bluuebunny/crossref_metadata_2025 huggingface dataset:
Weak Property Rights and Holdup in R&D
Authors: Anand Bharat N. , Galetovic Alexander
Published: January 2004

We study how the sequence of financing of R&D varies according to the ease with which property rights over knowledge can be defined. There are two financiers: a venture capitalist (VC) and a corporation. The knowledge acquired in costly research becomes embodied in the researcher's human capital, and she may hold up the financier and walk away with the project to develop it elsewhere. The main results are: (1) When property rights are strong, research is always funded by the VC, development is performed efficiently, and breakaways from the VC to the corporation are observed in equilibrium. (2) When property rights are weak, projects may be financed by the VC or the corporation, or may remain unfunded. (3) When property rights are weak, no breakaways occur in equilibrium; local spillovers and strong product market competition increase the likelihood that research projects will get funding. (4) The equilibrium sequence of R&D finance need not be first‐best efficient. (5) In equilibrium, and controlling for the strength of property rights, VCs finance projects that are more profitable on average.
The Structure and Conduct of Corporate Lobbying: How Firms Lobby the Federal Communications Commission
Authors: de Figueiredo John M. , Tiller Emerson H.
Published: January 2004

This paper examines the amount and organization (individual vs. collective) of lobbying by firms in administrative agencies. It explores the power and limitations of the collective‐action theories and transaction‐cost theories in explaining lobbying. It introduces a dataset of over 900 lobbying contacts covering 101 issues at the Federal Communications Commission (FCC) in early 1998. It finds that the structure and conduct of large‐firm lobbying at the FCC is consistent with the predictions of theories of transaction costs and the main results of theories of collective action. Small firms show little sensitivity to collective‐action issues or transaction‐cost issues in the organization of their lobbying, but they do lobby less when having to reveal proprietary information. In sum, large firms behave in a manner largely consistent with theoretical predictions, while small firms do not.
Saints and Markets: Activists and the Supply of Credence Goods
Authors: Feddersen Timothy J. , Gilligan Thomas W.
Published: January 2004

This paper contains a theoretical exploration of the potential effects of an information‐supplying activist on a market for credence goods. Using a non‐cooperative game‐theoretic model with incomplete information, we find that such an activist can alter the decisions of firms and consumers and enhance the social welfare of market exchange. We also find that an activist can support equilibria in which firms differentiate their products on some credence characteristic even though this characteristic remains unknown to the consumer both prior and subsequent to consumption. In general, our analysis has several implications for the study of private collective action in markets.
The Social Cost of Cheap Pseudonyms
Authors: Friedman* Eric J. , Resnick Paul
Published: January 2004

We consider the problems of societal norms for cooperation and reputation when it is possible to obtain cheap pseudonyms, something that is becoming quite common in a wide variety of interactions on the Internet. This introduces opportunities to misbehave without paying reputational consequences. A large degree of cooperation can still emerge, through a convention in which newcomers “pay their dues” by accepting poor treatment from players who have established positive reputations. One might hope for an open society where newcomers are treated well, but there is an inherent social cost in making the spread of reputations optional. We prove that no equilibrium can sustain significantly more cooperation than the dues‐paying equilibrium in a repeated random matching game with a large number of players in which players have finite lives and the ability to change their identities, and there is a small but nonvanishing probability of mistakes. Although one could remove the inefficiency of mistreating newcomers by disallowing anonymity, this is not practical or desirable in a wide variety of transactions. We discuss the use of entry fees, which permits newcomers to be trusted but excludes some players with low payoffs, thus introducing a different inefficiency. We also discuss the use of free but unreplaceable pseudonyms, and describe a mechanism that implements them using standard encryption techniques, which could be practically implemented in electronic transactions.
Product Differentiation and Upstream‐Downstream Relations
Authors: Pepall Lynne , Norman George
Published: January 2004

This paper examines the relationship between a differentiated downstream market and a specialized upstream market. We analyze three different types of vertical relation between the upstream and downstream sectors when the upstream market supplies specialized and complementary inputs to a downstream product‐differentiated market. The first is the benchmark case of decentralized markets, the second is a network of alliances among upstream suppliers, and the third is partial vertical integration. We identify the perfect equilibrium for a symmetric model in each case and show that there is no simple relationship between the degree of connection between upstream and downstream firms and profitability. The key factor affecting prices and the relative profitability of the different market organizations is the degree of product differentiation among the downstream firms, because it affects the intensity of competition among upstream suppliers. We show that vertical foreclosure is not an equilibrium strategy.
Corners in Auctions
Authors: Chakraborty Indranil , Engelbrecht‐Wiggans Richard
Published: January 2004

Different pricing rules in multiunit auctions provide different incentives for a bidder to corner the auction and thus require different levels of effort from the seller to deter cornering. We consider three different types of auctions: the pay‐your‐bid or “discriminatory” auction commonly used by the US Treasury, the lowest‐winning‐bid uniform‐price auction used in the current Treasury experiment, and the highest‐losing‐bid uniform‐price auction considered by Vickrey almost four decades ago. We show that the pay‐your‐bid auction provides the greatest incentive to corner the market, that the experimental Treasury auction provides less incentive, and that the highest‐losing‐bid uniform‐price auction provides the least. Arguably, the less the incentive to corner the market, the easier it will be for sellers to deter cornering, and the greater their expected revenue (net of the cost to deter cornering) will be in otherwise expected‐revenue‐equivalent auctions.
Electricity Auctions
Authors: Léautier Thomas‐Olivier
Published: January 2004

