Your browser doesn't support javascript.
loading
Show: 20 | 50 | 100
Results 1 - 20 de 32
Filter
1.
Transfus Apher Sci ; 58(1): 65-71, 2019 Feb.
Article in English | MEDLINE | ID: mdl-30591410

ABSTRACT

BACKGROUND: The development of alloantibodies may complicate the management of patients with ß-thalassemia. An extended antigenic matching may reduce the risk of alloimmunization. Our previous study showed that the introduction of molecular red blood cell (RBC) typing allows finding suitable blood units for multi-transfused patients. The aim of this study was to evaluate the benefit of RBC transfusion with extended antigenic match. MATERIALS AND METHODS: At the University of Campania "L. Vanvitelli", we selected ß-thalassemia major patients (age ≤23 years), without preformed alloantibodies. Data of patients receiving transfusion of leukoreduced RBC units for a period of one year with partial better match (PBM) including ABO, RhD, C/c, E/e, K/k antigens and consecutive one year with extended match (EM) including ABO, RhD, C/c, E/e, K/k, Fya/Fyb, Jka/Jkb, M/N, S/s antigens, were compared. RESULTS: Eighteen patients, 8 males and 10 females with a mean age of 15.4 years (6.4 SD) received a mean number of 41.2 (6.0 SD) RBC units transfused with PBM and 41.8 (6.2 SD) with EM protocols. After two years of RBC transfusions with both antigen matching protocols, no new alloantibodies were developed in patients. No significant differences in Hb concentration and volume of RBC transfused were found between PBM and EM protocols. CONCLUSIONS: Thalassemia patients may benefit from receiving RBC transfusions based on extended antigen matching as demonstrated by the lack of new alloantibodies. However, our data show a high concordance between PBM and EM protocols considering pre-transfusion Hb, increment of Hb and volume of RBC transfused.


Subject(s)
Blood Transfusion/methods , beta-Thalassemia/immunology , Adolescent , Female , Humans , Male
2.
Transfus Apher Sci ; 56(2): 206-213, 2017 Apr.
Article in English | MEDLINE | ID: mdl-28040400

ABSTRACT

Red cell alloimmunization is a serious problem in chronically transfused patients. A number of high-throughput DNA assays have been developed to extend or replace traditional serologic antigen typing. DNA-based typing methods may be easily automated and multiplexed, and provide reliable information on a patient. Molecular genotyping promises to become cheaper, being not dependent on serologic immunoglobulin reagents. Patients with hemoglobinopathies could benefit from receiving extended genomic typing. This could limit post transfusional complications depending on subtle antigenic differences between donors and patients. Patient/donor compatibility extended beyond the phenotype Rh/Kell may allows improved survival of transfused units of red blood cells (RBC) and lead to reduced need for blood transfusion and leading to less iron overload and reduced risk of alloimmunization. Here we discuss the advantages and limitations of current techniques, that detect only predefined genetic variants. In contrast, target enrichment next-generation sequencing (NGS) has been used to detect both known and de novo genetic polymorphisms, including single-nucleotide polymorphisms, indels (insertions/deletions), and structural variations. NGS approaches can be used to develop an extended blood group genotyping assay system.


Subject(s)
Blood Group Antigens/genetics , Blood Grouping and Crossmatching/methods , Genotype , Genotyping Techniques/methods , Hemoglobinopathies/genetics , Animals , Female , Male
3.
Acta Myol ; 27: 90-7, 2008 Dec.
Article in English | MEDLINE | ID: mdl-19472918

ABSTRACT

The term limb-girdle muscular dystrophies (LGMD) identify about two dozens of distinct genetic disorders. Additional genes must play a role, since there are LGMD families excluded from any known locus. The aim of our work is to test a number of candidate genes in unclassified LGMD patient and control DNA samples. We selected the following 11 candidate genes: myozenin 1, 2 and 3, gamma-filamin, kinectin-1, enolase-3 beta, ZASP, TRIM 11 and TRIM 17, OZZ and zeta-sarcoglycan. These candidates were chosen for a combination of different reasons: chromosomal position, sequence homology, interaction properties or muscular dystrophy phenotypes in animal models. The exon and flanking intron sequences were subjected to molecular testing by comparative mutation scanning by HT-DHPLC of LGMD patients versus control. We identified a large number of variations in any of the genes in both patients and controls. Correlations with disease or possible modifying effects on the LGMD phenotype remain to be investigated.


