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1.
Transfus Med ; 15(5): 435-42, 2005 Oct.
Article in English | MEDLINE | ID: mdl-16202060

ABSTRACT

Apparent deviation from Mendelian rules of blood group inheritance is rarely observed. Blood group O parents with children expressing weak A subgroups have occasionally been described but not explained. A detailed serological investigation of such a family is described here. The ABO locus was analysed by PCR-ASP/restriction fragment length polymorphism genotyping and DNA sequencing. The propositus' RBCs were very weakly agglutinated with monoclonal anti-A but distinctly with polyclonal anti-A,B, i.e. typical for Ax. Serum anti-A1 (titre 4) and -B were present. Her parents' blood groups were both clearly O, with titres of serum anti-A1, and -A at 16 and 4, respectively. Adsorption/ elution studies demonstrated A antigen on the daughter's cells only. The ABO genotypes were: mother, AxO1; father, O1vO2; and propositus, AxO2. The Ax allele was an A1-O1v hybrid allele with a crossing-over breakpoint between positions 235 and 446 in intron 6 (Ax-4). Compared to the A1 glycosyltransferase, this allele predicts a protein with two amino acid substitutions (Phe216Ile and Met277Val) known to yield either weakly expressed or no A antigen on RBCs. This study suggests that the nature of the ABO allele in trans can influence A antigen expression, a phenomenon previously described as allelic enhancement (or reinforcement). Potential mechanisms for this are discussed.


Subject(s)
ABO Blood-Group System/genetics , Alleles , Crossing Over, Genetic , Gene Expression , Polymorphism, Restriction Fragment Length , Quantitative Trait Loci , Family , Female , Genotype , Humans , Male
2.
Vox Sang ; 88(4): 256-64, 2005 May.
Article in English | MEDLINE | ID: mdl-15877647

ABSTRACT

BACKGROUND AND OBJECTIVES: Many phenotypic variations in the expression of blood group A have been explained by variations in gene structure, but unresolved samples are frequently encountered in the reference laboratory. Among ABO subgroups, A(bantu) has the highest frequency in a specified population. The molecular basis of this phenotype is now described. MATERIALS AND METHODS: Blood from Black donors phenotyped as A(bantu) was subjected to genomic ABO screening and direct sequencing of polymerase chain reaction (PCR)-amplified ABO exons 1-7 and introns 2-6. Total RNA was extracted and ABO cDNA was synthesized by reverse transcription (RT)-PCR. Control material comprised Black South African, Swedish, Jordanian and Brazilian blood samples with common phenotypes. RESULTS: Genomic ABO typing indicated the presence of an A(2) allele in each A(bantu) donor, in combination with an O allele. No previously reported mutations associated with weak A or B expression were found. Direct sequencing indicated the common A(2) sequence with a single nucleotide deletion (AGGT>AGT) at the exon 4/intron 4 junction, predicted either to disrupt the reading frame (resulting in a premature stop codon) or to cause erroneous splicing (resulting in the exclusion of exon 4 from the mRNA). O mRNA, but no transcripts from the A(bantu) allele, could be detected. Surprisingly, the splice-site mutation was also found in approximately 5% of O alleles in Black South Africans, but not in other blood donors, or in non-O(1) alleles. Utilizing intron polymorphisms, the A(bantu) allele was shown to be a recombination between a new allelic lineage (O(1bantu)) and A(2), with a cross-over region near exon 5. CONCLUSION: The A(bantu) phenotype is caused by an O(1bantu)-A(2) hybrid at the ABO locus.


Subject(s)
ABO Blood-Group System/genetics , Alleles , Black People/genetics , Mutation , RNA Splice Sites/genetics , Recombination, Genetic , Ethnicity/genetics , Exons , Frameshift Mutation , Gene Frequency , Genetic Testing , Humans , Introns , Phenotype , RNA, Messenger/genetics
3.
Transfus Med ; 14(2): 173-80, 2004 Apr.
Article in English | MEDLINE | ID: mdl-15113382

