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1.
Anaesthesia ; 65(2): 119-23, 2010 Feb.
Article in English | MEDLINE | ID: mdl-19889112

ABSTRACT

This prospective, time series, cross-sectional study was designed to compare the quality of handwritten vs computerised prescriptions in a tertiary 25-bedded cardiothoracic intensive care unit. A total of 14,721 prescriptions for 613 patients were analysed over three periods of investigation: 7 months before; and 5 and 12 months after implementation of a clinical information system with computerised physician order entry capability. Errors in prescribing were common. Only (53%) of handwritten charts analysed had all immediate administration drugs prescribed correctly. Errors included omission of route 81 (8.0%), date of prescription 78 (7.7%), and time to be given 255 (25.2%), and 119 (11.7%) had no dose or an incorrect dose prescribed. All errors of completeness were abolished following implementation. The computerised system led to a significant improvement in prescribing safety, in a clinical area previously highlighted as having a high rate of adverse drug errors. Legibility, completeness and traceability are no longer possible sources of medication errors.


Subject(s)
Drug Prescriptions/standards , Intensive Care Units/standards , Medical Order Entry Systems/standards , Medication Errors/statistics & numerical data , Medication Systems, Hospital/organization & administration , Practice Patterns, Physicians'/standards , Cross-Sectional Studies , England , Handwriting , Humans , Intensive Care Units/organization & administration , Medical Order Entry Systems/organization & administration , Medication Errors/prevention & control , Pharmacy Service, Hospital/organization & administration , Pharmacy Service, Hospital/standards , Prospective Studies , Thoracic Surgical Procedures
2.
Burns ; 30(6): 565-8, 2004 Sep.
Article in English | MEDLINE | ID: mdl-15302422

ABSTRACT

Hepatomegaly is a common finding at autopsy in severely burned children surviving less than 6 months. This study validates a reliable ultrasound method which can be used to identify changes in liver size in severely burned children during acute hospitalization. Thirty-eight children, age 0.5-17 years with burns covering over 40% of their total surface area were studied at autopsy. Liver weight was measured at autopsy and compared to predicted liver weight for age and height. Eighteen had liver size measured by ultrasound within 10 days of death while five had ultrasound liver measures after death just prior to autopsy. All burned children who survived 7 days or more (n = 33) had liver weights at autopsy that were greater than predicted for age and height while all 23 livers measured by ultrasound were greater than predicted. Autopsy weights correlated well with weights estimated by ultrasound, R = 0.824. At autopsy, those who survived 7 days or more had enlarged livers ranging from 142 to 406% of their predicted normal age and height. Common histologic findings include large and small-droplet fat deposits, and cholestasis. The degree of these histologic abnormalities correlated with the increase in liver weight, R = 0.652. Ultrasound is a valid, noninvasive method for measuring liver weight changes in severely burned children during acute hospitalization. Ninety-five percent of the severely burned children from this institute had significant hepatomegaly identified at autopsy.


Subject(s)
Burns/diagnostic imaging , Liver/diagnostic imaging , Adolescent , Autopsy , Body Surface Area , Burns/mortality , Burns/pathology , Child , Child, Preschool , Female , Hepatomegaly/diagnostic imaging , Hepatomegaly/pathology , Humans , Infant , Liver/pathology , Male , Organ Size/physiology , Ultrasonography
3.
Intern Med J ; 34(4): 167-75, 2004 Apr.
Article in English | MEDLINE | ID: mdl-15086696

