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PubMed1987

Genomic organization of human centromeric alpha satellite DNA: characterization of a chromosome 17 alpha satellite sequence.

We characterized a recombinant clone E7 containing a 1.6-kb Eco RI insert of human alpha satellite DNA (alpha DNA) which hybridized in situ predominantly to the centromere of chromosome 17. Three thousand copies of this sequence were detected on chromosome 17, although a lesser number of copies were also found on the centromeres of chromosomes 11, X, and the other human chromosomes, except Y. In the human genome, sequences homologous to E7 were organized principally as five major polymorphic (Pst I) forms of tandem alpha DNA repeats with molecular weights between 2.0 and 2.7 kb. We We studied the higher-order organization of these major forms using a series of 12 cosmid clones. Close linkage of the different polymorphic forms was demonstrated, with no two cosmids showing an identical linkage pattern. Six of the cosmid clones carried a considerable amount (20-25%) of nonhomologous (non-alpha) DNA, indicating that the repeat arrays are relatively frequently interrupted by other genomic DNA. In none of the cosmid inserts were the repeat arrays bound on both sides by non-alpha DNA, suggesting that short arrays are not common. However, some of the intervening non-alpha DNA sequences were relatively short, and vary in size from 6 to 24 kb. Our results suggest an irregular and complex pattern of organization of alpha DNA in the human genome.

Chromosome Mapping↗
PubMed2003

Repeat sequence of Epstein-Barr virus-encoded nuclear antigen 1 protein interrupts proteasome substrate processing.

The Epstein-Barr virus thwarts immune surveillance through a Gly-Ala repeat (GAr) within the viral Epstein-Barr virus-encoded nuclear antigen 1 protein. The GAr inhibits proteasome processing, an early step in antigen peptide presentation, but the mechanism of proteasome inhibition has been unclear. By embedding a GAr within ornithine decarboxylase, a natural proteasome substrate that does not require ubiquitin conjugation, we now demonstrate inhibition in a purified system, excluding involvement of ubiquitin conjugation or of proteins extraneous to substrate and proteasome. We show further that the GAr acts as a stop-transfer signal in proteasome substrate processing, resulting in vivo in partial proteolysis that halts just short of the GAr. Similarly, introducing a GAr into green fluorescent protein destabilized by the ornithine decarboxylase degradation domain also stops the progress of proteolysis, leading to the accumulation of partial degradation products. We postulate that the ATP motor of the proteasome slips when it encounters the GAr, impeding further insertion and, in this way, halting degradation.

Animals↗
PubMed1994

Cryptic and polar variation of the fragile X repeat could result in predisposing normal alleles.

Fragile X syndrome results from the expansion of a CGG repeat that is normally interrupted by occasional AGG triplets. Linkage disequilibrium suggests that certain normal haplotypes may contribute unequally to the pool of fragile X chromosomes. Sequence analysis of normal alleles demonstrates haplotype-specific variation of the cryptic nature of the repeat. Variation occurs principally at the 3' end of the repeat, suggesting stability differences between the leading and lagging strands of DNA replication. Normal alleles with greater than 24 perfect 3' CGG repeats appear more frequently on haplotypes overrepresented among fragile X chromosomes. Such alleles are found in 2% of normal chromosomes and could comprise the ancestral allelic pool from which fragile X chromosomes are derived. These data also may imply that equilibrium between certain predisposed alleles and fragile X expansions has not yet been attained, indicating ongoing evolutionary change at this locus.

Alleles↗
PubMed2026

Clinical Application of Long-Read Sequencing for FMR1 Gene Mutation Detection in Populations From Shandong, China.

BACKGROUND: Fragile X syndrome (FXS) is a common inherited intellectual disability. In this study, long-read sequencing was used for the FMR1 gene detection. METHODS: Men with familial inherited intellectual disability and women with indications for FXS screening were defined as high-risk populations and were included in this study along with non-high-risk reproductive-aged women. PCR-capillary electrophoresis was used for preliminary screening of non-high-risk reproductive-aged women, and long-read sequencing was performed on abnormal samples and samples from high-risk populations. Prenatal diagnosis using long-read sequencing was performed for pregnant women in need. RESULTS: The prevalence of mutation in high-risk females was 3.10% (7/226). 3 mutations were detected in male samples, with a mutation ratio of approximately 8.3% (3/36). The three most common CGG repeats were 29, 30, and 36, respectively. Analysis of AGG interruption pattern in 242 samples identified 908 AGG interruptions, involving 67 different patterns. The most frequent AGG interruption pattern was (CGG)9AGG(CGG)9AGG(CGG)9. Furthermore, long-read sequencing was successfully applied for prenatal diagnosis in two pregnant women, and dynamic mutation of CGG repeat was detected within one family. CONCLUSION: Long-read sequencing-based assay cannot only accurately detect CGG repeat and AGG interruption, but also simultaneously identify other abnormalities of the FMR1 gene. Long-read sequencing offers a broader detection scope and better characterization of FXS-related genetic features.

