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Biomedical subjects

R Geiger

Publications and source records attributed to R Geiger.

At least 19 recordsLinked to original sources
PubMed2001

Altered arterial expression patterns of inducible and endothelial nitric oxide synthase in pulmonary plexogenic arteriopathy caused by congenital heart disease.

Flow-associated pulmonary hypertension leads to pulmonary plexogenic arteriopathy (PPA), a specific pulmonary vascular disease that includes vascular lesions characterized by abnormal vasodilatation and endothelial cell proliferation. Increased local production of NO has been suggested in this condition. Because reported data on the expression of endothelial NO-synthase (ecNOS) have been contradictory, we speculated that the expression of the inducible isoform of NOS (iNOS) is enhanced in this form of pulmonary hypertension. We investigated immunohistochemically the expression of ecNOS and iNOS in lung tissue of patients with flow-associated pulmonary hypertension (n = 18) and compared the findings with those in patients with increased pulmonary blood flow but normal pulmonary artery pressure (n = 10), with congestive vasculopathy (n = 6) and control subjects (n = 4). Immunoreactivity for ecNOS and iNOS was present both in normal and diseased pulmonary arteries. Marked immunoreactivity to both isoforms was present within the advanced lesions of PPA, including plexiform lesions. Semiquantitative analysis of immunoreactivity, both for ecNOS and iNOS, showed no correlation with the severity of morphologic vascular lesions (p = 0.29 and p = 0.23, respectively). In contrast to ecNOS, immunoreactivity for iNOS was increased in patients with flow-associated pulmonary hypertension compared with other patients (p = 0.02). The present study has demonstrated enhanced expression of iNOS in patients at risk for advanced PPA, but not in patients with other forms of pulmonary arteriopathy. Moreover, high expression of both ecNOS and iNOS were present in advanced lesions of PPA. These data suggest differentiated roles for different isoforms of NOS in the pathogenesis of this specific pulmonary arteriopathy.

Analysis of Variance↗
PubMed2000

Enhanced expression of vascular endothelial growth factor in pulmonary plexogenic arteriopathy due to congenital heart disease.

Congenital heart disease (CHD) leading to increased pulmonary blood pressure and flow is an important cause of pulmonary plexogenic arteriopathy (PPA). This type of arteriopathy tends to progress to an irreversible stage, hallmarked histologically by the emergence of a number of characteristic lesions, which include concentric laminar intimal proliferation and fibrosis, and plexiform lesions. The pathogenesis of these lesions, which connote a very poor prognosis, is not well understood. Since endothelial cell proliferation has been demonstrated in these lesions, it was hypothesized that vascular endothelial growth factor (VEGF), a key mediator of angiogenesis, might play a role in their pathogenesis. Thirty-nine patients with various types of CHD, who underwent cardiac catheterization and subsequent cardiac surgery, were studied prospectively. On the basis of a detailed assessment of the type of cardiac defect, the haemodynamic abnormalities, and the histopathological features evident from open lung biopsies, taken in all instances, patients were histologically grouped into cases with moderate PPA (n=18), advanced PPA (n=7), pulmonary congestive vasculopathy (PCV, n=5), and controls lacking pulmonary hypertension or increased pulmonary blood flow (n=4). Five patients were excluded from analysis because of inadequate sample size or quality. The presence of VEGF was assessed immunohistochemically using standard procedures and was correlated with haemodynamic and histological data. Immunoreactive VEGF was detected in pulmonary arterial smooth muscle cells and endothelial cells in 13 out of 34 cases and was more frequent and more pronounced in patients with the histological lesions of advanced PPA than in those with moderate PPA (p<0.01). VEGF positivity was particularly prominent in the lesions characteristic of advanced PPA. No difference in VEGF expression was observed between controls, PVC, and moderate PPA cases. Measured haemodynamic parameters did not differ significantly between VEGF-positive and VEGF-negative cases. We conclude that VEGF may play a role in the angioproliferative changes of advanced PPA.

Child↗
PubMed2000

Comparison between c-ELISA and CFT in detecting antibodies to Mycoplasma mycoides mycoides biotype SC in cattle affected by CBPP in Botswana.

