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Biomedical subjects

G Klinger

Publications and source records attributed to G Klinger.

At least 37 records · Page 2Linked to original sources

[Intraoperative findings and postoperative computer tomographic follow up of inflammatory aortic aneurysm].

PURPOSE: Retrospective evaluation of postoperative long-term results after surgery of inflammatory aortic aneurysms (IAAA) with computed tomography (CT). Findings in CT were analysed with particular attention to the development of inflammatory tissue adjacent to the aneurysm site. MATERIAL AND METHODS: Of 2101 patients operated on an aortic aneurysm 5.4% (114 patients) presented typical intraoperative features of inflammatory aortic aneurysms. 54 of these 114 patients (47%) were examined via computed tomography pre- and post-operatively. On an average the follow-up-study was performed 2.5 years postoperatively. RESULTS: All follow-up-studies revealed a correct location of the aortic prostheses. In 85.1% of the cases there was either no or negligible persisting inflammatory tissue with a diameter of less than 2 mm. 10.6% of the patients demonstrated remaining but reduced inflammatory tissue. In 4.3% of the cases the extent of the inflammatory tissue had not changed. Aneurysms of the anastomoses (n = 4), morphologic renal changes (n = 7) and an aorto-enteric fistula were demonstrated by CT as postoperative complications. CONCLUSIONS: In evaluating recurrence of the aneurysm and possible complications as well as the development of the inflammatory tissue, postoperatively performed computed tomography proved a reliable diagnostic method.

Aortic Aneurysm, Abdominal↗

Increased prevalence of urinary tract infections and anomalies in infants with pyloric stenosis.

We performed a retrospective analysis of all patients admitted to our institution with a diagnosis of infantile hypertrophic pyloric stenosis (IHPS) during a 10-year period from 1985-95 in order to assess the possible association between IHPS and urinary tract infections (UTIs). All 285 patients with IHPS had radiological or ultrasonographic confirmation of that diagnosis and underwent the Ramstedt procedure. Those who continued to be symptomatic were evaluated for UTI by urine analysis and culture. Positive cases were further evaluated for urinary system anomalies. The male:female ratio of IHPS was 3.4:1. Concomitant UTI was diagnosed in 8 patients by suprapubic aspiration or bladder catheterization. The prevalence of UTI in this series was 2.8%, 20-fold higher than the expected prevalence. Three of the 8 patients with UTI (37.5%) had urinary tract anomalies. These findings suggest an association between IHPS and UTI. We recommend that all IHPS patients be evaluated for UTI and positive cases undergo further evaluation for urinary anomalies.

Female↗

Labor affects cytokine production in newborns.

PROBLEM: To investigate whether the mode of delivery or the drugs given to the mother during labor may affect the newborns' immune system. METHOD OF STUDY: Three groups of term newborns were included: A, spontaneously delivered with i.v. analgesia (n = 37); B, spontaneously delivered with epidural analgesia (n = 26); and C, delivered by cesarean section under general anesthesia (n = 29). Natural killer (NK) cell cytotoxicity, mitogenic response, and the capacity of peripheral blood mononuclear cells (PBMCs) to produce interleukin (IL)-1 beta, IL-2, IL-3, IL-6, and tumor necrosis factor (TNF)-alpha were examined. RESULTS: NK cell cytotoxicity increased significantly in all three groups of newborns on the second day of life. Decreased IL-2 production was observed in newborns delivered by cesarean section. Spontaneous IL-1 beta secretion was higher in newborns to mothers treated with epidural analgesia. Spontaneous IL-6 secretion was elevated in infants to mothers undergoing general anesthesia and surgery or epidural analgesia. TNF-alpha production was increased in newborns delivered by cesarean section. CONCLUSION: The immune response of the newborn is affected by the mode of delivery and/or drugs given to the mother during labor.

Analgesia, Epidural↗

Early-onset and adult periodontitis associated with abnormal cytokine production by activated T lymphocytes.

