Improving transfusion safety: implementation of a comprehensive computerized bar code-based tracking system for detecting and preventing errors.

BACKGROUND: To transfuse blood products safely, health care workers must accurately identify patients, blood samples, and the blood components. A comprehensive bar code-based computerized tracking system was developed and implemented to identify and prevent transfusion errors. STUDY DESIGN AND METHODS: A data network, wireless devices, and bar-coded labels were pilot tested before the system was introduced hospitalwide. The system provided a complete audit trail for all transactions. Data from before and after implementation were analyzed. RESULTS: Incident reports decreased from a mean of 41.5 reports per month in the 6 months before the system was implemented to a mean of 7.2 reports per month after implementation. The blood sample rejection rate decreased from 1.82 percent to a mean of 0.17 percent after implementation. Errors detected by the new system were sorted into misscans, skipped steps, wrong steps, and prevented identification errors (PIEs). Misscans and skipped steps were the most common errors in the first 10 months after implementation. During the final transfusion step, PIEs occurred at the rate of about one per month and scans were omitted approximately 1 percent of the time. Therefore, it is estimated that mistransfusions could occur about once every 100 months on average with the new system. CONCLUSIONS: The bar code-based computerized tracking system detected and prevented identification and matching errors, thereby reducing the proportion of blood samples rejected and increasing patient safety.

The R100Q mutation of the GABA(A) alpha(6) receptor subunit may contribute to voluntary aversion to ethanol in the sNP rat line.

We have investigated the GABA(A) alpha(6) subunit molecular composition in two rat lines selectively bred for high or low ethanol preference and consumption, namely Sardinian alcohol-preferring (sP) and Sardinian non-alcohol-preferring (sNP) rats, which have been bred at the University of Cagliari, Italy, since 1981. A total of 27 sP, 22 sNP and 25 control rats belonging to five other different strains, were studied by direct sequencing and amplification refractory mutation system analysis. Among the sNPs, only one was found to be normal, 11 heterozygotes, and 10 homozygotes for the G-->A substitution in codon 100, the same R100Q point mutation previously described in Alcohol Non Tolerant rats, while no other animal showed any mutated allele. Pharmacological studies have extensively demonstrated that this substitution in the mature peptide changes the benzodiazepine-insensitive receptor to a sensitive one. In order to test the functional significance of this mutation in native cerebellar GABA(A) receptors, selective breeding from Q/R rats was employed to obtain a sufficient number of R/R homozygotes. Xenopus laevis oocytes were then injected with cerebellar synaptosomes extracted from Q/Q, R/Q and R/R sNP rats. Consistently, utilizing the two-electrode voltage-clamp technique, GABA-evoked currents mediated by GABA(A) receptors containing the mutated alpha(6) subunit were potentiated by diazepam with about a two-fold increased potency, as compared to receptors containing the wild-type, benzodiazepine-insensitive alpha(6) subunit. Our data show for the first time that a mutated GABA(A) alpha(6) receptor subunit segregates in a rat line which voluntarily avoids alcohol consumption, and further support a possible involvement of the GABA(A) receptor containing a mutated alpha(6) subunit in the genetic predisposition to alcohol preference.

The synthetic cannabinoid WIN55212-2 decreases the intraocular pressure in human glaucoma resistant to conventional therapies.

The search for new ocular hypotensive agents represents a frontier of current eye research because blindness due to optic neuropathy occurs insidiously in 10% of all patients affected by glaucoma. Cannabinoids have been proposed to lower intraocular pressure by either central or peripheral effects but a specific mechanism for this action has never been elucidated. We recently demonstrated the presence of the central cannabinoid receptor (CB(1)) mRNA and protein in the human ciliary body. In the present study we show that the synthetic CB(1) receptor agonist, WIN 55212--2, applied topically at doses of 25 or 50 microg (n = 8), decreases the intraocular pressure of human glaucoma resistant to conventional therapies within the first 30 min (15 +/- 0.5% and 23 +/- 0.9%, respectively). A maximal reduction of 20 +/- 0.7% and 31 +/- 0.6%, respectively, is reached in the first 60 min. These data confirm that CB(1) receptors have direct involvement in the regulation of human intraocular pressure, and suggest that, among various classes of promising antiglaucoma agents, synthetic CB(1) receptor agonists should deserve further research and clinical development.

Narrative notes in a nursing information system (NIS).