This article examines auctions in the electricity industry. We find that the laws of physics that rule power transmission networks defeat ex post productive efficiency: the cheapest combination of generating plants is not always selected, not even in the optimal auction. Furthermore, neither the pay‐your‐bid nor the uniform‐price auction coincides in general with the optimal auction, nor do they yield productive efficiency. Our analysis also sheds light on behavior observed in existing power markets, and leads to policy recommendations. First, producers protected by transmission constraints must see their bids capped in the short run to curb their ability to extract large rents. Second, producers apparently hurt by the unavailability of transmission capacity may benefit from it. Hence, contrary to common wisdom, policy makers cannot rely on them to finance or advocate transmission expansion.
Implicit Contracts, Managerial Incentives, and Financial Structure
Authors: Dessí Roberta
Published: January 2004

This paper examines how managers may be given incentives to exert effort, and to implement efficient implicit contracts with workers. Under certain assumptions, this can be achieved by tying managerial compensation to shareholder value. However, if reputation effects are weak, it is more efficient to adopt an incentive scheme in which the manager is punished by outside investor intervention when performance falls below a critical level, and otherwise retains control, receiving a fixed reward. The required form of outside intervention can be implemented through a financial structure combining hard debt with a dispersed ownership structure.
Trade Secrets and Information Sharing
Authors: Rønde Thomas
Published: January 2004

If trade secrets are weakly protected by law, firms risk losing their valuable information when employees are hired by competitors. It may therefore be optimal to limit the number of employees who share the trade secrets even if it reduces the firm's productive efficiency. The benefits of limited information sharing are greatest if the efficiency cost is low and the competition in the market is neither very tough nor very weak. It is shown that it is more profitable to reduce the information sharing by giving the employees different information than by giving some employees more information than others.
Second‐Mover Advantages in Dynamic Quality Competition
Authors: Hoppe Heidrun C. , Lehmann‐Grube Ulrich
Published: January 2004

This paper explores a dynamic model of product innovation, extending the work of Dutta, Lach, and Rustichini (1995). It is shown that if R&D costs for quality improvements are low, the dynamic competition is structured as a race for being the pioneer firm with payoff equalization in equilibrium, but switches to a waiting game with a second‐mover advantage in equilibrium if R&D costs are high. Moreover, the second‐mover advantage increases monotonically as R&D becomes more costly.
Endogenously Asynchronous Entries into an Uncertain Industry
Authors: Hirokawa Midori , Sasaki Dan
Published: January 2004

We model and analyze a priori symmetric duopoly where supply quantity adjustment is slow and time‐consuming. The state of demand is ex ante uncertain, and becomes observable a certain time period after at least one firm's entry. We characterize those conditions under which sequential entries can be endogenously chosen either as an asymmetric pure‐strategy equilibrium or as a consequence of a symmetric mixed‐strategy equilibrium. Also, in the limit where information revelation is infinitely fast (i.e., the time period it requires becomes infinitesimally short), the expected waiting time until the first entry does not necessarily become proportionately short, whilst the time interval between the leader's entry and the follower's entry does become infinitesimally short. This suggests that chronologically nearly simultaneous entry should not necessarily be interpreted as counterevidence against leader‐follower relations. In addition to equilibrium comparative statics, we also analyze some of the welfare issues associated with strategic timing of entry.
Strategic and Queue effects on Entry in Spanish Banking
Authors: Fuentelsaz Lucio , Gomez Jaime
Published: January 2004

This paper analyzes the factors that influence entry and geographic diversification decisions, a topic of special strategic interest in a context of growing globalization. The empirical model we propose is tested in a framework— the Spanish savings‐bank market—where recent deregulation has eliminated the legal barriers to entry. Our results show two important conclusions for the evolution of the effects of branching deregulation in Europe and the US. First, it seems that entry in new geographical markets has been impeded by the strategic interactions between entrants and incumbents. Second, savings banks exhibit a preference for closer locations at the time of expanding, which may have undermined the effects of deregulation and its potential benefits for consumers.
Financially Interlinked Business Groups*
Authors: Ghatak Maitreesh , Kali Raja
Published: January 2004

Financial interlinkage, in the form of cross‐holding of equity and debt between firms, characterizes business groups in many countries. We suggest that such financial interlinkage can be viewed as a way to solve credit rationing caused by asymmetric information. If firms possess better information about each other than a bank, then business groups can be a mechanism to induce firms to sort on the basis of this information. Banks can offer a menu of contracts that vary in the extent of financial interlinkage to induce firms to self‐select on the basis of the equilibrium composition of the business groups they can form.
Managed Care Incentives and Inpatient Complications
Authors: Haile Philip A. , Stein Rebecca M.
Published: January 2004

