Subject(s)
Hereditary Sensory and Autonomic Neuropathies/genetics , Point Mutation/genetics , Receptor, trkA/genetics , 3T3 Cells , Amino Acid Substitution/genetics , Animals , Base Sequence , Exons/genetics , Female , Humans , Male , Mice , Pedigree , Receptor, trkA/chemistry , Receptor, trkA/metabolismABSTRACT
The increased risk of hemodialysis patients for infections sustained by hepatitis viruses is likely to extend to a newly discovered parenterally transmitted virus, HGBV-C/HGV, able to cause acute and chronic hepatitis. The aim of this study was to assess the prevalence and clinical relevance of this infection in Italian hemodialysis patients. Nineteen of 100 patients (19%) on maintenance hemodialysis were viremic for HGBV-C/HGV, and all of them were infected with a HGV-like genotype. Eight of these patients were coinfected by hepatitis B or hepatitis C viruses. A clinical picture of chronic hepatitis was not appreciable in patients with isolated HGV infection and the presence of HGV did not appear to modify the clinical course of hepatitis B and hepatitis C infections.
Subject(s)
Flaviviridae , Hepatitis, Viral, Human/epidemiology , Kidney Failure, Chronic/epidemiology , Kidney Failure, Chronic/virology , Renal Dialysis , Adult , Aged , Blood Transfusion , DNA, Viral/analysis , Female , Hepacivirus , Hepatitis B virus , Humans , Italy/epidemiology , Kidney Failure, Chronic/therapy , Male , Middle Aged , Molecular Sequence Data , Prevalence , Risk Factors , Sequence Homology, Nucleic AcidABSTRACT
To put Council's project on improving access to hospice and specialist palliative care services by members of the black and minority ethnic communities into context, palliative care will be defined, and the scope of palliative care services currently available in the UK outlined. Palliative care is the active total care of patients whose disease no longer responds to curative treatment. It is provided through a network of home-care, day-care, hospital support and hospital or hospice based in-patient services. These services are accessed mainly through GPs or hospital consultants and the extent to which people are referred depends on the knowledge of hospital consultants and GPs, and their perception of the value of the palliative care service to their patients. Council's project on improving access was supported by Cancer Relief Macmillan Fund and Help the Hospices as well as receiving a grant from the NHS Ethnic Minorities Unit. The report describes how the specialist palliative care services are currently provided in three areas with high minority ethnic populations and contains a series of recommendations around ethnic monitoring, equal opportunities strategies, staff training, communications and the provision of a more culturally sensitive service provision.
Subject(s)
Black or African American , Ethnicity , Health Services Accessibility , Hospices , Minority Groups , Neoplasms/therapy , Palliative Care , Aged , Black People , Humans , Middle Aged , Socioeconomic Factors , United KingdomABSTRACT
The Drosophila dishevelled gene (dsh) encodes a secreted glycoprotein, which regulates cell proliferation, acting as a transducer molecule for developmental processes, including segmentation and neuroblast specification. We have isolated and characterized cDNA clones from two different human dsh-homologous genes, designated as DVL-1 and DVL-3. DVL-1 and DVL-3 putative protein products show 64% amino acid identity. The DVL-1 product is 50% identical to dsh and 92% to a murine dsh homologue (Dvl-1). Both human DVL genes are widely expressed in fetal and adult tissues, including brain, lung, kidney, skeletal muscle and heart. DVL-1 locus maps to chromosome 1p36 and DVL-3 to chromosome 3q27. DVL-1 locus on chromosome 1 corresponds to the murine syntenic region where Dvl-1 is located. DVL-1 and DVL-3 are members of a human dsh-like gene family, which is probably involved in human development. Although the precise role of these genes in embryogenesis is only conjectural at present, the structural and evolutionary characteristics suggest that mutations at their loci may be involved in neural and heart developmental defects.
