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Biomedical subjects

L Maier

Publications and source records attributed to L Maier.

At least 19 recordsLinked to original sources
PubMed2006

Effect of oestradiol and progesterone replacement on bronchopulmonary dysplasia in extremely preterm infants.

OBJECTIVE: To study whether postnatal replacement of oestradiol and progesterone may help to prevent bronchopulmonary dysplasia (BPD). METHODS: This randomised placebo-controlled double-blind study enrolled 83 infants of <29 weeks gestational age and 1000 g birth weight requiring mechanical ventilation within 12 h after birth. Oestradiol (2.5 mg/kg/day) and progesterone (22.5 mg/kg/day) were given by continuous intravenous infusion of a standard lipid emulsion (15 ml/kg/day) in the replacement group (ESTRA-PRO). The placebo group received the same lipid emulsion without oestradiol or progesterone. A replacement period of at least 2 weeks but not >4 weeks was strived for and defined as "according to protocol". The primary outcome variable was the incidence of BPD or death. RESULTS: The median birth weight was 670 g (min-max 400-990 g) and the gestational age 25 weeks (23.1-28.1 weeks). The incidence of BPD or death was 48% in the placebo group and 44% in the ESTRA-PRO group (p = 0.38, one-sided testing, intention to treat analysis). In infants treated according to protocol, 32% (9 of 28) in the placebo group and 14% (3 of 21) in the ESTRA-PRO group developed BPD (p = 0.08). CONCLUSION: Replacement of oestradiol and progesterone was not effective for prevention of BPD or death in extremely preterm born infants. Better-powered trials are needed to evaluate this new approach.

Birth Weight↗
PubMed2006

[Delta(9)-tetrahydrocannabinol and the opioid receptor agonist piritramide do not act synergistically in postoperative pain].

BACKGROUND: It is concluded from animal experiments that cannabinoid receptor and mu-opioid receptor agonists act synergistically with respect to antinociception. In order to demonstrate this effect under clinical conditions, we conducted a randomized double blind trial with patients after radical prostatectomy. PATIENTS AND METHODS: From the evening before the operation until the morning of the second postoperative day, all patients received eight oral doses of either placebo or 5 mg Delta(9)-tetrahydrocannabinol (dronabinol). Postoperatively patients had access to patient-controlled analgesia with the micro-opioid agonist piritramide for 48 h. We expected patients receiving dronabinol to require significantly less piritramide compared to patients on placebo. RESULTS: The consumption of piritramide was recorded in 100 patients after radical retropubic prostatectomy with regional lymphadenectomy. Patients in the placebo group consumed 74 mg (median), interquartile range (IQR) 44-90 mg, patients in the verum group consumed 54 mg (median) IQR 46-88 mg. The difference between groups was not statistically significant. Plasma concentrations of Delta(9)-THC were measurable in all patients in the verum group. The levels (median) were 1.5 ng/ml (IQR 0.6-2.3), 1.3 ng/ml (IQR 0.5-2.2) and 1.9 ng/ml (IQR 0.8-2.7) on the day of operation, the first and second postoperative day, respectively. CONCLUSION: We found neither a synergistic nor even an additive antinociceptive interaction between Delta(9)-tetrahydrocannabinol and the micro-opioid agonist piritramide in a setting of acute postoperative pain.

Aged↗
PubMed2006

Trends in antibiotic use at a university hospital: defined or prescribed daily doses? Patient days or admissions as denominator?

BACKGROUND: Hospital antibiotic use can be measured by calculating daily doses as defined by the WHO/ATC index (DDD) divided by the number of patient or occupied bed days. We wondered whether changes in antibiotic use density over time at a university hospital using this data format are similar in order of magnitude when compared with a different, alternative dose definition and the number of admissions rather than the number of patient days as denominator. METHODS: Data obtained from the hospital pharmacy for the medical and surgical services of a 1,000-bed university hospital for the period 1992 through 2003 were expressed both in daily doses per 100 patient days and daily doses per admission. A PDD dose definition (prescribed daily doses), defining doses that reflect the usually prescribed dose in adult hospitalized patients with normal renal function was compared with the WHO/ATC 2001 DDD dose definitions. The percent changes using the different data formats between two 3-year averages (1992-1994 and 2001-2003) were calculated. RESULTS AND CONCLUSION: The DDD/100 patient days data format overestimated antibiotic use density changes in this hospital both in medicine (81% vs 48%) as well as in surgery (69% vs 39%) when compared with PDD/100 patient days. Due to changes in the number of admissions and length of stay over the years, the percent change between the two periods expressed in doses per 100 patient days in addition differed substantially from that estimated by using the DDD per admission or PDD per admission data format. Studies evaluating the evolution of hospital antibiotic use need to address the limitations and adequacy of the different data formats.