There is growing evidence for an important role of the immune system in the pathogenesis of periodontitis. To further characterize the possible immunoregulatory dysfunction of peripheral blood mononuclear cells (PBMC) in periodontitis patients, we investigated functional aspects of PBMC from patients with early-onset periodontitis (EOP) and adult periodontitis (AP). Compared to controls, we observed decreased proliferative responses of PBMC from patients with EOP following stimulation with a mitogenic stimulus (phytohemagglutinin). To investigate whether this abnormality reflects a modulation in cytokine production, we measured the in vitro production of interleukin (IL)-3, IL-5, granulocyte macrophage colony-stimulating factor (GM-CSF), and interferon-gamma (IFN-gamma) by activated PBMC. PBMC in EOP patients expressed significantly decreased levels of IFN-gamma protein in response to mitogenic stimulation. Reduced IFN-gamma secretion was associated with decreased IFN-gamma and IL-2 mRNA expression in these cells, as well as decreased HLA-DR surface expression on monocytes. On the other hand, we observed significantly higher levels of IL-5 and GM-CSF in the same system using PBMC from AP patients. These were comparable to the levels observed for patients with allergic asthma. These data imply that EOP is associated with decreased Th1-like cytokine expression, and that the PBMC response from patients with AP is predominantly Th2/Th0 in nature.

Adolescent↗

Normal pulmonary function in a monoamniotic twin discordant for bilateral renal agenesis: report and review.

Renal agenesis and obstructive urinary tract anomalies causing oligohydramnios usually result in pulmonary hypoplasia. We report on the first female monoamniotic twin born with a combination of bilateral renal agenesis, agenesis of the urinary collecting system, absent external genitalia, anal atresia and single umbilical artery, compatible with VATER association but with normal pulmonary function. The infant had none of the manifestations of Potter sequence, in particular the facial changes and pulmonary hypoplasia typically associated with bilateral renal a/dysgenesis. The monoamniotic cotwin had normal renal function, such that sufficient amniotic fluid volume was maintained. This patient emphasizes the importance of adequate amniotic fluid volume for normal pulmonary development. The possible underestimation of genital malformations in the VATER association should be considered. Also noteworthy is the rare absence of external genitalia.

Abnormalities, Multiple↗

[Sex hormones and antioxidant status].

Physiologically, an influence of sex steroids on the antioxidative capacity can be seen at least as a short-term effect. First of all the steroid effects are due to the estrogen component rather than the progestin component. The antioxidative potential of natural estrogens is several times higher than that of vitamin E. Long-term studies should be performed to verify this in perimenopausal hormone replacement.

Adult↗

alpha-thalassemia caused by a 16 bp deletion in the 3' untranslated region of the alpha 2-globin gene including the first nucleotide of the poly A signal sequence.

We have identified a 16 bp deletion in the 3' untranslated region of the alpha 2-globin gene, including the first nucleotide of the polyadenylation signal sequence. The propositus, her mother and one of her brothers, all heterozygotes for the above deletion, have mild microcytic anemia. This is the first description of a deletion in the alpha gene involving both the 3' untranslated region and the polyadenylation signal sequence, causing alpha-thalassemia.

Anemia↗

[Effect of ethinyl estradiol-dienogest combination on serum androgen concentrations].

