bluuebunny/crossref_metadata_2025 huggingface dataset:
Follow-up care by patient's own general practitioner after contact with out-of-hours care. A descriptive study
Authors: van Uden Caro JT , Zwietering Paul J , Hobma Sjoerd O , Ament Andre JHA , Wesseling Geertjan , van Schayck Onno CP , Crebolder Harry FJM
Published: June 2005

Background

Little is known about the care process after patients have contacted a GP cooperative for out-of-hours care. The objective of this study was to determine the proportion of patients who seek follow-up care after contact with a GP cooperative for out-of-hours care, and to gain insight into factors that are related to this follow-up care.

Methods

A total of 2805 patients who contacted a GP cooperative for out-of-hours care were sent a questionnaire. They were asked whether they had attended their own GP within a week after their contact with the cooperative, and for what reason. To investigate whether other variables are related to follow-up care, a logistic regression analysis was applied. Variables that entered in this analysis were patient characteristics (age, gender, etc.) and patient opinion on correctness of diagnosis, urgency and severity of the medical complaint.

Results

The response rate was 42%. In total, 48% of the patients received follow-up care from their own GP. Only 20% were referred or advised to attend their own GP. Others attended because their medical condition worsened or because they were concerned about their complaint. Variables that predicted follow-up care were the patient's opinion on the correctness of the diagnosis, patient's health insurance, and severity of the medical problem.

Conclusion

Almost half of all patients in this study who contacted the GP cooperative for out-of-hours care attended their own GP during office hours within a week, for the same medical complaint. The most important factor that predicted follow-up care from the patient's own GP after an out-of-hours contact was the patient's degree of confidence in the diagnosis established at the GP cooperative. Despite the limited generalisability, this study is a first step in providing insight into the dimension of follow-up care after a patient has contacted the GP cooperative for out-of-hours primary care.
PSA testing for prostate cancer: an online survey of the views and reported practice of General Practitioners in the UK
Authors: Brett Jo , Watson Eila , Hewitson Paul , Bukach Colleen , Edwards Adrian , Elwyn Glyn , Austoker Joan
Published: June 2005

Background

The role of Prostate Specific Antigen (PSA) testing in the early detection of prostate cancer is controversial. Current UK policy stipulates that any man who wishes to have a PSA test should have access to the test, provided he has been given full information about the benefits and limitations of testing. This study aimed to determine UK GPs' current reported practice regarding PSA testing, and their views towards informed decision-making and PSA testing.

Method

Online questionnaire survey, with a sample of 421 GPs randomly selected from a database of GPs across the UK.

Results

95% (400/421) of GPs responded. 76% of GPs reported having performed a PSA test for an asymptomatic man at least once in the previous three months, with 13% reported having tested more than five men in this period. A majority of GPs reported they would do a PSA test for men presenting with a family history and requesting a test, for asymptomatic men requesting a test and also for men presenting with lower urinary tract symptoms. Reported testing rates were highest for men with a family history. Amongst men with lower urinary tract symptoms and men with no symptoms, reported testing rates were significantly higher for older than younger men.

The majority of GPs expressed support for the current policy (67%), and favoured both the general practitioner and the man being involved in the decision making process (83%). 90% of GPs indicated that they would discuss the benefits and limitation of testing with the man, with most (61%) preferring to ask the man to make a further appointment if he decides to be tested.

Conclusion

This study indicates that PSA testing in asymptomatic men is a regular occurrence in the UK, and that there is general support from GPs for the current policy of making PSA tests available to 'informed' men who are concerned about prostate cancer. While most GPs indicated they would discuss the benefits and limitations prior to PSA testing, and most GPs favoured a shared approach to decision making, it is not known to what extent men are actually being informed. Research is needed to evaluate the most effective approach to assisting men in making an informed decision about whether or not to have a PSA test.
Agreement between diagnoses reached by clinical examination and available reference standards: a prospective study of 216 patients with lumbopelvic pain
Authors: Laslett Mark , McDonald Barry , Tropp Hans , Aprill Charles N , Öberg Birgitta
Published: June 2005

Background

The tissue origin of low back pain (LBP) or referred lower extremity symptoms (LES) may be identified in about 70% of cases using advanced imaging, discography and facet or sacroiliac joint blocks. These techniques are invasive and availability varies. A clinical examination is non-invasive and widely available but its validity is questioned. Diagnostic studies usually examine single tests in relation to single reference standards, yet in clinical practice, clinicians use multiple tests and select from a range of possible diagnoses. There is a need for studies that evaluate the diagnostic performance of clinical diagnoses against available reference standards.

Methods

We compared blinded clinical diagnoses with diagnoses based on available reference standards for known causes of LBP or LES such as discography, facet, sacroiliac or hip joint blocks, epidurals injections, advanced imaging studies or any combination of these tests. A prospective, blinded validity design was employed. Physiotherapists examined consecutive patients with chronic lumbopelvic pain and/or referred LES scheduled to receive the reference standard examinations. When diagnoses were in complete agreement regardless of complexity, "exact" agreement was recorded. When the clinical diagnosis was included within the reference standard diagnoses, "clinical agreement" was recorded. The proportional chance criterion (PCC) statistic was used to estimate agreement on multiple diagnostic possibilities because it accounts for the prevalence of individual categories in the sample. The kappa statistic was used to estimate agreement on six pathoanatomic diagnoses.