Managed care organizations control costs through restrictions on patient access to specialized services, oversight of treatment protocols, and financial incentives for providers. We investigate possible effects of such practices on the care patients receive by studying frequencies of in‐hospital complications. We find significant differences in complication rates between managed care and fee‐for‐service patients. We investigate the sources of this variation by comparing probabilities of complications among patients with different types of managed care coverage and patients treated in different hospitals. For several patient categories, the differences in outcomes we find appear to arise not from differential treatment of patients within hospitals or from heterogeneity in patients, but from variations in care across hospitals that tend to treat patients with different insurance types.
Health Insurance, Moral Hazard, and Managed Care
Authors: Albert Ma Ching‐To , Riordan Michael H.
Published: January 2004

If an illness is not contractible, then even partially insured consumers demand treatment for it when the benefit is less than the cost, a condition known as moral hazard. Traditional health insurance, which controls moral hazard with copayments (demand management), can result in either a deficient or an excessive provision of treatment relative to ideal insurance. In particular, treatment for a low‐probability illness is deficient if illness per se has little effect on the consumer's marginal utility of income and if the consumer's price elasticity of expected demand for treatment is large relative to the risk‐spreading distortion when these are evaluated at a copayment that brings forth the ideal provision of treatment. Managed care, which controls moral hazard with physician incentives, can either increase or decrease treatment delivery relative to traditional insurance, depending on whether demand management results in deficient or excessive treatment.
Public and Private Provision of Health Care
Authors: Barros Pedro Pita , Martinez‐Giralt Xavier
Published: January 2004

One of the mechanisms that are implemented in the cost containment movement in the health care sectors in western countries is the definition, by the third‐party payer, of a set of preferred providers. The insured patients have different access rules to such providers when ill. The rules specify the copayments patients must pay when using an out‐of‐plan care provider. This paper studies the competitive process among providers in terms of both prices and qualities. Competition is influenced by the status of providers as in‐plan or out‐of‐plan care providers. Also, there is a moral hazard of provider choice related to the trade‐off between freedom to choose and the need to hold down costs. It is possible to achieve the first‐best allocation by an appropriate definition of the reimbursement scheme when decisions on prices and qualities are taken simultaneously (as in primary health care sectors). In contrast, some type of regulation is needed to achieve the optimal solution when decisions are sequential (as in specialized health care sectors). We also derive normative conclusions on how price controls should be implemented in some European Union member states.
An Economic Approach to the Psychology of Change: Amnesia, Inertia, and Impulsiveness
Authors: Hirshleifer David , Welch Ivo
Published: January 2004

This paper examines the effect of memory loss on the continuity of behavior. We consider a player (individual or firm) who remembers previous actions but not underlying rationales. In a stable environment, relative to a full‐recall scenario, memory loss increases the probability of following old policies (inertia). In a volatile environment, memory loss can decrease this probability (impulsiveness). The model provides a memory‐loss explanation for some documented psychological biases, implies that inertia and organizational routines should be more important in stable environments than in volatile ones, and provides empirical implications relating memory and environmental variables to economic decisions.
Bundling and the Reduction of the Winner's Curse
Authors: Chakraborty Indranil
Published: January 2004

The paper studies the effects of bundling on the bidding strategies and seller revenues in auctions when the bidders have common values for the objects. Bundling of objects before the auction reduces the problem of the winner's curse, and the bidders bid more aggressively. This does not mean that a bundled auction is always better for the seller's revenue. Indeed, there is another effect that makes the bundled auction preferable (from the seller's standpoint) if and only if the number of bidders is small. While this is the only effect present in an independent‐private‐values model, it does not vanish when bidders have pure common values for the objects. The paper concludes that a bundled auction is unambiguously better for the seller than separate auctions when the number of bidders is small.
Private Politics
Authors: Baron David P.
Published: January 2004

This paper introduces the subject of private politics, presents a research agenda, and provides an example involving activists and a firm. Private politics addresses situations of conflict and their resolution without reliance on the law or government. It encompasses the political competition over entitlements in the status quo, the direct competition for support from the public, bargaining over the resolution of the conflict, and the maintenance of the agreed‐to private ordering. The term private means that the parties do not rely on public order, i.e., lawmaking or the courts. The term politics refers to individual and collective action in situations in which people attempt to further their interests by imposing their will on others. Four models of private politics are discussed: (1) informational competition between an activist and a firm for support from the public, (2) decisions by citizen consumers regarding a boycott, (3) bargaining to resolve the boycott, and (4) the choice of an equilibrium private ordering to govern the ongoing conflicting interests of the activist and the firm.
R&D Competition when firms Choose Variance
Authors: Cabral Luís M. B.
Published: January 2004

I consider an infinite‐period race where players choose between low‐ and high‐variance motion technologies. I provide sufficient conditions under which, in equilibrium, the leader chooses a safe technology and the laggard a risky one, thus formalizing the sports intuition that the laggard has nothing to lose. Various examples and empirical implications are presented.
Patents, Invalidity, and the Strategic Transmission of Enabling Information
Authors: Anton James J. , Yao Dennis A.
Published: January 2004

The patent system encourages innovation and knowledge disclosure by providing exclusivity to inventors. Exclusivity is limited, however, because a substantial fraction of patents have some probability of being ruled invalid when challenged in court. The possibility of invalidity—and an ensuing market competition—suggests that when an innovator's capability (e.g., cost of production) is private information, there is potential value to an innovator from signaling strong capability via a disclosure that transfers technical knowledge to a competitor. We model a product‐innovation setting in which a valid patent gives market exclusivity and find a unique signaling equilibrium. One might expect that as the probability that a patent will be invalid becomes low, greater disclosure will be induced. We do not find this expectation to be generally supported. Further, even where full disclosure arises in equilibrium, it is only the less capable who make full disclosures. The equilibrium analysis also highlights many of the novel and appealing features of enabling knowledge disclosure signals.
Minimum Differentiation in Commercial Media Markets
Authors: Gal‐Or Esther , Dukes Anthony
Published: January 2004

