Transnasal oesophagoscopy: diagnostic and management outcomes in a prospective cohort of 257 consecutive cases and practice implications.

OBJECTIVES: To determine the success rate, patient tolerability and impact of introducing transnasal oesophagoscopy on clinical practices. DESIGN: Prospective cohort with review of electronic patient records for outcomes. SETTING: UK tertiary centre Otolaryngology Department. PARTICIPANTS: The cohort comprised of two hundred and fifty-seven patients, 128 females (50%) and 129 males (50%) with an age range of 20-91 years; mean age 59 years (sd 13.6). MAIN OUTCOME MEASURES: Success rates, indications, findings and outcomes of patients undergoing transnasal oesophagoscopy and impact on rigid examinations of the pharynx and oesophagus were also considered. RESULTS: Transnasal oesophagoscopy has a high success rate of 97%; it is well tolerated by patients, and poor views are uncommon. Pathology was detected in 44% of patients. The most common indications for transnasal oesophagoscopy were unexplained throat symptoms (50%) and dysphagia (25%). Common positive findings were hiatus hernia (7%), Barrett's oesophagus (5%), dysmotility (5%) and oesophageal candidiasis (5%). Following transnasal oesophagoscopy, 59% of patients were discharged to their referring clinician, 17% continued to undergo otolaryngology follow-up, and 13% were referred to our gastrointestinal colleagues. Following the introduction of transnasal oesophagoscopy, there was a reduction in the number of rigid examinations of the pharynx and oesophagus in the subsequent years, despite an increase in total referrals. CONCLUSIONS: Transnasal oesophagoscopy is a well-tolerated procedure that allows otolaryngologists to make management decisions on common referrals swiftly in the clinic setting avoiding unnecessary investigations, follow-up and referral.

B-type natriuretic peptide receptors in hypertrophied adult rat cardiomyocytes.

Brain natriuretic peptide (BNP) binds to three types of natriuretic peptide receptors, NPR-A, -B and -C (NPRs). The expression shape of BNP and NPRs seems to be an important modulator factor in the pathogenesis of cardiac hypertrophy. The aim of this study was to evaluate the expression of NPRs in an animal model of pressure overload hypertrophy. Left ventricular hypertrophy was induced by chronic abdominal aortic banding in adult male Wistar rats. After six weeks, NPRs gene expression was evaluated with RT-PCR, BNP plasma concentration and BNP positive myocytes were measured with ELISA and immunohistochemistry techniques respectively. NPR-A and NPR-C mRNA expression was significantly increased in left ventricular hypertrophied cardiomyocytes by 1.6-fold and 2.1-fold respectively (P<0.01). Abdominal aortic banding increased significantly BNP plasma concentration (630+/-8pg/ml vs 106+/-4pg/ml; P<0.01). The percentage of BNP positive cells in normal myocardial tissue were 40% while in the hypertrophied one it raised to 80%. The data suggest that in our left ventricular hypertrophy model, the NPR-A and NPR-C receptors were increased in association to the increased BNP level. This relationship may amplify beneficial paracrine/autocrine effects of BNP on cardiac remodelling in response to hemodynamic overload.

[Left segmental omental infarction in a child: conservative treatment]. / Infarctus segmentaire gauche du grand épiploon chez l'enfant: traitement conservateur.

Omental infarction is a rare cause of acute abdomen that usually occurs on the right side. Left omental ischemia is rare in adults and to our knowledge not yet described in children. Its diagnosis, although difficult, is important because it can avoid surgery. We report a case of left segmental omental infarction in an 11-year-old child, diagnosed by imaging studies, treated conservatively, and followed up by ultrasound until complete disappearance of the lesion.

A phase II trial of fractionated vinorelbine/doxorubicin as first-line therapy for advanced breast cancer.

In western countries breast cancer is still the leading cause of death of women. Very promising results have been obtained by combining vinorelbine and doxorubicin, two of the most active drugs in metastatic breast cancer. However, despite the activity reported, this combination has shown a 10% rate of grade 2-4 cardiac toxicity, mainly due to the total cumulative doses of anthracycline delivered. The aim of this study was to divide the total dose of doxorubicin into two administrations on days 1 and 8, in order to cut down its toxicity while maintaining the same activity. Fifty-two chemotherapy naïve patients with metastatic breast cancer entered into the study and were treated with vinorelbine 25 mg/m2 plus doxorubicin 25 mg/m2 both on days 1 and 8 every three weeks. Fifty-one patients were eligible and evaluable for toxicity while 47 of them were evaluable for activity. Haematological toxicity was predominantly related to neutropenia, with grade 3/4 in 16% of cycles. Non-haematological toxicity was represented by alopecia grade 3 (which affected 65% of the patients), local phlebitis and severe constipation. No clinically significant cases of neuropathy or cardiac dysfunction were seen. With regard to activity, 38 out of 47 patients (80%) responded to therapy, nine of them achieving complete responses (19%). Median response duration was 16 months and the median overall survival was 22.7 months. We conclude that the fractionated administration of vinorelbine and doxorubicin is associated with excellent haematological and non-haematological tolerability (especially as regards cardiac toxicity), coupled with high levels of activity comparable to those observed using regimens based on unfractionated administration of treatment.