Results

In a sample of chronic LBP patients (n = 216) with high levels of disability and distress, 67% received a patho-anatomic diagnosis based on available reference standards, and 10% had more than one tissue origin of pain identified. For 27 diagnostic categories and combinations, chance clinical agreement (PCC) was estimated at 13%. "Exact" agreement between clinical and reference standard diagnoses was 32% and "clinical agreement" 51%. For six pathoanatomic categories (disc, facet joint, sacroiliac joint, hip joint, nerve root and spinal stenosis), PCC was 33% with actual agreement 56%. There was no overlap of 95% confidence intervals on any comparison. Diagnostic agreement on the six most common patho-anatomic categories produced a kappa of 0.31.

Conclusion

Clinical diagnoses agree with reference standards diagnoses more often than chance. Using available reference standards, most patients can have a tissue source of pain identified.
Geographic variations of childhood asthma hospitalization and outpatient visits and proximity to ambient pollution sources at a U.S.-Canada border crossing
Authors: Oyana Tonny J , Rivers Patrick A
Published: June 2005

Background

Childhood asthma is a significant public health problem in the United States and evidence is accumulating regarding the contribution from traffic and ambient air pollution. This study is a companion piece of a related Buffalo asthma study in adults recently published in the July 2004 issue of American Journal of Public Health. This study focuses on children under 18 years of age diagnosed with asthma during a three-year period (2000–2002). In order to determine the effects of particulate air pollution on public health, we conducted an ecologic study of childhood asthma and point-source respirable particulate air pollution in patients diagnosed with asthma (n = 6,425). Patients diagnosed with gastroenteritis (n = 5,132) were used as controls.

Results

Although the results of this study show spatial patterns similar to the ones observed in the adult study, a multiple-comparison test shows that EPA-designated focus sites located in Buffalo's east side are statistically (p < 0.008) more linked to childhood asthma than sites located elsewhere.

Conclusion

Findings of this study can be useful in geographic targeting and in the design of optimal and preventive measures.
A space-time analysis of the proportion of late stage breast cancer in Massachusetts, 1988 to 1997
Authors: Sheehan T Joseph , DeChello Laurie M
Published: June 2005

Background

Early detection is the best way to control breast cancer. This observational epidemiologic study uses ten years of data, 1988–1997, to determine whether the observed variations in the proportion of breast cancers diagnosed at late stage are simply random or are statistically significant with respect to both geographical location and time.

Results

A total of three spatial-temporal areas were found to deviate significantly from randomness in the unadjusted analysis; one of the three areas contained statistically significant excesses in proportion of late stage, while two areas were identified as significantly lower than expected. The area of excess spanned the first three years of the study period, while the low areas spanned the last five years of the study period. Some of these areas were no longer statistically significant when adjustments were made for SES and urban/rural status.

Conclusion

Although there was an area of excess in eastern Massachusetts, it only spanned the first three years of the study period. The low areas were fairly consistent, spanning the last five years of the study period.
Enhanced detergent extraction for analysis of membrane proteomes by two-dimensional gel electrophoresis
Authors: Churchward Matthew A , Butt R Hussain , Lang John C , Hsu Kimberly K , Coorssen Jens R
Published: June 2005

Background

The analysis of hydrophobic membrane proteins by two-dimensional gel electrophoresis has long been hampered by the concept of inherent difficulty due to solubility issues. We have optimized extraction protocols by varying the detergent composition of the solubilization buffer with a variety of commercially available non-ionic and zwitterionic detergents and detergent-like phospholipids.

Results

After initial analyses by one-dimensional SDS-PAGE, quantitative two-dimensional analyses of human erythrocyte membranes, mouse liver membranes, and mouse brain membranes, extracted with buffers that included the zwitterionic detergent MEGA 10 (decanoyl-N-methylglucamide) and the zwitterionic lipid LPC (1-lauroyl lysophosphatidylcholine), showed selective improvement over extraction with the common 2-DE detergent CHAPS (3 [(3-cholamidopropyl)dimethylammonio]-1-propanesulfonate). Mixtures of the three detergents showed additive improvements in spot number, density, and resolution. Substantial improvements in the analysis of a brain membrane proteome were observed.

Conclusion

This study demonstrates that an optimized detergent mix, coupled with rigorous sample handling and electrophoretic protocols, enables simple and effective analysis of membrane proteomes using two-dimensional electrophoresis.
A review of the economic burden of ADHD
Authors: Matza Louis S , Paramore Clark , Prasad Manishi
Published: June 2005

