Soluble P-selectin glycoprotein ligand - a possible new target in ulcerative colitis.

BACKGROUND: The main characteristic of active inflammatory bowel disease (IBD) is the neutrophil infiltration into the intestinal lamina propria, where neutrophils usually do not reside. Selectins are cell surface glycoproteins responsible for binding the leukocytes to vascular cells and their extravasation into the surrounding tissue. They show high affinity to P-selectin glycoprotein ligand-1 (PSGL-1) receptors. PSGL-1 is expressed on the surface of all leukocytes and they mediate the rolling of neutrophils on P-selectin. Soluble PSGL-1 acts competitively with cellular PSGL in many physiological and pathological processes.The aim of our study was to compare serum sPSGL-1 concentration in the blood of patients with ulcerative colitis (UC) and healthy control subjects. METHODS: Serum concentrations of sPSGL-1 were measured in 20 patients with UC and 20 control subjects. Two-layer immunoenzyme procedure (ELISA) was used. RESULTS: The mean (± standard deviation) serum concentrations of sPSGL-1 in patients with UC and controls were 349.97±75.40 U/mL and 284.39±52.40 U/mL, respectively (p=0.003). CONCLUSION: In the present study, we showed that patients with UC had significantly higher sPSGL-1 blood values in comparison with healthy subjects. A short-term blockade with anti-PSGL-1 antibodies could block the transport of neutrophils and decrease UC activity. Thus it could possibly be employed in a new therapeutic approach to the treatment of UC (Fig. 1, Ref. 25).

Microsatelite GT polymorphism in the toll-like receptor 2 is associated with colorectal cancer.

Factors underlying genetic predisposition for development of sporadic colorectal cancer are largely unknown. The fact that this cancer is more common in patients suffering from inflammatory bowel disease raises the question of the relationship between chronic inflammation and cancer. Toll-like receptors 2 (TLR2) and 4 (TLR4) are critical in initiating innate immune response and inflammation toward various bacteria commonly found in the intestine. Recent evidence about the association of polymorphisms in these genes with ulcerative colitis and Crohn's disease, as well as other inflammatory conditions, was the basis for our investigation of their role in sporadic colorectal cancer. We assessed genotype and allele frequencies of TLR2 GT microsatelite polymorphism, TLR2 Arg753Gln, TLR4 Asp299Gly and TLR4 Thr399Ile polymorphisms in 89 colorectal cancer patients and 88 age- and sex-matched controls. The frequency of TLR2 GT microsatelite alleles with 20 and 21 GT repeats was decreased (p = 0.0044 and p = 0.001, respectively), while the frequency of the allele with 31 GT repeats was increased (p = 0.0147) in patients. The mutant allele Asp299Gly of TLR4 gene was slightly more frequent in colorectal cancer patients (p = 0.0269). In conclusion, we report an association of microsatelite GT polymorphisms of TLR2 gene and Asp299Gly polymorphism of the TLR4 gene with sporadic colorectal cancer among Croatians.

Should we screen for asymptomatic left ventricular dysfunction in glaucoma patients?

BACKGROUND: The aim of the study was to assess the frequency of asymptomatic left ventricular dysfunction in primary open-angle glaucoma patients. PATIENTS AND METHODS: Two-dimensional and pulsed Doppler echocardiography of transmitral flow was performed on 31 glaucoma patients and 27 controls. RESULTS: No significant difference was found in early (E) and late (A) transmitral filling velocity, velocity time integral E wave (VTIE) and A wave (VTIA), left ventricular end-diastolic pressure, pulmonary capillary wedge pressure, left ventricular ejection fraction (EF) and fractional shortening (FS). A significant difference was found in ratio E/A (P=0.04) and ratio VTIA/VTIE (P=0.05), although all obtained values were within the 95% confidence limit for the corresponding age. CONCLUSION: Our study tends to indicate the possibility of dysfunction of myocardial relaxation in glaucoma patients, which might be partially attributed to systemic vascular dysregulation.

Evaluation and appraisal of randomized controlled trials in myeloma.

