Ferroic multipolar order and disorder in cyanoelpasolite molecular perovskites.

We use a combination of variable-temperature high-resolution synchrotron X-ray powder diffraction measurements and Monte Carlo simulations to characterize the evolution of two different types of ferroic multipolar order in a series of cyanoelpasolite molecular perovskites. We show that ferroquadrupolar order in [C3N2H5]2Rb[Co(CN)6] is a first-order process that is well described by a four-state Potts model on the simple cubic lattice. Likewise, ferrooctupolar order in [NMe4]2B[Co(CN)6] (B = K, Rb, Cs) also emerges via a first-order transition that now corresponds to a six-state Potts model. Hence, for these particular cases, the dominant symmetry breaking mechanisms are well understood in terms of simple statistical mechanical models. By varying composition, we find that the effective coupling between multipolar degrees of freedom-and hence the temperature at which ferromultipolar order emerges-can be tuned in a chemically sensible manner. This article is part of the theme issue 'Mineralomimesis: natural and synthetic frameworks in science and technology'.

PDGF-C is a new protease-activated ligand for the PDGF alpha-receptor.

Platelet-derived growth factors (PDGFs) are important in many types of mesenchymal cell. Here we identify a new PDGF, PDGF-C, which binds to and activates the PDGF alpha-receptor. PDGF-C is activated by proteolysis and induces proliferation of fibroblasts when overexpressed in transgenic mice. In situ hybridization analysis in the murine embryonic kidney shows preferential expression of PDGF-C messenger RNA in the metanephric mesenchyme during epithelial conversion. Analysis of kidneys lacking the PDGF alpha-receptor shows selective loss of mesenchymal cells adjacent to sites of expression of PDGF-C mRNA; this is not found in kidneys from animals lacking PDGF-A or both PDGF-A and PDGF-B, indicating that PDGF-C may have a unique function.

PDGFB regulates the development of the labyrinthine layer of the mouse fetal placenta.

PDGFB is a growth factor which is vital for the completion of normal prenatal development. In this study, we report the phenotypic analysis of placentas from mouse conceptuses that lack a functional PDGFB or PDGFRbeta gene. Placentas of both types of mutant exhibit changes in the labyrinthine layer, including dilated embryonic blood vessels and reduced numbers of both pericytes and trophoblasts. These changes are seen from embryonic day (E) 13.5, which coincides with the upregulation of PDGFB mRNA levels in normal placentas. By E17, modifications in shape, size, and number of the fetal blood vessels in the mutant placentas cause an abnormal ratio of the surface areas between the fetal and the maternal blood vessels in the labyrinthine layer. Our data suggest that PDGFB acts locally to contribute to the development of the labyrinthine layer of the fetal placenta and the formation of a proper nutrient-waste exchange system during fetal development. We point out that the roles of PDGFB/Rbeta signaling in the placenta may be analogous to those in the developing kidney, by controlling pericytes in the labyrinthine layer and mesangial cells in the kidney.

Defective oligodendrocyte development and severe hypomyelination in PDGF-A knockout mice.

There is a class of oligodendrocyte progenitors, called O-2A progenitors, that is characterized by expression of platelet-derived growth factor &agr;-receptors (PDGFR(&agr;)). It is not known whether all oligodendrocytes are derived from these PDGFRalpha-progenitors or whether a subset(s) of oligodendrocytes develops from a different, PDGFR alpha-negative lineage(s). We investigated the relationship between PDGF and oligodendrogenesis by examining mice that lack either PDGF-A or PDGF-B. PDGF-A null mice had many fewer PDGFR alpha-progenitors than either wild-type or PDGF-B null mice, demonstrating that proliferation of these cells relies heavily (though not exclusively) on PDGF-AA homodimers. PDGF-A-deficient mice also had reduced numbers of oligodendrocytes and a dysmyelinating phenotype (tremor). Not all parts of the central nervous system (CNS) were equally affected in the knockout. For example, there were profound reductions in the numbers of PDGFR alpha-progenitors and oligodendrocytes in the spinal cord and cerebellum, but less severe reductions of both cell types in the medulla. This correlation suggests a close link between PDGFRalpha-progenitors and oligodendrogenesis in most or all parts of the CNS. We also provide evidence that myelin proteolipid protein (PLP/DM-20)-positive cells in the late embryonic brainstem are non-dividing cells, presumably immature oligodendrocytes, and not proliferating precursors.

A foodborne outbreak of Campylobacter jejuni (O:33) infection associated with tuna salad: a rare strain in an unusual vehicle.