Antiandrogens or progestins with an antiandrogenic component usually have only a weak antigonadotropic activity. It is thus possible that the antiandrogenic effect on the cellular level is cancelled or at least reduced by an increased ovarian androgen production. The aim of the four submitted clinical studies of the progestin and antiandrogen dienogest alone (0.5-2 mg/day) or of a combined regimen of ethinylestradiol (0.03 mg) plus dienogest (2 mg) (EE/DNG) was to examine the influence on the serum androgen and SHBG concentrations as well as on the serum FSH, LH, progesterone and 17 beta-estradiol concentrations in young women. Like the progesterone derivatives, dienogest has a relatively low antigonadotropic activity. Inhibition of ovulation is mainly produced by peripheral mechanisms such as the reduction of preovulatory 17 beta-estradiol secretion. Dienogest alone has no significant effects on the serum SHBG and androgen concentrations. Unlike this, the combination of EE plus DNG markedly increases SHBG concentrations (to 2.1-3.7 fold the basal levels). The decrease in serum androgens with total testosterone (by 17 and 40%), free testosterone (by 48 and 54%) and dehydroepiandrosterone sulfate (by 51%) corresponds to the values shown in the literature for other oral contraceptives with modern progestins. EE/DNG does not affect the serum concentrations of 5 alpha-dihydrotestosterone (DHT), although the marker of the peripheral transformation from T to DHT, androstanediol glucuronide, is distinctly reduced (by 38%). In a double-blind comparison no differences are found between EE/DNG and a regimen combining 0.02 mg of ethinylestradiol and 0.150 mg of desogestrel. Solely the SHBG concentrations, with EE/DNG, as expected, are significantly higher. In a sequential regimen, dienogest, chlormadinone acetate and desogestrel (progestins without binding to SHBG) enhance the inhibitory effect of ethinylestradiol sulfonate on free testosterone, whereas norethindrone acetate and levonorgestrel (progestins with a strong binding to SHBG) reduce this effect of the estrogen significantly. These results exclude the possibility that the very distinct antiandrogenic effect of dienogest on a cellular level is neutralised or reduced by an increased systemic supply of androgen.

Adolescent↗

Can grapefruit juice influence ethinylestradiol bioavailability?

The effects of grapefruit juice on the bioavailability of 17 alpha-ethinylestradiol (EE2) after a single oral administration of 50 micrograms EE2 have been investigated. The pharmacokinetics of EE2 were studied in an open, randomized, cross-over study in which 13 healthy volunteers were administered the drug with herbal tea or grapefruit juice (naringin, 887 mg/ml). In contrast to herbal tea, grapefruit juice increased the peak plasma concentration (Cmax) significantly to 137% (mean; range 64% to 214%, p = 0.0088) and increased the area under plasma concentration-time curve from 0 to 8 hours (AUC0-8) to 128% (mean; range 81% to 180%, p = 0.0186). This study shows that grapefruit juice increases the bioavailable amount of EE2. A possible explanation may be that grapefruit juice inhibits the metabolic degradation of EE2. Whether the increased bioavailability of EE2 following grapefruit juice administration is of clinical importance should be investigated in long-term studies.

Administration, Oral↗

Increased creatine kinase brain isoenzyme concentration in cerebrospinal fluid with meningitis.

CPK-BB (CK-BB) isoenzyme is an intracellular enzyme released in various neurologic conditions, including central nervous system (CNS) infections. Activity of CK-BB in cerebrospinal fluid (CSF) was determined in 80 children by electrophoresis and densitometry. The possible correlation between CNS infection and CK concentrations was assessed. Significantly elevated concentrations of CK activity (P < 0.01) in the CSF were found in children with bacterial meningitis as compared with children with either aseptic meningitis or normal CSF findings. The data suggest the possibility of utilizing CSF CK activity to differentiate between bacterial and viral meningitis in situations where a routine CSF examination is inconclusive.

Adolescent↗

Losartan in heart failure. Hemodynamic effects and tolerability. Losartan Hemodynamic Study Group.

