Association of residential greenness with the risk of metabolic syndrome in Chinese older adults: a longitudinal cohort study.

AIMS: We aimed to investigate the association between residential greenness and MetS in older Chinese adults. METHODS: Longitudinal data on sociodemographic characteristics and lifestyle were collected from the Shenzhen Healthy Ageing Research (SHARE) cohort. Greenness exposure was assessed through satellite-derived Normalized Difference Vegetation Index (NDVI) values in the 250-m, 500-m, and 1250-m radius around the residential address for each participant. MetS was defined by standard guidelines for the Chinese population. RESULTS: A total of 49,893 older Chinese adults with a mean age of 70.96 (SD = 5.26) years were included in the study. In the fully adjusted models, participants who lived in the highest quartile of NDVI250-m, NDVI500-m, and NDVI1250-m had a 15% (odds ratio, OR = 0.85, 95% confidence interval, CI: 0.80-0.90), 12% (OR = 0.88, 95% CI: 0.83-0.93), and 11% (OR = 0.89, 95% CI: 0.85-0.95) lower incidence of MetS, respectively, than those living in the lowest quartile (all p-trend < 0.01). Interactions and subgroup analyses showed that age, sex, smoking status, and drinking status were significant effect modifiers (p-interaction for all NDVI < 0.05). CONCLUSIONS: Residential greenness is associated with a lower risk of MetS in Chinese older adults, especially for young older adults, females, non-smokers, and non-drinkers.

Advances in endovascular treatment of acute ischaemic stroke.

Over the past decade, there have been rapid advancements in ischaemic stroke reperfusion treatments. However, clear clinical benefit is yet to be shown in large clinical trials. In this review, the major studies in different types of endovascular treatments including intra-arterial thrombolysis, aspiration devices, mechanical clot retrievers and the new stent retrievers are discussed. First-generation mechanical thrombectomy devices such as the MERCI Retriever (Stryker, Kalamazoo, MI, USA) and Penumbra aspiration device (Penumbra Inc., Alameda, CA, USA) demonstrated safety and higher rates of recanalisation in the MERCI and Penumbra Pivotal Stroke Trial; however, there was no significant improvement in clinical outcome. Second-generation endovascular stent retrieval devices Solitaire (ev3 Neurovascular, Irvine, CA, USA) and Trevo (Stryker) have shown promising results. In preliminary trials, SOLITAIRE with the Intention for Thrombectomy (SWIFT) and Thrombectomy Revascularization of Large Vessel Occlusions (TREVO), both showed rates of recanalisation close to 90% and significantly improved clinical outcomes compared with the MERCI study, but the recent landmark studies for endovascular treatment (Interventional Management of Stroke (IMS III), Mechanical Retrieval and Recanalisation of Stroke Clots Using Embolectomy (MR-RESCUE) and SYNTHESIS) did not show any clinical benefit from endovascular treatment compared with standard intravenous therapy. However, moving forward, the recent Multicenter Randomized Clinical Trial of Endovascular Treatment for Acute Ischaemic Stroke in the Netherlands (MR-CLEAN) study results have shown marked improvements in recanalisation, reperfusion and functional outcome in patients receiving endovascular treatment (97% using stent retrievers) within 6 h in addition to standard medical care. Overall, although evidence regarding the efficacy of endovascular treatment in acute stroke has been equivocal, recent publications of large multicentre randomised controlled trials indicate benefit of intra-arterial stent retriever reperfusion in patients selected by appropriate imaging and treated early by experienced operators, and it will likely remain an important adjunct to established medical treatment with intravenous tPA.

Is general anaesthesia preferable to conscious sedation in the treatment of acute ischaemic stroke with intra-arterial mechanical thrombectomy? A review of the literature.

