Neuropharmacological study of aged MAM-treated rats.

After evaluation of activity in an open field, norepinephrine (NE), serotonin (5HT), 5-hydroxyindolacetic acid (5HIAA), homovanillic acid (HVA), and choline acetyltransferase (CAT) were investigated in cortex of 26-month-old rats poisoned with methylazoxymethanol (MAM) as compared to control rats of the same age. NE and 5HT concentrations showed a marked increase, but levels were normal when expressed as total content, just as in MAM-exposed young adults. Concentrations of 5HIAA were also increased but to a lesser extent than 5 HT. Aged MAM rats did not show any modification of spontaneous activity although hyperactivity is characteristic of young adults exposed to MAM. Together with this behavioral observation, a significant decrease in total HVA content was measured. Because HVA levels seem correlated with activity in MAM-exposed rats, we speculate that the behavioral abnormality recovers in old age. Total CAT activity was also reduced. These results indicate that the neurochemical pattern of young adult MAM-poisoned rats is conserved in aged rats except for some changes in the dopaminergic and cholinergic systems.

Impaired resistance to oxidation of low density lipoprotein in cystic fibrosis: improvement during vitamin E supplementation.

Antioxidants such as vitamin E protect unsaturated fatty acids of LDL against oxidation. In the ex vivo model used, LDL was exposed to Cu2+ ions, a potent prooxidant capable of initiating the oxidation of LDL. The lag time, indicating the delay of conjugated diene formation in LDL due to antioxidant protection, was measured in 54 cystic fibrosis (CF) patients with plasma alpha-tocopherol levels below (Group A, n = 30) or above (Group B, n = 24) 15.9 mumol/L (mean - 2 SD of Swiss population). Patients were reevaluated after 2 months on 400 IU/d of oral RRR-alpha-tocopherol. In group A, alpha-tocopherol concentrations in LDL increased significantly from 3.2 +/- 1.6 mol/mol LDL to 8.2 +/- 2.8 mol/mol (P < 0.001) and lag times increased from 79 +/- 33 min to 126 +/- 48 min (P < 0.001), whereas in the vitamin E sufficient group B no further increase neither in LDL alpha-tocopherol concentrations or in lag times was observed. LDL oleic acid concentrations were higher, and linoleic acid concentrations were lower in patients than in controls. After efficient vitamin E supplementation, lag times were positively related to LDL alpha-tocopherol (P < 0.01) and negatively to LDL linoleic and arachidonic acid content (P < 0.001). The maximum rate of oxidation correlated positively with linoleic and arachidonic acid concentrations, as did the maximum conjugated diene absorbance. These results indicate that LDL resistance to oxidation is impaired in vitamin E deficient CF patients but can be normalized within 2 months when alpha-tocopherol is given in sufficient amounts. Linoleic and arachidonic acid content exhibit a major influence on the LDL resistance to oxidation.

High performance liquid chromatography of a new 1,4-dihydropyridine: applications to pharmacokinetic study in dogs.

A new nitrendipine derivative [ethyl-2-(1-piperidino)ethyl-1,4-dihydro-2,6-dimethyl-4-(3-nitrophenyl)- 3,5-pyridine dicarboxylate hydrochloride;1] was assayed in plasma by high-performance liquid chromatography. After deproteinization and extraction, 1 and nitrendipine, as the external standard, were separated by ion-pair chromatography and measured by UV detection (254 nm). The method is rapid and specific: the limit of sensitivity of the assay was 5 ng/mL and the concentration range was linear between 5 and 2000 ng/mL. In vitro studies showed that, in contrast to nifedipine and nicardipine, 1 and nitrendipine were stable when exposed to light for at least 4 h. Pharmacokinetic parameters obtained in three beagle dogs after oral and intravenous administration are reported. Comparison with a nicardipine pharmacokinetic study showed similar results for the distribution and elimination characteristics of these two drugs.

The relationship of self-rated function and self-rated health to concurrent functional ability, functional decline, and mortality: findings from the Nun Study.

We investigated the relationship of self-rated function (i.e., the ability to take care of oneself) and self-rated health to concurrent functional ability, functional decline, and mortality in participants in the Nun Study, a longitudinal study of aging and Alzheimer's disease. A total of 629 of the 678 study participants self-rated their function and health and completed an initial functional assessment in 1991-93. Survivors completed a second assessment in 1993-94. Overall, self-rated function had a stronger relationship to functional ability at the first assessment and to functional decline between the first and second assessments than did self-rated health. Self-rated function also had a stronger relationship to mortality than did self-rated health. Self-rated function may be a better marker of global function than is self-rated health and may be a useful addition to clinical assessment and scientific investigation of the relationships among function, health, and disease.

