Lipoprotein(a): a genetically determined lipoprotein containing a glycoprotein of the plasminogen family

Lp(a) represents a genetically transmitted class of plasma LDL having apo B-100 linked by a disulfide bridge to a glycoprotein, apo(a). Lp(a) is heterogeneous in size and density. Apo(a) is also heterogeneous in size (molecular weight between approximately 300,000 and 700,000) due probably to the polymorphism of both polypeptide and carbohydrate chains. Recent studies have shown that apo(a) has a striking amino acid sequence homology with plasminogen, a serine protease zymogen that following activation to plasmin enters the fibrinolytic system. Apo(a) is severalfold larger than plasminogen (molecular weight approximately 90,000) and also differs from it because it fails to be activated to plasmin. This is due to the fact that arginine is replaced by serine at the site of cleavage by streptokinase, urokinase, or tissue plasminogen activator. A single gene locus appears to control the Lp(a) polymorphism as well as the concentration of the Lp(a) phenotypes in the plasma. Patients with high plasma levels of Lp(a) have been shown to have an increased incidence of cardiovascular disease but a causal relationship has not been firmly established. The information that is being rapidly acquired on the structure of Lp(a) should facilitate the understanding of the molecular basis of the polymorphism of this genetic variant and of the role that the various Lp(a) phenotypes play in atherosclerosis and thrombosis. The potential physiologic role of Lp(a) remains open to inquiry.     

脂蛋白（a）和载脂蛋白（a）多态性与女性冠心病的相关性研究

冠心病（ＣＨＤ）在病因、发病年龄等诸多方面存在性别差异。载脂蛋白（ａ）［ａｐｏ（ａ）］多态性与脂蛋白（ａ）［Ｌｐ（ａ）］血浆水平对女性ＣＨＤ影响的资料甚少。我们通过检测３５例女性ＣＨＤ患者和４５例女性正常对照者的ａｐｏ（ａ）多态表型及Ｌｐ（ａ）水平，并与相应的男性组对比分析，发现含有等位基因Ｓ１、Ｓ２、Ｂ的ａｐｏ（ａ）低分子量表型的ＣＨＤ患者，女性占３７．１４％，显著高于对照组，而男性仅占２５．７１％，与对照组比较差异无显著性。在女性中低分子量表型发生ＣＨＤ危险度为对照组的４．７倍，在男性中仅为１．４倍。提示：低分子量表型对女性ＣＨＤ的影响大于男性。Ｌｐ（ａ）水平在两性ＣＨＤ组均明显高于对照组，而两性之间则差异无显著性。     

Utility of a repeated EUS at a tertiary-referral center

BACKGROUND: The utility of a repeated EUS by experts is not known. OBJECTIVE: To define the utility of a repeated EUS for the same indication. DESIGN: A retrospective case series. SETTING: Tertiary-referral hospital in Indianapolis, Indiana. PATIENTS: Consecutive subjects, with and without cancer, who, between January 2000 and September 2006, underwent an initial EUS elsewhere within 6 and 12 weeks of a repeated EUS at our hospital. INTERVENTIONS: A repeated EUS. MAIN OUTCOME MEASUREMENTS: Clinical impact of a repeated EUS. RESULTS: Of 8936 EUS examinations, 73 repeated procedures (0.8%) were identified, and 24 were excluded. The 49 initial EUS procedures (26 men, median age 59 years) were done in Indiana (n = 44) or another state (n = 5) by one of 15 physicians in private practice (n = 48) or at a teaching hospital (n = 1). An EUS-guided FNA (EUS-FNA) was performed during an initial EUS in 21 patients (no biopsy diagnostic for cancer) and was not attempted in 14 patients. The principle indication for a repeated EUS (n = 35) was for an EUS-FNA after the initial tissue sampling was benign, nondiagnostic, or not done. A second EUS had no clinical impact in 18 patients (37%). In the remaining 31 patients (63%), a repeated EUS provided a new or changed clinical diagnosis (n = 12), the initial diagnosis of primary pancreatic cancer (n = 5) or GI stromal tumor (GIST) (n = 1) after a previous nondiagnostic biopsy; or the initial diagnosis of primary (n = 4) or metastatic (n = 2) pancreatic cancer, metastatic esophageal cancer (n = 1), hilar cholangiocarcinoma (n = 1), GIST (n = 1), or pancreatic neuroendocrine tumor (n = 1), or an initial aspiration of a pancreatic cyst (n = 3) after a previous EUS-FNA was not able to be performed. LIMITATIONS: A retrospective design; a small number of nonpancreatic indications. CONCLUSIONS: In this study, a repeated EUS at a tertiary-referral center had a clinical impact in 63% of patients when performed by experts for a similar clinical indication.     