Contagious bovine pleuropneumonia (CBPP), caused by Mycoplasma mycoides mycoides biotype small colony (SC) (MmmSC) appears to be making a serious comeback in Africa after successful control programs in many parts of the continent during the 1960s and 1970s. Botswana, a country that has been free from the disease for more than 50 years, was affected in 1995. An eradication policy was adopted by the Government of Botswana in which 320,000 cattle in the affected district of Ngamiland, Northwestern Botswana were slaughtered. This was followed by a restocking exercise in which 70,000 cattle were sent to the outbreak areas as replacement stock. It became necessary to carry out serosurveillance in order to ensure that the disease did not reenter Botswana and to ensure that the replacement stock remained free from the disease. The specificity and sensitivity of the complement fixation test (CFT) in Botswana was assessed in 82 cattle affected by the disease and held in a double fenced quarantine camp. The newly developed competitive ELISA was made available to the National Veterinary Laboratory (NVL) through the FAO/IAEA Joint Division in Vienna, Austria. Using postmortem lesions as the gold standard and a 2 x 2 contingency table, the two tests were compared in terms of their sensitivity and specificity in detecting antibodies to MmmSC. The CFT was found to be slightly more sensitive than the c-ELISA, and this could be related to the stage of the disease. A long-term study comparing the progression of the disease with the two tests is, therefore, essential.

Animals↗
PubMed1998

Interleukin-1 receptor antagonist and interleukin-6 for early diagnosis of neonatal sepsis 2 days before clinical manifestation.

BACKGROUND: Neonatal sepsis is a common and life-threatening disorder, particularly among preterm infants. Early initiation of antibiotic therapy is frequently delayed because the first clinical signs of sepsis are non-specific and there are no reliable early laboratory indicators. We investigated the time course of expression and the prognostic power of the early inflammatory mediators interleukin-1 receptor antagonist (IL-1ra), interleukin-6 (IL-6), and circulating intercellular adhesion molecule-1 (cICAM-1) before clinical diagnosis of sepsis. METHODS: In a prospective multicentre study, we monitored 182 very-low-birthweight infants in six intensive-care units for occurrence of sepsis. During routine or clinically indicated blood sampling, an additional sample was collected for measurement of IL-1ra, IL-6, cICAM-1, and C-reactive protein (CRP). Infants were grouped into those with proven sepsis, no infection, or unclassified. The mean study duration was 34 days. Whenever sepsis occurred, a study period of 10 days was defined: day 0 was the day of clinical diagnosis of sepsis; days -4 to -1 were the 4 days before diagnosis; days +1 to +5 were the 5 days after. We compared the concentrations of the immune mediators during the 10-day study period with group-specific baseline values from before day -4. FINDINGS: 101 infants were included in the analysis: 21 with proven sepsis, 20 with no infection, and 60 unclassified. We excluded 57 because of incomplete datasets and 24 who had early-onset sepsis. IL-1ra and IL-6 increased significantly 2 days before diagnosis of sepsis; maximum median increases within the study period were 15-fold for IL-1ra and 12-fold for IL-6. The diagnostic sensitivities of IL-1ra, IL-6, and CRP concentrations on day 0 of diagnosis were 93%, 86%, and 43%, respectively; corresponding values on day -1 were 64%, 57%, and 18%. The specificities of IL-1ra, IL-6, and CRP concentrations were 92%, 83%, and 93%. cICAM-1 had a specificity of only 64%. INTERPRETATION: IL-1ra and IL-6 are superior to cICAM-1 and CRP as predictors of sepsis 1 or more days before clinical diagnosis. Ad-hoc measurement of these cytokines could allow earlier initiation of antibiotic therapy with corresponding improvement in outcome in very-low-birthweight infants with sepsis.

Austria↗
PubMed1998

Hepatitis caused by antidepressive therapy with maprotiline and opipramol.

There are few published reports of antidepressive therapy induced hepatotoxicity. In most cases antidepressants cause only slight elevation of liver enzymes without clinical relevance. However, our patient with recidivation of unipolar depressive disorder developed severe laboratory abnormalities and clinical symptoms during therapy with maprotiline (Ludiomil) and opipramol (Insidon). To our knowledge, this is the first case report of bioptically proven severe acute hepatitis caused by these antidepressants. After their withdrawal, the patient's fatigue symptoms, scleric jaundice, and marked increase of liver enzymes completely disappeared. Hepatic side effects should be considered during antidepressive therapy with maprotiline and opipramol especially when additional clinical symptoms emerge.