ABSTRACT

BACKGROUND: Even after high dose chemotherapy (HDT) and autologous haemopoietic stem cell transplantation, the majority of patients with multiple myeloma eventually relapse. AIM: The aim of the present study was to study the -feasibility and outcome of delivering a regimen including in vivo and in vitro purging and double HDT in patients with multiple myeloma. METHODS: Thirty-four patients with advanced multiple myeloma were enrolled in a program of vincristine, doxorubicin and dexamethasone chemotherapy, high dose cyclophosphamide/granulocyte macrophage colony stimulating factor (GM-CSF) stem cell mobilisation, CD34 selection of harvested stem cells (in vitro purging), double HDT (cyclophosphamide/epirubicin in the first, busulphan/melphalan in the second) rescued by CD34(+)-selected cells, the second rescue using cells harvested following the first HDT (in vivo purging) and interferon maintenance. RESULTS: Forty-four per cent of patients completed the program. Fifty-three per cent of withdrawals were as a result of insufficient stem cells. This correlated to previous chemotherapy. Therapy-related mortality was 6%. CD34(+) selection achieved more than a 2-log reduction of CD38(++) cells; in vivo purging achieved 80%. Although similar numbers of CD34(+) cells were reinfused at both HDT, platelet recovery was slower after the second HDT. Additional complete remissions were achieved after each phase of therapy, 3% at the end of vincristine, doxorubicin and dexamethasone and 33% after completing planned HDT. Factors associated with longer overall survival included age less than 60 years (P = 0.044), serum beta-2-microglobulin below 3 micro gamma/L at entry (P = 0.042) and less than 2 months between the two HDT (P = 0.024). The only factor associated with a longer event-free survival was less than 2 months between HDT on study (P = 0.038). CONCLUSIONS: (i) dose intensification with two HDT delivered within 2 months might be associated with a better patient outcome, (ii) early mobilisation should be incorporated in multiple myeloma HDT programs and (iii) higher CD34(+) doses may be required for tandem transplants.


Subject(s)
Antineoplastic Combined Chemotherapy Protocols/administration & dosage , Bone Marrow Purging/methods , Multiple Myeloma/therapy , Stem Cell Transplantation/methods , Adult , Antigens, CD34/immunology , Combined Modality Therapy , Feasibility Studies , Female , Follow-Up Studies , Hematopoietic Stem Cell Mobilization/methods , Humans , Male , Middle Aged , Stem Cells/immunology , Survival Analysis , Time Factors , Transplantation, Autologous , Treatment Outcome
4.
Leuk Lymphoma ; 44(12): 2117-22, 2003 Dec.
Article in English | MEDLINE | ID: mdl-14959857

ABSTRACT

The optimal conditions required to harvest dendritic cells (DC) for immunotherapy were investigated in a series of preliminary investigations using peripheral blood stem cell (PBSC) harvests and blood from patients with myeloma. There was no difference in the number of DC (CMRF44+, CD19-, CD14-) in PBSC mobilized with G-CSF (mean 0.28%, n = 7) compared with GM-CSF (mean 0.24%, n = 6) and apheresis itself did not concentrate DC. In longitudinal studies (n = 10), the peak DC count (day 12 post PBSC harvest) did not correlate with the peak CD34+ cell count or white cell count. A simple affinity purification of DC resulted in a mean 63-fold purification. Affinity enriched suspensions from normal blood contained more DC (mean = 18.8%; n = 5) than those from patients with myeloma (mean = 9.9%; n = 13). The percentage of DC with a lymphoid phenotype (CD11c-, CDw123hi+) was significantly higher in G-CSF mobilized PBSC harvests (22.7%; n = 6) than in peripheral blood samples from patients with myeloma (7.0%; n = 13; p = 0.01). DC endocytosis was normal and did not change throughout the course of the disease. Neither DC numbers nor subsets changed significantly between days 1 and 3 of culture. Current mobilization procedures, optimized for PBSC, need to be altered when harvesting DC.


Subject(s)
Antibodies, Monoclonal/metabolism , Cancer Vaccines , Dendritic Cells/cytology , Dendritic Cells/metabolism , Multiple Myeloma/immunology , Stem Cells/immunology , Antigens, CD34/biosynthesis , Antineoplastic Agents, Alkylating/therapeutic use , Biotinylation , Cyclophosphamide/therapeutic use , Dendritic Cells/immunology , Endocytosis , Flow Cytometry , Granulocyte Colony-Stimulating Factor/metabolism , Granulocyte-Macrophage Colony-Stimulating Factor/metabolism , Humans , Immunotherapy , Leukocytes, Mononuclear/immunology , Phenotype , Time Factors
5.
J Med Genet ; 39(8): 559-66, 2002 Aug.
Article in English | MEDLINE | ID: mdl-12161593