Adult↗
PubMed2005

Simultaneous measurement of beta- decay to bound and continuum electron states.

We report the first measurement of a ratio lambda(beta(b))/lambda(beta(c)) of bound-state ((lambda(beta(b))) and continuum-state (lambda(beta(c))) beta(-)-decay rates for the case of bare 207Tl81+ ions. These ions were produced at the GSI fragment separator FRS by projectile fragmentation of a 208Pb beam. After in-flight separation with the Brho-deltaE-Brho method, they were injected into the experimental storage-ring ESR at an energy of 400.5A MeV, stored, and electron cooled. The number of both the 207Tl81+ ions and their bound-state beta(-)-decay daughters, hydrogen-like 207Pb81+ ions, were measured as a function of storage time by recording their Schottky-noise intensities. The experimental result, lambda(beta(b))/lambda(beta(c)) = 0.188(18), is in very good agreement with the value of 0.171(1) obtained from theory employing spectra of allowed transitions.

Journal Article↗
PubMed2001

Absorption, distribution, metabolism and excretion of [14C]levocetirizine, the R enantiomer of cetirizine, in healthy volunteers.

The main goal of the present study was to investigate the absorption and disposition of levocetirizine dihydrochloride, the R enantiomer of cetirizine dihydrochloride, following a single oral administration (5 mg) of the 14C-labelled compound in healthy volunteers. Configurational stability was also investigated. Levocetirizine was rapidly and extensively absorbed: 85.4% and 12.9% of the radioactive dose were recovered 168 h post-dose in urine and faeces, respectively. Levocetirizine and/or its metabolites were not, or only very poorly, associated with blood cells, as the blood-to-plasma ratio was 0.51 to 0.68. The mean apparent volume of distribution (Vz/F) was 26.9 1 (0.3 l/kg) indicating that the distribution of levocetirizine is restrictive. The protein binding of radiolabelled levocetirizine was 96.1% l h after administration. In vitro, at concentrations ranging from 0.2 microg/ml to 1 microg/ml, the protein binding was 94.8% to 95.0%. Levocetirizine is very poorly metabolised. The cumulative 48-h excretion as parent compound accounted for 85.8% of the oral dose, equivalent to 95% of the total radioactivity excreted at this time. At least 13 minor metabolites were detected in urine and represented 2.4% of the dose at 48 h. The metabolic pathways involved in levocetirizine metabolism are oxidation (hydroxylation, O-dealkylation, N-oxidation and N-dealkylation), glucuroconjugation, taurine conjugation and glutathione conjugation with formation of the mercapturic acids. There was no evidence of chiral inversion of levocetirizine in humans. This result is consistent with that obtained in preclinical studies.

Adult↗
PubMed2001

Beryllium sensitization, chronic beryllium disease, and exposures at a beryllium mining and extraction facility.

In this study, we examine beryllium sensitization, chronic beryllium disease (CBD), and workplace exposures at a beryllium mining (mine) and extraction facility (mill) in Delta, Utah. Historical airborne beryllium data collected between 1970-1999 included general area (GA), breathing zone (BZ), and personal lapel (LP) measurements and calculations of job-specific quarterly daily-weighted averages (DWVAs). We compared GA, BZ, and DWA data to airborne beryllium data from a mixed beryllium products facility and a beryllium ceramics facility located in Elmore, Ohio and Tucson, Arizona, respectively. At the Delta facility, jobs involving beryllium hydrolysis and wet-grinding activities had the highest air concentrations; annual median GA concentrations were less than 0.3 microg/m3 or both areas. Annual median GA sample concentrations ranged from 0.1-0.4 microg/m(-3) at Delta. These levels were generally lower than Elmore (0.1-1.0 microg/m3) and were comparable to the Tucson facility (0.1-0.4 microg/m3). Median BZ concentrations were higher, whereas DWAs were lower at the Delta facility than at the other two facilities. Among the 87 employees at the Delta facility, 75 participated in the medical survey; there were three persons sensitized, one with CBD. The individual with CBD previously worked at the Elmore facility for 10 years. Cumulative CBD incidence rates were significantly lower at the Delta facility: 0.3 percent compared to 2.0 percent for Elmore and 2.5 percent for the Tucson facility. Sensitization and CBD prevalence rates determined from cross-sectional surveys for the Delta facility were lower than but not significantly different from rates at the other two facilities. There was no sensitization or CBD among those who worked only at the mine where the only exposure to beryllium results from working with bertrandite ore. Although these results are derived from a small sample, this study suggests that the form of beryllium may affect the likelihood of developing CBD. Specifically, exposure to beryl and bertrandite ore dusts or to beryllium salts, in the absence of exposure to beryllium oxide particulates appears to pose a lower risk for developing CBD.