Antidepressive Agents, Second-Generation↗
PubMed1997

Randomised trial of transjugular-intrahepatic-portosystemic shunt versus endoscopy plus propranolol for prevention of variceal rebleeding.

BACKGROUND: The transjugular-intrahepatic-portosystemic shunt is a new interventional treatment for portal hypertension. The aim of our study was to compare the transjugular shunt with endoscopic treatment for the prophylaxis of recurrent variceal bleeding. METHODS: Between March, 1993, and March, 1996, 126 patients with variceal bleeding were randomly assigned either transjugular shunt (n = 61) or endoscopic treatment (n = 65). Patients were followed up for a median of 14 (IQR 8-25) months and 13 (8-25) months, respectively. In 31 (51%) of the shunted patients, simultaneous transjugular-variceal embolisation was done at the time of shunt placement. Endoscopic treatment consisted of sclerotherapy and/or banding ligation and was combined with propranolol medication. FINDINGS: Technical success was achieved in all patients assigned to the shunt group. During follow-up, the cumulative 1-year variceal rebleeding rates in the shunted and endoscopically treated patients were 15% and 41% and the 2-year rates were 21% and 52% (p = 0.001), respectively. In nine (12%) patients from the endoscopic group treatment failed and the patients received the transjugular-shunt treatment. A total of 19 bleeding episodes from any source occurred in 15 patients in the shunt group compared with 100 episodes in 33 patients in the endoscopic group. There was no difference in survival with estimated 1-year survival rates for shunted and endoscopically treated patients of 90% and 89%, and 2-year survival rates of 79% and 82%, respectively. The incidence of clinically significant hepatic encephalopathy after 1 year was higher in the shunt group (36% vs 18%, p = 0.011). INTERPRETATION: These results suggest, that the transjugular shunt is more effective than endoscopic treatment in prevention of variceal rebleeding but has a considerable risk of hepatic encephalopathy. Survival is similar in the two groups.

Adult↗
PubMed1997

Changes in left ventricular function in shocked newborns.

OBJECTIVE: To assess whether the change in cardiac output after volume replacement is due to elevation of stroke volume or heart rate and to determine the effect of mechanical ventilation on the hemodynamic situation. DESIGN: Prospective study. SETTING: A ten-bed neonatal intensive care unit (level III) at a university hospital. PATIENTS: 15 consecutive newborns with blood pressure below the 10th percentile related to age and weight. INTERVENTIONS: Volume replacement with Ringer's lactate 20 ml/kg body weight. MEASUREMENTS AND RESULTS: Before and after volume replacement, arterial pressure recordings, blood gas analysis, and an echocardiographic study were carried out. Left ventricular and aortic diameters were measured by the two-dimensional M-mode technique and velocity time integral of aortic flow by the pulsed color Doppler technique. From these data, stroke volume and cardiac output were calculated. Cardiac output (703 +/- 204 vs 826 +/- 166 ml/ min, p < 0.005) and cardiac index (267 +/- 69 vs 302 +/- 55 ml/min per kg body weight, p < 0.01) changed significantly due to an appreciable elevation in stroke volume (5.2 +/- 1.7 vs 5.8 +/- 1.7 ml, p < 0.05), whereas heart rate was unaltered (140 +/- 12 vs 142 +/- 20 beats/min; NS). The change in blood pressure (32 +/- 5 vs 38 +/- 8 mm Hg, p < 0.01) was also significant. Cardiac index before and after volume replacement showed a significant inverse correlation with the severity of respiratory disease expressed as alveolar-arterial oxygen difference (A-aDO2) (A-aDO2 vs cardiac index before volume replacement: r = -0.77, p < 0.001; after volume replacement: r = -0.73, p < 0.005) or oxygenation index (oxygenation index vs cardiac index before volume replacement: r = -0.73, p < 0.005; after volume replacement: r = -0.73, p < 0.005). Changes in left ventricular diastolic diameter, left ventricular systolic diameter, and fractional shortening were not significant. CONCLUSIONS: These results indicate that the major regulator of left ventricular output in newborns with hypovolemic or cardiogenic shock is stroke volume and not heart rate and that cardiac output depends on the severity of the respiratory disease.

Cardiac Output↗
PubMed1997

Stridor as the major presenting symptom in riboflavin-responsive multiple acyl-CoA dehydrogenation deficiency.