Subject(s)
Chromosome Mapping , Chromosomes, Human, Pair 1/genetics , Chromosomes, Human, Pair 3/genetics , DNA, Complementary/genetics , Phosphoproteins , Proteins/genetics , Adaptor Proteins, Signal Transducing , Adult , Amino Acid Sequence , Animals , Cloning, Molecular , Dishevelled Proteins , Drosophila/genetics , Drosophila Proteins , Gene Expression Regulation, Developmental , Humans , Molecular Sequence Data , Organ Specificity , RNA, Messenger/analysis , Sequence Analysis, DNA , Sequence Homology, Amino Acid , Sequence Homology, Nucleic AcidABSTRACT
DiGeorge syndrome (DGS) is a developmental defect of some of the neural crest derivatives. Most DGS patients show haploinsufficiency due to interstitial deletions of the proximal long arm of chromosome 22. Deletions of 22q11 have also been reported with patients with the velocardio-facial syndrome and familial conotruncal heart defects. It has been suggested that the wide phenotype spectrum associated with 22q11 monosomy is a consequence of contiguous-gene deletions. We report the isolation of human cDNAs homologous to the Drosophila dishevelled (dsh) segment-polarity gene. Sequences homologous to the 3' UTR of these transcripts (DVL-22) were positioned within the DGS critical region and were found to be deleted in DGS patients. Human DVL mRNAs are expressed in several fetal and adult tissues, including the thymus and, at high levels, the heart. Two transcripts, 3.2 and 5kb, were detected, in northern blot analysis, with different expression patterns in the surveyed tissues when different cDNAs were used. The isolated cDNAs exhibit high amino acid homology with the mouse and Xenopus Dvl-1 gene, the only other vertebrate dsh homologues so far isolated. The pivotal role of dsh in fly development suggests an analogous key function in vertebrate embryogenesis of its homologue genes. Since DGS may be due to perturbation of differentiation mechanisms at decisive embryological stages, a Dsh-like gene in the small-region overlap (SRO) might be a candidate for the pathogenesis of this disorder.
Subject(s)
DiGeorge Syndrome/genetics , Phosphoproteins , Proteins/genetics , Sequence Deletion , Sequence Homology, Nucleic Acid , Adaptor Proteins, Signal Transducing , Amino Acid Sequence , Animals , Base Sequence , Chromosome Mapping , Cloning, Molecular , DNA, Complementary/genetics , Dishevelled Proteins , Drosophila/genetics , Drosophila Proteins , Gene Expression Regulation, Developmental , Genes, Insect/genetics , Humans , Molecular Sequence Data , Organ Specificity , RNA, Messenger/analysis , Sequence Homology, Amino Acid , Xenopus ProteinsABSTRACT
A boy, born to first cousin parents of Algerian origin, first presented at the age of 9 years with growth failure, mental retardation, and dysmorphic facies. Progressive vitiligo developed from the age of 12 and distal duplication of the urethra was later recognised. The basis of this syndrome remains to be determined; autoimmune disease, chromosomal breakage syndromes, and other neurocutaneous syndromes have been excluded.
Subject(s)
Abnormalities, Multiple/genetics , Autoimmune Diseases/genetics , Growth Disorders/genetics , Intellectual Disability/genetics , Urethra/abnormalities , Vitiligo/genetics , Child , Humans , Male , SyndromeABSTRACT
We looked retrospectively for all cases of toxic epidermal necrolysis that occurred in France over a 5-year period to appreciate the incidence of this disorder and its drug etiology. Of the 399 cases identified, we obtained detailed information on 344 cases and validated 253 cases. From response rates (66% to 98%), we estimated the actual total number of cases to be 333, and the incidence of toxic epidermal necrolysis in France to 1.2 cases per million per year. An independent estimation derived from death certificates gave a figure of 1.3 cases per million per year. When the number of cases with a given drug present were related to the defined daily doses of that drug sold over the 5-year period, the highest ratios were for sulfadiazin (230.10(-8], isoxica (41.10(-8], oxyphenbutazone (18.10(-8], phenytoin (14.10(-8], fenbufen (13.10(-8], and cotrimoxazole (12.10(-8]. This first nationwide study confirmed the rarity of toxic epidermal necrolysis. Within the two main classes of responsible drugs (antibacterial sulfonamides and nonsteroidal anti-inflammatory agents) the risks linked to different drugs appeared quite different, even for closely chemically related products.