Subject(s)
Carrier Proteins/genetics , Contractile Proteins/genetics , Gene Expression Profiling , Genetic Testing/methods , Membrane Proteins/genetics , Microfilament Proteins/genetics , Muscle Proteins/genetics , Muscular Dystrophies, Limb-Girdle/genetics , Mutation/genetics , Adaptor Proteins, Signal Transducing/genetics , Case-Control Studies , Cohort Studies , Filamins , Humans , LIM Domain Proteins , Phosphopyruvate Hydratase/genetics , Sarcoglycans/genetics , Tripartite Motif Proteins , Ubiquitin-Protein Ligase Complexes , Ubiquitin-Protein Ligases/genetics
4.
J Med Genet ; 42(9): 686-93, 2005 Sep.
Article in English | MEDLINE | ID: mdl-16141003

ABSTRACT

BACKGROUND: The limb girdle muscular dystrophies (LGMD) are a heterogeneous group of Mendelian disorders highlighted by weakness of the pelvic and shoulder girdle muscles. Seventeen autosomal loci have been so far identified and genetic tests are mandatory to distinguish among the forms. Mutations at the calpain 3 locus (CAPN3) cause LGMD type 2A. OBJECTIVE: To obtain unbiased information on the consequences of CAPN3 mutations. PATIENTS: 530 subjects with different grades of symptoms and 300 controls. METHODS: High throughput denaturing HPLC analysis of DNA pools. RESULTS: 141 LGMD2A cases were identified, carrying 82 different CAPN3 mutations (45 novel), along with 18 novel polymorphisms/variants. Females had a more favourable course than males. In 94% of the more severely affected patient group, the defect was also discovered in the second allele. This proves the sensitivity of the approach. CAPN3 mutations were found in 35.1% of classical LGMD phenotypes. Mutations were also found in 18.4% of atypical patients and in 12.6% of subjects with high serum creatine kinase levels. CONCLUSIONS: A non-invasive and cost-effective strategy, based on the high throughput denaturing HPLC analysis of DNA pools, was used to obtain unbiased information on the consequences of CAPN3 mutations in the largest genetic study ever undertaken. This broadens the spectrum of LGMD2A phenotypes and sets the carrier frequency at 1:103.


Subject(s)
Calpain/genetics , Genetic Testing/methods , Muscle Proteins/genetics , Muscular Dystrophies, Limb-Girdle/genetics , Phenotype , Adult , Chromatography, High Pressure Liquid/methods , Cohort Studies , DNA/blood , DNA/metabolism , Female , Genes, Recessive , Humans , Male , Mutation , Polymorphism, Genetic
5.
Proc AMIA Symp ; : 344-8, 2001.
Article in English | MEDLINE | ID: mdl-11825208

ABSTRACT

The efficient and reliable capture of vital signs and other bedside data in the non-ICU setting has been a challenging problem for the medical informatics community. The problem is compounded by the complexities associated with storage of this data into an electronic medical record system (EMRS). There are a lack of off-the-shelf solutions that satisfy the basic system requirements of bedside data capture, user authentication, data validation prior to storage, error handling, and convenience. With the current state of technology available, we feel the solution to this problem requires the presence of a PC with custom interface software at the bedside. This allows for the successful interface between available vital signs capture devices, existing EMRS s, and the user. This report summarizes the alternatives we found and our proposed solution to this important problem.


Subject(s)
Medical Records Systems, Computerized , Microcomputers , Monitoring, Physiologic/instrumentation , Point-of-Care Systems , Computer Security , Computer Systems , Humans , Medical Records Systems, Computerized/organization & administration , Microcomputers/economics , Point-of-Care Systems/economics , Systems Integration
6.
J Biol Chem ; 275(21): 15851-60, 2000 May 26.
Article in English | MEDLINE | ID: mdl-10747910