We report a foodborne outbreak of Campylobacter jejuni infection in a summer camp. Outbreak-related cases occurred in 79 persons including 3 secondary cases in campers. Campylobacter jejuni was isolated from stool specimens from 16 of 21 patients who submitted a sample; 13 viable isolates were serotyped and all were serotype O:33 (somatic O scheme) or HL:18 (heat-labile scheme), and biotype III (Lior scheme). This serotype is widely distributed geographically but rarely isolated from humans. Samples of water from the wells supplying the camp were negative for faecal coliforms, and raw milk had not been served in the camp. A matched (1:1) case-control study identified tuna salad served for lunch on 19 July as the likely food item associated with illness (matched odds ratio=22; 95% confidence intervals (CI)=3.6-908). Swimming in the camp pool and other recreational water use in area lakes by the campers were not statistically associated with illness. The precise mechanism of introduction of the organism into the tuna salad remains unknown; contamination most likely occurred through cross-contamination with another food product, the hands of a food handler, or a work surface. Several deficiencies in the operation of the camp kitchen were identified. In Wisconsin, kitchens of such camps are subject to different inspection rules than restaurants. Camp staff, administrators, counselors, food managers, and infirmary staff, should fulfil important roles in their respective areas to prevent future outbreaks.

Placebo--the forgotten drug.

The placebo effect is seen in patients who have been the target of intervention believed to lack specific action. This effect seems to be an important, and possibly the only, contribution to the positive effect of alternative medicine sometimes reported. The risks involved in the uncritical utilization of the placebo effect are, however, great and must be carefully considered. Most of the information available on this effect has been obtained from double-blind studies in connection with the introduction of new drugs. Depending on the kind of effect that is expected, improvements of up to 30% or more can be noted. Many attempts have been made to explain the nature of the placebo effect. Thus it has been suggested that a placebo acts by decreasing anxiety. Another explanation is that a placebo acts by meeting the expectations of the patient. It has also been proposed that the human placebo response has characteristics of a conditioned response.

PDGF-A signaling is a critical event in lung alveolar myofibroblast development and alveogenesis.

A mouse platelet-derived growth factor A chain (PDGF-A) null allele is shown to be homozygous lethal, with two distinct restriction points, one prenatally before E10 and one postnatally. Postnatally surviving PDGF-A-deficient mice develop lung emphysema secondary to the failure of alveolar septation. This is apparently caused by the loss of alveolar myofibroblasts and associated elastin fiber deposits. PDGF alpha receptor-positive cells in the lung having the location of putative alveolar myofibroblast progenitors were specifically absent in PDGF-A null mutants. We conclude that PDGF-A is crucial for alveolar myofibroblast ontogeny. We have previously shown that PDGF-B is required in the ontogeny of kidney mesangial cells. The PDGFs therefore appear to regulate the generation of specific populations of myofibroblasts during mammalian development. The two PDGF null phenotypes also reveal analogous morphogenetic functions for myofibroblast-type cells in lung and kidney organogenesis.

Lack of effect of omeprazole, cimetidine, and ranitidine on the pharmacokinetics of ethanol in fasting male volunteers.

The effects of three gastric antisecretory drugs on the pharmacokinetics of ethanol have been studied in a randomized crossover experiment. Male medical students (n = 12) took ethanol 0.8 g/kg body weight at 08.00 h after an overnight fast. On seven successive days before drinking ethanol they were given omeprazole 20 mg, cimetidine 800 mg, ranitidine 300 mg, or no drug, with a period of at least 7 days between treatments. The peak blood ethanol concentration of 21.9 to 22.8 mmol.l-1 occurred at 64 to 70 min after the end of drinking. The rate of disappearance of ethanol from the blood ranged from 3.0 to 3.3 mmol.l-1.h-1 and the rate of removal from the whole body ranged from 8.0 to 8.5 g.h-1. The apparent volume of distribution of ethanol was almost the same for all four treatments: mean 0.68 l.kg-1, corresponding to a mean total body water of 44 l (59% body weight). Mean areas under the concentration-time profiles of ethanol ranged from 83 to 87 mmol.l-1.h for the four treatments. It is concluded that omeprazole, cimetidine and ranitidine do not alter the kinetics of a moderate dose of ethanol.

Splenectomy for haematological diseases.

Two hundred patients with various haematological diseases underwent splenectomy between 1974 and 1986. The diagnoses were: Hodgkin's disease (n = 76), hairy cell leukaemia (n = 25), idiopathic thrombocytopenic purpura (n = 20), chronic lymphatic leukaemia (n = 19), haemolytic anaemia (n = 18), non-Hodgkin lymphoma (n = 16), myelofibrosis (n = 10), chronic myeloid leukaemia (n = 6), spherocytosis (n = 4), and miscellaneous (n = 6). Many of the patients were treated with corticosteroids and in poor general condition, partly as a result of chemotherapy. There were 37 postoperative complications in 29 patients (14.5%); two died, both of septicaemia. Pneumonia, bleeding, and wound infection were the most common complications, occurring in 9, 8, and 6 patients, respectively. Twelve patients required reoperation, eight for bleeding, two for intra-abdominal abscesses, and one each for pancreatitis and bowel perforation. There was no association between the diagnosis and the type of postoperative complication, but patients whose spleens weighed more than 2 kg had an increased incidence of postoperative complications (30%). We conclude that elective splenectomy is a safe treatment for haematological diseases, even in high risk patients.

Quality of alternative medicine--complications and avoidable deaths.

