Determination of lamellar body phospholipids in amniotic fluid: a method to predict when the fetal lung becomes mature

Lamellar body material was isolated by highspeed centrifugation from the amniotic fluids of 10 mildly diseased patients followed longitudinally and of 60 other women. Three stages of development were defined: (1) immature stage: the phospholipid concentration is less than 20 mumol/l and phosphatidylcholine (PC) is approximately 50%; (2) transitional stage: the phospholipid concentration is between 18 and 40 mumol/l, of which PC is approximately 75% and phosphatidylinositol (PI) 10%. Phosphatidylglycerol (PG) is absent or present at very low concentrations; (3) mature stage: the phospholipid concentration is above 40 mumol/l; its PC percentage is 75% or more. PG is present and the percentage of PI decreases. An increase in phospholipid concentration of 3.27 +/- (SD) 0.75 mumol/l/day was found during the transitional stage. The rate of increase enables us therefore to approximate the number of days that it will take before the fetal lung is mature.     

Intrauterine hypercarbia and lamb lung surfactant synthesis

Prenatal asphyxia resulting in hypoxia, hypercarbia and amniotic fluid aspiration reduces the synthesis of the pulmonary surfactant. Using 135-day fetal lambs we studied the in utero effects of hypercarbic acidosis alone on fetal breathing activity, excised lung pressure-volume relationships and lamellar body (LB) surfactant disaturated phosphatidylcholine (DSPC) pool size and specific activity for [14C]palmitate. Fetal PaCO2 levels greater than 125 mm Hg for 30 min were associated with pH values less than 7.0 and very vigorous breathing activity. Analysis 22 h after the period of hypercarbic acidosis demonstrated no differences in pressure-volume relationships or the quantity of lamellar body surfactant DSPC. The specific activity of lamellar body DSPC also was not different although total label (dpm) per gram dry weight was higher and label was detected in the lavage fluid earlier in the acidotic lambs than controls. We conclude from these data that hypercarbic acidosis does not influence the synthesis or function of the pulmonary surfactant as assessed in this system. From these results and prior work from our laboratory we can infer that hypoxia remains the most probable cause for reduced surfactant synthesis in the asphyxiated fetus.     

Separation of lymphocyte subpopulations in carp Cyprinus carpio L. by monoclonal antibodies: immunohistochemical studies.

Lymphoid cell populations in various organs of the carp Cyprinus carpio L. were investigated using a series of mouse monoclonal antibodies raised against carp thymocytes and carp serum Ig. Clones have been designated as Ig+T+, Ig+T- or Ig-T+ on the basis of the reactivity with thymocytes and serum Ig in the enzyme-linked immunosorbent assay (ELISA) screening. Their reaction to the lymphoid organs of carp was investigated on cryostat sections and cytocentrifuge slides using immunoperoxidase techniques. IG+T+ clones could be subdivided into those that stained reticular fibres around blood vessels in various organs (R+) and those that did not (R-). The former stained most thymocytes and most peripheral lymphocytes as well as plasma cells whereas the latter did not stain cortical thymocytes and some peripheral lymphocytes. IG+T- clones were negative for thymocytes but positive for plasma cells and a certain population of peripheral lymphocytes. Ig-T+ clones reacted similarly to Ig+T+R- clones. It is concluded that fish lymphoid cell populations can be distinguished based upon differences in cell surface and/or cytoplasmic determinants. The monoclonal antibodies described can be used for further structural analysis of the determinants and for functional separation of T- and B-like cells in the 'lower' vertebrates.     

Intermediate filament cDNAs from BHK-21 cells: demonstration of distinct genes for desmin and vimentin in all vertebrate classes.

Recombinant cDNA plasmids for the intermediate filament proteins desmin and vimentin were constructed from baby hamster kidney (BHK-21) mRNA. Analysis of four desmin clones gave a sequence of 1574 nucleotides, which is 75% of the total mRNA length. The derived amino acid sequence for hamster desmin shows 92% overall homology with chicken desmin; the homology with hamster vimentin is highest in the alpha-helical middle part (74%). The 3'-noncoding region of desmin mRNA is found to be 677 nucleotides long. With the aid of 5'- and 3'-specific probes, it has been established that there is a single gene for desmin in the hamster genome. This gene expresses a single mRNA species of 2.2 kilobases. Hybridization experiments of a number of DNAs with desmin and vimentin probes show that there are distinct restriction enzyme fragments carrying vimentin and desmin sequences in the genome of representatives of all vertebrate classes.     

The effect of acute hypoxia on the efflux and surface activity of lung fluid in fetal lambs

Oxytocin has been measured in fetal and maternal plasma samples obtained serially from 6 sheep during late pregnancy, spontaneous labor and labor induced by intrafetal infusion of Synacthen (ACTH_1–24). Fetal plasma contained significantly (P < 0.001) greater concentrations of oxytocin than maternal plasma. Concentrations of oxytocin rose in maternal plasma during the later stages of spontaneous and induced labor, whereas concentrations in fetal plasma did not exhibit a consistent trend.     