Attention-deficit hyperactivity disorder (ADHD) is a common disorder that is associated with broad functional impairment among both children and adults. The purpose of this paper is to review and summarize available literature on the economic costs of ADHD, as well as potential economic benefits of treating this condition. A literature search was performed using MEDLINE to identify all published articles on the economic implications of ADHD, and authors were contacted to locate conference abstracts and articles in press that were not yet indexed. In total, 22 relevant items were located including published original studies, economic review articles, conference presentations, and reports available on the Internet. All costs were updated and presented in terms of year 2004 US dollars. A growing body of literature, primarily published in the United States, has demonstrated that ADHD places a substantial economic burden on patients, families, and third-party payers. Results of the medical cost studies consistently indicated that children with ADHD had higher annual medical costs than either matched controls (difference ranged from $503 to $1,343) or non-matched controls (difference ranged from $207 to $1,560) without ADHD. Two studies of adult samples found similar results, with significantly higher annual medical costs among adults with ADHD (ranging from $4,929 to $5,651) than among matched controls (ranging from $1,473 to $2,771). A limited number of studies have examined other economic implications of ADHD including costs to families; costs of criminality among individuals with ADHD; costs related to common psychiatric and medical comorbidities of ADHD; indirect costs associated with work loss among adults with ADHD; and costs of accidents among individuals with ADHD. Treatment cost-effectiveness studies have primarily focused on methylphenidate, which is a cost-effective treatment option with cost-effectiveness ratios ranging from $15,509 to $27,766 per quality-adjusted life year (QALY) gained. As new treatments are introduced it will be important to evaluate their cost-effectiveness to provide an indication of their potential value to clinicians, patients, families, and third-party payers.
Preoperative diagnosis of a mediastinal granular cell tumor by EUS-FNA : A case report and review of the literature
Authors: Bean Sarah M , Eloubeidi Mohamad A , Eltoum Isam A , Cerfolio Robert J , Jhala Darshana N
Published: June 2005

We report the first case of a posterior mediastinal granular cell tumor initially diagnosed on cytologic material obtained via endoscopic ultrasound-guided fine needle aspiration (EUS-FNA) in a 51-year-old male with a prior history of colon cancer. Aspirates obtained were cellular and composed of polygonal cells with abundant granular cytoplasm and small, round dark nuclei. An immunoperoxidase stain performed on the cell block for antibodies to S-100 protein showed strong, diffuse staining of the cytoplasmic granules. Electron microscopy performed on the cell block revealed numerous cytoplasmic lysosomes. This is the first case report in the English literature of a definitive preoperative diagnosis of a mediastinal granular cell tumor utilizing material obtained via EUS-FNA.
Greatly increased occurrence of breast cancers in areas of mammographically dense tissue
Authors: Ursin Giske , Hovanessian-Larsen Linda , Parisky Yuri R , Pike Malcolm C , Wu Anna H
Published: June 2005

Introduction

Mammographic density is a strong, independent risk factor for breast cancer. A critical unanswered question is whether cancers tend to arise in mammographically dense tissue (i.e. are densities directly related to risk or are they simply a marker of risk). This question cannot be addressed by studying invasive tumors because they manifest as densities and cannot be confidently differentiated from the densities representing fibrous and glandular tissue. We addressed this question by studying ductal carcinoma in situ (DCIS), as revealed by microcalcifications.

Method

We studied the cranio-caudal and the mediolateral-oblique mammograms of 28 breasts with a solitary DCIS lesion. Two experienced radiologists independently judged whether the DCIS occurred in a mammographically dense area, and determined the density of different areas of the mammograms.

Results

It was not possible to determine whether the DCIS was or was not in a dense area for six of the tumors. Of the remaining 22 lesions, 21 occurred in dense tissue (test for difference from expected taken as the percentage of density of the 'mammographic quadrant' containing DCIS; P < 0.0001). A preponderance of DCIS (17 out of 28) occurred in the mammographic quadrant with the highest percentage density.

Conclusion

DCIS occurs overwhelmingly in the mammographically dense areas of the breast, and pre-DCIS mammograms showed that this relationship was not brought about by the presence of the DCIS. This strongly suggests that some aspect of stromal tissue comprising the mammographically dense tissue directly influences the carcinogenic process in the local breast glandular tissue.
Clinical investigation: thyroid function test abnormalities in cardiac arrest associated with acute coronary syndrome
Authors: Iltumur Kenan , Olmez Gonul , Arıturk Zuhal , Taskesen Tuncay , Toprak Nizamettin
Published: June 2005

Introduction

It is known that thyroid homeostasis is altered during the acute phase of cardiac arrest. However, it is not clear under what conditions, how and for how long these alterations occur. In the present study we examined thyroid function tests (TFTs) in the acute phase of cardiac arrest caused by acute coronary syndrome (ACS) and at the end of the first 2 months after the event.

Method

Fifty patients with cardiac arrest induced by ACS and 31 patients with acute myocardial infarction (AMI) who did not require cardioversion or cardiopulmonary resuscitation were enrolled in the study, as were 40 healthy volunteers. The patients were divided into three groups based on duration of cardiac arrest (<5 min, 5–10 min and >10 min). Blood samples were collected for thyroid-stimulating hormone (TSH), tri-iodothyronine (T3), free T3, thyroxine (T4), free T4, troponin-I and creatine kinase-MB measurements. The blood samples for TFTs were taken at 72 hours and at 2 months after the acute event in the cardiac arrest and AMI groups, but only once in the control group.

