Curbing the drugs bill.
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Costs and Cost Analysis↗
Biomedical subjects
M Dean
Publications and source records attributed to M Dean.
Mental care versus public safety in the UK.
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Health Policy↗
Record spending on UK health, but still a long way to go.
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Health Expenditures↗
Subscapularis tendon disruption after Bankart reconstruction for anterior instability.
After undergoing a Bankart repair with a subscapularis tendon and capsular incising technique, four patients were identified who had failure of their subscapularis tendon repair. All had a traumatic event or injury to their shoulder between 1 day and 4 months after operation. The patients presented with findings including recurrent instability, weakness in internal rotation, an abnormal liftoff test, and increased external rotation of the affected extremity. Surgical exploration demonstrated failure of the Bankart repair in two cases in addition to failure of the subscapularis tendon repair in all four. In one patient magnetic resonance imaging was diagnostic of subscapularis tendon disruption. After reoperation was performed, stability was achieved in three of four patients, return of normal internal rotation strength in two, and a normal liftoff test in two. Prompt reexploration and repair of the subscapularis tendon-capsule complex is recommended.
Adolescent↗
Transcriptional activation of immunoglobulin alpha heavy-chain genes by translocation of the c-myc oncogene.
Our previous studies with the mouse myeloma MOPC 315 (IgA, lambda 2) cell line, using myeloma mutants that had deleted the productive alpha heavy (H)-chain gene, had shown that the excluded alpha constant-region (C alpha) allele in these cells is transcriptionally active. Recent reports from several laboratories have demonstrated that in many BALB/c mouse myelomas, including MOPC 315, the DNA segment encoding the c-myc oncogene is translocated to a C alpha allele. The mRNA coding strand of DNA for the c-myc gene is on the opposite strand from the immunoglobulin gene in this locus. We have now investigated the relationship between the c-myc translocation and transcriptional activity of excluded C alpha alleles in IgA- and IgG-producing mouse myeloma lines. We report here that c-myc-C alpha recombination events correlate with demethylation and transcription of C alpha genes. Several novel C alpha RNA species are produced, which are transcribed from the immunoglobulin-gene sense strand. The larger C alpha RNAs appear to contain c-myc sequences. Thus the anti-sense strand of the c-myc gene provides a promoter for transcription of the C alpha gene. This result suggests that in other transformed cells with a c-myc-immunoglobulin gene translocation, including many Burkitt's lymphomas, activation of the adjacent immunoglobulin gene would occur.
Animals↗
A closely linked genetic marker for cystic fibrosis.
Cystic fibrosis is a recessive genetic disorder, characterized clinically by chronic obstructive lung disease, pancreatic insufficiency and elevated sweat electrolytes; affected individuals rarely live past their early twenties. Cystic fibrosis is also one of the most common genetic diseases in the northern European population. The frequency of carriers of mutant alleles in some populations is estimated to be as high as 1 in 20, carrying a concomitant burden of about one affected child in 1,500 births. Because little is known of the essential biochemical defect caused by the mutant gene, a genetic linkage approach based on arbitrary genetic markers and family studies is indicated to determine the chromosomal location of the cystic fibrosis (CF) gene. We have now obtained evidence for tight linkage between the CF locus and a DNA sequence polymorphism at the met oncogene locus. This evidence, combined with the physical localization data for the met locus presented in the accompanying paper, places the CF locus in the middle third of the long arm of chromosome 7, probably between bands q21 and q31.
Chromosome Mapping↗
The human met oncogene is related to the tyrosine kinase oncogenes.
The met oncogene was previously isolated from a chemically transformed human cell line, MNNG-HOS. Recent evidence has demonstrated that two classes of transcripts are expressed from the met proto-oncogene locus. The met oncogene, however, expresses an aberrant RNA which has sequences in common with both transcripts. We now report partial nucleotide sequencing of the human met oncogene and show that met is related to the protein kinase oncogenes and growth factor receptors. The met nucleotide sequence is not identical to that of any published gene, and it is more closely homologous to the tyrosine kinases than to the serine/threonine kinases. Within the tyrosine kinase family, the sequenced met domains are most closely related to the human insulin receptor and the viral abl gene. In situ chromosome hybridization has mapped met to human chromosome 7 band 7q21-q31, a location distinct from that of other kinases. This is also a region associated with nonrandom chromosomal deletions observed in a portion of patients with acute nonlymphocytic leukaemia. The accompanying paper shows that this chromosomal locus is also tightly linked with the human heredity disease cystic fibrosis.
Base Sequence↗
Two novel missense mutations (R766M and R792G) in exon 13 of the CFTR gene in a patient with congenital bilateral absence of the vas deferens.
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Arginine↗
The gatekeeper: an often overlooked part of reform.
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Adult↗
The pharmacokinetics of salicylate in the pregnant Wistar rat.
Sodium salicylate, in a single dose of 50 mg/kg, was administered by iv injection to nonpregnant female and 20-day pregnant Wistar rats. Blood samples (for serum) and urine were collected and analyzed for salicylate, gentisic acid, salicyluric acid, and salicyl glucuronides by HPLC. Pregnant rats showed a significant decrease in body weight-normalized total clearance but no change in absolute total clearance of salicylate. On a body weight-adjusted basis there was a slight increase in the apparent volume of salicylate distribution in pregnancy but this increase becomes highly significant if expressed in absolute terms. The biological half-life of salicylate was significantly increased in late pregnancy. Serum protein binding of salicylate is decreased in pregnancy relative to nonpregnant females but in both groups binding shows a concentration dependence. The partial clearances of both salicyluric and gentisic acids were reduced by pregnancy in the rat whereas that of the salicyl glucuronides appeared unchanged. This latter result in intact pregnant animals contrasts with previously reported decreases in glucuronyltransferase activity in isolated liver preparations from pregnant rats.
Animals↗
Antipyrine pharmacokinetics in the pregnant rat.
Pronounced differences in pharmacokinetic parameters of antipyrine have been found in the 20-day pregnant hooded Wistar rat when compared with nonpregnant controls. Total body clearance falls significantly from 5.93 to 3.5 ml/min/kg in the pregnant rat whereas no significant increase in antipyrine volume of distribution occurs. These changes result in an increase in antipyrine half-life from 109 to 223 min in the pregnant rat. This study demonstrates that reduced hepatic mono-oxygenase capacity exists in the pregnant rat and that this can markedly affect drug clearance in there animals.
Animals↗