Adult↗
PubMed2001

Management of the extremely preterm infant: is the replacement of estradiol and progesterone beneficial?

This review presents data to suggest that postnatal estradiol and progesterone replacement therapy may be beneficial in preterm infants. During pregnancy, maternal plasma levels of estradiol and progesterone increase up to 100-fold compared to the nonpregnant status. The fetus is also exposed to these increasing hormone levels. After delivery, estradiol and progesterone levels drop by a factor of 100 within 1 day. Whereas this is a physiological condition for an infant born at term, preterm delivery means withdrawal from the placental supply of these hormones at an earlier developmental stage. Seventy years ago, the idea was raised that preterm infants may benefit from the replacement of estrogens. Studies in which estrogen was injected subcutaneously showed only a slightly better bodyweight gain compared to placebo-treated controls and therefore routine use was not established. The effective treatment of postmenopausal osteoporosis with hormone replacement therapy led to a pilot study of estradiol and progesterone therapy to prevent osteopenia of prematurity. The highest median bone mineral accretion rate was found in the replacement group when the supplementation with calcium and phosphorus was also sufficient. None of the previous studies dealing with estrogen replacement controlled for achieved plasma levels of estradiol in the infants. In our controlled randomised pilot study with 30 preterm infants (15 in each group), we aimed to maintain intra-uterine plasma levels of estradiol and progesterone. Preterm infants with replacement of estradiol and progesterone for 6 weeks postnatally showed trends to higher bone mineral accumulation. In addition, a trend towards a lower incidence of chronic lung disease was found. Neurodevelopmental follow-up showed normal psychomotor development in infants given estradiol and progesterone, whereas the untreated infants (controls) showed a trend towards delayed development. Recent research emphasises that estradiol and progesterone may be important for brain development. Thus, while there is data indicating that postnatal estradiol and progesterone replacement therapy may be beneficial in preterm infants, experience with this new therapy is limited and extensive research is needed to address the potential benefits and to rule out adverse effects.

Estrogen Replacement Therapy↗
PubMed2000

Detection of beryllium sensitivity using a flow cytometric lymphocyte proliferation test: the Immuno-Be-LPT.

Measurement of lymphocyte proliferation to detect hypersensitivity to beryllium (Be-LPT) in vitro is done presently using a method based on tritiated thymidine incorporation. Although this method is sensitive it gives no information on cell viability or responding lymphocyte subsets. We have developed reliable and simple flow cytometric assays for lymphocyte proliferation testing (Immuno-Be-LPT) by combining immunophenotyping with bromodeoxyuridine (BrdU) incorporation or DNA content using propidium iodide (PI) or 4'6'-diimidazolin-2-phenylindole (DAPI). Evaluation of beryllium-induced lymphocyte proliferation in blood cells from seven patients with chronic beryllium disease (CBD) and 120 beryllium workers by both the Bc-LPT and the Immuno-Be-LPT showed agreement between the tests. The Immuno-Bc-LPT provided additional information about the specific type of lymphocytes responding. CD4+ lymphocytes proliferated in response to beryllium in blood samples from all seven CBD individuals and CD8+ lymphocytes proliferated in six of the seven. Four beryllium workers without CBD had positive responses to beryllium primarily in the CD8+ cells. The use of the individual's own plasma supported a greater beryllium or tetanus-induced proliferation of CD4+ lymphocytes when compared to commercial human serum. The response of CD4+ lymphocytes measured in the Immuno-Be-LPT may provide a new marker for the diagnosis of CBD.

Antibodies, Monoclonal↗
PubMed1999

17Beta-estradiol and progesterone supplementation in extremely low-birth-weight infants.