BACKGROUND: The aim of the present study was to assess the short- and long-term effects of multiple doses of the angiotensin II receptor antagonist losartan in heart failure. METHODS AND RESULTS: A multicenter, placebo-controlled, oral, multidose (2.5, 10, 25, and 50 mg losartan once daily) double-blind comparison in patients with symptomatic heart failure and impaired left ventricular function (ejection fraction < 40%). Invasive 24-hour hemodynamic assessment was performed after the first dose and after 12 weeks of treatment. Clinical status and tolerability of treatment with losartan over the 12-week period were also evaluated. One hundred fifty-four patients were enrolled, of which 134 met the protocol criterion of baseline pulmonary capillary wedge pressure > or = 13 mm Hg. During short-term administration, systemic vascular resistance (SVR) (largest reduction against placebo of 197 dyne.s-1.cm-5 at 4 hours) and blood pressure fell significantly with 50 mg, lesser decreases were seen with 25 mg, and no discernible effects were seen with 2.5 and 10 mg. After 12 weeks of treatment, similar effects were seen on SVR and blood pressure (maximal fall in SVR against placebo, 318 dyne.s-1.cm-5 at 5 hours with 50 mg). In addition, pulmonary capillary wedge pressure fell with 2.5, 25, and 50 mg (largest reduction against placebo of 6.3 mm Hg at 6 hours with 50 mg), cardiac index rose with 25 and 50 mg, and heart rate was lower with all active treatment groups. Active treatment was well tolerated, and excess cough was not reported. CONCLUSIONS: This study showed that oral losartan administered to patients with symptomatic heart failure resulted in beneficial hemodynamic effects with short-term administration, with additional beneficial hemodynamic effects seen after 12 weeks of therapy. Clear effects were seen with both 25 and 50 mg, with the greatest effect seen with 50 mg.

Aged↗

[Selenium and antioxidant status in various diseases].

All healthy mammalian organisms are characterized by an equilibrium between the occurrence of highly reactive oxygen species and their destruction by anti-oxidants. Numerous diseases go hand in hand with a disturbance of the homoeostatis. In order to avoid or minimize the destructive effect of the oxidant stress on biological structures, therapies utilizing drugs with anti-oxidant effects are increasingly being applied. Preconditions for these therapies are a characterisation and a follow-up of the anti-oxidant status in the diseased organism. In the course of the present study selenium, glutathione peroxidase and malondialdehyde were determined in patients with various clinical pictures (terminal renal insufficiency, septic shock, high-risk gravidieties, arterioscleroisis, pulmonary carcinoma, acute myocardial infarction, test patients taking the contraceptive pill). Patients with terminal renal insufficiency and those suffering from septic shock syndromes clearly show a selenium decrease in serum and whole blood as well as a drop in the GSH-Px-activity, and increased malondialdehyde concentrations in the serum. Both are a reflection of an increased lipid peroxidation. First results of a selenium therapy are available for patients with therminal renal insufficiency and post-traumatically induced renal failure. The interpretation of the findings in the categories "high-risk gravidity" and "women on the contraceptive pill", which show a normal GSH-Px-activity and significantly increased malondialdehyde concentrations, seems problematic. The organism counteracts an increased lipid peroxidation with a normal plasma-GSH-Px-activity, clearly a sign of a still normal anti-oxidant potential.

Acute Kidney Injury↗

Influence of ethinylestradiol-containing combination oral contraceptives with gestodene or levonorgestrel on caffeine elimination.

In a controlled clinical trial, the elimination of caffeine was examined in 20 healthy women prior to and during one cycle of treatment with either of two oral contraceptive formulations, one containing 0.075 mg gestodene and 0.03 mg ethinylestradiol and one containing 0.125 mg levonorgestrel and 0.03 mg ethinylestradiol. In addition, caffeine clearance was determined 1 month after the last intake of the oral contraceptives. Compared with pretreatment values, the clearance of caffeine was reduced by about 54% and 55% after one treatment cycle with gestodene- and the levonorgestrel-containing oral contraceptive, respectively. Other pharmacokinetic parameters of caffeine, such as tmax and Cmax, were not affected. Clearance values returned to pretreatment values 1 month after the last administration of the oral contraceptives. There was no difference in the reduction of caffeine clearance between contraceptive formulations. A small, but significant difference in the AUC(0-24 h) values of ethinylestradiol was noted between both preparations. There was no correlation between the AUC(model) values of caffeine and the AUC(0-24 h) values of ethinylestradiol. In the present study, a somewhat more pronounced effect on the elimination of caffeine was observed than in previous investigations, where several contraceptive steroids were administered only for a period of 2 weeks.

