Investigative MRI cholangiopancreatography for primary sclerosing cholangitis-type lesions in children with IBD.

OBJECTIVES: The aim of the study was to estimate the frequency of primary sclerosing cholangitis (PSC)-type lesions in children with inflammatory bowel disease (IBD) by means of magnetic resonance cholangiopancreatography (MRCP), and to investigate the association between a series of easily applicable data on the one hand and the presentation of such lesions at MRCP on the other hand. METHODS: Collected demographic, laboratory, and magnetic resonance enterography data from the records of 73 children with IBD were cross-sectionally related to the MRCP-based diagnosis. RESULTS: Around the time of MRCP, the distribution of IBD subtypes was 64.4%, 24.7%, and 11% for Crohn disease, indeterminate colitis, and ulcerative colitis, respectively. A total of 11 patients (15.1%) were identified with PSC-type lesions. Demographic and magnetic resonance enterography data were unrelated to the MRCP outcome. Biochemical abnormalities were of low prevalence (<50%) among patients with PSC. The abnormality prevalences of aspartate transaminase, alanine transaminase, and γ-glutamyl transferase were significantly higher in the PSC group, both at initial diagnosis of IBD and at the time of MRCP. Less-consistent results were documented for bilirubin and alkaline phosphatase, especially at initial diagnosis of IBD. CONCLUSIONS: The abnormality prevalences of aspartate transaminase, alanine transaminase, and γ-glutamyl transferase were significantly higher in the PSC group. Nevertheless, PSC-type lesions frequently occur in pediatric IBD, even if the biochemical profile is hardly indicative of this probability.

Polymeric prostaglandin PGBx and other prostaglandin polymers prolong survival of the heart of the hypoxic mouse.

A new chemical method for prolongation of survival under hypoxia is reported. Polymeric prostaglandin PGBx which shows beneficial effects on damaged mitochondria in vitro was used. Survival time of the intact hypoxic (6% O2) mouse as measured by electrocardiogram is prolonged by 100% or more by standard PGBx (mean polymer chain length = 7). Prostaglandin polymers of mean chain lengths of 2 to 3 also produced marked prolongation of survival. Monomeric prostaglandin PGB1 was not effective for prolongation of survival.

Chronic effects of PGBx, a polymeric prostaglandin, on blood leukocyte counts.

PGBx, a polymeric prostaglandin, in chronic doses therapeutic for hereditary diabetes and hereditary obesity in mice, produces significant increases of blood neutrophils and lymphocytes in normal mice, hereditary diabetic mice, and hereditary obese mice. For lymphocytes, but not for neutrophils, the direction of the PGBx effect reverses at doses above 10 micrograms/g of body weight.

Mechanism of polymeric prostaglandin PGBx for in vitro stabilization of rat liver mitochondrial oxidative phosphorylation.

The mechanism of the in vitro PGBx effect on mitochondria was studied by determining the specific requirements of the assay system composition. These studies showed that (a) rat liver mitochondria must first be exposed to hypotonic media containing PGBx under aerobic conditions, (b) oxygen, Pi, Mg++, phosphate acceptor (nucleotides), and some oxidizable substrates are essential components to yield optimal phosphorylation values. KCl and bovine serum albumin are non-essential components. With regard to nucleotide acceptor specificity, the AMP, ADP, and glucose-ADP-hexokinase systems were satisfactory. With regard to substrate specificity, only beta-hydroxybutyrate and externally reduced NAD+ were unsatisfactory. The requirement for oxygen was twofold: (a) as an absolute requirement for oxidative phosphorylation, and (b) as a requirement for the hypotonic degradation of mitochondria. These results suggest that PGBx reacts with mitochondria to "protect" against degradation during aerobic hypotonic exposure.

Studies on the mechanism of mitochondrial protection by polymeric prostaglandin PGBx.

On the basis of the interaction between tritiated PGBx and rat liver mitochondria, it appears that PGBx interacts with rat liver mitochondria to form a complex. At low PGBx-mitochondrial ratios, one effect of this complex formation is to stabilize the phosphorylation activity of rat liver mitochondria when exposed for short times to hypotonic solutions. At higher PGBx-mitochondrial ratios, PGBx fails to show this effect. At low PGBx concentrations, PGBx is also shown to inhibit release of amino acids and proteins as well as glutamic acid dehydrogenase and monoamine oxidase from the mitochondria and to inhibit mitochondrial swelling.

Characteristics of the initial medical interview associated with patient satisfaction and understanding.

This study examines the relationship between selected interview characteristics, particularly physicians' verbal behaviors, and levels of patient satisfaction and understanding. Twenty-nine initial patient interviews by 11 physicians at the University of Washington Hospital Family Medical Center were videotaped and rated using a modified Bales' technique. Questionnaires provided measures of patient satisfaction and understanding. Results of correlation analysis indicate that higher patient satisfaction was associated with greater interview length, increases in the proportional time spent by the physician in presenting information and discussing prevention, and shorter chart review times. Increased patient understanding was associated with increases in the proportional time spent presenting both information and opinions, close physical proximity, and reduced chart review time. Implications of the results are discussed as well as methodological issues relating to further research.

Structural features of PGBX (a prostaglandin polymer) deduced by analogies with dimers derived from 15-keto-prostaglandin B.