Results

The T3 and free T3 levels at 72 hours in the cardiac arrest group were significantly lower than in both the AMI and control groups (P < 0.0001). On the other hand, there were no significant differences between T4, free T4 and TSH levels between the three groups (P > 0.05). At the 2-month evaluation, a dramatic improvement was observed in T3 and free T3 levels in the cardiac arrest group (P < 0.0001). In those patients whose cardiac arrest duration was in excess of 10 min, levels of T3, free T3, T4 and TSH were significantly lower than those in patients whose cardiac arrest duration was under 5 min (P < 0.001, P < 0.001, P < 0.005 and P < 0.05, respectively).

Conclusion

TFTs are significantly altered in cardiac arrest induced by ACS. Changes in TFTs are even more pronounced in patients with longer periods of resuscitation. The changes in the surviving patients were characterized by euthyroid sick syndrome, and this improved by 2 months in those patients who did not progress into a vegetative state.
Short-term effects of positive end-expiratory pressure on breathing pattern: an interventional study in adult intensive care patients
Authors: Haberthür Christoph , Guttmann Josef
Published: June 2005

Introduction

Positive end-expiratory pressure (PEEP) is used in mechanically ventilated patients to increase pulmonary volume and improve gas exchange. However, in clinical practice and with respect to adult, ventilator-dependent patients, little is known about the short-term effects of PEEP on breathing patterns.

Methods

In 30 tracheally intubated, spontaneously breathing patients, we sequentially applied PEEP to the trachea at 0, 5 and 10 cmH2O, and then again at 5 cmH2O for 30 s each, using the automatic tube compensation mode.

Results

Increases in PEEP were strongly associated with drops in minute ventilation (P < 0.0001) and respiratory rate (P < 0.0001). For respiratory rate, a 1 cmH2O change in PEEP in either direction resulted in a change in rate of 0.4 breaths/min. The effects were exclusively due to changes in expiratory time. Effects began to manifest during the first breath and became fully established in the second breath for each PEEP level. Identical responses were found when PEEP levels were applied for 10 or 60 s. Post hoc analysis revealed a similar but stronger response in patients with impaired respiratory system compliance.

Conclusion

In tracheally intubated, spontaneously breathing adult patients, the level of PEEP significantly influences the resting short-term breathing pattern by selectively affecting expiratory time. These findings are best explained by the Hering–Breuer inflation/deflation reflex.
Effect of boldine, secoboldine, and boldine methine on angiotensin II-induced neurtrophil recruitment in vivo
Authors: Estellés Rossana , Milian Lara , Nabah Yafa Naim Abu , Mateo Teresa , Cerdá-Nicolás Miguel , Losada Mercedes , Ivorra María Dolores , Issekutz Andrew C , Cortijo Julio , Morcillo Esteban J , Blázquez María Amparo , Sanz María-Jesús
Published: June 2005

Angiotensin-II (Ang-II) has inflammatory activity and is involved in different diseases associated with the cardiovascular system. This study has evaluated the effect of boldine (B), and two phenanthrene alkaloids semisynthesized by us, secoboldine (SB) and boldine methine (BM), on Ang-II-induced neutrophil recruitment. Intraperitoneal administration of 1 nM Ang-II induced significant neutrophil accumulation, which was maximal at 4–8 h. BM inhibited neutrophil infiltration into the peritoneal cavity at 4 h and 8 h by 73% and 77%, respectively, SB at 8 h by 55%, and B had no effect on this response. Although BM inhibited the release of cytokine-inducible neutrophil chemoattractant/keratinocyte-derived chemokine, macrophage inflammatory protein-2 (MIP-2), and platelet-activating factor (PAF) elicited by Ang-II, SB only reduced the release of MIP-2 after 4 h of its administration. Sixty-minute superfusion of the rat mesentery with 1 nM Ang-II induced a significant increase in the leukocyte-endothelial cell interactions and P-selectin up-regulation, which were inhibited by 1 μM BM and SB. The generation of reactive oxygen species (ROS) in endothelial cells stimulated with Ang-II was inhibited significantly by the three alkaloids tested. BM also diminished Ang-II-induced interleukin-8 release from endothelial cells and blocked the PAF receptor on human neutrophils (concentration of the compound needed to produce 50% inhibition value: 28.2 μM). Therefore, BM is a potent inhibitor of Ang-II-induced neutrophil accumulation in vivo. This effect appears to be mediated through inhibition of CXC chemokine and PAF release, ROS scavenging activity, and blockade of the PAF receptor. Thus, it may have potential therapeutic interest for the control of neutrophil recruitment that occurs in inflammation associated with elevated levels of Ang-II.
Prodefensins are matrix proteins of specific granules in human neutrophils
Authors: Faurschou Mikkel , Kamp Søren , Cowland Jack B , Udby Lene , Johnsen Anders H , Calafat Jero , Winther Henrik , Borregaard Niels
Published: June 2005