ABSTRACT

Dystrophin is the scaffold of a protein complex, disrupted in inherited muscular dystrophies. At the last 3' terminus of the gene, a protein domain is encoded, where syntrophins are tightly bound. These are a family of cytoplasmic peripheral membrane proteins. Three genes have been described encoding one acidic (alpha1) and two basic (beta1 and beta2) proteins of approximately 57-60 kDa. Here, we describe the characterization of two novel putative members of the syntrophin family, named gamma1- and gamma2-syntrophins. The human gamma1-syntrophin gene is composed of 19 exons and encodes a brain-specific protein of 517 amino acids. The human gamma2-syntrophin gene is composed of at least 17 exons, and its transcript is expressed in brain and, to a lesser degree, in other tissues. We mapped the gamma1-syntrophin gene to human chromosome 8q11 and the gamma2-syntrophin gene to chromosome 2p25. Yeast two-hybrid experiments and pull-down studies showed that both proteins can bind the C-terminal region of dystrophin and related proteins. We raised antibodies against these proteins and recognized expression in both rat and human central neurons, coincident with RNA in situ hybridization of adjacent sections. Our present findings suggest a differentiated role of a modified dystrophin-associated complex in the central nervous system.


Subject(s)
Dystrophin-Associated Proteins , Dystrophin/metabolism , Membrane Proteins/genetics , Muscle Proteins/genetics , Nerve Tissue Proteins/genetics , Amino Acid Sequence , Animals , Calcium-Binding Proteins , Chromosome Mapping , Chromosomes, Human, Pair 2 , Chromosomes, Human, Pair 8 , Cloning, Molecular , Exons , Humans , Immunohistochemistry , In Situ Hybridization , Introns , Membrane Proteins/chemistry , Molecular Sequence Data , Muscle Proteins/analysis , Muscle Proteins/chemistry , Nerve Tissue Proteins/metabolism , Protein Binding , RNA, Messenger/metabolism , Rats , Recombinant Fusion Proteins , Sequence Alignment
7.
Proc Natl Acad Sci U S A ; 97(7): 3130-5, 2000 Mar 28.
Article in English | MEDLINE | ID: mdl-10706618

ABSTRACT

Co-immunoprecipitation experiments in cell extract from cultured cells or target tissues indicated that estrogen receptor was complexed with the retinoblastoma binding protein RIZ in a ligand-dependent manner. Mapping of interaction sites indicated that in both proteins the same regions and motifs responsible for the interaction of transcriptional co-activator and nuclear receptors were involved. In cultured cells, estradiol induced a redistribution of RIZ protein within the nucleus and in the cytoplasm. A similar effect was produced in vivo, in prepuberal rat endometrium, by administration of a physiological dose of estradiol. Therefore, RIZ protein could be a specific effector of estrogen action downstream of the hormone-receptor interaction, presumably involved in proliferation control.


Subject(s)
DNA-Binding Proteins , Estrogens/physiology , Nuclear Proteins/metabolism , Transcription Factors , Zinc Fingers , Base Sequence , Cell Line , DNA Primers , Histone-Lysine N-Methyltransferase , Humans , Receptors, Estrogen/metabolism
8.
Biochem Biophys Res Commun ; 264(3): 983-9, 1999 Nov 02.
Article in English | MEDLINE | ID: mdl-10544042

ABSTRACT

Double-stranded DNA fragments were selected from a random pool by repeated cycles of estrogen receptor-specific immunoprecipitation in the presence of a nuclear extract and PCR amplification (cyclic amplification and selection of target, CAST, for multiple elements). Fragments were cloned and sequence analysis indicated the 5-nucleotide word TTGGC was the most recurrent sequence unrelated to the known estrogen responsive element. Screening a HeLa cell expression library with a probe designed with multiple repeats of this sequence resulted in the identification of a 1700-aa protein showing a complete homology with the product of the human retinoblastoma-interacting zinc-finger gene RIZ. In transfection experiments, RIZ protein was able to bestow estrogen inducibility to a promoter containing an incomplete estrogen responsive element and a TTGGC motif. RIZ protein present in MCF-7 cell nuclear extract retarded the TTGGC-containing probe in an EMSA. Estrogen receptor was co-immunoprecipitated from MCF-7 cell extract by antibodies to RIZ protein and vice versa, thus indicating an existing interaction between these two proteins.


