Exercise is Associated With Impaired Left Ventricular Systolic Function in Patients With Lamin A/C Genotype.

Background Lamin A/C cardiomyopathy is a malignant and highly penetrant inheritable cardiomyopathy. Competitive sports have been associated with adverse events in these patients, but data on recreational exercise are lacking. We aimed to explore associations between exercise exposure and disease severity in patients with lamin A/C genotype. Methods and Results Lamin A/C genotype positive patients answered a questionnaire on exercise habits from age 7 years until genetic diagnosis. We recorded exercise hours >3 metabolic equivalents and calculated cumulative lifetime exercise. Patients were grouped in active or sedate based on lifetime exercise hours above or below median. We performed echocardiography, 12-lead ECG, Holter monitoring, and biomarkers including NT-proBNP (N-terminal pro-B-type natriuretic peptide). We defined left ventricular ejection fraction <45% as a clinically significant impairment of left ventricular function. We included 69 patients (age 42±14 years, 41% probands, 46% women) with median lifetime exercise 4160 (interquartile range 1041-6924) hours. Active patients were more frequently probands (53% versus 29%, P=0.04), had lower left ventricular ejection fraction (43±13% versus 51±11%, P=0.006), and higher NT-proBNP (78 [interquartile range 32-219] pmol/L versus 30 [interquartile range 13-64] pmol/L, P=0.03) compared with sedate, while age did not differ (45±13 years versus 40±16 years, P=0.16). The decrease in left ventricular ejection fraction per tertile increment in lifetime exercise was 4% (95% CI -7% to -0.4%, P=0.03), adjusted for age and sex and accounting for dependence within families. Left ventricular ejection fraction <45% was observed at a younger age in active patients (log rank P=0.007). Conclusions Active lamin A/C patients had worse systolic function compared with sedate which occurred at younger age. Our findings may improve exercise recommendations in patients with lamin A/C.

[An apothecary apprentice crosses his tracks--about Ibsen's prescriptions]. / En apotekerlaerling krysser sitt spor--om Ibsens medisinbestillinger.

As a youngster, Henrik Ibsen (1828-1906) worked as an apothecary apprentice for six years at the apothecary in Grimstad. Here, he learnt apothecary Latin, which he later on used in his literary works. Also in his own life, he used this knowledge during his last years of life when he prescribed drugs for himself. Ibsen's last six years were characterized by disease. The National Library in Oslo has three prescriptions in which the poet prescribes two different kinds of drugs, even though they should have been prescribed by a medical doctor. One of the drugs was iodide of sodium, a well-known drug for arteriosclerosis at that time. The other drug was a laxative called Brandt's Schweizer pills. Iodide of sodium was a relatively new drug introduced to the market at the end of the 19th century. Even though there was uncertainty about the effect and mode of action, it had become an established part of medical practice. That was not the case for Brandt's Schweizer pills. They were produced by the German apothecary Richard Brandt (1828-1903) in 1877. Medical doctors warned against using them. It was a so-called arcanum, i.e. the producer kept the content secret. The use of such drugs came out of control in the 1890ies and was a serious community problem.

[Reduced mortality after acute myocardial infarction]. / Reduksjon i dødelighet etter akutt hjerteinfarkt.

BACKGROUND: The mortality of cardiovascular disease has decreased substantially in later years though it is uncertain whether this decrease is due to a better profile of risk factors in the population or to improvements in medical treatment. MATERIAL AND METHODS: In 1982 to 1984 and 1997 to 1999 all patients admitted to Hedmark Central Hospital in Norway, with acute myocardial infarction were registered and followed for reinfarction and survival over up to three years. A total of 1,236 patients were included in the study, 641 in the first time period and 595 in the second. RESULTS: A significant decrease in case fatality was observed in the second population. The seven days fatality rate decreased from 17.9% to 11.4%, and the one month fatality rate from 22.9% to 16.1%. The median number of days in hospital decreased from ten to six. A Kaplan-Meier estimate for survival in the total follow-up period showed a 43% higher relative death risk in the 1982-1984 cohort compared to the 1997-1999 cohort. A Cox regression revealed that this difference could not be explained by demographic differences between the populations. INTERPRETATION: By evaluating variables registered during the course of infarction in the multivariate Cox model, it is concluded that improved survival in the recent cohort is related to modern treatment of acute myocardial infarction.

