans cells has not been universally accepted. In our study, the polymerase chain reaction was used to look for proviral HIV-DNA in epidermal cells collected by the suction blister technique. The primers flanked sequences of the gp41-encoding region of the env gene and hybridized with highly conserved HIV-DNA sequences. Amplified sequences were detected by the dot-blot technique. The PCR revealed HIV-DNA in epidermals cells of four HIV patients. In addition, HIV-DNA was detected in the mononuclear cells of the blood in the same patients by the PCR. These results strongly support the notion that in addition to blood cells, epidermal cells of HIV patients are also infected with HIV.

DNA, Viral

[Reexamination of cantilever bridges-a cross-section study].

In the present study reexaminations of 28 cantilever bridges and 26 conventional bridges were carried out. The aim was to evaluate the periodontal conditions and to give recommendations for use. Parameters were PI, GI, tooth mobility, pocket depth, gingival recession and BOP. Deducing from the results, which were statistical analysed, we recommend the cantilever bridges by right using. Special attention should be directed to antagonistical dentition.

Analysis of Variance

Lack of influence of pantoprazole on the disposition kinetics of theophylline in man.

The potential influence of pantoprazole (BY1023/SK&F96022), a newly developed selective inhibitor of the gastric H+,K(+)-ATPase, on therapeutic serum theophylline concentrations was investigated in a crossover study in 8 healthy male volunteers (age 25-30 [median 27] years, body weight 63-80 [median 68] kg). Steady-state serum theophylline concentrations were obtained by a two-step intravenous infusion scheme of approximately 350 mg theophylline each over 0.5 h and subsequently over approximately 10 h, respectively. In the test period, 30 mg pantoprazole were injected over 2 min on 5 consecutive days and theophylline was infused on day 4. In the reference period, placebo was administered i.v. on 2 consecutive days and theophylline on day 1. Serum pantoprazole concentrations were measured up to 12 h, serum theophylline concentrations up to 36 h. Pantoprazole was well tolerated with and without theophylline. There were no clinically relevant changes in blood pressure, heart rate, ECG and routine clinical laboratory parameters. Primary characteristic for confirmative assessment of no interaction was the area under the concentration/time curve (AUC). Lack of interaction in the sense of equivalence was concluded both for theophylline (with and without pantoprazole) and pantoprazole (with and without theophylline), as the 90%-confidence intervals of the AUC-ratio test/reference were within the equivalence range of 0.8 to 1.25. Further explorative analysis of theophylline disposition kinetics revealed this inclusion also for clearance and volume of distribution, but not for the half-life. In the case of pantoprazole, the corresponding 90%-confidence intervals for any of the secondary characteristics clearance, volume of distribution and half-life were within the above mentioned range.(ABSTRACT TRUNCATED AT 250 WORDS)

2-Pyridinylmethylsulfinylbenzimidazoles

Lack of pharmacokinetic interaction as an equivalence problem.

The demonstration that concomitant administration of drug B does not affect the pharmacokinetics of drug A can be adequately handled as an equivalence problem. Administration of drug A alone serves as reference and simultaneous administration of drugs A and B as test situation. The range of clinically acceptable variation in the pharmacokinetic characteristics of drug A defines the equivalence range. This will usually correspond to the bioequivalence range accepted for the comparison of different formulations of drug A. Equivalence, i.e. lack of pharmacokinetic interaction, is concluded if the 90%-confidence interval for the ratio (difference) of the expected medians for test and reference is entirely within the equivalence range. This decision procedure ensures that the consumer risk of incorrectly concluding "lack of interaction" is limited to 5%. Moreover, the producer risk of incorrectly concluding "interaction" can be controlled by appropriate sample sizes.

2-Pyridinylmethylsulfinylbenzimidazoles