Efectos de los opioides en endocrinología / Opioids effects in endocrinology

El uso de opioides ha aumentado en forma significativa en las últimas décadas, lo que nos ha permitido conocer sus diversos efectos en el sistema endocrino. Estos efectos están sub diagnosticados, en parte porque los síntomas se confunden con los de la misma enfermedad que lleva al uso de opioides y porque no los buscamos de forma dirigida. El hipogonadismo y la insuficiencia suprarrenal son sus efectos más establecidos, sin embargo, otros efectos como los provocados en el tejido óseo requieren de especial atención. La evaluación de los ejes gonadotropo, adrenal y de la salud ósea debe tenerse en consideración en los usuarios crónicos de opioides, particularmente frente a la presencia de síntomas. La suspensión o reducción del uso de opioides es el primer tratamiento del compromiso endocrinológico.

The use of opioids has increased significantly in recent decades, which has allowed us to understand its effects on the endocrine system. These effects are underdiagnosed, the symptoms are confused with those of the same disease that leads to the use of opioids and we do not look for them in a targeted way. Hypogonadism and adrenal insufficiency are its most established effects, however, other effects such as the ones caused on bone tissue require special attention. Evaluation of gonadotropic and adrenal axes as well as bone health should be taken into consideration in chronic opioid users, particularly in the presence of symptoms. Stopping or reducing opioid use is the first treatment for endocrine compromise.

Beneficios positivos de cuidar en la motivación y el bienestar del personal de enfermería: un estudio de diario sobre el papel de las habilidades de regulación emocional en el trabajo / Positive benefits of caring on nurses’ motivation and well-being: A diary study about the role of emotional regulation abilities at work

La investigación reciente revela que no todas las demandas de trabajo tienen efectos negativos sobre el bienestar de los trabajadores, y sugiere que los efectos negativos o positivos de éstas dependen del sector laboral que se esté abordando. Específicamente, las demandas emocionales en el trabajo, que son el corazón del trabajo de enfermería, pueden ser interpretadas por el personal de enfermería como un reto que promueve la motivación y bienestar entre estos profesionales, especialmente cuando hay recursos personales y laborales disponibles. El estudio tuvo dos objetivos. En primer lugar, examinar si las exigencias emocionales diarias dentro del contexto del trabajo de enfermería tienen un efecto positivo en la motivación diaria del personal de enfermería en el trabajo (vigor) y en el bienestar en el hogar (vitalidad y sentimientos positivos). En segundo lugar, explorar si este efecto positivo podría mejorarse por las habilidades de regulación emocional del personal de enfermería. Esta investigación utilizó un diseño de diario para explorar las experiencias cotidianas y analizar cómo las variaciones de las características laborales y personales específicas pueden afectar los niveles de motivación y bienestar a lo largo de los días. Cincuenta y tres enfermeras que trabajan en diferentes hospitales españoles y centros sanitarios de atención primaria completaron un cuestionario diario durante 5 días laborables consecutivos en dos momentos diferentes, después del trabajo y por la noche (N = 53 participantes y N = 265 observaciones). En línea con nuestras hipótesis, el análisis multinivelreveló que, por un lado, las demandas emocionales en eltrabajo durante el día tuvieron un efecto positivo en el vigor en el trabajo y en la vitalidad en casa. Por otra parte, los análisis mostraron que el personal de enfermería con más habilidades de regulación emocional presentó mayores niveles de motivación en el trabajo y bienestar en el hogar cuando se enfrentaban a altas demandas emocionales en el trabajo, mostrando un efecto 'spillover' después del trabajo. Estos hallazgos apoyan la idea de que las demandas emocionales de la profesión de enfermería pueden actuar como desafíos que promueven la motivación y el bienestar, especialmente si se dispone de los recursos emocionales adecuados