Subject(s)
DNA-Binding Proteins/genetics , Nuclear Proteins/genetics , Receptors, Estrogen/genetics , Transcription Factors , Base Sequence , DNA-Binding Proteins/metabolism , HeLa Cells , Histone-Lysine N-Methyltransferase , Humans , Molecular Sequence Data , Nuclear Proteins/metabolism , Receptors, Estrogen/metabolism , Sequence Analysis , Transfection , Zinc Fingers
9.
Int J Med Inform ; 54(3): 225-53, 1999 Jun.
Article in English | MEDLINE | ID: mdl-10405881

ABSTRACT

Entrusted with the records for more than 1.5 million patients, the Regenstrief Medical Record System (RMRS) has evolved into a fast and comprehensive data repository used extensively at three hospitals on the Indiana University Medical Center campus and more than 30 Indianapolis clinics. The RMRS routinely captures laboratory results, narrative reports, orders, medications, radiology reports, registration information, nursing assessments, vital signs, EKGs and other clinical data. In this paper, we describe the RMRS data model, file structures and architecture, as well as recent necessary changes to these as we coordinate a collaborative effort among all major Indianapolis hospital systems, improving patient care by capturing city-wide laboratory and encounter data. We believe that our success represents persistent efforts to build interfaces directly to multiple independent instruments and other data collection systems, using medical standards such as HL7, LOINC, and DICOM. Inpatient and outpatient order entry systems, instruments for visit notes and on-line questionnaires that replace hardcopy forms, and intelligent use of coded data entry supplement the RMRS. Physicians happily enter orders, problems, allergies, visit notes, and discharge summaries into our locally developed Gopher order entry system, as we provide them with convenient output forms, choice lists, defaults, templates, reminders, drug interaction information, charge information, and on-line articles and textbooks. To prepare for the future, we have begun wrapping our system in Web browser technology, testing voice dictation and understanding, and employing wireless technology.


Subject(s)
Medical Records Systems, Computerized , Computer Terminals , Electronic Data Processing , Hospitals, University , Indiana , Information Storage and Retrieval , Inpatients , Internet , Medical Record Linkage , Microcomputers , Patient Care , Point-of-Care Systems , User-Computer Interface
10.
J Cell Biol ; 141(6): 1301-10, 1998 Jun 15.
Article in English | MEDLINE | ID: mdl-9628887

ABSTRACT

A 104-kD protein was coimmunoprecipitated with the estrogen receptor from the flowtrough of a phosphocellulose chromatography of MCF-7 cell nuclear extract. mAbs to this protein identified several cDNA clones coding for the human 104-kD major vault protein. Vaults are large ribonucleoprotein particles of unknown function present in all eukaryotic cells. They have a complex morphology, including several small molecules of RNA, but a single protein species, the major vault protein, accounts for >70% of their mass. Their shape is reminiscent of the nucleopore central plug, but no proteins of known function have been described to interact with them. Western blot analysis of vaults purified on sucrose gradient showed the presence of estrogen receptor co-migrating with the vault peak. The AER317 antibody to estrogen receptor coimmunoprecipitated the major vault protein and the vault RNA also in the 20,000 g supernatant fraction. Reconstitution experiments of estrogen receptor fragments with the major vault protein mapped the site of the interaction between amino acids 241 and 280 of human estrogen receptor, where the nuclear localization signal sequences are located. Estradiol treatment of cells increased the amount of major vault protein present in the nuclear extract and coimmunoprecipitated with estrogen receptor, whereas the anti-estrogen ICI182,780 had no effect. The hormone-dependent interaction of vaults with estrogen receptor was reproducible in vitro and was prevented by sodium molybdate. Antibodies to progesterone and glucocorticoid receptors were able to coimmunoprecipitate the major vault protein. The association of nuclear receptors with vaults could be related to their intracellular traffic.