We examine a model of locational choice in commercial media markets. Commercial media (stations) compete for audiences with their choice of programming variety in order to attract advertising revenues from advertisers. These advertisers (producers) compete in a differentiated product market and rely on advertising to inform consumers about their product. We use the model to show that media have incentives to minimize the extent of differentiation between them. This incentive is an implication of the assumed role of advertising as information and as an ultimate nuisance to the audience. When stations minimally differentiate their programming offerings, producers choose lower levels of advertising. Consequently, lower levels of product information are available to consumers, permitting producers to gain higher margins on product sales. As a result, stations can negotiate higher payments for advertising space.
The Role of Network Effects in the US VCR Market, 1978–1986
Authors: Ohashi Hiroshi
Published: January 2004

This paper estimates the importance of indirect network effects in the US video cassette recorder (VCR) market between 1978 and 1986. Estimation reveals the significant role of networks in the format competition between VHS and Beta. The paper also finds that if Sony, the system sponsor of Beta, had aggressively introduced its VCRs at the early stage of competition, Beta would likely have dominated the market in 1985; instead, the format disappeared in 1989. Finally, the paper measures consumer welfare for the value of network effects in VCRs, and assesses the consumer welfare effect of standardization.
Board Efficiency and Internal Corporate Control Mechanisms
Authors: Graziano Clara , Luporini Annalisa
Published: January 2004

We analyze the interactions between internal and external control mechanisms in a framework in which the board selects the CEO and then decides whether to retain or dismiss him after observing a signal regarding his ability. The novel aspect of our paper is that we consider both the hiring and the firing of the CEO by the board. The type of board is defined by its ability to select a good CEO, so that the quality of the CEO depends on the type of board. Then, the dismissal‐retention decision provides information not only on the quality of the CEO but also on the board's type. We show that the board's behavior depends on the pressure from the takeover market and on whether its type is publicly known. When the pressure from the takeover market is high and the type of board is private information, the board prefers not to dismiss the manager even if it has received a very low signal regarding his quality. Hence, our model endogenously derives a collusion between board and CEO in which the board does not fire a bad CEO. This behavior emerges as an attempt to hide the board's inability to accomplish the first task, CEO selection, by distorting the second task, the CEO retention‐dismissal decision.
Hamburger Prices and Spatial Econometrics
Authors: Kalnins Arturs
Published: January 2004

This paper applies spatial econometrics to hamburger price data to assess the degree of substitutability of products and locations of spatially dispersed franchised chains. First, while intrachain price variation exists, I find that hamburger prices at neighboring outlets of different chains are spatially uncorrelated. I conclude that their products are not close substitutes, which provides an explanation for why price promotions have not raised market share. I do find spatial price correlation, however, among proximate outlets of separate franchisees within the same chain. This finding implies that customers view proximate locations of a chain as substitutes.
Plasma and urine levels of urinary trypsin inhibitor in patients with chronic liver diseases and hepatocellular carcinoma
Authors: LIN SHI DE , ENDO RYUJIN , KURODA HIDEKATSU , KONDO KORYO , MIURA YOSHIAKI , TAKIKAWA YASUHIRO , KATO AKINOBU , SUZUKI KAZUYUKI
Published: January 2004

Background and Aim:  Because urinary trypsin inhibitor (UTI) is synthesized by hepatocytes and excreted into the urine, plasma and urine levels of UTI may alter in liver diseases. However, there are few reports on the changes in these levels in chronic liver diseases and hepatocellular carcinoma (HCC). The aim of the present study was to evaluate the relationships between plasma and urine UTI levels and the severity of liver damage or progression of HCC in patients with chronic liver diseases and HCC.

Methods:  Plasma and urine UTI levels were measured by a newly developed enzyme‐linked immunosorbent assay in 16 patients with chronic hepatitis (CH), 19 patients with liver cirrhosis (LC) and 39 patients with HCC.

Results:  Plasma UTI level exhibited a significant positive correlation with the urine UTI level. Plasma and urine UTI levels significantly decreased in LC patients compared with those of normal controls. In contrast, the plasma UTI level in HCC patients was higher than that in LC patients, but there was no difference betwen the groups in the urine UTI level. Plasma and urine UTI levels in LC and HCC patients were significantly correlated with the degree of liver damage according to the Child‐Pugh classification. Although neither the plasma nor urine level of UTI in HCC patients were related to the clinical stage of HCC, both levels were closely associated with the level of protein induced by vitamin K absence or antagonist‐II.

Conclusions:  The present findings indicate that the levels of plasma and urine UTI in patients with LC reflect the severity of liver damage. In HCC patients, these levels may also reflect progression of HCC, although further study is required.