Recent research reveals that not all job demands have negative effects on workers’ well-being and suggests that the negative or positive effects of specific job demands depend on the occupational sector. Specifically, emotional job demands form the heart of the work for nurses and for this reason they can be interpreted by nurses as a challenge that promotes motivation and well-being among these professionals, especially if personal and job resources become available.The study had two objectives. First,to examine whether daily emotional demands within a nursing work context have a positive effect on nurses’ daily motivation atwork (vigour) and well-being at home (vitality and positive affect). Second, to explore whether this positive effect could be enhanced by nurses’ emotional regulation abilities. This research used a diary design to explore daily experiences and to analyze how variations in specific job or personal characteristics can affect levels of motivation and well-being across days. Fifty-three nurses working in different Spanish hospitals and primary health care centres completed a general questionnaire and a diary booklet over 5 consecutive working days in two different moments, after work and at night (N = 53 participants and N = 265 observations). In line with our hypotheses, multi-level analyses revealed that, on the one hand, day-level emotional demands at work had a positive effect on vigour at work and on vitality at home. On the other hand, analyses showed that nurses with higher emotional regulation abilities have more motivation at work and well-being at home when they have to face high emotional demands at work, showing a spill over effect after work. These findings support the idea that emotional demands from the nursing profession can act as challenges which promote motivation and well-being, especially if internal emotional resources become available

The role of a computed tomography-based image registered navigation system for natural orifice transluminal endoscopic surgery: a comparative study in a porcine model.

BACKGROUND AND STUDY AIMS: Most natural orifice transluminal endoscopic surgery (NOTES) procedures have been performed in animal models through the anterior stomach wall, but this approach does not provide efficient access to all anatomic areas of interest. Moreover, injury of the adjacent structures has been reported when using a blind access. The aim of the current study was to assess the utility of a CT-based (CT: computed tomography) image registered navigation system in identifying safe gastrointestinal access sites for NOTES and identifying intraperitoneal structures. METHODS: A total of 30 access procedures were performed in 30 pigs: anterior gastric wall (n = 10), posterior gastric wall (n = 10), and anterior rectal wall (n = 10). Of these, 15 procedures used image registered guidance (IR-NOTES) and 15 procedures used a blind access (NOTES only). Timed abdominal exploration was performed with identification of 11 organs. The location of the endoscopic tip was tracked using an electromagnetic tracking system and was recorded for each case. Necropsy was performed immediately after the procedure. The primary outcome was the rate of complications; secondary outcome variables were number of organs identified and kinematic measurements. RESULTS: A total of 30 animals weighting a mean (± SD) of 30.2 ± 6.8 kg were included in the study. The incision point was correctly placed in 11 out of 15 animals in each group (73.3 %). The mean peritoneoscopy time and the number of properly identified organs were equivalent in the two groups. There were eight minor complications (26.7 %), two (13.3 %) in the IR-NOTES group and six (40.0 %) in the NOTES only group ( P = n. s.). Characteristics of the endoscope tip path showed a statistically significant improvement in trajectory smoothness of motion for all organs in the IR-NOTES group. CONCLUSION: The image registered system appears to be feasible in NOTES procedures and results from this study suggest that image registered guidance might be useful for supporting navigation with an increased smoothness of motion.

Magnetic resonance for assessment of disease activity and severity in ileocolonic Crohn's disease.

OBJECTIVE: Assessment of disease extension and activity is crucial to guide treatment in Crohn's disease. The objective of the current cross-sectional study was to determine the accuracy of MR for this assessment. DESIGN: 50 patients with clinically active (n = 35) or inactive (n = 15) Crohn's disease underwent ileocolonoscopy (reference standard) and MR. T2-weighted and precontrast and postcontrast-enhanced T1-weighted sequences were acquired. Endoscopic activity was evaluated by CDEIS (Crohn's Disease Endoscopic Index of Severity); in addition endoscopic lesions were classified as absent, mild (inflammation without ulcers) or severe (presence of ulceration). RESULTS: The comparison of intestinal segments with absent, mild and severe inflammation demonstrated a progressive and significant (p<0.001) increase in the following MR parameters: wall thickness, postcontrast wall signal intensity, relative contrast enhancement, presence of oedema, ulcers, pseudopolyps and lymph node enlargement. Independent predictors for CDEIS in a segment were wall thickness (p = 0.007), relative contrast enhancement (p = 0.01), presence of oedema (p = 0.02) and presence of ulcers at MR (p = 0.003). There was a significant correlation (r = 0.82, p<0.001) between the CDEIS of the segment and the MR index calculated according to the logistic regression analysis coefficients. The MR index had a high accuracy for the detection of disease activity (area under the receiver operating characteristic (ROC) curve 0.891, sensitivity 0.81, specificity 0.89) and for the detection of ulcerative lesions (area under the ROC curve 0.978, sensitivity 0.95, specificity 0.91) in the colon and terminal ileum. CONCLUSION: The accuracy of MR for detecting disease activity and assessing severity brings about the possibility of using MR as an alternative to endoscopy in the evaluation of ileocolonic Crohn's disease.