The polymeric prostaglandin, PGBX, has a beneficial effect on oxidative phosphorylation of damaged mitochondria in vitro and has manifested interesting effects in vivo. Its chemical structure has been partially elucidated by comparison of its 13C-NMR (nuclear magnetic resonance) spectrum with the spectra of prostaglandin monomers. Reported here is subsequent comparison of PGBX with two prostaglandin dimers derived from 15-keto-PGB1, which provide more complete structural information. The two prostaglandin dimers were synthesized and analyzed by 13C-MNR and by other techniques, with particular attention to positions of linkages between the two monomeric prostaglandin subunits of the dimers. Based on these data, some proposals are presented regarding probable locations of linkages between prostaglandin monomeric subunits in the polymeric PGBX.

Interaction of bovine serum albumin with PGBx (polymeric 15-keto-prostaglandin B1).

Bovine serum albumin (BSA) interacts with PGBx, a polymeric derivative of 15-keto-prostaglandin B1, to form a complex that does not exhibit the fluorescence of free BSA. The complex is soluble at pH 5.2 in contrast to free PGBx, which is insoluble. Molar ratio of the BSA-PGBx complex is 1:18. This complexing appears to suppress the ability shown by non-complexed PGBx to reactivate phosphorylation in degraded isolated rat liver mitochondria.

Dose-dependent reduction of hereditary obesity in the non-diabetic mouse by polymeric prostaglandin PGBx.

Mice genetically obese but not diabetic show large reductions of excessive body weight and excessive food intake when treated with polymeric prostaglandin PGBx. Larger doses of PGBx produce greater reduction of both body weight and food consumption, in agreement with dose-dependent effects of PGBx observed previously in the genetically diabetic mouse. Only minor effects of PGBx on blood glucose were observed. This suggests that PGBx effects on obesity and appetite are not mediated through a blood glucose mechanism.

Protection and reactivation of oxidative phosphorylation in mitochondria by a stable free-radical prostaglandin polymer (PGBx).

A stable free-radical polymeric derivative of prostaglandin B1 (PGBx) has been synthesized that exhibits regenerative effects on oxidative phosphorylation in aged mitochondria. The molecular weights of the most active preparations fall between 2000 and 2600. PGBx is characterized by a single-line electron spin resonance spectrum that is stable at room temperature. PGBx restores phosphorylating ability and net ATP synthesis in isolated mitochondria aged for 4 days at 0 degrees C and protects against further degradation of phosphorylating activity when such aged mitochondria are preincubated at 28 degrees C in the absence of adenine nucleotide phosphate acceptors. This compound has been reported to exert beneficial effects in vivo in experimental pathological conditions, such as regional ischemia, in which the mitochondria of the ischemic region may have been damaged.

Studies on PGBx, a polymeric derivative of prostaglandin B1: I. Synthesis and purification of PGBx.

PGBx, a new polymeric derivative of PGB1, previously was shown to (a) restore oxidative phosphorylation to degraded isolated rat liver mitochondria in vitro and (b) to reverse the effects of cardiogenic ischemia in monkeys and cerebral ischemia in rabbits. This report describes in detail the synthesis and purification of PGBx via PGB1, starting with azelaic acid. Details of the in vitro mitochondrial assay are also reported. Purified PGBx exhibiting maximal reactivation of mitochondrial phosphorylation has a mean molecular weight of 2350. Yield of PGBx based on azelaic acid is 4% and based on PGB1 is 25%.

Dose dependence of PGBX, a polymeric derivative of prostaglandin B1, for normalization of hereditary diabetes of the mouse.

A polymeric derivative of prostaglandin B1, PGBX, which reactivates phosphorylation in damaged mitochondria, is shown to normalize the high blood glucose, obesity, and excessive appetite of the hereditary diabetic mouse. The degree of normalization is shown to vary with dosage.

Life change and illness onset: importance of concepts for family physicians.

The questions of illness susceptibility and the how and why of the onset of illness are of great concern to family physicians, who are constantly presented with a bewildering array of maladies. This paper presents a model of illness onset as related to life change which is felt to be a highly relevant and useful concept for family physicians. This model has been developed over many years and proposes that illness onset is predictably related to life change, which in turn is a reflection of the amount of coping required. The specific development of these concepts is presented in detail including the development and quantitation of the social readjustment rating scale which quantifies life changes.

Some in vitro and in vivo effects of a new prostaglandin derivative.

PIP: In vitro experiments were carried out under the premise that fatigue/stress could be defined bodily in terms of energy demand under conditions of limited supply. The experiments demonstrated some new biochemical correlates of stress and some of their hormonal control factors. It was seen that both physical and psychological stress--e.g., sleep deprivation, combat flying--caused an elevation of phospholipid G (phosphatidyl glycerol). This reaction was consistent, despite the type of stress. Other phospholipids varied with the stress conditions. The triggering factor for this raised phospholipid level may be explained by the fact that injection of various PGs (prostaglandins) causes major elevation in G and lesser changes in other phospholipids. The different types of PGs cause varying reactions in the different phospholipids. The work with PGs indicates a means of channelling biological energy in ways that will enhance bodily tolerance to stress.^ieng