© 2004 Blackwell Publishing Asia Pty Ltd
Role of γ‐glutamyl transferase activity in patients with chronic hepatitis C virus infection
Authors: SILVA IVONETE SS , FERRAZ MARIA LUCIA CG , PEREZ RENATA M , LANZONI VALERIA P , FIGUEIREDO VIRGINIA M , SILVA ANTONIO EB
Published: January 2004

Background:  Increased serum γ‐glutamyl transferase (GGT) levels are frequently observed in chronic hepatitis C virus (HCV) infection. However, the significance of this finding remains unclear. The purpose of the present paper was to assess the relationship between GGT levels and clinical, biochemical and histological features in chronic HCV‐infected carriers.

Methods:  Patients with a liver biopsy presenting anti‐HCV and HCV‐RNA were evaluated. Age, gender, risk factors of transmission, serum alanine aminotransferase (ALT), GGT and alkaline phosphatase (ALP) levels and histological features were assessed in all. Data were analyzed statistically by the χ2 test and multivariate logistic regression analysis.

Results:  Among 201 patients studied, elevated GGT levels and bile duct damage were observed in 48% and 35% of them, respectively. No association was seen between GGT level and bile duct damage or between GGT level and hepatic steatosis. Inititally, age > 40 years (P = 0.007), elevated ALT (P = 0.01), grading of inflammatory activity (P = 0.004) and staging of fibrosis (P < 0.001) were found to be associated with elevated GGT levels. After multivariate regression analysis, histology grading 3 and 4 inflammation activity (P = 0.01) and staging 3 and 4 fibrosis (P = 0.01) remained independently associated with elevated GGT level.

Conclusions:  A significant number of patients with chronic HCV infection had elevated serum GGT levels. Furthermore, this enzyme seemed to be useful as an indirect marker of more advanced liver disease in chronic hepatitis C.

© 2004 Blackwell Publishing Asia Pty Ltd
High frequency of chronic end‐stage liver disease and hepatocellular carcinoma in a Hispanic population
Authors: PEREZ ADRIANA , ANZALDUA MONICA , MCCORMICK JOSEPH , FISHER‐HOCH SUSAN
Published: January 2004

Background:  Texas has the highest mortality from hepatocellular carcinoma in the USA. Because end‐stage liver disease mortality is most marked in the Hispanic population in the Lower Rio Grande Valley, the aim of the present paper was to estimate the prevalence of end‐stage liver disease and associated factors in Brownsville.

Methods:  A cross‐sectional study was carried out, abstracting medical charts in a community‐based clinic and a hospital. A matched case‐control analysis was performed. Cases had an International Classification of Disease (9th revision; ICD9) code 155.0 or 571.0–9 (primary liver cancer or chronic liver disease) recorded; age‐ and sex‐matched controls did not have these codes. A total of 176 cases and 352 controls was collected. The main outcome measure was the prevalence and risk factors for end‐stage liver disease.

Results:  Conservative prevalence of end‐stage liver disease: 126/100 000 (386/100 000, male). Eleven out of 176 had hepatocellular carcinoma. Median age was 57 years; 72% male, 94% Hispanic. Among significant risk factors were history of hepatitis (odds ratio (OR): 19.3; 95% confidence interval (CI): 8.0–46.4), any history of alcohol use (OR: 6.6; 95%CI: 4–10.8) and history of illegal drug use (OR: 1.9; 95%CI: 1.2–2.9). Fifteen cases with no known risk factors were classified as cryptogenic cirrhosis. Only four cases out of 176 had been referred for liver transplant.

Conclusions:  The prevalence of end‐stage liver disease in the Lower Rio Grande Valley is extremely high, with no single satisfactory explanation and with acute health disparities. Careful follow up of cryptogenic cirrhosis in this population may or may not lead to a new source of liver disease.

© 2004 Blackwell Publishing Asia Pty Ltd
Prevalence of colonic polyps is not increased in patients with acromegaly: Analysis of 60 patients from India
Authors: BHANSALI ANIL , KOCHHAR RAKESH , CHAWLA YOGESH K , REDDY SOMASHEKARA , JIBAN DASH RADHARAMAN
Published: January 2004

Background:  There are conflicting data on the prevalence of colorectal adenomas in patients with acromegaly. It has been suggested that the risk of colorectal adenomas may be dependent on the geographic and ethnic origin of the patients.

Materials:  Sixty consecutive patients with active acromegaly due to somatotropinoma underwent colonoscopy prior to definitive surgery. They included 35 men and 25 women with a mean (± SD) age of 37.4 ± 13.2 years and a lag time between symptomatology and diagnosis of acromegaly of 64.6 ± 58.0 months. The control group included 160 patients (88 men, 72 women; mean age, 38.2 ± 14.0 years) with a diagnosis of irritable bowel syndrome who were also subjected to colonoscopy. None of these patients had previous or family history of colonic neoplasm, bleeding or colonic surgery.

Results:  Colonoscopic examination was complete to the cecum in 52 patients (88%), and to the splenic flexure in the remaining 12% . In the control group, it was complete to the cecum in 144 patients (90%). Four of the acromegalic patients (6.7%) and five in the control group (3.1%; P = 0.24) had hyperplastic polyps. No patient in either of the groups had adenomatous polyps or colonic adenocarcinoma. The group of acromegalic patients with and without polyps did not differ significantly in age, duration of disease, growth hormone levels or glycemic status. The number of skin tags, however, was significantly higher (P = 0.04) in the polyp group as compared to those without polyps.