Patients with diseases, known to respond well to treatment within the conventional medical system, may be adversely affected if treatment with alternative medicine is given instead. In order to analyse to what extent this may occur in Sweden, a mail survey was carried out. Two hundred and forty-two heads of departments of pediatrics, internal medicine, rheumatology, neurology and oncology were asked to supply case reports where such alternative treatment had resulted in either a delay of diagnosis of a disease, where effective therapy was available, or in substitution of effective conventional therapy with alternative medicine. Eighty-four out of 233 clinics reported 123 cases from the period 1984-1988, most of them from internal medicine. Six patients died following alternative treatment and 27 had to be treated in intensive care units after severe complications of alternative treatment. In most cases health resort managers had withdrawn effective medication or instituted vegetarian diets for patients with severe catabolic conditions, such as collagen diseases, renal insufficiency or inflammatory bowel disease. Twenty-three children had been treated by alternative medicine in violation of the Swedish law against quackery, but legal action had not been taken in any case. The study, which, by design, may only reveal the tip of an iceberg, suggests that apart from the well-known direct complications, associated with alternative treatment, such treatment may further prevent patients from obtaining.

Stereoselective interaction of omeprazole with warfarin in healthy men.

The effect of concomitant treatment with omeprazole (20 mg/day) on the plasma concentration and anticoagulation effect of warfarin was studied in 21 young healthy men. An initial three weeks' treatment with warfarin alone was administered to determine the doses required for the subjects' vitamin K-dependent coagulation factors to fall within 10-20% of the normal range, as determined by the Trombotest. Omeprazole and placebo were then administered concomitantly with warfarin for 2 weeks each in a double-blind, randomized, crossover fashion. Plasma concentrations of (R)- and (S)-warfarin, and Trombotest values were measured daily on weekdays throughout the crossover period. Omeprazole had no apparent effect on the mean (S)-warfarin plasma concentration (379 ng/ml with, versus 387 ng/ml without, omeprazole), but caused a slight (12%) although statistically significant increase in the mean (R)-warfarin concentration from 490 to 548 ng/ml (95% confidence interval for difference of means: 28-88). The Trombotest values exhibited large inter- and intrasubject variability during both omeprazole and placebo treatment; however, there was a small, although statistically significant decrease in the mean value from 21.1% without to 18.7% with omeprazole treatment (95% CI for difference of means: -4.6- -0.1). Those subjects with Trombotest values nearest the therapeutic range (5-15%) exhibited less change during omeprazole treatment, and no changes occurred that required a change in warfarin dosing. The interaction of omeprazole with warfarin was attributed to a stereoselective inhibition of the hepatic metabolism of the less potent (R)-warfarin enantiomer. The small effect of omeprazole on the anticoagulation activity of warfarin is not likely to be of clinical importance.

Investigation on trichothecene-stimulated lipid peroxidation and toxic effects of trichothecenes in animals.

Three experiments were performed with mice intoxicated with trichothecene-contamined feed or directly into the stomach. Lipid peroxidation was estimated by the TBA value from liver samples, but since such a test seldom provided reliable results, lipid hydroperoxides and total carbonyl were also analyzed. The formation of aldehydes and ketones was compared in vivo and in vitro. The same investigations were conducted on chickens, rainbow trouts and numerous fur animals suspected of chronic intoxication by trichothecenes. The vitamin A concentration was used as a parameter to detect alterations caused in chickens by trichothecenes. Our investigation provided evidence that lipid peroxidation is associated with trichothecene poisoning. The T-2 toxin, even in small concentrations, seems to induce strong lipid peroxidation. When DON and 3-AcDON were given together at a dosage of 180 micrograms/kg feed, 1 week's feeding caused clear lipid peroxidation in mice. Particular attention should be paid to the fact that mycotoxins may already be present in the feed before any experiment is conducted.

Deactivation of sulindac-sulphide by human renal microsomes.

The renal metabolism of sulindac-sulphide was studied in subcellular fractions from human kidney. It was shown that renal microsomes, in the presence of NADPH, effectively catalyzed the sulphoxidation of sulindac-sulphide. Also the mitochondrial fraction catalyzed the reaction but at a ten-fold lower rate than the microsomes. Carbon monoxide, metyrapone and n-octylamine did not inhibit renal sulphoxidation of sulindac-sulphide and the reaction could occur in a monooxygenase containing fraction free from NADPH-cytochrome P-450 reductase. Hydroxylation of lauric acid was studied in microsomes and in the purified monooxygenase containing fraction under the same experimental condition as sulindac-sulphide sulphoxidation. Lauric acid is a substrate known to be metabolized by a renal cytochrome P-450 to 11 and 12-hydroxylated products. This reaction was sensitive to carbon monoxide and did not occur in the absence of NADPH cytochrome P-450 reductase. Based on these results we conclude that cytochrome P-450 plays at the most a limited role in human kidney metabolism of sulindac-sulphide. In contrast, sulphoxidation of sulindac-sulphide was substantially reduced in the presence of methimazole suggesting a role of the flavin-containing monooxygenase in the renal biotransformation of sulindac-sulphide in man.