Today s rapidly changing health care environment creates pressure for the computerization of the patient record. Two requirements for inclusion of nursing activities into the computerized patient record (CPR) are a standardized nursing language of sufficient granularity and a database that allows for one time collection of data for multiple uses. Documentation systems raise issues of data completeness. Using a descriptive methodology, nursing documentation in one CPR was examined for prevalence and content of free text documentation in an otherwise structured nursing information system (NIS). Results demonstrate house wide use of free text (narrative note) fields. Variability in use unrelated to patient acuity suggests idiosyncratic individual or unit documentation practices. Findings support the use of quality management activities to improve documentation practices and point to areas of database enhancement and information system development.

Oral isobutyramide therapy in patients with thalassemia intermedia: results of a phase II open study.

A pilot phase II open study on 12 patients with thalassemia intermedia (7 men, 5 women; age 31 +/- 2.0 years SE) treated with oral isobutyramide, a derivative of butyric acid (150 mg/kg body wt/day), was performed in order to evaluate the effect of this compound in stimulating hemoglobin F (HbF) production. No patient underwent blood transfusion in the 1-year time frame prior to the study. Nine patients were splenectomized. Safety was monitored by clinical and laboratory tests. Efficacy was assessed in terms of the non-alpha/alpha globin chain biosynthetic ratio and the percentage increase of HbF. The study design consisted of a screening phase, a treatment phase of 28 days, and a posttreatment follow-up of 28 days. All patients completed the study. Compliance to treatment was 100%. No drug-related adverse event was recorded. We observed little or no increase in the non-alpha/alpha ratio in the majority of patients. Six patients showed a percentage increase of HbF at the end of treatment and in 5 of those 6 further increases at the end of the follow-up period were observed. The change in percentage of HbF over time was close to significance both in the treatment period (P = 0. 06) and in the follow-up period (P = 0.08). These results indicate that butyrate derivatives can stimulate fetal hemoglobin in patients with intermediate thalassemia. Testing of the effects of different schedules of administration of isobutyramide will be required in order to determine the optimal use of this compound in the treatment of the beta-thalassemia syndromes.

The human eye expresses high levels of CB1 cannabinoid receptor mRNA and protein.

We used reverse transcriptase polymerase chain reaction to detect the expression of the central and peripheral cannabinoid receptors (CB1 and CB2, respectively) mRNA, and Western blotting to show the presence of the CB1 protein in subregions of the human eye. CB2 mRNA transcripts were undetectable, while levels of CB1 mRNA were significantly expressed in the human retina (25.8 +/- 2.46%), ciliary body (210 +/- 11.55%) and iris (62.7 +/- 5.94%) when compared with those of the normalizing reference gene beta2 microglobulin. The CB1 gene encodes a functional protein which is detected in its glycosylated (63 kDa) and unglycosylated (54 kDa) form in the same areas by a specific purified antibody raised against the amino terminus (residues 1-77) of the CB1 receptor. These results further support the proposed role of the CB1 receptor in controlling intraocular pressure, helping to explain the antiglaucoma properties of marijuana.

The role of stress in the pathophysiology of the dopaminergic system.

In this review, we will examine the most recent preclinical evidence in support of the fact that both acute and chronic stress may have a detrimental impact on the normal function of the dopaminergic system. In recent decades, the term stress has changed its meaning from that of a 'non-specific body response' to a 'monitoring system of internal and external cues'; that is a modality of reaction of the mammalian central nervous system (CNS) which is critical to the adaptation of the organism to its environment. Compelling results have demonstrated that the dopaminergic system is important not only for hedonic impact or reward learning but also, in a broader sense, for reactivity to perturbation in environmental conditions, for selective information processing, and for general emotional responses, which are essential functions in the ability (or failure) to cope with the external world. In this, stress directly influences several basic behaviors which are mediated by the dopaminergic system such as locomotor activity, sexual activity, appetite, and cross sensitization with drugs of abuse. Studies using rat lines which are genetically different in dopamine (DA) physiology, have shown that even small alterations in the birth procedure or early life stress events may contribute to the pathophysiology of psychiatric disorders-in particular those involving central DA dysfunction-and may cause depression or psychotic derangement in the offspring. Finally, the fact that the dopaminergic system after stress responds, preferentially, in the medial prefrontal cortex (MFC), is thought to serve, in humans, as a protection against positive psychotic symptoms, since the increased DA activity in the MFC suppresses limbic DA transmission. However, excessive MFC dopaminergic activity has a negative impact on the cognitive functions of primates, making them unable to select and process significant environmental stimuli. Thus it appears that a critical range of DA turnover is necessary for optimal cognitive functioning after stress, in the response of the CNS to ever-changing environmental demands. Molecular Psychiatry (2000) 5, 14-21.