Conclusion:  The present study has failed to demonstrate the high prevalence rate of colonic neoplasia in patients with acromegaly as compared to reports from the Western world.

© 2004 Blackwell Publishing Asia Pty Ltd
Role of L‐carnitine in the prevention of acute liver damage induced by carbon tetrachloride in rats
Authors: DEMIRDAG KUTBEDDIN , BAHCECIOGLU IBRAHIM HALIL , OZERCAN IBRAHIM HANIFI , ÖZDEN MEHMET , YILMAZ SEVAL , KALKAN AHMET
Published: January 2004

Background and Aim:  Lipid peroxidation is the most important mechanism in the pathogenesis of acute liver damage with carbon tetrachloride (CCl4). L‐carnitine may prevent lipid peroxidation and thus may protect against liver damage. In the present study we investigated the protective effect of L‐carnitine in experimental acute liver damage induced by CCl4.

Methods:  Fifty rats were allocated to five equal groups. The first group was the control (group 1), the second group received an intraperitoneal CCl4 injection for 3 days (group 2), and the third group received a 50 mg/kg subcutaneous L‐carnitine injection for 4 days, beginning a day before CCl4 injection. The CCl4 injection was continued for 3 days in the concerned group (group 3). Group 4 was given a CCl4 injection for 7 days and group 5 received a 50 mg/kg subcutaneous L‐carnitine injection for 8 days, beginning a day before CCl4 injection. This group continued to receive a CCl4 injection for 7 days. Rats in groups 2 and 3 were killed on the fifth day. Rats in groups 1, 4 and 5 were killed on the ninth day. Plasma and liver tissue malondialdehyde (MDA) levels, glutathione peroxidase (GSH‐Px) activity and liver enzyme levels were studied. Histopathological investigations were conducted.

Results:  Liver tissue MDA levels decreased significantly in group 3 compared to group 2 (P < 0.001). Liver tissue MDA levels in group 5 decreased significantly in comparison to those of group 4 (P < 0.001). Liver tissue GSH‐Px activity in group 5 was significantly lower than that in group 4 (P < 0.05). There were no significant differences between groups 3 and 4 regarding GSH‐Px activity (P > 0.05). Steatosis, inflammation and necrosis in group 3 were significantly reduced when compared to group 2 (P < 0.01). Fibrosis development was not identified in groups 2 and 3. Steatosis in group 5 was significantly lower than that in group 4 (P < 0.05) and there were no significant differences between groups 4 and 5 with regards to inflammation and necrosis (P > 0.05). Mild fibrosis development was identified in groups 4 and 5 but the difference between the groups was not significant.

Conclusion:  It appears that L‐carnitine has a protective effect in the early stage of experimental acute liver damage induced by CCl4. As the toxic effect or damage continues, its effect lessens.

© 2004 Blackwell Publishing Asia Pty Ltd
Weight loss in obese diabetic and non‐diabetic individuals and long‐term diabetes outcomes – a systematic review
Authors: Aucott L. , Poobalan A. , Smith W. C. S. , Avenell A. , Jung R. , Broom J. , Grant A. M.
Published: January 2004

The aim was to review the evidence for the long‐term effects of weight loss on diabetes outcomes in obese people or for those at risk of developing type 2 diabetes. Current evidence is mostly based on short‐term studies. This is a systematic review of long‐term outcomes of weight loss in studies published between 1966 and 2001. Eleven long‐term studies with a follow up of more than 2 years were included. Results show that those with diabetes who lost weight intentionally significantly reduced their mortality risks by 25%. Additionally, weight loss of 9–13 kg was most protective. Patients with the risk of developing diabetes due to either family history of diabetes or impaired glucose tolerance, saw a reduction in this risk. Those with large weight losses achievable with surgical interventions reduced their risk by at least 63%. Metabolic handling of glucose improved in 80% of those already with type 2 diabetes who lost weight. Based on one large study, intentional weight loss in obese patients appears to have a beneficial effect on mortality risk for those with type 2 diabetes. Clearly, further studies are needed to endorse this. The risk of developing diabetes being reduced by weight loss was shown in seven studies. However, the results were from studies with different analytical adjustments and outcome indices, making it difficult to make direct comparisons and should be viewed with caution. More long‐term prospective studies need to be conducted with commitment to improving the methodological quality and standardization, in order to accurately assess the long‐term effects of weight loss for obese diabetic and non‐diabetic individuals.
Signalling pathways involved in retinal endothelial cell proliferation induced by advanced glycation end products: inhibitory effect of gliclazide
Authors: Mamputu J.‐C. , Renier G.
Published: January 2004

Aim:  We have previously demonstrated that advanced glycation end products (AGEs) stimulate bovine retinal endothelial cell (BREC) proliferation through induction of vascular endothelial growth factor (VEGF) production by these cells. We have also shown that gliclazide, a sulfonylurea which decreases oxidative stress, inhibits this effect. The aim of the present study was to characterize the signalling pathways involved in AGE‐induced BREC proliferation and VEGF production and mediating the inhibitory effect of gliclazide on these biological events.

