Treatment patterns and intensification within 5 year of follow-up of the first-line anti-TNFα used for the treatment of IBD: Results from the VERNE study.

BACKGROUND: Anti-TNFα represent one of the main treatment approaches for the management of inflammatory bowel diseases (IBD). Therefore,the evaluation of their treatment patterns over time provides valuable insights about the clinical value of therapies and associated costs. AIMS: To assess the treatment patterns with the first anti-TNFα in IBD. METHODS: Retrospective, observational study. RESULTS: 310 IBD patients were analyzed along a 5-year follow-up period. 56.2% of Crohn's disease (CD) patients started with adalimumab (ADA), while 43.8% started with infliximab (IFX). 12.9% of ulcerative colitis (UC) patients initiated with ADA, while 87.1% initiated with IFX. Treatment intensification was required in 28.9% of CD and 37.1% of UC patients. Median time to treatment intensification was shorter in UC than in CD (5.3 vs. 14.3 months; p = 0.028). Treatment discontinuation due to reasons other than remission were observed in 40.7% of CD and 40.5% of UC patients, although, in UC patients there was a trend to lower discontinuation rates with IFX (36.6%) than with ADA (66.7%). Loss of response accounted for approximately one-third of discontinuations, in both CD and UC. CONCLUSIONS: Around one-third of IBD biologic-naive patients treated with an anti-TNFα required treatment intensification (earlier in UC) and around 40% discontinued the anti-TNFα due to inappropriate disease control.

Influence of digital hypothermia on lamellar events related to IL-6/gp130 signalling in equine sepsis-related laminitis.

BACKGROUND: Interleukin-6 (IL-6) is consistently increased in the digital lamellae in different studies of sepsis-related laminitis (SRL). IL-6 signalling through the gp130 receptor activates similar signalling (i.e. mTORC1-related signalling) previously reported to be activated in models of endocrinopathic laminitis. OBJECTIVES: To assess the activation state of signalling proteins downstream of IL-6/gp130 receptor complex activation in an experimental model of SRL. STUDY DESIGN: Randomised experimental study. METHODS: Lamellar phospho-(P) protein concentrations downstream of the IL-6/gp130 receptors were assessed in the oligofructose (OF) model of SRL. Fifteen Standardbred horses were administered water (CON, n = 8) or oligofructose (OF, n = 7) via a nasogastric tube. At 12 h post-OF/water administration, one randomly assigned forelimb was exposed to continuous digital hypothermia (CDH) by placement in ice water (ICE, maintained at <7°C); the other forelimb was maintained at ambient temperature (AMB). Lamellar tissue samples were collected after 24 h of CDH from both ICE and AMB forelimbs and immediately snap-frozen. Lamellar proteins of interest were assessed by immunoblotting and immunofluorescence. RESULTS: Immunoblotting revealed increase (P<0.05) in the phosphorylation states of Akt (Ser 473), RPS6 (Ser235/236), RPS6 (Ser240/244), STAT3 (Ser727) and STAT3 (Tyr705) in lamellar tissue from OF-treated animals (AMB OF vs. AMB CON limbs); CDH resulted in decreased (P<0.05) lamellar concentrations of phosphorylated Akt, p70S6K, RPS6 (235/236), RPS6 (240/244) and STAT3 (S727) in OF-treated animals (AMB OF vs. ICE OF). Immunofluorescence showed that activated/phosphorylated forms of RPS6 and STAT3 were primarily localised to lamellar epithelial cells. MAIN LIMITATIONS: The nature, sequence and timing of sub-cellular events in this experimental model may differ from those that accompany naturally occurring sepsis. CONCLUSIONS: There were increased lamellar concentrations of activated signalling proteins downstream of the IL-6/Gp130 receptor complex in OF-treated horses; CDH inhibited this activation for the majority of the proteins assessed. These results demonstrate similar lamellar signalling (e.g. mTORC1-related signalling) and, therefore, possible therapeutic targets occurring in sepsis-related laminitis as previously reported in models of endocrinopathic laminitis.

