Short- and long-term prognostic importance of complete bundle-branch block complicating acute myocardial infarction

Among 1013 consecutive patients with acute myocardial infarction (AMI), 104 (10%) developed complete bundle-branch block (BBB). The clinical characteristics and the short- and long-term prognosis were similar in the 53 patients with right and the 51 patients with left BBB. Compared to the 909 patients without this conduction disturbance, these 104 patients were older (64 +/- 9 vs. 58 +/- 10 years, p less than 0.001), more frequently women (26 vs. 17%, p less than 0.05), had a larger infarct (peak CK 1672 +/- 1124 vs. 1356 +/- 1089 IU/l, p less than 0.001), more frequently anterior (60 vs. 37%, p less than 0.001). They had a higher incidence of Killip class greater than 1 (63 vs. 38%, p less than 0.001), pericarditis (40 vs. 23%, p less than 0.001), atrial fibrillation or flutter (22 vs. 12%, p less than 0.01), ventricular fibrillation (15 vs. 9%, p less than 0.05), and atrioventricular block (23 vs. 11%, p less than 0.001). Both hospital mortality (32 vs 10%, p less than 0.001) and 3-year posthospital mortality (37 vs. 18%, p less than 0.001) were much higher among patients with complete BBB. Transient BBB had the same deleterious prognosis as BBB persistent at discharge (mortality 33 vs. 39%, NS). The prognostic importance of BBB was more prominent during the first 6 months after infarction (mortality between 6 and 36 months: 18% with BBB vs. 11% without BBB, NS).     

Pearson syndrome and the role of deletion dimers and duplications in the mtDNA

Pearson syndrome is an often fatal multisystem disease associated with mitochondrial DNA rearrangements. Here we report a patient with a novel mtDNA deletion of 3.4 kb ranging from nucleotides 6097 to 9541 in combination with deletion dimers. The mutation percentage in different tissues (blood, muscle and liver) varied between 64% and 95%. After a remission period of about a year, the patient suddenly died at the age of 3 years owing to a severe lactic acidosis. A second patient with a previously reported deletion of 8 kb and a milder phenotype was found to have mitochondrial duplications and died at the age of 10 years. From these data and data from previous reports, we hypothesize that duplications might be beneficial in the clinical course of the disease and in life expectancy.     

Two simple and inexpensive methods for preparing DNA suitable for digital PCR from a small number of cells in 96‐well plates

BackgroundAlthough DNA of high quality can be easily prepared from cultured cells with commercially available kits, many studies involve a large number of samples which increases the cost drastically. We optimized two simple and inexpensive methods for preparing DNA suitable for digital PCR from a small number of cells directly from wells of 96‐well plates.MethodsCells (number: 10³‐10⁴) were lysed with a Direct PCR^® lysis buffer or a 10% Chelex100® solution. The lysates were further purified and concentrated by means of DNA precipitation with a blue‐colored glycogen as a carrier. PCR and digital PCR were used to evaluate the efficiency of the two methods.ResultsFor 1000 cells from one primary culture and two tumor cell lines, DNA was reproducible and obtained with recovery rate (obtained/expected amount of DNA) in the range of 50%‐90% as measured by the fluorometer dyes instrument Qubit. Using 8 out of a total of 10 µL DNA solution for 1000 cells, both conventional PCR and digital PCR were successful. For digital PCR, more than 1600 positive droplets were obtained for DNA from 1000 cells using the Direct PCR^® method, corresponding to a yield efficiency of approximately 80%. Further reducing the number of cells down to 100 would be possible with 160 positive droplets expected. Both reagents are inexpensive (0.08€/sample).ConclusionsTwo methods are efficient, especially the Direct PCR^® reagent‐based method provides a simple and inexpensive method for preparing DNA suitable for digital PCR from small number of cells.     

Life Change Events,Ballistocardiography and Coronary Death

Abstract

Thirty-six men and women who experienced a documented myocardial infarction, half of whom ultimately died from their disease and half of whom survived over a six-year period, provided longitudinal recent life changes and ballistocardiographic data. The 18 patients who died from their coronary disease indicated a significant buildup in life changes which peaked approximately one year prior to death; their serial ballistocardiograms indicated a significant buildup in average force of contraction which was seen to peak approximately six months prior to death. The 18 post-infarction patients who survived the six-year follow-up showed neither a buildup in life change nor a buildup in the ballistocardiographic index of cardiac contraction force. These findings of a life change peak preceding ballistocardiographic evidence of an “overworked” heart are discussed in terms of their possible medical and psychophysiological significances.     