Defensins are potent antimicrobial and proinflammatory peptides. The human neutrophil defensins human neutrophil peptide (HNP)-1–3 are synthesized as 94 amino acide (aa) preproHNPs, which are converted to 75 aa proHNPs by cotranslational removal of a 19 aa endoplasmic reticulum signal peptide. At the promyelocytic stage of myelopoiesis, proHNPs are further proteolytically modified and accumulate in azurophil granules as 29–30 aa HNPs. In contrast, proHNPs produced by more mature myeloid cells are not subjected to proteolytic cleavage and undergo a high degree of constitutive exocytosis. The proHNPs are devoid of antimicrobial potential, and the significance of their secretion is unknown. To investigate whether mature neutrophils contain proHNPs, we developed antibodies against proHNP-1 by DNA immunization of rabbits. In addition, antibodies against the 45 aa proHNP pro-piece were raised by conventional immunization procedures. These antibodies allowed detection of proHNPs in homogenates of peripheral blood neutrophils. The proHNPs were isolated by affinity chromatography, and their identity was confirmed by mass spectrometry and N-terminal aa sequence analysis. Finally, the neutrophil proHNPs were identified as novel matrix proteins of specific granules by subcellular fractionation experiments, release studies, and immunoelectron microscopy. Thus, human neutrophils not only store large amounts of mature defensins in azurophil granules but also contain a more easily mobilized reservoir of unprocessed prodefensins in specific granules.
Human exposures to tilmicosin reported to poison centres, Texas, 1998-2003
Authors: Forrester Mathias B
Published: June 2005

Tilmicosin, or 20-deoxo-20-(3,5-dimethylpiperidin-1-yl)desmycosin, is a macrolide antibiotic primarily utilized in livestock. This study examined 46 human exposure calls involving tilmicosin received by Texas poison centres during 1998 - 2003. The majority (91%) of the calls were received from northern and central Texas. All of the cases were unintentional exposures. The most frequent route of exposure was parenteral (48%). The majority of the patients were males (80%) and adults (84%). Only 46% of the patients were managed outside of health care facilities. Some sort of adverse medical outcome was reported in 93% of parenteral exposures and 54% of other-route exposures. However, only 21% of parenteral exposures and 15% of other-route exposures involved medical outcomes that were judged to be moderate or worse. No deaths were reported. The most frequently reported clinical effects among parenteral cases were dermal (79%), while only 9% of other-route exposures had dermal effects. Cardiovascular clinical effects were observed in a single case of parenteral exposure and a single case of other-route exposure. Although the majority of cases were managed with the assistance of health care facilities, the medical outcomes were usually not serious. Outcome depended on the route of exposure.
How much is enough to accept hormesis as the default? or ‘At what point, if ever, could/should hormesis be employed as the principal dose-response default assumption in risk assessment?'
Authors: Jayjock Michael A
Published: June 2005

Hormesis as the principal human dose-response default assumption must reasonably await the development of the science of toxicology and molecular biology before this dramatic change can occur. The inherent quality of typical toxicological data is simply too limited to allow for an understanding of what really occurs in human tissues at the relatively low doses generally extant in the environment. Thus, forwarding or asserting the quantitative use of hormesis (or any model of low doseresponse) without this reasonable knowledge is simply an argument without data. It is this writer's opinion that any widespread and default acceptance of hormesis will need to look forward to and draw upon the inevitable development and use of tools from the realm of molecular biology and a resulting and distinct change in the entire toxicological testing paradigm.
Examining the risks and benefits of replacing traditional dose-response with hormesis
Authors: Pickrell John A , Oehme Frederick W
Published: June 2005

In responding to Drs Calabrese and Baldwin's question, ‘At what point, if ever, should hormesis be employed as the principal dose response default assumption in risk assessment?’, we examined the benefits of replacing traditional dose-response with hormesis. In general, hormesis provides more complete useful information for risk assessment than does traditional dose-response. A major limitation of using hormesis as a default assumption in risk estimation is the difficulty of differentiating complex low-level hormetic responses from the placebo effect. A second limitation is that hormesis merely further defines one response. Most toxicoses have many responses. The most complete information takes all responses and their connections into account.
Hormesis and risk assessment
Authors: Rozman Karl K
Published: June 2005

It is postulated in this paper that at low doses all chemicals have hormetic/hormoligotic (beneficial) effects in living organisms. It has been known since Paracelsus that at high doses all chemicals are toxic. The combination of low and high dose effects can be empirically described by a β-curve or an inverted β-curve. A mathematical method is suggested to determine the maximum of the β-curve or the minimum of the inverted β-curve, yielding a point estimate for risk assessment.
Hormesis: how it could affect the risk assessment process
Authors: Calabrese E J , Cook R R
Published: June 2005

If the hormetic dose-response were accepted as the default dose-response model for risk assessment it could have important implications for environmental exposure standards for noncarcinogens and especially for carcinogens. Most notably it would lead to the recognition that carcinogens act via a threshold process rejecting the concept of linearity at low doses. The hormetic concept also provides agencies with a broader range of toxicologically-based exposure options, which permit a consideration for avoiding harm, as well as possibly enhancing benefits for both normal and high risk segments of the population. By dismissing hormesis, regulatory agencies such as EPA deny the public the opportunity for optimal health and avoidance of disease.
Comparisons of thresholds for carcinogenicity on linear and logarithmic dosage scales
Authors: Waddell William J
Published: June 2005