Mortality after a cholecystectomy: a population-based study

Background

The trade-off between the benefits of surgery for gallstone disease for a large population and the risk of lethal outcome in a small minority requires knowledge of the overall mortality.

Methods

Between 2007 and 2010, 47 912 cholecystectomies for gallstone disease were registered in the Swedish Register for Cholecystectomy and endoscopic retrograde cholangiopancreatography (ERCP) (GallRiks). By linkage to the Swedish Death Register, the 30-day mortality after surgery was determined. The age- and sex-standardized mortality ratio (SMR) was estimated by dividing the observed mortality with the expected mortality rate in the Swedish general population 2007. The Charlson Comorbidity Index (CCI) was estimated by International Classification of Diseases (ICD) codes retrieved from the National Patient Register.

Results

Within 30 days after surgery, 72 (0.15%) patients died. The 30-day mortality was close [SMR = 2.58; 95% confidence interval (CI): 2.02–3.25] to that of the Swedish general population. In multivariable logistic regression analysis, predictors of 30-day mortality were age >70 years [odds ratio (OR) 7.04, CI: 2.23–22.26], CCI > 2 (OR 1.93, CI: 1.06–3.51), American Society of Anesthesiologists (ASA) > 2 (OR 13.28, CI: 4.64–38.02), acute surgery (OR 10.05, CI:2.41–41.95), open surgical approach (OR 2.20, CI: 1.55–4.69) and peri-operative complications (OR 3.27, CI: 1.74–6.15).

Discussion

Mortality after cholecystectomy is low. Co-morbidity and peri-operative complications may, however, increase mortality substantially. The increased mortality risk associated with open cholecystectomy could be explained by confounding factors influencing the decision to perform open surgery.     

Report of a case of a giant phytobezoar in a patient with a duodenal bulb ulcer.

A case of a large phytobezoar (750 g weight and with the length of 29 cm) due to Khormalou (Persimmon) is being reported in a young patient with chief complaint of abdominal pains and concomitant duodenal ulcer. Review of the literature in this subject shows that bezoars of this size and weight are relatively rare in healthy individuals.     

Calculating the risk of a pancreatic fistula after a pancreaticoduodenectomy: a systematic review

BackgroundA post‐operative pancreatic fistula (POPF) is a major cause of morbidity and mortality after a pancreaticoduodenectomy (PD). This systematic review aimed to identify all scoring systems to predict POPF after a PD, consider their clinical applicability and assess the study quality.MethodAn electronic search was performed of Medline (1946–2014) and EMBASE (1996–2014) databases. Results were screened according to Preferred Reporting Items for Systematic Reviews and Meta‐Analyses (PRISMA) guidelines, and quality assessed according to the QUIPS (quality in prognostic studies) tool.ResultsSix eligible scoring systems were identified. Five studies used the International Study Group on Pancreatic Fistula (ISGPF) definition. The proposed scores feature between two and five variables and of the 16 total variables, the majority (12) featured in only one score. Three scores could be fully completed pre‐operatively whereas 1 score included intra‐operative and two studies post‐operative variables. Four scores were internally validated and of these, two scores have been subject to subsequent multicentre review. The median QUIPS score was 38 out of 50 (range 16–50).ConclusionThese scores show potential in calculating the individualized patient risk of POPF. There is, however, much variation in current scoring systems and further validation in large multicentre cohorts is now needed.     