Self-rated function, self-rated health, and postmortem evidence of brain infarcts: findings from the Nun Study.

OBJECTIVES: Self-rated function is a new global measure. Previous findings suggest that self-rated function predicts future functional decline and is strongly associated with all-cause mortality. We hypothesized that the strength of the relationship of self-rated function to all-cause mortality was in part due to functional decline, such as would occur with brain infarcts. METHODS: Self-ratings of function and health (on a 5-point scale, ranging from excellent to poor) were assessed annually on 630 participants in the Nun Study. Mortality surveillance extended from October 31, 1991 to March 1, 1998, and, among those who died, neuropathological examination determined postmortem evidence of brain infarcts. Cox regression modeling with self-rated function and health as time-dependent covariates and stratification by assessment period were used in these analyses. RESULTS: Self-rated function and health ratings of good, fair, and poor were significantly associated with doubling of the risk of mortality, compared with ratings of very good and excellent. Self-rated function ratings of fair or poor were associated with a threefold increase in the risk of mortality with brain infarcts, but self-rated function and health ratings of fair and poor were comparable in their association with all-cause mortality and mortality without brain infarcts. DISCUSSION: Self-rated function was significantly associated with mortality with brain infarcts, suggesting that brain infarcts may be experienced as functional loss but not recognized or labeled as disease. Our results suggest that self-rated function and health should be explored simultaneously in future research.

Comparison of preoperative sonography with intraoperative findings in congenital hypertrophic pyloric stenosis.

In 17 infants with hypertrophic pyloric stenosis, the pyloric diameter was measured preoperatively by ultrasound. The mean pyloric diameter was 15.12 +/- 2.11 mm (mean +/- SD), range 11 to 19 mm. During pyloromyotomy, the hypertrophic pylorus was precisely measured craniocaudally and dorsoventrally, and measurements were obtained concerning muscular thickness and length of the pylorus. The preoperative and intraoperative measurements were subsequently compared. Differences of 0.76 +/- 1.68 mm and 1.24 +/- 2.04 mm were found for the dorsoventral and craniocaudal diameters, respectively. The intraoperative measurements were consistently greater than the sonographic findings. The length of the pylorus averaged 22.0 +/- 2.66 mm, the muscular thickness 6.53 +/- 1.68 mm, respectively. This prospective study confirms the diagnostic value of sonography in congenital hypertrophic pyloric stenosis.

Evaluation of first pass effect and biliary excretion of diperdipine in the dog.

Intravenous, oral and intraportal doses of diperdipine were given to bile duct cannulated dogs in order to assess the impact of first pass effect on the pharmacokinetics of this compound. After intravenous and oral doses, absolute bioavailability was calculated to be 18.7%. Biliary excretion accounted for about 0.1% of the total clearance of diperdipine and did not contribute to the overall elimination of the drug. After intraportal administration, the bioavailable fraction of diperdipine was increasing up to 44.3% suggesting a prehepatic site of loss of the drug. This was also substantiated by the fact that after oral administration a lesser fraction was excreted in the bile, than after the intraportal dose. The drug was highly bound to plasma proteins (greater than 96%) and was largely distributed in the blood cells for which a concentration dependent process was observed.

[Results of treatment of early stomach cancer]. / Rezul'taty lecheniia bol'nykh rannim rakom zheludka.

The results of surgical treatment of 40 patients with early gastric cancer are analysed. 57.5% of patients were operated on. Radical resection was performed in 41% and palliative one--in 20.5% of cases. The mortality rates in the radical surgery and palliative resection groups in postoperative period were 43.7 and 50%, respectively. 12.5% of radically-operated patients survived over 5 years. Pathogenetic forms of cancer developing in the gastric stump as well as optimal terms of the commencement of a regular follow-up are discussed.

First description of three patients with multifocal lymphangiomatosis and protein-losing enteropathy following palliation of complex congenital heart disease with total cavo-pulmonary connection.

The objective was to identify abdominal lymphatic malformations in pediatric patients with protein-losing enteropathy after palliation of complex congenital heart disease with total cavo-pulmonary connection (TCPC). In 2006, we performed complete hemodynamic and laboratory workup and thoracic and abdominal MRT screens in three patients who newly presented with symptoms of protein-losing enteropathy. All three patients, aged 3, 5, and 7 years, showed excellent TCPC hemodynamics with central venous pressures of 10-13 mm Hg. None of the patients had right-to-left overflow. All three patients showed extensive thoracic and mesenterial lymphangiomatosis. One patient died after 18 months of therapy, which included long-term parenteral nutrition, somatostatin, subcutaneous heparin injections, and frequent albumin and immunoglobulin substitution. The other two patients are in stable condition. Lymphangiomatosis might play an unknown role in the pathogenesis of protein-losing enteropathy after TCPC. It remains unclear whether lymphangiomatosis is a primary congenital disease related to the cardiac disease or if it is triggered by repeated surgery or venous congestion. The presence of lymphangiomatosis should be given diagnostic and therapeutic consideration in TCPC patients in the future.