During pregnancy, 17beta-estradiol (E2) and progesterone (P) plasma concentrations increase up to 100-fold. The fetus is exposed to these increasing amounts of E2 and P. Within 1 d after delivery, E2 and P concentrations fall to nonpregnancy concentrations in the mother and the infant. Extremely premature infants are cut off from the placental supply of E2 and P at a very early developmental stage, and therefore they suffer from this deprivation for a longer period than infants born at term. Nothing is known about the consequences of this deprivation. The purpose of this study was to investigate how intrauterine concentrations of E2 and P could be maintained after birth. In 13 infants with a median gestational age of 26.4 wk (24.1-28.7), a phospholipid-stabilized soybean oil emulsion available for parenteral nutrition that contains different amounts of E2 and P was continuously administered, starting within the first postnatal hours. The supplementation was continued as long as venous access was indicated but not longer than 6 wk (median 20 d, 12-44). To maintain intrauterine plasma concentrations of 2000-6000 pg/mL E2 and 300-600 ng/mL P, 2.30 mg x kg(-1) x d(-1) E2 (1.13-3.42 mg x kg(-1) x d(-1)) and 21.20 mg x kg(-1) x d(-1) P (11.23-27.36 mg x kg(-1) x d(-1)) were needed. We conclude that supplementation of E2 and P to maintain intrauterine concentrations in extremely premature infants is possible intravenously. The infants in this study are enrolled in a randomized, controlled pilot study to evaluate the potential benefits of E2 and P supplementation.

Dietary Supplements↗
PubMed1999

Effects of postnatal estradiol and progesterone replacement in extremely preterm infants.

The fetus is supplied from the placenta with estradiol (E2) and progesterone (P) in increasing amounts during gestation. After delivery of a premature infant, placental supply is disrupted, resulting in a rapid decrease in E2 and P. Replacement of these placental hormones may restore intrauterine conditions and may be beneficial for bone mineral accretion, clinical course, and outcome. Thirty female infants with a median gestational age of 26.6 weeks (between 24.1-28.7) and a birth weight of 675 g (370-990) were randomized to receive E2 and P replacement, aiming to maintain plasma levels equaling the intrauterine levels, or no replacement. The E2 and P replacement was started iv and was followed by transepidermal administration for a total duration of 6 weeks. Repeated measurements included plasma levels of E2, P, FSH, and LH; uterine volume; calcium and phosphorus in spot urine specimens; and bone mineral accretion by single photon absorption densitometry. Further, the incidence of chronic lung disease and various clinical outcome data were recorded. The plasma levels of E2 and P were within the intrauterine range with median replacements of 2.30 mg/kg x day E2 (1.13-6.23) and 21.20 mg/kg x day P (11.23-27.36), iv. Three- and 6-fold higher doses of E2 and P were needed via the transepidermal route. The uterine volumes increased, and FSH and LH as indicators for biological effectiveness were significantly lowered with replacement. The bone mineral accretion rates tended to be higher, and the incidence of chronic lung disease tended to be lower (0% vs. 29%; P = 0.097). E2 and P replacement via iv and transepidermal routes is capable of maintaining plasma levels as high as those in utero with biological effectiveness. Trends toward improved postnatal bone mineral accretion and less chronic lung disease were found with the hormone replacement. Further and more extensive studies are warranted to address the role of this new approach in the care of extremely premature infants.

Birth Weight↗
PubMed1995

Phosphinic acid analogues of GABA. 2. Selective, orally active GABAB antagonists.

In 1987, 25 years after the synthesis of the potent and selective GABAB agonist baclofen (1), Kerr et al. described the first GABAB antagonist phaclofen 2. However, phaclofen and structurally similar derivatives 3-5 did not cross the blood-brain barrier and hence were inactive in vivo as central nervous system agents. As a consequence, the therapeutic potential of GABAB antagonists remained unclear. In exploring GABA and baclofen derivatives by replacing the carboxylic acid residue with various phosphinic acid groups, we discovered more potent and water soluble GABAB antagonists. Electrophysiological experiments in vivo demonstrated that some of the new compounds were capable of penetrating the blood-brain barrier after oral administration. Neurotransmitter release experiments showed that they interacted with several presynaptic GABAB receptor subtypes, enhancing the release of GABA, glutamate, aspartate, and somatostatin. The new GABAB antagonists interacted also with postsynaptic GABAB receptors, as they blocked late inhibitory postsynaptic potentials. They facilitated the induction of long-term potentiation in vitro and in vivo, suggesting potential cognition enhancing effects. Fifteen compounds were investigated in various memory and learning paradigms in rodents. Although several compounds were found to be active, only 10 reversed the age-related deficits of old rats in a multiple-trial one-way active avoidance test after chronic treatment. The cognition facilitating effects of 10 were confirmed in learning experiments in Rhesus monkeys. The novel GABAB antagonists showed also protective effects in various animal models of absence epilepsy.