Passive entry of a DNA molecule into a small pore

I consider a vesicle with an open pore of small radius rp, exposed to a DNA solution. The crucial moment is the entry, when a chain end faces the pore and enters it. I discuss qualitatively the following three characteristic times: (i) the duration of the entry of one chain end (defining the minimum lifetime of the pore) taue approximately 10(-4) sec, (ii) the transfection time taut (the time required to be sure that one chain has gone in) taut approximately hours, and (iii) the sliding time tauS (the time between entry of one end and entry of the other end) approximately 1 sec. A fortunate feature is that sliding may proceed even if the pore tends to close itself after entry.     

Lipoprotein(a) as a cardiovascular risk factor

Lipoprotein(a) [Lp(a)] is a class of lipoprotein particles having the lipid composition of plasma low-density lipoprotein (LDL), but with a distinct protein moiety comprised of two proteins linked together by a disulfide bridge. The two proteins are apoB100, the protein moiety of LDL, and apo(a), a heavily glycosylated protein that is specific for Lp(a). Apo(a) has a strong structural similarity to plasminogen and has a wide-size polymorphism that has a genetic origin and is partially responsible for the size and density heterogeneity of Lp(a). High plasma levels of Lp(a) are associated with an increased risk for cardiovascular disease that is related to the atherogenic and thrombogenic potentials of this lipoprotein enhanced by the presence of other risk factors, among which are high plasma levels of LDL or low levels of high-density lipoprotein. The factors determining the plasma levels of Lp(a) have not been clearly identified except for an association with different alleles of the apo(a) gene, which is located in the long arm of chromosome 6. Currently there are no generally accepted ways to normalize the plasma levels of Lp(a) by either dietary and/or pharmacologic means. Until further progress in this area is made, patients with high plasma levels of Lp(a) should be advised to correct modifiable risk factors in order to decrease the cardiovascular pathogenicity of this lipoprotein class.     

Living donor liver transplantation in a recipient with anti-Fy(a) and Jk(a) antibodies

We report a case of a living donor liver transplantation using right lobe graft to a recipient having anti-Fy(a) and Jk(a) antibodies. The red blood cell (RBC) antigens of the donor were Fy (a+) and Jk (a-). We attempted to eliminate donor RBCs remaining in the graft by perfusing histidine-tryptophan-ketoglutarate. Further, Fy (a-)/Jk (a-) RBC concentrates were transfused during the operation. However, the anti-Fy(a) titer increased approximately 8-fold on the seventh postoperative day. On the same day, serum levels of transaminase and total bilirubin increased presumably due to acute cellular rejection. Steroid administration immediately reduced levels of transaminase, total bilirubin and anti-Fy(a) titer. The increase of anti-Fy(a) titer may be due to a secondary immune response to the donor's Fy(a) antigen on RBCs remaining in the graft.     

Hyperlipoproteinaemia(a) is a common cause of autosomal dominant hypercholesterolaemia