Folate measurements in patients on regular hemodialysis treatment.

Patients on regular hemodialysis treatment may develop megaloblastic anemia caused by folate deficiency, but whether folate supplementation is required is still controversial, particularly during erythropoietin administration. Erythrocyte folate concentration is a better indicator of folate status than serum folate, although the latter is the variable generally measured. We measured serum and erythrocyte folate in blood samples from 112 regular hemodialysis patients (57 men, 55 women, 50 treated with erythropoietin, and 62 not) by Stratus Folate immunoenzymatic assay (Dade). Patients with very low serum (<2.87 ng/mL) but normal erythrocyte folate were reinvestigated 4 months later without receiving folate supplementation meanwhile. Serum folate concentrations were 0.48 to 12.76 ng/mL (median, 3.40) and erythrocyte folate 0.19 to 1.85 microg/mL (median, 0.42). Only 37% serum folate values were in the relevant reference interval compared with 80.2% erythrocyte folate values (3.08 to 17.65 ng/mL and 0.24 to 0.64 microg/mL, respectively). A significant correlation was found between serum and erythrocyte folate concentrations, without clinical relevance caused by the wide scatter around the regression line. Serum and erythrocyte folate did not vary significantly between patients given erythropoietin and those not so treated. The folate status of the 24 patients with very low serum folate was almost unchanged 4 months later. According to the serum folate test, 63% of patients needed folate supplementation, whereas the erythrocyte folate test, a better indicator of folate status, suggested that only 1.8% of patients needed folate supplementation. Erythropoietin therapy appears not to be an indication for standard folate supplementation in hemodialysis patients.

Delta9-tetrahydrocannabinol increases sequence-specific AP-1 DNA-binding activity and Fos-related antigens in the rat brain.

Delta-9-tetrahydrocannabinol (delta9-THC), the psychoactive principle of marijuana, has been shown to upregulate the mRNA levels of immediate-early genes in the rat brain. Using electrophoretic mobility-shift assay and one-dimensional Western blot, we here report that delta9-THC increases Activator protein-1 (AP-1) DNA-binding and Fos-related antigen activity in discrete areas of the rat brain. One hour after the intraperitoneal administration of delta9-THC at a dose of 10 or 15 mg/kg, AP-1 DNA-binding activity in the nucleus accumbens increased by 33 and 49%, respectively, while Western blot showed an increase in both c-Fos, FosB, Fra-1 (Fos-related antigen) and Fra-2. In the cingulate cortex and caudate-putamen, delta9-THC significantly increased AP-1 DNA-binding activity only at the highest dose used (57 and 71%, respectively). While in the caudate-putamen the increase in AP-1 DNA binding was mainly due to an elevation of the c-Fos and FosB proteins, the same phenomenon depended on the FosB, Fra-1 and Fra-2 peptides in the cingulate cortex. The effect of delta9-THC on the AP-1 DNA binding and the Fos-related antigens in the nucleus accumbens was blocked by the specific cannabinoid antagonist SR141716 A (3 mg/kg i.p.). delta9-THC failed to modify Specificity protein 1 (Sp1) DNA-binding activity. The results indicate that delta9-THC activates gene coding for AP-1 DNA-binding proteins by acting on cannabinoid receptors, and induces a different transcriptional program on the early-immediate gene of the Fos family, in different areas in the rat brain, suggesting that this mechanism might be involved in the central actions of cannabinoids.

Cannabinoid receptor CB1 mRNA is highly expressed in the rat ciliary body: implications for the antiglaucoma properties of marihuana.

We used RT-PCR to measure relative differences in cannabinoid receptor (CB) mRNAs in the rat eye, comparing CB1 or CB2 transcripts to that of the normalizing reference gene beta2 microglobulin (beta2m). Significantly higher levels of CB1 mRNA levels were found in the ciliary body (0.84+/-0.05% of beta2m) than in the iris, (0.34+/-0.04% of beta2m), retina (0.07+/-0.005% of beta2m) and choroid (0.06+/-0.005% of beta2m). CB2 mRNA was undetectable. This expression pattern supports a specific role for the CB1 receptor in controlling intraocular pressure, helping to explain the antiglaucoma property of cannabinoids.