Ocular surface epithelium induces expression of human mucosal lymphocyte antigen (HML-1) on peripheral blood lymphocytes.

BACKGROUND/AIMS: Peripheral blood CD8+ lymphocytes that home to mucosal surfaces express the human mucosal lymphocyte antigen (HML-1). At mucosal surfaces, including the ocular surface, only intraepithelial CD8+ lymphocytes express HML-1. These lymphocytes are retained in the intraepithelial compartment by virtue of the interaction between HML-1 and its natural ligand, E-cadherin, which is expressed on epithelial cells. The purpose of this study was to determine whether ocular surface epithelial cells (ocular mucosa) could induce the expression of human mucosal lymphocyte antigen on peripheral blood lymphocytes. METHODS: Human corneal and conjunctival epithelial cells were co-cultured with peripheral blood lymphocytes. Both non-activated and activated lymphocytes were used in the experiments. After 7 days of incubation, lymphocytes were recovered and analysed for the antigens CD8/HML-1, CD4/HML-1, CD3/CD8, CD3/CD4, CD3/CD25, CD8/CD25, and CD4/CD25 by flowcytometry. RESULTS: Significant statistical differences were observed in the CD8/HML-1 expression when conjunctival epithelial cells were co-cultured with non-activated and activated lymphocytes (p = 0.04 for each) and when corneal epithelial cells were co-cultured with non-activated lymphocytes (p = 0.03). Significant statistical difference in CD4/HML-1 expression was observed only when conjunctival epithelial cells were co-cultured with activated lymphocytes (p = 0.02). CONCLUSION: Ocular surface epithelial cells can induce the expression of human mucosal lymphocyte antigen on CD8+ (and to some extent on CD4+) lymphocytes. This may allow the retention of CD8+ and CD4+ lymphocytes within the epithelial compartment of the conjunctiva and play a part in mucosal homing of lymphocytes.

Factors related to non-participation in a population-based breast cancer screening programme.

The main objectives were to describe the measures taken by women to detect breast disease prior to invitation to participate in a screening programme for breast cancer, and to identify factors related to non-participation in this programme. A cross-sectional study was designed at the Breast Cancer Early Detection Program of Sabadell-Cerdanyola (BCEDP), using data collected in interviews conducted face to face or over the telephone with 13 760 women participating in the programme and 280 non-participants. A total of 74.2% of the participants versus 70.4% of the non-participants reported having taken measures to detect breast disease, and 71.7% of the participants had undergone mammography versus 69.6% of the non-participants. Of the 10 057 women who had had mammograms, 58% had done so less than 2 years previously. Factors found to be associated to non-participation in the multivariate analysis were: higher level of education, higher occupational skills or working at home, self- or gynaecological examination of breasts, and having received hormone replacement therapy. Higher age group was the only factor that increased the probability of not having undergone mammography previously. Despite the high prevalence of prior measures to detect breast cancer and the similar prevalence between participating and non-participating women, this behaviour is much less prevalent in the group of women 60 years of age or older.

A novel gene for autosomal dominant Stargardt-like macular dystrophy with homology to the SUR4 protein family.