Not Another ACS Rule Out.

CASE: A 50 year old African-American woman with diabetes, hypertension, and hyperlipidemia presented with progressively worsening retro-sternal chest pain, exacerbated by activity and relieved by rest. She also endorsed a thirty-pound unintentional weight loss, and dysphagia. She was dysarthric with left-sided Bell's Palsy and a palpable left axillary lymph node. She had been evaluated at several hospitals in the previous months for similar typical chest pain. Her troponin values were normal, and an EKG showed T-wave inversions in leads I and aVL. On echocardiography, her ejection fraction was 45 percent with anterolateral hypokinesis. She was treated for NSTEMI, and an angiogram showed 95 percent stenosis of the right coronary artery. A modified barium swallow study revealed weakened swallowing with aspiration of thin liquids. An MRI Brain demonstrated scattered T2/ FLAIR hyper-intense foci in the subcortical white matter and focal meningeal thickening. ANA, dsDNA, ANCA, and Lyme antibodies were all negative, and a chest CT showed hilar lymphadenopathy. Cardiac MRI demonstrated scattered foci of delayed enhancement in the mid-myocardium and sub-epicardium without infarction. An endobronchial biopsy of hilar lymph nodes showed two small epithelioid granulomas, consistent with Sarcoidosis. She was started on high-dose corticosteroids with rapid improvement. A repeat modified barium swallow study was normal and a repeat echocardiogram demonstrated recovered ejection fraction of 55 percent with improved wall motion in the septum and apex. Additionally, her left-sided Bell's Palsy and dysarthria improved after several days of therapy. DISCUSSION: To our knowledge, this report is the third case of multi-organ Sarcoidosis presenting as ACS. This case depicts the simultaneous presentation of neurologic, pharyngeal, pulmonary, and cardiac Sarcoidosis. Myocardial involvement in Sarcoidosis is rare and usually presents as conduction abnormalities with arrhythmia rather than ACS. Though her symptoms were consistent with Sarcoidosis, she had multiple risk factors for coronary atherosclerosis including diabetes, hypertension, and hyperlipidemia. This case highlights the importance of including Sarcoidosis in the differential diagnosis for patients with recurrent typical chest pain of uncertain etiology.

Informing etiologic research priorities for squamous cell esophageal cancer in Africa: A review of setting-specific exposures to known and putative risk factors.

Esophageal squamous cell carcinoma (ESCC) is one of the most common cancers in most Eastern and Southern African countries, but its etiology has been understudied to date. To inform its research agenda, we undertook a review to identify, of the ESCC risk factors which have been established or strongly suggested worldwide, those with a high prevalence or high exposure levels in any ESCC-affected African setting and the sources thereof. We found that for almost all ESCC risk factors known to date, including tobacco, alcohol, hot beverage consumption, nitrosamines and both inhaled and ingested PAHs, there is evidence of population groups with raised exposures, the sources of which vary greatly between cultures across the ESCC corridor. Research encompassing these risk factors is warranted and is likely to identify primary prevention strategies.

Prolonged exposure to arsenic in UK private water supplies: toenail, hair and drinking water concentrations.

Chronic exposure to arsenic (As) in drinking water is an established cause of cancer and other adverse health effects. Arsenic concentrations >10 µg L(-1) were previously measured in 5% of private water supplies (PWS) in Cornwall, UK. The present study investigated prolongued exposure to As by measuring biomarkers in hair and toenail samples from 212 volunteers and repeated measurements of As in drinking water from 127 households served by PWS. Strong positive Pearson correlations (rp = 0.95) indicated stability of water As concentrations over the time period investigated (up to 31 months). Drinking water As concentrations were positively correlated with toenail (rp = 0.53) and hair (rp = 0.38) As concentrations - indicative of prolonged exposure. Analysis of washing procedure solutions provided strong evidence of the effective removal of exogenous As from toenail samples. Significantly higher As concentrations were measured in hair samples from males and smokers and As concentrations in toenails were negatively associated with age. A positive association between seafood consumption and toenail As and a negative association between home-grown vegetable consumption and hair As was observed for volunteers exposed to <1 As µg L(-1) in drinking water. These findings have important implications regarding the interpretation of toenail and hair biomarkers. Substantial variation in biomarker As concentrations remained unaccounted for, with soil and dust exposure as possible explanations.

