The Well-being Model: A New Drug Interaction Model for Positive and Negative Effects

Background: Drugs are routinely combined in anesthesia and pain management to obtain an enhancement of the desired effects. However, a parallel enhancement of the undesired effects might take place as well, resulting in a limited therapeutic usefulness. Therefore, when addressing the question of optimal drug combinations, side effects must be taken into account.

Methods: By extension of a previously published interaction model, the authors propose a method to study drug interactions considering also their side effects. A general outcome parameter identified as patient's well-being is defined by superposition of positive and negative effects. Well-being response surfaces are computed and analyzed for varying drugs pharmacodynamics and interaction types. In particular, the existence of multiple maxima and of optimal drug combinations is investigated for the combination of two drugs.

Results: Both drug pharmacodynamics and interaction type affect the well-being surface and the deriving optimal combinations. The effect of the interaction parameters can be explained in terms of synergy and antagonism and remains unchanged for varying pharmacodynamics. For all simulations performed for the combination of two drugs, the presence of more than one maximum was never observed.     

Transport of estrogen-induced oxytocin receptors in the ventromedial hypothalamus.

The modulation of oxytocin (OT) receptors (OTRs) by estrogen was investigated in the ventromedial hypothalamus by in vitro receptor autoradiography. Treatment of ovariectomized and adrenalectomized rats with various doses of estradiol benzoate (EB) increased OTR binding not only in the ventromedial nuclei of the hypothalamus (VMN), but also in the area lateral to the nuclei (IVMN). After a single injection of EB, OTRs first were induced within the ventrolateral parts of the VMN, and only hours later they appeared in the IVMN. This is consistent with the interpretation that OTRs are first induced within the estrogen-sensitive neurons of the ventrolateral VMN and then are transported laterally out of the nuclei. Two additional experiments confirmed this interpretation. First, local infusion of a low dose (10 micrograms) of the neuronal transport inhibitor vinblastine blocked the appearance of OTRs in the IVMN but did not prevent the induction of OTRs by EB within the nuclei. Second, a knife cut placed lateral to the VMN prevented the spread of OTRs out of the nuclei. However, even after treatment with a high dose of EB (2 x 10 micrograms), progesterone (P) was required for a maximal extension of the area covered by OTRs. Thus, the OTR is an estrogen-induced neurotransmitter receptor that is transported to its site of action, the lateral ventromedial hypothalamus, where it is modulated by P and where estrogen-induced OT immunoreactivity is found.     

Differentialdiagnose von Ovarialtumoren — hilft dem Gynäkologen die NMR-Tomographie

Ohne Zusammenfassung     

Family-oriented nutrition intervention for a lipid clinic population

We have developed a unique, family-oriented approach to lowering plasma cholesterol concentrations in persons with familial hyperlipidemias. The approach includes individual clinic visits and group nutrition classes and uses dietary goals outlined in The New American Diet. A series of 13 nutrition classes is presented to small groups, usually composed of relatives from pedigrees with familial hypercholesterolemia or other familial hyperlipidemias. Dietary action goals, cooking demonstrations, food tasting, and finger-stick plasma cholesterol determinations are important components of the classes. Problem-solving discussion is encouraged in the group. Over the past 4 years, 143 hyperlipidemic individuals, along with at least 94 unaffected family members, have participated in 31 groups, which have met for at least six classes. Many clinic participants lower plasma cholesterol by 20% or more. Keys to the success of this program include emphasizing dietary therapy, using the family setting for nutrition intervention, providing hands-on experience with food and recipes, promoting problem solving for dietary action goals, measuring blood cholesterol during classes, and encouraging long-term follow-up for participants with physicians and dietitians.     

Neonatal vocal cord paralysis following extracorporeal membrane oxygenation

Five cases of unilateral vocal cord paralysis/paresis were diagnosed following extracorporeal membrane oxygenation for newborn respiratory failure. All were right sided and transient in nature. None of the five patients had other findings commonly associated with vocal cord palsy. The extracorporeal membrane oxygenation procedure requires surgical dissection in the carotid sheath on the right side of the neck, an area immediately adjacent to both the vagus and recurrent laryngeal nerve. It is speculated that vocal cord paralysis in these infants was acquired as a result of the extracorporeal membrane oxygenation cannulation. Although the vocal cord paralysis resolved in all cases, two patients had difficult courses after extracorporeal membrane oxygenation. Therefore, laryngoscopic examination should be considered for patients after extracorporeal membrane oxygenation.     

Calcinosis at the site of leakage from extravasation of calcium disodium edetate intravenous chelator therapy in a child with lead poisoning

Painful calcinosis appeared at the wrist of an eight-year-old girl with lead poisoning. Careful history revealed that calcification occurred at the site of previous extravasation of calcium disodium edetate (EDTA) used in chelation therapy. Light microscopic, ultrastructural, electron activation, and X-ray diffraction studies demonstrated apatites with some suggestion of an admixture of octacalcium phosphate.     