UNLABELLED: Inspiratory stridor of unknown origin was the leading clinical symptom in an 11-month-old boy. The stridor increased over a period of 4 weeks, and assisted ventilation became necessary. Selective urinary screening by gas chromatography/mass spectrometry analysis revealed excretion of ethylmalonic and 3-OH-isovaleric acid and of N-isobutyryl-, N-2-methylbutyryl-, N-isovaleryl-, N-hexanoyl- and N-suberylglycine. Neither hypoglycaemia nor metabolic acidosis were noticed. Treatment with 200 mg of riboflavin per day led to a dramatic clinical improvement with restoration of normal respiration and an increase in muscular tone within 2 months. During this period, metabolite excretion in urine completely normalized. Riboflavin-sensitive multiple acyl-CoA dehydrogenation deficiency was confirmed in cultured fibroblasts. With riboflavin supplementation, the development of the child has been favourable, with normal school attendance now at an age of 9 years. CONCLUSION: As respiratory symptoms might precede other symptoms in disorders of mitochondrial oxidation, we propose determination of urinary organic acids in all cases of unexplained laryngeal stridor.

Adipates↗
PubMed1997

Comparative genomic hybridization reveals a partial de novo trisomy 6q23-qter in an infant with congenital malformations: delineation of the phenotype.

We report the use of comparative genomic hybridization (CGH) to define the origin of a small extra segment (unidentifiable by classical cytogenetics) present in a de novo add(13)q34 chromosome that we found in the karyotype of a newly born boy with congenital heart defects, brain anomalies and dysmorphic signs. Initial investigation with fluorescence in situ hybridization (FISH) and a chromosome-13-specific library revealed that the excess material was not derived from chromosome 13. To uncover the origin of the unknown chromosome material, CGH was carried out on DNA isolated from blood lymphocytes of the patient. By using a conventional fluorescence microscope with no digital imaging devices, a single distinct region with gain of fluorescent intensity was observed on distal chromosome 6q. Confirmation of this finding by FISH with a chromosome-6-specific paint and a subtelomeric yeast artificial chromosome clone from 6q26-q27, in combination with the band morphology of the small extra chromosomal segment, allowed us to diagnose the additional material as being derived from chromosome 6q23-qter. FISH with a telomere 13q probe detected a terminal deletion of 13q34-qter on the derivative chromosome 13, indicating that the der(13) was a result of a translocation event. Genotyping of the hypervariable apolipoprotein (a) gene, which lies within 6q26-q27, showed that the additional chromosome 6 material was inherited from the mother. The karyotype of the proposita is therefore: 46,XY,-13,+der(13)t(6;13)(q23;q34) de novo (mat). Our results confirm the usefulness of CGH as an attractive alternative method for the characterization of constitutional small genetic imbalances and contribute to the delineation of the trisomy 6q23-qter phenotype.

Abnormalities, Multiple↗
PubMed1996

Circulating interleukin-1 receptor antagonist levels in neonates.

UNLABELLED: Circulating interleukin-1 receptor antagonist (IL-1 Ra) levels have been shown to reflect disease activity in certain conditions in adults. We determined circulating IL-1Ra references values for healthy neonates (healthy preterms and term infants with mild disease only) on days 2 (n = 17) and 4 of life (n = 23). Mean gestational age was 35 +/- 2.6 weeks. On the 2nd day of life IL1-Ra levels were 0.78 ng/ml (0.49/2.65), on day 4 0.38 ng/ml (0.20/0.48) (median, 25th/75th percentile, P = 0.01). The values were not influenced by gender. In neonates with severe illness (septicaemia, asphyxia, neonatal respiratory distress syndrome), who received invasive intensive care, circulating IL-1Ra levels were significantly higher than in the reference group of healthy newborns. On the 2nd day of life (14.72 ng/ml (4.38/18.67) versus 0.78 ng/ml (0.49/2.65), P < 0.0001; on day 4 of life, 3.38 ng/ml (0.80/11.99) versus 0.38 ng/ml (0.20/0.48), P < 0.005 (values are median; 25th/75th percentile, Mann-Whitney U-Wilcoxon Rank Sum W Test, two-tailed P). CONCLUSION: Compared to healthy individuals beyond the neonatal period, Il-1Ra concentrations are physiologically elevated within the first days of life and decline to low levels within days. In contrast, IL-1Ra levels are strikingly elevated in sick neonates.

Biomarkers↗
PubMed1995

Persistent rubella infection after erroneous vaccination in an immunocompromised patient with acute lymphoblastic leukemia in remission.