Whole blood folate concentrations: comparison between Stratus Folate (DADE) and radioassay (DPC) methods.

The analytical performance of the Stratus Folate assay for intra-erythrocyte folate determination in normal subjects and in patients affected by folate-related diseases was compared with that of the radioassay (DPC) routinely employed by us. Folate concentrations were measured in freshly obtained EDTA whole blood from 100 subjects. Haemolysis was performed with the appropriate lysis reagent. In addition, to compare two different haemolysis procedures folate determination was carried out in 51 samples haemolysed according to the two procedures in parallel. Data were analyzed using Wilcoxon's test and standardized principal component analysis. Stratus Folate assay and radioassay performances were comparable in terms of analytical characteristics as well as in individual intraerythrocyte folate values across the range of whole blood concentrations examined in the survey. Significant differences were detected between the two different haemolysis procedures only for the radioassay. In conclusion, we observed no significant differences between the two folate determination methods despite their different analytical principles, which indicates the suitability of routine use of the automated non-isotopic Stratus Folate assay for clinical purposes. Moreover, with the latter assay the laboratory staff could choose the more convenient haemolysis procedure.

Plasma homocysteine levels in 10 patients with polycythemia.

Polycythemia and hyperhomocysteinemia are risk factors for thrombosis. Since red blood cells actively metabolize methionine to homocysteine, we investigated whether or not patients with polycythemia have increased plasma levels of homocysteine, which might contribute to their increased thrombotic risk. In ten patients with polycythemia, the plasma homocysteine levels were measured before phlebotomy, three days after the procedure and 1-2 months later. The baseline mean plasma homocysteine levels in patients (9.7 +/- 1.6 mumol/L [+/-SD]) did not differ significantly from that found in 30 sex- and age-matched healthy controls (12.2 +/- 6.9). Despite a fall in the patients' mean [+/-SD] hematocrit from 0.50 +/- 0.02 at baseline to 0.47 +/- 0.03 three days after phlebotomy (significant at 95%) and to 0.48 +/- 0.02 after 1 to 2 months (not significant), the mean plasma homocysteine levels did not change significantly (9.9 +/- 2.3 mumol/L at 3 days and 9.7 +/- 2.1 mumol/L at 1-2 months). It is unlikely that high plasma homocysteine levels contribute to the increased thrombotic risk of polycythemic patients.

Implementation of standardized nursing languages (NIC, NOC) in on-line care planning and documentation.

At the University of Iowa Hospitals and Clinics (UIHC), the Standardized Nursing Languages (SNLs) of Nursing Interventions Classification (NIC) and Nursing-sensitive Outcomes Classification (NOC) are being implemented in on-line care planning and documentation. NIC and NOC are being integrated in the INFORMM NIS (Information Network For Retrieval & Medical Management Nursing Information System). The implementation process for SNLs includes six components: objectives, programming, database content, education, utilization, and evaluation. This process has been used successfully in NIC implementation and will be applied in NOC field testing.

Cytokine regulation of the liver transcription factor hepatocyte nuclear factor-3 beta is mediated by the C/EBP family and interferon regulatory factor 1.

Three distinct hepatocyte nuclear factor-3 (HNF-3) proteins (alpha, beta, and gamma) regulate the transcription of numerous liver-enriched genes. The HNF-3 proteins bind DNA via a homologous winged helix motif common to a number of proteins known to be critical for determination events in embryogenesis. We have demonstrated previously that two binding sites in the -184 HNF-3 beta promoter are recognized by widely distributed factors and that there is also a critical autoregulatory site, we identified a binding site for a cell-specific factor, LF-H3 beta, that may function in restricting HNF-3 beta gene expression to hepatocytes. Our present study demonstrates that members of the C/EBP and proline and acidic amino acid-rich subfamilies of basic region leucine zipper transcription factors bind the LF-H3 beta site, and cotransfection of HepG2 cells shows that these factors are able to activate an HNF-3 beta promoter reporter construct. The LF-H3 beta-C/EBP binding sequence also confers HNF-3 beta promoter stimulation in response to interleukin (IL)-1 and IL-6. Upstream of this HNF-3 beta proximal promoter region, an IFN-stimulated response element core sequence (-231 to -210) was found that mediates transcriptional induction by IFN-gamma but not IFN-alpha. Gel mobility supershift assay demonstrates that an IFN-gamma-induced protein-DNA complex is disrupted by an antibody specific for interferon regulatory factor-1/interferon-stimulated gene factor-2. Consistent with this finding, we observed that IFN-gamma induction requires ongoing protein synthesis. Surprisingly, the effect of the three cytokines (IL-1, IL-6, and IFN-gamma) in combination as assayed by the same model is not synergistic. HNF-3beta joins the C/EBP family on the list of liver-enriched transcription factors, the expression of which is modulated by cytokines.