INTRODUCTION: Intra-arterial mechanical thrombectomy (IAMT) is an endovascular technique that allows for the acute retrieval of intravascular thrombi and is increasingly being used for the treatment of acute ischaemic stroke (AIS). There are currently two anaesthetic options during IAMT: general anaesthesia (GA) and conscious sedation (CS). The decision to use GA versus CS is the source of controversy, as it requires careful balance between patient pain, movement and airway protection whilst minimising time delay and haemodynamic fluctuations. This review examines and summarises the evidence for the use of GA versus CS in the treatment of AIS by IAMT. METHODS: Studies were identified using systematic bibliographic searches. The five applicable studies were analysed with reference to overall outcomes and the key parameters that govern the decision to use GA or CS. The key parameters included the impact of GA and CS on pain, complication rates, time delays, airway protection and haemodynamic stability. RESULTS: Several retrospective analyses have shown that the use of GA is associated with adverse outcomes. CONCLUSION: Intra-arterial mechanical thrombectomy under general anaesthesia is associated with poor outcomes in observational studies. It is reasonable to offer conscious sedation as the preferred option where adverse patient factors such as agitation are lacking.

Does intra-arterial thrombolysis have a role as first-line intervention in acute ischaemic stroke?

Minimization of the clinical impact of acute ischaemic stroke depends largely on prompt restoration of blood flow to underperfused regions of the brain. Intravenous thrombolysis (IVT) is currently the first-line intervention for acute ischaemic stroke, with proven efficacy in randomized controlled trials. There are several major limitations associated with IVT, in particular, the relatively poor outcomes in large artery occlusions. A major emerging modality in acute stroke management is intra-arterial thrombolysis (IAT), whereby clot-retrieval or thrombolytics are applied under angiographic guidance to the site of the clot. Strong arguments exist for the use of IAT as first-line ischaemic stroke management in preference of IVT, especially with large intracranial artery occlusion. Despite these arguments, the lack of data from randomized controlled studies in IAT means that it is appropriate to continue the current practice of IVT as first-line treatment for the majority of acute ischaemic strokes at this stage. Advanced neuroimaging techniques, in particular a 'multimodal' computed tomography (CT) approach combining non-contrast CT, CT angiography and perfusion CT, may serve as a valuable triage tool for patient selection. Ongoing research is required in endovascular approaches to stroke; in particular, randomized controlled trials with a focus on clinical outcomes and tackling the inherent delays between symptom onset and treatment.

Targeting mTOR-dependent tumours with specific inhibitors: a model for personalized medicine based on molecular diagnoses.

Cancer cells are characterized by aberrant growth arising from deregulated signalling pathways. The mammalian target of rapamycin (mTOR) pathway integrates multiple growth signals coming from both intracellular and extracellular cues. In this short review, we summarize what is known about the efficacy of targeting the mTOR pathway to treat cancer patients, and we explain the rationale behind promising new inhibitors that could show more potent tumour growth inhibition than did the first generation of these drugs.

The CT Swirl Sign Is Associated with Hematoma Expansion in Intracerebral Hemorrhage.

BACKGROUND AND PURPOSE: Hematoma expansion is an independent determinant of poor clinical outcome in intracerebral hemorrhage. Although the "spot sign" predicts hematoma expansion, the identification requires CT angiography, which limits its general accessibility in some hospital settings. Noncontrast CT, without the need for CT angiography, may identify sites of active extravasation, termed the "swirl sign." We aimed to determine the association of the swirl sign with hematoma expansion. MATERIALS AND METHODS: Patients with spontaneous intracerebral hemorrhage between 2007 and 2014 who underwent an initial and subsequent noncontrast CT at a single center were retrospectively identified. The swirl sign, on noncontrast CT, was defined as iso- or hypodensity within a hyperdense region that extended across 2 contiguous 5-mm axial CT sections. RESULTS: A total of 212 patients met the inclusion criteria. The swirl sign was identified in 91 patients with excellent interobserver agreement (κ = 0.87). The swirl sign was associated with larger initial hematoma (P < .001) and earlier initial CT (P < .001) and hematoma expansion (P = .028). Multivariable regression modeling demonstrated that if one assumed similar initial hematoma volume, onset-to-first scan, and time between CT scans, the median absolute hematoma growth was 5.77 mL (95% CI, 2.37-9.18 mL; P = .001) and relative growth was 35.6% (95% CI, 18.5%-52.6%; P < .001) higher in patients with the swirl sign compared with those without. CONCLUSIONS: The NCCT swirl sign was reliably identified and is associated with hematoma expansion. We propose that the swirl sign be included in risk stratification of intracerebral hemorrhage and considered for inclusion in clinical trials.