A 16-year-old male patient with acute lymphoblastic leukemia in complete remission and on maintenance treatment with weekly oral methotrexate and daily oral 6-mercaptopurine for 3 months was immunized in error with the WI-RA 27/3-HDC live attenuated rubella vaccine. Increasing rubella HAI antibodies were noted from 3 to 7 months post-vaccination as well as high levels of IgM antibody up to 8 months in three different tests. High HAI antibody titers persisted for 12-18 months after vaccination. Persisting rubella virus was indicated by PCR detection of rubella-specific nucleic acid in whole blood, non-stimulated and stimulated mononuclear cells 8 months following vaccination. Further attempts to detect rubella virus RNA in two subsequent blood samples were negative. Since acute arthritis and arthralgia occurred in the second month (days 51-63) after vaccination, antileukemic chemotherapy had to be interrupted. Evidence of higher risk for chronic or relapsing rubella-associated arthropathy in immunologically compromised patients and the need to interrupt antileukemic chemotherapy should warrant immunoprophylaxis with polyvalent immune globulin in rubella-susceptible patients who are immunocompromised.

Adolescent↗
PubMed1994

Synthesis and characterization of a bioluminogenic substrate for alpha-chymotrypsin.

6-(N-Acetyl-L-phenylalanyl)-aminoluciferin as an example for a new class of highly sensitive bioluminogenic substrates that has been synthesized and characterized. These peptide derivatives can be used regarding to the peptide residue as highly sensitive substrates for different proteinases. Here we demonstrate the use of 6-(N-acetyl-L-phenylalanyl)-aminoluciferin as a novel bioluminogenic substrate for alpha-chymotrypsin. The kinetic parameters determined for 6-(N-acetyl-L-phenylalanyl)-aminoluciferin are Km = 0.38 mmol/liter, kcat = 6.5 s-1, and kcat/Km = 17,100 (liter/mol.s). The test principle of the coupled bioluminogenic assay is the release of aminoluciferin by enzymatic cleavage of 6-(N-acetyl-L-phenylalanyl)-aminoluciferin. Aminoluciferin is a very sensitive substrate of firefly luciferase and can be easily quantified in a luminometric assay. Amounts of chymotrypsin down to 0.3 ng per assay can be routinely determined.

Chromatography, High Pressure Liquid↗
PubMed1993

Quantitative cytochemical study of some enzymatic activities in preovulatory bovine oocytes after in vitro maturation.

In the present study quantitative cytochemical assays were used to measure some enzymatic activities in situ in bovine meiotically immature oocytes and oocytes matured in vitro, since the special metabolic activity of the growing oocytes may be a pivotal factor in stabilizing the meiotically arrested oocytes. Modifications of this particular metabolism might destabilize the arrested meiosis. Preovulatory oocytes, mostly at the germinal vesicle stage, were obtained by puncturing follicles ranging from 2 to 6 mm in diameter with a hypodermic needle. A group of collected oocytes was incubated in maturation medium CRML 1066 to obtain metaphase II oocytes. Succinate, lactate and glucose-6-phosphate dehydrogenase activities in just collected meiotically immature and in vitro matured oocytes were assayed cytochemically. Microdensitometric measurements were made with a Vickers M85a scanning microdensitometer. Our findings show that: 1) succinate dehydrogenase activity was significantly increased in matured oocytes; 2) lactate dehydrogenase activity was present and very strong in immature oocytes but was detectable in only about 50% of matured oocytes, with significantly lower integrated optical density values; 3) glucose-6-phosphate dehydrogenase activity was very high in immature oocytes but significantly decreased after in vitro maturation; 4) there was no linear correlation between the integrated optical densities of the three enzymatic activities and the diameters of the oocytes. We suggest that the ability to utilize glucose may appear earlier in bovine oocytes than in other species and takes place at the time of maturation.

Animals↗
PubMed1993

Bioluminescence-enhanced immunoassays: an ultrasensitive method.

Ultrasensitive bioluminescence immunoassays for the determination of peptides and proteins are illustrated in this paper with the enzyme immunological determination of total IgE in human serum. The usable range of standard curves is from 5 pg to 5000 pg per liter. The intra- and interassay coefficients of variation of this test are in the same range as obtained for chromogenic enzyme immunoassays.

Antigen-Antibody Reactions↗