A presenilin 1 mutation (L420R) in a family with early onset Alzheimer disease,seizures and cotton wool plaques,but not spastic paraparesis

Over 100 mutations in the presenilin‐1 gene (PSEN1) have been shown to result in familial early onset Alzheimer disease (EOAD), but only a relatively few give rise to plaques with an appearance like cotton wool (CWP) and/or spastic paraparesis (SP). A family with EOAD, seizures and CWP was investigated by neuropathological study and DNA sequencing of the PSEN1 gene. Aβ was identified in leptomeningeal vessels and in cerebral plaques. A single point mutation, p.L420R (g.1508T > G) that gives rise to a missense mutation in the eighth transmembrane (TM8) domain of PS1 was identified in two affected members of the family. p.L420R (g.1508T > G) is the mutation responsible for EOAD, seizures and CWP without SP in this family.     

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.     

Complete obstruction of the sigmoid colon treated by primary resection and anastomosis—An improved technique (preliminary report)

Three patients with complete colonic obstruction treated by primary resection and anastomosis with intraoperative colon tube decompression and bowel lumen sterilization without a protective colostomy are presented. An improved colonic decompressor was used. It is postulated that this procedure is an alternative safe technique in patients with colonic obstruction in whom an end-colostomy, mucous fistula, or Hartmann pouch would be necessary.