PURPOSE: To critically appraise therapeutic innovations tested in randomized controlled trials (RCTs) in multiple myeloma from 1966-1998. DESIGN: We performed a comprehensive search to identify published RCTs in multiple myeloma. Quality dimensions of the design, conduct, analysis and reporting of each trial were assessed. RESULTS: We identified 136 RCTs reported in 114 papers. Overall, therapeutic efforts in multiple myeloma resulted in a 5% absolute gain in five-year survival at a cost of a 0.35% increase in treatment related deaths. Hence on average a patient enrolled in a RCT in myeloma is 14 (5/35) times more likely to be helped than harmed. However, when the RCTs were critically appraised for key quality dimensions of trials' conduct, we found that only 7%) of the trials (10 of 136) were analyzed according to intention-to-treat (ITT), 9% (12 of 136) reported a power analysis (beta error), 32% (35 of 111) adequately concealed treatment allocation, 78% (106 of 136) provided a detailed description of patient withdrawals, and 83%) (19 of 22) of the double blind RCTs had appropriately described methodology. CONCLUSIONS: Therapeutic innovations tested through RCTs have improved the outcomes of patients with multiple myeloma. However, the quality of RCT reporting and methodology in multiple myeloma could be substantially improved. Most therapeutic strategies in multiple myeloma are based on modest quality, low power evidence. Despite these shortcomings our findings suggest patients may often clinically benefit from enrollment in clinical trials when available. Patients on average received modest benefit from innovative therapies tested in RCTs at little additional risk of side effects.

Liver angiosarcoma and hemangiopericytoma after occupational exposure to vinyl chloride monomer.

Various malignant tumors of the liver, especially liver angiosarcoma, have been described after occupational exposure to vinyl chloride monomer. We present the case records and pathologic findings of two plastic industry workers who had been exposed to high concentrations of vinyl chloride. These workers developed hepatic neoplasms, angiosarcoma, or hemangiopericytoma. We discuss the histogenesis of these tumors; the common vascular origin and the mutual transformation of these two tumors suggest that the hemangiopericytoma may also have developed during occupational exposure to high concentrations of vinyl chloride monomer.

Linking evidence-based medicine therapeutic summary measures to clinical decision analysis.

OBJECTIVE: Evidence-based medicine (EBM) seeks to improve clinical practice by evaluating the quality of clinical evidence and ensuring that only the "best" evidence from clinical research is used in the management of individual patients. EBM has contributed to our understanding of the meaning of the benefit and harm of treatment as reported in the literature, and it is often promoted as an aid to clinical decision making. However, EBM therapeutic summary measures reflect only a single dimension of clinical decision making. The purpose of this work is to show how EBM therapeutic summary measures can be effectively incorporated into medical decision making. DESIGN: The effective application of the therapeutic summary measures advocated by EBM requires their integration into the framework of clinical decision analysis. Clinical decision analysis involves not only the identification and specification of the probabilities of clinical events but also the assessment of their relative values or utilities. We present here several analytic models for the integration of EBM therapeutic summary measures within the framework of clinical decision analysis. MAIN RESULTS: As expected, our analysis demonstrated that treatment should never be administered if its harm is greater than its efficacy, which is generally expressed as relative risk reduction. Likewise, a diagnostic test should never be ordered if the therapeutic harm is greater than the therapeutic efficacy. Intervention is always favored if the number needed to treat to avoid one adverse outcome (NNT) is smaller than the number needed to treat to harm one individual (NNH). When faced with a choice between two therapeutic options, the action threshold above which an intervention is favored can be expressed in terms of the harm inflicted (H) as H x NNT or NNT/NNH. If a patient's preferences are taken into account as relative value judgments (RV) of adverse events relative to that of therapeutic events, the action threshold is defined as NNT x (RV/NNH). CONCLUSIONS: In the setting of clinical decision making, EBM summary measures derived from population studies can be effectively used to define diagnostic and therapeutic action thresholds that may help in the management of individual patients.

Endoluminal stenting for subclavian artery stenosis in Takayasu's arteritis.

We describe a patient with Takayasu's arteritis (type I): occlusion of all large vessels of the aortic arch except the left subclavian artery which was, however, almost completely occluded, resulting in a characteristic subclavian steal syndrome. Elective left main subclavian artery balloon angioplasty followed by endoluminal stenting was performed with excellent results. After prolonged immunosuppressive treatment, at the 12-month follow-up there was no evidence of restenosis. In selected patients with Takayasu's arteritis and subclavian stenosis, elective endoluminal stenting can be used as a definitive procedure or as a bridge to surgical revascularization.

Gender differences in triggering of acute myocardial infarction.

The frequencies of potential triggers of acute myocardial infarction differ between men and women. There is a possibility that anti-ischemic drugs protect against trigger-related infarctions.

Acceptable regret in medical decision making.

When faced with medical decisions involving uncertain outcomes, the principles of decision theory hold that we should select the option with the highest expected utility to maximize health over time. Whether a decision proves right or wrong can be learned only in retrospect, when it may become apparent that another course of action would have been preferable. This realization may bring a sense of loss, or regret. When anticipated regret is compelling, a decision maker may choose to violate expected utility theory to avoid regret. We formulate a concept of acceptable regret in medical decision making that explicitly introduces the patient's attitude toward loss of health due to a mistaken decision into decision making. In most cases, minimizing expected regret results in the same decision as maximizing expected utility. However, when acceptable regret is taken into consideration, the threshold probability below which we can comfortably withhold treatment is a function only of the net benefit of the treatment, and the threshold probability above which we can comfortably administer the treatment depends only on the magnitude of the risks associated with the therapy. By considering acceptable regret, we develop new conceptual relations that can help decide whether treatment should be withheld or administered, especially when the diagnosis is uncertain. This may be particularly beneficial in deciding what constitutes futile medical care.