Chronic imipramine, L-sulpiride and mianserin decrease corticotropin releasing factor levels in the rat brain.

Among clinically effective antidepressant drugs, the action mechanism of mianserin has recently been related to variations in corticotropin releasing factor (CRF) levels in the rat locus coeruleus. We describe a specific effect on CRF levels after chronic treatment with different antidepressants: mianserin (10 mg/kg), imipramine (20 mg/kg), both for 21 days, or L-sulpiride (1 mg/kg) for 15 days. While all antidepressants used greatly decreased CRF concentrations in the hypothalamus, only mianserin decreased CRF concentrations by 40% in extrahypothalamic sites. Acute treatments failed to modify CRF levels. Chronic treatment with mianserin did not affect CRF density either in the hypothalamus or the extrahypothalamic areas. This new finding may add another facet to the therapeutic action of certain antidepressants and in particular to the atypical profile of mianserin.

Decreased expression of hepatocyte nuclear factor 3 alpha during the acute-phase response influences transthyretin gene transcription.

Three distinct hepatocyte nuclear factor 3 (HNF-3) proteins (alpha, beta, and gamma) are known to regulate the transcription of numerous liver-specific genes. The HNF-3 proteins bind to DNA as monomers through a winged-helix motif, which is also utilized by a number of developmental regulators, including the Drosophila homeotic fork head (fkh) protein. We have previously characterized a strong-affinity HNF-3S site in the transthyretin (TTR) promoter region which is essential for expression in human hepatoma (HepG2) cells. In the current study, we identify an activating protein 1 (AP-1) site which partially overlaps the HNF-3S sequence in the TTR promoter. We show that in HepG2 cells the AP-1 sequence confers 12-O-tetradecanoylphorbol-13-acetate inducibility to the TTR promoter and contributes to normal TTR transcriptional activity. We also demonstrate that the HNF-3 proteins and AP-1 bind independently to the TTR AP-1-HNF-3 site, and cotransfection experiments suggest that they do not cooperate to activate an AP-1-HNF-3 reporter construct. In addition, 12-O-tetradecanoylphorbol-13-acetate exposure of HepG2 cells results in a reciprocal decrease in HNF-3 alpha and -3 gamma expression which may facilitate interaction of AP-1 with the TTR AP-1-HNF-3 site. In order to explore the role of HNF-3 in the liver, we have examined expression patterns of TTR and HNF-3 during the acute-phase response and liver regeneration. Partial hepatectomy produced minimal fluctuation in HNF-3 and TTR expression, suggesting that HNF-3 expression is not influenced by proliferative signals induced during liver regeneration. In acute-phase livers, we observed a dramatic reduction in HNF-3 alpha expression which correlates with a decrease in the expression of its target gene, the TTR gene. Furthermore, consistent with previous studies, the acute-phase livers are induced for c-jun but not c-fos expression. We propose that the reduction in TTR gene expression during the acute phase is likely due to lower HNF-3 alpha expression levels and that the induction of primarily c-jun homodimers, which are poor transcriptional activators, is insufficient to maintain normal TTR expression levels. We also discuss the role of reduced HNF-3 alpha expression in mediating decreased transcription of HNF-3 target genes which respond negatively to cytokine signalling.

Members of the HNF-3/forkhead family of transcription factors exhibit distinct cellular expression patterns in lung and regulate the surfactant protein B promoter.