Effects of controlled interruption of the enterohepatic circulation of bile salts by biliary diversion and by ileal resection on bile salt secretion, synthesis, and pool size in the rhesus monkey.

The effects of controlled interruption of the enterohepatic circulation (EHC) of bile salts by biliary diversion on bile volume, bile salt secretion and synthesis rates, bile salt pool size, and the relationship to fecal fat excretion were studied in 16 rhesus monkeys. Bile from a chronic bile fistula was returned to the intestine through an electronic stream-splitter which, by diverting different percentages of bile to a collecting system, provided graded and controlled interruption of the EHC. The increase in hepatic bile salt synthesis in response to interruption of the EHC was limited and reached a maximum rate at 20% interruption of the EHC. Up to this level of biliary diversion, the increased hepatic synthesis compensated for bile salt loss so that bile salt secretion and pool size were maintained at normal levels. With diversion of 33% or more, there was no further increase in hepatic bile salt synthesis to compensate for external loss, and as a result there was diminished bile salt secretion, a reduction in bile salt pool size, and steatorrhea was observed. The effects of interruption of the EHC by the streamsplitter were compared with those produced by resection of the distal one-third or two-thirds of small bowel. While ileal resection appreciably reduced bile salt secretion, the EHC was by no means abolished. Bile salt reabsorption from the residual intestine was greater after one-third than after two-thirds small bowel resection. These observations suggest that jejunal reabsorption of bile salts occurs and may well contribute to the normal EHC.

Biliary lipid secretion and bile composition after acute and chronic interruption of the enterohepatic circulation in the Rhesus monkey. IV. Primate biliary physiology.

Bile salts and phospholipids are both required to solubilize biliary cholesterol. Since interruption of the enterohepatic circulation (EHC) depletes bile of bile salts, we have examined in the rhesus monkey the effects of controlled interruption of the EHC on biliary secretion of bile salt, phospholipid, and cholesterol and on the relative proportions of these components in bile. Immediately after complete interruption of the EHC, bile secretion and bile composition remained normal for 2-3 hr. During the next 3 hr, however, secretion of all components decreased. Bile salt decreased to a greater extent than phospholipid and cholesterol, and the bile was now supersaturated with cholesterol. 12-24 hr after interruption of the EHC, a new steady state was reached in which there was a relative deficiency of bile salt and a relative increase in phospholipid and cholesterol. The resulting bile, although somewhat more saturated with cholesterol, was not supersaturated with cholesterol but was stable with respect to cholesterol solubility. Thus, bile instability conducive to gallstone formation occurs transiently within hours after interruption of the EHC. Prolonged large interruptions in the steady state animal also produce a relative bile salt deficiency, but in this situation cholesterol remains soluble in the bile of these animals because there occurs a concomitant relative increase in phospholipid. When the EHC was only partially interrupted, secretion rates and the relative concentration of bile salt, phospholipid, and cholesterol did not change significantly from control values until more than 20% of the bile was diverted. Modest changes in the relative composition of bile occurred when 33 and 66% of the bile was diverted, and these changes were very similar to those produced by resection of the distal small bowel.

Action of neomycin on the intraluminal phase of lipid absorption.