Use of laser capture microdissection for the assessment of equine lamellar basal epithelial cell signalling in the early stages of laminitis.

REASONS FOR PERFORMING STUDY: Dysadhesion of laminar basal epithelial cells (LBECs) from the underlying dermis is the central event leading to structural failure in equine laminitis. Although many studies of sepsis-related laminitis have reported multiple events occurring throughout the lamellar tissue, there is minimal information regarding signalling events occurring specifically in LBECs. OBJECTIVES: To determine signalling events in the LBECs during the early stages of carbohydrate-induced laminitis. STUDY DESIGN: Experimental study. METHODS: Eight horses were given an overload of carbohydrate (CHO) consisting of corn starch mixture via nasogastric tube. Prior to administration of CHO, lamellar biopsies were taken from the left forefoot (control [CON]). Biopsies were taken from the left hind foot at the onset of fever (developmental [DEV]) and from the right forefoot at the onset of Obel grade 1 lameness (OG1). Laminar basal epithelial cells were isolated from cryosections using a laser capture microdissection (LCM) microscope. Next generation sequencing (RNA-seq) was used to identify transcripts expressed in the LBECs for each time point and bioinformatic analysis was performed with thresholds for between group comparisons set at a greater than 2-fold change and P value ≤0.05. RESULTS: Forty genes (22 increased/18 decreased) were significantly different from DEV time vs. CON and 107 genes (57 increased/50 decreased) were significantly different from OG1 time vs. CON. Significant increases in inflammatory genes were present in addition to significantly altered expression of genes related to extracellular matrix composition, stability and turnover. CONCLUSIONS: Signalling related to inflammatory response and extracellular matrix regulation was strongly represented at the DEV and OG1 times. These results indicate that the LBEC is not only a casualty but also an active participant in lamellar events leading to structural failure of the digital lamellae in equine laminitis.

Laminar inflammatory events in lean and obese ponies subjected to high carbohydrate feeding: Implications for pasture-associated laminitis.

REASONS FOR PERFORMING STUDY: Acute, massive enteral carbohydrate overload is associated with laminar inflammation in equids; it is unclear if the same is true for a more prolonged period of moderate dietary carbohydrate intake. OBJECTIVES: To characterise laminar inflammation in ponies exposed to a dietary carbohydrate challenge meant to mimic acute pasture exposure. STUDY DESIGN: In vivo experiment. METHODS: Mixed-breed ponies (n = 22) received a diet of hay chop (nonstructural carbohydrate [NSC] ∼7% on a dry matter [DM] basis) for 4 weeks prior to initiation of the experimental feeding protocol. Following dietary acclimation, ponies were stratified into either Lean (n = 11, body condition score [BCS] ≤4) or Obese (n = 11, BCS ≥7) groups and each group further stratified to either remain on the control, low NSC diet (n = 5 each for Obese and Lean) or receive a high NSC diet (hay chop supplemented with sweet feed and oligofructose, total diet ∼42% NSC; n = 6 each for Obese and Lean) for a period of 7 days. Laminar samples were collected following euthanasia and sections stained immunohistochemically for CD163, MAC387/calprotectin and cyclo-oxygenase-2 (COX-2) using commercially available antibodies. The number of CD163 (+) and MAC387(+) cells was quantified for each section; the distribution of COX-2 expression was qualitatively assessed. Laminar mRNA concentrations of several proinflammatory molecules (interleukin-1ß [IL-1ß], IL-6, tumour necrosis factor-α [TNFα], IL-8, IL-10, monocyte chemoattractant protein-1 [MCP-1], MCP-2), inducible nitric oxide synthase (iNOS), intercellular adhesion molecule-1 (ICAM-1), E-selectin, plasminogen activator inhibitor-1 (PAI-1) and COX-2 were evaluated using real-time quantitative polymerase chain reaction (qPCR). RESULTS: High carbohydrate feeding resulted in no increase in laminar proinflammatory cytokine expression; laminar COX-2 expression was increased by high carbohydrate feeding. No laminar leucocyte infiltration was observed in response to high carbohydrate feeding. CONCLUSIONS: These results suggest that the marked laminar inflammation observed in models of sepsis-associated laminitis may not play a central role in the pathophysiology of pasture-associated laminitis.