Subject(s)
Breast Neoplasms/metabolism , Neoplasm Proteins/metabolism , Receptors, Estrogen/metabolism , Ribonucleoproteins/metabolism , Vault Ribonucleoprotein Particles , Animals , Estradiol/pharmacology , Estrogens/metabolism , Estrogens/pharmacology , Female , HeLa Cells , Humans , Mice , Mice, Inbred BALB C , Neoplasm Proteins/genetics , Precipitin Tests , RNA , Receptors, Cytoplasmic and Nuclear/metabolism , Receptors, Estrogen/genetics , Recombinant Fusion Proteins/genetics , Recombinant Fusion Proteins/metabolism , Ribonucleoproteins/genetics , Tumor Cells, Cultured
11.
FEBS Lett ; 425(1): 7-13, 1998 Mar 20.
Article in English | MEDLINE | ID: mdl-9540997

ABSTRACT

A new member of the dystrobrevin gene family was identified using a bioinformatics approach. Sequence analysis indicates that this gene, named DTN-B, is highly homologous to the rabbit A0, the previously described dystrobrevin (DTN), Torpedo 87 kDa and to the C-terminus of dystrophin. The coiled-coil domain, shown to be the site of interaction between dystrobrevins and dystrophin, is highly conserved. Immunostaining studies indicate that DTN-B and DTN expression is absent in affected muscle fibers from DMD patients and carriers.


Subject(s)
Dystrophin-Associated Proteins , Multigene Family , Neuropeptides/genetics , Amino Acid Sequence , Animals , Blotting, Northern , Blotting, Western , Chromosome Mapping , Chromosomes, Artificial, Yeast , Chromosomes, Human, Pair 2 , DNA, Complementary , Heterozygote , Humans , In Situ Hybridization, Fluorescence , Mice , Molecular Sequence Data , Muscle, Skeletal/metabolism , Muscular Dystrophies/genetics , RNA Splicing , Rabbits , Sequence Homology, Amino Acid , Tumor Cells, Cultured
12.
Hum Mol Genet ; 6(4): 601-7, 1997 Apr.
Article in English | MEDLINE | ID: mdl-9097966

ABSTRACT

The BIO14.6 hamster is a widely used model for autosomal recessive cardiomyopathy. These animals die prematurely from progressive myocardial necrosis and heart failure. The primary genetic defect leading to the cardiomyopathy is still unknown. Recently, a genetic linkage map localized the cardiomyopathy locus on hamster chromosome 9qa2.1-b1, excluding several candidate genes. We now demonstrate that the cardiomyopathy results from a mutation in the delta-sarcoglycan gene that maps to the disease locus. This mutation was completely coincident with the disease in backcross and F2 pedigrees. This constitutes the first animal model identified for human sarcoglycan disorders.


Subject(s)
Cardiomyopathies/genetics , Cytoskeletal Proteins/genetics , Membrane Glycoproteins/genetics , Amino Acid Sequence , Animals , Base Sequence , Blotting, Southern , Blotting, Western , Chromosome Mapping , Cricetinae , Cytoskeletal Proteins/chemistry , Cytoskeletal Proteins/deficiency , Disease Models, Animal , Female , Genetic Linkage , Humans , In Situ Hybridization, Fluorescence , Male , Membrane Glycoproteins/chemistry , Membrane Glycoproteins/deficiency , Mesocricetus , Molecular Sequence Data , Mutation/genetics , Polymerase Chain Reaction , Sarcoglycans , Sequence Deletion , Sequence Homology, Amino Acid
13.
FEBS Lett ; 403(2): 143-8, 1997 Feb 17.
Article in English | MEDLINE | ID: mdl-9042955

ABSTRACT

We found a novel dystrophin-associated protein (DAP) exhibiting almost the same mobility as gamma-sarcoglycan on SDS-PAGE. This novel DAP with basic charge is separated from gamma-sarcoglycan by 2-dimensional PAGE or de-N-glycosylation followed by SDS-PAGE. This DAP is most likely the rabbit homologue of "delta-sarcoglycan", the gamma-sarcoglycan-like protein identified previously [Nigro et al. (1996) Hum. Mol. Genet. 5, 1179-1186], since an internal amino acid sequence from the DAP matched the predicted amino acid sequence of "human delta-sarcoglycan" within the limits of species difference and this DAP was recognized by anti-"delta-sarcoglycan" antibody. The DAP was found to be contained in the sarcoglycan fraction which was prepared by treatment of the dystrophin-DAP complex with n-octyl beta-D-glucoside and crosslinked with beta- and/or gamma-sarcoglycan by a chemical crosslinker, dithiobis(succinimidyl propionate). Therefore, we concluded that the DAP is the fourth component of the sarcoglycan complex.


