Future Directions to Establish Lipoprotein(a) as a Treatment for Atherosclerotic Cardiovascular Disease

In both epidemiologic and genetic studies, increased levels of Lp(a) have been associated with increased risk for cardiovascular diseases as well as aortic stenosis. However, until recently, it has been difficult to lower levels of Lp(a). Diet and lifestyle have little effect on plasma levels of Lp(a) which are mainly genetically determined. Emerging therapeutic agents which have recently become available, or which are undergoing clinical trials, can significantly lower Lp(a) levels. Studies with these agents will hopefully be able to provide more direct information whether reductions in Lp(a) will reduce CVD events independently of reduction in LDL-cholesterol levels.     

Detection and quantification of circulating immature platelets: agreement between flow cytometric and automated detection

Immature platelets—also termed reticulated platelets (RP)—are platelets newly released into the circulation, and have been associated with a variety of pathological thrombotic events. They can be assessed by flow cytometry after staining with thiazole orange (TO) or by using a module added to a fully automated analyzer that is currently in wide clinical use and expressed as a fraction of the total platelet count (IPF). We sought to assess the correlation and agreement between these two methods. IPF was measured using Sysmex XE 2100—and at the same time point- we used TO staining and flow cytometry to measure RP levels. Two different gates were used for the flow cytometry method, 1 and 0.5 %. Measurements from the automated analyzer were then compared separately to measurements performed using each gate. Agreement between methods was assessed using Bland–Altman method. Pearson’s correlation coefficient was also calculated. 129 subjects were enrolled and stratified into 5 groups: (1) Healthy subjects, (2) End stage renal disease, (3) Chronic stable coronary artery disease, (4) Post Coronary artery bypass surgery, (5) Peripheral thrombocytopenia. Median IPF levels were increased for patients in groups 2, 3, 4 and 5 (4.0, 4.7, 4.3, and 8.3 % respectively) compared to healthy subjects (2.5 %) p = 0.0001. Although the observed correlation between the two methods tended to be good in patients with high IPF values (i.e., group 5), the overall observed correlation was poor (Pearson’s correlation coefficient r = 0.27). Furthermore, there was poor agreement between the two methods in all groups. Despite the good correlation that was observed between the two methods at higher IPF values, the lack of agreement was significant.     

Sir James Mackenzie: from auricular paralysis and nodal rhythm to auricular fibrillation

The aim of this paper is to underline the role of Sir James Mackenzie in stating that atrial fibrillation is a distinct and clinically important arrhythmia and that it is a common condition in patients with cardiac disease. Around 1900, a few clinical researchers were dealing with cardiac arrhythmias with the use of arterial and venous pulse tracings. Sir James Mackenzie, who has been one of the fathers of modern cardiology, introduced registration of the venous pulse at the bedside using the clinical polygraph he had invented. He applied the results of his experimental and clinical discoveries to the explanation of many kinds of arrhythmias before ECG introduction. In our paper, we have especially considered the three steps of his approach to atrial fibrillation, the first two developed in the pre-ECG era. The invention of an instrument of precision, the electrocardiograph, revolutionized the diagnosis of heart disease and catalyzed the formation of cardiology as a specialty.     

Circadian melatonin profiles during single 24-h shifts in anesthetists

Purpose  

It has been shown that shift work constitutes a great health hazard, particularly when chronodisruption is involved. Anesthetists are used to working for a certain number of 24-h shifts every month. The work-related lack of sleep in combination with light exposure is suspected to alter melatonin courses. The main aim of the present study was to analyze circadian melatonin profiles before, during, and after a 24-h shift in anesthetists and medical students (controls). Furthermore, we evaluated possible differences in melatonin profiles between the groups. Interactions between specific parameters were calculated.     

Improving Genetic Testing for Gitelman’s Syndrome

Gitelman’s syndrome (GS) is a rare, autosomal recessive, salt-losing tubulopathy caused by mutations in the SLC12A3 gene, which encodes the thiazide-sensitive NaCl cotransporter (NCC). Because 18 to 40% of suspected GS patients carry only one SLC12A3 mutant allele, large genomic rearrangements may account for unidentified mutations. Here, we directly sequenced genomic DNA from a large cohort of 448 unrelated patients suspected of having GS. We found 172 distinct mutations, of which 100 were unreported previously. In 315 patients (70%), we identified two mutations; in 81 patients (18%), we identified one; and in 52 patients (12%), we did not detect a mutation. In 88 patients, we performed a search for large rearrangements by multiplex ligation-dependent probe amplification (MLPA) and found nine deletions and two duplications in 24 of the 51 heterozygous patients. A second technique confirmed each rearrangement. Based on the breakpoints of seven deletions, nonallelic homologous recombination by Alu sequences and nonhomologous end-joining probably favor these intragenic deletions. In summary, missense mutations account for approximately 59% of the mutations in Gitelman’s syndrome, and there is a predisposition to large rearrangements (6% of our cases) caused by the presence of repeated sequences within the SLC12A3 gene.     

Age-related oxidative decline of mitochondrial functions in rat brain is prevented by long term oral antioxidant supplementation

A combination of antioxidants (N-acetyl cysteine, α-lipoic acid, and α-tocopherol) was selected for long term oral supplementation study in rats for protective effects on age-related mitochondrial alterations in the brain. Four groups of rats were chosen: young control (6–7 months); aged rats (22–24 months); aged rats (22–24 months) on daily antioxidant supplementation from 18 month onwards and young rats (6–7 months) on daily antioxidant supplementation from 2 month onwards. The brain mitochondrial functional parameters, status of antioxidant enzymes and accumulation of oxidative damage markers were measured in the four groups of rats. A significant decrease in complex IV activity and a loss of transmembrane potential and phosphorylation capacity along with an increased accumulation of oxidative damage markers and compromised antioxidant enzyme status were noticed in aged rat brain mitochondria as compared to that in young controls, but in aged rats supplemented with oral antioxidants the mitochondrial alterations were largely prevented. Antioxidant supplementation in young rats had no effect on mitochondrial parameters investigated in this study. The results have implications in biochemical and functional deficits of brain during aging as well as in neurodegenerative disorders.     

Corticosteroids Modulate Angiogenic Soluble Factors in Ulcerative Colitis Patients

Aims  

The aim of this study was to compare angiogenic factors in serum levels of active ulcerative colitis (UC) patients and in healthy controls, and to analyze these angiogenic levels depending on the achievement of remission after oral corticosteroid treatment throughout treatment, and according to the Truelove–Witts activity index.     

Management of rupture of choledochal cyst

One of the rare complications of choledochal cysts is rupture. In majority of the cases, the cause of rupture is unknown. Reconstructive surgery is the treatment of choice. We describe three patients with choledochal cyst rupture, who were admitted with acute abdomen. Diagnosis of biliary ascites with peritonitis was made in all the three patients. At surgery, two patients underwent T-tube placement, and definitive repair was done electively. One patient underwent definitive repair of ruptured choledochal cyst, but died due to septicemia. External bile drainage would be safer in emergency condition.     

Efficacy of rapid maxillary expansion in children with obstructive sleep apnea syndrome: 36 months of follow-up

Purpose  

In view of the positive outcome of orthodontic treatment using rapid maxillary expansion (RME) on sleep-disordered breathing, we generated data on RME in children with obstructive sleep apnea (OSA) by evaluating objective and subjective data over a 36-month follow-up period, to determine whether RME is effective in the long-term treatment of OSA. We selected all patients with dental malocclusions and OSA syndrome (OSAS) confirmed by polysomnography.