Serum prolactin levels after seizure and syncopal attacks.

Loss of consciousness and falling are the key features of syncope. Common accompaniments include tonic and myoclonic muscle activity, eye deviations, automatisms, vocalizations and hallucinations that may render the distinction from epileptic seizures difficult. The frequently increased levels of serum prolactin (SPRL) were observed immediately after generalized and complex partial seizures. Presumably, the hormone release is caused by the propagation of epileptic activity, usually from the temporal lobe to the hypothalamic pituitary axis. Numerous reports have demonstrated that the post-ictal SPRL level may be used to differentiate between epileptic and syncopal, non-epileptic attacks. In order to confirm the hypothesis, the SPRL levels were measured in patients with complex partial seizures (CPS) and patients with vaso-vagal syncopal attacks (VVS). The SPRL levels were prospectively measured for each patient as soon as possible after the event (within 1 hour), then 1 hour after the first determination and finally blood was sampled 24 hours later. During the study period (18 months), 18 patients with CPS and 15 patients with VVS were investigated in total. The mean values of SPRL levels in both groups were increased immediately after the event (CPS group: 1142 +/- 305 mIU/l; VVS group: 874 +/- 208 mIU/l). The elevated SPRL levels were found in 14 (78%) patients immediately after CPS and in 9 (60%) patients immediately after VVS. After examining the results of the present study we conclude that the elevated serum prolactin level after an epileptic attack is of no significant value in differential diagnosis between epileptic and vaso-vagal syncopal attacks.

Using the Internet to calculate clinical action thresholds.

Understanding the risks and benefits of available treatments represents an essential element of clinical practice. Previous work has demonstrated that knowledge of net benefits and net risks can relate to our decisions on whether or not to administer a particular treatment or order a diagnostic test. A wider application of this model has been difficult because data on net benefits and net risks are not directly reported. We used more frequently reported data on treatment efficacy (E) and risks (Rrx) to obtain an equation for the treatment threshold probability above which treatment should be given and below which it should be withheld. The diagnostic test should only be performed if the probability of a disease is between the testing threshold and the treatment threshold. We first described a theoretical background for these calculations. We then used a JavaScript programming language to write a computer program which physicians can use to calculate these threshold probabilities effortlessly through the Internet. In most clinical situations we do not have to achieve maximum diagnostic certainty in order to act. However, we should never treat or order a diagnostic test if the risk of the treatment is greater than its efficacy. The minimally required E/R ratio of a particular treatment is equal to the reciprocal value of the mortality/morbidity of untreated disease. Similarly, the lowest number of patients needed to be treated (NNT) for therapy to be worth administering is equal to the reciprocal of the treatment risk. We show how evidence-based summary measures of therapeutic effects, such as the treatment efficacy, harms, and NNT, can successfully be integrated within a decision analytic model. This in turn will facilitate wider use of the quantitative benefit-risk analysis. Accessing the Internet for direct and immediate approach to the formulas described here should make this task even easier in everyday clinical decision making.

Influence of betaxolol and timolol on the venous tone in glaucoma patients.

The aim of this study was the assessment of physiological venous reflexes in 40 glaucoma patients treated with topically applied timolol maleate 0.50% and betaxolol HCL 0.50%. They were divided into two groups of twenty each; one group being given timolol and the other betaxolol. The assessment of the venous tone was performed by testing venous reflexes. We found no statistically significant difference between timolol and betaxolol; however, when the influence of circulating catecholamines and the other vasoactive substances was excluded by suprasphygmatic insufflation of a pediatric cuff, a significant difference was found in the Valsalva's maneuver (125.5 +/- 8.1 vs 85.0 +/- 34.3 venoconstrictive units VCUs, p = 0.03). The IOP was significantly decreased in both treatment group, although the pressure reduction effect was more pronounced in the timolol group. Our study suggests that timolol and betaxolol have a slightly different mode of action on the venous side of circulation under topical medications. It is possible that the use of betaxolol topically may reduce a systemic venoconstriction.

[Algorithms in ultrasonic diagnosis of diseases of the hepatobiliary tract]. / Algoritmi kod ultrazvucne dijagnostike bolesti hepatobilijarnog trakta.