Subject(s)
Cytoskeletal Proteins/chemistry , Dystrophin/chemistry , Membrane Glycoproteins/chemistry , Amino Acid Sequence , Animals , Blotting, Western , Cross-Linking Reagents , Cytoskeletal Proteins/immunology , Cytoskeletal Proteins/metabolism , Dystrophin/immunology , Dystrophin/metabolism , Glycosylation , Humans , Hydrolysis , Membrane Glycoproteins/immunology , Membrane Glycoproteins/metabolism , Molecular Sequence Data , Rabbits , Sarcoglycans , Sequence Homology, Amino Acid
14.
Nat Genet ; 14(2): 195-8, 1996 Oct.
Article in English | MEDLINE | ID: mdl-8841194

ABSTRACT

Limb-girdle muscular dystrophies (LGMD) are a heterogeneous group of inherited neuromuscular disorders characterized by proximal muscular weakness of the pelvic and shoulder girdles and a variable progression with symptoms, ranging from very severe to mild. One autosomal dominant (LGMD1A, at chromosome 5q22.3-31.3) (ref. 3) and five autosomal recessive (AR) loci responsible for this phenotype have been identified: LGMD2A at 15q (ref. 4); LGMD2B at 2p (ref. 5), LGMD2C at 13q (ref. 6), LGMD2D at 17q (ref. 7) and LGMD2E at 4q (refs 8,9). In the muscle membrane, dystrophin associates with several proteins and glycoproteins organized in two main subcomplexes: the dystroglycan (DG) and sarcoglycan (SG) complexes. The genes for LGMD2C, LGMD2D and LGMD2E code for proteins of the SG complex. We recently mapped a sixth AR form of LGMD, LGMD2F, to chromosome 5q33-34 in two Brazilian families. In the same chromosomal interval we also mapped the delta SG gene, encoding a novel 35-kD component of the sarcoglycan (SG) complex. We now show that a homozygous mutation in the delta SG gene (a single nucleotide deletion that alters its reading frame) is the cause of LGMD2F.


Subject(s)
Cytoskeletal Proteins/genetics , Frameshift Mutation/genetics , Genes, Recessive/genetics , Membrane Glycoproteins/genetics , Muscular Dystrophies/genetics , Adolescent , Adult , Brazil , Child , Child, Preschool , Chromosomes, Human, Pair 5/genetics , Cytoskeletal Proteins/analysis , DNA Mutational Analysis , DNA, Complementary/genetics , Dystrophin/analysis , Female , Homozygote , Humans , Male , Membrane Glycoproteins/analysis , Molecular Sequence Data , Muscle, Skeletal/pathology , Muscular Dystrophies/pathology , Pelvis , Sarcoglycans , Sarcolemma/chemistry , Shoulder
15.
Hum Mol Genet ; 5(8): 1179-86, 1996 Aug.
Article in English | MEDLINE | ID: mdl-8842738

ABSTRACT

Mutations in any of the genes encoding the alpha, beta or gamma-sarcoglycan components of dystrophin-associated glycoproteins result in both sporadic and familial cases of either limb-girdle muscular dystrophy or severe childhood autosomal recessive muscular dystrophy. The collective name 'sarcoglycanopathies' has been proposed for these forms. We report the identification of a fourth member of the human sarcoglycan family. We named this novel cDNA delta-sarcoglycan. Its mRNA expression is abundant in striated and smooth muscles, with a main 8 kb transcript, encoding a predicted basic transmembrane glycoprotein of 290 amino acids. Antibodies specifically raised against this protein recognized a single band at 35 kDa on western blots of human and mouse muscle. Immunohistochemical staining revealed a unique sarcolemmal localization. FISH, radiation hybrid and YAC mapping concordantly linked the delta-sarcoglycan gene to 5q33, close to D5S487 and D5S1439. The gene spans at least 100 kb and is composed of eight exons. The identification of a novel sarcoglycan component modifies the current model of the dystrophin-glycoprotein complex.