Effect of dietary nonstructural carbohydrate content on activation of 5'-adenosine monophosphate-activated protein kinase in liver, skeletal muscle, and digital laminae of lean and obese ponies.

BACKGROUND: In EMS-associated laminitis, laminar failure may occur in response to energy failure related to insulin resistance (IR) or to the effect of hyperinsulinemia on laminar tissue. 5'-Adenosine-monophosphate-activated protein kinase (AMPK) is a marker of tissue energy deprivation, which may occur in IR. HYPOTHESIS/OBJECTIVES: To characterize tissue AMPK regulation in ponies subjected to a dietary carbohydrate (CHO) challenge. ANIMALS: Twenty-two mixed-breed ponies. METHODS: Immunohistochemistry and immunoblotting for total AMPK and phospho(P)-AMPK and RT-qPCR for AMPK-responsive genes were performed on laminar, liver, and skeletal muscle samples collected after a 7-day feeding protocol in which ponies stratified on body condition score (BCS; obese or lean) were fed either a low-CHO diet (ESC + starch, approximately 7% DM; n = 5 obese, 5 lean) or a high-CHO diet (ESC + starch, approximately 42% DM; n = 6 obese, 6 lean). RESULTS: 5'-Adenosine-monophosphate-activated protein kinase was immunolocalized to laminar keratinocytes, dermal constituents, and hepatocytes. A high-CHO diet resulted in significantly decreased laminar [P-AMPK] in lean ponies (P = .03), but no changes in skeletal muscle (lean, P = .33; obese, P = .43) or liver (lean, P = .84; obese, P = .13) [P-AMPK]. An inverse correlation existed between [blood glucose] and laminar [P-AMPK] in obese ponies on a high-CHO diet. CONCLUSIONS AND CLINICAL IMPORTANCE: Laminar tissue exhibited a normal response to a high-CHO diet (decreased [P-AMPK]), whereas this response was not observed in liver and skeletal muscle in both lean (skeletal muscle, P = .33; liver, P = .84) and obese (skeletal muscle, P = .43; liver, P = .13) ponies.

Inflammatory bowel disease and thromboembolism. Is inflammation at the centre of the clot?

Thromboembolic events are well recognised in patients with inflammatory bowel disease (IBD). We present three cases which highlight the need for vigilance with respect to this complication. We also propose that consideration be given to re-evaluating disease activity in those patients who develop thromboembolic complications.

Medium term results of per-operative knee arthroscopy in confirming suitability for unicompartmental arthroplasty.

INTRODUCTION: The status of the lateral compartment of the knee is a determining factor in the long-term outcome of medial unicompartmental arthroplasty (UKA). Various methods of assessing the lateral compartment have been used including stress radiography, radioisotope bone scanning, magnetic resonance imaging and visualisation at the time of surgery. Arthroscopy is another means of directly assessing the integrity of the articular cartilage and the meniscus in the lateral compartment. PURPOSE: This study aims to show that per-operative arthroscopy is a safe and effective means of deciding whether to proceed with UKA or convert to total knee arthroplasty (TKA). METHOD: We have used arthroscopy of the lateral compartment to assess suitability for UKA in 151 knees over 8 years. RESULTS: At time of arthroscopy 34 knees underwent a change of surgical plan from UKA to TKA (22.5%). There has been one revision to TKA and 2 bearing exchanges for dislocation. CONCLUSION: Immediate per-operative arthroscopy is a reliable method for assessing the suitability of a knee for UKA, in particular the lateral compartment.