PURPOSE: To describe a novel gene causing a Stargardt-like phenotype in a family with dominant macular dystrophy and the exclusion of all known genes within the disease locus. METHODS: Meiotic breakpoint mapping in a family of 2314 individuals enabled refinement of the location of the disease gene. The genomic organization and expression profile of known and putative genes within the critical region were determined using bioinformatics, cDNA cloning, and RT-PCR. The coding sequence of genes expressed within the retina was scanned for mutations, by using DNA sequencing. RESULTS: The disease-causing gene (STGD3) was further localized to 562 kb on chromosome 6 between D6S460 and a new polymorphic marker centromeric to D6S1707. Of the four genes identified within this region, all were expressed in the retina or retinal pigment epithelium. The only coding DNA sequence variant identified in these four genes was a 5-bp deletion in exon 6 of ELOVL4. The deletion is predicted to lead to a truncated protein with a net loss of 44 amino acids, including a dilysine endoplasmic reticulum retention motif. The ELOVL4 gene is the fourth known example of a predicted human protein with homology to mammalian and yeast enzymes involved in the membrane-bound fatty acid chain elongation system. The genomic organization of ELOVL4 and primer sets for exon amplification are presented. CONCLUSIONS: ELOVL4 causes macular dystrophy in this large family distributed throughout North America and implicates fatty acid biosynthesis in the pathogenesis of macular degeneration. The PCR-based assay for the 5-bp deletion will facilitate more accurate genetic counseling and identification of other branches of the family.

Autosomal dominant Stargardt-like macular dystrophy.

Autosomal dominant Stargardt-like macular dystrophy is one of the early onset macular dystrophies. It is characterized clinically in its early stages by visual loss and by the presence of atrophic macular changes with or without the presence of yellowish flecks. It is an important retinal dystrophy to study, not only because it has implications in the care and treatment of patients with the condition, but because it also provides important information regarding retinal function. Review of the literature suggests that many of the reported families are linked to chromosome 6q. Genetic and genealogical evidence suggests that these families have descended from a common ancestor or founder. The recent identification of a disease-causing gene that is involved in fatty acid metabolism may have implications in the study of the more common age-related macular degeneration. We review the recent clinical, genetic, and genealogical aspects of autosomal dominant Stargardt-like macular dystrophy.

Experimental autoimmune uveoretinitis in mice (Biozzi ABH and NOD) expressing the autoimmune-associated H-2A(g7) molecule: identification of a uveitogenic epitope.

To determine whether Biozzi ABH (H-2A(g7)) mice were susceptible to chronic experimental autoimmune uveoretinitis (EAU). Biozzi ABH were immunized with the two retinal antigens, interphotoreceptor retinoid binding protein (IRBP) and soluble antigen (S-Ag). Biozzi ABH mice were found to be susceptible to EAU induction with native bovine IRBP. Recombinant protein domains were used to identify IRBP domain 2 (EcR2) as the uveitogenic domain. Histopathological examination indicated that EcR2-induced disease was of a chronic, non-destructive nature in the Biozzi ABH. Using synthetic overlapping peptides corresponding to EcR2, a uveitogenic and immunogenic epitope was identified corresponding to human IRBP511-530. Non-obese diabetic (NOD) mice share the same MHC class II (H-2A(g7)) molecule as the Biozzi ABH, and were also found to be susceptible to EAU induction with EcR2. This study has identified a novel mouse model of EAU, whereby disease is of a chronic, non-destructive nature, which has potential to be used in immune manipulation and neuroprotection studies.

Autosomal dominant Stargardt-like macular dystrophy: founder effect and reassessment of genetic heterogeneity.