Subject(s)
Chromosomes, Human, Pair 5/genetics , Cytoskeletal Proteins/genetics , Membrane Glycoproteins/genetics , Amino Acid Sequence , Animals , Base Sequence , Child , Chromosome Mapping , Cytoskeletal Proteins/chemistry , DNA, Complementary/genetics , DNA, Complementary/isolation & purification , Gene Expression , Humans , Immunohistochemistry , Membrane Glycoproteins/chemistry , Mice , Models, Biological , Molecular Sequence Data , Molecular Weight , Muscles/metabolism , Mutation , Rabbits , Sarcoglycans , Sarcolemma/chemistry , Sequence Homology, Amino Acid , Tissue Distribution
16.
Aliment Pharmacol Ther ; 6(5): 597-607, 1992 Oct.
Article in English | MEDLINE | ID: mdl-1420751

ABSTRACT

A multicentre, randomized, double-blind, placebo-controlled study was conducted to evaluate the efficacy and safety of ranitidine 150 mg and 300 mg in 342 patients with erosive oesophagitis. Treatment was given four times daily, and continued for 12 weeks or until healing (that is, normal or only erythematous mucosa). Erosive oesophagitis healing rates, as determined by endoscopy, were significantly greater in ranitidine-treated patients by 4 weeks compared with those of placebo-treated patients. By 12 weeks, erosive oesophagitis healing rates were 83 and 81% for ranitidine-treated patients (150 and 300 mg, respectively) and 58% for placebo-treated patients (P less than or equal to 0.001, ranitidine vs. placebo). Symptomatic relief was achieved within 24 hours after starting either dosage of ranitidine. Heartburn frequency (P less than 0.001) and severity (P less than 0.001), as well as antacid consumed per week (P less than 0.001), were reduced in both ranitidine groups in comparison with placebo. Healing rates and symptom relief were similar in the two ranitidine groups. Both dosages of ranitidine were well tolerated. Ranitidine (150 mg) given four times daily appears to be as effective as 300 mg ranitidine given four times daily in patients with moderate to severe oesophageal erosions.


Subject(s)
Esophagitis/drug therapy , Ranitidine/therapeutic use , Adult , Antacids/therapeutic use , Circadian Rhythm/physiology , Dose-Response Relationship, Drug , Double-Blind Method , Esophagus/drug effects , Esophagus/physiology , Female , Heartburn/drug therapy , Heartburn/prevention & control , Humans , Male , Ranitidine/adverse effects
17.
J Appl Physiol (1985) ; 68(3): 1265-74, 1990 Mar.
Article in English | MEDLINE | ID: mdl-2187851

ABSTRACT

Movements of the suprasternal fossa during spontaneous breathing monitored with the surface inductive plethysmograph (SIP) have been shown to reflect changes of intrapleural pressure in conscious humans. Calibration of this device in anesthetized intubated dogs was accomplished by adjusting the electrical gain of its analog waveform to be equivalent to changes of airway pressure during inspiratory efforts against an occluded airway. This procedure, denoted the occlusion test, was also used to identify the site of esophageal balloon catheter placement for its recording of intrapleural pressure deflections. The validity of SIP-derived estimates of inspiratory and expiratory pulmonary resistances and lung compliance was established by finding close agreement with measurements obtained with intraesophageal pressure changes during 1) unimpeded spontaneous breathing, 2) inspiratory resistive loading, 3) bronchoprovocation with aerosolized carbachol, 4) mechanical ventilatory modalities, and 5) induced pulmonary edema. Therefore, movements of the suprasternal fossa with respiration can be reliably transformed into quantitative or semiquantitative changes of intrapleural pressure in anesthetized intubated dogs during major alterations of pulmonary mechanics.


Subject(s)
Pleura/physiology , Respiratory Mechanics/physiology , Airway Resistance/physiology , Animals , Bronchial Provocation Tests , Carbachol/pharmacology , Dogs , Intermittent Positive-Pressure Breathing , Lung Compliance/physiology , Movement , Plethysmography , Positive-Pressure Respiration , Pressure , Pulmonary Edema/physiopathology , Respiratory Mechanics/drug effects , Stress, Mechanical
18.
J Appl Physiol (1985) ; 66(1): 410-20, 1989 Jan.
Article in English | MEDLINE | ID: mdl-2917945