ABSTRACT

A discrepancy in the ABO blood groups between a newborn child and her parents was identified. Serological and DNA investigative techniques were performed. A weak variant of B (B(w)) was detected on the erythrocytes of the child, her grandmother and great-uncle. Adsorption-elution studies showed that their erythrocytes adsorb and yield anti-B on elution. The B(w) antigenic strength of the A(1)B(w) cells of her mother and maternal aunt was reduced when compared to that of the A(2)B(w) from another family member. Only one of 15 different anti-B sera agglutinated the A(1)B(w) erythrocytes. Agglutinin anti-B that reacted strongly with normal B erythrocytes and did not agglutinate the B(w) cells, was found in the sera of the A(1)B(w) individuals. The B(w) serum glycosyltransferase could not convert O cells into B cells and no B substance was found in saliva. All family members with the B(w)/AB(w) phenotypes were heterozygous for a B allele and DNA sequencing revealed a novel missense mutation in exon 7 of the B allele (556A > G), resulting in M186V. This substitution changes a highly conserved region of the enzyme, proposed to be a disordered loop near the enzyme cleft, and is expected to diminish the enzyme's activity, leading to this B(w) phenotype.


Subject(s)
ABO Blood-Group System , Point Mutation , ABO Blood-Group System/blood , ABO Blood-Group System/classification , ABO Blood-Group System/genetics , Adult , DNA Mutational Analysis , Family Health , Female , Glycosyltransferases/genetics , Heterozygote , Humans , Immune Sera , Infant, Newborn , Male , Mutation, Missense , Pedigree
4.
Transfus Med ; 11(4): 295-313, 2001 Aug.
Article in English | MEDLINE | ID: mdl-11532186

ABSTRACT

The blood group ABO gene codes for a glycosyltransferase that adds the ultimate monosaccharide to a glycoconjugate and forms the A or B blood group specific antigen. The DNA structure of the three major alleles of the human blood group ABO system was first described in 1990. This review describes the subsequent developments, including the increasing number of variants of these common alleles and the underlying mutations thought to be responsible for the occurrence of some of the weak subgroups of blood group A and B. Several inactive (O) alleles are also now known. Our knowledge of the DNA sequence of the normal A and B alleles and of the rare and intriguing cisAB and B(A) phenotypes has resulted in plausible explanations for these. Allelic variations outside the translated exons have been investigated and resulted in detection of lineage-specific intron mutations and the discovery of an enhancer VNTR region affecting the rate of transcription at this locus. The occurrence of hybrid alleles can also explain hitherto abnormal inheritance in some pedigrees. The detection of hybrid alleles has been made possible by the presence of numerous polymorphisms found in the various ABO alleles. The role of chi (chi) sequences is discussed. Finally, the various genotyping methods available are summarized and their advantages and limitations are analysed in the light of the increasing allelic variation.


Subject(s)
ABO Blood-Group System/genetics , Blood Grouping and Crossmatching/methods , Galactosyltransferases/genetics , N-Acetylgalactosaminyltransferases/genetics , ABO Blood-Group System/metabolism , Alleles , Consensus Sequence , DNA Mutational Analysis , Exons/genetics , Galactosyltransferases/biosynthesis , Gene Expression Regulation , Genes , Genetic Variation , Genome, Human , Genotype , Humans , Introns/genetics , Minisatellite Repeats , Multigene Family , N-Acetylgalactosaminyltransferases/biosynthesis , Oligosaccharides/metabolism , Oligosaccharides, Branched-Chain , Phenotype , Polymerase Chain Reaction , Polymorphism, Genetic , Polymorphism, Restriction Fragment Length , Polymorphism, Single-Stranded Conformational , Racial Groups/genetics , Recombination, Genetic , Trisaccharides/metabolism
5.
Blood ; 98(5): 1585-93, 2001 Sep 01.
Article in English | MEDLINE | ID: mdl-11520811