ABSTRACT

EEC syndrome is an autosomal dominant disorder with the cardinal signs of ectrodactyly, ectodermal dysplasia, and orofacial clefts. EEC syndrome has been linked to chromosome 3q27 and heterozygous p63 mutations were detected in unrelated EEC families. In addition, homozygous p63 null mice exhibit craniofacial abnormalities, limb truncations, and absence of epidermal appendages, such as hair follicles and tooth primordia. In this study, we screened 39 syndromic patients, including four with EEC syndrome, five with syndromes closely related to EEC syndrome, and 30 with other syndromic orofacial clefts and/or limb anomalies. We identified heterozygous p63 mutations in three unrelated cases of EEC syndrome, two Iowa white families and one sporadic case in a Filipino boy. One family is atypical for EEC and has features consistent with Hay-Wells syndrome. In this family, the mutation ablates a splice acceptor site and, in the other two, mutations produce amino acid substitutions, R280C and R304Q, which alter conserved DNA binding sites. Germline mosaicism was detected in the founder of the mutation in one case. These three cases show significant interfamilial and intrafamilial variability in expressivity. We also screened p63 in 62 patients with non-syndromic orofacial clefts, identifying an intronic single nucleotide polymorphism but finding no evidence of mutations that would explain even a subset of non-syndromic orofacial clefts. This study supports a common role for p63 in classical EEC syndrome, both familial and sporadic, but not in other related or non-syndromic forms of orofacial clefts.


Subject(s)
Abnormalities, Multiple/genetics , Cleft Lip/genetics , Cleft Palate/genetics , Ectodermal Dysplasia/genetics , Limb Deformities, Congenital/genetics , Membrane Proteins , Mutation/genetics , Phosphoproteins/genetics , Syndactyly/genetics , Trans-Activators/genetics , Asian People/genetics , DNA Mutational Analysis/methods , DNA-Binding Proteins , Exons/genetics , Female , Genes, Tumor Suppressor , Humans , Introns/genetics , Male , Pedigree , RNA Splice Sites/genetics , Syndrome , Transcription Factors , Tumor Suppressor Proteins , White People/genetics
6.
West Indian med. j ; 50(3): 198-202, Sept. 2001. tab
Article in English | MedCarib | ID: med-302

ABSTRACT

The purpose of this study was to determine the prevalence and to assess the efficacy of a single one gram oral dose of azithromycin under direct observed therapy of genital discharge due to Neisseria gonorrhoeae and Chlamydia trachomatis infections in STD clinic attenders in Trinidad and Tobago. All patients with genital discharge and their contacts were given one gram oral dose of azithromycin under direct supervision after collection of urethral and cervical swabs for N gonorrhoeae culture and smear and for C trachomatis antigen detection by ELISA. Clinical and microbiological evaluation was done on those who returned after 7 to 10 days for follow up. Of the 735 patients who were enrolled in the study, 319 (43.4 percent) had N gonorrhoeae and 100 (13.6 percent) had C trachomatis. Only 151 (36 percent) of the 419 patients with a pathogeneic isolate returned for clinical and microbiological assessment. The remaining 268 (64 percent) of the 419 patients were lost to follow up. One hundred and forty three patients (94.7 percent) had total abatement of signs and symptoms after taking azithromycin. One patient (0.65 percent), who had both N gonorrhoeae and C trachomatis, improved clinically with the drug. Seven patients (six with N gonorrhoeae and one with C trachomatis) failed to respond clinically to azithromycin. Microbiological eradication was achieved in 115 (100 percent) patients who had single infection with N gonorrhoeae and in 23 patients (96 percent) with C trachomatis infections, N gonorrhoeae and C trachomatis were eradicated in 10 and 12 patients, respectively, after initial treatment. In two patients with combined infection, N gonorrhoeae continued to be isolated after treatment with azithromycin. A single one gram oral dose of azithromycin under direct supervision is useful in the treatment of uncomplicated genital infection with N gonorrhoeae and C trachomatis in STD clinic attenders in Trinidad. (AU)


Subject(s)
Female , Humans , Male , Adult , Adolescent , Aged , Middle Aged , Gonorrhea/drug therapy , Chlamydia Infections/drug therapy , Azithromycin/administration & dosage , /administration & dosage , Chlamydia trachomatis/drug effects , Patient Compliance , Sexually Transmitted Diseases, Bacterial/drug therapy , Trinidad and Tobago/epidemiology , Aged, 80 and over , Dose-Response Relationship, Drug , Neisseria gonorrhoeae/drug effects , Sexually Transmitted Diseases, Bacterial/epidemiology
7.
West Indian med. j ; 50(3): 198-202, Sept. 2001.
Article in English | LILACS | ID: lil-333375