Administration, Oral↗
PubMed1991

Carotenoid replacement therapy in Drosophila: recovery of membrane, opsin and visual pigment.

Rhabdomeres are substantially smaller and visual pigment is nearly eliminated when Drosophila are carotenoid-deprived from egg to adult. Rhabdomeres enlarge and visual pigment increases with carotenoid replacement in adults using carrot juice. We used a monoclonal antibody to the opsin in R1-6 receptors in the compound eye to further quantify opsin recovery in such carotenoid replacement therapy. Density of immunogold, specific to R1-6 (vs. R7), increases between days 1 and 3 of replacement as visual pigment and rhabdomeres recover. In summary, visual pigment, opsin and the opsin-containing organelle recover during carotenoid replacement therapy in carotenoid-deprived Drosophila.

Animals↗
PubMed1990

Microphotometric, ultrastructural, and electrophysiological analyses of light-dependent processes on visual receptors in white-eyed wild-type and norpA (no receptor potential) mutant Drosophila.

We examined a white-eyed strain of the norpA mutant (norpA;cn bw) and white (w)norpA+ controls using microspectrophotometry (MSP), electron microscopy (EM), and electroretinography (ERG). These studies revealed that light mediates receptor demise in norpA even though norpA lacks phototransduction. Rhodopsin and the rhabdomere which houses it decrease with increasing age in norpA but not in w with rearing on a 12 h light/12-h dark cycle or in constant light. At higher temperature in norpA;cn bw and w reared in constant light, visual pigment decreases, rhabdomeres diminish, and cells die. Importantly, dark rearing blocked visual pigment loss in norpA;cn bw; the M-potential, an ERG reflection of visual pigment level, corroborated this finding. MSP showed that norpA's visual pigment loss was not due to acute loss of metarhodopsin, rhodopsin's photoproduct. NorpA blocks certain processes expected to be light elicited. The alteration of visual pigment as a function of time of day, present in w controls, is absent in white-eyed norpA, suggesting that light-induced depolarization may be necessary to entrain the rhythm. Microspectrofluorometry using the fluorescent dye, Lucifer yellow, suggested that norpA lacks a light-induced uptake mechanism; using control flies, we determined the stimulus parameters required for uptake in vivo. An attempt to "cure" norpA;cn bw by replacement "therapy" using phospholipase C, missing in norpA's phototransduction cascade, was largely unsuccessful.

Animals↗
PubMed1986

Enzyme activities in single electrophysiologically identified crab muscle fibres.

The superficial muscle fibres in the proximal part of the closer muscle in the crab Eriphia can be separated into four fibre groups (I-IV) on the basis of electrophysiological and histochemical characteristics. The activity levels of glyceraldehydephosphate dehydrogenase (GAPDH), lactate dehydrogenase (LDH), citrate synthase (CS), NADP-isocitrate dehydrogenase (IDH) and 3-hydroxyacyl-CoA dehydrogenase (HAD), determined in single electrophysiologically identified fibres, differed significantly among the different fibre groups. In addition, fibres belonging to the same group, with similar electrophysiological characteristics, demonstrated variability with regard to metabolic enzyme activities. Nevertheless, comparison of absolute enzyme activities and enzyme activity ratios permitted the discrimination of at least three groups. These groups corresponded with those defined according to electrophysiological and histochemical characteristics. The group I fibres (tonic fibres) are intermediate in oxidative potential and show the lowest values of glycolytic enzymes. The group II and group III fibres can be regarded as fast oxidative fibres. The high ratio between activity levels of enzymes for glycolytic and oxidative metabolism found for group IV fibres (fast fibres) demonstrated that this group depends strongly on anaerobic metabolism.

3-Hydroxyacyl CoA Dehydrogenases↗
PubMed1984

pH lability of myosin ATPase activity permits discrimination of different muscle fibre types in crustaceans.

Myofibrillar actomyosin ATPase activity has been studied histochemically in the closer muscle of the crab Eriphia spinifrons. Preincubation at pH 4.6 and 5.0 reveals differences in the lability of the ATPase. This permits the discrimination of four fibre types. Of these, three represent subgroups of rapidly contracting fibres. The histochemically defined fibre types correspond well with four groups defined according to electrophysiological criteria.

Actomyosin↗