Comparisons on a linear and the Rozman logarithmic scale for dosage versus carcinogenicity in rodents are presented for methyl eugenol (ME), nitrosodiethylamine (NDEA), ethyl carbamate (EC) and 2-acetylaminofluorene (AAF). Each of these chemicals has been shown to be carcinogenic in experimental animals and, in addition, humans are regularly exposed to at least three of these compounds (ME, NDEA, EC) in foods. Although the source of adducts from AAF is not known, the aminofluorene (AF) adduct is present in humans. Plotted on the same graphs are either some doses from common foods (ME, NDEA, EC) or adducts (AF) on human haemoglobin, for perspective, with their thresholds for carcinogenesis in animals. Use of a linear scale when comparing doses administered to animals in studies of carcinogenicity with doses of those same chemicals to which humans are exposed does not provide useful, comparative information. On the other hand, the Rozman logarithmic scale for dose allows one to put these relative doses in perspective. It is also evident that forcing a linear extrapolation through the zero, zero origin does not agree with the experimental data. Further analyses for goodness of fit for these dose responses reveal that the dose response for three of these compounds (ME, NDEA, EC) appears to be linear with the logarithm of the dose. However, AAF appears to be linear with the logarithm of the dose for bladder, but not for liver. It is suggested that the high background incidence of tumours in the BALB/c StCrlfC3Hf/Nctr mouse liver may confound the interpretation of dose response from AAF carcinogenesis in mouse liver.
Chemopreventive effects of mustard (Brassica compestris) on chemically induced tumorigenesis in murine forestomach and uterine cervix
Authors: Gagandeep  , Dhiman M , Mendiz E , Rao A R , Kale R K
Published: June 2005

As there is a strong correlation between diet and cancer, the dietary constituents that inhibit mutagenesis and/or carcinogenesis are of paramount importance for the prevention of human cancer. In the present study, cancer chemopreventive potentials of different doses of mustard (Brassica compestris) seed mixed diets were evaluated against benzo(a)pyrene [B(a)P]-induced forestomach tumorigenesis and 3-methylcholantrene (MCA)-induced uterine cervix tumorigenesis. Results showed a significant inhibition of stomach tumour burden (tumours/ mouse) by mustard seeds. Tumour burden was 7.08±2.47 in the B(a)P-treated control group, whereas it was reduced to 1.369±1.12 (P<0.001) by the 2.5% dose and 1.189±0.87 (P<0.001) by the 5% dose of mustard seeds. The cervical carcinoma incidence, as compared to MCA-treated control group (73.33%), was reduced to nil (P<0.05) by the 5% diet of mustard seeds and to 13.33% (P<0.05) by the 7.5% diet of mustard seeds. The effect of the 2.5% and 5% mustard seed mixed diets was also examined on the antioxidant enzymes, glutathione content, lactate dehydrogenase (LDH) and lipid peroxidation in the liver of Swiss albino mice. The glutathione-Stransferase-specific activity was increased (P<0.05) by the 2.5% dose, whereas there was no significant change in the activity of DT-diaphorase. In antioxidant systems, significant elevation of the specific activities of superoxide dismutase and catalase was observed with both doses of mustard seeds (P <0.05). The level of reduced glutathione (GSH) measured as nonprotein sulphydryl content was elevated by the 2.5% dose of mustard seeds only (P<0.05). Lipid peroxidation measured as formation of thiobarbituric acid reactive substances production showed significant inhibition (P<0.05) by the 5% dose of mustard seed mixed diet. LDH activity was decreased significantly (P<0.05) by both the doses. The results strongly suggest the cancer chemopreventive potentials of mustard seeds and their ability to enhance the antioxidant defence system and in turn provide protection against the toxic effects of carcinogens. It is likely that the use of mustard seeds in the diet may contribute to reducing the risk of cancer incidence and burden in the human population.
Lipids, lipid peroxidation and 7-ketocholesterol in workers exposed to lead
Authors: Kasperczyk Slawomir , Birkner Ewa , Kasperczyk Aleksandra , Kasperczyk Janusz
Published: June 2005

The study population included healthy men and hypertensive employees of zinc and lead steelworks in the south of Poland. Workers exposed to lead (n=137) were divided into two groups: the first included employees with low exposure to lead (LL) with mean blood lead (PbB) 25-40 μg/dL and the second one with PbB over 40 μg/dL (HL group). The administration workers (n=35) were the control group. Evaluation of lipids and oxidative changes of cholesterol and lipids were estimated in blood samples. No significant changes in concentration of 7-ketocholesterol and blood lipids (cholesterol, HDL, LDL, triglycerides) were found. Lipid peroxidation (LP) was significantly higher in both exposed groups in plasma and in the HL group in erythrocytes when compared with control. There can be two independent sources of LP increase: the first is connected with the direct effect of lead’s ions on erythrocytes, the second is the prooxidative effect of delta-aminolevulinic acid. Hypertension in the HL group when compared with people with PbB below 40 μg/dL (OR 4.4, 95%CI 1.4-40 mg/dL was found more often. LP significantly increased by about 71% and concentration of 7-ketocholesterol by about 122% in hypertensives when compared with normotensives in the HL group.
The potential impact of the use of homeopathic and herbal remedies on monitoring the safety of prescription products
Authors: Woodward K N
Published: June 2005