Humans↗
PubMed2005

Influence of intermediate and uninterrupted FMR1 CGG expansions in premature ovarian failure manifestation.

BACKGROUND: Studies attempting to precisely define the range of fragile mental retardation 1 (FMR1) expansions and its inf luence in premature ovarian failure (POF) manifestation are partially lacking. To this aim, we evaluated a large cohort of POF patients for the size and, in selected cases, for the sequence of the CGG expansion. Furthermore, the correlation between POF and X-inactivation was investigated in FRAXA families. METHODS: By fluorescent PCR, 190 POF and 200 control women were sized for the CGG tract; some subjects were also characterized by sequencing and for the FMR1 activation ratio. RESULTS AND CONCLUSION: We found a significant association (19/190, 10%, P < 1 x 10(-6)) between POF and FMR1 premutation (range 63-163 repeats) and a significant enrichment (9/190, 4.7%, P = 0.021) of POF carriers of intermediate expansions (range 41-58 repeats). Interestingly, intermediate alleles were entirely composed of CGG repeats. Furthermore, the analysis of three pairs of siblings with similar FMR1 expansions and discordant for the POF phenotype showed a direct correlation between the expression of the intermediate/premutated allele and POF manifestation. The results obtained strengthen the correlation between FMR1 expansion and POF and suggest that the manifestation of the ovarian dysfunction could be influenced both by the pattern of interruption of the CGG repeat and by X-inactivation.

Adult↗
PubMed1997

The Friedreich ataxia GAA triplet repeat: premutation and normal alleles.

The most common mutation causing Friedreich ataxia (FRDA), an autosomal recessive neurodegenerative disease, is the hyperexpansion of a polymorphic GAA triplet repeat localized within an Alu sequence (GAA-Alu) in the first intron of the frataxin (X25) gene. GAA-Alu belongs to the AluSx subfamily and contains several polymorphisms in strong linkage disequilibrium either with a subgroup of normal alleles, or with hyperexpanded FRDA-associated alleles. GAA repeat sizes in 300 normal chromosomes (97 from carriers and 203 from controls) were distributed in two separate groups: 83% of them contained between six and 10 triplets (small normal alleles), while the remaining 17% had more than 12 triplets, up to 36 (large normal alleles). Sequence analysis showed that no normal, stable allele contained more than 27 uninterrupted GAA triplets. All longer normal alleles were interrupted by a hexanucleotide repeat (GAGGAA). An allele containing an uninterrupted run of 34 GAA triplets was stably transmitted in four instances, but in one case underwent hyperexpansion to 650 triplets. Overall, our results suggest that the FRDA-associated expanded GAA repeats originate from normal alleles by recurrent expansions of alleles at risk.

Alleles↗
PubMed1982

Abrogation by subsequent feeding of antibody response including IgE, in parenterally immunized mice.

We have investigated the possibility of oral administration of ovalbumin (OVA) to prevent a secondary antibody response and interrupt reaginic antibody production. Repeated feeding seems necessary for both. Quality of results was dependent on the number of ingestions. Differences in abrogation of antibody response between mice strains were observed. Best results were obtained with AKR mice, good suppression was seen in C3H strain, and inconsistent results were obtained with DBA/2. 10 OVA oral doses were necessary to prevent a secondary antibody response in parenterally immunized mice, but 4 doses interrupted reaginic production in sensitized AKR mice. These results demonstrate that antigen feeding can prevent a secondary antibody response and interrupt reaginic antibody production.

Administration, Oral↗
PubMed1996

Decrease in the CGGn trinucleotide repeat mutation of the fragile X syndrome to normal size range during paternal transmission.