Administration of a single 1 g dose of neomycin sulfate to five healthy subjects simultaneously with a test meal caused a marked increase in the proportion of fatty acid and bile acid in the ultracentrifuged deposit of aspirated intestinal contents. Labeled cholesterol was precipitated in a similar manner in two hypercholesterolemic patients. Neomycin had no effect on the pancreatic lipase concentration or on the pH of intestinal contents. These results confirm that the ability of neomycin to precipitate micellar lipids is due to interaction between the polybasic neomycin molecule and ionized fatty acids and bile acids. This mechanism provides an explanation for both the steatorrhea and hypocholesterolemia induced by this compound.

Association between CYP2C19 Polymorphisms and Outcomes in Cerebral Endovascular Therapy.

BACKGROUND AND PURPOSE: Differing responses to clopidogrel following endovascular treatment of cerebrovascular diseases may increase the risk of vascular complications. CYP2C19 gene polymorphisms influence clopidogrel activity. We aimed to study the clinical impact of CYP2C19 gene polymorphisms in patients undergoing endovascular treatment. MATERIALS AND METHODS: This was a prospective, longitudinal, observational study. Information on demographics and cerebrovascular status was collected as baseline. Clopidogrel response was tested by the VerifyNow P2Y12 assay. CYP2C19 genotyping was undertaken by polymerase chain reaction-restriction fragment length polymorphism. Three-month follow-up data included vascular complications, mortality, and modified Rankin Scale score. Associations were investigated among CYP2C19 genotypes, clopidogrel responsiveness, and clinical outcomes. RESULTS: One hundred and eight participants were included. Median age was 56 years (interquartile range, 48.8-65.0 years), and 35 (32.4%) were male. Forty-four participants were classified into group 1 (homozygous CYP2C19*1/*1); 31, into group 2 (25 with CYP2C19*1/*2, two with CYP2C19*1/*3, three with CYP2C19*3/*3, one with CYP2C19*2/*3); 28, into group 3 (24 with CYP2C19*1/*17, four with CYP2C19*17/*17); and 5, into group 4 (CYP2C19*2/*17). A significantly higher proportion of participants in group 3 experienced ischemic events (9 of 28, 32.1%) compared with group 1 (5 of 44, 11.4%; P = .04; odds ratio, 3.7; 95% confidence interval, 1.1-12.6). There was no significant difference in clopidogrel response among the 4 genotype groups. CONCLUSIONS: Individuals with CYP2C19*17 may have increased risk of ischemic events following endovascular treatment, independent of clopidogrel responsiveness. Larger studies are required to confirm the influence of CYP2C19*17 on clinical outcomes and to understand the mechanisms for increased ischemic events.

A prospective evaluation of treatment with Selective Internal Radiation Therapy (SIR-spheres) in patients with unresectable liver metastases from colorectal cancer previously treated with 5-FU based chemotherapy.

BACKGROUND: To prospectively evaluate the efficacy and safety of Selective Internal Radiation (SIR) spheres in patients with inoperable liver metastases from colorectal cancer who have failed 5FU based chemotherapy. METHODS: Patients were prospectively enrolled at three Australian centres. All patients had previously received 5-FU based chemotherapy for metastatic colorectal cancer. Patients were ECOG 0-2 and had liver dominant or liver only disease. Concurrent 5-FU was given at investigator discretion. RESULTS: Thirty patients were treated between January 2002 and March 2004. As of July 2004 the median follow-up is 18.3 months. Median patient age was 61.7 years (range 36-77). Twenty-nine patients are evaluable for toxicity and response. There were 10 partial responses (33%), with the median duration of response being 8.3 months (range 2-18) and median time to progression of 5.3 mths. Response rates were lower (21%) and progression free survival shorter (3.9 mths) in patients that had received all standard chemotherapy options (n = 14). No responses were seen in patients with a poor performance status (n = 3) or extrahepatic disease (n = 6). Overall treatment related toxicity was acceptable, however significant late toxicity included 4 cases of gastric ulceration. CONCLUSION: In patients with metastatic colorectal cancer that have previously received treatment with 5-FU based chemotherapy, treatment with SIR-spheres has demonstrated encouraging activity. Further studies are required to better define the subsets of patients most likely to respond.