ABSTRACT

The purpose of this study was to determine the prevalence and to assess the efficacy of a single one gram oral dose of azithromycin under direct observed therapy of genital discharge due to Neisseria gonorrhoeae and Chlamydia trachomatis infections in STD clinic attenders in Trinidad and Tobago. All patients with genital discharge and their contacts were given one gram oral dose of azithromycin under direct supervision after collection of urethral and cervical swabs for N gonorrhoeae culture and smear and for C trachomatis antigen detection by ELISA. Clinical and microbiological evaluation was done on those who returned after 7-10 days for follow-up. Of the 735 patients who were enrolled in the study, 319 (43.4) had N gonorrhoeae and 100 (13.6) had C trachomatis. Only 151 (36) of the 419 patients with a pathogenic isolate returned for clinical and microbiological assessment. The remaining 268 (64) of the 419 patients were lost to follow-up. One hundred and forty-three patients (94.7) had total abatement of signs and symptoms after taking azithromycin. One patient (0.65), who had both N gonorrhoeae and C trachomatis, improved clinically with the drug. Seven patients (six with N gonorrhoeae and one with C trachomatis) failed to respond clinically to azithromycin. Microbiological eradication was achieved in 115 (100) patients who had single infection with N gonorrhoeae and in 23 patients (96) with C trachomatis infection. Of 12 patients with combined infections, N gonorrhoeae and C trachomatis were eradicated in 10 and 12 patients, respectively, after initial treatment. In two patients with combined infection, N gonorrhoeae continued to be isolated after treatment with azithromycin. A single one gram oral dose of azithromycin under direct supervision is useful in the treatment of uncomplicated genital infection with N gonorrhoeae and C trachomatis in STD clinic attenders in Trinidad.


Subject(s)
Humans , Male , Female , Adolescent , Adult , Middle Aged , Gonorrhea , Chlamydia trachomatis , Azithromycin , Anti-Bacterial Agents , Patient Compliance , Sexually Transmitted Diseases, Bacterial/drug therapy , Chlamydia Infections/drug therapy , Trinidad and Tobago , Aged, 80 and over , Chlamydia trachomatis , Neisseria gonorrhoeae , Sexually Transmitted Diseases, Bacterial/epidemiology , Dose-Response Relationship, Drug
8.
J Burn Care Rehabil ; 22(2): 104-10, 2001.
Article in English | MEDLINE | ID: mdl-11302596

ABSTRACT

Chest radiographs (CXRs) have previously been used as a diagnostic tool to detect changes in lung water. In this study CXR changes in severely burned adults, in the absence of an inhalation injury, preceded detectable increases in extravascular lung thermal volume (ELTV) by 3 to 5 days. The hypothesis that early CXR density changes in burned patients have an infectious cause, not related to changes in ELTV, was tested. Blood cultures, CXRs, and ELTV were evaluated during the first 15 days after injury in severely burned adults who had no identified inhalation injury. Chest radiographs were scored daily on a 1 to 5 scale, with 1 = normal, 2 = peribronchial cuffing, 3 = mild interstitial infiltrates, 4 = severe interstitial infiltrates, and 5 = alveolar infiltrates. In all patients, except those who were septic, increases in their CXR density scores correlated well with increases in ELTV. The ELTV/CXR score ratios for septic burn patients on days 1 to 6 postburn was 1.7 +/- 0.2 compared with 4.2 +/- 0.4, (means +/- SEM) for nonseptic (P < .001), whereas the ELTV/CXR score ratios for septic and nonseptic patients, 7 to 15 days postburn, were 3.8 +/- 0.4 and 3.4 +/- 0.5, respectively. We suggest that before any measurable change in ELTV early increases in CXR density scores in burned patients without a concomitant inhalation injury are caused by intraalveolar pneumonitis or hyaline membrane atelectasis and not increased ELTV.


Subject(s)
Burns/complications , Lung Volume Measurements , Lung/diagnostic imaging , Pulmonary Edema/diagnostic imaging , Pulmonary Edema/etiology , Aged , Analysis of Variance , Body Water/metabolism , Burns/metabolism , Dye Dilution Technique , Humans , Least-Squares Analysis , Middle Aged , Radiography, Thoracic , Sepsis/etiology , Sepsis/metabolism
9.
West Indian Med J ; 50(3): 198-202, 2001 Sep.
Article in English | MEDLINE | ID: mdl-11769023