ABSTRACT

Since the cloning in 1990 of complementary DNA corresponding to messenger RNA transcribed at the blood group ABO locus, polymorphisms and phenotype-genotype correlations have been reported by several investigators. Exons 6 and 7, constituting 77% of the gene, have been analyzed previously in samples with variant phenotypes but for many subgroups the molecular basis remains unknown. This study analyzed 324 blood samples involved in ABO grouping discrepancies and determined their ABO genotype. Samples from individuals found to have known subgroup alleles (n = 53), acquired ABO phenotypes associated with different medical conditions (n = 65), probable chimerism (n = 3), and common red blood cell phenotypes (n = 109) were evaluated by ABO genotype screening only. Other samples (n = 94) from apparently healthy donors with weak expression of A or B antigens were considered potential subgroup samples without known molecular background. The full coding region (exons 1-7) and 2 proposed regulatory regions of the ABO gene were sequenced in selected A (n = 22) or B (n = 12) subgroup samples. Fifteen novel ABO subgroup alleles were identified, 2 of which are the first examples of mutations outside exon 7 associated with weak subgroups. Each allele was characterized by a missense or nonsense mutation for which screening by allele-specific primer polymerase chain reaction was performed. The novel mutations were encountered in 28 of the remaining 60 A and B subgroup samples but not among normal donors. As a result of this study, the number of definable alleles associated with weak ABO subgroups has increased from the 14 previously published to 29.


Subject(s)
ABO Blood-Group System/genetics , Alleles , ABO Blood-Group System/classification , Blood Grouping and Crossmatching , Chimera/blood , Chimera/genetics , DNA, Complementary/genetics , Exons/genetics , Female , Fetofetal Transfusion , Genotype , Hematologic Diseases/blood , Hematologic Diseases/genetics , Humans , Male , Neoplasms/blood , Phenotype , Polymorphism, Genetic , Pregnancy , RNA, Messenger/genetics , Sequence Analysis, DNA , Terminology as Topic , Twins/genetics
6.
Transfus Med Rev ; 15(3): 177-200, 2001 Jul.
Article in English | MEDLINE | ID: mdl-11471121

ABSTRACT

The blood group ABO gene shows considerable polymorphism in most of the 7 exons. Introns examined so far have also shown blood group-related polymorphisms, as has an upstream enhancer region. Several polymorphisms affect the specificity of the gene product (glycosyltransferase) and explain the occurrence of blood group A and B. Various lethal mutations result in blood group O. Other mutations are presumed to alter the activity rather than the specificity of the enzyme and result in weaker A and B blood group phenotypes. In total, 27 A alleles, 15 B alleles, 26 O alleles, and 4 AB hybrid alleles are described and surely more will surface in the near future. Variation in geographic/ethnic distribution of allele frequencies is discussed, along with the confusing nomenclatures currently in use.


Subject(s)
ABO Blood-Group System/genetics , Alleles , Genetic Variation , Glycosyltransferases , Humans , Mutation , Racial Groups/genetics
7.
Transfus Med ; 9(3): 219-26, 1999 Sep.
Article in English | MEDLINE | ID: mdl-10555816

ABSTRACT

Since the cloning in 1990 of cDNA corresponding to mRNA transcribed at the blood group ABO locus, polymorphisms at the ABO locus and phenotype-genotype correlation have been analysed by several investigators. An enhancer-active minisatellite motif reported to contain four 43-bp repeats has been analysed by PCR in blood samples from 160 random Swedish blood donors. Different sizes of the DNA fragments obtained led to further analysis by direct sequencing. Fragments with either one or four 43-bp repeats were identified. A nucleotide substitution (G-->A) at nt. 41 of 43 was found in all alleles with only one repeat. Correlation with the ABO genotypes of the samples, as determined by a panel of ABO genotyping techniques, revealed an allele-related variable number of tandem repeats (VNTR). The A1 and the infrequent O2 allele had only one repeat whilst A2, B, O1 and O1v had four repeats and thus generated longer (by 129 bp) fragments. A further 74 samples obtained from various geographical areas/ethnic groups indicated a widespread correlation with few exceptions. In conclusion, a novel ABO polymorphism located in the 5'-nontranslated region involved in transcriptional regulation of the ABO gene is reported and its relationship to common alleles at this locus defined.