Picture-to-puncture time in acute stroke endovascular intervention: are we getting faster?

BACKGROUND: In acute stroke management, time efficiency in the continuum of patient management is critical. We aimed to determine if implementation of system improvements at our institution translated to reduced picture-to-puncture (P2P) times over a 6-year period. METHODS: We conducted a single-center retrospective analysis using a prospective acute stroke database of patients treated with intra-arterial therapy from October 2007 to October 2013. Patient demographics, stroke severity, neuroimaging and treatment time points were collected. Annual P2P times, defined as the interval between pretreatment neuroimaging (picture) and commencement of intra-arterial therapy (puncture), were assessed and compared. RESULTS: From 2007 to 2013 a total of 189 patients were identified, of which 181 met the study criteria. At initial presentation, median baseline NIH Stroke Severity score was 17.00 (IQR 11.00-22.00). Annual median P2P times decreased from 171 to 123.5 min, showing a median decrease of 11.5 min per annum (95% CI -23.9 to 0.9) and trending towards statistical significance (p=0.069). Plotted data revealed longer P2P times in instances where stroke onset or CT acquisition times were out-of-hours. Using median regression modeling, the annual decrease in P2P median time reached statistical significance when independently adjusting for CT acquisition time (13.5 min P2P median time reduction, 95% CI -27.0 to -0.1, p=0.048) and for stroke onset time (14.5 min annual P2P median time reduction, 95% CI -26.1 to -2.8, p=0.015). CONCLUSIONS: As a consequence of systems improvement at our institution, we were able to demonstrate improved annual median P2P times from 2007 to 2013.

Nuclear magnetic resonance spectroscopy to determine the micellar cholesterol in human bile.

The cholesterol of gallstones comes from the vesicular rather than the micellar phase of bile. Progress in this field has been limited because conventional analytical methods disturb the distribution of cholesterol between the two phases. The resonance of the cholesterol C6 proton occurs at a chemical shift of 5.4 ppm, to be shown by 2D NMR to be specific for biliary cholesterol, and arises only from the micellar mode. Thus integration of the C6 proton resonance peak area provides a direct non-invasive determination of the cholesterol distribution in human bile.

Outcome of chenodeoxycholic acid (CDCA) treatment in 125 patients with radiolucent gallstones. Factors influencing efficacy, withdrawal, symptoms and side effects and post-dissolution recurrence.

Of 125 patients with radiolucent gallstones in functioning gallbladders treated with chenodeoxycholic acid (CDCA) between 1971 and 1977, 47 showed complete gallstone dissolution--an overall efficacy of 38%. However, a retrospective analysis of factors governing efficacy carried out in 1976 showed that in patients with stones less than 15 mm in diameter, treated with greater than 13 mg CDCA kg-1 day-1 for not less than one year who developed unsaturated bile (n = 27), efficacy rose to 78% complete and 93% partial plus complete gallstone dissolution. The usefulness of this selection/management approach was then confirmed prospectively in 42 comparable patients selected for treatment since 1977, efficacy (complete gallstone dissolution) reached 76%. The median duration of treatment for complete gallstone dissolution was 7.5 months for stones less than 5 mm in diameter, 12.0 for 5-10 mm stones; 22.0 for 10-15 mm stones and 28.5 for the only two patients (of 26) with large (greater than 15 mm) stones who ultimately showed complete gallstone dissolution. Seventy-eight patients withdrew from therapy, 21 within 6 months of starting CDCA (before their first follow-up cholecystogram): the remaining 57 withdrew because of: complications of gallstones (11 patients), inadequate treatment (dose and/or duration, 20 patients), inappropriate selection or unsuitable stones (19 patients) and resistance to CDCA (7 patients). Diarrhea, although common, was usually mild or transient. Biliary colic and non-specific dyspepsia tended to improve during therapy. To date, gallstone recurrence has been detected in 14 patients (30%), 3 months to 5 years after discontinuing treatment with CDCA.