OBJECTIVES: To characterize a disease-associated haplotype in 7 families with autosomal dominant Stargardt-like macular dystrophy and to determine whether these families share a common ancestor. METHODS: Twenty-five polymorphic DNA markers spanning known dominant Stargardt-like gene loci were used to determine the haplotype associated with disease. In addition, an extensive genealogical investigation searching for a common ancestor shared by all of the 7 families was performed. RESULTS: We clinically evaluated 171 patients and genotyped 145 samples. The same DNA haplotype on chromosome 6q16 was shared by all evaluated affected members within the 7 families. In addition, we were able to genealogically join all of the families into one larger family consisting of 31 branches and 2314 individuals. Twenty-seven branches have known living descendants, with 7 branches having affected family members. In addition, we refined the critical region for the gene to approximately 1000 kilobases (kb) and eliminated part or all of 9 candidate disease-causing genes. CONCLUSIONS: Our study indicates that most reported cases of autosomal dominant Stargardt-like macular dystrophy in North America are part of a single larger family associated with a gene locus on chromosome 6q16. Furthermore, the DNA haplotype associated with disease is useful in excluding individuals with phenotypically similar retinal conditions. CLINICAL RELEVANCE: The disease-associated haplotype allows for more accurate genetic counseling to be given to individuals with a Stargardt-like phenotype inherited in an autosomal dominant pattern.

Malattia leventinese presenting with subretinal neovascular membrane and hemorrhage.

PURPOSE: To report a case of malattia leventinese involving subretinal hemorrhage. METHODS: Case report. RESULTS: Two weeks after initial presentation, the visual acuity of this 34-year-old man decreased to LE: 20/100. Funduscopic evaluation revealed a subretinal hemorrhage involving the center of the foveal in the left eye that was interpreted as secondary to a neovascular membrane on fluorescein angiography. The patient did well after the removal of the submacular material by pars plana vitrectomy. CONCLUSION: Patients with malattia leventinese may occasionally present with submacular hemorrhage. Prompt diagnosis and intervention may enhance the patient's chance for visual improvement.

Stargardt's macular dystrophy--a patient's perspective.

PURPOSE: The purpose of this paper was to evaluate life experience, including disease characteristics, daily-living activities, employment, interactions with health care professionals, and support services in patients diagnosed with Stargardt's macular dystrophy. METHODS: More than 200 patients with Stargardt's disease responded to a 68-question survey. Results were analyzed using SAS Statistical Analysis Package. RESULTS: Of 203 responders, 142 (70%) were women. Early disease onset occurred in more than 60% of patients. Blurred vision (134, 66%) and glare (183, 90.1%) were the leading symptoms reported. Reading (116, 57.1%), driving (86, 42.4%), and recognizing faces (66, 32.5%) were daily-living activities most difficult to perform. Patients with early disease onset had worse vision at presentation (p = 0.001), faster progression of visual loss (p = 0.007), and were more often diagnosed with a non-physiological visual loss (p = 0.007). Patients with late disease onset had more difficulty with orientation and coping skills (p = 0.02). Sixty-five percent of evaluated adults (108 of 165) were employed. CONCLUSIONS: Although the study illustrates that patients with Stargardt's disease can contribute and function well in contemporary society, issues related to depression, and availability and quality of health care, are still major concerns for this patient population. The study shows differences in progression of visual loss between patients, with early versus late disease onset indicating that age at onset and visual acuity at presentation might be two important factors influencing patient's visual prognosis. Finally, the study suggests parallels in psychological profiles between late age at onset Stargardt's disease and age-related macular degeneration patients.

Efficacy of low and standard midazolam doses for gastroscopy. A randomized, double-blind study.

AIM: To evaluate the efficacy and safety of two different doses of intravenous midazolam (35 and 70 microg/kg) compared to placebo in patients undergoing gastroscopy. PATIENTS AND METHODS: Sixty patients scheduled for diagnostic gastroscopy were selected according to factors previously reported to affect tolerance (Eur J Gastroenterol Hepatol 1999; 11:201-204) and were randomly assigned to receive premedication with midazolam 35 microg/kg iv, midazolam 70 microg/kg iv or placebo iv. Oxygen saturation was continuously monitored during the procedure. Patients' tolerance, time to discharge and post-sedative inconvenience were evaluated using visual analogue scales and a questionnaire. RESULTS: Patients receiving either dose of midazolam showed better tolerance of gastroscopy than those receiving the placebo. Fewer patients receiving 70 or 35 microg/kg of midazolam were reluctant to undergo a further gastroscopy compared to those receiving the placebo (2, 1 and 9 patients respectively, P = 0.01). Compared to patients receiving midazolam 70 microg/kg, those receiving midazolam 35 microg/kg were discharged earlier (29.3+/-14.4 versus 43.1+/-12.4 min respectively, P < 0.001), experienced less post-sedative inconvenience (8 versus 15 patients slept for > 1 h at home respectively, P = 0.02), and suffered fewer clinically relevant desaturation episodes (< 90%) (0 versus 5 patients respectively, P = 0.04). CONCLUSIONS: Low doses of intravenous midazolam (35 microg/kg) are adequate and safe when sedation is indicated for gastroscopy.