Subject(s)
ABO Blood-Group System/genetics , Alleles , Genetic Variation , Minisatellite Repeats , Transcription, Genetic , Blood Donors , Genotype , Humans , Point Mutation , Polymerase Chain Reaction , Sequence Analysis, DNA , Sweden
8.
Transfus Med ; 8(3): 231-8, 1998 Sep.
Article in English | MEDLINE | ID: mdl-9800297

ABSTRACT

The Ax phenotype is an important subgroup of the ABO blood group system. Its inheritance does not always follow Mendelian rules and recent studies suggested that different alleles can result in this phenotype. This suggestion has been explored by cloning and sequencing exons 6 and 7 of the ABO gene and the intervening intron from members of six unrelated families expressing the Ax phenotype. Two families showed the previously described T646A 'Ax' mutation as the only deviation from the consensus A1 allele. In two other families the Ax phenotype was inherited as two different recombinational gene products. Combination of exon 6 derived from A or B/O2 alleles with exon 7 from the O1v allele created two novel alleles that have four O1v-characteristic nucleotide substitutions in exon 7, including T646A. Sequencing and analysis of polymorphisms in intron 6 defined the crossing-over zones of these hybrid alleles. Southern blot confirmed the hybrid formation by detecting ABO-related polymorphisms approximately 1.35 kb downstream from the ABO reading frame. The remaining two families expressed the Ax phenotype via an allele having A2-specific mutations. Thus, a heterogeneous molecular background leads to the serologically defined Ax phenotype and may well explain the different modes of inheritance observed.


Subject(s)
ABO Blood-Group System/genetics , ABO Blood-Group System/immunology , Alleles , Blood Grouping and Crossmatching , Blotting, Southern , Female , Genetic Heterogeneity , Genotype , Humans , Introns/genetics , Male , Pedigree , Phenotype , Polymorphism, Restriction Fragment Length , Recombination, Genetic/genetics , Sequence Analysis, DNA
10.
Vox Sang ; 75(1): 47-51, 1998.
Article in English | MEDLINE | ID: mdl-9745153

ABSTRACT

BACKGROUND AND OBJECTIVES: The published sequence of the weak. A subgroup Ael gene from Swedish individuals showed a G insertion in exon VII, causing a frameshift at codon 268 (the A1 gene has 353 codons). We wished to sequence exons VI and VII of two Norwegian Ael individuals and compare the expression of A substance on RBC from different Ael individuals. MATERIALS AND METHODS: Exon VI and VII were amplified by PCR, cloned in M13 and sequenced. A structure expression on Ael RBC was studied by the immunogold technique. RESULTS: In contrast to the Swedish Ael individuals, the two Norwegians had consensus A1 sequences in exon VI and VII. However, the patterns of A expression were indiscernible from the Swedish cases as visualized by immunogold labeling in SEM. In both cases, a few (1-2%) RBC were very strongly labeled, some were weakly labeled and the majority (95%) were unlabeled. CONCLUSION: Although some Ael individuals have an inserted nucleotide in exon VII of the ABO gene, others have consensus A1 sequence in exon VI and VII. However, we could not find any differences in phenotype by immunogold labeling in SEM.


Subject(s)
ABO Blood-Group System/biosynthesis , Chromosomes, Human, Pair 9/genetics , Erythrocyte Membrane/chemistry , Gene Expression Regulation , N-Acetylgalactosaminyltransferases/genetics , ABO Blood-Group System/genetics , Cloning, Molecular , Consensus Sequence , Erythrocyte Membrane/ultrastructure , Exons/genetics , Female , Genotype , Humans , Immunohistochemistry , Microscopy, Electron, Scanning , Microscopy, Immunoelectron , Mutagenesis, Insertional , N-Acetylgalactosaminyltransferases/chemistry , Norway , Polymerase Chain Reaction , Recombinant Fusion Proteins/chemistry , Sweden
11.
Vox Sang ; 74(1): 46-50, 1998.
Article in English | MEDLINE | ID: mdl-9481861

ABSTRACT

BACKGROUND AND OBJECTIVES: Amerindians are blood group O, but the distribution of the various O alleles is unknown. Their ABO genotypes were compared with samples from other Brazilian ethnic groups. MATERIALS AND METHODS: Genomic DNA was examined by PCR-RFLP analysis, PCR-SSP and direct sequencing. RESULTS: An unusual allele distribution was found, with 91% of the O alleles being O1variant. Almost half of these alleles had an additional novel mutation (G542A), which was also detected in a few other Brazilian and European samples. The O alleles correlated completely with ABO-related haplotypes previously determined by Southern blot. CONCLUSION: The three Amerindian tribes represent a homogeneous (ABO blood group) population, except for the G542A mutation. The presence of this mutation in all other populations examined suggests that it originated before the migration of man into America.