Summary Autosomal dominant hypercholesterolaemias (ADH) are a heterogeneous group of monogenic lipid disorders. The plasma level of lipoprotein(a) (Lp(a)) is a heritable trait associated with increased coronary heart disease (CHD) risk. Objective To evaluate the frequency of elevated Lp(a) as a cause of ADH and the characteristics of subjects with high Lp(a) (hyperLp(a)). Material and methods 200 healthy subjects and 933 unrelated Spanish subjects with a clinical diagnosis of ADH who were screened for low-density lipoprotein receptor (LDLR) and apolipoprotein B (APOB) gene mutations. Standard cardiovascular risk factors and blood lipid levels, including Lp(a), were evaluated. HyperLp(a) was defined as Lp(a) levels ≥95th centile of control values. Results Lp(a) was higher in 263 subjects without LDLR or APOB mutations (nonLDLR/nonAPOB group) than in 670 subjects with mutations (FH group): 40.0 mg/dl (interquartile range (IR) 15.0–89.0) versus 31.0 mg/dl (IR 11.0–73.7) respectively, p = 0.002. HyperLp(a) was present in 23% of ADH subjects (odds ratio (OR) 5.6 (95% CI, 2.9 to 10.7) versus controls) and 29% of nonLDLR/nonAPOB subjects (OR 7.7; 3.9 to 15.4). After adjusting for Lp(a), LDL cholesterol levels were <95th centile in 28 (10.6%) nonLDLR/nonAPOB subjects and in 9 (1.3%) FH subjects. Lp(a) levels were nonsignificantly higher in ADH subjects with early-onset CHD than in those without (43.5 mg/dl, (IR, 12.0–82.0) versus 31.7 mg/dl (11.8–76.5), respectively). Conclusions HyperLp(a) is responsible for ADH in approximately 6% of nonLDLR/nonAPOB subjects. HyperLp(a) would not appear to be a risk factor for early-onset CHD in ADH, independently of whether genetic defects have or have not been demonstrated. Electronic Supplementary Material The online version of this article (doi:) contains supplementary material, which is available to authorized users. Competing interests: None declared References to electronic databases: Familial hypercholesterolaemia: OMIM #143890. Familial defective apo B: OMIM #144010. PCSK9: OMIM *607786. Neural apoptosis-regulated convertase 1: OMIM *607786. Lipoprotein(a): OMIM +152200.     

Molecular dynamics of a grid-mounted molecular dipolar rotor in a rotating electric field

Classical molecular dynamics is applied to the rotation of a dipolar molecular rotor mounted on a square grid and driven by rotating electric field E(nu) at T approximately 150 K. The rotor is a complex of Re with two substituted o-phenanthrolines, one positively and one negatively charged, attached to an axial position of Rh(2)(4+) in a [2]staffanedicarboxylate grid through 2-(3-cyanobicyclo[1.1.1]pent-1-yl)malonic dialdehyde. Four regimes are characterized by a, the average lag per turn: (i) synchronous (a < 1/e) at E(nu) = /E(nu)/ > E(c)(nu) [E(c)(nu) is the critical field strength], (ii) asynchronous (1/e < a < 1) at E(c)(nu) > E(nu) > E(bo)(nu) > kT/mu;, [E(bo)(nu) is the break-off field strength], (iii) random driven (a approximately 1) at E(bo)(nu) > E(nu) > kT/mu, and (iv) random thermal (a approximately 1) at kT/mu > E(nu). A fifth regime, (v) strongly hindered, W > kT, E(mu), (W is the rotational barrier), has not been examined. We find E(bo)(nu)/kVcm(-1) approximately (kT/(mu))/kVcm(-1) + 0.13(nu/GHz)(1.9) and E(c)(nu)/kVcm(-1) approximately (2.3kT/(mu))/kVcm(-1) + 0.87(nu/GHz)(1.6). For nu > 40 GHz, the rotor behaves as a macroscopic body with a friction constant proportional to frequency, eta/eVps approximately 1.14 nu/THz, and for nu < 20 GHz, it exhibits a uniquely molecular behavior.     

Changing indications for a total pancreatectomy: perspectives over a quarter of a century

Introduction

The indications for a total pancreatectomy (TP), its peri-operative management, provision of pancreatic surgical services and medical treatment of the inherent exo- and endocrine deficient states have all changed considerably over recent decades. The effects of these upon the incidence, indications for and outcomes of TP are unclear. Patients undergoing TP at a single institution over a quarter of a century were reviewed to try to address these issues.

Methods

Data on patients who underwent elective (el-) and emergency TP (em-TP) between 1987 and 2013 were reviewed. Patient demographics, indications, intra-operative details, peri-operative management and long-term outcomes were analysed. Absolute numbers of TP were reported relative to partial pancreatectomy rates.