The hallmark in clinical diagnostic in last two decade is ultrasound. Today, the diagnosis of numerous diseases detected was using US diagnostic. US the first diagnostic procedure in medical practice of all specialties, especially in abdominal disease. Liver and spleen diffuse or focal lesions, and other abdominal disease very easy will be detected using by US. There are some diagnostic algorithms that solved diagnostic dilemmas, for instance in the case of jaundice, focal and diffuse liver and spleen lesions, and other gallbladder, biliary ducts, pancreas disease and abdominal solid or liquid collections. The algorithms in diagnostic of abdominal disease are the choice for successful diagnostic procedure, very often used in medical practice.

Calculating confidence intervals for threshold and post-test probabilities.

We describe a method and a computer program, written in JavaScript, for calculating confidence intervals. The method uses Taylor's series to approximate the standard errors of a post-test probability and threshold probabilities and, from them, to obtain the associated confidence intervals. This method is valid if the variables of interest are stochastically independent.

Dermatological indicators of coronary risk: a case-control study.

OBJECTIVE: We examined the association of dermatological signs such as baldness, thoracic hairiness, hair greying and diagonal earlobe crease with the risk of myocardial infarction in men under the age of 60 years. METHODS: A hospital-based, case-control study included 842 men admitted for the first non-fatal myocardial infarction, the controls were 712 men admitted with noncardiac diagnoses, without clinical signs of coronary disease. The relative risks were estimated as odds ratios. Logistic regression was used to control for the confounding variables. RESULTS: Baldness, thoracic hairiness and earlobe crease were approximately 40% more prevalent in cases (P<10(-6) in each case). In both cases and controls, baldness and thoracic hairiness were frequently coexistent, as well as hair greying and earlobe crease (P<10(-4) in each case). After allowing for age and other established coronary risk factors, the relative risk of myocardial infarction for fronto-parietal baldness compared with no hair loss was 1.77 (95% CI 1.27-2.45) and it was 1.83 (95 CI 1.4-2.3) for men with thick, extended thoracic hairiness. The presence of a diagonal earlobe crease yielded a relative risk of 1.37 (95% CI 1.25-1.5), while hair greying was associated with myocardial infarction only in men under the age of 50 years. CONCLUSION: It appears that baldness, thoracic hairiness and diagonal earlobe crease indicate an additional risk of myocardial infarction in men under the age of 60 years, independently of age and other established coronary risk factors.

High-Dose Chemotherapy in the Adjuvant Treatment of Breast Cancer: Benefit/Risk Analysis.

BACKGROUND: High-dose chemotherapy (HDRx) may improve the prognosis of patients with high-risk breast cancer but at the expense of increased toxicity. However, no randomized, controlled trials have been published that clearly demonstrate the superiority of HDRx over conventional adjuvant chemotherapy. METHODS: We developed a simple model to compare benefits and risks of HDRx with conventional adjuvant chemotherapy (SDRx). The model integrates data on efficacy and risks of two competing treatment strategies into a single decision rule. RESULTS AND CONCLUSIONS: Using data from phase II studies, we show that if a disease-free survival is considered to be the most important outcome, HDRx should be administered when the probability of breast cancer relapse at five years exceeds 54% to 71% for patients with 4 to 9 positive nodes and exceeds 29% to 40% for patients with >9 positive nodes. If the endpoint of interest is five-year overall survival, then the treatment should be administered when the probability of relapse exceeds 77% to 83% for patients with 4 to 9 nodes involved and 22% to 31% for those with >9 lymph nodes involved. While awaiting results of randomized, controlled trials to definitively establish the efficacy rate of HDRx, we also found that HDRx could be considered in the management of high-risk breast cancer if its efficacy rate is at least 54% to 60% superior to SDRx in reducing relapse risk in breast cancer patients with 4 to 9 nodes and at least 31% to 38% for >9 positive nodes. If survival data are used instead of disease-free survival outcomes, HDRx efficacy should be at least 47% to 48% superior to SDRx in reducing death risk in breast cancer patients with 4 to 9 nodes and at least 27% to 30% superior for >9 positive nodes to consider its use in the adjuvant setting.

Two new cases of liver angiosarcoma: history and perspectives of liver angiosarcoma among plastic industry workers.

In this report of two new cases of liver angiosarcoma (ASL) among plastic industry workers, the authors present the history and perspectives of this problem. The first cases of ASL have been registered since 1974, and in 1984, the European register of angiosarcoma was founded. In this register, 11 cases of ASL and one case of haemangiopericytoma have been registered from Croatia, all from a single plastics plant near Split. Two new cases of ASL (in retired autoclave cleaners, who were exposed to a concentration of 500-1000 ppm vinyl chloride monomer (VCM) during the working process) in the same plant are represented. They were detected with combined techniques of ASL detection, and both are still alive. The diagnoses have been histologically confirmed: one of them was surgically treated with segmental liver resection. The appearance of new cases of ASL confirms the perspective presented in the last report by the same authors.