Subject(s)
ABO Blood-Group System/genetics , Indians, South American/genetics , Alleles , Brazil , Gene Frequency , Genetic Heterogeneity , Haplotypes , Humans , Polymerase Chain Reaction , Polymorphism, Restriction Fragment Length
12.
Biochem Biophys Res Commun ; 234(3): 779-82, 1997 May 29.
Article in English | MEDLINE | ID: mdl-9175793

ABSTRACT

The blood group ABO genotypes of 138 group O individuals with three different ethnic origins in Brazil were determined, including Whites, Blacks and Amerindians. Several previously undescribed O alleles were found, predominantly in the Black group, in which about a third of the samples did not conform to previously known O allele structures. It has been well documented for the first time that some new alleles can arise from crossing-over events between known alleles in the ABO system. This was made possible by both restriction endonuclease analysis and direct sequencing of exons 3-7 in the ABO gene. The anticipated relatively high frequency of some of these new alleles in certain populations, necessitates great care when interpreting results from existing genotype screening methods.


Subject(s)
ABO Blood-Group System/genetics , Alleles , Crossing Over, Genetic , Ethnicity , Point Mutation , Brazil , Humans
13.
Transfusion ; 36(4): 309-13, 1996 Apr.
Article in English | MEDLINE | ID: mdl-8623129

ABSTRACT

BACKGROUND: The common ABO allele sequences are known, but little or no genetic information is available on the rare but important A subgroups. STUDY DESIGN AND METHODS: Blood group ABO polymorphism was analyzed in genomic DNA from 45 rare subgroup A individuals by sequence-specific primer polymerase chain reaction and amplified fragment length polymorphism investigating exons VI and VII in the ABO genes. These methods are used to detect specific mutations only, and not all changes that might be present can be detected. ABO genotypes discriminating six alleles (A1, A2, B, O1, O1var, and O2) were determined. RESULTS: The C-->T substitution at nucleotide position 467 (C467T) is not restricted to A2 and cis-AB individuals, but was found also in some A subgroups. Detection of the functionally more relevant C1060-single-point deletion in A2 was accomplished by a novel sequence-specific primer polymerase chain reaction approach. A 100-percent correlation between the C467T and the C1060-mutations was found. Fifteen of 17 samples showing the T646A mutation (described earlier in one case of Ax) showed a positive correlation with the C771T mutation in a frequently occurring O1var allele. The two exceptions were defined serologically as Ax. CONCLUSION: Indications have been found of an evolutionary relationship between A1 alleles and Ael and A3 subgroups as well as between A2 alleles and Aend and Aweak subgroups. Genetic heterogeneity within the Ax and Aint subgroups was also seen.


Subject(s)
ABO Blood-Group System/genetics , Blood Donors , Base Sequence , Humans , Molecular Sequence Data , Polymerase Chain Reaction , Polymorphism, Genetic , Polymorphism, Restriction Fragment Length
14.
Vox Sang ; 71(2): 113-7, 1996.
Article in English | MEDLINE | ID: mdl-8873422

ABSTRACT

Using a recently introduced multiplex polymerase chain reaction and restriction fragment length polymorphism ABO genotype screening method we have found an anomalous ABO genotype (A2O1variant) not correlating with the serological phenotype (blood group O). The blood group was confirmed by absorption/elution and detection of blood group substances in saliva. Sequencing of exons 6 and 7 in the ABO genes of the propositus indicated an A2 gene (C467T and C1060-) apparently inactivated by the same single nucleotide insertion recently reported in individuals with the ABO subgroup Ael. Investigation of relatives confirmed the inheritance of this new inactive hybrid allele.


Subject(s)
ABO Blood-Group System/genetics , Alleles , DNA Transposable Elements , Female , Gene Deletion , Humans , Male , Pedigree , Polymerase Chain Reaction
15.
Vox Sang ; 70(1): 26-30, 1996.
Article in English | MEDLINE | ID: mdl-8928487

ABSTRACT

Blood group ABO polymorphism was analysed in genomic DNA isolated from 150 blood donors by restriction endonuclease digestion of three polymerase chain reaction-amplified exons in the ABO genes and by sequencing of randomly selected samples. An anomalous O1 allele first described in a cancer cell line is now shown to account for approximately 40% of the O alleles described to date. This is 10 times more frequent than the only other known variant O allele (O2). This variant O1 allele has at least seven point mutations when compared to the consensus gene, in addition to the deletion characterising the normal O1 allele.