Subject(s)
Stevens-Johnson Syndrome/epidemiology , Adolescent , Adult , Child , Death Certificates , Drug-Related Side Effects and Adverse Reactions , Female , France/epidemiology , Humans , Incidence , Male , Middle Aged , Reproducibility of Results , Retrospective Studies , Risk Factors , Stevens-Johnson Syndrome/etiology , Stevens-Johnson Syndrome/mortality , SurvivalABSTRACT
Eighty-seven patients with toxic epidermal necrolysis were observed at Hôpital Henri Mondor in Créteil, France, over the last 12 years. The mean percentage of body surface area involved was 39%. Erosive mucous membrane lesions, identical to those of Stevens-Johnson syndrome, were present in all but three cases. Necrolysis was sometimes generalized within 24 hours but usually spread progressively after a Stevens-Johnson syndrome-like aspect at the onset. Mortality was 25%. Infection, mainly with Staphylococus aureus and Pseudomonas aeruginosa, was the first cause of death, clearly responsible in ten of 20 cases. Age, extension of necrolysis, idiopathic nature of toxic epidermal necrolysis, ingestion of many drugs, elevation of urea, creatinine, and glucose levels, neutropenia, lymphopenia, and thrombocytopenia were statistically linked to a bad prognosis. A multivariant analysis showed that three of these prognosis factors are of paramount importance, namely: age, area of necrolysis, and serum urea level. Pigmentary changes and sicca syndrome were frequently observed sequelae in survivors.
Subject(s)
Stevens-Johnson Syndrome , Adolescent , Adult , Aged , Aged, 80 and over , Child , Child, Preschool , Diagnosis, Differential , Eye Diseases/etiology , Female , Follow-Up Studies , Humans , Male , Middle Aged , Prognosis , Skin/pathology , Staphylococcal Scalded Skin Syndrome/diagnosis , Stevens-Johnson Syndrome/complications , Stevens-Johnson Syndrome/diagnosis , Stevens-Johnson Syndrome/mortality , Stevens-Johnson Syndrome/pathology , Stevens-Johnson Syndrome/physiopathology , Xerophthalmia/etiologySubject(s)
Stevens-Johnson Syndrome/therapy , Anti-Bacterial Agents/therapeutic use , Bacterial Infections/drug therapy , Fluid Therapy , Humans , Plasmapheresis , Steroids/administration & dosage , Steroids/adverse effects , Steroids/therapeutic use , Stevens-Johnson Syndrome/complications , Surgical FlapsABSTRACT
Between 1972 and 1985, 87 patients with toxic epidermal necrolysis (TEN) were admitted to the dermatological intensive care unit at Hôpital Henri Mondor, Créteil, France. The culpable drug was determined by standardized criteria. Only three patients had received no drugs before the onset of TEN. Most patients (71 of 87) were receiving more than one drug. Patients had taken an average of 4.4 +/- 3.4 drugs each. A culpable drug was determined in 67 patients (77%). The mean time from first drug administration to onset of TEN was 13.6 +/- 8.4 days. The culprit drugs included the following: sulfonamides, 18 cases, and especially sulfamethoxazole and trimethoprim, 12; anticonvulsants, seven (barbiturates and carbamazepine only); nonsteroidal anti-inflammatory drugs, 29 (especially the phenylbutazone derivative, 16, and oxicam derivatives, 10); allopurinol, three; chlormezanone, three; and others, seven. Aspirin, antipyretics, and antibiotics are infrequently implicated in this series. The pattern of culprit drugs changed with years. The level of sulfonamide-related TEN remained the same, while incidence of nonsteroidal anti-inflammatory drug-induced TEN increased sharply, the introduction of oxicam derivatives being in part responsible.
Subject(s)
Drug-Related Side Effects and Adverse Reactions , Stevens-Johnson Syndrome/etiology , Adolescent , Adult , Aged , Aged, 80 and over , Anti-Inflammatory Agents, Non-Steroidal/adverse effects , Child , Child, Preschool , Female , Humans , Male , Middle Aged , Stevens-Johnson Syndrome/mortality , Sulfonamides/adverse effects , Time FactorsABSTRACT
Epidermal cells (EC) were cultured without stimulation and the effect of these EC culture supernatants (ECCS) on human in vitro B-cell response was determined. Supernatants obtained between Days 5 and 7 were able to replace monocytes in the antibody response to the particulate antigen trinitrophenyl-polyacrylamide (TNP-PAA). These results were obtained when highly monocyte-depleted cultures (less than 0.5% peroxidase-positive cells) were used and were reproduced with supernatants from several different EC cultures. ECCS could not substitute for T cells in the T-dependent response to TNP-PAA. They contained an interleukin 1 (IL-1) activity but no interleukin 2 or B-cell growth factor (BCGF) activities. We tested the effect of ECCS on the proliferative response of highly monocyte-depleted B cells cultured at low cell density costimulated with anti-u antibody and BCGF. ECCS had no BCGF-like activity of its own but did potentiate the effect of BCGF. Thus EC cultures produce IL-1-like factor(s) which act directly on the early stages of B-cell activation.