The fragile X syndrome, the most common inherited form of mental retardation, is caused by the expansion of a CGGn trinucleotide repeat in the FMR-1 gene. Although the repeat number usually increases during transmission, few cases with reduction of an expanded CGGn repeat back to the normal size range have been reported. We describe for the first time a family in which such reduction has occurred in the paternal transmission. The paternal premutation (delta = 300 bp) was not detected in one of the five daughters or in the son of this daughter, although he had the grandpaternal RFLP haplotype. Instead, fragments indicating the normal CGGn repeat size were seen on a Southern blot probed with StB12.3. PCR analysis of the CGGn repeat confirmed this; in addition to a maternal allele of 30 repeats, an allele of 34 repeats was detected in the daughter and, further, in her son. Sequencing of this new allele revealed a pure CGGn repeat configuration without AGG interruptions. No evidence for a somatic mosaicism of a premutation allele in the daughter or a normal allele in her father was detected when investigating DNA derived from blood lymphocytes and skin fibroblasts. Another unusual finding in this family was lack of the PCR product of the microsatellite marker RS46 (DXS548) in one of the grandmaternal X chromosomes, detected as incompatible inheritance of RS46 alleles. The results suggest an intergenerational reduction in the CGGn repeat from premutation size to the normal size range and stable transmission of the contracted repeat to the next generation. However, paternal germ-line mosaicism could not be excluded as an alternative explanation for the reverse mutation.

Base Sequence↗
PubMed1990

Multiple non-B-DNA conformations of polypurine.polypyrimidine sequences in plasmids.

A polypurine.polypyrimidine (Pur.Pyr) sequence with a central interruption in a plasmid can adopt multiple non-B-DNA conformations depending on the conditions as revealed by specific chemical probes (OsO4, diethyl pyrocarbonate, and dimethyl sulfate) and two-dimensional electrophoresis. The relatively long mirror repeat Pur.Pyr sequences (GAA)9TTC(GAA)8 and (GGA)9TCC(GGA)8 form single canonical intramolecular triplexes at pH 7.0-6.0 in negatively supercoiled plasmids as isolated from Escherichia coli. With a lowering of the pH and/or an increase in the degree of negative supercoiling, these sequences undergo a novel conformational change as revealed by diethyl pyrocarbonate hypermodification of adenines in the middle of the polypurine strand and OsO4 reaction with thymines in the center and the quarter points of the polypyrimidine strand. To evaluate this structure, a family of related Pur.Pyr sequences were cloned and studied. The non mirror repeat sequence (GGA)9TCC(GAA)8 forms a non-B conformation only under acidic pH conditions, but the structural properties are different from those of the mirror repeat sequences. Furthermore, when the central interruptions of a mirror repeat sequence were increased from 3 to 9 bp, two canonical triplexes formed independently at pH 5.0 [at the (GAA)9 and (GAA)8 regions in the sequence (GAA)9TTAATTCGC(GAA)8]. Thus, if an interruption is sufficiently long, the two halves of the Pur.Pyr sequence do not interact with each other. Novel types of folded DNA geometries which explain these results are described.

Base Sequence↗
PubMed1995

Two mutant alleles of the insulin receptor gene in a family with a genetic form of insulin resistance: a 10 base pair deletion in exon 1 and a mutation substituting serine for asparagine-462.

Mutations in the insulin receptor gene cause several genetic syndromes associated with extreme insulin resistance. We have studied three insulin resistant siblings with acanthosis nigricans, dental abnormalities, and acral hypertrophy. The female patient also had primary amenorrhea due to hyperandrogenism. All three patients were compound heterozygotes with two mutant alleles of the insulin receptor gene. One allele had a 10-bp deletion in the region of exon 1 encoding the hydrophobic signal peptide; this leads to a frameshift and premature chain termination at codon 61. The deletion occurs at the site of a direct repeat of a hexanucleotide sequence interrupted by a tetranucleotide sequence; the deletion may have resulted from recombination between the upstream and downstream hexanucleotide repeats. In the other mutant allele, there is a missense mutation substituting serine for Asn462-a mutation identified previously in one allele of the insulin receptor gene in a patient with type-A insulin resistance. The Ser462 mutation impaired the ability of acidic pH to dissociate insulin from the receptor. Thus, Thus, like the previously described Glu460 mutation, the Ser462 mutation may retard dissociation of insulin from the receptor in the acidic compartment of the endosome and may, as a result, accelerate the rate of receptor degradation.

Alleles↗
PubMed1999

Spinocerebellar ataxias in Spanish patients: genetic analysis of familial and sporadic cases. The Ataxia Study Group.