Methods:  BRECs were treated or not treated with AGEs in the presence or absence of gliclazide, antioxidants, protein kinase C (PKC), mitogen‐activated protein kinase (MAPK) or nuclear factor‐κB (NF‐κB) inhibitors. BREC proliferation was assessed by measuring [3H]‐thymidine incorporation into DNA. Activation of PKC, MAPK and NF‐κB signal transduction pathways and determination of VEGF expression were assessed by Western blot analysis using specific antibodies. MAPK activity was also determined by an in vitro kinase assay.

Results:  Treatment of BRECs with AGEs significantly increased cell proliferation and VEGF expression. AGEs induced PKC‐β translocation, extracellular signal‐regulated protein kinase 1/2 and NF‐κB activation in these cells. Pharmacological inhibition of these signalling pathways abolished AGE effects on cell proliferation and VEGF expression. Exposure of BRECs to gliclazide or antioxidants such as vitamin E or N‐acetyl‐l‐cysteine resulted in a significant decrease in AGE‐induced activation of PKC‐, MAPK‐ and NF‐κB‐signalling pathways.

Conclusions:  Our results demonstrate the involvement of PKC, MAPK and NF‐κB in AGE‐induced BREC proliferation and VEGF expression. Gliclazide inhibits BREC proliferation by interfering with these intracellular signal transduction pathways.
A placebo‐controlled crossover study comparing the effects of nateglinide and glibenclamide on postprandial hyperglycaemia and hyperinsulinaemia in patients with type 2 diabetes
Authors: Barnett A. H. , Anderson D. M. , Shelley S. , Morgan R. , Owens D. R.
Published: January 2004

Aim:  This was a randomized, double blind, three period crossover study. The objective was to compare glucose, insulin and C‐peptide 24 h profiles in patients with type 2 diabetes mellitus after dosing with nateglinide (given preprandially before three test meals), glibenclamide (administered once before breakfast) or placebo (given before three test meals).

Methods:  Fourteen patients underwent screening followed within 3 weeks by three treatment periods of 1 day, each separated by 7 days. Dosing followed a six‐sequence balanced, two 3 × 3‐replicated Latin square.

Results:  Mean peak serum insulin levels were lower after nateglinide (115 mU/l) than after glibenclamide (145 mU/l.h; p = 0.017) but higher than after placebo (79 mU/l; p = 0.001). However, peak insulin levels were reached earlier after nateglinide [mean time to peak (tmax) 1.7 h] compared to glibenclamide (mean tmax 2.1 h, p = 0.06). Total insulin exposure over the day was higher after glibenclamide compared with that following nateglinide (1216 vs. 1067 mU/l.h; p = 0.009). Similar findings were seen with serum C‐peptide. Despite this, mean peak plasma glucose concentrations were lower following nateglinide (11.4 mmol/l from a baseline of 8.3 mmol/l) compared with glibenclamide (13.2 mmol/l from a baseline of 8.5 mmol/l; p = 0.001) and placebo (14.0 mmol/l from a baseline of 8.0 mmol/L; p < 0.001).

Conclusions:  Nateglinide improves early prandial measures of insulin and glucose response to a standard meal, more so than glibenclamide, in people with type 2 diabetes.
The effect of high‐fat and high‐fructose diets on glucose tolerance and plasma lipid and leptin levels in rats
Authors: Huang B.‐W. , Chiang M.‐T. , Yao H.‐T. , Chiang W.
Published: January 2004

Aim:  High‐fat and high‐fructose diets are usually used to induce animal model diabetes mellitus. The purposes of this research were to compare the abnormalities of glucose metabolism caused by high‐fructose diet and a high‐fat diet and the effects of the high‐fructose diet and high‐fat diet on plasma leptin.

Methods:  In this research, 24 Sprague–Dawley rats were used as the experimental animals, which were divided into three groups: chow diet (control group), high‐fructose diet (60% fructose w/w) and high‐fat diet (20% lard w/w). They were fed for a period of 8 weeks, during which an oral glucose tolerance test was conducted in the seventh week, and after completion of the eighth week, the abdominal adipose tissue and liver of the rats were excised and weighed, and the plasma cholesterol, triglyceride, insulin and leptin concentrations were assayed.

Results:  The high‐fat diet group presented a fasting blood glucose concentration that was higher than that of the control group. Furthermore, after 2 h of glucose challenge, the rats in the high‐fat and high‐fructose diet groups all presented higher plasma glucose concentrations than did the control group. The high‐fat diet group showed higher body weight, higher relative liver weight, a higher plasma cholesterol concentration and higher amylase activity than did the other groups, whereas the high‐fructose diet group showed higher fasting insulin and triglyceride concentrations. As for adipose tissue, the high‐fat diet group presented an amount that was higher than that of the high‐fructose and control groups, but the plasma leptin concentration of the high‐fructose group was higher than that of the control group.

Conclusions:  It can be concluded from the above‐mentioned experimental results that a high‐fructose diet can cause hyperinsulinaemia, while a high‐fat diet can result in impaired pancreatic function of insulin secretion and glucose intolerance, indicating that high‐fructose diet and a high‐fat diet may exert divergent effects on glucose metabolism in rats.
The metabolic syndrome as a link between smoking and cardiovascular disease
Authors: Dzien A. , Dzien‐Bischinger C. , Hoppichler F. , Lechleitner M.
Published: January 2004

Objective:  Smoking is associated with a significant increase in the cardiovascular risk. The possible relationship of smoking with insulin resistance might further enhance the cardiovascular risk of the patients and is therefore of great clinical interest.