Health experiences and employment status in subjects with chronic back pain: a long-term perspective.

The purpose of this study was to describe health experiences, focused on gender and return to work, in subjects with chronic low back pain in a long-term perspective. The convenient sample consisted of 12 subjects who had attended a pain rehabilitation program 6 years earlier. Typed interviews were transcribed, and a content analysis approach was used. Five categories were found: coping, root causes, control/influence, pain, and sleep. The interviews showed that the subjects expressed well-being, although pain had become part of their daily life. However, both gender and well-being group differences were identified. The women and the group with reduced well-being used the root causes category in a higher degree than the men and the well-being group did. The conclusion is that there are differences according to both gender and return to work within the subjects with chronic pain and that these differences are related to both root causes and coping pattern.     

Comparative early and midterm results of open juxtarenal and infrarenal aneurysm repair

Background and aims Since the introduction of endovascular aortic aneurysm repair (EVAR) for aortic aneurysms, the number of juxtarenal aortic aneurysms (JRA) has been growing steadily due to selection bias (neck morphology for EVAR). This case-match study compares the perioperative outcome and midterm results of suprarenally clamped JRA with infrarenal aortic aneurysms (AAA). Methods From 1997 to 2004, patients who received open surgery with suprarenal clamping for JRA were included in the study and compared to matched patients with infrarenal clamping (AAA). Measurements analyzed were the in-hospital mortality and morbidity. Midterm results were obtained through clinical investigation and magnetic resonance angiography imaging. Results Thirty-five patients (mean age, 68.4 years; 30 male and 5 female) received suprarenal cross-clamping for JRA. The overall in-hospital mortality for JRA and for the controls (AAA) with elective aortic repair was 4.5% (6.1% JRA; 3% AAA, p = 0.058). The morbidity of JRA was elevated according to the rate of pulmonary complications (p = 0.021) and the need for re-operation (p = 0.019). The mean follow-up time was 2.3 years (range, 8–96 months). At follow-up, 28 patients (80%) from the JRA group and 29 patients from the AAA group (82.9%) were alive. Conclusion Open aortic surgery for JRA with the need for suprarenal cross-clamping shows a slightly elevated in-hospital mortality rate without statistical significance and equal midterm mortality results in comparison with infrarenally clamped aortic aneurysms.     

Lung function development in the first 2 yr of life is independent of allergic diseases by 2 yr

The aim of the study was to assess if lung function at birth predicts lung function at 2 yr and secondly, if lung function development was influenced by the common phenotypes of recurrent bronchial obstruction (rBO) or atopic eczema (AE) by 2 yr. Lung function was assessed at birth (n = 802) and at 2 yr within the prospective birth cohort study 'the Environment and Childhood Asthma Study' in Oslo. The 135 children with lung function measured at birth by tidal flow volume (TFV) loops and passive respiratory mechanics, who were included in a nested case-control study were reinvestigated at 2 yr with clinical examination, TFV loops (n = 90) (mean age 26.6 (3.7 s.d.) months), skin prick test and parental interview. Children were categorized into quartiles (lower, middle two, upper) according to time to peak tidal expiratory flow/total expiratory time (t(PTEF)/t(E)) at birth as well as clinical phenotype based on the presence of rBO and/or AE (ever) by 2 yr. The observed reduction in mean t(PTEF)/t(E) from birth to 2 yr within the quartiles, were not significantly different after controlling for 'regression to the mean'. t(PTEF)/t(E) at birth correlated significantly with t(PTEF)/t(E) at 2 yr, (r = 0.475, p < 0.001). Children with both rBO and AE by 2 yr had significantly lower t(PTEF)/t(E) at 2 yr (p = 0.002) and at birth (p = 0.027), compared with children with no rBO or AE. Clinical phenotype at 2 yr did not influence the change in t(PTEF)/t(E) from birth to 2 yr. This study demonstrates a clear tracking of lung function from birth, not influenced by rBO or AE by 2 yr.     

Characteristics of antibody responses in tick-borne encephalitis vaccination breakthroughs

Tick-borne encephalitis (TBE) virus is an important human pathogenic flavivirus that is endemic in Europe and Asia. The disease can be effectively prevented by inactivated vaccines and vaccination breakthroughs (VBTs) are rare. We investigated the characteristics of antibody responses in such VBTs in comparison to those in unvaccinated TBE patients. In contrast to the unvaccinated controls, most of the VBTs displayed a delayed IgM antibody response and had high avidity and strongly neutralizing antibodies already in the first sample taken upon hospitalization. The antibody profile of these patients therefore had the characteristics of an anamnestic immune response. In the VBTs analyzed, immunological priming and memory were apparently not sufficient or fast enough to prevent the disease.