Results

In total, 136 patients underwent TP [98 (72.1%) el-TP; 38 (27.9%) em-TP]. There was a significant change in indication for el-TP with it increasingly performed for (an intraductal papillary mucinous neoplasm (IPMN) and renal cell metastases whereas there was a decrease in the number of el-TP performed for chronic pancreatitis (P = 0.025). The relative rates of el-TP, however, did not change significantly across the study period (P = 0.225). The median length of stay after el-TP decreased from 19 days pre-1997 to 12 days post-1997 (P = 0.009). The relative use of em-TP declined by 0.28 percentage points per year [P = 0.018; 95% confidence interval (CI): 0.04–0.41].

Conclusions

The indications for el-TP have changed; it is being performed more frequently although the proportion relative to other pancreatic resections has not changed. A decrease in the rate of em-TP is likely to reflect improved peri-operative management of a pancreatic fistula and its complications after a pancreaticoduodenectomy.     

Lipoprotein(a) is a potential coronary risk factor

Lipoprotein(a) (Lp(a)) is recognized as a new coronary risk factor, but few studies have quantitatively assessed the relationship of serum Lp(a) levels with other coronary risk factors in many patients undergoing coronary cineangiography. Seventeen coronary risk factors were quantified (i.e., age, gender, hypertension, impaired glucose tolerance, cerebrovascular accident, hyperuricemia, smoking, family history of ischemic heart disease (IHD), history of hyperlipidemia, Lp(a), total cholesterol, high density lipoprotein (HDL)-cholesterol, triglyceride, low density lipoprotein-cholesterol, apolipoproteins(apo)A-I,B, E) to determine their relationship with the numbers of involved coronary vessels using multiple regression test in 1,006 patients who underwent coronary cineangiogram (280 non-IHD patients: 144 men, 136 women; 726 IHD patients: 460 men, 266 women; age 16-84 years, mean 60.5+/-0.3). Multiple regression test indicated R = 0.506 and items that showed high beta weight and significant p level were age, Lp(a), impaired glucose tolerance, total cholesterol, cerebrovascular accidents, HDL-cholesterol, smoking, gender, family history of IHD, and apo-A-I (0.221, p<0.001; 0.174, p<0.001; 0.616, p<0.001; 0.138, p<0.001; 0.122, p<0.001; -0.12, p<0.001; 0.092, p<0.01; 0.091, p<0.01; 0.067, p<0.05; -0.065, p<0.05; respectively). It was concluded that Lp(a) is an independent, potential, and modifiable coronary risk factor, and that reduction of serum Lp(a) is important in the clinical management of patients with IHD.     

Conformation for a beta-cyclodextrin monosubstituted with a cyclic dipeptide.

The structural characterization of a beta-cyclodextrin monosubstituted with the peptide cyclo(L-His-L-Leu) is reported. This work provides an x-ray example of a covalently bound group that folds in such a way that the terminal apolar side chain is retained in the hydrophobic interior of the cone-shaped cyclodextrin cavity. 6-Deoxy-6-cyclo(L-histidyl-L-leucyl)-beta-cyclodextrin crystallizes in the space group P1 with cell dimensions a = 14.728(8) A, b = 15.084(7) A, c = 18.182(10) A, alpha = 94.36(6) degrees, beta = 95.81(5) degrees, gamma = 116.08(9) degrees; overall isotropic agreement R = 10.6% for 5703 observed reflections (Fo greater than 3 sigma). The molecular structure consists of two independent molecules with the formula C54H86N4O36.7.25H2O. Each molecule assumes a "sleeping swan"-like overall shape with the hydrophobic leucine side chain inserted inside the cavity of the macrocycle. The two independent units give rise to a head-to-tail dimer linked by hydrogen bonds occurring between primary and secondary hydroxyl groups of the two monomers. The packing of the dimers produces cavities containing water molecules. There are infinite hydrophilic channels running in the crystal, which is similar to what is found in the structures of cyclic peptides.     

Clostridium difficile as a cause of acute diarrhea: a prospective study in a tertiary care center

Introduction

Clostridium difficile-associated diarrhea (CDAD) is an increasing problem. Recent reports suggest presence of community acquired CDAD (CA CDAD). Studies in India have shown varied results.