The purpose of this paper is to explore the possibility that adverse reactions and drug interactions arising from the use of homeopathic and herbal medicines could lead to confusion when adverse reactions to conventional medicines are reported. An extensive literature review was conducted on the occurrence of adverse reactions and drug interactions following the use of homeopathic or herbal remedies, and the potential for these to confound adverse event reporting to conventional medicines considered. The survey demonstrates the potential for herbal remedies and homeopathic products, to produce adverse drug reactions or drug interactions, and shows the scope for potential for confusion with those arising from conventional medicines. There is a need for greater awareness that adverse reactions apparently due to a conventional medicine, might in reality be due to a herbal medicine or a drug interaction between a herbal medicine and a conventional drug, particularly when a health professional is unaware of the extent of a patient's selfmedication with alternative therapies.
Modulation of N-nitrosodiethylamine (NDEA) induced oxidative stress by vitamin E in rat erythrocytes
Authors: Bansal A K , Bansal M , Soni G , Bhatnagar D
Published: June 2005

Nitrosamines, such as N-nitrosodiethylamine (NDEA), induced oxidative stress due to the generation of reactive oxygen species, which are capable of initiating peroxidative damage to the cell. The present study was designed to establish whether pre-treatment with vitamin E (40 mg/kg body wt, intraperitoneally (ip), twice a week for 4 weeks) to NDEA induced rats provides protection against oxidative stress caused by NDEA. A single necrogenic dose of NDEA (200 mg/kg body wt) was administered intraperitoneally (ip) to the rats with or without vitamin E pre-treatment and the animals were sacrificed on Day 7, 14 or 21 after NDEA administration. Lipid peroxidation (LPO) and the activities of antioxidant enzymes were determined in erythrocytes as indices of oxidative damage. The result showed elevated levels of LPO in erythrocytes with NDEA treatment, however, vitamin E pre-treated rats administered NDEA showed decreased LPO (Day 14 and 21). Superoxide dismutase (SOD) enzyme activity and the glutathione (GSH) content increased with NDEA treatment and remained high in vitamin E pre-treated group. Catalase (CAT), glutathione reductase (GSH-R) and glutathione-S-transferase (GST) enzyme activities declined with NDEA treatment; however, vitamin E pre-treated rats administered NDEA, showed elevation in the enzyme activities. Glutathione peroxidase (GSH-Px) activity increased in erythrocytes in vitamin E pre-treated rats administered NDEA, while SeGSH-Px activity was not affected significantly. This study demonstrates that the pre-treatment with vitamin E prior to the administration of NDEA was effective in counteracting and modulating oxidative stress in rat erythrocytes in a time-dependent manner.
In vitro assessment of the genotoxicity of ethyl paraoxon in newborns and adults
Authors: Islas-González K , González-Horta C , Sánchez-Ramírez B , Reyes-Aragón E , Levario-Carrillo M
Published: June 2005

This in vitro experiment measured the genotoxic effects of ethyl paraoxon, the active metabolite of ethyl parathion. To assess genotoxicity, we used the micronuclei (MN) technique by blocking cytokinesis, and the ‘comet’ assay. We cultured peripheral blood samples from healthy adults and umbilical cord blood samples from four clinically healthy newborns to identify the frequency of MN. After 48 hours, we added the following ethyl paraoxon concentrations to the cultures: 0.0, 0.075, 0.100, 0.160, and 0.200 μg/mL. For the comet assay, following Singh's technique, we treated the blood samples for 2 hours with similar doses of the metabolite. The comet assay results, at a concentration of 0.075 μg/mL, showed that ethyl paraoxon causes a greater DNA migration that followed a dose-response pattern, a greater intensity being observed in lymphocytes from newborns. A comparison of the treatment and control groups indicated that only the 0.200 μg/mL concentration produced a slight increase in MN. In conclusion, our study identified primary DNA damage due to ethyl paraoxon, with a major effect on newborn lymphocytes, as well as an effect on the frequency of MN in the study groups at high concentrations only.
Anticoagulation in the trauma patient
Authors: Karnik Leena , Murray Jim
Published: June 2005

The trauma patient presents several challenges in areas of anticoagulation and haemostasis. Low molecular weight heparins are the mainstay of thrombopro phylaxis of trauma patients; however, new agents are being studied in trials and may soon be available. Patients already on oral anticoagulation may need reversal using plasma or prothrombin complex concentrates. Heparin-induced thrombo cytopenia needs a high index of suspicion and prompt treatment by clinicians treating trauma patients. Disseminated intravascular coagulation can be seen in the context of major trauma. Correction of the underlying cause and supportive blood component use are the mainstays of treatment.
Use of tissue expanders in trauma
Authors: O’Brien CM , Moiemen N
Published: June 2005

Tissue expansion has enjoyed a wide range of clinical applications. It is an important although arguably underutilized resource in trauma reconstruction. This article aims to highlight the history, mechanism and uses of the technique in addition to the various designs of expander that are available. Importantly it addresses reconstruction of the head and neck, trunk and extremities following trauma, highlighting practical considerations as well as complications to be pre-empted.
High pressure injection injuries
Authors: Smith GD
Published: June 2005