ABSTRACT

The purpose of this study was to determine the prevalence and to assess the efficacy of a single one gram oral dose of azithromycin under direct observed therapy of genital discharge due to Neisseria gonorrhoeae and Chlamydia trachomatis infections in STD clinic attenders in Trinidad and Tobago. All patients with genital discharge and their contacts were given one gram oral dose of azithromycin under direct supervision after collection of urethral and cervical swabs for N gonorrhoeae culture and smear and for C trachomatis antigen detection by ELISA. Clinical and microbiological evaluation was done on those who returned after 7-10 days for follow-up. Of the 735 patients who were enrolled in the study, 319 (43.4%) had N gonorrhoeae and 100 (13.6%) had C trachomatis. Only 151 (36%) of the 419 patients with a pathogenic isolate returned for clinical and microbiological assessment. The remaining 268 (64%) of the 419 patients were lost to follow-up. One hundred and forty-three patients (94.7%) had total abatement of signs and symptoms after taking azithromycin. One patient (0.65%), who had both N gonorrhoeae and C trachomatis, improved clinically with the drug. Seven patients (six with N gonorrhoeae and one with C trachomatis) failed to respond clinically to azithromycin. Microbiological eradication was achieved in 115 (100%) patients who had single infection with N gonorrhoeae and in 23 patients (96%) with C trachomatis infection. Of 12 patients with combined infections, N gonorrhoeae and C trachomatis were eradicated in 10 and 12 patients, respectively, after initial treatment. In two patients with combined infection, N gonorrhoeae continued to be isolated after treatment with azithromycin. A single one gram oral dose of azithromycin under direct supervision is useful in the treatment of uncomplicated genital infection with N gonorrhoeae and C trachomatis in STD clinic attenders in Trinidad.


Subject(s)
Anti-Bacterial Agents/administration & dosage , Azithromycin/administration & dosage , Chlamydia Infections/drug therapy , Chlamydia trachomatis , Gonorrhea/drug therapy , Patient Compliance , Sexually Transmitted Diseases, Bacterial/drug therapy , Adolescent , Adult , Aged , Aged, 80 and over , Chlamydia trachomatis/drug effects , Dose-Response Relationship, Drug , Female , Humans , Male , Middle Aged , Neisseria gonorrhoeae/drug effects , Outcome Assessment, Health Care , Sexually Transmitted Diseases, Bacterial/epidemiology , Trinidad and Tobago/epidemiology
10.
Br J Haematol ; 110(1): 203-9, 2000 Jul.
Article in English | MEDLINE | ID: mdl-10930999

ABSTRACT

The presence of T-cell clones in peripheral blood has been previously shown to be associated with a survival advantage in patients with multiple myeloma and suggests that the expanded T-cell populations may be involved in an anti-tumour response. We studied the T-cell receptor (TCR) repertoire of 38 patients with myeloma to identify and characterize the expanded T-cell populations by flow cytometry. T-cell expansions were found in 79% of the patients. The expansions occurred randomly among the 21 variable regions of the TCR beta chain (Vbeta) studied, representing 62% of the V-beta repertoire, and were stable during an 18-month follow-up. The phenotype of the expanded V-beta populations was predominantly CD8+, CD57+, CD28- and perforin+, which differed significantly from the other non-expanded Vbeta populations. The expression of the apoptosis markers Fas (CD95) and bcl-2 were similar between the expanded and non-expanded Vbeta populations. In conclusion, expanded T-cell populations were frequent in patients with myeloma, they remained unchanged during follow-up and had phenotypic characteristics of cytotoxic T cells. These data add further support to the concept that the T-cell expansions may have an immunoregulatory role in myeloma.


Subject(s)
Multiple Myeloma/immunology , Receptors, Antigen, T-Cell, alpha-beta/immunology , T-Lymphocytes, Cytotoxic/immunology , Aged , Analysis of Variance , CD57 Antigens/analysis , CD8 Antigens/analysis , Female , Flow Cytometry , Humans , Immunophenotyping , Linear Models , Male , Membrane Glycoproteins/analysis , Middle Aged , Perforin , Pore Forming Cytotoxic Proteins , Reference Values
11.
Bone Marrow Transplant ; 25(11): 1175-84, 2000 Jun.
Article in English | MEDLINE | ID: mdl-10849530

