Quality improvement report: The “jaundice hotline” for the rapid assessment of patients with jaundice

ProblemPatients with jaundice require rapid diagnosis and treatment, yet such patients are often subject to delay.DesignAn open referral, rapid access jaundice clinic was established by reorganisation of existing services and without the need for significant extra resources.

Background and setting

A large general hospital in a largely rural and geographically isolated area.

Key measures for improvement

Waiting times for referral, consultation, diagnosis, and treatment, length of stay in hospital, and general practitioners'' and patients'' satisfaction with the service.

Strategies for change

Referrals were made through a 24 hour telephone answering machine and fax line. Initial assessment of patients was carried out by junior staff as part of their working week. Dedicated ultrasonography appointments were made available.

Effects of change

Of 107 patients seen in the first year of the service, 62 had biliary obstruction. The mean time between referral and consultation was 2.5 days. Patients who went on to endoscopic retrograde cholangiopancreatography waited 5.7 days on average. The mean length of stay in hospital in the 69 patients who were admitted was 6.1 days, compared with 11.5 days in 1996, as shown by audit data. Nearly all the 36 general practices (95%) and the 30 consecutive patients (97%) that were surveyed rated the service as above average or excellent.

Lessons learnt

An open referral, rapid access service for patients with jaundice can shorten time to diagnosis and treatment and length of stay in hospital. These improvements can occur through the reorganisation of existing services and with minimal extra cost.     

Rapid corepressor exchange from the trp-repressor/operator complex: An NMR study of [ul-13C/15N]-l-tryptophan

Summary [ul-¹³C/¹⁵N]-l-tryptophan was prepared biosynthetically and its dynamic properties and intermolecular interaction with a complex of Escherichia coli trp-repressor and a 20 base-pair operator DNA were studied by heteronuclear isotope-edited NMR experiments. The resonances of the free and bound corepressor (l-Trp) were unambiguously identified from gradient-enhanced ¹⁵N–¹H HSQC, ¹³C–¹H HSQC, ¹³C-and ¹⁵N-edited 2D NOESY spectra. The exchange off-rate of the corepressor between the bound and free states was determined to be 3.4±0.52 s^–1 at 45°C, almost three orders of magnitude faster than the dissociation of the protein-DNA complex. Examination of the experimental NOE buildup curves indicates that it may be desirable to use longer mixing times than would normally be used for a large molecule, in order to detect weak intermolecular NOEs in the presence of exchange. Intermolecular NOEs from bound corepressor to trp-repressor and DNA were analyzed with respect to the mechanism of ligand exchange. This analysis suggests that, in order for the ligand to diffuse out of the complex, there must be significant movement or breathing of the protein and/or DNA.Abbreviations NOESY nuclear Overhauser enhancement spectroscopy - HSQC heteronuclear single-quantum coherence - PFG pulsed field gradient - l-Trp l-tryptophan     

Pregnant teens in prison. Prevalence,management, and consequences.

To estimate the number of pregnant and parenting teens currently incarcerated and to assess the correctional health care and social services provided to this target population, we surveyed 430 juvenile detention and long-term correctional facilities in the United States that incarcerate adolescent girls. Of these, 261 (61%) institutions responded and are included in the analysis. Of these facilities, 68% estimated that they were holding 1 to 5 pregnant adolescents on a given day, with a reported yearly (September 1991 to September 1992) census of 2,000 pregnant teenagers and 1,200 teenaged mothers. Nearly half of the facilities (45%) continue to incarcerate after it is determined that a youth is pregnant. Of those institutions that incarcerate pregnant adolescents, 31% provide no prenatal services and 70% provide no parenting classes. Of these facilities, 60% reported at least 1 obstetric complication in their pregnant population. A substantial number of pregnant and parenting adolescents are in custody in the United States. General community standards of health and social services for pregnant and parenting teenagers are not being met by the institutions that incarcerate them.     

Monoclonal antibodies against chicken type V collagen: production, specificity, and use for immunocytochemical localization in embryonic cornea and other organs