Autosomal dominant cerebellar ataxias (ADCA) are a clinically heterogeneous group of neurodegenerative disorders caused by unstable CAG repeat expansions encoding polyglutamine tracts. Five spinocerebellar ataxia genes (SCA1, SCA2, SCA3, SCA6 and SCA7) and another related dominant ataxia gene (DRPLA) have been cloned, allowing the genetic classification of these disorders. We present here the molecular analysis of 87 unrelated familial and 60 sporadic Spanish cases of spinocerebellar ataxia. For ADCA cases 15% were SCA2, 15% SCA3, 6% SCA1, 3% SCA7, 1% SCA6 and 1% DRPLA, an extremely rare mutation in Caucasoid populations. About 58% of ADCA cases remained genetically unclassified. All the SCA1 cases belong to the same geographical area and share a common haplotype for the SCA1 mutation. The expanded alleles ranged from 41 to 59 repeats for SCA1, 35 to 46 [corrected] for SCA2, 67 to 77 for SCA3, and 38 to 113 for SCA7. One SCA6 case had 25 repeats and one DRPLA case had 63 repeats. The highest CAG repeat variation in meiotic transmission of expanded alleles was detected in SCA7, this being of +67 units in one paternal transmission and giving rise to a 113 CAG repeat allele in a patient who died at 3 years of age. Meiotic transmissions have also shown a tendency to more frequent paternal transmission of expanded alleles in SCA1 and maternal in SCA7. All SCA1 and SCA2 expanded alleles analyzed consisted of pure CAG repeats, whereas normal alleles were interrupted by 1-2 CAT trinucleotides in SCA1, except for three alleles of 6, 14 and 21 CAG repeats, and by 1-3 CAA trinucleotides in SCA2. No SCA or DRPLA mutations were detected in the 60 sporadic cases of spinocerebellar ataxia, but one late onset patient was identified as a recessive form due to GAA-repeat expansions in the Friedreich's ataxia gene.

Adult↗
PubMed1999

DNA analysis of Huntington's disease: five years of experience in Germany, Austria, and Switzerland.

OBJECTIVE: To review the direct DNA testing for Huntington's disease (HD) in Germany, Switzerland, and Austria from 1993 to 1997, and to analyze the population with regard to age structure, gender, and family history. METHODS: Twelve laboratories (nine in Germany, two in Austria, and one in Switzerland) recorded data pertaining to repeat number, gender, age at molecular diagnosis, and family history of probands. The molecular test was categorized as either diagnostic (for symptomatic individuals), presymptomatic (for individuals at risk), and prenatal (for pregnancies at risk). RESULTS: A total of 3,090 HD patients, 992 individuals at risk, and 24 fetuses were investigated using DNA analysis. The clinical diagnosis was confirmed in 65.6% of patients. A total of 38.5% of individuals at risk inherited an expanded CAG repeat. The female-to-male ratio showed a distinct predominance of women both in the diagnostic and presymptomatic groups. Of the fetuses tested, six were carriers of an expanded CAG repeat. Two pregnancies were interrupted; one pregnancy was not. No information about the parents' decision was obtained for the remaining three pregnancies. CONCLUSIONS: Approximately 20% of the estimated 10,000 HD patients living in Germany, Switzerland, and Austria have been identified by DNA analysis (total population, approximately 100 million; incidence of HD, 1:10,000). Assuming a ratio of HD patients to individuals at risk of 1:3, approximately 30,000 individuals are, in principle, eligible for a presymptomatic test. Less than 3 to 4% of individuals at risk have requested a presymptomatic test. This shows that the assumed enormous request of predictive testing has not occurred. More surprisingly, prenatal diagnoses were found to be rare.

Adult↗
PubMed2006

Characterization of Schistosoma mansoni Sds homologue, a leucine-rich repeat protein that interacts with protein phosphatase type 1 and interrupts a G2/M cell-cycle checkpoint.

The suppressor of the dis2 mutant (sds22+) has been shown to be an essential regulator in cell division of fission and budding yeast where its deletion causes mitotic arrest. Its role seems to take place through the activation of PP1 (protein phosphatase type 1) in Schizosaccharomyces pombe. In the trematode Schistosoma mansoni, we have identified the Sds22 homologue (SmSds), and the PP1 (SmPP1). We showed by using a GST (glutathione S-transferase) pull-down assay that the SmSds gene product interacts with SmPP1 and that the SmSds-SmPP1 complex is present in parasite extracts. Furthermore, we observed that SmSds inhibited PP1 activity. Functional studies showed that the microinjection of SmSds into Xenopus oocytes interacted with the Xenopus PP1 and disrupted the G2/M cell-cycle checkpoint by promoting progression to GVBD (germinal vesicle breakdown). Similar results showing the appearance of GVBD were observed when oocytes were treated with anti-PP1 antibodies. Taken together, these observations suggest that SmSds can regulate the cell cycle by binding to PP1.