An ELISA assay for murine interleukin-1 beta.

An ELISA assay was developed for murine IL-1 beta (mIL-1 beta) using a polyclonal antibody generated in rabbits. The antibody was purified by affinity chromatography on protein A coupled to Sepharose followed by chromatography on mIL-1 beta coupled to Sepharose. The protein A and affinity purified populations were compared using radiolabeled mIL-1 beta and the results used to develop the conditions for the ELISA. The assay developed is sensitive to pg/ml concentrations of mIL-1 beta, is comparable in sensitivity to one which uses a hamster monoclonal antibody as the capture antibody, and can be used to detect IL-1 beta in peritoneal washings or tissue lysates from either mouse or rat. There is no cross reaction with any cytokine tested. The use of ELISA enhancement kits can increase the resolution at the lower concentration ranges without affecting assay sensitivity. This assay should prove useful for defining the presence and potential role for IL-1 beta in animal models of disease.

HLA-class II antigen expression in human heart-lung allografts.

Long-term survival in heart-lung transplantation has ben hindered by the development of bronchiolitis obliterans (OB), which is believed to be a manifestation of chronic rejection of the lung. Since HLA-class II antigens are involved in the rejection response, the distribution of the class II products HLA-DR, HLA-DQ, and HLA-DP were studied in normal lung, and in transplanted lung with and without OB, utilizing frozen-section immunohistochemical techniques. All three allelic products are usually expressed on the epithelial, endothelial, and mesenchymal components of the lung. Sequential transbronchial biopsies from 4 recipients before and concurrent with the diagnosis of OB were stained with serial dilutions of monoclonal antibodies to assess the level of expression of the above class II products. Increased levels of HLA-DR and HLA-DP antigens may be seen on the bronchial and bronchiolar epithelium during OB, but the changes are subtle and complicated by many other variables. Additional studies are needed to confirm these preliminary results.

Improved immunosuppression with aerosolized cyclosporine in experimental pulmonary transplantation.

Rejection remains a major obstacle to long-term success of pulmonary transplantation. Direct delivery of cyclosporine to lung allografts may produce better control of rejection by generating high intragraft concentrations of drug with decreased systemic delivery and toxicity. The efficacy of inhaled cyclosporine in preventing allograft rejection was compared with systemic delivery by intramuscular injections in a rat model of lung transplantation (Brown-Norway to Lewis). Group 1 animals were given no immunosuppression. Group 2 received a single i.m. injection of 25 mg/kg CsA on the day of operation while group 3 received daily doses on postoperative days 0-3. Groups 4-7 received aerosolized CsA daily for seven days. The aerosol generator produced an airborne concentration of CsA of 180 mg/m3 with a mean particle size of 0.7 mu and estimated pulmonary depositions of CsA of 0.98-3.6 mg/kg/day. Animals were killed on POD 7, and the transplanted lungs graded histologically in a blinded fashion. All control animals showed destructive grade 4 changes by POD 7. Animals receiving high-dose aerosolized CsA (groups 6 and 7) showed minimal changes with a mean rejection grade of 1.3. A single i.m. dose of CsA (group 2) failed to prevent rejection; the mean grade was 2.2. Animals given four i.m. doses of CsA had a mean grade of 1.8. Aerosolized CsA provided significantly better control of rejection than did systemic CsA (groups 6 and 7 vs. groups 2 and 3; P less than 0.0002 and less than 0.0054, respectively). Local delivery of CsA by aerosol inhalation is effective in limiting acute rejection of the rat lung allograft.