Dopaminergic drugs and the risk of hip or femur fracture: a population-based case�Ccontrol study

Summary

The effect of dopaminergic medication on the risk of hip/femur fractures is not clear. Our results showed a nearly twofold increased risk of hip/femur fractures in current dopaminergic drug users. Concomitant use of antidepressants further increased this risk. Fracture risk assessment may be warranted in elderly users of dopaminergic drugs.

Introduction

Dopaminergic drugs, often used in the treatment of Parkinson??s disease, have several pharmacological effects that may increase or decrease the risk of falling and fractures. Thus, the effect of dopaminergic medication on the risk of hip/femur fractures is not clear. The objective of the study was to examine the effect of dopaminergic medication and concomitant use of psychotropics on the risk of hip/femur fractures taking into account the timing of dopaminergic drug use.

Methods

A population-based case?Ccontrol study in the PHARMO database was conducted for the period 1991 to 2002. Cases were patients aged 18?years and older with a first hip or femur fracture and matched to four control patients by year of birth, sex and geographical region.

Results

The study population included 6,763 cases and 26,341 controls. Current use of dopaminergic drugs (1?C30?days before the index date) was associated with an increased risk of hip/femur fractures compared to never use (OR_adj 1.76, 95% CI?=?1.39?C2.22), but this excess risk rapidly dropped to baseline levels when treatment had been discontinued >1?year ago. Concomitant use of antidepressants among current dopaminergic drug users further increased the risk of hip/femur fractures (OR_adj 3.51, 95% CI?=?2.10?C5.87) while there was no additional risk with concomitant use of other psychotropics.

Conclusions

Although the observed association between dopaminergic drugs and fracture risk may not be entirely causal, due to absence of information on the (severity of the) underlying disease, fracture risk assessment may be warranted in elderly users of dopaminergic drugs.     

Safety of tibolone in the treatment of vasomotor symptoms in breast cancer patients--design and baseline data 'LIBERATE' trial

Many patients with a history of breast cancer (BC) will suffer from vasomotor symptoms, which can be induced or exacerbated by treatment with tamoxifen or aromatase inhibitors. The LIBERATE trial was designed as a randomized, double-blind, multicenter trial to demonstrate that tibolone 2.5mg/day (Livial) is non-inferior to placebo regarding BC recurrence in women with vasomotor symptoms surgically treated for primary BC within the last 5 years. Secondary objectives are effects on vasomotor symptoms as well as overall survival, bone mineral density and health-related quality of life. Mean age at randomization was 52.6 years, and the mean time since surgery was 2.1 years. The mean daily number of hot flushes and sweating episodes was 7.3 and 6.1, respectively. For the primary tumor, Stage IIA or higher was reported for >70% of the patients. In subjects whose receptor status was known, 78.2% of the tumors were estrogen receptors positive. At randomization, tamoxifen was given to 66.2% of all patients and aromatase inhibitors to 7%. Chemotherapy was reported by 5% at randomization. The adjuvant tamoxifen use in LIBERATE allows a comparison with the Stockholm trial (showing no risk of BC recurrence associated with hormone therapy), which was stopped prematurely subsequent to HABITS. The LIBERATE trial is the largest, ongoing, well-controlled study for treatment of vasomotor symptoms in BC patients.     

Pharmacogenetics of antiparkinsonian drug treatment: a systematic review

Pharmacotherapy is the mainstay in the treatment of Parkinson's disease and the armamentarium of drugs available for the therapy of this disease is still expanding. Anti-Parkinson's disease drugs are effective in reducing the physical symptoms, such as hypokinesia, bradykinesia, rigidity and tremor. However, there is a large interindividual variability in response to anti-Parkinson's disease drugs with respect to both drug efficacy and toxicity. It is thought that genetic variability in genes encoding drug-metabolizing enzymes, drug receptors and proteins involved in pathway signaling is an important factor in determining interindividual variability in drug response. Pharmacogenetics aims at identifying genetic markers associated with drug response. Ideally, knowledge of these genetic markers will enable us to predict an individual's drug response in terms of both efficacy and toxicity. The role of pharmacogenetics in the treatment of Parkinson's disease is relatively unexplored. Therefore, we aim to present a systematic review of the published pharmacogenetic studies in Parkinson's disease and to describe polymorphic genes of interest for future research.     

Anti-Xa activity after subcutaneous administration of dalteparin in ICU patients with and without subcutaneous oedema: a pilot study

Introduction  

Intensive care unit (ICU) patients often suffer from subcutaneous oedema, due to administration of large fluid volumes and the underlying pathophysiological condition. It is unknown whether the presence of subcutaneous oedema impairs the absorption of dalteparin, a low molecular weight heparin, when it is given by subcutaneous administration for venous thromboembolism prophylaxis. The objective of this study is to compare the anti-Xa activity of dalteparin after subcutaneous administration in ICU patients with and without subcutaneous oedema.