The framing of teenage health care: organizations, culture, and control.

Adolescent health is one of the most polemical health issues that has swept the United States in recent years. This study is about documenting the process of a project on teenage sex, drug, and alcohol abuse in a small rural California town. It illustrates a dynamic set of concerns that impinge on health issues: development and underdevelopment, experts and lay people, young and old, in a context of the transformation of a rural economy to a prison-based industry. It is also about covert forms of control, pacification, burnout, and teenagers caught in the crossfire between bureaucratic institutions and contradictory messages about adolescent health as they correspond to changing conditions between institutional power holders.

The human papillomavirus type 16 E7 gene product interacts with and trans-activates the AP1 family of transcription factors.

The E7 gene product of human papillomavirus type 16 (HPV16) binds to the retinoblastoma gene product (pRb) and dissociates pRb-E2F complexes. However, the observation that the ability of E7 to bind pRb is not required for the HPV16-induced immortalization of primary keratinocytes prompted a search for other cellular factors bound by E7. Using a glutathione-S-transferase (GST) fusion protein system, we show that E7 complexes with AP1 transcription factors including c-Jun, JunB, JunD and c-Fos. The ability of E7 to complex with c-Jun in vivo is demonstrated by co-immunoprecipitation and the yeast two-hybrid system. An analysis of E7 point mutants in the GST system indicates that the E7 zinc-finger motif, but not the pRb binding domain, is involved in these interactions. Using c-Jun deletion mutants, E7 binding maps between amino acids 224 and 286 of c-Jun. E7 trans-activates c-Jun-induced transcription from a Jun responsive promoter, and this activity correlates with the ability of E7 mutants to bind Jun proteins. Finally, a transcriptionally inactive c-Jun deletion, which can bind E7, interferes with the E7-induced transformation of rat embryo fibroblasts in cooperation with an activated ras, indicating that the Jun-E7 interaction is physiologically relevant and that Jun factors may be targeted in the E7 transformation pathway.

Nuclear magnetic resonance studies of 6-fluorotryptophan-substituted rat cellular retinol-binding protein II produced in Escherichia coli. Analysis of the apoprotein and the holoprotein containing bound all-trans-retinol and all-trans-retinal.

Rat cellular retinol-binding protein II (CRBP II) is a 15.6-kDa intestinal protein which binds all-trans-retinol and all-trans-retinal but not all-trans-retinoic acid. We have previously analyzed the interaction of Escherichia coli-derived rat apoCRBP II with several retinoids using fluorescence spectroscopic techniques. Interpretation of these experiments is complicated, because the protein has 4 tryptophan residues. To further investigate ligand-protein interactions, we have utilized 19F nuclear magnetic resonance (NMR) spectroscopy of CRBP II labeled at its 4 tryptophan residues with 6-fluorotryptophan. Efficient incorporation of 6-fluorotryptophan (93%) was achieved by growing a tryptophan auxotroph of E. coli harboring a prokaryotic expression vector with a full-length rat CRBP II cDNA on defined medium supplemented with the analog. Comparison of the 19F NMR spectra of 6-fluorotryptophan-substituted CRBP II with and without bound all-trans-retinol revealed that resonances corresponding to 2 tryptophan residues (designated WA and WB) undergo large downfield changes in chemical shifts (2.0 and 0.5 ppm, respectively) associated with ligand binding. In contrast, 19F resonances corresponding to two other tryptophan residues (WC and WD) undergo only minor perturbations in chemical shifts. The 19F NMR spectra of 6-fluorotryptophan-substituted CRBP II complexed with all-trans-retinal and all-trans-retinol were very similar, suggesting that the interactions of these two ligands with the protein are similar. Molecular model building, based on the crystalline structures of two homologous proteins was used to predict the positions of the 4 tryptophan residues of CRBP II and to make tentative resonance assignments. The fact that ligand binding produced residue-specific changes in the chemical shifts of resonances in CRBP II suggests that NMR analysis of isotopically labeled retinoid-binding proteins expressed in E. coli will provide an alternate, albeit it complementary, approach to fluorescence spectroscopy for examining the structural consequences of their association with ligand.