Distributing medical images with internet technologies: a DICOM web server and a DICOM java viewer.

With the advent of filmless radiology, it becomes important to be able to distribute radiologic images digitally throughout an entire hospital. A new approach based on World Wide Web technologies was developed to accomplish this objective. This approach involves a Web server that allows the query and retrieval of images stored in a Digital Imaging and Communications in Medicine (DICOM) archive. The images can be viewed inside a Web browser with use of a small Java program known as the DICOM Java Viewer, which is executed inside the browser. The system offers several advantages over more traditional picture archiving and communication systems (PACS): It is easy to install and maintain, is platform independent, allows images to be manipulated and displayed efficiently, and is easy to integrate with existing systems that are already making use of Web technologies. The system is user-friendly and can easily be used from outside the hospital if a security policy is in place. The simplicity and flexibility of Internet technologies makes them highly preferable to the more complex PACS workstations. The system works well, especially with magnetic resonance and computed tomographic images, and can help improve and simplify interdepartmental relationships in a filmless hospital environment.

Cloning of the human monocarboxylate transporter MCT3 gene: localization to chromosome 22q12.3-q13.2.

Lactate transport across cell membranes is mediated by a family of proton-coupled monocarboxylate transporters (MCTs). The retinal pigment epithelium (RPE) expresses a unique member of this family, MCT3. A portion of the human MCT3 gene was cloned by polymerase chain reaction using primers designed from rat RPE MCT3 cDNA sequence. The human genomic sequence was used to design primers to clone human MCT3 cDNA and to identify a bacterial artificial chromosome clone containing the human MCT3 gene. The human MCT3 cDNA contained a 1512-nucleotide open reading frame with a deduced amino sequence 85% identical to rat MCT3. Comparison of the cDNA and genomic sequences revealed that the MCT3 gene was composed of five exons distributed over 5 kb of DNA. The exon-intron borders were conserved between the human and the chicken MCT3 genes. Using radiation hybrid mapping, the MCT3 gene was mapped to chromosome 22 between markers WI11639 and SGC30687. A search of chromosome 22 in the Sanger Centre database confirmed the location of the human MCT3 gene at 22q12.3-q13.2.

Epitope discovery using bacteriophage display: the minimum epitope of an anti-IRBP antibody.

The purpose of this study was to determine, using random peptide library (RPL) technologies, the minimal epitope requirements of the mouse monoclonal anti-interphotoreceptor-retinoid-binding protein antibody, H3B5. This previously characterized antibody is used as an example to examine whether RPL's offer a relatively easy and rapid route to obtaining detailed epitope mapping data.A pentadecamer random peptide library (RPL) displayed on the major coat protein (gene 8) of filamentous bacteriophage (F88-4-15) was used as a target for selection by the anti-IRBP monoclonal antibody, H3B5. Three rounds of library selection were performed, and 90 of the resultant RPL clones were examined for affinity to H3B5 by enzyme-linked immunosorbent assay (ELISA). DNA sequencing of ELISA positive clones provided sequence of the region encoding the random peptide. After three rounds of selection of the RPL, 76.7% of clones examined interacted with H3B5, 17.7% did not show significant binding and 6.6% bound to control antibody also. The essential elements of the peptide epitope were determined by sequence comparison of 24 clones to be the four amino-acid sequence (Aspartic or glutamic acid)-Proline-Arginine-(Leucine, Isoleucine or Valine). This motif [(D/E) PR (L/I/V)] is in agreement, but at greater resolution, than previous synthetic peptide studies where the motif AASEDPRL was identified. Other motifs were found which bound to H3B5 but did not share primary structure similarities (peptidomimetics). Selection from a RPL has rapidly defined the minimal requirements for the H3B5 epitope in fine detail. Such a process offers great potential for investigating antibody-antigen interactions and core sequences of an epitope, and enables the identification of motifs in other proteins which may be recognized by the antibody, providing information on possible cross-reactivity.