Efecto antiinflamatorio de la enoxolona en un modelo exvivo de mucosa gingival humana / Antiinflammatory effect of enoxolone in an exvivo model of human gingival mucosa

Introducción. Este estudio tenía por finalidad precisar las modalidades de utilización y el mecanismo de acción antiinflamatoria de la enoxolona contenida en un dentífrico y en una solución bucal. Material y método. Por medio de un modelo de encía humana mantenida con sobrevida, se pudo inducir una reacción inflamatoria mediante la aplicación de mediadores proinflamatorios (SP y LPS) y realizar, en doble ciego contra placebo, una evaluación de los parámetros histológicos y bioquímicos (IL8) de la inflamación previa aplicación del dentífrico. Para la solución bucal, la evaluación bioquímica se realizó por dosificación del IL 1. Resultados. El dentífrico generó una disminución significativa del edema, de la dilatación de los capilares y de la excreción del IL8. La solución generó una disminución de la excreción del IL l. Discusión. La enoxolona ejerce un efecto antiinflamatorio, cualquiera sea el vehículo utilizado.

Relapsing tubulointerstitial nephritis in an adolescent with inflammatory bowel disease without aminosalicylate exposure.

A 14-year-old boy presented with ongoing constipation as a manifestation of newly diagnosed Crohn's disease (CD) and a concomitant decline in renal function with biopsy-proven interstitial nephritis. Initiation of steroid therapy and mesalazine was associated with an improvement in symptoms and renal function. We describe a rare case of a 5-aminosalicylic acid (5-ASA)-naïve patient who developed interstitial nephritis in association with CD with no evidence of other primary glomerulopathy. A unique feature of the case being a profound systemic inflammatory response at the time of diagnosis and a relapse in nephritis 2 months after cessation of mesalazine in the absence of any macroscopic colitis.

Antimicrobial peptide modulation in a differentiated reconstructed gingival epithelium.

Gingival innate immunity has been studied by using biopsies and normal or transformed epithelial cell monolayers. To overcome individual biological variabilities and as a physiological alternative, we have proposed using a reconstructed tissue equivalent. In this study, we investigated the functionality and the stage of differentiation of a reconstructed human gingival epithelium. We also characterized this epithelium at the molecular level to investigate its differentiation stage compared with native human gingival epithelium. The expression levels and localization of markers related to proteins and lipids of well-differentiated stratified epithelium, such as cytokeratins, cornified envelope proteins and enzymes, or to factors in lipid synthesis and trafficking were examined. Immunohistochemistry revealed similar localization patterns in both types of epithelia and mRNA quantification showed a close resemblance of their expression profiles. We further revealed that, like native gingiva, reconstructed gingival epithelium was able to respond to pro-inflammatory or lipopolysaccharide stimuli by producing antimicrobial peptides hbetaD-2, hbetaD-3 or LL-37. Finally, we demonstrated that reconstructed human gingival epithelium, as a model, was good enough to be proposed as a functional equivalent for native human gingival epithelium in order to study the regulation of gingival innate immunity against periodontal infections.

Endocapsular iris reconstruction implants for acquired iris defects: a clinical study.