Aims

The following are the aims of this study: (a) the prevalence of CDAD and CA CDAD in patients with acute diarrhea; (b) the incremental yield of second stool sample for the diagnosis of C. difficile infection (CDI); and (c) the risk factors for CDI.

Patients and Methods

Patients with acute diarrhea (<4 weeks) between April 2009 and December 2010 had two stool sample tested for C. difficile toxin (CDT) by enzyme-linked immunofluorescent assay. Demographic, clinical data, risk factors, clinical course, complications, treatment, and response were noted.

Results

Of 150 patients (mean age, 47.3 years; 76 males), 12 (8 %) had their first stool sample positive for CDT. Two patients (1.3 %) had community acquired CDI. The study group was compared with 138 patients (“control group”, stool samples negative for CDT). Compared to the controls, the study group were more likely to have had intensive care unit (ICU) stay (p?=?0.018) and tube feeding (p?=?0.035). Eleven patients were treated with metronidazole. One patient did not respond to metronidazole and was treated with vancomycin. No patient developed complications of CDAD.

Conclusions

The prevalence of CDAD in our population was 8 % and of CA CDAD was 1.3 %. There was no advantage of testing two samples. ICU stay and tube feeding were major risk factors for the CDAD. Metronidazole was an effective first-line therapy.     

Hijacking a hydroxyethyl unit from a central metabolic ketose into a nonribosomal peptide assembly line

Nonribosomal peptide synthetases (NRPSs) usually catalyze the biosynthesis of peptide natural products by sequential selection, activation, and condensation of amino acid precursors. It was reported that some fatty acids, α-ketoacids, and α-hydroxyacids originating from amino acid metabolism as well as polyketide-derived units can also be used by NRPS assembly lines as an alternative to amino acids. Ecteinascidin 743 (ET-743), naphthyridinomycin (NDM), and quinocarcin (QNC) are three important antitumor natural products belonging to the tetrahydroisoquinoline family. Although ET-743 has been approved as an anticancer drug, the origin of an identical two-carbon (C(2)) fragment among these three antibiotics has not been elucidated despite much effort in the biosynthetic research in the past 30 y. Here we report that two unexpected two-component transketolases (TKases), NapB/NapD in the NDM biosynthetic pathway and QncN/QncL in QNC biosynthesis, catalyze the transfer of a glycolaldehyde unit from ketose to the lipoyl group to yield the glycolicacyl lipoic acid intermediate and then transfer the C(2) unit to an acyl carrier protein (ACP) to form glycolicacyl-S-ACP as an extender unit for NRPS. Our results demonstrate a unique NRPS extender unit directly derived from ketose phosphates through (α,β-dihydroxyethyl)-thiamin diphosphate and a lipoyl group-tethered ester intermediate catalyzed by the TKase-ACP platform in the context of NDM and QNC biosynthesis, all of which also highlights the biosynthesis of ET-743. This hybrid system and precursor are distinct from the previously described universal modes involving the NRPS machinery. They exemplify an alternate strategy in hybrid NRPS biochemistry and enrich the diversity of precursors for NRPS combinatorial biosynthesis.     

Outcomes comparing a pancreaticogastrostomy (PG) and a pancreaticojejunostomy (PJ) after a pancreaticoduodenectomy (PD)

BackgroundThe advantage of a pancreaticogastrostomy (PG) over a pancreaticojejunostomy (PJ) after a pancreaticoduodenectomy (PD) is not clear.AimThe aim of the present study was to compare the pancreatic fistula (PF, defined according to the International Study Group for Pancreatic Fistula classification) rate and other complications between both methods.MethodsRetrospective analysis of prospectively collected data of 424 [median: 65 years (17–83)] patients who underwent PG (239, 56.4%) and PJ (185, 43.6%) reconstruction between January 2005 and December 2009.ResultsPF occurred in 55 (23.5%) in the PG and 30 (16.2%, P= 0.067) patients in the PJ group. Grade A PF occurred in 19 (7.9%), B in 22 (9.2%) and C in 14 (5.8%) in the PG compared with 5 (2.7%), 12 (6.5%) and in 13 (7.0%), respectively, in the PJ group. The median hospital was 10 days in both groups. The morbidity was higher in the PG group (108, 45.2 vs. 62, 33.5%, P= 0.015). However, there was no significant difference in the 90-day mortality between both groups (PG-17, 7.0% vs. PJ-16, 8.6%, P= 0.558).ConclusionThere was no difference in the overall PF rate, hospital stay and overall mortality between PG and PJ reconstruction methods. However, the grade A PF rate was higher in the PG group.     