ABSTRACT

A potential problem of autologous transplantation in the treatment of multiple myeloma (MM) is the infusion of tumor cells. CD34+ selection has been used to purge autografts in MM and it is also possible to reduce tumour cell contamination of autografts by cytotoxic drug therapy prior to peripheral blood stem cell (PBSC) collection. To evaluate the effectiveness of a protocol combining multiple cycles of high-dose therapy and CD34+ selection to reduce tumour contamination of PBSC autografts, 34 MM patients were entered on a treatment schedule comprising two sequential cycles of mobilisation, CD34+ selection, and transplantation following high-dose therapy. In the second cycle of mobilisation there was a five-fold reduction in tumour contamination of the stem cell harvest (0.5 x 106/kg) compared with the first cycle (2.5 x 106/kg). In the 97 CD34+ selection procedures performed a median of 185 x 108 mononuclear cells (MNC) were processed yielding a median of 0.98 x 108 CD34+-enriched cells. CD34+ cells were enriched 68-fold from 1. 3% to 88.6%. The median yield of CD34+ cells was 42.2%. Following CD34+ selection the tumour cell contamination of the leukapheresis product was reduced by a median of 2.7 logs. This study demonstrates that in multiple myeloma a significant reduction in the malignant contamination of stem cell autografts can be achieved by combining the in vivo purging effect of cytotoxic therapy with in vitro purging by CD34+ selection.


Subject(s)
Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Hematopoietic Stem Cell Mobilization , Hematopoietic Stem Cell Transplantation , Multiple Myeloma/therapy , Adult , Antigens, CD34/blood , Biomarkers/blood , Combined Modality Therapy , Cyclophosphamide/administration & dosage , Epirubicin/administration & dosage , Female , Granulocyte-Macrophage Colony-Stimulating Factor/therapeutic use , Humans , Leukapheresis , Male , Middle Aged , Recombinant Proteins , Regression Analysis , Transplantation, Autologous
12.
WEST INDIAN MED. J ; 46(suppl. 2): 42, Apr. 1997.
Article in English | MedCarib | ID: med-2447

ABSTRACT

An open, non-randomized and non-comparative clinical study was undertaken to assess the efficacy of a single gram dose of azithromycin under supervision in patients with uncomplicated genital discharge and contacts of known STD cases. 151/435 patients (36 percent) with +ve culture for N. gonorrhoeae and antigen +ve for C. trachomatis by ELISA were available for evaluation of azithromycin. There were 119 males (median age 28 years) and 32 females (median age 23 years). Clinical cure was achieved in 95 percent of patients. Bacteriological eradication of N. gonorrhoeae was achieved in all patients with a single infection (115) and in 5/12 with dual infection with C. trachomatis 7 patients had persistence N. gonorrhoeae (5 smear positive and two culture positive) and were subsequently treated with spectinomycin C. trachomatis was eradicated in 23/24 (96 percent) patients with single, and 100 percent patients with mixed, infection during a follow-up assessment with repeat ELISA tests. No patients receiving oral azithromycin reported side effects. This study showed that a single one gram oral dose of azithromycin under supervision is effective in the syndromic management of genital discharge due to N. gonorrhoeae and C. trachomatsis. (AU)


Subject(s)
Humans , Male , Female , Adult , Azithromycin/administration & dosage , Gonorrhea/drug therapy , Chlamydia Infections/drug therapy , Trinidad and Tobago
14.
Genomics ; 24(1): 185-6, 1994 Nov 01.
Article in English | MEDLINE | ID: mdl-7896277

ABSTRACT

SCNN1, a gene encoding a nonvoltage-gated sodium channel, was detected using a rat colon cDNA probe with homology to Caenorhabditis elegans degenerin genes. Human SCNN1 was assigned to chromosome 12 using the NIGMS hybrid mapping panel 2. Mouse SCNN1 was mapped to a conserved linkage group on distal chromosome 6. The observed order of mouse genes was centromere-Raf1-(2.1 +/- 2.1)-Scnn1, Vwf-(1.9 +/- 1.9)-Ntf3, with 0/101 recombinants between Scnn1 and Vwf. No rearrangements of genomic DNA were detected in the linked mouse mutations deaf waddler (dfw) and opisthotonus (opt).


