Distinct time courses of increase in cytochromes P450 1A2, 2A5 and glutathione S-transferases during the progressive hepatitis associated with Helicobacter hepaticus

Mice naturally infected by Helicobacter hepaticus develop a chronic active hepatitis leading to hepatocellular carcinoma. This mouse model of liver cancer was used to examine the impact of bacterial infection on the hepatic expression and activity of enzymes involved in carcinogen bioactivation (phase I enzymes) and detoxification (phase II enzymes). No major differences in total cytochrome P450 (CYP) content were found between control and infected mice during the course of the study. The most striking modulations of individual isoenzymes were the increases in immunohistochemical staining observed for CYP1A and CYP2A5 in relation to increasing age and liver lesions. The increase in CYP2A5 in mice aged over 12 months was confirmed by the observed increases in coumarin 7-hydroxylation (CYP2A5 substrate) in vitro and CYP2A5 mRNA levels by Northern blot analysis. Immunoblotting confirmed the specific induction of CYP1A2 in infected mice 12 and 18 months of age. Perfusion of liver with nitroblue tetrazolium, an indicator for superoxide formation, demonstrated that in livers of infected mice, hepatocytes often co-expressed CYP2A5 and formazan deposition. Concerning phase II enzymes, an enhancement of glutathione S-transferase (GST) activities, related to the disease process, was observed in infected mice. An age- specific increase of GSTpi and A4.4 (early stage of disease) and GST YaYa (>9 months) expression was also demonstrated by immunohistochemical staining. In contrast, catalase and glutathione- peroxidase activities, as well as reduced glutathione content were decreased in the early stages of disease (3-9 months) in infected mice compared to age-matched control mice. Overall, these results suggest that alterations in CYP and GST expression may contribute to the aetiology of tumour incidence due to H. hepaticus infection via production of reactive oxygen species.      

Relationship between acetylator status, smoking, and diet and colorectal cancer risk in the north-east of England

Some previous studies have suggested that the fast phenotype of the N- acetyltransferase NAT2 may confer susceptibility to colorectal cancer because of greater activation of dietary heterocyclic amines, particularly in individuals who also consume well-done red meat, but other studies have not supported this. We describe a large case-control study examining the interaction between dietary, smoking and drinking habits, and acetylation genotype in relation to susceptibility to colorectal cancer. One-hundred-and-seventy-four incident cases and 174 matched controls were recruited. Genotyping for polymorphisms in NAT2 was performed using a method that detects >95% of slow alleles and data on personal habits were collected using a standardized questionnaire. We found no difference in the frequency of the fast acetylator genotype between cases and controls [odds ratio = 0.95 (95% CI 0.61-1.49)], and analysis by sex, age and site also revealed no difference in acetylator genotype. There was, however, considerable heterogeneity in dietary risk factors between fast and slow acetylators. Analysis by acetylator type shows that recent smoking was more frequent in slow acetylator cases than matched controls [OR = 2.31 (1.16-4.6)] and that heavy alcohol consumption was also more frequent in the slow acetylator cases than controls [OR = 2.5 (1.02-7.29)]. In contrast, frequent fried meat intake was seen more frequently in fast acetylator cases than matched controls [OR = 6.0 (1.34-55)]. The odds ratio for the combination of fast acetylator status and frequent fried meat consumption in cases was 6.04 (1.6-26). Our study suggests that there may be different risk factors for colorectal cancer in slow and fast acetylators, and reveals a new observation that slow acetylators may be at risk of colon cancer from smoking. In our community, the overall effect of acetylator status on colorectal cancer risk is neutral.      

Cystic fibrosis identified by neonatal screening: incidence, genotype, and early natural history

The incidence of cystic fibrosis over the last 10 years in East Anglia (a region of the United Kingdom with a population of 2.1 million) has halved. This has happened during the establishment of a neonatal screening programme, which has enabled early diagnosis, genetic counselling, and lately the option of prenatal diagnosis in subsequent pregnancies. One hundred and seven children were born with cystic fibrosis between 1981 and 1990, eight of whom were siblings. The Guthrie blood spots of 82 infants detected by neonatal immunoreactive trypsin screening between 1981 and 1990 were examined for the presence of the most common cystic fibrosis gene mutation (delta F508). It was present in 135 (82%) of the 164 cystic fibrosis genes analysed with 54 (66%) cases being homozygous and 27 (33%) heterozygous. Sixty nine per cent of infants were symptomatic at the time of diagnosis regardless of genotype. No association was found between the early clinical or biochemical features of the disease and homozygosity or heterozygosity for this mutation. Screening for cystic fibrosis using the blood immunoreactive trypsin assay alone remains an effective method of identifying infants with the disease soon after birth, thereby allowing early therapeutic intervention. Genetic counselling and prenatal diagnosis have contributed to a reduction in the number of children born with cystic fibrosis, but may not entirely explain the decreasing incidence of the disease.     

Effect of the neuropeptide tuftsin and its derivatives on metabolism in various structures of the brain

A study was made of the effect of the neuropeptide tuftsin and its derivatives on some indicators of the metabolism in limbic structures and cortex of the brain in 200 rats. It was shown that tuftsin and its derivatives raise the content of nicotinamide coenzymes at the expense of the oxidized forms of NAD, activate cytochrome-c-oxidase and dehydrogenases largely in the limbic structures. Thus the peptides under study were found to increase the intensity of cell respiration and to enhance intracellular redox processes, i. e. to largely activate the vital activity of the cells of the brain emotiogenous structures.     

The lateralising significance of hypergraphia in temporal lobe epilepsy

Six patients with hypergraphia and epilepsy are presented and their clinical features compared with other patients reported in the literature. It is suggested that hypergraphia occurs more frequently in patients with right-sided non-dominant temporal lobe lesions, in contrast for example to the schizophreniform presentation of left-sided lesions. Other features of psychopathology possibly associated with non-dominant lesions, including elation, hypereligiosity and déjà vu experiences, are also discussed.     

Pacemaker Implantation in a toddler: A case report

An 18-month-old child who had recurrent Stokes-Adams episodes due to congenital complete heart block underwent permanent programmable myocardial pacemaker implantation. To the best of our knowledge this is the youngest patient reported to have received a pacemaker in this country.     

Zur indikationsstellung der operativen behandlung der unterschenkelfraktur

Vergleichende Nachuntersuchungen von insgesamt 324 in den Jahren 1980 bis 1985 in einem Peripheriekrankenhaus operativ versorgten Unterschenkelbrüchen brachten insgesamt gute Ergebnisse. Neben einer Pseiidarthrosenrate von 0% sind die ermittelten niedrigen Zahlen für Infektion, Refraktur, verzögerte Heilung und Thrombose erwähnenswert und mit anderen Literatlirangaben vergleichbar. Verantwortlich für unsere relativ guten Ergebnisse sind einerseits die Struktur des Krankenguts, welches vorwiegend aus sportlich aktiven, jungen Patienten bestand. Andererseits war es schon aus organisatorischen und auch ökonomischen Gründen notwendig, auf einfache, rasch durchzuführende und zuverlässige Methoden zurückzugreifen, um den oft hohen Anfall an Verletzungen am späten Nachmittag nach Schließen der Skilifte zu bewältigen. Schließlich muß auch die Tatsache bedacht werden, daß die Versorgung der Patienten in vorwiegend einer Hand lag. welche mit den genannten Methoden ein großes Maß an Erfahrung sammeln konnte.