Cerebellar developmental deficits underlie neurodegenerative disorder spinocerebellar ataxia type 23

Spinocerebellar ataxia type 23 (SCA23) is a late‐onset neurodegenerative disorder characterized by slowly progressive gait and limb ataxia, for which there is no therapy available. It is caused by pathogenic variants in PDYN, which encodes prodynorphin (PDYN). PDYN is processed into the opioid peptides α‐neoendorphin and dynorphins (Dyn) A and B; inhibitory neurotransmitters that function in pain signaling, stress‐induced responses and addiction. Variants causing SCA23 mostly affect Dyn A, leading to loss of secondary structure and increased peptide stability. PDYN ^R212W mice express human PDYN containing the SCA23 variant p.R212W. These mice show progressive motor deficits from 3 months of age, climbing fiber (CF) deficits from 3 months of age, and Purkinje cell (PC) loss from 12 months of age. A mouse model for SCA1 showed similar CF deficits, and a recent study found additional developmental abnormalities, namely increased GABAergic interneuron connectivity and non‐cell autonomous disruption of PC function. As SCA23 mice show a similar pathology to SCA1 mice in adulthood, we hypothesized that SCA23 may also follow SCA1 pathology during development. Examining PDYN ^R212W cerebella during development, we uncovered developmental deficits from 2 weeks of age, namely a reduced number of GABAergic synapses on PC soma, possibly leading to the observed delay in early phase CF elimination between 2 and 3 weeks of age. Furthermore, CFs did not reach terminal height, leaving proximal PC dendrites open to be occupied by parallel fibers (PFs). The observed increase in vGlut1 protein—a marker for PF‐PC synapses—indicates that PFs indeed take over CF territory and have increased connectivity with PCs. Additionally, we detected altered expression of several critical Ca²⁺ channel subunits, potentially contributing to altered Ca²⁺ transients in PDYN ^R212W cerebella. These findings indicate that developmental abnormalities contribute to the SCA23 pathology and uncover a developmental role for PDYN in the cerebellum.     

Effect of BH4 on blood phenylalanine and tyrosine variations in patients with phenylketonuria

BackgroundIn patients with phenylketonuria, stability of blood phenylalanine and tyrosine concentrations might influence brain chemistry and therefore patient outcome. This study prospectively investigated the effects of tetrahydrobiopterin (BH4), as a chaperone of phenylalanine hydroxylase on diurnal and day-to-day variations of blood phenylalanine and tyrosine concentrations.MethodsBlood phenylalanine and tyrosine were measured in dried blood spots (DBS) four times daily for 2 days (fasting, before lunch, before dinner, evening) and once daily (fasting) for 6 days in a randomized cross-over design with a period with BH4 and a period without BH4. The sequence was randomized. Eleven proven BH4 responsive PKU patients participated, 5 of them used protein substitutes during BH4 treatment. Natural protein intake and protein substitute dosing was adjusted during the period without BH4 in order to keep DBS phenylalanine levels within target range. Patients filled out a 3-day food diary during both study periods. Variations of DBS phenylalanine and Tyr were expressed in standard deviations (SD) and coefficient of variation (CV).ResultsBH4 treatment did not significantly influence day-to-day phenylalanine and tyrosine variations nor diurnal phenylalanine variations, but decreased diurnal tyrosine variations (median SD 17.6 μmol/l, median CV 21.3%, p = 0.01) compared to diet only (median SD 34.2 μmol/l, median CV 43.2%). Consequently, during BH4 treatment diurnal phenylalanine/tyrosine ratio variation was smaller, while fasting tyrosine levels tended to be higher.ConclusionBH4 did not impact phenylalanine variation but decreased diurnal tyrosine and phenylalanine/tyrosine ratio variations, possibly explained by less use of protein substitute and increased tyrosine synthesis.     

Analysis of outcome for elderly patients after microvascular flap surgery: a monocentric retrospective cohort study

Objectives

Increasingly, aging societies pose a challenge, particularly in the most developed countries. This trend leads to an increasing group of old and very old patients presenting unique requirements and challenges. One of these challenges consists in reassessment and adaption of established treatment strategies for the elderly patients. There is an ongoing discussion taking place among cranio-maxillo-facial surgeons about the appropriate extent of reconstructive flap surgery for old patients.

Materials and methods

This monocentric retrospective cohort study investigated 281 reconstructions with microvascular flaps by comparing the risk for a negative outcome, which was defined as revision, flap loss, and patient death, between three subgroups of elderly patients and younger patients. The three subgroups of elderly patients were defined as—1: young old (65–74 years), 2: old (75–84 years), and 3: oldest old (≥ 85 years). The group of the younger patients was defined by age between 50 and 64 years. Data were obtained within a defined period of 42 months.

Results

Significant correlations with a negative outcome were found for the variables stay on IMC/ICU, multiple flaps, and radiotherapy prior surgery. Our data showed no significant correlation between age and a higher risk for a negative outcome.

Conclusion

Defect reconstruction with microvascular flaps in old patients is not related with a higher risk for a negative outcome.

Clinical relevance

Independently of age, treatment with microvascular flaps is an option for all operable patients, with an indication for oncologic surgery. For optimal therapy planning, individual patient resources and preferences should be considered instead of chronologic age.