Subject(s)
Chromosomes, Human, Pair 12 , Chromosomes , Genetic Linkage , Sodium Channels/genetics , Animals , Epithelium/metabolism , Humans , Mice , Mice, Inbred C57BL , Rats
15.
Genomics ; 23(2): 309-20, 1994 Sep 15.
Article in English | MEDLINE | ID: mdl-7835879

ABSTRACT

The semidominant mutation Krd (kidney and retinal defects) was identified in transgenic line Tg8052. Krd/+ mice have a high incidence of kidney defects including aplastic, hypoplastic, and cystic kidneys. Retinal defects in Krd/+ mice include abnormal electroretinograms and a reduction of cell numbers that is most extreme in the inner cell and ganglion layers. Viability of Krd/+ mice is strongly influenced by genetic background, and growth retardation is observed in young animals. Homozygosity results in early embryonic lethality. Fluorescence in situ hybridization of a transgene-specific probe localized the insertion site to the distal region of mouse Chromosome 19. The sequence of the insertion site revealed transgene insertion into a LINE element with deletion of a single nucleotide from the 3' terminus of the transgene. A polymorphic microsatellite, D19Umi1, was identified in a junction clone and mapped in several large crosses. D19Umi1 is located 1.7 +/- 1.0 cM distal to Pax2, which encodes a paired type transcription factor expressed in embryonic kidney and eye. Deletion of Pax2 from the transgenic chromosome was demonstrated by Southern analysis of genomic DNA from (Krd/+ x SPRET/Ei)F1 mice. Additional genetic and molecular data are consistent with an approximately 7-cM deletion that includes the loci stearoyl CoA desaturase (Scd1), pale ear (ep), D19Mit17, D19Mit24, D19Mit27, D19Mit11, and Pax2. This deletion, Del(19)TgN8052Mm, will be useful for genetic and functional studies of this region of mouse Chromosome 19.


Subject(s)
Abnormalities, Multiple/genetics , Kidney/abnormalities , Mutation , Retina/abnormalities , Animals , Base Sequence , Chromosome Deletion , Chromosome Mapping , DNA Primers/genetics , DNA, Satellite/genetics , Female , Genes, Homeobox , Genes, Recessive , Genetic Complementation Test , Genetic Markers , Male , Mice , Mice, Inbred C3H , Mice, Inbred C57BL , Mice, Transgenic , Molecular Sequence Data , Polycystic Kidney Diseases/genetics
16.
Hum Mol Genet ; 3(8): 1281-6, 1994 Aug.
Article in English | MEDLINE | ID: mdl-7987303

ABSTRACT

We previously described sequence tags from 58 novel directionally cloned human cDNAs from an enriched retinal pigment epithelial cell line library (Gieser and Swaroop, 1992). The nucleotide sequence of one of the cDNA clones, AA35 (D3S1231E), showed strong homology to the yeast SEC13 gene, required for vesicle biogenesis from endoplasmic reticulum during the transport of proteins. We have designated the human gene SEC13R (SEC13-Related). The amino acid sequence of the SEC13R gene product shows 70% similarity to yeast Sec13p, suggesting that SEC13R may be the human homolog of SEC13. The deduced polypeptide sequence contains several beta-transducin like 'WD40' repeats, and is rich in serine and threonine residues. The 1.4 kb transcript of SEC13R is detected by Northern analysis in many human tissues. However, RT-PCR analysis using two primer sets from different regions of the gene suggests differential expression of alternately spliced transcripts in various tissues. Somatic cell hybrid and in situ hybridization studies localized the SEC13R gene to human chromosome 3p24-p25. A related sequence was mapped to chromosome 18q11.2-q12. SEC13R was physically mapped to a yeast artificial chromosome (YAC) clone spanning the D3S720 marker from the region of the Von Hippel-Lindau disease locus. The mouse Sec13r gene was mapped to the conserved linkage group on chromosome 6 that corresponds to human chromosome 3p24-p25.


Subject(s)
Chromosome Mapping , Chromosomes, Human, Pair 3 , Genetic Linkage , Amino Acid Sequence , Animals , Base Sequence , Humans , Mice , Molecular Sequence Data , Polymerase Chain Reaction , Saccharomyces cerevisiae/genetics , von Hippel-Lindau Disease/genetics
17.
Genomics ; 19(2): 388-90, 1994 Jan 15.
Article in English | MEDLINE | ID: mdl-8188273

ABSTRACT

The mouse genes encoding early growth response 4 (Egr4), annexin IV (Anx4), and transforming growth factor alpha (Tgfa) have been mapped to a linkage group on mouse chromosome 6 that is conserved on human chromosome 2p11-p13. The genes are closely linked, with 0/215 recombinants between Anx4 and Tgfa and 1/215 recombinants between these genes and Egr4. The genes are located approximately 2 cM distal to mnd2, a mouse mutation causing neuromuscular disease. The results demonstrate that mnd2 is located at an internal position within this conserved linkage group.