Amino Acid Motifs↗
PubMed2006

Pharmaceutical policies: effects of reference pricing, other pricing, and purchasing policies.

BACKGROUND: Pharmaceuticals can be important for people's health. At the same time drugs are major components of health care costs. Pharmaceutical pricing and purchasing policies are used to determine or affect the prices that are paid for drugs. Examples are price controls, maximum prices, price negotiations, reference pricing, index pricing and volume-based pricing policies. The essence of reference pricing is to establish a maximum level of reimbursement for a group of drugs assumed to be therapeutically equivalent. OBJECTIVES: To determine the effects of pharmaceutical pricing and purchasing policies on drug use, healthcare utilisation, health outcomes and costs (expenditures). SEARCH STRATEGY: We searched the following databases and web sites: Effective Practice and Organisation of Care Group Register (date of last search: 22/08/03), Cochrane Central Register of Controlled Trials (15/10/03), MEDLINE (07/09/05), EMBASE (07/09/05), ISI Web of Science (08/09/05), CSA Worldwide Political Science Abstracts (21/10/03), EconLit (23/10/03), SIGLE (12/11/03), INRUD (21/11/03), PAIS International (23/03/04), International Political Science Abstracts (09/01/04), NHS EED (20/02/04), PubMed (25/02/04), NTIS (03/03/04), IPA (22/04/04), OECD Publications & Documents (30/08/05), SourceOECD (30/08/05), World Bank Documents & Reports (30/08/05), World Bank e-Library (04/05/05), JOLIS (22/08/05), Global Jolis (22/08/05 and 23/08/05), WHOLIS (29/08/05). SELECTION CRITERIA: Policies in this review were defined as laws, rules, financial and administrative orders made by governments, non-government organisations or private insurers. To be included a study had to include an objective measure of at least one of the following outcomes: drug use, healthcare utilisation, health outcomes, and costs (expenditures); the study must be a randomised controlled trial, non-randomised controlled trial, interrupted time series analysis, repeated measures study or controlled before-after study of a pharmaceutical pricing or purchasing policy for a large jurisdiction or system of care. DATA COLLECTION AND ANALYSIS: Two reviewers independently extracted data and assessed study limitations. Quantitative analysis of time series data, for studies with sufficient data, and qualitative analyses were undertaken. MAIN RESULTS: We included 10 studies of reference pricing and one study of index pricing. Most of the reference pricing studies were for senior citizens in British Columbia, Canada. The use (dispensing) of reference drugs increased in five studies, between 60% and 196% immediately after introduction of reference drug pricing, whereas the use of cost sharing drugs decreased by between 19% and 42% in four studies. In three studies the reference drug group expenditures decreased (range 19% - 50%), whereas in the fourth study the expenditures increased by 5% in the short term. The results after six months of reference pricing do not show any clear pattern in relationship to the immediate effects. We found no evidence of adverse effects on health and no clear evidence of increased health care utilisation. For index pricing the evidence was much more limited than for reference drug pricing. A small reduction in drug prices was found. AUTHORS' CONCLUSIONS: We found relatively few studies of pricing policies. The majority of the studies dealt with reference pricing. They had few methodological limitations. Based on the evidence in this review, mostly from senior citizens in British Columbia, Canada, reference drug pricing can reduce third party drug expenditures by inducing a shift in drug use towards less expensive drugs. We found no evidence of adverse effects on health and no clear evidence of increased health care utilisation. The analysis and reporting of the effects on patient drug expenditures were limited in the included studies and administration costs were not reported.

Cost Control↗
PubMed1993

Trypsin-resistant regions of thyroglobulin: possible relationship with intermonomeric contact site(s).

Upon incubation of bovine thyroglobulin with trypsin at high enzyme/substrate ratio, some fragments with apparent masses between 18 and 31 kDa resisted prolonged digestion. Their NH2-terminal sequences were determined. All fragments overlapped with some of the Cys-rich repeats that compose a large part of thyroglobulin and are predicted to have a rigid structure. Among the inserts that interrupt the cysteine-rich repeats, for which several data indicate a location at the surface of thyroglobulin, the insert of repeat 1.7 was unique because of its resistance to proteolysis. This insert, although exposed at the surface of the protein, may be hidden in a region of contact between thyroglobulin monomers.