High pressure injection injuries are infrequent occurrences but their innocuous appearance leads to underestimation of their severity and results in significant morbidity. A good history and early referral of these injuries to a hand surgeon may help in reducing this morbidity. The nature of the substance injected (its volume, viscosity and toxicity), its site of injection and distribution of spread, the pressure of injection and delay to surgical debridement are all believed to be factors that contribute to the outcome of these injuries. Early surgical debridement should be the mainstay of treatment of these injuries. Any decision to treat these injuries nonoperatively should be made by an experienced hand surgeon and is only appropriate in selected cases. Most patients will require postoperative hand therapy, will experience a prolonged time to healing and will be left with long term motor and sensory deficits.
Equipoise in the Enhanced Supression of the Platelet IIb/IIIa Receptor with Integrilin Trial (ESPRIT): a critical appraisal
Authors: Mann Howard , London Alex John , Mann Jeffrey
Published: June 2005

Enhanced Supression of the Platelet IIb/IIIa Receptor with Integrilin Trial (ESPRIT) was a multicenter randomized controlled clinical trial in which participants were randomized between eptifibatide and placebo. A “clinical hold” was initially placed on the trial by the US Food and Drug Administration (FDA), which was concerned about the placebo-only control arm. The hold was lifted after additional information concerning the use of platelet glycoprotein IIb/IIIa inhibitors in clinical practice, derived from a survey of interventional cardiologists, was provided. The trial's principal investigator and colleagues have described how these issues were resolved, and advance a claim of equipoise for the trial. In this critical appraisal we examine the information and arguments proffered in support of the trial design and conclude that they evidence a misunderstanding of equipoise. We believe that a placebo-only control arm was not justified by the information provided by the trialists.
Where's the utility in Bayesian data-monitoring of clinical trials?
Authors: Ashby Deborah , Tan Say-Beng
Published: June 2005

Background Data monitoring is now an established part of good practice in clinical trials. Bayesian procedures for data-monitoring of treatment trials have been proposed and used, but sometimes without explicit consideration of utilities. A natural statistical framework for evidence-based medicine is a Bayesian approach to decision-making that incorporates an integrated summary of the available evidence and associated uncertainty with assessment of utilities.

Methods We explore this approach to data monitoring, explicitly addressing separately the individual, scientific and public health perspectives. The Data Monitoring Committee's decision can then be thought of as a weighted combination of these perspectives. These ideas are illustrated with a trial of treatments for oesophageal cancer.

Results For a Bayesian approach without explicit utilities we show that a utility structure is, in fact, implicit, and that it may be viewed as a weighted sum of the individual and scientific utilities.

Conclusions We argue that explicit consideration of utilities leads to decisionmaking that is more transparent, and lays foundations for data monitoring of more complex trials.
The use of systematic reviews when designing studies
Authors: Cooper Nicola J , Jones David R , Sutton Alex J
Published: June 2005

Background The importance of systematic reviews in identifying gaps in the evidence base and providing a quantitative basis for informing new research initiatives is widely acknowledged, but little is known about what actually happens in practice. Our objective was to assess the use made of results of reviews in the designing of new studies.

Methods Of all Cochrane reviews published in 1996, those updated in 2002 or 2003 were identified. Authors of trials added in the updates were contacted and asked if use had been made of the 1996 Cochrane or other reviews in designing their study.

Results Of 32 authors of studies newly included in 33 Cochrane reviews which met our inclusion criteria, 24 (75%) responded. Eleven (46%) respondents were aware of the relevant Cochrane review at the time they designed their study. In eight (33%) cases the design of the new study had been influenced by a review; in two (8%) this was the relevant Cochrane review.

Conclusions Cautious interpretation of these results is necessary, but it is apparent that the proportion of study investigators using Cochrane or other systematic reviews in designing their new studies was very limited. Inclusion of encouragement in publication or application guidelines to consider and cite review results is desirable.
Trialkyltin Compounds Bind Retinoid X Receptor to Alter Human Placental Endocrine Functions
Authors: Nakanishi Tsuyoshi , Nishikawa Jun-ichi , Hiromori Youhei , Yokoyama Hideaki , Koyanagi Mihoko , Takasuga Shinri , Ishizaki Jun-ichi , Watanabe Mai , Isa Shun-ichi , Utoguchi Naoki , Itoh Norio , Kohno Yutaka , Nishihara Tsutomu , Tanaka Keiichi
Published: June 2005

Retinoid X receptor (RXR) is a nuclear receptor that plays important and multiple roles in mammalian development and homeostasis. We previously reported that, in human choriocarcinoma cells, tributyltin chloride and triphenyltin hydroxide, which are typical environmental contaminants and cause masculinization in female mollusks, are potent stimulators of human chorionic gonadotropin production and aromatase activity, which play key endocrine functions in maintaining pregnancy and fetal development. However, the molecular mechanism through which these compounds stimulate these endocrine functions remains unclear. Our current study shows that trialkyltin compounds, including tributyltin chloride and triphenyltin hydroxide, function as RXR agonists. Trialkyltins directly bind to the ligand-binding domain of RXR with high affinity and function as transcriptional activators. Unlike the natural RXR ligand, 9-cis-retinoic acid, the activity of trialkyltins is RXR specific and does not activate the retinoic acid receptor pathway. In addition, trialkyltins activate RXR to stimulate the expression of a luciferase reporter gene containing the human placental promoter I.1 sequence of aromatase, suggesting that trialkyltins stimulate human placental endocrine functions through RXR-dependent signaling pathways. Therefore, our results suggest that activation of RXR may be a novel mechanism by which trialkyltins alter human endocrine functions.