ABSTRACT

We describe a single-posture method for deriving the proportionality constant (K) between rib cage (RC) and abdominal (AB) amplifiers of the respiratory inductive plethysmograph (RIP). Qualitative diagnostic calibration (QDC) is based on equations of the isovolume maneuver calibration (ISOCAL) and is carried out during a 5-min period of natural breathing without using mouthpiece or mask. In this situation, K approximates the ratio of standard deviations (SD) of the uncalibrated changes of AB-to-RC volume deflections. Validity of calibration was evaluated by 1) analyzing RIP waveforms during an isovolume maneuver and 2) comparing changes of tidal volume (VT) amplitude and functional residual capacity (FRC) level measured by spirometry (SP) with RIP values. Comparisons of VT(RIP) to VT(SP) were also obtained in a variety of postures during natural (uninstructed) preferential RC and AB breathing and with voluntary changes of VT amplitude and FRC level. VT(RIP)-to-VT(SP) comparisons were equal to or closer than published reports for single posture, ISOCAL, multiple- and linear-regression procedures. QDC of RIP in supine posture with comparisons to SP in that posture and others showed better accuracy in horizontal than upright postures.


Subject(s)
Plethysmography/methods , Respiration , Calibration , Functional Residual Capacity , Humans , Models, Theoretical , Posture , Tidal Volume
19.
Ann Intern Med ; 102(5): 573-6, 1985 May.
Article in English | MEDLINE | ID: mdl-3885813

ABSTRACT

Recently the Food and Drug Administration approved cimetidine for the treatment of benign gastric ulcer. Approval was based in part on the results of our large multicenter trial involving 172 patients with benign gastric ulcer between 0.5 and 2.5 cm in diameter: 87 were randomly assigned to receive cimetidine (300 mg four times daily) and 85 to receive placebo. Cimetidine treatment resulted in significantly more rapid healing than placebo; after 2 and 6 weeks of therapy, 10.0% and 44.8% of patients receiving placebo were healed, as compared to 22.6% and 65.1% receiving cimetidine. The results of our study were compared with the time-response curve previously published (0, 4, and 8 weeks of therapy). The combined data yielded linear healing rates for the first 8 weeks of therapy (r greater than 0.99 for both cimetidine and placebo). These studies can be used to define expectations for healing of benign gastric ulcer, and we recommend follow-up intervals of 8 and, if unhealed, 16 weeks.


Subject(s)
Cimetidine/therapeutic use , Stomach Ulcer/drug therapy , Adult , Aged , Clinical Trials as Topic , Double-Blind Method , Female , Gastroscopy , Humans , Male , Middle Aged , Placebos , Random Allocation , Research Design , Stomach Ulcer/pathology , Time Factors
20.
Am Rev Respir Dis ; 130(4): 588-93, 1984 Oct.
Article in English | MEDLINE | ID: mdl-6486558

ABSTRACT

Both scalar tracings and XY plots of rib cage (RC) and abdominal (AB) excursions were analyzed to detect asynchronous and/or paradoxic motion of one compartment with respect to the other in an effort to distinguish differences between normal subjects and patients with chronic obstructive pulmonary disease (COPD). An inspiratory asynchrony index (IAI) was obtained by connecting a straight line from beginning inspiration to end inspiration of the RC-AB loop, and dividing the area enclosed by the inspiratory portion by the tidal volume. In like manner, an expiratory asynchrony index (EAI) was computed. Values of IAI and EAI in the supine posture were greater in patients with COPD than in normal subjects, and such differences were consistently demonstrated during natural and voluntarily controlled abdominal breathing. Paradoxic motion as percent of volume or time period of inspiratory and expiratory compartmental excursions was indicated when RC or AB compartments moved in an opposite direction to the sum of the two. During natural breathing, paradoxic motion was almost absent in normal subjects and variably present in patients with COPD. Voluntarily controlled breathing patterns produced increased IAI, EAI, and paradoxic motion. Passive tilting from supine to the upright posture did not affect indexes in normal subjects but reduced asynchronous and paradoxic motion of the RC in patients with COPD. Other indexes of loop analysis, such as phase angle and maximal compartment amplitude/tidal volume, were not as consistent in distinguishing between normal subjects and patients with COPD during natural and voluntarily controlled breathing patterns.(ABSTRACT TRUNCATED AT 250 WORDS)


Subject(s)
Abdomen/physiopathology , Lung Diseases, Obstructive/physiopathology , Movement , Ribs/physiopathology , Adult , Female , Humans , Male , Middle Aged , Posture , Respiration , Tidal Volume , Time Factors
SELECTION OF CITATIONS
SEARCH DETAIL
...