PURPOSE: To report the clinical efficacy, safety, and long-term follow-up data on the use of endocapsular iris reconstruction implants (IRIs) during cataract surgery in patients with acquired iris defects. METHODS: Single centre, retrospective, noncomparative, interventional case series. Five eyes of four patients with acquired iris defects and visually significant cataracts underwent clear cornea phacoemulsification and intraocular lens (IOL) implantation combined with insertion of endocapsular IRI. Data on the best-corrected visual acuity (BCVA), degree of preoperative and postoperative glare, photophobia, surgical complications, and long-term implant stability were analysed. RESULTS: In all patients, IRI were successfully placed within the capsular bag during cataract surgery. There were no intraoperative or postoperative complications. Mean follow-up period was 29 months (range, 16-42). BCVA, subjective glare, and photophobia improved in all five eyes. Desired anatomic results were achieved in all of them. CONCLUSIONS: In patients with acquired iris defects, implantation of endocapsular IRI during cataract surgery appears to be a safe and effective procedure. At a mean time gate of 29 months, both IOLs and IRI appeared to remain stable within the capsular bag.

[Wound healing effect of Eludril in a model of human gingival mucosa]. / L'effet cicatrisant d'Eludril sur un modèle de muqueuse gingivale humaine.

INTRODUCTION: The aim of this study was to evaluate and to compare the potential for wound healing of the buccal mucosa with the use of two mouth rinses; one containing 0.10% chlorhexidine with alcohol, the second containing 0.12% chlorhexidine without alcohol. MATERIAL AND METHOD: Using a model of human buccal mucosa kept alive ex vivo, an immunohistochemical assessment of the mitotic potential of epithelial cells and a biochemical evaluation of the capacity of the fibroblasts of the gingival mucosa to synthesize collagen was performed. RESULTS: A mouth rinse containing 0.10% chlorhexidine with alcohol (Eludril) did not alter the potential for epithelial proliferation and for collagen synthesis within the gingival chorion grown in survival conditions. The results revealed a significant difference between the two mouth rinses for each of the parameters studied. The most favourable results were obtained with the mouth rinse containing alcohol. DISCUSSION: The presence of alcohol in a mouth rinse containing 0.10% chlorhexidine has no deleterious effects on healing capacity. On the contrary, it helps stimulate wound healing. The combination of chlorhexidine plus alcohol is superior for healing, chlorhexidine alone does not show any significant difference compared with the control.

The meniscal flounce: a valuable arthroscopic sign.

PURPOSE: The purpose of this study was to characterise the incidence and significance of the meniscal flounce. TYPE OF STUDY: Prospective Cohort Study. METHOD: A prospective study of 1088 consecutive knee arthroscopies. RESULTS: Intact menisci tended to have a flounce of characteristic size and position. The presence of this 'normal' flounce was closely correlated with an intact meniscus (p<0.0001). For the medial meniscus with a small flounce in zone 3 the sensitivity, specificity, and positive predictive value (PPV) for an intact medial meniscus were 68.5%; 92.9%; and 92.1% respectively. Conversely the presence of meniscal pathology correlated closely with either an absent or abnormal flounce (p<0.0001). The absence of a medial flounce had sensitivity, specificity, and PPV for a meniscal tear of 82.8%; 84.9%; and 81.9% respectively. CONCLUSIONS: The findings of this study are useful for arthroscopists especially when there is difficulty visualising all of the posterior half of the meniscus. In this situation the presence of a normal flounce is likely to signify an intact meniscus. However the presence of an abnormal or absent flounce may be the sign of an occult meniscal tear requiring better exposure.

Evaluation of the inclusion of soybean oil and soybean processing by-products to soybean meal on nutrient composition and digestibility in swine and poultry.