Chronic colitis due to an epithelial barrier defect: the role of kindlin-1 isoforms.

Kindlin-1 is an epithelium-specific phosphoprotein and focal adhesion adaptor component. Mutations in the corresponding gene (KIND1) cause Kindler syndrome (KS), which is manifested by skin blistering, poikiloderma, photosensitivity and carcinogenesis. Some patients also exhibit gastrointestinal symptoms, but it has remained unclear whether these represent a feature of Kindler syndrome or a coincidence. We examined kindlin-1 in human gastrointestinal epithelia and showed that it is involved in the aetiopathology of Kindler syndrome-associated colitis. Kindlin-1 expression was assessed by indirect immunofluorescence, western blot and RT-PCR. Kindlin-1 is expressed in oral mucosa, colon and rectum. Both the full-length 74 kDa kindlin-1 protein and a 43 kDa isoform were detected in CaCo2 cells, the latter resulting from alternative splicing. In the first months of life, patients (homozygous for null mutations) had severe intestinal involvement with haemorrhagic diarrhoea and showed morphological features of severe ulcerative colitis. Later in childhood, histopathology demonstrated focal detachment of the epithelium in all segments of the colon, chronic inflammation and mucosal atrophy. These findings define an intestinal phenotype for Kindler syndrome as a consequence of a primary epithelial barrier defect. The different clinical intestinal manifestations in Kindler syndrome patients may be explained by partial functional compensation of kindlin-1 deficiency by the intestinal isoform or by the presence of truncated mutant kindlin-1.

[The influence on the outcome of pregnancies of sociologic and medical changes during 1963--1972. II. Special section: prenatal dystrophy, diabetogenic fetal disease, the impact of previous miscarriages and twins (author's transl)]. / Einfluss soziologischer und medizinischer Veränderungen 1963--1972 auf das Schwangerschaftsergebnis. II. Spezieller Teil: Pränatale Dystrophie, diabetogene Fetalkrankheit, Bedeutung vorangegangerner missglückter Graviditäten, Zwillinge

Analysis of 16 486 obstetric and neonatal case histories of the years 1963--1972. 30.7% of all neonates of Austrian (A) mothers showed one or more signs of placentar insufficiency. Pronounced prenatal dystrophy (p.d.) occurs in similar numbers in women with or without EPH gestosis, but has other important causes as well. In p.d. excentric umbilical cord insertion is more common than in neonates without dystrophy (56.4 : 52.4). Very young mothers often have neonates with p.d. During the ten year period p.d. increased considerably until 1967. After that it decreased slightly but not to the numbers at the start. These changes in frequency apply to all maternal age groups equally. Pronounced and highgrade p.d. in foreign workers' (f.w.) children is significantly more common than with A mothers (p 0.0001). Cushing's syndrome as a symptom of fetal disease due to diabetes has become rarer by over 50% owing to more intensive preventive measures; at the same time still-births of those weighing 4000 g or more have disappeared. The frequency of Cushing's syndrome rises according to the age of the mother from 0.8% to 3.5%. In Austrian mothers the number of previous abortions has decreased during these 10 years, just as has the number of births. The chances of actual pregnancies are the worse the higher the number of previous abortions. In f.w. mothers previous artificial abortions are far more numerous, but the outcome of pregnancy does not deteriorate with an increase in previous abortions. In A mothers the effects of previous premature or still births are the same as after abortions but much more pronounced. The percentage of normal births following premature births has fallen somewhat in A mothers during the ten year period, also after one miscarriage from 86% to 71%, probably owing to effective prevention of late abortions. Of 173 pairs of twins the first-born was heavier than the second in 71 instances. It is confirmed that the second twin is still-born almost twice as often as the first-born and this in twins of whom the second is heavier than the first. 11% of individual twins weith more than 3000 g and 28% between 2501 and 3000 g. The heavier the twins the lower the average age of the mother (from 30.8 to 26.6). The mothers whose first twin weighs more than 2500 g, the second less, appear to be younger than those with an inverse ratio (27.6 : 30.7).