Termination of a tachyarrhythmia by flunarizine is not a specific marker for a triggered mechanism

BACKGROUND: Prior studies have indicated that tachyarrhythmia termination by flunarizine demonstrates a triggered mechanism. This concept was not confirmed in atrial tachyarrhythmias. OBJECTIVE: The purpose of this study was to test the hypothesis that flunarizine will not terminate reentrant atrial flutter (AFL). METHODS: We administered flunarizine (2 mg/kg intravenously over 2 minutes) in 11 episodes of reproducibly inducible, sustained AFL in eight canines with sterile pericarditis. If flunarizine terminated AFL, we studied AFL reinducibility. We also studied pacing thresholds, refractoriness, and intra-atrial conduction time during closed-chest studies and pacing at selected cycle lengths (CLs) from selected sites before and after flunarizine administration. Atrial mapping (510 electrodes) assessed the epicardial activation sequence during AFL and its termination in six episodes. Four AFL episodes were studied in the closed-chest state. RESULTS: Flunarizine increased AFL CL in all episodes (mean 21 ms; range 7-49 ms), which is explained by slowing conduction in the AFL reentrant circuit, principally in the area of slow conduction. AFL was terminated in 10/11 episodes after drug initiation (mean 3.7 minutes; range 0.5-6.5 minutes) by block in the area of slow conduction. AFL was then not immediately reinducible until >20 minutes after drug administration. Flunarizine had no meaningful effect on atrial pacing thresholds for capture or refractoriness and only affected conduction time in the area of slow conduction in the reentrant circuit. CONCLUSIONS: Flunarizine (1) causes progressive slowing and block in the area of slow conduction of the AFL reentrant circuit in the canine sterile pericarditis model and (2) is effective in terminating reentrant AFL and so is not a specific marker for a triggered mechanism.     

Apolipoprotein(a) polymorphism and its association with plasma lipoprotein(a) levels: a north Indian study

Elevated levels of lipoprotein(a) has been regarded as an independent risk factor for coronary, peripheral and cerebral atherosclerosis. The enormous intra-personal variation in the plasma concentration of lipoprotein(a) is almost entirely controlled by the apolipoprotein(a) i.e. gene locus on the chromosome 6q 26-27. The apolipoprotein(a) molecule is highly polymorphic and is known to exist in multiple, genetically determined isoforms. These polymorphisms may be responsible for difference in promoter activity, variable size of apolipoprotein(a) and thereby variation in plasma lipoprotein(a) concentration. We studied the effect of two types of polymorphisms, (i) variation in length of the pentanucleotide repeat in the 5' flanking region starting -1373 bp upstream of AUG codon, and (ii) the Kringle-4 type 2 size polymorphism, on plasma lipoprotein(a) levels in North Indian population. The study group consisted of 88 angiographically assessed male coronary artery disease patients (age range 30-70 years) and 83 age- and sex-matched healthy controls. The pentanucleotide repeat polymorphism was analysed using polymerase chain reaction. In all, 8/11 pentanucleotide repeat isoforms were observed. Using SDS-agarose gel electrophoresis and immunoblotting isoforms having 12-50 Kringle-4 type 2 repeats were detected. Our study indicates a strong association of elevated plasma lipoprotein(a) concentration with coronary artery disease. An inverse correlation was seen between lipoprotein concentration and isoform size for both the pentanucleotide repeat polymorphism and the Kringle-4 type 2 polymorphisms; statistically significant difference (p = 0.001) was, however, observed only for the later.