Subject(s)
ABO Blood-Group System/genetics , Alleles , Base Sequence , Gene Frequency , Humans , Molecular Sequence Data , Point Mutation
16.
Biochem Biophys Res Commun ; 216(2): 642-7, 1995 Nov 13.
Article in English | MEDLINE | ID: mdl-7488159

ABSTRACT

Genomic DNA from each of four Acl individuals (genotypes AO1, AO1var, AO2) and one AclB individual was used as a template for amplifying exons 6 and 7 of the ABO genes, which were subsequently sequenced. In all the Ael alleles a single nucleotide insertion, compared to the A consensus sequence, was observed that would alter the amino acid sequence of the glycosyltransferase immediately after its postulated nucleotide sugar binding site and furthermore extend the translated protein by 37 amino acids (16 more than the A2 enzyme). A sequence-specific primer PCR assay was developed to detect the nucleotide insertion. It was possible to differentiate all 20 serologically defined Acl/AclB individuals available from 145 blood donors with normal ABO phenotypes and genotypes and 26 individuals with various A subgroups other than A1, A2 and Acl. This mutation explains the Acl phenotype and forms the basis of a method for detecting the Ael allele.


Subject(s)
ABO Blood-Group System/genetics , DNA Transposable Elements , Polymerase Chain Reaction/methods , Alleles , Base Sequence , Consensus Sequence , DNA/genetics , DNA Primers , Exons , Female , Genotype , Humans , Male , Molecular Sequence Data , Oligonucleotides, Antisense , Pedigree , Templates, Genetic
17.
Vox Sang ; 69(3): 242-7, 1995.
Article in English | MEDLINE | ID: mdl-8578738

ABSTRACT

An ABO genotype screening method discriminating the common alleles A1, A2, B, O1 and O2 at the ABO locus was made possible by the discovery of a novel nucleotide substitution (G1096A) present only in B and O2 alleles. A rapid and reliable single-tube approach using multiplex PCR with four primers amplifying exons 6 and 7 of the ABO genes followed by simultaneous addition of two restriction enzymes was developed and validated in a population of 150 Swedish blood donors. This technique is the most cost-efficient and informative ABO genotyping method reported to date.


Subject(s)
ABO Blood-Group System/genetics , Genetic Testing , Point Mutation , Alleles , Base Sequence , Blood Donors , Chromosome Mapping , Cloning, Molecular , Genotype , Humans , Molecular Sequence Data , Polymerase Chain Reaction , Reproducibility of Results , Time Factors
18.
Vox Sang ; 65(2): 126-35, 1993.
Article in English | MEDLINE | ID: mdl-8212667

ABSTRACT

Highly efficient anti-blood group A and B immunoadsorbents for extracorporeal treatment were developed by immobilizing A and B trisaccharide and A tetrasaccharide haptens on Sepharose 4FF and Fractogel TSK using three different methods. The adsorption of the IgG and IgM anti-A antibodies was essentially the same regardless of the A hapten used or the method of oligosaccharide coupling. The adsorption of IgM anti-A was found to be more sensitive than IgG anti-A to changes in column flow rate. The binding of both the IgM and IgG antibodies was slightly lower at 37 degrees C than at 22 degrees C. An anti-A/anti-B adsorbent column potentially suitable for treatment of patients was prepared. A column switching system resulted in a more efficient adsorption of antibodies. Hapten leakage from the column was very low. No nonspecific adsorption of plasma proteins to the column (other than traces of albumin) could be detected.