The hepatocyte nuclear factor-3 (HNF-3)/forkhead (fkh) proteins consist of an extensive family of tissue-specific and developmental gene regulators which share homology within the winged helix DNA binding motif. We report on the isolation of a new family member, HNF-3/forkhead homolog 8 (HFH-8), from lung cDNA libraries and the derivation of the complete amino acid sequences for the HFH-8 protein as well as previously identified HFH-1 and HFH-4 proteins. The HFH proteins contain several sequence motifs found in activation domains of other transcription factors and HNF-3/fkh family members. In situ hybridization with the HNF-3, HFH-4, and HFH-8 probes in adult lung demonstrate that the HNF-3/fkh cellular expression patterns are regionally specified. Whereas HNF-3 alpha and HNF-3 beta are normally coexpressed in the hepatocyte, their expression patterns in the lung are different. The HNF-3 alpha and HFH-4 genes are coexpressed in the bronchiolar epithelium (clara cells), whereas the HNF-3 beta probe exhibits prominent hybridization with the smooth muscle surrounding arterioles and bronchioles. In contrast, HFH-8 probes labeled the type II pneumocyte cells lining the respiratory surfaces of terminal bronchioles and alveolar sac. We have identified an HNF-3 consensus DNA binding sequence in the proximal surfactant protein B (SPB) promoter region (SPB-f2, -78 to -88). SPB gene transcription is restricted to bronchiolar and alveolar epithelium which colocalizes with the expression pattern of the HNF-3 alpha and HFH-8 genes, respectively. We show that the SPB-f2 sequence is recognized by both HNF-3 alpha and HFH-8 proteins and that these cDNA expression vectors activate the SPB promoter in cotransfection assays through the HNF-3 consensus sequence. Our results suggest that SPB promoter activity is regulated by HNF-3 alpha and HFH-8 proteins in a cell type-specific manner.

Hepatocyte nuclear factor-3 (HNF-3) binds to the insulin response sequence in the IGF binding protein-1 (IGFBP-1) promoter and enhances promoter function.

IGF binding protein-1 is an important short-term modulator of IGF bioavailability. Hepatic transcription of IGFBP-1 is increased by glucocorticoids and suppressed by insulin. We previously identified adjacent glucocorticoid and insulin response sequences approximately 90 bp 5' to the RNA cap site in the IGFBP-1 promoter. This insulin response sequence contains a sequence highly related (10/12 bases) to a consensus HNF-3 binding sequence. Gel shift and supershift studies confirm that this sequence binds HNF-3 alpha, beta and gamma. Co-expression of HNF-3 beta enhances IGFBP-1 promoter activity in NIH-3T3 cells. Mutation of this HNF-3 binding sequence disrupts this effect as well as the ability of glucocorticoids to stimulate and of insulin to inhibit IGFBP-1 promoter activity in H4IIE and HepG2 hepatoma cells. HNF-3 binding at this site may play an important role in the multihormonal regulation of hepatic IGFBP-1 gene expression.

The DNA-binding specificity of the hepatocyte nuclear factor 3/forkhead domain is influenced by amino-acid residues adjacent to the recognition helix.

Three distinct hepatocyte nuclear factor 3 (HNF-3) proteins (HNF-3 alpha, -3 beta, and -3 gamma) are known to regulate the transcription of liver-specific genes. The HNF-3 proteins bind to DNA as a monomer through a modified helix-turn-helix, known as the winged helix motif, which is also utilized by a number of developmental regulators, including the Drosophila homeotic forkhead (fkh) protein. We have previously described the isolation, from rodent tissue, of an extensive family of tissue-specific HNF-3/fkh homolog (HFH) genes sharing homology in their winged helix motifs. In this report, we have determined the preferred DNA-binding consensus sequence for the HNF-3 beta protein as well as for two divergent family members, HFH-1 and HFH-2. We show that these HNF-3/fkh proteins bind to distinct DNA sites and that the specificity of protein recognition is dependent on subtle nucleotide alterations in the site. The HNF-3, HFH-1, and HFH-2 consensus binding sequences were also used to search DNA regulatory regions to identify potential target genes. Furthermore, an analysis of the DNA-binding properties of a series of HFH-1/HNF-3 beta protein chimeras has allowed us to identify a 20-amino-acid region, located adjacent to the DNA recognition helix, which contributes to DNA-binding specificity. These sequences are not involved in base-specific contacts and include residues which diverge within the HNF-3/fkh family. Replacement of this 20-amino-acid region in HNF-3 beta with corresponding residues from HFH-1 enabled the HNF-3 beta recognition helix to bind only HFH-1-specific DNA-binding sites. We propose a model in which this 20-amino-acid flanking region influences the DNA-binding properties of the recognition helix.

Primary optic neuritis evolved in multiple sclerosis: an epidemiological study.

Sixty-nine cases of Optic Neuritis were studied in order to evaluate the percentage of evolution into multiple sclerosis. We observed an incidence rate of 53.6% which is somewhat high respect to data present in literature. The various findings obtained in the present study were compared with those of the literature and the similarities and discrepancies underlined.