Amino Acid Sequence↗
PubMed1994

Biliary motility. Changes in detailed characteristics correlated to duodenal migrating motor complex and effects of morphine and motilin in dogs.

The temporal relationship of biliary motility to the duodenal migrating motor complex and effects of morphine and motilin were studied in five dogs prepared with a duodenal cannula. Common bile duct, sphincter of Oddi, and duodenal manometry were performed awake. Sphincter of Oddi phasic contractions occurred even during the quiescent period of duodenal phase I and its activity increased from phase II to III. Minimum basal pressure of sphincter of Oddi and common bile duct pressure decreased from phase I to phase III. Both morphine and motilin induced premature phase III in the sphincter of Oddi and duodenum. Latencies of the effect were 0.2 min for morphine and 3.2 min for motilin (P < 0.01). After morphine, vigorous continuous contractions with high basal pressure occurred, being interrupted by brief and repeated inactive periods, similar to spontaneous phase III. Motilin-induced phase III appeared indistinguishable from spontaneous phase III. Although both agents induced phase III in the sphincter of Oddi, differences in the latency and contraction pattern suggest different mechanisms of action of these agents on the sphincter of Oddi.

Animals↗
PubMed1999

Structural analysis, expression, and chromosomal localization of the mouse ikba gene.

The pleiotropic transcription factor NF-kappaB is localized in the cytoplasm bound to its inhibitory subunit IkappaB. The predominant form of NF-kappaB is a p50/p65 heterodimer which can be released from IkappaB-alpha and migrate to the nucleus. Previous studies have shown that IkappaB-alpha-/- mice die 8 to 10 days postnatally, showing runting and a severe dermatitis. However, the organ distribution of mouse IkappaB-alpha, the exon-intron structure, and the chromosomal localization of ikba have not been determined so far. A mouse Sv129 genomic DNA library was screened with a human IkappaB-alpha/MAD-3 cDNA probe. One clone (P1) was isolated, spanning the complete ikba gene and the promoter/enhancer region. We show that the exon-intron structure between mouse and pig ikba is completely conserved. In contrast to human ikba, the ankyrin repeat 5 is not interrupted by an intron. Furthermore, the mouse ikba promoter contains 6 putative NF-kappaB binding sequences, which are conserved in mouse, pig, and human, underlining the importance of NF-kappaB as a key regulator of ikba transcription. The deduced amino acid sequence shows >90% similarity between mouse, pig, and human ikba. Chromosome mapping localized the mouse ikba gene to chromosome 12. Northern blot analysis demonstrated predominant expression in lymphoid tissue (lymph node and thymus). However, IkappaB-alpha mRNA was detected as well in liver tissue, the gastrointestinal tract, and the reproductive tract. The cloning and determination of the structure are a prerequisite for the construction of vectors for conditional gene targeting experiments.

Amino Acid Sequence↗
PubMed1990

Retrograde coronary sinus cardioplegia for aortic valve operations: a clinical report on 500 patients.

Retrograde delivery of cardioplegic solutions has recently been the subject of renewed interest, but the reliability of this technique has not been assessed in large clinical series. From 1980 to 1989, we used retrograde coronary sinus perfusion as the exclusive means of cardioplegia delivery in 500 consecutive patients undergoing aortic valve replacement, either isolated (359 patients) or combined with another valve or coronary procedure (141 patients). The coronary sinus was always cannulated under direct vision after bicaval cannulation with snaring. Cold crystalloid cardioplegia was delivered retrogradely at an average flow rate of 100 mL/min in conjunction with topical and systemic (25 degrees C) hypothermia. The mean cross-clamp time was 83 +/- 23 minutes (+/- the standard deviation). There were 31 hospital deaths (6.2%), 20 of which were cardiac related. Transient hemodynamic instability (defined as a need for inotropic agents for less than 24 hours postoperatively) occurred in 16 patients (3.2%), whereas a true low-output syndrome developed in 60 patients (12%). The incidence of clinically significant supraventricular arrhythmias and of permanent conduction defects was 7.4% and 1.2%, respectively. There were three nonfatal coronary venous injuries during our early experience. We conclude that coronary sinus perfusion is a safe and effective means of delivering cardioplegia in aortic valve operations. While providing a degree of myocardial protection similar to that reported with anterograde cardioplegia, the coronary sinus technique offers distinct advantages, in particular, the avoidance of perfusion-related coronary artery complications and the opportunity to repeat cardioplegia administration without interrupting the procedure.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