Autosomal dominant Stargardt-like macular dystrophy: I. Clinical characterization, longitudinal follow-up, and evidence for a common ancestry in families linked to chromosome 6q14.

PURPOSE: Characterize the phenotype of autosomal dominant Stargardt-like macular dystrophy in two families linked to chromosome 6q14 and determine whether they share a common ancestry. METHODS: Two families spanning 10 generations were identified and studied independently. Participating members were examined and genetic linkage and genotyping performed. RESULTS: Presenting symptoms included decreased vision, hemeralopia, and mild photophobia. The subjective onset of visual loss ranged from age 3 to 50 with a mean of 14 years. A Snellen acuity of 20/200 occurred at a mean age of 22 years. Over decades, the macular lesion enlarged and visual acuity decreased to 20/300 to 20/800. The typical phenotype was well-circumscribed, homogenous atrophy of the retinal pigment epithelium and choriocapillaris in the macula, with surrounding yellow flecks and temporal optic nerve pallor. The phenotypic spectrum included a pattern dystrophy-like appearance, diffuse geographic atrophy, and extensive fundus flecks. Genotyping revealed that the two families were linked to chromosome 6q14 and shared a common haplotype spanning 21 cM between D6S430 and D6S300. The two families were subsequently shown by genealogic investigation to represent different branches of a common kindred. CONCLUSIONS: Families with autosomal dominant Stargardt-like macular dystrophy linked to chromosome 6q14 share a common phenotype and in some cases can be distinguished from similar dystrophies by inheritance pattern and clinical features. The finding that these two families shared a common ancestor suggests the existence of a founder effect. Characterization of the gene for autosomal dominant Stargardt-like macular dystrophy may enable better understanding of this condition and elucidation of its potential role in other forms of macular degeneration.

Identification of factors that influence tolerance of upper gastrointestinal endoscopy.

OBJECTIVE: Unsedated gastroscopy is unpleasant for some patients. The identification of factors related to tolerance would permit the selection of patients for sedation. The aim of the present study was to identify these factors. METHODS: Five hundred and nine patients underwent diagnostic gastroscopy after the administration of topical pharyngeal anaesthesia, without sedation. Patients were grouped as to whether they had undergone prior examinations or not. Tolerance was assessed with a visual analogue scale and a questionnaire. RESULTS: Two hundred and seventy-three (54%) patients underwent gastroscopy for the first time, and 236 (46%) patients had prior experience. Patient tolerance was poor in 84 of 273 (31%) patients undergoing gastroscopy for the first time, and in 61 of 236 (26%) patients with prior experience. Logistic regression analysis identified the following variables related to poor tolerance: (a) in patients undergoing gastroscopy for the first time: presence of gag reflex (odds ratio (OR) = 3.42, 95% confidence interval (CI) 1.90-6.17), apprehension (OR = 2.57, CI 1.33-4.95), young age (OR = 0.95, CI 0.93-0.98) and high level of anxiety (OR = 1.91, CI 0.96-3.89); (b) in patients with prior experience: apprehension (OR = 4.21, CI 1.93-9.20), poor tolerance of prior examinations (OR = 4.92, CI 1.93-12.5) and female (OR = 2.23, CI 1.09-4.57). CONCLUSIONS: The above-mentioned factors are predictive of poor tolerance, and may enable the identification of those patients who might benefit more from sedation for gastroscopy.