Review: pathogenesis of gallstones.

The aim of this article is to review selected aspects of the pathogenesis of cholesterol-rich, gall-bladder stones (GBS)--with emphasis on recent developments in biliary cholesterol saturation, cholesterol microcrystal nucleation, statis within the gall-bladder and, particularly, on the roles of intestinal transit and altered deoxycholic acid (DCA) metabolism, in GBS development. In biliary cholesterol secretion, transport and saturation, recent developments include evidence in humans and animals, that bile lipid secretion is under genetic control. Thus in mice the md-2 gene, and in humans the MDR-3 gene, encodes for a canalicular protein that acts as a 'flippase' transporting phospholipids from the inner to the outer hemi-leaflet of the canalicular membrane. In the absence of this gene, there is virtually no phospholipid or cholesterol secretion into bile. Furthermore, when inbred strains of mice that have 'lith genes' are fed a lithogenic diet, they become susceptible to high rates of GBS formation. The precipitation/nucleation of cholesterol microcrystals from supersaturated bile remains a critical step in gallstone formation. methods of studying this phenomenon have now been refined from the original 'nucleation time' to measurement of cholesterol appearance/detection times, and crystal growth assays. Furthermore, the results of recent studies indicate that, in addition to classical Rhomboid-shape monohydrate crystals, cholesterol can also crystallize, transiently, as needle-, spiral- and tubule-shaped crystals of anhydrous cholesterol. A lengthy list of promoters, and a shorter list of inhibitors, has now been defined. There are many situations where GB stasis in humans is associated with an increased risk of gallstone formation--including iatrogenic stone formation in acromegalic patients treated chronically with octreotide (OT). As well as GB stasis, however, OT-treated patients all have 'bad' bile which is supersaturated with cholesterol, has excess cholesterol in vesicles, rapid microcrystal mulceation times and a two-fold increase in the percentage DCA in bile. This increase in the proportion of DCA seems to be due to OT-induced prolongation of large bowel transit time (LBTT). Thus LBTT is linearly related to (i) the percentage of DCA in serum; (ii) the DCA pool size; and (III) the DCA input or 'synthesis' rate. Furthermore, the intestinal prokinetic, cisapride, counters the adverse effects of OT on intestinal transit, and 'normalizes' the percentage of DCA in serum/bile. Patients with spontaneous gallstone disease also have prolonged LBTTs, more colonic gram-positive anaerobes, increased bile acid metabolizing enzymes and higher intracolonic pH values, than stone-free controls. Together, these changes lead to increased DCA formation, solubilization and absorption, Thus, in addition to the 'lithogenic liver' and 'guilty gall-bladder' one must now add the 'indolent intestine' to the list of culprits in cholesterol gallstone formation.

Drug-induced hypochlorhydria causes high duodenal bacterial counts in the elderly.

BACKGROUND: Small bowel bacterial overgrowth secondary to drug-induced hypochlorhydria may be of particular importance in the elderly, in whom anti-ulcer drugs are commonly prescribed and the consequences of malabsorption may be severe. METHODS: Duodenal aspirates were obtained from elderly individuals before (n = 24) and during a 2-month treatment course with either omeprazole (20 mg daily; n = 8) or ranitidine (300 mg b.d.; n = 6), and from six patients with small bowel bacterial overgrowth who had diarrhoea and malabsorption. RESULTS: Before treatment, duodenal bacterial counts were normal (< 10(4) colony forming units/mL) in 23 elderly subjects (96%). However, six of 14 patients (43%) treated with omeprazole (5 of 8) or ranitidine (1 of 6) developed bacterial counts > 10(5) cfu/mL. All remained asymptomatic and had normal lactulose breath H2 profiles during treatment. CONCLUSION: Drug-induced hypochlorhydria causes high duodenal bacterial counts in the elderly but, in the short term, this bacterial overgrowth is not associated with malabsorption.