Aspirin non-responsiveness as measured by PFA-100 in patients with coronary artery disease.

INTRODUCTION: The purpose of the present study was to study the concept of aspirin resistance or non-responsiveness by investigating the response to long-term aspirin therapy in patients with a former acute myocardial infarction (AMI). MATERIALS AND METHODS: Patients with an AMI (n=202) randomly assigned to aspirin 160 mg/day (n=71), aspirin 75 mg/day and warfarin (INR 2.0-2.5) (n=58) or warfarin (INR 2.8-4.2) (n=73) were evaluated by the PFA-100(R), biochemical variables and clinical events after a mean treatment period of 4 years. RESULTS: The limit for being an aspirin non-responder was defined as the 95th percentile value in the warfarin alone group (196 s) with the epinephrine cartridge. In patients on aspirin alone 25/71 (35%) were non-responders and on the combination 23/58 (40%). With the adenosine diphosphate (ADP) cartridge only minor differences were found. The levels of thromboxane B(2) in both aspirin groups, in responders as well as in non-responders, were extremely low compared to the warfarin alone group. Evaluating both aspirin groups together (n=129), the levels of soluble P-selectin were significantly higher in non-responders as compared to responders (p=0.012). During the observation period of 4 years with limited number of events, there was a tendency for higher event rates in non-responders as compared to responders (36% vs. 24%, p=0.28). CONCLUSIONS: In our evaluation of the PFA-100(R) a considerable number of post-AMI patients seemed to be non-responders to long-term aspirin therapy in doses of 75 and 160 mg/day. Circulating levels of P-selectin were higher in the non-responders. A tendency to higher incidence of clinical events among non-responders was observed.

Phylogeny and functional expression of ribulose 1,5-bisphosphate carboxylase/oxygenase from the autotrophic ammonia-oxidizing bacterium Nitrosospira sp. isolate 40KI.

The autotrophic ammonia-oxidizing bacteria (AOB), which play an important role in the global nitrogen cycle, assimilate CO(2) by using ribulose 1,5-bisphosphate carboxylase/oxygenase (RubisCO). Here we describe the first detailed study of RubisCO (cbb) genes and proteins from the AOB. The cbbLS genes from Nitrosospira sp. isolate 40KI were cloned and sequenced. Partial sequences of the RubisCO large subunit (CbbL) from 13 other AOB belonging to the beta and gamma subgroups of the class Proteobacteria are also presented. All except one of the beta-subgroup AOB possessed a red-like type I RubisCO with high sequence similarity to the Ralstonia eutropha enzyme. All of these new red-like RubisCOs had a unique six-amino-acid insert in CbbL. Two of the AOB, Nitrosococcus halophilus Nc4 and Nitrosomonas europaea Nm50, had a green-like RubisCO. With one exception, the phylogeny of the AOB CbbL was very similar to that of the 16S rRNA gene. The presence of a green-like RubisCO in N. europaea was surprising, as all of the other beta-subgroup AOB had red-like RubisCOs. The green-like enzyme of N. europaea Nm50 was probably acquired by horizontal gene transfer. Functional expression of Nitrosospira sp. isolate 40KI RubisCO in the chemoautotrophic host R. eutropha was demonstrated. Use of an expression vector harboring the R. eutropha cbb control region allowed regulated expression of Nitrosospira sp. isolate 40KI RubisCO in an R. eutropha cbb deletion strain. The Nitrosospira RubisCO supported autotrophic growth of R. eutropha with a doubling time of 4.6 h. This expression system may allow further functional analysis of AOB cbb genes.