Administration, Oral↗

The influence of Microgynon and Diane-35, two sub-fifty ovulation inhibitors, on voice function in women.

The early days of oral contraceptives showed some evidence that these medications may have caused undesirable side effects on the voice, mainly in terms of virilization. In a random study carried out at the university hospitals of Jena and Berlin (Charité), two more recent drugs were tested in this regard, one containing cyproterone acetate (Diane-35) and the other one levonorgestrel (Microgynon), both from Schering. Ninety-one patients took part in extensive clinical and instrumental phoniatric investigations of voice function over a period of one year. No significant side effects on the voice could be proven for the two preparations. Gynecological and clinical effects of both Diane-35 and Microgynon were similar during the one-year study period. Women taking Diane-35 had less intracyclic bleedings and amenorrhea. Also, acne was more favorably influenced by Diane-35.

Adolescent↗

Pharmacokinetics of ethinylestradiol and levonorgestrel after administration of two oral contraceptive preparations.

Serum concentration profiles and pharmacokinetic parameters (cmax, tmax, AUC24, AUC0-00, MRT) of ethinylestradiol (EE2) and levonorgestrel (LNG) were obtained following administration of two combined oral contraceptives. The constituents of the preparations were as follows: Gravistat (0.05 mg EE2, 0.125 mg LNG); Minisiston (0.03 mg EE2, 0.125 mg LNG). In 20 of the volunteers blood samples were taken before and up to 36 hours following the intake of a single table. In 11 women the investigation was carried out at day 21 of a treatment cycle (steady-state condition). In spite of pronounced interindividual variations of the pharmacokinetic data, a clear dependency of EE2 concentration curves on the estrogen dose of the respective preparation could be demonstrated. Under the condition of steady-state (21st day of administration) there was a slight but significant rise of the EE2 peak serum concentrations and a pronounced increase of the LNG levels, closely reflected by elevation of the AUC values. SHBG serum concentration was significantly increased by the 10th day of treatment in all subjects receiving Gravistat, whereas the mean value in the Minisiston-group did not remarkably change. Although LNG is known to be bound to SHBG with high affinity, the missing parallelism between LNG- and SHBG-concentrations suggests other (additional?) mechanisms for the elevated LNG-binding capacity in women taking combined EE2-LNG preparations.

Administration, Oral↗

In vitro phagocytosis by crevicular phagocytes in various forms of periodontitis.

Phagocytes from the gingival crevice fluid (CF-cells) of 11 patients with localized juvenile and post-juvenile periodontitis (LJP/PJP), 14 with rapidly progressive periodontitis (RPP), 11 with adult periodontitis (AP), and 14 controls without periodontal disease were examined. Phagocytic activity in vitro was assessed. Crevicular washings were obtained from healthy sites of controls and diseased sites of patients after completion of the oral hygiene phase (professional and home care). The cells were carefully processed to avoid mechanical damage. The in vitro phagocytosis by uptake of opsonized C. albicans was performed in a moist chamber (30 minutes, 37 degrees C) and examined by light microscopy. CF-cells were differentiated on the basis of their morphological appearance. The majority of cells in crevicular washings were PMNs, some macrophages, and few lymphocytes. Phagocytic activity in patients with LJP/PJP and RPP was significantly decreased in comparison with that from AP and the control group. The decreased percentage of cells phagocytosing opsonized C. albicans was associated with the enhanced adherence of opsonized C. albicans. Moreover cell viability of CF-cells from LJP/PJP sites was significantly reduced. The data from the present study suggest that the in vitro phagocytosis of crevicular phagocytes in juvenile and rapidly progressive periodontitis lesions is diminished.

Adolescent↗