Two monoclonal antibodies have been produced against chick type V collagen and shown to be highly specific for separate, conformational dependent determinants within this molecule. When used for immunocytochemical tissue localization, these antibodies show that a major site for the in situ deposition of type V is within the extracellular matrices of many dense connective tissues. In these, however, it is largely in a form unavailable to the antibodies, thus requiring a specific “unmasking” treatment to obtain successful immunocytochemical staining. The specificity of these two IgG antibodies was determined by inhibition ELISA, in which only type V and no other known collagen shows inhibition. In ELISA, mixtures of the two antibodies give an additive binding reaction to the collagen, suggesting that each is against a different antigenic determinant. That both antigenic determinants are conformational dependent, being either in, or closely associated with, the collagen helix is demonstrated by the loss of antibody binding to molecules that have been thermally denatured. The temperature at which this occurs, as assayed by inhibition ELISA, is very similar to that at which the collagen helix melts, as determined by optical rotation. This gives strong additional evidence that the antibodies are directed against the collagen. The antibodies were used for indirect immunofluorescence analyses of cryostat sections of corneas and other organs from 17 to 18-day-old chick embryos. Of all tissues examined only Bowman’s membrane gave a strong staining reaction with cryostat sections of unfixed material. Staining in other areas of the cornea and in other tissues was very light or nonexistent. When, however, sections were pretreated with pepsin dissolved in dilute HAc or, surprisingly, with the dilute HAc itself dramatic new staining by the antibodies was observed in most tissues examined. The staining, which was specific for the anti-type V collagen antibodies, was largely confined to extracellular matrices of dense connective tissues. Experiments using protease inhibitors suggested that the “unmasking” did not involve proteolysis. We do not yet know the mechanism of this unmasking; however, one possibility is that the dilute acid causes swelling or conformational changes in a type-V collagen-containing supramolecular structure. Further studies should allow us to determine whether this is the case.     

A note on the heterofermentative Lactobacillus isolated from kefir grains

M arshall , V.M., C ole , W.M. & F arrow , J.A.E. 1984. A note on the heterofermentative Lactobacillus isolated from kefir grains. Journal of Applied Bacteriology 56 , 503–505.
Heterofermentative lactobacilli have been isolated from kefir grains obtained from four different sources. A number of these isolates ferment only L-arabinose and gluconate and are similar to the species 'Lactobacillus desidiosus' . The DNA of these isolates, however, have 85–109% homology with 'L. caucasicus' NCDO 190 which is now regarded as L. kefir . The relationship between these strains is discussed.     

Effect of deletions 5′ to the translation initiation sequence on the expression of an mRNA in animal cells

To learn if an mRNA·18S rRNA interaction or a special secondary structure in the mRNA start region is essential for translation in eukaryotic cells, we constructed recombinant plasmids with the SV40 early promoter 5 to part of the Escherichia coli tuf B-lacZ gene. Deletion of bases potentially complementary to the 18S rRNA highly increased the transient -galactosidase expressed in transfected CHO cells. Deletion of bases that fostered formation of potential hairpins with the mRNA 5-terminus or altered the structure of the coding region reduced -galactosidase activity suggesting that these features of the mRNA secondary structure may be essential for initiation of translation. Computer aided analysis of the potential structure of 290 mRNAs suggests these are conserved features of the initiation region.     

Sterol content and enzyme defects of nystatin-resistant mutants of Neurospora crassa.

Summary Non-saponifiable cell extracts of wild type and sterol mutants of N. crassa were analysed by means of gas-liquid chromatography. The wild-type contained ergosterol and episterol in a 10:1 ratio. None of the mutants was able to synthesize ergosterol. Three of the mutants carry single recessive gene mutations causing blocks in the terminal steps of ergosterol biosynthesis: erg-1 has an inactive ^{8 7} isomerase, erg-2 has an inactive 24(28) hydrogenase, and erg-4 has an inactive C-24 methyl transferase. Some of the mutants accumulated novel sterols as a result of their enzyme defects. The genes erg-1 and erg-2 were mapped close to inl on the right arm of chromosome V.     

Glucocorticoid ligands specify different interactions with NF-kappaB by allosteric effects on the glucocorticoid receptor DNA binding domain

Glucocorticoids inhibit inflammation by acting through the glucocorticoid receptor (GR) and powerfully repressing NF-kappaB function. Ligand binding to the C-terminal of GR promotes the nuclear translocation of the receptor and binding to NF-kappaB through the GR DNA binding domain. We sought how ligand recognition influences the interaction between NF-kappaB and GR. Both dexamethasone (agonist) and RU486 (antagonist) promote efficient nuclear translocation, and we show occupancy of the same intranuclear compartment as NF-kappaB with both ligands. However, unlike dexamethasone, RU486 had negligible activity to inhibit NF-kappaB transactivation. This failure may stem from altered co-factor recruitment or altered interaction with NF-kappaB. Using both glutathione S-transferase pull-down and bioluminescence resonance energy transfer approaches, we identified a major glucocorticoid ligand effect on interaction between the GR and the p65 component of NF-kappaB, with RU486 inhibiting recruitment compared with dexamethasone. Using the bioluminescence resonance energy transfer assay, we found that RU486 efficiently recruited NCoR to the GR, unlike dexamethasone, which recruited SRC1. Therefore, RU486 promotes differential protein recruitment to both the C-terminal and DNA binding domain of the receptor. Importantly, using chromatin immunoprecipitation, we show that impaired interaction between GR and p65 with RU486 leads to reduced recruitment of the GR to the NF-kappaB-responsive region of the interleukin-8 promoter, again in contrast to dexamethasone that significantly increased GR binding. We demonstrate that ligand-induced conformation of the GR C-terminal has profound effects on the functional surface generated by the DNA binding domain of the GR. This has implications for understanding ligand-dependent interdomain communication.