Design, Setting and Subjects:  We have retrospectively evaluated data of 3804 non‐diabetic men attending a medical outdoor clinic. Clinical [body mass index (BMI), percentage of body fat, waist‐to‐hip ratio] and laboratory results were compared between smokers (n = 124) and non‐smokers (n = 1915) without cardiovascular disease, as well as between smokers (n = 759) and non‐smokers (n = 1006) with cardiovascular disease.

Results:  Smokers without clinically manifest cardiovascular disease revealed significantly higher fasting glucose (5.8 ± 0.6 mmol/l) and triglyceride levels (1.8 ± 0.9 mmol/l) than non‐smokers (fasting glucose: 5.1 ± 0.7 mmol/l, p < 0.010; triglycerides: 1.5 ± 0.8 mmol/l, p < 0.030). The adverse metabolic profile of smokers was even more pronounced in patients with cardiovascular disease. An age‐matched analysis of smokers could demonstrate that cardiovascular patients revealed higher BMI values (27.3 ± 2.4 kg/m2) and a higher percentage of body fat (25.5 ± 5.5%) than those without cardiovascular disease (BMI: 25.7 ± 2.2 kg/m2, p < 0.010; percentage of body fat: 23.0 ± 5.5%, p < 0.030).

Conclusion:  In men with and without clinically manifest cardiovasular disease, smoking was associated with a metabolic profile indicating a higher degree of insulin resistance.
The effects of oral anti‐hyperglycaemic medications on serum lipid profiles in patients with type 2 diabetes
Authors: Buse J. B. , Tan M. H. , Prince M. J. , Erickson P. P.
Published: January 2004

Aim:  Patients with type 2 diabetes often have dyslipidaemia, putting them at risk of cardiovascular disease, and are frequently treated with oral anti‐hyperglycaemic medications (OAMs). This review compares the effects of OAMs on serum lipids [total cholesterol (TC), low‐density lipoprotein cholesterol (LDL‐C), high‐density lipoprotein cholesterol (HDL‐C), triglycerides (TGs) and free fatty acids (FFAs)] in patients with type 2 diabetes.

Methods:  medline was searched for entries indexed from January 1966 to November 2002; search terms included the names of OAMs and serum lipids, limited to English language and human subjects. We selected clinical studies in type 2 diabetes of OAM monotherapy that included serum lipid data, treated all patients in a treatment group with the same drug, used therapeutic OAM doses not higher than the maximum recommended in the USA, compared therapy with baseline or placebo and specified statistical tests used. One unblinded investigator selected studies for inclusion. Data reported include number of patients, study length, OAM dose, serum lipid data at baseline and endpoint, p‐values and statistical tests.

Results:  Data on the serum lipid effects of sulphonylureas, repaglinide, nateglinide and miglitol were inconclusive. Acarbose increased HDL‐C and decreased LDL‐C and voglibose reduced TC. Metformin at higher doses reduced TC; data on its effects on other lipids were inconclusive. Rosiglitazone increased LDL‐C, HDL‐C and TC and reduced FFAs but had no effect on TGs. Pioglitazone increased HDL‐C and reduced TGs and FFAs but did not affect LDL‐C or TC.

Conclusions:  Lipid changes as a result of improved glycaemic control are not uniform findings associated with anti‐diabetic therapy. Only metformin, acarbose, voglibose, rosiglitazone and pioglitazone had significant effects on the lipid profile. These effects should be considered when selecting OAMs for patients with type 2 diabetes.
Prevention of weight gain in type 2 diabetes requiring insulin treatment
Authors: De Boer H. , Jansen M. , Koerts J. , Verschoor L.
Published: January 2004

Background: Patients with type 2 diabetes who are failing on oral agents will generally gain a large amount of body fat when switched to insulin treatment. This adverse effect may be related to chronic hyperinsulinism induced by long‐acting insulin compounds.

Aim: To test the concept that regain of glycaemic control can be achieved without causing weight gain, using a regimen free of long‐acting insulin.

Methods: In a 3‐month open‐label pilot study including 25 patients with moderate overweight and secondary failure, we investigated whether nocturnal glycaemic control could be achieved with glimepiride administered at 20:00 hours. The starting dose was 1–2 mg, with subsequent titration up to a maximum of 6 mg. Rapid‐acting insulin analogues were used three times daily to regain postprandial glucose control.

Results: Glycaemic control at 3 months was established with glimepiride in a dose of 4.4 ± 0.3 mg/day (mean ± standard error of the mean), and a total daily insulin dose of 24.1 ± 2.6 IU. Fasting glucose levels decreased from 12.7 ± 0.6 mmol/l to 8.1 ± 0.3 mmol/l (p < 0.001), and target levels were reached in 14 of 25 patients (56%). Mean HbA1c decreased from 10.5 ± 0.4 to 7.7 ± 0.2% (p < 0.001). Symptomatic nocturnal hypoglycaemia was not reported. Body weight did not change (85.7 ± 3.6 kg vs. 85.7 ± 3.3 kg, p = 0.99).

Conclusion: The data suggest that this new approach may be useful in about 50% of type 2 diabetes patients presenting with failure on maximal oral treatment.