Subject(s)
Annexin A4/genetics , Genes , Mice/genetics , Transcription Factors/genetics , Transforming Growth Factor alpha/genetics , Animals , Chromosome Mapping , Genetic Linkage , Humans , Neuromuscular Diseases/genetics , Recombination, Genetic , Zinc Fingers
18.
Dig Dis Sci ; 38(6): 996-1003, 1993 Jun.
Article in English | MEDLINE | ID: mdl-8389688

ABSTRACT

Enteric coating of a capsule has been used to deliver a bolus of radioisotope to the ileocecal region. This has allowed quantitative assessment of regional colonic transit in a group of healthy subjects whose proximal colonic transit was accelerated by lactulose 20 ml thrice daily. In this experimental model of diarrhea, codeine delayed transit from mouth to terminal ileum and also delayed transit through the ascending colon from 5.3 +/- 2.5 hr to 7.4 +/- 2.5 hr, N = 11, P < 0.05. Furthermore, codeine delayed whole colon transit, as assessed by geometric center analysis, which showed the delay to be most marked in the right colon with little effect noted in the left colon. In addition, codeine significantly reduced the number of retrograde movements observed and reduced the colonic response to eating. The antidiarrheal effect of codeine appears to be due to a combination of delayed mouth-cecum transit plus an additional delay in the ascending colon. This colonic delay may be partially explained by a reduction in postprandial propulsive movements that were seen in this model of diarrhea.


Subject(s)
Codeine/administration & dosage , Diarrhea/drug therapy , Adult , Capsules , Colon/diagnostic imaging , Colon/drug effects , Colon/physiopathology , Diarrhea/chemically induced , Diarrhea/diagnostic imaging , Diarrhea/physiopathology , Female , Gastrointestinal Transit/drug effects , Humans , Lactulose , Male , Particle Size , Radionuclide Imaging , Sodium Pertechnetate Tc 99m/administration & dosage , Tablets, Enteric-Coated , Time Factors
20.
J Hepatol ; 16(3): 332-7, 1992 Nov.
Article in English | MEDLINE | ID: mdl-1487610

ABSTRACT

The possible aggravation of liver injury by impaired cellular antioxidant function was investigated. A vitamin E-deficient diet (0.5 mg/kg alpha-tocopherol; control 100 mg/kg) significantly reduced rat liver alpha-tocopherol concentrations after 4 weeks (1.8 +/- 1.7 micrograms/g; control 34.4 +/- 2.4 micrograms/g, p < 0.001). The effects of copper loading (Cu, 3 g/kg diet); galactosamine (GalN, 0.85 g/kg i.p.); or carbon tetrachloride (CCl4, 10 mmol/kg i.p.) were examined. Serum aspartate transaminase activity was elevated slightly by vitamin E deficiency but not by hepatic copper accumulation. In vitamin E-replete (E+) and vitamin E-deficient (E-) rats, GalN or CCl4 caused a large and comparable elevation in serum AST and OCT activity. This effect on AST was markedly reduced by copper loading in vitamin E replete (E+) rats, but in E(-) rats copper had significantly less protective effect. Copper also diminished the OCT response to GalN in E+, though not E-, rats. A significant rise in total hepatic alpha-tocopherol content followed administration of GalN or CCl4 in both normocupric and copper-laden E(-) rats. Thus alpha-tocopherol deficiency (a) was not hepatotoxic per se; (b) failed to potentiate the toxicity of copper, GalN or CCL4; but (c) partially abolished the protection by copper against toxin-induced liver injury. Retention of hepatic alpha-tocopherol after liver damage may partly explain low serum vitamin E levels seen in clinical liver disease.


Subject(s)
Chemical and Drug Induced Liver Injury/metabolism , Vitamin E Deficiency/complications , Vitamin E/metabolism , Animals , Chemical and Drug Induced Liver Injury/enzymology , Chemical and Drug Induced Liver Injury/etiology , Male , Oxidoreductases Acting on CH-NH Group Donors/blood , Rats , Rats, Inbred Strains , Vitamin E Deficiency/enzymology
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