Subject(s)
ABO Blood-Group System/immunology , Haptens , Isoantibodies/isolation & purification , Antigen-Antibody Reactions , Humans , Immunoglobulin G/isolation & purification , Immunoglobulin M/isolation & purification , Immunosorbent Techniques , Isoantibodies/blood , Molecular Structure
19.
CMAJ ; 146(6): 891-7, 1992 Mar 15.
Article in English | MEDLINE | ID: mdl-1371946

ABSTRACT

OBJECTIVE: To provide guidelines for the institution and maintenance of a continuous subcutaneous narcotic infusion program for cancer patients with chronic pain through an analysis of the narcotic requirements and treatment outcomes of patients who underwent such therapy and a comparison of the costs of two commonly used infusion systems. DESIGN: Retrospective study. SETTING: Tertiary care facilities and patients' homes. PATIENTS: Of 481 patients seen in consultation for cancer pain between July 1987 and April 1990, 60 (12%) met the eligibility criteria (i.e., standard medical management had failed, and they had adequate supervision at home). INTERVENTION: Continuous subcutaneous infusion with hydromorphone hydrochloride or morphine started on an inpatient basis and continued at home whenever possible. OUTCOME MEASURES: Patient selectivity, narcotic dosing requirements, discharge rate, patient preference for analgesic regimen, side effects, complications and cost-effectiveness. RESULTS: The mean initial maintenance infusion dose after dose titration was almost three times higher than the dose required before infusion (hydromorphone or equivalent 6.2 v. 2.1 mg/h). Eighteen patients died, and the remaining 42 were discharged home for a mean of 94.4 (standard deviation 128.3) days (extremes 12 and 741 days). The mean maximum infusion rate was 24.1 mg/h (extremes 0.5 and 180 mg/h). All but one of the patients preferred the infusion system to their previous oral analgesic regimen. Despite major dose escalations nausea and vomiting were well controlled in all cases. Twelve patients (20%) experienced serious systemic toxic effects or complications; six became encephalopathic, which necessitated dose reduction, five had a subcutaneous infection necessitating antibiotic treatment, and one had respiratory depression. The programmable computerized infusion pump was found to be more cost-effective than the disposable infusion device after a break-even point of 8 months. CONCLUSIONS: Continuous subcutaneous infusion of opioid drugs with the use of a portable programmable pump is safe and effective in selected patients who have failed to respond to standard medical treatment of their cancer pain. Dose titration may require rapid dose escalation, but this is usually well tolerated. For most communities embarking on such a program a programmable infusion system will be more cost-effective than a disposable system.


Subject(s)
Hydromorphone/administration & dosage , Morphine/administration & dosage , Neoplasms/drug therapy , Pain, Intractable/drug therapy , Costs and Cost Analysis , Female , Humans , Infusion Pumps , Male , Middle Aged , Palliative Care/economics , Patient Satisfaction , Retrospective Studies
20.
Arch Biochem Biophys ; 265(2): 390-406, 1988 Sep.
Article in English | MEDLINE | ID: mdl-3421714

ABSTRACT

Nine neutral and five acidic oligosaccharides were isolated from feces of a preterm (30th postmenstrual week) blood group A nonsecretor infant fed on pooled breast milk. Structural analyses were carried out using sugar and methylation analyses, fast atom bombardment mass spectrometry, and 1H NMR. The acidic oligosaccharides are well-known components of human milk. The neutral oligosaccharides are characteristic of nonsecretor milk. Surprisingly, no secretor gene-dependent oligosaccharides were present in the feces. Another preterm (27th postmenstrual week) blood group A, secretor infant fed on pooled breast milk showed the same fecal oligosaccharide pattern as above during the first week after birth, despite being a secretor individual. Also notable was the absence of blood group A-active oligosaccharides in this sample. Another sample of feces collected 8 weeks later from the latter infant contained the expected blood group A-active oligosaccharides. Furthermore, free sialic acid was present at the cost of the sialyl oligosaccharides seen earlier. Thus, infants born prematurely do not show the same degree of development of oligosaccharide metabolism as their more mature counterparts.


Subject(s)
Feces/analysis , Infant, Premature/metabolism , Milk, Human/metabolism , Oligosaccharides/analysis , Carbohydrate Conformation , Chromatography, Affinity , Disaccharides/analysis , Female , Gas Chromatography-Mass Spectrometry , Gestational Age , Hexoses/analysis , Humans , Infant, Newborn , Magnetic Resonance Spectroscopy , Male , Monosaccharides/analysis , N-Acetylneuraminic Acid , Sialic Acids/analysis
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