This experiment was designed to evaluate the effects of selected soybean (SB) processing byproducts (gums, oil, soapstock, weeds/trash) when added back to soybean meal (SBM) during processing on the resulting nutrient composition, protein quality, nutrient digestibility by swine, and true metabolizable energy (TMEn) content and standardized AA digestibility by poultry. To measure ileal DM and nutrient digestibility, pigs were surgically fitted with a T-cannula in the distal ileum. The concentration of TMEn and the standardized AA digestibility by poultry were determined using the precision fed cecectomized rooster assay. Treatments in the swine experiment included SBM with no by-products; SBM with 1% gum; SBM with 3% gum; SBM with 0.5% soapstock; SBM with 1.5% soapstock; SBM with 2% weeds/trash; SBM with a combination of 3% gum, 1.5% soapstock, and 2% weeds/trash; SBM with 5.4% soybean oil; and roasted SB. A 10 x 10 Latin square design was utilized. The experiment was conducted at the University of Illinois, Urbana-Champaign, and at The Ohio State University, Columbus. In the swine experiment, apparent ileal DM, OM, CP, and AA digestibilities were reduced (P < 0.05) when pigs consumed the combination by-product diet compared with the diet containing no by-products. Apparent ileal digestibilities of DM, CP, and total essential, total nonessential, and total AA were lower (P < 0.05) for any diet containing by-products compared with the diet with no by-products. Apparent ileal digestibilities of DM, OM, CP, and AA were lower (P < 0.05) for the roasted SB-compared with the SB oil-containing diet. In the rooster experiment, TMEn values were greater (P < 0.05) for roasted SB compared with SBM with no by-products and increased linearly as the addition of soapstock increased. Individual, total essential, total nonessential, and total AA digestibilities were lower (P < 0.05) for roosters fed roasted SB versus SBM devoid of by-products. Gums, soapstock, and weeds/trash reduce the nutritive value of the resultant meal when they are added back during processing.

Differential effects of temperature and maturity stage on hepatic estrogen receptor characteristics of Atlantic salmon.

In order to determine if elevated temperature during vitellogenesis had a detrimental effect on hepatic estrogen receptors of Atlantic salmon (Salmo salar), 3H-estradiol saturation binding analysis, using one- and two-site binding models, was carried out on extracts of hepatic cytosols from fish held at 14, 18 or 22 degrees C over the austral period of peak vitellogenesis (February to April). With one-site binding analysis, no temperature related difference in either receptor affinity (Kd) or number (Bmax) was found at each sampling point, but there was an apparent decrease in both affinity and number at each temperature over the period of the study. However, some analyses, notably at 22 degrees C during February, were best described using a two-site binding model. At this temperature and time, there was a clear separation of binding affinity into high and low components (Kd = 0.67+/-S.E. 0.05 and 20+/-S.E. 5.6 nM, respectively) (n = 4), which suggests that February was a critical time of temperature related hepatic sensitivity to estrogen. These results support those of other studies where we found that February was also a sensitive time with respect to temperature impairment of in vitro follicular estrogen synthesis, and the greatest period of in vivo temperature sensitivity.

Premedication for bronchoscopy in older patients: a double-blind comparison of two regimens.

INTRODUCTION: Older patients are the most prevalent age cohort requiring bronchoscopy. Prior sedation should be offered to improve patient comfort and operator technical ease. Older patients have increased sensitivity to centrally acting drugs increasing the procedural risk. This perceived risk may limit access to bronchoscopy in older patients. There have been no systematic prospective placebo-controlled studies in older patients. We compared a novel premedication regimen-oral temazepam plus nebulised Lignocaine (new treatment) to an established regimen of intravenous alfentanyl (control). METHODS: Consecutive patients 75 years and older referred for bronchoscopy were considered. Twenty-five patients were randomly assigned to each group. The primary outcome measure was the lowest oxygen saturation recorded from the administration of IV drugs and for 30 min post-bronchoscopy. RESULTS: The lowest mean oxygen saturation in the new treatment group was 92.2% (90.3-94.2) and in the control group 91.1% (89.2-93.1). This was not statistically different (P = 0.370). There were no adverse events. CONCLUSION: This is the largest prospective study to date on an older population undergoing bronchoscopy supporting previous retrospective findings regarding the safety of this procedure. Determined by oxygen saturations there is no difference in safety between premedication regimens comprising oral temazepam/nebulised lignocaine or intravenous alfentanyl.